Pharmazie最新文献

The present study aimed to investigate the efficacy and safety of flumatinib in patients newly diagnosed with chronic myeloid leukemia in the chronic phase (CML-CP). A retrospective study was conducted using five patients newly diagnosed with CML-CP who received flumatinib (600 mg/day). Results of the present study demonstrated that all five patients with CML-CP that were treated with flumatinib achieved the optimal molecular response within three months. In addition, two patients experienced major molecular response (MMR), and one patient acquired undetectable molecular residual disease, which was maintained for more than one year. Moreover, one patient exhibited grade 3 hematological toxicity, two patients exhibited transient diarrhea, one patient exhibited vomiting and one patient exhibited a rash with pruritus. No second-generation tyrosine kinase inhibitor-specific adverse cardiovascular events occurred in any patients. In conclusion, flumatinib exhibits high efficacy and high early molecular response rate in patients newly diagnosed with CML-CP. The majority of patients obtained MMR within three months, and the adverse reactions experienced were mild and tolerable.

The aim of the present study was to investigate the potential inhibitory effects of nodakenin, a coumarin glucoside derivative from the root extract of Angelica gigas Nakai (AGN), on melanogenesis and its underlying mechanisms in B16F10 melanoma cells. The inhibitory effects of nodakenin on melanogenesis were evaluated by determining melanin contents and tyrosinase activity in α -melanocyte stimulating hormone (α-MSH)-treated B16F10 melanoma cells. The mechanisms associated with the anti-pigmentation effect of nodakenin were investigated by quantitative real-time PCR and immunoblotting analysis. Using the UVB-irradiated conditioned media culture system and UVB-irradiated co-cultivation system of HaCaT keratinocytes and B16F10 melanoma cells mimicking in vivo melanin biosynthesis, the effect of nodakenin on melanin production was evaluated. Melanin content analysis showed that nodakenin decreased cellular melanin biosynthesis in α-MSH-treated B16F10 cells. Immunoblotting revealed that CREB phosphorylation, MITF, a mastering transcription factor of melanogenesis and its downstream genes tyrosinase, tyrosinase-related protein 1, and tyrosinase-related protein 2 were downregulated by nodakenin in a dose-dependent manner. Interestingly, nodakenin did not affect the phosphorylation of PKA and p38 MAPK but the phosphorylation of ERK1/2 and MSK1. In addition, the inhibition of melanin accumulation by nodakenin in the UVB-irradiated conditioned media culture system and UVB-irradiated co-cultivation system of HaCaT and B16F10 cells suggests that nodakenin has potential as an anti-pigmentation activity. These data suggest that nodakenin inhibits the melanogenesis in B16F10 cells by interfering the ERK/ MSK1/CREB axis and thus preventing MITF expression.

The disintegration time is critical for characterizing orally disintegrating tablets (ODTs), according to regulatory standards. The current study aimed to assess the effect of superdisintegrants such as sodium starch glycolate, croscarmellose sodium, and crospovidone on the disintegration of ODTs using simulated wetting and in vitro disintegration tests. The results showed that the wetting time of ODTs containing sodium starch glycolate and croscarmellose sodium was 17 - 21 s, but the wetting time of ODTs containing crospovidone was 9 - 12 s. In contrast, there was no significant difference in in vitro disintegration time among ODTs using different disintegrants (ca. 14 to 18 s) The quick wetting time of ODTs with crospovidone may be attributed to strong capillary characteristics of crospovidone. It is suggested that determining the disintegration time of ODTs just through simulated wetting test is insufficient and may lead to biases. As a result of the findings, it is recommended that an additional disintegration test, imitating saliva fluid absorption and tablet breaking, to provide a more precise evaluation of ODTs.

BRAF ^V600E-mutated colorectal cancer (CRC) is very aggressive and responds poorly to standard treatment. In this study, BRAF^V600E-mutant mice with CRC were treated with intragastric cyasterone, a compound commonly used in traditional Chinese herbal medicine, for 21 days. Microbial DNA was extracted from mouse intestinal contents for 16S ribosomal RNA gene amplicon sequencing and analyzed. Our results indicated that cyasterone enhanced the diversity of the gut microbiota. The abundance of beneficial bacteria, such as Prevotellaceae, Muribaculaceae, and Ruminococcaceae was significantly higher in cyasterone-treated mice than controls. The abundance of Erysipelotrichaceae, a family of bacteria that promotes inflammation in the gut, was significantly positively correlated with tumor weight. Cyasterone is a potential inhibitor of BRAF^V600E-mutant CRC via its effects on intestinal flora.

