What is the easier and more reliable dose calculation for iv Phenytoin in children at risk of developing convulsive status epilepticus, 18 mg/kg or 20 mg/kg?

Background: With the Convulsive Status Guidelines due for renewal, we wondered if a phenytoin dose of ‘20 mg/kg’ would be easier to calculate correctly and therefore safer than the current ‘18 mg/kg’. An educational exercise in dose calculation was therefore undertaken to assess ease of calculation. Method: A standard question paper was prepared, comprising five clinical scenarios with children of varying ages and estimated body weights. Medical students, trainee doctors at registrar and senior house officer level, and consultant paediatricians were asked to complete the exercise, in private, by one of two medical students (SD, PS). Calculations were done with and without a calculator, for 18 mg/kg and for 20 mg/kg in randomised order. Speed and errors (greater than 10%) were determined. The data analysis was performed using SPSS version 18. Results: All answered all 20 scenarios, giving a total of 300 answers per doctor/student group, and 300 answers per type of calculation. When comparing the 2 doses, the numbers of errors more than 10% were significantly less in 20 mg/kg dose (0.33%) as compared to the 18 mg/kg dose (9.3%) (p<0.0001). Speed off calculation was significantly decreased in 20 mg/kg dose when compared with 18 mg/kg dose, with (p<0.001) or without (p<0.0001) the calculator. Speed was more than halved and errors were much less frequent by using a calculator, for the 18 mg/kg dose but no difference with or without the calculator for 20 mg/kg dose. Conclusion: We recommend that the future guidelines should suggest iv Phenytoin at 20 mg/kg rather than 18 mg/kg. This will make the calculation easier and reduce the risk of significant errors

A pseudo feedback-based annotated TF-IDF technique for dynamic crypto-ransomware pre-encryption boundary delineation and features extraction

The cryptography employed against user files makes the effect of crypto-ransomware attacks irreversible even after detection and removal. Thus, detecting such attacks early, i.e. during pre-encryption phase before the encryption takes place is necessary. Existing crypto-ransomware early detection solutions use a fixed time-based thresholding approach to determine the pre-encryption phase boundaries. However, the fixed time thresholding approach implies that all samples start the encryption at the same time. Such assumption does not necessarily hold for all samples as the time for the main sabotage to start varies among different crypto-ransomware families due to the obfuscation techniques employed by the malware to change its attack strategies and evade detection, which generates different attack behaviors. Additionally, the lack of sufficient data at the early phases of the attack adversely affects the ability of feature extraction techniques in early detection models to perceive the characteristics of the attacks, which, consequently, decreases the detection accuracy. Therefore, this paper proposes a Dynamic Pre-encryption Boundary Delineation and Feature Extraction (DPBD-FE) scheme that determines the boundary of the pre-encryption phase, from which the features are extracted and selected more accurately. Unlike the fixed thresholding employed by the extant works, DPBD-FE tracks the pre-encryption phase for each instance individually based on the first occurrence of any cryptography-related APIs. Then, an annotated Term Frequency-Inverse Document Frequency (aTF-IDF) technique was utilized to extract the features from runtime data generated during the pre-encryption phase of crypto-ransomware attacks. The aTF-IDF overcomes the challenge of insufficient attack patterns during the early phases of the attack lifecycle. The experimental evaluation shows that DPBD-FE was able to determine the pre-encryption boundaries and extract the features related to this phase more accurately compared to related works

Hybrid and multifaceted context-aware misbehavior detection model for vehicular ad hoc network

Vehicular Ad Hoc Networks (VANETs) have emerged mainly to improve road safety and traffic efficiency and provide user comfort. The performance of such networks’ applications relies on the availability of accurate and recent mobility-information shared among vehicles. This means that misbehaving vehicles that share false mobility information can lead to catastrophic losses of life and property. However, the current solutions proposed to detect misbehaving vehicles are not able to cope with the dynamic vehicular context and the diverse cyber-threats, leading to a decrease in detection accuracy and an increase in false alarms. This paper addresses these issues by proposing a Hybrid and Multifaceted Context-aware Misbehavior Detection model (HCA-MDS), which consists of four phases: data-collection, context-representation, context-reference construction, and misbehavior detection. Data-centric and behavioral-detection-based features are derived to represent the vehicular context. An online and timely updated context-reference model is built using unsupervised nonparametric statistical methods, namely Kalman and Hampel filters, through analyzing the temporal and spatial correlation of the consistency between mobility information to adapt to the highly dynamic vehicular context. Vehicles’ behaviors are evaluated locally and autonomously according to the consistency, plausibility, and reliability of their mobility information. The results from extensive simulations show that HCA-MDS outperforms existing solutions in increasing the detection rate by 38% and decreasing the false positive rate by 7%. These results demonstrate the effectiveness and robustness of the proposed HCA-MDS model to strengthen the security of VANET applications and protocols

Zebrafish Krüppel-Like Factor 4a Represses Intestinal Cell Proliferation and Promotes Differentiation of Intestinal Cell Lineages

