Digital steganography is becoming a common tool for protecting sensitive communications in various applications such as crime/terrorism prevention whereby law enforcing personals need to remotely ...compare facial images captured at the scene of crime with faces databases of known criminals/suspects; exchanging military maps or surveillance video in hostile environment/situations; privacy preserving in the healthcare systems when storing or exchanging patient’s medical images/records; and prevent bank customers’ accounts/records from being accessed illegally by unauthorized users. Existing digital steganography schemes for embedding secret images in cover image files tend not to exploit various redundancies in the secret image bit-stream to deal with the various conflicting requirements on embedding capacity, stego-image quality, and undetectibility. This paper is concerned with the development of innovative image procedures and data hiding schemes that exploit, as well as increase, similarities between secret image bit-stream and the cover image LSB plane. This will be achieved in two novel steps involving manipulating both the secret and the cover images, prior to embedding, to achieve higher 0:1 ratio in both the secret image bit-stream and the cover image LSB plane. The above two steps strategy has been exploited to use a bit-plane(s) mapping technique, instead of bit-plane(s) replacement to make each cover pixel usable for secret embedding. This paper will demonstrate that this strategy produces stego-images that have minimal distortion, high embedding efficiency, reasonably good stego-image quality and robustness against 3 well-known targeted steganalysis tools.
Well logs were utilized to investigate petrophysical properties of the Khurmala Formation’s surface outcrops in Shaqlawa Subdistrict and Tawke Oilfield, e.g., lithology, shale volume, porosity, and ...fracture. The thickness of the formation is about 15 m in the Shaqlawa section and 42 m in the Tawke Oilfield. Porosity logs were used to estimate porosity; where the porosity values reached a maximum of 52% from the sonic log, 48% from the density log, and 35% from the neutron porosity log. The reservoir quality of the Khurmala Formation, as determined through the analysis of thin sections, which were obtained from outcrop samples, is deemed to be of low quality. The determined shale volume within the examined interval exhibits a moderate level of clay constituents, with the highest gamma-ray measurement indicating a shale content of 29% at some locations within the reservoir. This integrated method using various conventional well logs suggests a great probability of petrophysical properties in the Khurmala Formation to be considered as the reservoir.
Abstract
Background
Early and appropriate antibiotic dosing is associated with improved clinical outcomes in critically ill patients, yet target attainment remains a challenge. Traditional antibiotic ...dosing is not suitable in critically ill patients, since these patients undergo physiological alterations that strongly affect antibiotic exposure. For beta-lactam antibiotics, the unbound plasma concentrations above at least one to four times the minimal inhibitory concentration (MIC) for 100% of the dosing interval (100%ƒT > 1–4×MIC) have been proposed as pharmacodynamic targets (PDTs) to maximize bacteriological and clinical responses. The objectives of this study are to describe the PDT attainment in critically ill patients and to identify risk factors for target non-attainment.
Methods
This prospective observational study was performed in two ICUs in the Netherlands. We enrolled adult patients treated with the following beta-lactam antibiotics: amoxicillin (with or without clavulanic acid), cefotaxime, ceftazidime, ceftriaxone, cefuroxime, and meropenem. Based on five samples within a dosing interval at day 2 of therapy, the time unbound concentrations above the epidemiological cut-off (ƒT > MIC
ECOFF
and ƒT > 4×MIC
ECOFF
) were determined. Secondary endpoints were estimated multivariate binomial and binary logistic regression models, for examining the association of PDT attainment with patient characteristics and clinical outcomes.
Results
A total of 147 patients were included, of whom 63.3% achieved PDT of 100%ƒT > MIC
ECOFF
and 36.7% achieved 100%ƒT > 4×MIC
ECOFF
. Regression analysis identified male gender, estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m
2
, and high body mass index (BMI) as risk factors for target non-attainment. Use of continuous renal replacement therapy (CRRT) and high serum urea significantly increased the probability of target attainment. In addition, we found a significant association between the 100%ƒT > MIC
ECOFF
target attainment and ICU length of stay (LOS), but no significant correlation was found for the 30-day survival.
