OBJECTIVES: This review investigates the effects of TDM-guided piperacillin dosing on pharmacokinetic target attainment and clinical outcomes in CRRT patients, analyses correlations with clinical outcomes, provides optimal dosing strategies for piperacillin and identifies future research areas.
METHODS: A systematic search of PubMed, Scopus and Web of Science was conducted until December 2023, identifying studies on piperacillin pharmacokinetics and clinical outcomes in adult CRRT patients. Data on study characteristics, piperacillin exposures, TDM use, target attainment rates, mortality and length of stay were extracted. The risk of bias was assessed using the Newcastle-Ottawa Scale.
RESULTS: Eleven observational studies were included. High pharmacokinetic variability was evident, with piperacillin target non-attainment in up to 74% of cases without TDM. Two studies with routine TDM showed increased target attainment rates of 80%-100%. Mortality ranged from 17% to 56%, with supratherapeutic concentrations (≥100 mg/L) associated with higher mortality. The impact of optimized piperacillin exposures on outcomes was inconclusive. Most studies demonstrated a low risk of bias.
CONCLUSIONS: TDM-guided piperacillin dosing in CRRT patients improved target attainment rates (≥80%). Mortality rates ranged from 17% to 56%, with inconsistent correlations between drug exposures and survival. Supratherapeutic concentrations were linked to higher mortality. Standardized TDM protocols are needed. Future research should establish clear exposure-response relationships and the impact of TDM on clinical outcomes.
METHODS: Patients were recruited from 4 hospitals in Malaysia. Clinical data were recorded, and blood samples were taken for pharmacokinetic and genetic studies. Population pharmacokinetic parameters were estimated by nonlinear mixed-effects modeling in Monolix. Age, weight, baseline immunoglobulin G concentration, ethnicity, sex, genotype, disease type, and comorbidity were investigated as potential covariates. Models were evaluated using the difference in objective function value, goodness-of-fit plots, visual predictive checks, and bootstrap analysis.
FINDINGS: A total of 292 blood samples were analyzed from 79 patients. The IVIG concentrations were best described by a 2-compartment model with linear elimination. Weight was found to be an important covariate for volume of distribution in the central compartment (Vc), volume of distribution in the peripheral compartment (Vp), and clearance in the central compartment, whereas disease type was found to be an important covariate for Vp. Goodness-of-fit plots indicated that the model fit the data adequately. Genetic polymorphism of the FCGRT gene encoding the neonatal Fc receptor did not affect the pharmacokinetic properties of IVIG.
IMPLICATIONS: This study supports the use of dosage based on weight as per current practice. The study findings highlight that Vp is significantly influenced by the type of disease being treated with IVIG. This relationship suggests that different disease types, particularly inflammatory and autoimmune conditions, may alter tissue permeability and fluid distribution due to varying degrees of inflammation. Increased inflammation can lead to enhanced permeability and retention of IVIG in peripheral tissues, reflecting higher Vp values.
AREAS COVERED: In this review, we delve into utilization of nanoparticular platforms to enhance the delivery of repurposed drugs for treatment of AD. Firstly, the review begins with the elucidation of intricate pathology underpinning AD, subsequently followed by rationale behind drug repurposing in AD. Covered are explorations of nanoparticle-based repurposing of drugs in AD, highlighting their clinical implication. Further, the associated challenges and probable future perspective are delineated.
EXPERT OPINION: The article has highlighted that extensive research has been carried out on the delivery of repurposed nanomedicines against AD. However, there is a need for advanced and long-term research including clinical trials required to shed light upon their safety and toxicity profile. Furthermore, their scalability in pharmaceutical set-up should also be validated.
METHODS: This umbrella review was conducted following the Joanna Briggs Institute (JBI) methodology to assess the efficacy and safety of stem cell therapy for treating various types of fistulas. A comprehensive search was performed across multiple electronic databases including PubMed, Embase, Cochrane Register, and Web of Science up to 5 May 2024. Systematic reviews focusing on stem cell therapy for fistulas were included, with data extracted on study design, stem cell types, administration methods, and outcomes. The quality of the reviews was assessed using the AMSTAR 2 tool, and meta-analyses were conducted using R software version 4.3.
RESULTS: Nineteen systematic reviews were included in our umbrella review. The stem cell therapy demonstrated by significant improvements in clinical remission rates, with a relative risk (RR) of 1.299 (95% CI: 1.192-1.420). Stem cell therapy enhanced fistula closure rates, both short-term (RR=1.481; 95% CI: 1.036-2.116) and long-term (RR=1.422; 95% CI: 1.091-1.854). The safety analysis revealed no significant increase in the risk of adverse events with stem cell therapy, showing a pooled RR of 0.972 (95% CI: 0.739-1.278) for general adverse events and 1.136 (95% CI: 0.821-1.572) for serious adverse events, both of which indicate a safety profile comparable to control treatments. Re-epithelialization rates also improved (RR=1.44; 95% CI: 1.322-1.572).
CONCLUSION: Stem cell therapy shows promise as an effective and safe treatment for fistulas, particularly in inducing remission and promoting closure of complex fistulas. The findings advocate for further high-quality research to confirm these benefits and potentially incorporate stem cell therapy into standard clinical practice for fistula management. Future studies should focus on long-term outcomes and refining stem cell treatment protocols to optimize therapeutic efficacy.
METHODS: Two types of phantoms were developed: phantoms A and B. Phantom A was made from a base material consisting of polyvinyl chloride-plastisol with the addition of glycerol, whereas phantom B consisted of polyvinyl chloride-plastisol with the addition of graphite. Each phantom had a stiff and soft lesion shaped like a sphere, with a diameter of 1.4 cm. The phantoms were cuboids with dimensions of 10 × 10 cm2 and a thickness of 5 cm. A series of phantom evaluations was performed, consisting of density, elasticity, acoustic properties, B-mode ultrasound images, and strain ratio.
RESULTS: The characterisation results show that background A closely resembles fibroglandular tissue in terms of density and acoustic properties (<5% variation); background B only resembles fibroglandular tissue in terms of density (-1.8% variation). In terms of elasticity, both backgrounds were close to the minimum value of fibroglandular tissue elasticity. The soft lesion on the phantom had a slightly lower density and elasticity than the carcinoma, whereas its acoustic properties (speed of sound and attenuation coefficient) were slightly higher than those of the reference carcinoma. Both phantoms were consistent with the literature in terms of strain ratio, geometric accuracy, lesion detection, and mean pixel value and showed good potential stability over one year.
CONCLUSION: This study successfully described the fabrication and evaluation sequence of a phantom equivalent to breast fibroglandular tissue and its evaluation via ultrasound imaging.
IMPLICATIONS FOR PRACTICE: This study offers proprietary information essential for the fabrication of phantoms that can be used for quality assurance and control in ultrasound imaging.