A Real-World Study on the Clinical Characteristics, Outcomes, and Relationship between Antibiotic Exposure and Clostridioides difficile Infection.

Clostridioides difficile is a Gram-positive bacteria that causes nosocomial infections, significantly impacting public health. In the present study, we aimed to describe the clinical characteristics, outcomes, and relationship between antibiotic exposure and Clostridioides difficile infection (CDI) in patients based on reports from two databases. Thus, we conducted a retrospective study of patients diagnosed with CDI from Sibiu County Clinical Emergency Hospital (SCCEH), Romania, followed by a descriptive analysis based on spontaneous reports submitted to the EudraVigilance (EV) database. From 1 January to 31 December 2022, we included 111 hospitalized patients with CDI from SCCEH. Moreover, 249 individual case safety reports (ICSRs) from EVs were analyzed. According to the data collected from SCCEH, CDI was most frequently reported in patients aged 65-85 years (66.7%) and in females (55%). In total, 71.2% of all patients showed positive medical progress. Most cases were reported in the internal medicine (n = 30, 27%), general surgery (n = 26, 23.4%), and infectious disease (n = 22, 19.8%) departments. Patients were most frequently exposed to ceftriaxone (CFT) and meropenem (MER). Also, in the EV database, most CDI-related ADRs were reported for CFT, PIP/TAZ (piperacillin/tazobactam), MER, and CPX (ciprofloxacin). Understanding the association between previous antibiotic exposure and the risk of CDI may help update antibiotic stewardship protocols and reduce the incidence of CDI by lowering exposure to high-risk antibiotics.

Biopolymeric Prodrug Systems as Potential Antineoplastic Therapy.

Nowadays, cancer represents a major public health issue, a substantial economic issue, and a burden for society. Limited by numerous disadvantages, conventional chemotherapy is being replaced by new strategies targeting tumor cells. In this context, therapies based on biopolymer prodrug systems represent a promising alternative for improving the pharmacokinetic and pharmacologic properties of drugs and reducing their toxicity. The polymer-directed enzyme prodrug therapy is based on tumor cell targeting and release of the drug using polymer-drug and polymer-enzyme conjugates. In addition, current trends are oriented towards natural sources. They are biocompatible, biodegradable, and represent a valuable and renewable source. Therefore, numerous antitumor molecules have been conjugated with natural polymers. The present manuscript highlights the latest research focused on polymer-drug conjugates containing natural polymers such as chitosan, hyaluronic acid, dextran, pullulan, silk fibroin, heparin, and polysaccharides from Auricularia auricula.

Valorization of Grape Pomace and Berries as a New and Sustainable Dietary Supplement: Development, Characterization, and Antioxidant Activity Testing.

Grape pomace and berries represent natural sources of phytochemicals that can increase the quality of life of consumers by contributing to the prevention of chronic diseases; thus, the development of a dietary supplement was necessary. The raw material (r.m.) used for the development of the dietary supplement consisted of dried and powdered bilberries (Vaccinium myrtillus L.), red currants (Ribes rubrum L.), and red fermented pomaces (Vitis vinifera L.) from Feteasca Neagra and Cabernet Sauvignon cultivars. The particle size distribution, powder flow, total phenolic content (TPC), HPLC-DAD phenolic profile assessment, and radical scavenging assay (RSA) were employed for the analysis of the raw material. After encapsulation, the average mass and uniformity of mass, the disintegration, and the uniformity of content for the obtained capsules were performed to obtain a high-quality dietary supplement. All the assays performed complied to the compendial requirements and the TPC was determined at 9.07 ± 0.25 mg gallic acid equivalents/g r.m. and RSA at 48.32 ± 0.74%. The highest quantities of phenolic compounds determined were 333.7 ± 0.50 µg/g r.m. for chlorogenic acid, followed by rutin, ferulic acid, and (+)-catechin with 198.9 ± 1.60 µg/g r.m., 179.8 ± 0.90 µg/g r.m. and 118.7 ± 0.75 µg/g r.m., respectively. The results of this study can be used for the manufacturing and assessing of pilot scale-up capsule batches and thinking of quality assurance, we recommend that the industrial batch extracts should be standardized in polyphenols, and the manufacturing process should be validated.

Advantages of Hyaluronic Acid and Its Combination with Other Bioactive Ingredients in Cosmeceuticals.

