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Background: The support system for research activities has not been sufficiently established in clinical settings. A survey should be conducted to identify the causes of low research activity among pharmacists and the characteristics of pharmacists who could serve as mentors to build a support system at the regional level. Methods: A retrospective cross-sectional survey was conducted with 156 pharmacists, including hospital and community pharmacists, who attended a webinar on research ethics held once a year in Mie Prefecture. Decision tree (DT) analysis was performed to extract the low research activities and pharmacists who could serve as mentors in research activities using independent factors identified by multivariate logistic regression analysis. Results: The questionnaire response rate was 72.4% (113/156), and most respondents were community pharmacists (81.4%). In the DT model, pharmacists who did not belong to academic societies (78%, 46/59) or those who belonged to one or two academic societies but had no certifications (100%, 5/5) had low research activities. Pharmacists who read papers more than once a month and had a nearby mentor (73%, 11/15) were more likely to become mentors in research activities. Conclusions: The combination of the number of academic societies and the presence of certifications determines the efforts in research activities. In addition to reading at least one paper monthly, the presence of a mentor for writing research papers may also be a crucial factor in becoming a mentor. The proposed DT model may be helpful in building a support system for research activities at the regional level. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Although pharmacists often identify numerous clinical questions, they face several barriers, including the lack of mentors for research activities in clinical settings. Therefore, a workshop for the appropriate selection of a study design, which is a fundamental first step, may be necessary. The purpose of this study was to evaluate the effectiveness of a workshop on study design for hospital and community pharmacists. Moreover, the characteristics of pharmacists with little involvement in research activities were extracted using decision-tree analysis to guide the design of future workshops. Methods: A workshop was conducted on October 1, 2023. It comprised three parts: lectures, group work, and presentations. Questionnaire-based surveys were conducted with workshop participants regarding their basic information, their background that influenced research activities, their satisfaction, and their knowledge/awareness. For the questions on knowledge/awareness, the same responses were requested before and after the workshop using a five-scale scoring system. Multivariate logistic regression analysis was conducted to identify independent factors influencing research activities. Decision tree analysis was performed to extract low-effort characteristics of the research activities. Results: Of the 40 workshop attendees, the overall satisfaction score for the workshop was 4.38 of 5, and the score for each question was 4 or higher. Significant increases were observed in the scores of knowledge/awareness after the workshop. Moreover, 95% of the pharmacists answered that it would be highly useful to conduct a joint workshop between hospitals and community pharmacists. Although independent influencing factors were not detected in the multivariate logistic regression analysis, the decision tree analysis revealed that pharmacists who were no member of an academic society (85%, 11/13) or members without any certifications or accreditations related to pharmacy practice (80%, 4/5) were the least active in clinical research. In contrast, those belonging to academic societies and holding certifications or accreditations related to pharmacy practice frequently conducted clinical research. Conclusion: The present study revealed that a joint workshop on study design may have the potential to change pharmacists' knowledge and awareness of research activities. Moreover, future workshops should be conducted with pharmacists who do not belong to academic societies. [ABSTRACT FROM AUTHOR]

Background: Polypharmacy, defined as the concurrent use of over six drugs, is common in the treatment of heart failure (HF); however, unpredictable drug interactions with bepridil may occur. In this study, we have elucidated the influence of polypharmacy on plasma bepridil concentrations in patients with HF. Methods: We conducted a multicenter retrospective study involving 359 adult patients with HF who received oral bepridil. Because QT prolongation is an adverse effect following plasma bepridil concentrations ≥800 ng/mL, the risk factors for patients achieving these concentrations at steady state were elucidated via multivariate logistic regression. The correlation between bepridil dose and plasma concentration was examined. The effect of polypharmacy on the value of the concentration-to-dose (C/D) ratio was investigated. Results: A significant