Medicines (Basel, Switzerland)最新文献

Hypertension frequently coexists with obesity, diabetes, hyperlipidemia, or metabolic syndrome, anditsassociation with cardiovascular disease is well established. The identification and management of these risk factors is an important part of overall patient management. In this paper, we find the most relevant patterns of hospitalized patients with cardiovascular diseases, consideringaspects of their comorbidities, such as triglycerides, cholesterol, diabetes, hypertension, and obesity. To find the most relevant patterns, several clusterizations were made, playing with the dimensions of comorbidity and the number of clusters. There are three main patient types who require hospitalization: 20% whose comorbidities are not so severe, 44% with quite severe comorbidities, and 36% with fairly good triglycerides, cholesterol, and diabetes but quite severe hypertension and obesity. The comorbidities, such as triglycerides, cholesterol, diabetes, hypertension, and obesity, were observed in different combinations in patients upon hospital admission.

Background: Better understanding of the different phenotypes/subgroups of non-U.S. citizen kidney transplant recipients may help the transplant community to identify strategies that improve outcomes among non-U.S. citizen kidney transplant recipients. This study aimed to cluster non-U.S. citizen kidney transplant recipients using an unsupervised machine learning approach; Methods: We conducted a consensus cluster analysis based on recipient-, donor-, and transplant- related characteristics in non-U.S. citizen kidney transplant recipients in the United States from 2010 to 2019 in the OPTN/UNOS database using recipient, donor, and transplant-related characteristics. Each cluster's key characteristics were identified using the standardized mean difference. Post-transplant outcomes were compared among the clusters; Results: Consensus cluster analysis was performed in 11,300 non-U.S. citizen kidney transplant recipients and identified two distinct clusters best representing clinical characteristics. Cluster 1 patients were notable for young age, preemptive kidney transplant or dialysis duration of less than 1 year, working income, private insurance, non-hypertensive donors, and Hispanic living donors with a low number of HLA mismatch. In contrast, cluster 2 patients were characterized by non-ECD deceased donors with KDPI <85%. Consequently, cluster 1 patients had reduced cold ischemia time, lower proportion of machine-perfused kidneys, and lower incidence of delayed graft function after kidney transplant. Cluster 2 had higher 5-year death-censored graft failure (5.2% vs. 9.8%; p < 0.001), patient death (3.4% vs. 11.4%; p < 0.001), but similar one-year acute rejection (4.7% vs. 4.9%; p = 0.63), compared to cluster 1; Conclusions: Machine learning clustering approach successfully identified two clusters among non-U.S. citizen kidney transplant recipients with distinct phenotypes that were associated with different outcomes, including allograft loss and patient survival. These findings underscore the need for individualized care for non-U.S. citizen kidney transplant recipients.

Background: Hachimijiogan (HJG) and Bakumijiogan (BJG), two derivative prescriptions of Rokumijiogan (RJG), were selected to investigate their renoprotective potential in the 5/6 nephrectomized (5/6Nx) rat model. Methods: Rats were treated with HJG and BJG orally at 150 mg/kg body weight/day once daily for 10 weeks after resection of 5/6 of the renal volume, and their renoprotective effects were compared with 5/6Nx vehicle-treated and sham-operated control rats. Results: Improvements in renal lesions, glomerulosclerosis, tubulointerstitial injury, and arteriosclerotic lesions estimated by histologic scoring indices in the HJG-treated group were compared with those in the BJG-treated group. HJG- and BJG-treated groups ameliorated the renal function parameters. Elevated levels of renal oxidative stress-related biomarkers were reduced, while decreased antioxidant defence systems (superoxide dismutase and the glutathione/oxidized glutathione ratio) were increased in the HJG-treated group rather than the BJG-treated group. In contrast, BJG administration significantly reduced expression of the inflammatory response through oxidative stress. The HJG-treated group showed a decrease in inflammatory mediators through the JNK pathway. To gain a deeper understanding of their therapeutic action, the effects of the main components detected in HJG and BJG were evaluated using the LLC-PK₁ renal tubular epithelial cell line, which is the renal tissue most vulnerable to oxidative stress. Corni Fructus and Moutan Cortex-originated compositions afforded important protection against oxidative stress induced by peroxynitrite. Conclusions: From our described and discussed analyses, it can be concluded that RJG-containing prescriptions, HJG and BJG are an excellent medicine for chronic kidney disease. In the future, appropriately designed clinical studies in people with chronic kidney disease are necessary to evaluate the renoprotective activities of HJG and BJG.