Conclusions
Traditional beta-lactam dosing results in low target attainment in the majority of critically ill patients. Male gender, high BMI, and high eGFR were significant risk factors for target non-attainment. These predictors, together with therapeutic drug monitoring, may help ICU clinicians in optimizing beta-lactam dosing in critically ill patients.
Trial registration
Netherlands Trial Registry (EXPAT trial),
NTR 5632
. Registered on 7 December 2015.
Recent studies demonstrated that failure of achieving pharmacodynamic targets of commonly used antibiotics is common in critically ill patients. Therapeutic drug monitoring (TDM) can contribute to ...optimize the exposure of beta-lactams and ciprofloxacin. While evidence for TDM of these antibiotics is growing, translation into clinical implementation remains limited. Therefore, perceived barriers and facilitators are important for implementing TDM in this population. The primary aim of this study was to identify healthcare professionals' barriers and facilitators for the implementation of TDM of beta-lactams and ciprofloxacin in Dutch intensive care units (ICU). We conducted a nationwide cross-sectional online survey among healthcare professionals (HCPs) involved in antibiotic treatment of ICU patients. An adapted version of the Measurement Instrument for Determinants of Innovations was sent out. Items were considered barriers when greater than or equai to 20% of participants responded with a negative answer. If greater than or equai to 80% of the participants responded with a positive answer, the item was considered a facilitator. Sixty-four HCPs completed the survey, of which 14 were from academic hospitals, 25 from general hospitals, and 25 from teaching hospitals. Most participants were hospital pharmacists (59%) or medical specialists (23%). Eleven barriers and four facilitators for implementation of TDM of beta-lactams were identified; 17 barriers for TDM of ciprofloxacin and no facilitators. The most important barriers were a lack of conclusive evidence, organizational support, and low availability of assays. Additional barriers were a lack of consensus on which specific patients to apply TDM and which pharmacodynamic targets to use. Identified facilitators for beta-lactam TDM implementation are low complexity and high task perception, combined with the perception that TDM is important to prevent side effects and to adequately treat infections. Twenty-eight percent of participants reported that flucloxacillin could be analyzed in their hospital. Assay availability of other beta-lactams and ciprofloxacin was lower (3-17%). Several barriers were identified that could obstruct the implementation of TDM of beta-lactams and ciprofloxacin in the ICU. In particular, education, clear guidelines, and organizational support should be considered when creating tailored implementation strategies. Finally, evidence of beneficial clinical outcomes on TDM of beta-lactams and ciprofloxacin can enhance further implementation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Emerging evidence supports the importance of optimized antibiotic exposure in pediatric intensive care unit (PICU) patients. Traditional antibiotic dosing is not designed for PICU patients, as the ...extreme pharmacokinetic (PK) behavior of drugs threatens the achievement of optimal antibiotic treatment outcomes. Scavenged sampling is a sampling strategy which may have positive implications for routine TDM and PK research, as well as monitoring other biomarkers. EXPAT Kids study was designed to analyze whether current empiric dosing regimens of frequently used beta-lactam antibiotics achieve defined therapeutic target concentrations in PICU patients.
A mono-centre, exploratory pharmacokinetic and pharmacodynamic study was designed to assess target attainment of beta-lactam antibiotics. One hundred forty patients will be included within 24 months after start of inclusion. At various time points serum concentration of the study antibiotic (cefotaxime, ceftazidime, ceftriaxone, cefuroxime, flucloxacillin, and meropenem) are determined. In parallel with these sampling moments, residual material is collected to validate the use of blood of scavenged heparinized astrup syringes for the quantification of antibiotic exposure. The primary outcome is the time that the free (unbound) concentration of the study antibiotic remains above one to four the minimal inhibitory concentration during a dosing interval (100%ƒT > MIC and 100%ƒT>4xMIC). Other included outcomes are disease severity, safety, length of stay, and inflammatory biomarkers.
