Journal of Pharmaceutical Health Care and Sciences最新文献

Background: Morphine is effective in palliative care for patients with end-stage heart failure; however, its use is avoided in patients with impaired renal function because it tends to induce adverse effects. Although oxycodone has been reported to be a useful alternative, the evidence is insufficient. Therefore, we investigated the safety and efficacy of oxycodone in eight patients with end-stage heart failure complicated by chronic kidney disease.  METHODS: This single-center retrospective study reviewed patients with end-stage heart failure who were referred to the heart failure multidisciplinary team at our institution and administered oxycodone for refractory dyspnea during hospitalization between January 2011 and December 2018. We examined the details of oxycodone usage, vital signs, and the Modified Borg Scale (MBS), which quantifies the symptoms of dyspnea and adverse events.

Results: Oxycodone was administered for refractory dyspnea in eight patients with end-stage heart failure [mean age: 81 years, men: 4, New York Heart Association functional class IV: 8, median left ventricular ejection fraction: < 40% (n = 6) and ≥ 50% (n = 2)]. Renal function was reduced in all patients; the estimated glomerular filtration rate (eGFR) in seven patients was < 30 mL/min/1.73 m². The median initial intravenous dose of oxycodone was 7.05 mg/day (range: 5-10 mg/day), and the average duration of administration was 15.8 days. Significant decreases in MBS (before: median 9, range 7-10 vs. after: median 2.5, range 1-8; p < 0.01) were observed at a median of 2.0 days (range: 2 h to 7 days) after beginning oxycodone administration. Systolic blood pressure, heart rate, and respiratory rate were not significantly altered after treatment. Adverse events, including constipation, nausea, and tremors, were observed in three patients. However, no lethal adverse events related to oxycodone treatment occurred during treatment.

Conclusions: This study revealed the clinical practice of oxycodone treatment and suggested that it is an alternative therapy as a viable palliative for refractory dyspnea in patients with end-stage heart failure who should avoid the use of morphine.

Background: Concerns persist regarding the potential reduction in driving performance due to taking second-generation antihistamines or performing hands-free calling. Previous studies have indicated a potential risk to driving performance under an emergency event when these two factors are combined, whereas a non-emergency event was operated effectively. Currently, there is a lack of a discriminative index capable of detecting the potential risks of driving performance impairment. This study aims to investigate the relationship between driving performance and eye movements under combined conditions of taking second-generation antihistamines and a calling task, and to assess the usefulness of eye movement measurements as a discriminative index for detecting potential risks of driving performance impairment.

Methods: Participants engaged in a simulated driving task, which included a calling task, both under taking or not taking second-generation antihistamines. Driving performance and eye movements were monitored during both emergency and non-emergency events, assessing their correlation between driving performance and eye movements. The study further evaluated the usefulness of eye movement as a discriminative index for potential driving impairment risk through receiver operating characteristic (ROC) analysis.

Results: In the case of a non-emergency event, no correlation was observed between driving performance and eye movement under the combined conditions. Conversely, a correlation was observed during an emergency event. The ROC analysis, conducted to assess the discriminative index capability of eye movements in detecting the potential risk of driving performance impairment, demonstrated a high discriminative power, with an area under the curve of 0.833.

Conclusions: The findings of this study show the correlation between driving performance and eye movements under the concurrent influence of second-generation antihistamines and a calling task, suggesting the usefulness of eye movement measurement as a discriminant index for detecting potential risks of driving performance impairment.

Background: Understanding the roles and competencies of professions outside of one's specialty is essential for providing efficient healthcare. However, it is difficult for medical professionals to understand the roles and competencies of other related professions while performing their duties. This study examined the impact of clinical practice-based interprofessional education (IPE) on pharmacy students, who are future medical professionals.

Methods: Sixty-eight pharmaceutical students undergoing clinical practice were divided into non-IPE or IPE groups, with the IPE group attending an educational program with medical students conducted by doctors, pharmacists, and teachers during the clinical practice period. The effect was evaluated through a group survey using self-administered questionnaires focusing on contributing to multidisciplinary team medicine based on the Readiness for Interprofessional Learning Scale. The survey included specific behavioral objectives (SBOs), the Readiness for Interpersonal Learning Scale (RIPLS), and Kikuchi's Scale of Social Skills (KiSS-18).

