Effect of chlorhexidine digluconate on antimicrobial activity,cell viability and physicochemical properties of three endodontic sealers

ObjectiveAssess the biological and physicochemical properties of AH Plus, BioRoot RCS and Pulp Canal Sealer (PCS) leachates with and without chlorhexidine (CHX).MethodsThe sealers were studied in no contact and 1-minute contact with CHX. For biological properties (antibacterial activity and cytotoxicity), leachates were formed in saline of freshly mixed, 1-, 7- and 28 days set sealers. The antibacterial properties of sealer leachates were investigated for planktonic and biofilm growth of E. faecalis, S. mutans, S.epidermidis and S.aureus. The 3-(4,5 dimethylthiazolyl-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to evaluate murine fibroblast cell viability after exposure to the leachates. The physical properties (water uptake, sorption, solubility, porosity, surface characteristics) of sealers and the pH of the immersion liquid (saline or distilled water) were also assessed over a 28-days period.ResultsCHX improved the antibacterial properties of the sealer leachates and reduced cell viability for all sealer leachates, except for freshly mixed PCS. BioRoot RCS leachates presented the highest antibacterial properties and cell viability with and without CHX contact. PCS was the material most affected by CHX in terms of physical properties, whereas for AH Plus, solubility was increased. CHX did not affect the physical properties of BioRoot RCS, except for solubility that was decreased. CHX contact did not change sealers’ alkalinity in distilled water whereas it increased it for AH Plus and BioRoot RCS in saline.SignificanceCHX improved the antibacterial efficacy of sealer leachates and either compromised or did not affect cell viability. CHX affected to various extent sealers’ physicochemical properties.     

Effect of antiseptic bathing with chlorhexidine or octenidine on central line–associated bloodstream infections in intensive care patients: a cluster-randomized controlled trial

ObjectivesOur study aimed to compare the effect of daily bathing with chlorhexidine, octenidine, or water and soap (routine care = control) on central line (CL)–associated bloodstream infection (CLABSI) rates in intensive care units (ICUs).MethodsA multicentre cluster-randomized controlled trial was done with a 12-month intervention period from February 1, 2017 to January 31, 2018 (octenidine and routine care group) or from June 1, 2017 to May 31, 2018 (chlorhexidine group). Wards were randomly assigned to one of two decolonization regimes or routine care (control). Intervention included daily bathing with 2% chlorhexidine-impregnated cloths or 0.08% octenidine wash mitts for 12 months, whereas the control group used water and soap (routine care). The primary outcome was incidence density of CLABSI per 1000 CL days. Poisson regression and generalized estimating equation models were applied.ResultsA total of 72 ICUs with 76 815 patients (22 897 patients in the chlorhexidine group, 25 127 in the octenidine group, and 28 791 in the routine care group) were included. Incidence densities were 0.90 CLABSI per 1000 CL days (95% CI 0.67–1.19) in the chlorhexidine group, 1.47 (95% CI 1.17–1.81) in the octenidine group, and 1.17 (95% CI 0.93–1.45) in the routine care group. Adjusted incidence rate ratios of CLABSI were 0.69 (95% CI 0.37–1.22, p = 0.28) in the chlorhexidine group and 1.22 (95% CI 0.54–2.75, p = 0.65) in the octenidine group (compared with routine care).DiscussionAntiseptic bathing with 2% chlorhexidine-impregnated cloths and 0.08% octenidine wash mitts lacks a significant preventive effect on CLABSI rates in ICUs. However, our trial has a high likelihood of being underpowered because CLABSI rates in the routine care group were approximately 40% lower than initially assumed.     

Treatment of Patients with Metastatic Hormone-Sensitive Prostate Cancer: A Systematic Review of Economic Evaluations

The management of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has been significantly modified by the availability of innovative but expensive treatments, increasing the economic burden of prostate cancer. Here, we aimed to systematically identify and review published economic evaluations (EEs) related to the treatment of mHSPC and assess their quality. A systematic search was performed of the PubMed and Cochrane databases. Three reviewers independently selected EEs by defined inclusion and exclusion criteria. They extracted all data from each EE (general information, study population, data about the EE, interventions and comparators, and outcomes). They also assessed the quality of the selected EEs according to Drummond's checklist. Fourteen EEs published between 2016 and 2021 were eligible for the systematic review. The EEs found ADT + docetaxel to be the most cost-effective of all available treatments as a first-line strategy for mHSPC (abiraterone acetate plus prednisone, enzalutamide, and apalutamide). Five EEs showed that a simple price reduction of abiraterone acetate of 50% to 75% could change the results to render this treatment also cost-effective relative to that with docetaxel. Twelve EEs were of high quality, with a Drummond score ≥ 7. Analysis of the 14 EEs identified by our systematic review, amongst which 78.6% met high quality standards, showed that ADT + docetaxel tends to be the most cost-effective alternative for mHSPC. These results were assessed by sensitivity analysis. The data provided by this systematic review help to provide a better understanding of these treatments and the better use of healthcare resources.     

