Journal of Pharmaceutical Health Care and Sciences最新文献

Background: V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations are present in approximately 5% of Japanese patients with colorectal cancer (CRC) who receive BRAF-targeted triplet therapy, consisting of encorafenib (a BRAF inhibitor), binimetinib (a mitogen-activated protein kinase inhibitor [MEKi]), and cetuximab. This combination therapy is associated with an increased risk of cardiac dysfunction (CD), primarily attributed to MEKi. However, the detailed clinical course of this adverse event remains unclear. Here, we report a case of severe symptomatic CD that developed during this triplet therapy.

Case presentation: The patient was a 70-year-old Japanese man diagnosed with BRAF-mutated CRC with multiple metastases. BRAF-targeted triplet therapy was initiated as a third-line treatment. His baseline left ventricular ejection fraction (LVEF) was 66% and he had no history of heart disease. On Day 106, a pharmacist conducting the patient's consultation suspected CD associated with binimetinib because of symptoms such as deterioration of general condition and dyspnea. The pharmacist immediately recommended an echocardiography that revealed a significant decline in LVEF to 33%. The patient was referred to a cardiologist and treatment with enalapril, followed by bisoprolol, was initiated while triplet therapy was discontinued. Within 1 week of treatment interruption, the patient's general condition improved rapidly and his symptoms resolved. Therefore, cancer treatment was resumed as doublet therapy without binimetinib. Under close multidisciplinary monitoring, no recurrence of CD symptoms was observed. Doublet therapy was continued until Day 168, when disease progression occurred. This exceeded the median progression-free survival reported in the phase III BEACON-CRC trial.

Conclusions: This case highlights two crucial insights into BRAF/MEK inhibitor-associated CD. First, even severe symptomatic CD can be effectively managed and reversed upon immediate discontinuation of binimetinib and initiation of cardiotropic medications. Second, in such a severe case, rapid recovery is observed. Once stabilized, BRAF-targeted treatment could be continued as doublet therapy without binimetinib to ensure safety and disease control. However, regular echocardiographic surveillance is essential, with an interval shorter than 4 months, based on the clinical course of this case. Additionally, early recognition of CD may be improved by closely monitoring patients' symptoms and complaints through a multidisciplinary approach.

Background: Invasive treatment and the associated stress are known risk factors for sodium-glucose cotransporter 2 inhibitor (SGLT2i)-induced euglycemic diabetic ketoacidosis (euDKA) development. It is recommended that SGLT2is is discontinued at least 3 days prior to a scheduled surgery. However, it is unclear whether preoperative discontinuation of SGLT2is is effective and whether other factors contribute to the development of SGLT2i-induced perioperative euDKA.

Methods: We retrospectively investigated the incidence of euDKA postoperatively up to 30 days in patients receiving SGLT2is and undergoing surgery under general anesthesia. Multivariate logistic regression analysis was performed to identify the factors affecting euDKA development.

Results: Twenty-one of 1,169 eligible patients (1.8%) developed perioperative euDKA. The incidence of perioperative euDKA in patients who discontinued SGLT2is for ≥ 3 days prior to surgery was significantly lower than that in patients who did not discontinue SGLT2is for ≥ 3 days prior to surgery (p < 0.001). The multivariate analysis showed that discontinuation of SGLT2is for ≥ 3 days prior to surgery and preoperative use of insulin and glucose infusion were significant factors that affected the development of perioperative euDKA (odds ratios = 0.047 and 0.054, p = 0.003 and 0.005, respectively).

Conclusions: Our findings suggest that preoperative SGLT2i discontinuation for at least 3 days could prevent perioperative euDKA development and that preoperative insulin and glucose infusion could reduce the risk of developing euDKA, even in patients who cannot discontinue SGLT2is at least 3 days preoperatively.

Aim: Kampo medicines, which are covered under national health insurance, are widely accessible and affordable in Japan; however, knowledge about their current prescription practices remains limited. This study investigated the outpatient prescription practices of Kampo formulations at Kyoto University Hospital from April 2011 to March 2023.

Results: Kampo medicine was prescribed in all medical departments. A total of 42,453 prescriptions were recorded during the study period, with an average of 3,538 prescriptions per year. The gynecology and obstetrics department had the highest number of Kampo prescriptions, followed by anesthesiology. The anesthesiology department prescribed various formulations for 12 years. The usage rate of Processed Aconite Root-containing formulations increased with increasing patient age, reaching 3.3% in individuals in their teens, 6.6% in their twenties, 13.3% in their thirties, and over 30% in their eighties and nineties.