BACKGROUND:Mouse krüppel-like factor 4 (Klf4) is a zinc finger-containing transcription factor required for terminal differentiation of goblet cells in the colon. However, studies using either Klf4(-/-) mice or mice with conditionally deleted Klf4 in their gastric epithelia showed different results in the role of Klf4 in epithelial cell proliferation. We used zebrafish as a model organism to gain further understanding of the role of Klf4 in the intestinal cell proliferation and differentiation. METHODOLOGY/PRINCIPAL FINDINGS:We characterized the function of klf4a, a mammalian klf4 homologue by antisense morpholino oligomer knockdown. Zebrafish Klf4a shared high amino acid similarities with human and mouse Klf4. Phylogenetic analysis grouped zebrafish Klf4a together with both human and mouse Klf4 in a branch with high bootstrap value. In zebrafish, we demonstrate that Klf4a represses intestinal cell proliferation based on results of BrdU incorporation, p-Histone 3 immunostaining, and transmission electron microscopy analyses. Decreased PepT1 expression was detected in intestinal bulbs of 80- and 102-hours post fertilization (hpf) klf4a morphants. Significant reduction of alcian blue-stained goblet cell number was identified in intestines of 102- and 120-hpf klf4a morphants. Embryos treated with γ-secretase inhibitor showed increased klf4a expression in the intestine, while decreased klf4a expression and reduction in goblet cell number were observed in embryos injected with Notch intracellular domain (NICD) mRNA. We were able to detect recovery of goblet cell number in 102-hpf embryos that had been co-injected with both klf4a and Notch 1a NICD mRNA. CONCLUSIONS/SIGNIFICANCE:This study provides in vivo evidence showing that zebrafih Klf4a is essential for the repression of intestinal cell proliferation. Zebrafish Klf4a is required for the differentiation of goblet cells and the terminal differentiation of enterocytes. Moreover, the regulation of differentiation of goblet cells in zebrafish intestine by Notch signaling at least partially mediated through Klf4a

Identifying outcome-based indicators and developing a curriculum for a continuing medical education programme on rational prescribing using a modified Delphi process

<p>Abstract</p> <p/> <p>Background</p> <p>Continuing medical education (CME) is compulsory for physicians in Iran. Recent studies in Iran show that modifications of CME elements are necessary to improve the effectiveness of the educational programmes. Other studies point to an inappropriate, even irrational drug prescribing. Based on a needs assessment study regarding CME for general physicians in the East Azerbaijan province in Iran, rational prescribing practice was recognized as a high priority issue. Considering different educational methods, outcome-based education has been proposed as a suitable approach for CME. The purpose of the study was to obtain experts' consensus about appropriate educational outcomes of rational prescribing for general physicians in CME and developing curricular contents for this education.</p> <p>Methods</p> <p>The study consisted of two phases: The first phase was conducted using a two-round Delphi consensus process to identify the outcome-based educational indicators regarding rational prescribing for general physicians in primary care (GPs). In the second phase the agreed indicators were submitted to panels of experts for assessment and determination of content for a CME program in the field.</p> <p>Results</p> <p>Twenty one learning outcomes were identified through a modified Delphi process. The indicators were used by the panels of experts and six educational topics were determined for the CME programme and the curricular content of each was defined. The topics were 1) Principles of prescription writing, 2) Adverse drug reactions, 3) Drug interactions, 4) Injections, 5) Antibiotic therapy, and 6) Anti-inflammatory agents therapy. One of the topics was not directly related to any outcome, raising a question about the need for a discussion on constructive alignment.</p> <p>Conclusions</p> <p/> <p>Consensus on learning outcomes was achieved and an educational guideline was designed. Before suggesting widespread use in the country the educational package should be tested in the CME context.</p

Evaluation of drug administration errors in a teaching hospital

<p>Abstract</p> <p>Background</p> <p>Medication errors can occur at any of the three steps of the medication use process: prescribing, dispensing and administration. We aimed to determine the incidence, type and clinical importance of drug administration errors and to identify risk factors.</p> <p>Methods</p> <p>Prospective study based on disguised observation technique in four wards in a teaching hospital in Paris, France (800 beds). A pharmacist accompanied nurses and witnessed the preparation and administration of drugs to all patients during the three drug rounds on each of six days per ward. Main outcomes were number, type and clinical importance of errors and associated risk factors. Drug administration error rate was calculated with and without wrong time errors. Relationship between the occurrence of errors and potential risk factors were investigated using logistic regression models with random effects.</p> <p>Results</p> <p>Twenty-eight nurses caring for 108 patients were observed. Among 1501 opportunities for error, 415 administrations (430 errors) with one or more errors were detected (27.6%). There were 312 wrong time errors, ten simultaneously with another type of error, resulting in an error rate without wrong time error of 7.5% (113/1501). The most frequently administered drugs were the cardiovascular drugs (425/1501, 28.3%). The highest risks of error in a drug administration were for dermatological drugs. No potentially life-threatening errors were witnessed and 6% of errors were classified as having a serious or significant impact on patients (mainly omission). In multivariate analysis, the occurrence of errors was associated with drug administration route, drug classification (ATC) and the number of patient under the nurse's care.</p> <p>Conclusion</p> <p>Medication administration errors are frequent. The identification of its determinants helps to undertake designed interventions.</p

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome: insights from the LUNG SAFE study

Contains fulltext : 218568.pdf (publisher's version ) (Open Access)BACKGROUND: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. METHODS: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 >/= 0.60 during hyperoxemia). RESULTS: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). CONCLUSIONS: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. TRIAL REGISTRATION: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073