Impact of Addition of Metformin to Abiraterone in Metastatic Castration-Resistant Prostate Cancer Patients With Disease Progressing While Receiving Abiraterone Treatment (MetAb-Pro): Phase 2 Pilot Study

Background

There is evidence linking metformin to improved prostate cancer–related outcomes.

Nobiletin and its derivatives overcome multidrug resistance (MDR) in cancer: total synthesis and discovery of potent MDR reversal agents

Our recent studies demonstrated that the natural product nobiletin (NOB) served as a promising multidrug resistance (MDR) reversal agent and improved the effectiveness of cancer chemotherapy in vitro. However, low aqueous solubility and difficulty in total synthesis limited its application as a therapeutic agent. To tackle these challenges, NOB was synthesized in a high yield by a concise route of six steps and fourteen derivatives were synthesized with remarkable solubility and efficacy. All the compounds showed improved sensitivity to paclitaxel (PTX) in P-glycoprotein (P-gp) overexpressing MDR cancer cells. Among them, compound 29d exhibited water solubility 280-fold higher than NOB. A drug-resistance A549/T xenograft model showed that 29d, at a dose of 50 mg/kg co-administered with PTX (15 mg/kg), inhibited tumor growth more effective than NOB and remarkably increased PTX concentration in the tumors via P-gp inhibition. Moreover, Western blot experiments revealed that 29d inhibited expression of NRF2, phosphorylated ERK and AKT in MDR cancer cells, thus implying 29d of multiple mechanisms to reverse MDR in lung cancer.     

Factors associated with provision of depot medroxyprogesterone acetate to adolescents by US health care providers

ObjectiveIdentify factors associated with healthcare providers' frequency of depot medroxyprogesterone acetate (DMPA) provision to adolescents.Study designWe analyzed data from surveys mailed to a nationally representative sample of public-sector providers and office-based physicians (n=1984). We estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of factors associated with frequent DMPA provision to adolescents in the past year.ResultsAlthough most providers (>95%) considered DMPA safe for adolescents, fewer reported frequent provision (89% of public-sector providers; 64% of office-based physicians). Among public-sector providers, factors associated with lower odds of frequent provision included working in settings without Title X funding (aOR 0.44, 95% CI 0.30–0.64), reporting primary care as their primary clinical focus versus reproductive or adolescent health (aOR 0.42, 95% CI 0.28–0.61), and providing fewer patients with family planning services. Among office-based physicians, factors associated with lower odds of frequent provision included specializing in obstetrics/gynecology (aOR 0.50, 95% CI 0.27–0.91) and family medicine (aOR 0.21, 95% CI 0.09–0.47) versus adolescent medicine, completing training ≥15 versus <5 years ago (aOR 0.27, 95% CI 0.09–0.83), and reporting that 0–24% of patients pay with Medicaid or other government healthcare assistance versus ≥50% (aOR 0.23, 95% CI 0.09–0.61). The reason most commonly reported by providers for infrequent DMPA provision was patient preference for another method.ConclusionsWhile most providers reported frequently providing DMPA to adolescents, training on evidence-based recommendations for contraception, focused on subgroups of providers with lower odds of frequent DMPA provision, may increase adolescents' access to contraception.ImplicationsAlthough >95% of providers considered depot medroxyprogesterone (DMPA) a safe contraceptive for adolescents, only 89% of public-sector providers and 64% of office-based physicians reported frequently providing DMPA to adolescents. Provider training on evidence-based recommendations for contraception counseling and provision may increase adolescents' access to DMPA and all methods of contraception.     

Continuation of self-injected versus provider-administered contraception in Senegal: a nonrandomized,prospective cohort study

Objectives

The primary objective of this study was to compare the 12-month continuation rate for women who self-injected subcutaneous depot-medroxyprogesterone acetate (DMPA-SC) with that for women receiving intramuscular depot-medroxyprogesterone acetate (DMPA-IM) from a provider. This research contributes to the broader goal of identifying solutions to support women to use contraception for their full desired duration.