Potentially, scavenged sampling may enrich the EXPAT Kids dataset, and reduce additional blood sampling and workload for clinical personnel. The findings from the EXPAT Kids study will lead to new insights in the PK parameters of beta-lactams and consecutive effects on target attainment and clinical outcomes. Is there a need for more precision in dosing?
Trial NL9326.
Introduction: We describe a child with meningococcal sepsis who suffered cephalosporin-related neurotoxicity. Case Presentation: A four-year-old girl was treated with intravenous ceftriaxone and ...supportive therapy. After rapid improvement, inotropic and respiratory support was stopped within 2 days. However, she developed renal failure and, on day four, deteriorated neurologically. Research into the cause of her encephalopathy revealed supra-therapeutic ceftriaxone concentrations with greatly increased unbound fractions leading to the diagnosis of cephalosporin-related neurotoxicity. Ceftriaxone treatment was discontinued, and renal replacement therapy was initiated on day six. With both discontinuation of ceftriaxone and renal replacement therapy, the girl’s condition improved rapidly. Conclusion: We postulate that in the described case both renal impairment and hypoalbuminemia played an important role in the development of high unbound ceftriaxone serum levels. We advocate therapeutic drug monitoring for ceftriaxone in critically ill children with renal failure or hypoalbuminemia.
Optimal pharmacotherapy in pediatric patients with suspected infections requires understanding and integration of relevant data on the antibiotic, bacterial pathogen, and patient characteristics. ...Because of age-related physiological maturation and non-maturational covariates (e.g., disease state, inflammation, organ failure, co-morbidity, co-medication and extracorporeal systems), antibiotic pharmacokinetics is highly variable in pediatric patients and difficult to predict without using population pharmacokinetics models. The intra- and inter-individual variability can result in under- or overexposure in a significant proportion of patients. Therapeutic drug monitoring typically covers assessment of pharmacokinetics and pharmacodynamics, and concurrent dose adaptation after initial standard dosing and drug concentration analysis. Model-informed precision dosing (MIPD) captures drug, disease, and patient characteristics in modeling approaches and can be used to perform Bayesian forecasting and dose optimization. Incorporating MIPD in the electronic patient record system brings pharmacometrics to the bedside of the patient, with the aim of a consisted and optimal drug exposure. In this narrative review, we evaluated studies assessing optimization of antibiotic pharmacotherapy using MIPD in pediatric populations. Four eligible studies involving amikacin and vancomycin were identified from 418 records. Key articles, independent of year of publication, were also selected to highlight important attributes of MIPD. Although very little research has been conducted until this moment, the available data on vancomycin indicate that MIPD is superior compared to conventional dosing strategies with respect to target attainment. The utility of MIPD in pediatrics needs to be further confirmed in frequently used antibiotic classes, particularly aminoglycosides and beta-lactams.
Model-informed precision dosing (MIPD) might be used to optimize antibiotic treatment. Procalcitonin (PCT) is a biomarker for severity of infection and response to antibiotic treatment. The aim of ...this study was to assess the impact of MIPD on the course of PCT and to investigate the association of PCT with pharmacodynamic target (PDT) attainment in critically ill patients. This is a secondary analysis of the DOLPHIN trial, a multicentre, open-label, randomised controlled trial. Patients with a PCT value available at day 1 (T1), day 3 (T3), or day 5 (T5) after randomisation were included. The primary outcome was the absolute difference in PCT concentration at T1, T3, and T5 between the MIPD and the standard dosing group. In total, 662 PCT concentrations from 351 critically ill patients were analysed. There was no statistically significant difference in PCT concentration between the trial arms at T1, T3, or T5. The median PCT concentration was highest in patients who exceeded 10× PDT at T1 13.15 ng/mL (IQR 5.43-22.75). In 28-day non-survivors and in patients that exceeded PDT at T1, PCT decreased significantly between T1 and T3, but plateaued between T3 and T5. PCT concentrations were not significantly different between patients receiving antibiotic treatment with or without MIPD guidance. The potential of PCT to guide antibiotic dosing merits further investigation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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