The effects of pharmaceutical interventions on potentially inappropriate medications in older patients: a systematic review and meta-analysis.

Introduction: Potentially inappropriate medications (PIMs) is a particular concern in older patients and is associated with negative health outcomes. As various interventions have been developed to manage it, we performed a systematic review and meta-analysis to evaluate the effect of pharmaceutical interventions on outcomes of PIMs in older patients. Methods: Meta-analysis of eligible randomized controlled trials (RCTs) was conducted to report the outcomes of pharmaceutical interventions in older patients searching from the databases of Cochrane Library, PubMed, Embase, Web of Science, Clinicaltrials.gov, SinoMed and Chinese Clinical Trial Registry (ChiCTR). The PRISMA guidelines were followed and the protocol was registered in PROSPERO (CRD42019134754). Cochrane bias risk assessment tool and the modified Jadad scale were used to assess the risk bias. RevMan software was used for data processing, analysis and graphical plotting. Results: Sixty-five thousand, nine hundred seventy-one patients in 14 RCTs were included. Of the primary outcomes, pharmaceutical interventions could significantly reduce the incidence of PIMs in older patients (OR = 0.51, 95% CI: 0.42, 0.62; p < 0.001), and the number of PIMs per person (MD = -0.41, 95%CI: -0.51, -0.31; p < 0.001), accompanying by a low heterogeneity. Subgroup analysis showed that the application of computer-based clinical decision support for pharmacological interventions could remarkably decrease the incidence of PIMs and two assessment tools were more effective. Of the secondary outcomes, the meta-analysis showed that pharmacological interventions could reduce the number of drugs used per person (MD = -0.94, 95%CI: -1.51, -0.36; p = 0.001) and 30-day readmission rate (OR = 0.58, 95%CI: 0.36, 0.92; p = 0.02), accompanying by a low heterogeneity. However, the pharmaceutical interventions demonstrated no significant improvement on all-cause mortality and the number of falls. Conclusion: Our findings supported the efficacy of pharmaceutical interventions to optimize the use and management of drugs in older patients. Systematic review registration: https://clinicaltrials.gov/, CRD42019134754.

New perspectives on the induction and acceleration of immune-associated thrombosis by PF4 and VWF.

Platelet factor 4 (PF4), also known as chemokine (C-X-C motif) ligand 4 (CXCL4), is a specific protein synthesized from platelet α particles. The combination of PF4 and heparin to form antigenic complexes is an important mechanism in the pathogenesis of heparin-induced thrombocytopenia (HIT), but vaccine-induced immune thrombotic thrombocytopenia (VITT) related to the COVID-19 vaccine makes PF4 a research hotspot again. Similar to HIT, vaccines, bacteria, and other non-heparin exposure, PF4 can interact with negatively charged polyanions to form immune complexes and participate in thrombosis. These anions include cell surface mucopolysaccharides, platelet polyphosphates, DNA from endothelial cells, or von Willebrand factor (VWF). Among them, PF4-VWF, as a new immune complex, may induce and promote the formation of immune-associated thrombosis and is expected to become a new target and therapeutic direction. For both HIT and VITT, there is no effective and targeted treatment except discontinuation of suspected drugs. The research and development of targeted drugs based on the mechanism of action have become an unmet clinical need. Here, this study systematically reviewed the characteristics and pathophysiological mechanisms of PF4 and VWF, elaborated the potential mechanism of action of PF4-VWF complex in immune-associated thrombosis, summarized the current status of new drug research and development for PF4 and VWF, and discussed the possibility of this complex as a potential biomarker for early immune-associated thrombosis events. Moreover, the key points of basic research and clinical evaluation are put forward in the study.

Ferroptosis of Endothelial Cells in Vascular Diseases.

Endothelial cells (ECs) line the inner surface of blood vessels and play a substantial role in vascular biology. Endothelial dysfunction (ED) is strongly correlated with the initiation and progression of many vascular diseases. Regulated cell death, such as ferroptosis, is one of the multiple mechanisms that lead to ED. Ferroptosis is an iron-dependent programmed cell death associated with various vascular diseases, such as cardiovascular, cerebrovascular, and pulmonary vascular diseases. This review summarized ferroptosis of ECs in vascular diseases and discussed potential therapeutic strategies for treating ferroptosis of ECs. In addition to lipid peroxidation inhibitors and iron chelators, a growing body of evidence showed that clinical drugs, natural products, and intervention of noncoding RNAs may also inhibit ferroptosis of ECs.

[Experimental study of recovery force of surface-modified TiNi memory alloy rod].

The recovery force of Ti-Nb coated and uncoated TiNi shape memory alloy rods was investigated. The rods were 6.0 mm, 6.5 mm and 7.0 mm in diameter respectively. The mean transition temperature was 33.0 degrees C. The rods were stored at -18 degrees C and pre-bent with a three-point bending fixture, the span was 20. 0 centimeters and the deflections were 5.0 mm, 10.0 mm, 15.0 mm and 20.0 mm, respectively. The rods were then heated in a constant temperature saline solution chamber. The experimental temperature was 37.0 C and 50.0 C respectively. The recovery force was measured in a constant displacement mode on biomaterial test machine. The results showed that the recovery force of the memory alloy rod increased with increasing recovery temperature, rod diameter and deformation of both Ti-Nb coated and uncoated surface. The recovery force of Ti-Nb coated rods of 6.0 and 6.5 millimeter in diameter was lower than the uncoated rods in the same diameter. However, the recovery force of 7.0-mm-diameter rods showed no significant difference between coated and uncoated surface.