Photocrosslinkable methacrylated gelatin hydrogel as a cell-friendly injectable delivery system for chlorhexidine in regenerative endodontics

ObjectivesThis work sought to formulate photocrosslinkable chlorhexidine (CHX)-laden methacrylated gelatin (CHX/GelMA) hydrogels with broad spectrum of action against endodontic pathogens as a clinically viable cell-friendly disinfection therapy prior to regenerative endodontics procedures.MethodsCHX/GelMA hydrogel formulations were successfully synthesized using CHX concentrations between 0.12 % and 5 % w/v. Hydrogel microstructure was evaluated by scanning electron microscopy (SEM). Swelling and enzymatic degradation were assessed to determine microenvironmental effects. Compression test was performed to investigate the influence of CHX incorporation on the hydrogels’ biomechanics. The antimicrobial and anti-biofilm potential of the formulated hydrogels were assessed using agar diffusion assays and a microcosms biofilm model, respectively. The cytocompatibility was evaluated by exposing stem cells from human exfoliated deciduous teeth (SHEDs) to hydrogel extracts (i.e., leachable byproducts obtained from overtime hydrogel incubation in phosphate buffer saline). The data were analyzed using One- and Two-way ANOVA and Tukey’s test (α = 0.05).ResultsCHX/GelMA hydrogels were effectively prepared. NMR spectroscopy confirmed the incorporation of CHX into GelMA. The addition of CHX did not change the micromorphology (pore size) nor the swelling profile (p > 0.05). CHX incorporation reduced the degradation rate of the hydrogels (p < 0.001); whereas, it contributed to increased compressive modulus (p < 0.05). Regarding the antimicrobial properties, the incorporation of CHX showed a statistically significant decrease in the number of bacteria colonies at 0.12 % and 0.5 % concentration (p < 0.001) and completely inhibited the growth of biofilm at concentration levels 1 %, 2 %, and 5 %. Meanwhile, the addition of CHX, regardless of the concentration, did not lead to cell toxicity, as cell viability values were above 70 %.SignificanceThe addition of CHX into GelMA showed significant antimicrobial action against the pathogens tested, even at low concentrations, with the potential to be used as a cell-friendly injectable drug delivery system for root canal disinfection prior to regenerative endodontics.     

纤维支气管镜灌洗联合常规药物治疗变应性支气管肺曲霉病患者的效果

目的:观察纤维支气管镜灌洗联合常规药物治疗变应性支气管肺曲霉病(ABPA)患者的效果。方法:选取94例ABPA患者作为研究对象,按照随机数字表法分为观察组和对照组各47例。对照组采取常规药物治疗,观察组在对照组的基础上联合纤维支气管镜灌洗治疗。比较两组临床疗效和不良反应发生率。结果:观察组治疗总有效率为89.36%(42/47),明显高于对照组的72.34%(34/47),差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:纤维支气管镜灌洗联合常规药物治疗ABPA患者的效果优于单纯常规药物治疗,且安全性好。     

术前给予醋酸亮丙瑞林对子宫肌瘤腹腔镜剔除术手术效果研究

目的:研究术前给予醋酸亮丙瑞林对子宫肌瘤腹腔镜剔除术手术效果影响。方法:研究对象选取我院2012年10月到2017年10月间行子宫肌瘤腹腔镜剔除术患者120例，采用随机数字法将其分为对照组和观察组，每组各60例。对照组患者仅行子宫肌瘤腹腔镜剔除术治疗，观察组患者子宫肌瘤腹腔镜剔除术前，皮下注射醋酸亮丙瑞林预处理。比较两组患者的手术和术后效果指标，同时比较观察组患者治疗前后的血清黄体生成素、卵泡刺激素、雌二醇水平和月经量、子宫体积、肌瘤体积等。结果:观察组患者的术中出血量、盆腔引流量、首次下床活动时间、住院时间均明显低于对照组(P<0.01)，观察组患者治疗后的血清黄体生成素、卵泡刺激素、雌二醇水平均明显低于治疗前(P<0.01)，月经量、子宫体积、肌瘤体积均明显低于治疗前(P<0.01)。结论:子宫肌瘤腹腔镜剔除术术前给予醋酸亮丙瑞林治疗，能够有效调节患者激素水平和月经量，缩小子宫肌瘤体积，提高术前准备质量，有助于患者手术开展和术后恢复，值得在临床推广。