Results: Regardless of group, SBOs [non-IPE: 3.2, 95% CI (2.6-3.8), p < 0.001; IPE: 3.7, 95% CI (2.5-4.9), p < 0.001] and social skills [non-IPE: 4.0, 95% CI (2.5-6.1), p < 0.001; IPE: 6.7 95% CI (3.0-10.4), p < 0.001] showed improvement after the clinical practice. In RIPLS Factor 3, pharmacy students with IPE awareness scored significantly higher by 1.5 points [95% CI (0.2-2.8), p = 0.025] post-practice than those without IPE awareness.

Conclusions: This study suggests that IPE for students during clinical practice could enhance their expertise in multidisciplinary medicine and facilitate the development of seamless team care in the future.

Trial registration: This study was retrospectively registered and conducted in compliance with the "Ethical Guidelines for Medical Research Involving Human Subjects" and was approved by The Ethics Committee of Tokushima University Hospital (approval number: 3544).

Background: We examined whether denosumab-induced hypocalcaemia is evident in osteoporosis when given loop diuretics that promote urinary calcium excretion.

Methods: Japanese Spontaneous Adverse Drug Event Reports was analyzed to examine signals for denosumab-induced hypocalcaemia co-administered loop diuretics. We retrospectively included osteoporotic patients to detect predictors for denosumab-induced hypocalcaemia (corrected calcium level < 8.5 mg/dL) using multivariate logistic regression analysis. We compared differences in corrected calcium levels (ΔCa = nadir-baseline).

Results: A significant signal for hypocalcaemia was detected (Reporting odds ratio = 865.8, 95% confidence interval [95% CI]: 596.8 to 1255.9, p < 0.0001). Among 164 patients (hypocalcaemia, 12%), loop diuretics have a significant association with hypocalcaemia (odds ratio [OR] = 6.410, 95% CI: 1.005 to 40.90, p = 0.0494). However, hypocalcaemia was found to be lower in high corrected calcium levels at baseline (OR = 0.032, 95% CI: 0.005 to 0.209, p < 0.0001) and calcium and vitamin D supplementation (OR = 0.285, 95% CI: 0.094 to 0.868, p = 0.0270). In the non-hypocalcaemia, ΔCa decreased significantly in the denosumab plus loop diuretics than in the denosumab alone (-0.9 [-1.3 to -0.7] mg/dL vs. -0.5 [-0.8 to -0.3] mg/dL, p = 0.0156). However, ΔCa remained comparable in the hypocalcaemia despite loop diuretics co-administration (-1.0 [-1.2 to -0.8] mg/dL vs. -0.8 [-1.5 to -0.7] mg/dL, p = 0.7904).

Conclusions: Loop diuretics may predispose to developing denosumab-induced hypocalcaemia.

Background: Antimicrobial agents (AMAs) are essential for treating infections. A part of AMAs chelate with metal cations (MCs), reducing their blood concentrations. That drug-drug interaction could lead to a reduction of therapeutic efficacy and the emergence of drug-resistant bacteria. However, prescriptions ordering concomitant intake (co-intake) of AMAs and MCs are frequently seen in clinical settings. A method for preventing such prescriptions is urgently needed.

Methods: We implemented pop-up alerts in the hospital's ordering and pharmacy dispensation support system to notify the prescriptions ordering co-intake of AMAs and MCs for physicians and pharmacists, respectively. To assess the effectiveness of the pop-up alerts, we investigated the number of prescriptions ordering co-intake of AMAs and MCs and the number of pharmacist inquiries to prevent co-intake of AMAs and MCs before and after the implementation of pop-up alerts.

Results: Before the implementation of pop-up alerts, 84.5% of prescriptions containing AMA and MCs ordered co-intake of AMAs and MCs. Implementing pop-up alerts time-dependently reduced the proportion of prescriptions ordering co-intake of AMAs and MCs to 43.8% and 29.5% one year and two years later, respectively. The reduction of tetracycline-containing prescriptions was mainly significant. Before the implementation of pop-up alerts, the proportion of prescriptions in which pharmacists prevented co-intake of AMAs and MCs was 3.4%. Implementing pop-up alerts time-dependently increased proportions of such prescriptions to 20.9% and 28.2% one year and two years later.

