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Background: Reports on changes in circulating immune cells induced by immune checkpoint inhibitors (ICIs) and their association with therapeutic responses are limited. This study aimed to analyze the interaction between ICIs and circulating blood cells in real‐world practice and identify biomarkers associated with therapeutic efficacy. Materials and Methods: Patients with non‐small cell lung cancer who received nivolumab, pembrolizumab, or atezolizumab monotherapy were eligible. Blood samples were collected before and 7–21, and 22–42 days after treatment, and changes in the number and characteristics of neutrophils and lymphocytes in the peripheral blood were analyzed. The efficacy of ICIs was evaluated based on the best overall response up to 3 months after treatment. The patients were divided into the following groups: patients with non‐progressive disease (non‐PD) and those with progressive disease (PD). Blood immunological factors related to treatment response were analyzed. Results: There were 16 and 27 patients in the non‐PD and PD groups, respectively. The non‐PD group had significantly lower pretreatment CD56+ cell (CD56+ IFN‐γ+ cell), and neutrophil counts at 7–21 days after ICI administration than the PD group. Additionally, there was a significant increase in CD8+ IFN‐γ+, and CD8+CD28+ IFN‐γ+ T‐cell counts 7–21 days after ICI administration in the non‐PD group. CD8+CD28+IFN‐γ+ T‐cell count greater than 94.6 cells/μL at 7–21 days after ICI administration was highly predictive with an AUC greater than 0.8 in the ROC curve analysis. Conclusions: Predictors of disease progression include a low activated CD56+ cell count, no increase in the neutrophil count before ICI therapy, and an increase of activated CD8+ cell count early after ICI administration. The findings will contribute to selecting patients with a favorable therapeutic response and early prediction of therapeutic response to ICI. [ABSTRACT FROM AUTHOR]

Although dietary potassium restriction is an acceptable approach to hyperkalemia prevention, it may be insufficient for outpatients with chronic kidney disease (CKD). Most outpatients with CKD use community pharmacies owing to the free access scheme in Japan. The MieYaku-CKD project included a community pharmacist-led nutritional intervention for dietary potassium restriction, with the goal of determining its efficacy for patients' awareness of potassium restriction and serum potassium levels in outpatients with CKD. This was a five-community pharmacy multicenter prospective cohort study with an open-label, before-and-after comparison design. Eligible patients (n = 25) with an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 received nutritional guidance from community pharmacists. The primary outcome was a change in serum potassium levels at 12 weeks post-intervention. The eligible patients' knowledge, awareness, and implementation of potassium restriction were evaluated using a questionnaire. The median value of serum potassium was significantly reduced from 4.7 mEq/L before to 4.4 mEq/L after the intervention [p < 0.001, 95% confidence interval (CI): 0.156–0.500], with no changes in eGFR (p = 0.563, 95% CI: -2.427–2.555) and blood urine nitrogen/serum creatinine ratio (p = 0.904, 95% CI: -1.793–1.214). The value of serum potassium had a tendency of attenuation from 5.3 to 4.6 mEq/L (p = 0.046, 95% CI: 0.272–1.114) in the eGFR < 30 mL/min/1.73 m2 group. A questionnaire revealed that after the intervention, knowledge and attitudes regarding dietary potassium restriction were much greater than before, suggesting that the decrease in serum potassium levels may be related to this nutritional guidance. Our findings indicate that implementing a dietary potassium restriction guidance program in community pharmacies is feasible and may result in lower serum potassium levels in outpatients with CKD. [ABSTRACT FROM AUTHOR]

Aims: Genotype‐guided dosing algorithms can explain about half of the interindividual variability in prothrombin time–international normalized ratio (PT‐INR) under warfarin treatment. This study aimed to refine a published kinetic–pharmacodynamic model and guide warfarin dosage for an optimal PT‐INR based on renal function. Methods: Using a retrospective cohort of adult patients (>20 years) who were administered warfarin and underwent PT‐INR measurements, we refined the kinetic–pharmacodynamic model with age and the genotypes of cytochrome P450 2C9 and vitamin K epoxide reductase complex subunit 1 using the PRIOR subroutine in the nonlinear‐mixed‐effect modelling programme. We searched the significant covariates for parameters, such as the dose rate for 50% inhibition of coagulation (EDR50), using a stepwise forward and backward method. Monte Carlo simulation determined a required daily dose of warfarin with a target range of PT‐INR (2.0–3.0 or 1.6–2.6) based on the significant covariates. Results: A total of 350 patients with 2762 PT‐INR measurements were enrolled (estimated glomerular filtration rate [eGFR]: 47.5 [range: 2.6–199.0] mL/min/1.73 m2). The final kinetic–pharmacodynamic model showed that the EDR50 changed power functionally with body surface area, serum albumin level and eGFR. Monte Carlo simulation revealed that a lower daily dose of warfarin was required to attain the target PT‐INR range as eGFR decreased. Conclusions: Model‐informed precision dosing of warfarin is a valuable approach for estimating its dosage in patients with renal impairment. [ABSTRACT FROM AUTHOR]

Background: Isavuconazole is a novel triazole antifungal agent. However, the previous outcomes were highlighted by statistical heterogeneity. This meta‐analysis aimed to validate the efficacy and safety of isavuconazole for the treatment and prophylaxis of invasive fungal infections (IFIs) compared with other antifungal agents (amphotericin B, voriconazole and posaconazole). Methods: Scopus, EMBASE, PubMed, CINAHL and Ichushi databases were searched for relevant articles that met the inclusion criteria through February 2023. Mortality, IFI rate, discontinuation rate of antifungal therapy and incidence of abnormal hepatic function were evaluated. The discontinuation rate was defined as the percentage of therapy discontinuations due to adverse events. The control group included patients who received other antifungal agents. Results: Of the 1784 citations identified for screening, 10 studies with an overall total of 3037 patients enrolled. Isavuconazole was comparable with the control group in mortality and IFI rate in the treatment and prophylaxis of IFIs, respectively (mortality, odds rate (OR) 1.11, 95% confidential interval (CI) 0.82–1.51; IFI rate, OR 1.02, 95% CI 0.49–2.12). Isavuconazole significantly reduced the discontinuation rate in the treatment (OR 1.96, 95% CI 1.26–3.07) and incidence of hepatic function abnormalities in the treatment and prophylaxis, compared with the control group (treatment, OR 2.31, 95% CI 1.41–3.78; prophylaxis, OR 3.63, 95% CI 1.31–10.05). Conclusions: Our meta‐analysis revealed that isavuconazole was not inferior to other antifungal agents for the treatment and prophylaxis of IFIs, with substantially fewer drug‐associated adverse events and discontinuations. Our findings support the use of isavuconazole as the primary treatment and prophylaxis for IFIs. [ABSTRACT FROM AUTHOR]