Objective: The aim of this study was to evaluate the cost-effectiveness of different glucosamine formulations and preparations used for the management of osteoarthritis in Thailand compared with placebo.

Methods: We used a validated model to simulate the individual patient Utility score from aggregated data available from 10 different clinical trials. We then used the Utility score to calculate the quality-adjusted life year (QALY) over 3 and 6 months treatment period. We used the public costs of glucosamine products available in Thailand in 2019 to calculate the incremental cost-effectiveness ratio. We separated the analyses for prescription-grade crystalline glucosamine sulfate (pCGS) and other formulations of glucosamine. A cost-effectiveness cut-off of 3.260 USD/QALY was considered.

Results: Irrespective of the glucosamine preparation (tablet or powder/capsule), the data show that pCGS is cost-effective compared with placebo over a 3 and 6 months. However, the other glucosamine formulations (e.g., glucosamine hydrochloride) never reached the breakeven point at any time.

Conclusions: Our data show that pCGS is cost-effective for the management of osteoarthritis in the Thai context while other glucosamine formulations are not.

Introduction: The aim of our study is to evaluate the nutritional status of patients in an acute geriatric unit.

Methods: Patients included in the study were hospitalized in an acute geriatric unit over a period of 6 months. The nutritional status of each patient was evaluated with anthropometric measurements (the BMI and MNA scales), and biological measurements (albumin). Frailty was evaluated using three scales: the Fried scale, the CFS and the modified SEGA scale.

Results: A total of 359 patients were included, comprising 251 women (70%) with an average age of 85.28 years. The study showed that 102 elderly subjects were considered undernourished according to the BMI scale, 52 subjects were undernourished according to the MNA scale, and 50 subjects were undernourished according to their albumin levels. The relationships between undernutrition and frailty syndrome studied in our work show that elderly subjects who are undernourished according to the BMI and MNA scales are significantly frail according to Fried and Rockwood, whereas those who are undernourished according to their albumin levels are significantly frail according to Fried and the modified SEGA scale.

Conclusion: The relationship between undernutrition and the frailty syndrome is close, and their joint screening is necessary, whether on an outpatient or in-hospital basis, in order to prevent negative events related to comorbidities and geriatric syndromes.

Background: Abiraterone acetate is a cytochrome P450 17A1 (CYP17A1) inhibitor that is indicated for use in both castration-resistant and castration-sensitive prostate cancer patients. To manage the mineralocorticoid effects of CYP17A1 inhibition, a glucocorticoid such as dexamethasone is co-administered with abiraterone. The goal of the present study was to understand the effect of dexamethasone on the disposition of abiraterone. Methods: Adult male CD-1 mice were treated with either dexamethasone (80 mg/kg/day) or vehicle for three consecutive days, followed by the administration of a single dose of abiraterone acetate (180 mg/kg) as an oral gavage. Blood samples were collected by tail bleeding at timepoints between 0 to 24 h. Subsequently, abiraterone was extracted from the mouse serum using a neutral pH condition and serum abiraterone levels were determined using a liquid chromatography-mass spectrometry assay. Results: Our results demonstrated that dexamethasone lowered the maximum plasma concentration and area under the curve parameters by approximately five- and ten-fold, respectively. Similar effects were also observed on the plasma half-life and oral clearance parameters. This is the first report of dexamethasone effect on abiraterone disposition in vivo. Conclusions: We conclude that dexamethasone has the potential to reduce the plasma abiraterone level and thus compromise its CYP17A1 inhibitory ability in the procancerous androgen biosynthesis pathway. Thus, use of a higher abiraterone dose may be warranted when used alongside dexamethasone.