Conclusion: Implementing pop-up alerts reduced prescriptions ordering co-intake of AMAs and MCs and accelerated pharmacists to prevent co-intake of AMAs and MCs. The implementation of dual pop-up alerts in the hospital's ordering and pharmacy dispensation support system could help prevent co-intake of AMAs and MCs.

Background: Multimodal analgesia (MMA) is recommended for postoperative pain management; however, studies evaluating the effect of tramadol-including MMA on numerical rating scale (NRS)-based postoperative pain levels and the length of stay (LOS) in the hospital are limited. Therefore, this study aimed to compare the before and after effects of tramadol-including MMA application, and assess its effect on postoperative NRS scores and LOS.

Methods: Patients who underwent spinal surgery under general anesthesia at the Rakuwakai Marutamachi Hospital in fiscal years 2020 and 2022 were included in this study. The outcomes between the pre- and post-intervention groups were compared through propensity score matching.

Results: Following propensity score matching, 249 patients were included in each group. MMA application significantly decreased the median LOS from 10 to 9 days (p < 0.001). Additionally, the median NRS scores exhibited a significant decrease from 4 to 3 on postoperative day (POD) 3 (p = 0.0109) and from 3 to 2 on POD 5 (p = 0.0087). Following MMA application, the number of patients receiving additional analgesics decreased significantly, from 38 to 6 (p < 0.001).

Conclusions: The introduction of tramadol-including MMA can effectively reduce postoperative pain and decrease the LOS for patients undergoing spinal surgery.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been reported to have effects beyond lowering blood glucose levels, with certain SGLT2i expanding their indications to chronic kidney disease and chronic heart failure. We focused on the hepatoprotective and renoprotective effects of six SGLT2i and assessed whether the effects were unique to each drug or common class effects, in addition to whether the renal and hepatoprotective effects vary based on renal and hepatic status.

Methods: Patients with diabetes (ipragliflozin: 837, empagliflozin: 850, canagliflozin: 922, dapagliflozin: 590, tofogliflozin: 288, and luseogliflozin: 193) who initiated SGLT2i treatment and were monitored for one year were included. The propensity score (PS) was calculated using patient backgrounds (age, sex, height, weight, body mass index [BMI], disease duration, concomitant diabetes medications, underlying conditions, glycated hemoglobin [HbA1c], estimated glomerular filtration rate [eGFR], aspartate aminotransferase [AST], alanine aminotransferase [ALT], high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglyceride [TG] levels) as covariates. Additionally, the inverse probability of treatment weighting (IPTW) approach was used to compare liver and renal function test values.

Results: Pre- and 12-month post-treatment comparisons demonstrated a significant reduction in hepatic function (AST and ALT) and an increase in renal function (eCcr and eGFR) for all SGLT2i. Comparison of differences between pre- and 12-month post-treatment using the IPTW approach demonstrated no significant differences in AST, ALT, and eGFR levels between SGLT2i. At 12 months post-treatment, 67 patients were classified as having a more severe CKD than those at pre-treatment, representing only 1.8% of all patients (67/3,680). Similarly, 107 patients with AST and 147 patients with ALT were classified as having progressed to a more severe grade than at pre-treatment, representing only 2.9 and 4.0%, respectively.

Conclusions: Renoprotective and hepatoprotective effects are class effects of SGLT2i, and their effects are thought to be independent of kidney or liver status.

Background: Sacubitril/valsartan is an angiotensin receptor neprilysin inhibitor (ARNI) that inhibits the degradation of endogenous natriuretic peptides. Therefore, ARNIs may increase the efficacy of human atrial natriuretic peptide (hANP), a drug for acute heart failure, by mediating its pharmacological mechanism. This study was aimed at evaluating the effects of ARNIs on the pharmacological effects of hANP by using surrogate marker, such as urinary output, in patients with heart failure.

Methods: In this multicenter retrospective cohort study, adult patients with heart failure who were taking angiotensin II receptor blockers (ARB) or ARNIs combined with hANP were enrolled. Information on basic characteristics, clinical laboratory data, medical history, and severity of cardiac insufficiency were collected from electronic medical records. The primary outcome was the change in adjusted fluid balance, calculated by IN-volume (mL/day) - OUT-volume (mL/day) / daily hANP dosage (μg).