Conclusion: The substantial use of Kampo medicines across various departments indicates their critical role in specialized and general medical practice. The adaptability and personalized approach of treatments using Kampo medicines in the anesthesiology department are evident from the dynamic prescription patterns. Notably, the increasing use of Processed Aconite Root-containing formulations with advancing patient age suggests a potential age-related preference or therapeutic indication. These findings underscore the integral role of Kampo medicine in modern clinical practice and emphasize the necessity of further research into its age-specific applications and departmental prescribing trends.

Background: Pazopanib (PAZ) is an oral multi-kinase inhibitor used in the treatment of advanced soft tissue sarcoma. Gastric acid suppressants such as proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs) may reduce PAZ absorption by increasing gastric pH, potentially affecting its efficacy. This study aimed to evaluate the impact of concomitant use of acid suppressants on progression-free survival (PFS) and safety in patients with soft tissue sarcoma.

Methods: This retrospective study included patients with advanced or metastatic soft tissue sarcoma who were treated with PAZ at a single institution between 2015 and 2022. Patients were divided into two groups: those who received PAZ with concomitant acid suppressants (AS combination group) and those who did not (non-AS group). The primary outcome was PFS. Kaplan-Meier curves were used to estimate survival, and group differences were compared using the log-rank test. Multivariable Cox proportional hazards regression was performed to adjust for confounding factors.

Results: A total of 99 patients were included (77 in the AS combination group, 22 in the non-AS group). The median PFS was 116 days in the AS combination group and 403 days in the non-AS group (hazard ratio [HR]: 1.42; 95% confidence interval [CI]: 0.68-2.85; P = 0.361). No statistically significant difference in PFS was observed. Adverse events of any grade occurred in 84% of patients in the AS combination group and 68% in the non-AS group. Grade ≥ 3 adverse events occurred in 33 patients (43%) in the AS combination group and 9 patients (41%) in the non-AS group.

Conclusions: In our cohort of sarcoma patients, the concomitant use of acid-suppressive agents was not associated with a statistically significant difference in PFS. However, the substantial numerical difference in median PFS observed between the groups (403 days vs. 116 days), coupled with the study's limited sample size, suggests a potentially clinically meaningful negative effect that warrants caution and further investigation in larger, prospective studies. Our findings, therefore, do not rule out a detrimental interaction and underscore the need for careful consideration when co-prescribing these agents with pazopanib in this patient population.

Background: Triple Whammy (TW) therapy, a combination of renin-angiotensin system inhibitors (RASIs), diuretics, and non-steroidal anti-inflammatory drugs (NSAIDs), is associated with an increased risk of acute kidney injury (AKI). However, there is no consensus regarding the impact of NSAID type on the risk of AKI. Therefore, in this study, we evaluated the incidence and risk of NSAID-induced AKI in patients taking concomitant RASIs and diuretics, focusing on NSAID type.

Methods: We conducted an observational retrospective cohort study using a Japanese medical claims database. In the cohort analysis, 41,904 patients who received concomitant RASIs, diuretics, and newly added NSAIDs between April 2020 and March 2021 were included to estimate AKI incidence. In the case-crossover analysis, 2,909 patients who developed AKI while on RASIs and diuretics were analyzed to assess the short-term risk associated with NSAID use. Incidence rates were calculated using the person-year method. Conditional logistic regression was used to estimate adjusted odds ratios (aOR), accounting for surgical procedures and concomitant AKI risk drugs.

Results: Among 41,904 patients, 54 developed AKI (20.0 [95% CI: 14.8-25.6] per 1,000 person-years). The incidence rate ratio of TW to RASIs and diuretics without NSAIDs was 2.08 [95% CI: 1.58-2.74]. Case-crossover analysis showed an aOR of 1.44 [95% CI: 1.17-1.78] for AKI associated with NSAID use. No substantial differences were observed between COX-2 selective and nonselective NSAIDs (aOR: 0.99 [95% CI: 0.66-1.50]).

Conclusions: The addition of NSAIDs to RASIs and diuretics significantly increased AKI risk, emphasizing the need for careful monitoring regardless of the NSAID type.

Background: The evaluation of endogenous insulin secretory capacity is important in the selection of diabetes treatment. C-peptide, which is secreted in equivalent amounts as insulin, is a versatile test for this evaluation. Urinary C-peptide is widely used because it is less invasive. Sacubitril/valsartan, used to treat hypertension and chronic heart failure, has been reported to increase urinary C-peptide levels; however, its effect on endogenous insulin secretion remains unknown. In this report, we present a case in which insulin secretory capacity was evaluated according to a glucagon stimulation test in addition to urinary C-peptide levels in a patient receiving sacubitril/valsartan.