A lack of reliable information hinders the clinician evaluation of suspected herb-drug interactions. This pilot study was a survey-based study conceived as a descriptive analysis of real-life experiences with herb-drug interaction from the perspective of herbalists, licensed health-care providers, and lay persons. Reported dietary supplement-drug interactions were evaluated against the resources most commonly cited for the evaluation of potential supplement-drug interactions. Disproportionality analyses were performed using tools available to most clinicians using data from the U.S. Federal Adverse Event Reporting System (FAERS) and the US Center for Food Safety and Applied Nutrition (CFSAN) Adverse Event Reporting System (CAERS). Secondary aims of the study included exploration of the reasons for respondent use of dietary supplements and qualitative analysis of respondent's perceptions of dietary supplement-drug interaction. While agreement among reported supplement-drug interactions with commonly cited resources for supplement-drug interaction evaluation and via disproportionality analyses through FAERS was low, agreement using data from CAERS was high.

Background: The intraovarian administration of autologous platelet-rich plasma (PRP) acts beneficially for the stimulation of follicle production in women presenting different forms of ovarian dysfunction. This pilot study aimed to evaluate and provide significant data regarding the efficacy of PRP to rejuvenate the ovaries. Methods: A total of 253 women aged 22-56 years, were divided into five groups, based on their status. All participants signed for informed consent for the current study. Blood sampling, preparation of PRP and intraovarian infusion of the latter were performed on all participants. The evaluation of PRP efficacy, a two-month follow-up detecting the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and anti-mullerian hormone (AMH), was performed for all participants. For women with advanced ages (>48 years), the restoration and regularity of the menstrual cycle were additionally evaluated. Results: After the two-month follow-up, the majority of the participants presented improvement in their hormonal profiles. Additionally, 17% of the women in this pilot study successfully conceived. The restoration of the menstrual cycle was detected in 15% of the women with advanced ages. Conclusions: Intraovarian infusion of autologous PRP exhibited remarkable evidence and promising results to restore ovarian insufficiency.

Background: The intestinal ecosystem, including epithelium, immune cells, and microbiota, are influenced by diet and timing of food consumption. The purpose of this study was to evaluate various dietary protocols after ad libitum high fat diet (HFD) consumption on intestinal morphology and mucosal immunity.

Methods: C57BL/6 male mice were fed a 45% high fat diet (HFD) for 6 weeks and then randomized to the following protocols; (1) chow, (2) a purified high fiber diet known as the Daniel Fast (DF), HFD consumed (3) ad libitum or in a restricted manner; (4) caloric-restricted, (5) time-restricted (six hours of fasting in each 24 h), or (6) alternate-day fasting (24 h fasting every other day). Intestinal morphology and gut-associated immune parameters were investigated after 2 months on respective protocols.

Results: Consuming a HFD resulted in shortening of the intestine and reduction in villi and crypt size. Fasting, while consuming the HFD, did not restore these parameters to the extent seen with the chow and DF diet. Goblet cell number and regulatory T cells had improved recovery with high fiber diets, not seen with the HFD irrespective of fasting.

Conclusion: Nutritional content is a critical determinant of intestinal parameters associated with gut health.

Background: The regulation of microcirculation depends on the dynamic interaction of different factors: the autonomic nervous system plays a pivotal role in the blood flow and acupuncture can modulate it, obtaining different results depending on the site, the frequency, and the intensity of the stimulation. Methods: 18 healthy subjects have been enrolled and have undergone two sessions of electroacupuncture stimulations: one session using high frequency and one with low frequency. Microcirculation has been monitored continuously during stimulation using the laser Doppler method. Results: The microcirculatory parameters have shown a significant difference between high and low-frequency stimulation, suggesting that low-frequency stimulation is more effective for obtaining a vasodilator effect. Discussion: Our results show that low-frequency stimulation can increase the cutaneous microcirculatory flux, without significantly modifying blood pressure and heart rate. The auricular stimulation causes an increase in the activity of the vagus nerve, increasing the cholinergic activity without acting on post-junctional muscarinic receptors. Conclusion: Auricular acupuncture has a significant impact on the regulation of microcirculation.