Antimicrobials should be used appropriately to minimise the risk of resistant strains arising in association with overuse. De-escalation of antimicrobial therapy is one strategy used to ensure appropriate use, but its safety and efficacy in burn patients are unclear. The aim of this study was to evaluate the safety and efficacy of de-escalation therapy for treating infections in burn patients. This retrospective cohort study investigated patients admitted to our intensive care unit with burns and treated for infection between October 1, 2013, and September 30, 2020. Patients were classified into a de-escalation group (Group D) comprising patients treated with empiric antimicrobial therapy followed by de-escalation and a non-de-escalation group (Group ND) comprising patients who did not undergo de-escalation. Characteristics and outcomes were compared between groups. Forty-three patients met the inclusion criteria, including 15 patients in Group D and 28 patients in Group ND. Bacterial species commonly detected in these patients were Corynebacterium spp. (17.3%), Pseudomonas aeruginosa (16.1%), and Staphylococcus aureus (9.6%) . No inter-group difference was seen in 28-day mortality (6.7% vs 21.4%, p =0.391). Multidrug-resistant strains were detected significantly less frequently in Group D (13.0%) than in Group ND (26.1%, p =0.003). De-escalation was associated with use of two or more antimicrobials as empiric antimicrobial therapy. As the use of de-escalation in infection treatment did not impact 28-day mortality, de-escalation might be safe for treating infections in burn patients.

Structured risk screening for postoperative delirium (POD) considering prehospital medication is not established. We aimed to develop a POD-risk prediction score based on known risk factors and delirium-risk increasing drugs to be used by pharmacists during medication reconciliation at hospital admission, and to test for feasibility in a retrospective cohort of surgical patients. Therefore, established POD-risk factors and drugs were extracted from the literature and a score was generated. Following this, the score was tested for feasibility in a retrospective 3-month-cohort of surgical patients. For patients with higher scores suggesting higher probability of POD, patient charts were screened for documentation of POD. For development of the score, the following POD-risk factors were defined and points assigned for score calculation: age (≥65 years=1 point/≥75 years=2), male sex (1), renal insufficiency (RI; 1), hepatic impairment (HI; Model-of-endstage-liver-disease (MELD) 10-14=1/≥15=2), delirium-risk increasing drugs (1 point per drug class), anticholinergic drug burden (ACB; ≥3=1). In the retrospective test cohort of 1174 surgical patients these factors concerned: age ≥65 years 567 patients (48%)/≥75 years 303 (26%), male 652 (55%), RI 238 (20%), MELD 10-14 106 (9%)/≥15 65 (5%), ≥ 1 delirium-risk increasing drug 418 (36%), ACB ≥3 106 (9%). The median POD-risk prediction score was 2 (range 0-9). Of 146 patients (12%) with a score ≥ 5, POD was documented for 43 (30%), no evidence for POD for 91 (62%) and data inconclusive for 12 (8%). For scores of ≥ 7, POD was documented for 50% of the patients with sufficient POD documentation. Overall, POD documentation was poor. To summarize, we developed and successfully tested the feasibility of a POD-prediction-score assessable by pharmacists at medication reconciliation at hospital admission.

Long-term voriconazole use may increase the risk of cutaneous squamous cell carcinoma (cSCC), especially in immunocompromised patients. However, relatively little is known regarding voriconazole-induced cSCC in Japan. Thus, the purpose of this study was to evaluate the association between voriconazole use and cSCC in Japan using different national pharmacovigilance databases. First, using the Japanese Adverse Drug Event Report (JADER) database, we evaluated the association between voriconazole use and cSCC in Japan. Second, using the U. S. Food and Drug Administration Adverse Event Reporting System (FAERS) database, we examined regional differences in the occurrence of voriconazole-induced cSCC between Japan and other countries. We calculated reporting odds ratios (RORs) as disproportionality analysis to evaluate voriconazole-induced cSCC. In this study, cases in which one or more of "Bowen's disease", "Carcinoma in situ of skin", "Keratoacanthoma", "Squamous cell carcinoma in skin", or "Squamous cell carcinoma" were reported as adverse events were considered to be cSCC cases. The analysis based on the JADER database showed an association between voriconazole use and cSCC in Japan, with a ROR (95% confidence interval) of 35.37 (25.60-48.87). Further, the analysis based on the FAERS database revealed that signals were detected in Japan as well as in Western countries and Australia. This study is the first in which the association between voriconazole use and cSCC in Japan is assessed using national pharmacovigilance databases. Healthcare providers need to be fully aware of the potential for cSCC development owing to voriconazole use and in all countries, including Japan, ensure careful follow-up of patients' skin.