relationship was observed between bepridil dose and plasma concentration (p < 0.001), and the intensity of the correlation was moderate (r = 0.503). Based on multivariate logistic regression, the adjusted odds ratios for a daily dose of bepridil ≥1.6 mg/kg, polypharmacy, and concomitant of aprindine, a cytochrome P450 2D6 inhibitor, were 6.82 (95% coefficient interval: 2.104–22.132, p = 0.001), 2.96 (95% coefficient interval: 1.014–8.643, p = 0.047), and 8.63 (95% coefficient interval: 1.684–44.215, p = 0.010), respectively. Despite the moderate correlation in non-polypharmacy, the correlation was not observed in polypharmacy. Therefore, inhibiting metabolism, along with other mechanisms, may contribute to the polypharmacy-induced increase in plasma bepridil concentrations. Moreover, the C/D ratios in the groups receiving 6–9 and 10≤ concomitant drugs were 1.28- and 1.70-fold higher than in those receiving <6 drugs, respectively. Conclusions: Plasma bepridil concentrations may be influenced by polypharmacy. Moreover, the plasma bepridil concentration increased in correlation with the number of concomitant drugs used. Although the mechanism of this increase could not be determined, plasma bepridil concentrations should be periodically monitored for safe use in patients with HF. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic heart failure (CHF) are often treated using many diuretics for symptom relief; however, diuretic use may have to continue despite hypotension development in these patients. Here, we present a case of heart failure with preserved ejection fraction (HFpEF), which is defined as ejection fraction ≥50% in CHF, and refractory hypotension, which was treated with midodrine and droxidopa to normalize blood pressure. Case presentation: The patient was a 62-year-old man with a history of HFpEF due to mitral regurgitation and complaints of dyspnea on exertion. He had been prescribed multiple medications at an outpatient clinic for CHF management, including azosemide 60 mg/day, bisoprolol 2.5 mg/day, enalapril 2.5 mg/day, spironolactone 50 mg/day, and tolvaptan 15 mg/day. The systolic blood pressure (SBP) of the patient remained at 70–80 mmHg because the use of the diuretic could not be reduced or discontinued owing to edema and weight gain. He was hospitalized for the exacerbation of CHF. Although midodrine 8 mg/day was administered to improve hypotension, the SBP of the patient increased only up to 90 mmHg. On the 35th day after hospitalization, the urine volume decreased significantly (< 100 mL/day) due to hypotension. When droxidopa 200 mg/day replaced intravenous noradrenaline on the 47th day, the SBP remained at 100–120 mmHg and the urine volume increased. Conclusions: Oral combination treatment with midodrine and droxidopa might contribute to the maintenance of blood pressure and diuretic activity in HFpEF patients with refractory hypotension. However, further long-term studies evaluating the safety and efficacy of this combination therapy for patients with HFpEF are needed. [ABSTRACT FROM AUTHOR]

Background: Although recombinant human soluble thrombomodulin (rTM) has been widely used to treat disseminated intravascular coagulation (DIC) in Japan, there is no consensus regarding rTM efficacy. Therefore, if the factors influencing rTM efficacy is revealed, it may be possible to demonstrate the effectiveness of rTM by limiting the patients who use rTM. This study investigated the factors of rTM treatment which influence DIC status. Methods: This retrospective case-control study enrolled hospitalized adult patients treated with rTM from October 2010 to May 2020. Among these patients, 227 who were diagnosed with DIC according to the Japanese Association for Acute Medicine DIC scoring system were assessed. The primary endpoint was the 28-day mortality after rTM treatment. For Cox-proportional hazards model, explanatory factors determined using univariate analysis with p < 0.1 were used. In addition, some factors considered to affect DIC-related mortality such as age ≥ 75 years, rTM dose ≥380 U/kg, antithrombin III treatment, and diseases with a poor prognosis (sepsis, solid tumors, and trauma) were added as covariates. Results: Univariate analyses suggested that male sex (p = 0.029), treatment in intensive care unit (p = 0.061), and prothrombin time-international normalized ratio (PT-INR) (p < 0.001) were the factors influencing DIC-related 28-day mortality after rTM treatment. According to Cox-proportional hazard analysis, the adjusted odds ratio for DIC-related 28-day mortality in patients with PT-INR ≥ 1.67 was 2.23 (95% confidence interval: 1.451–3.433, p < 0.001), age ≥ 75 years was 1.57 (95% confidence interval: 1.009–2.439, p = 0.046), and male sex was 1.66 (95% confidence interval: 1.065–2.573, p = 0.025), respectively. As life-threatening bleeding events were not observed, prolonged PT-INR might directly or indirectly affect DIC-related mortality caused by rTM treatment. Conclusion: rTM treatment for DIC was less effective in male patients with PT-INR ≥ 1.67 and age ≥ 75 years. [ABSTRACT FROM AUTHOR]