Case presentation: A male patient in his 50s with type 2 diabetes and hypertension, without renal dysfunction, was treated with sacubitril/valsartan. The results of the glucagon stimulation test showed a C-peptide change of 2.28, and the C-peptide index on the same day was 1.25, indicating normal endogenous insulin secretory capacity. In contrast, 24-h urinary C-peptide excretion was abnormally high at 615.2 µg/day. After discontinuation of sacubitril/valsartan, urinary C-peptide excretion decreased over time (615.2 to 369.0 µg/day), but blood glucose levels did not increase during this period.

Conclusions: In this case, 24-h urinary C-peptide excretion was abnormally elevated despite preserved endogenous insulin secretory capacity, as assessed by the glucagon stimulation test. Although this observation is based on a single case and cannot be generalized, it suggests that sacubitril/valsartan may interfere with the interpretation of urinary C-peptide levels. Therefore, in such clinical contexts, dynamic tests such as the glucagon stimulation test may serve as a useful adjunct to avoid potential overestimation of insulin secretory capacity when relying solely on urinary C-peptide levels.

Introduction: Diabetic neuropathy is a prevalent and debilitating complication of type 2 diabetes, resulting in functional impairments. Crocin, a bioactive constituent of saffron (Crocus sativus), has long been utilized in traditional medicine for its potential therapeutic effects. This study aimed to evaluate the efficacy of Crocin in alleviating neuropathic symptoms in patients with type 2 diabetes.

Methods: In this triple-blind, randomized, placebo-controlled clinical trial, patients with type 2 diabetes and confirmed peripheral neuropathy were randomly assigned to receive either 15 mg/day of Crocin or a matching placebo for 12 weeks. Neuropathic symptoms were assessed using the Total Symptom Score (TSS), Visual Analog Scale (VAS), and the Michigan Neuropathy Screening Instrument (MNSI) at baseline and at 3-week intervals.

Results: Forty-two patients completed the study, with 21 participants in each group. By week 9, the Crocin group exhibited a significantly lower mean TSS (5.1 ± 1.39) compared to the placebo group (6.6 ± 1.00, P = 0.005). Similarly, VAS scores, reflecting pain intensity, were significantly reduced in the Crocin group at both weeks 6 and 9 (P = 0.019). MNSI scores at week 9 also favored the Crocin group (5.7 ± 1.1 vs. 6.8 ± 0.9, P = 0.03).

Conclusion: Crocin may offer promising therapeutic benefits in reducing pain and neuropathic symptoms in patients with type 2 diabetes. Its neuroprotective, antioxidant, and antihyperglycemic properties may contribute to these effects. While the findings support the potential beneficial effect of crocin in the management of diabetic neuropathy, further large-scale and more robust clinical trials are warranted to validate these results.

Trial registration: https//irct.ir/ IRCT20190810044500N8, Registration date 01/01/2021.

Background: The risk of hemorrhagic complications in patients with chronic liver disease during invasive procedures should be considered. Patients with low platelet counts were administered platelet products prior to procedures based on a physician's judgment. However, there are no standards for allocating the bleeding risk associated with each procedure, platelet counts to avoid these risks, or methods for determining platelet counts. In this study, we evaluated whether pharmacists could reduce the use of platelet products by suggesting thrombopoietin receptor agonists using protocol-based pharmacotherapy management to assess procedural bleeding risk and platelet counts.

Methods: Among patients with chronic liver disease who were scheduled to undergo invasive procedures between August 2022 and February 2023, those who were interviewed by a pharmacist prior to the procedures were defined as the intervention group (n = 80) and the others as the non-intervention group (n = 224). The protocol was to define the procedural bleeding risk and platelet count. Pharmacists suggested prescribing a thrombopoietin receptor agonist to patients with platelet counts below the recommended counts.

Results: The use of platelet products and thrombopoietin receptor agonists was 0% and 7.5% and 3.1% and 0% in the intervention and non-intervention groups, respectively. Among the patients who were required to receive lusutrombopag, all patients in the intervention groups did not receive platelet product but lusutrombopag alone. However, the rates of patients with the recommended platelet count were not different between the intervention and non-intervention groups.

Conclusions: The use of platelet products decreases without the increased incidences of hemorrhage if pharmacists suggest prescribing thrombopoietin receptor agonists based on their assessment of the platelet count and the bleeding risk of the procedure.