Medication-induced weight gain can be frustrating to patients and health care providers. Drug-induced weight gain is a profound side effect of numerous commonly used medications. The present study aimed to investigate FAERS reports about drug-induced weight gain in the last ten years. Using the US FDA Adverse Event Reporting System (FAERS) between 2012 and 2021, a retrospective, descriptive analysis was conducted to analyze the major reported Adverse Events about weight gain. During the last ten years, 137370 reports were submitted to FAERS about drug-induced weight gain. The most common drugs that are reported by the patients and that are associated with weight gain were risperidone (11.55%), adalimumab (3.94%), pregabalin (3.86%), aripiprazole (3.1%), etanercept (2.72%), and prednisone (2.70%). In conclusion, the present study showed that drug-induced weight gain is a common side effect of several medications frequently used to treat chronic diseases. Healthcare providers should educate their patients about the medicines that may cause weight gain.

Hypothyroidism is a common health problem among elder women. However, conflicting results were observed regarding the association between levothyroxine treatment and osteoporosis risk. Therefore, the current study aimed to evaluate the effect of levothyroxine replacement therapy on osteoporosis risk in the Saudi population. This study was a matched case-control study conducted from June to August 2020. Data were extracted from the electronic medical records and included sociodemographic, clinical characteristics, comorbid conditions, levothyroxine replacement therapy dose, duration, concomitant therapy, and bone mineral density. Cases were matched with controls (1:1 basis) by age; the study included 256 cases and 256 controls. In the multivariate conditional logistic regression analysis, thyroxine use was independently associated with an increased likelihood of osteoporosis. Therefore levothyroxine use in elderly females was associated with an increased risk of osteoporosis, and hence, clinicians must be aware of the levothyroxine replacement therapy outcomes in postmenopausal females at risk of osteoporosis.

Acute disseminated encephalomyelitis (ADEM) is a rare and immune-mediated inflammatory disorder of the central nervous system (CNS) that can be triggered by infections and vaccinations. To date, only anecdotal case studies have reported the association between ADEM incidence and seasonal influenza vaccines, and multiple studies have found no association. This study aimed to investigate the association between the incidence of ADEM and seasonal influenza vaccines in a real-world setting using data from the United States Vaccine Adverse Event Reporting System (VAERS). Further, propensity score matching and disproportionality analysis was performed by calculating the adjusted reporting odds ratio (ROR) of reported ADEM cases associated with seasonal influenza vaccines using multiple logistic regression. Additionally, we analysed the time-to-onset using Weibull shape parameters (WSPs). The VAERS database contained 390,352 adverse events reported from January 2011 to December 2020. The ROR of seasonal influenza vaccines for ADEM was 3.02 (95% confidence interval: 1.72-5.33). The median duration (interquartile range) of ADEM was 11.0 (5.0-33.0) days. The median duration of ADEM induced by egg culture-based influenza vaccine (Egg-based vaccine) and cell culture-based influenza vaccine (Cell-based vaccine) was 10.0 (5.0-24.0) and 91.0 (79.0-125.0) days (P < 0.001), respectively. Only Cell-based cases had WSP β > 1, indicating a wear-out failure type. The incidence of ADEM within 30 days after administration of egg- and Cell-based vaccines was 78.6% and 0.0%, respectively. Our findings indicate that ADEM incidence is associated with seasonal influenza vaccines; thus, careful monitoring of ADEM is required within the first month of Egg-based vaccination and after two months of Cell-based vaccination. Neurologists and general practitioners should exercise caution, as the timing for careful monitoring varies depending on the vaccine type.