Impact of Maximizing Css/MIC Ratio on Efficacy of Continuous Infusion Meropenem Against Documented Gram-Negative Infections in Critically Ill Patients and Population Pharmacokinetic/Pharmacodynamic Analysis to Support Treatment Optimization

Introduction: optimal treatment of Gram-negative infections in critically ill patients is challenged by changing pathophysiological conditions, reduced antimicrobial susceptibility and limited therapeutic options. The aim of this study was to assess the impact of maximizing Css/MIC ratio on efficacy of continuous infusion (CI) meropenem in treating documented Gram-negative infections in critically ill patients and to perform a population pharmacokinetic/pharmacodynamic analysis to support treatment optimization.Materials and Methods: Classification and regression tree (CART) analysis was used to identify whether a cutoff of steady-state meropenem concentration (Css)-to-minimum inhibitory concentration (MIC) (Css/MIC) ratio correlated with favorable clinical outcome. A non-parametric approach with Pmetrics was used for pharmacokinetic analysis and covariate evaluation. The probability of target attainment (PTA) of the identified Css/MIC ratio was calculated by means of Monte Carlo simulations. Cumulative fraction of response (CFRs) were calculated against common Enterobacterales, P. aeruginosa and A. baumannii as well.Results: a total of 74 patients with 183 meropenem Css were included. CART analysis identified a Css/MIC ratio ≥4.63 as cutoff value significantly associated with favorable clinical outcomes. Multivariate regression analysis confirmed the association [OR (95%CI): 20.440 (2.063–202.522); p < 0.01]. Creatinine clearance (CLCR) was the only covariate associated with meropenem clearance. Monte Carlo simulations showed that, across different classes of renal function, dosages of meropenem ranging between 0.5 and 2 g q6h over 6 h (namely by CI) may grant PTAs of Css/MIC ratios ≥4.63 against susceptible pathogens with an MIC up to the EUCAST clinical breakpoint of 2 mg/L. The CFRs achievable with these dosages were very high (>90%) against Enterobacterales across all the classes of renal function and against P. aeruginosa among patients with CLCR < 30 ml/min/1.73 m2, and quite lower against A. baumannii.Discussion: our findings suggest that Css/MIC ratio ≥4.63 may be considered the pharmacodynamic target useful at maximizing the efficacy of CI meropenem in the treatment of Gram-negative infections in critically ill patients. Dosages ranging between 0.5 g q6h and 2 g q6h by CI may maximize the probability of favorable clinical outcome against meropenem-susceptible Gram-negative pathogens among critically ill patients having different degrees of renal function.

Factors Influencing Self-Care Behavior and Treatment Adherence in Hemodialysis Patients

Low self-care and treatment adherence are found among hemodialysis patients. We aimed to identify the factors influencing self-care behavior and treatment adherence and examine the mediating effect of treatment adherence on self-care behavior. A questionnaire was administered through a social media community from 11 July to 13 August 2021. The data collected from 100 participants were analyzed using the independent t-test, one-way analysis of variance, Pearson’s correlation, multiple linear regression analysis, and hierarchical multiple regression analysis. The mean self-care behavior and treatment adherence scores were 3.52 ± 0.57 and 4.01 ± 0.48, respectively. The mean age and hemodialysis duration were 51.70 ± 9.40 and 7.57 ± 7.21 years, respectively. The common primary cause of end-stage renal disease was glomerulonephritis (n = 39, 39%). Self-care behavior varied with education, frequency of self-care behavior education, and social support and was positively correlated with treatment adherence and social support. Treatment adherence was positively correlated with social support. Treatment adherence, social support, and health status were influenced self-care behavior (54.5%. Self-care behavior and frequency of self-care behavior education influenced treatment adherence (61.3%). Treatment adherence partially mediated the relationship between social support and self-care behavior. Intervention strategies that increase both social support and treatment adherence can promote self-care behavior.

The Epigenetic Regulator Jumonji Domain-Containing Protein 6 (JMJD6) Is Highly Expressed but Not Prognostic in IDH-Wildtype Glioblastoma Patients

Patients with IDH-wildtype glioblastoma (GBM) generally have a poor prognosis. However, there is an increasing need of novel robust biomarkers in the daily clinico-pathological setting to identify and support treatment in patients who become long-time survivors. Jumonji domain-containing protein 6 (JMJD6) is involved in epigenetic regulation of demethylation of histones and has been associated with GBM aggressiveness. We investigated the expression and prognostic potential of JMJD6 tumor fraction score in 184 IDH-wildtype GBMs. Whole-slides were double-stained with an antibody against JMJD6 and an exclusion-cocktail consisting of 4 antibodies (CD31, SMA, CD45, and Iba-1), enabling evaluation of tumor cells only. Stainings were quantified with a combined software- and scoring-based approach. For comparison, IDH-mutated WHO grade II, III and IV astrocytic gliomas were also stained, and the JMJD6 tumor fraction score increased with increasing WHO grade, although not significantly. In multivariate analysis including age, gender, performance status and post-surgical treatment high JMJD6 tumor fraction score was associated with longer overall survival in IDH-wildtype GBMs (p = 0.03), but the effect disappeared when MGMT promoter status was included (p = 0.34). We conclude that JMJD6 is highly expressed in IDH-wildtype GBM but it has no independent prognostic value.

Protein Biomarkers in Glaucoma: A Review

Glaucoma is a multifactorial disease. Early diagnosis of this disease can support treatment and reduce the effects of pathophysiological processes. A significant problem in the diagnosis of glaucoma is limited access to the tested material. Therefore, intensive research is underway to develop biomarkers for fast, noninvasive, and reliable testing. Biomarkers indicated in the formation of glaucoma include chemical compounds from different chemical groups, such as proteins, sugars, and lipids. This review summarizes our knowledge about protein and/or their protein-like derived biomarkers used for glaucoma diagnosis since 2000. The described possibilities resulting from a biomarker search may contribute to identifying a group of compounds strongly correlated with glaucoma development. Such a find would be of great importance in the diagnosis and treatment of this disorder, as current screening techniques have low sensitivity and are unable to diagnose early primary open-angle glaucoma.

Strategies Adopted by Addiction Facilities during the Coronavirus Pandemic to Support Treatment for Individuals in Recovery or Struggling with a Substance Use Disorder: A Scoping Review

This review aimed to identify and synthesize strategies and actions adopted by addiction facilities to support and maintain treatment during the coronavirus disease 2019 (COVID-19) pandemic. A scoping review was conducted using the following information sources: Virtual Health Library, SCOPUS, Web of Science, PubMed, CINAHL, and Latin American and Caribbean Health Science Literature. From a total of 971 articles, 28 studies were included. The strategies to maintain the care offer were telehealth/telemedicine, counselling/screening, 24-h telephone, webinars, conducting group therapy and support among users, adaptation for electronic health records, increased methadone/naloxone dispensing, restriction in the number of medication dispensing/day, and electronic prescription and home delivery medications. These strategies can be used to support health professionals in addressing the impact of the pandemic on the treatment of those in recovery or struggling with a substance use disorder when in-person treatment is not possible.