This study proposes a review on hyaluronic acid (HA) known as hyaluronan or hyaluronate and its derivates and their application in cosmetic formulations. HA is a glycosaminoglycan constituted from two disaccharides (N-acetylglucosamine and D-glucuronic acid), isolated initially from the vitreous humour of the eye, and subsequently discovered in different tissues or fluids (especially in the articular cartilage and the synovial fluid). It is ubiquitous in vertebrates, including humans, and it is involved in diverse biological processes, such as cell differentiation, embryological development, inflammation, wound healing, etc. HA has many qualities that recommend it over other substances used in skin regeneration, with moisturizing and anti-ageing effects. HA molecular weight influences its penetration into the skin and its biological activity. Considering that, nowadays, hyaluronic acid has a wide use and a multitude of applications (in ophthalmology, arthrology, pneumology, rhinology, aesthetic medicine, oncology, nutrition, and cosmetics), the present study describes the main aspects related to its use in cosmetology. The biological effect of HA on the skin level and its potential adverse effects are discussed. Some available cosmetic products containing HA have been identified from the brand portfolio of most known manufacturers and their composition was evaluated. Further, additional biological effects due to the other active ingredients (plant extracts, vitamins, amino acids, peptides, proteins, saccharides, probiotics, etc.) are presented, as well as a description of their possible toxic effects.

Applications and Limitations of Dendrimers in Biomedicine.

Biomedicine represents one of the main study areas for dendrimers, which have proven to be valuable both in diagnostics and therapy, due to their capacity for improving solubility, absorption, bioavailability and targeted distribution. Molecular cytotoxicity constitutes a limiting characteristic, especially for cationic and higher-generation dendrimers. Antineoplastic research of dendrimers has been widely developed, and several types of poly(amidoamine) and poly(propylene imine) dendrimer complexes with doxorubicin, paclitaxel, imatinib, sunitinib, cisplatin, melphalan and methotrexate have shown an improvement in comparison with the drug molecule alone. The anti-inflammatory therapy focused on dendrimer complexes of ibuprofen, indomethacin, piroxicam, ketoprofen and diflunisal. In the context of the development of antibiotic-resistant bacterial strains, dendrimer complexes of fluoroquinolones, macrolides, beta-lactamines and aminoglycosides have shown promising effects. Regarding antiviral therapy, studies have been performed to develop dendrimer conjugates with tenofovir, maraviroc, zidovudine, oseltamivir and acyclovir, among others. Furthermore, cardiovascular therapy has strongly addressed dendrimers. Employed in imaging diagnostics, dendrimers reduce the dosage required to obtain images, thus improving the efficiency of radioisotopes. Dendrimers are macromolecular structures with multiple advantages that can suffer modifications depending on the chemical nature of the drug that has to be transported. The results obtained so far encourage the pursuit of new studies.

An Exploratory Research of 18 Years on the Economic Burden of Diabetes for the Romanian National Health Insurance System.

The prevalence of diabetes mellitus (DM) rises constantly each year worldwide. Because of that, the funds allocated for the DM treatment have increased over time. Regarding the number of DM cases, Romania is among the top ten countries in Europe. Based on the National Diabetes Programme (NDP), antidiabetic drugs and other expenditures (Self-monitoring blood glucose (SMBG) test, HbA1c, insulin pumps/insulin pumps supplies) are free of charge. This programme has undergone many changes in drugs supply, in the last two decades: re-organizing the NDP, authorization of new molecules with high prices (e.g., SGLT-2 inhibitors, etc.) or new devices (e.g., insulin pumps, etc.) The main purpose of this study is to identify and analyse the impact of the DM costs on the Romanian health budget and to highlight the evolution of these costs. A retrospective longitudinal research on the official data regarding the DM costs from 2000 to 2017 was performed. The DM funds (DMF) were adjusted with the inflation rate. In this period, the average share of DMF in the total funds allocated for health programmes was 21.3 ± 3.4%, and DMF average growth rate was 25.4% (r = 0.488, p = 0.047). On the other hand, the DMF increased more than 14 times, in spite of the patients' number having increased only about 2.5 times. Referring to the structure of DMF, the mean value of the antidiabetic drugs cost was of 96,045 ± 67,889 thousand EUR while for other expenditures it was of 11,530 ± 7922 thousand EUR (r = 0.945, p < 0.001). Between 2008 and 2017, the total DMF was 181,252 ± 74,278 thousand EUR/year. Moreover, the average patients' number was 667,384 ± 94,938 (r = 0.73, p = 0.016), and the cost of treatment was 215 ± 36 EUR/patient/year. Even if the cost is rising, the correct and optimal treatment is a main condition for the diabetic patient's health and for the prevention of its complications, which have multiple socio-economic repercussions.