A Nonparametric Pharmacokinetic Approach to Determine the Optimal Dosing Regimen for 30-Minute and 3-Hour Meropenem Infusions in Critically Ill Patients.

BACKGROUND: Pharmacokinetics of meropenem differ widely in the critically ill population. It is imperative to maintain meropenem concentrations above the inhibitory concentrations for most of the interdose interval. A population pharmacokinetic/pharmacodynamic model was developed to determine the probability of target attainment for 3-hour and 30-minute infusion regimens in this population. METHODS: This study was performed in an intensive care setting among adult patients who were initiated on meropenem at a dose of 1000 mg. Multiple blood specimens were collected at predetermined time points during the interdose period, and meropenem concentrations were measured using high performance liquid chromatography. Using Pmetrics, a pharmacokinetic/pharmacodynamic model was developed and validated. Monte Carlo simulation was performed, and probability of target attainment (100% T > minimum inhibitory concentration (MIC), with a probability >0.9) for doubling MICs was determined for different regimens of meropenem. RESULTS: A 2-compartment multiplicative gamma error model best described the population parameters from 34 patients. The pharmacokinetic parameters used in the final model were Ke (elimination rate constant from the central compartment), Vc (volume of distribution of central compartment), KCP and KPC (intercompartmental rate constants), and IC2 (the fitted amount of meropenem in the peripheral compartment). Inclusion of creatinine clearance (CLcreat) and body weight as covariates improved the model prediction (Ke = Ke0 × (Equation is included in full-text article.), Vc = Vc0 × Weight). The Ke and Vc [geometric mean (range)] of the individuals were 0.54 (0.01-2.61)/h and 9.36 (4.35-21.62) L, respectively. The probability of attaining the target, T > MIC of 100%, was higher for 3-hour infusion regimens compared with 30-minute infusion regimens for all ranges of CLcreat. CONCLUSIONS: This study emphasizes that extended regimens of meropenem are preferable for treating infections caused by bacteria with higher MICs. The nonparametric analysis using body weight and CLcreat as covariate adequately predicted the pharmacokinetics of meropenem in critically ill patients with a wide range of renal function.

The moderating effects of perceived social worth and organizational virtuousness on the relationship between emotional labor, precarious work, and organizational commitment among ASHA workers in India.

Accredited Social Health Activists (ASHAs) in India are the subjects of this study, which explores the complex relationships between emotional labor (EL) and unstable work environments and how these relationships affect organizational commitment (OC). The study also looked at how organizational virtuousness (OV) and perceived social value mediated the relationship between precarious work (PW), EL, and OC. This study included a total sample size of N = 467 ASHA personnel from a variety of healthcare settings. Hierarchical regression analysis was used to look at the moderating effects using the Hayes Process Macro. The findings suggest that there are noteworthy negative associations between EL, PW, and the OC of ASHA workers. Nevertheless, OV and perceived social worth (PSW) emerged as significant moderators. More precisely, elevated levels of PSW and OV mitigated the adverse effects of PW and EL on the OC of ASHA workers.

Dentinal defects before and after rotary root canal instrumentation with three different obturation techniques and two obturating materials.

AIM: To evaluate the role of rotary root canal instrumentation followed by obturation with three different techniques and two different materials on the incidence of dentinal defects. MATERIALS AND METHODS: One hundred and sixty mandibular premolars were divided into eight groups (n = 20). Group I was left untreated and served as control. The other seven groups were prepared with profile rotary instruments till #40.06 taper. After preparation, group II was left unfilled, groups III, IV, and V were obturated with Gutta-percha and AH Plus sealer using passive technique, lateral compaction and warm vertical compaction, respectively. Groups VI, VII, and VIII were obturated with Resilon and Realseal sealer using passive technique, lateral compaction, and warm vertical compaction, respectively. Roots were then sectioned at 3, 6, and 9 mm from the apex and inspected under a stereomicroscope (50×) for dentinal defects. Chi-square test was performed to compare the incidence of dentinal defects between the groups (P < 0.05). RESULTS: The unprepared control group had no dentinal defects. The instrumentation group (group II) and the obturation group (groups III-VIII) showed significantly more defects than the uninstrumented control group (group I) (P < 0.001). There was no significant difference between the root canal obturating techniques (group III-VIII) when compared with the instrumentation group (group II). On inter group comparison among the obturation groups the number of defects after lateral compaction with Gutta-percha (group IV) was significantly larger than passive Gutta-percha obturation (group III) (P < 0.05). CONCLUSIONS: The results suggest that root canal instrumentation significantly influenced the incidence of dentinal defects or fracture. Dentinal defects were more significantly attributed to the role of root canal instrumentation rather than the type of obturation technique or material. Lateral compaction with Gutta-percha significantly produces more defects than passive Gutta-percha obturation.