Results: Ninety-two and 62 patients in the ARB + hANP and ARNI + hANP groups, respectively, were eligible for analysis. The adjusted fluid balance in the ARNI + hANP group was significantly lower than that in the ARB + hANP group (p = 0.001). After propensity score matching, 27 patients from each group were included. Similarly, there was a significant reduction in adjusted fluid balance in the ARNI + hANP group after propensity score matching (p = 0.026).

Conclusions: These findings suggest that ARNIs may enhance the efficacy of hANP and the combination of the two may be effective in the treatment of heart failure.

Background: Brinzolamide (BRI) suspensions are used for the treatment of glaucoma; however, sufficient drug delivery to the target tissue after eye drop administration is hampered by poor solubility. To address this issue, we focused on nanocrystal technology, which is expected to improve the bioavailability of poor-solubility drugs, and investigated the effect of BRI nanocrystal formulations on corneal permeability and intraocular pressure (IOP)-reducing effect.

Methods: BRI nanocrystal formulations were prepared by the wet-milling method with beads and additives. The particle size was measured by NANOSIGHT LM10, and the morphology was determined using a scanning probe microscope (SPM-9700) and a scanning electron microscope (SEM). Corneal permeability was evaluated in vitro using a Franz diffusion cell with rat corneas and in vivo using rabbits, and the IOP-reducing effect was investigated using a rabbit hypertensive model.

Results: The particle size range for prepared BRI nanocrystal formulation was from 50 to 300 nm and the mean particle size was 135 ± 4 nm. The morphology was crystalline, and the nanoparticles were uniformly dispersed. In the corneal permeability study, BRI nanocrystallization exhibited higher corneal permeability than non-milled formulations. This result may be attributed to the increased solubility of BRI by nanocrystallization and the induction of energy-dependent endocytosis by the attachment of BRI nanoparticles to the cell membrane. Furthermore, the addition of tyloxapol to BRI nanocrystal formulation further improved the intraocular penetration of BRI and showed a stronger IOP-reducing effect than the commercial product.

Conclusions: The combination of BRI nanocrystallization and tyloxapol is expected to be highly effective in glaucoma treatment and a useful tool for new ophthalmic drug delivery.

Purpose: While nirmatrelvir/ritonavir (NMV-r) has been positioned as a first-line treatment for mild to moderate COVID-19, it has multiple and significant drug-drug interactions (DDIs). The use of NMV-r in Japan has been limited compared to the United States. This study aimed to describe the distribution of DDIs with NMV-r and their management in patients with COVID-19 under the control of a management system for the appropriate use of NMV-r.

Methods: A retrospective observational study was conducted at a Japanese university hospital. The management system included a flowchart for selecting antivirals and a list for reviewing DDI management, based on the National Institutes of Health guidelines and the guidance of the Japanese Society of Pharmaceutical Health Care and Sciences. Patients with mild to moderate COVID-19 and prescribed NMV-r or molnupiravir (MOV) were included. The primary outcome was DDI management practices, including the selected COVID-19 medications. The secondary outcome included the distribution of DDI classification and the 30-day all-cause mortality.

Results: This study included 241 patients (median age of 60 years, 112 [46.5%] females), of whom 126 and 115 received NMV-r and MOV, respectively. Of the 241 patients, 145 (60.2%) received concomitant medications that have DDIs with NMV-r. All 30 patients with severe renal impairment or insufficient details on concomitant medications received MOV. Forty-nine patients with concomitant medications required alternative COVID-19 therapy consideration due to DDIs, of whom 42 (85.7%) patients received MOV. Eighty-one patients had concomitant medications requiring temporary adjustment, of whom 44 (54.3%) patients received NMV-r, and 42 of these patients temporarily adjusted these concomitant medications. Five patients with concomitant medications that can continued by monitoring the effects/adverse effects, of whom 4 (80.0%) patients received NMV-r. Seventy-six patients without concomitant medications requiring DDI management, of whom 71 (93.4%) patients received NMV-r. The 30-day all-cause mortality for eligible patients was 0.9% [95% confidence interval, 0.1-3.1].

Conclusions: Most patients received appropriate antivirals according to the classification of DDIs, and most patients with concomitant medications requiring temporary adjustment received the recommended DDI management. Our management system is effective in promoting the use of NMV-r in the appropriate patients and managing problematic DDIs.