Urine Specimens from Pregnant and Nonpregnant Women Inhibitory to Amplification of \u3cem\u3eChlamydia trachomatis\u3c/em\u3e Nucleic Acid by PCR, Ligase Chain Reaction, and Transcription-Mediated Amplification: Identification of Urinary Substances Associated with Inhibition and Removal of Inhibitory Activity

The presence of endogenous amplification inhibitors in urine may produce false-negative results for the detection of Chlamydia trachomatis nucleic acids by tests such as PCR, ligase chain reaction (LCR), and transcription-mediated amplification (TMA). Consecutive urine specimens from 101 pregnant women and 287 nonpregnant women submitted for urinalysis were processed for C. trachomatis detection. Aliquots were spiked with the equivalent of one C. trachomatis elementary body and were tested by three commercial assays: AMPLICOR CT/NG, Chlamydia LCX, and Chlamydia TMA. The prevalence of inhibitors resulting in complete inhibition of amplification was 4.9% for PCR, 2.6% for LCR, and 7.5% for TMA. In addition, all three assays were partially inhibited by additional urine specimens. Only PCR was more often inhibited by urine from pregnant women than by urine from nonpregnant women (9.9 versus 3.1%; P = 0.011). A complete urinalysis including dipstick and a microscopic examination was performed. Logistic regression analysis revealed that the following substances were associated with amplification inhibition: beta-human chorionic gonadotropin (odd ratio [OR], 3.3) and crystals (OR, 3.3) for PCR, nitrites for LCR (OR, 14.4), and hemoglobin (OR, 3.3), nitrites (OR, 3.3), and crystals (OR, 3.3) for TMA. Aliquots of each inhibitory urine specimen were stored at 4 and -70°C and a dilution of 1:10 (84% for PCR, 100% for LCR, and 92% for TMA). Five urine specimens (three for PCR and two for TMA) required phenol-chloroform extraction to remove inhibitors. The results indicate that the prevalence of nucleic acid amplification inhibitors in female urine is different for each technology, that this prevalence may be predicted by the presence of urinary factors, and that storage and dilution remove most of the inhibitors

Development of a New Independent Monte Carlo Dose Calculation Quality Assurance Audit Tool for Clinical Trials

Introduction: Commercially available treatment planning systems (TPS) may use a number of different radiation dose calculation algorithms during the planning process. The Radiological Physics Center (RPC), tasked with ensuring clinically comparable and consistent dose delivery amongst institutions participating in NCI funded multi-institutional clinical trials, has traditionally relied upon measurements to achieve this objective. As a supplement to the tools used by the RPC, an independent dose calculation tool is needed to determine patient dose distributions in three dimensions so as to act as a quality assurance tool for the dose calculations. Methods: Multiple source models representing the output of Elekta 6MV and 10MV and Varian TrueBeam Flattening Filter Free (FFF) 6MV and FFF 10MV therapeutic x-ray beams were developed. The Monte Carlo technique, using the Dose Planning Method (DPM) algorithm, was used in radiation dose calculations. During validation calculations were compared to open field measurements in a water phantom. Benchmarking was a measurement based comparison of mock treatment plans in anthropomorphic phantoms. Treatment plans included intensity modulated radiation therapy and stereotactic body radiation therapy techniques. Past phantom treatment plans submitted through a remote auditing program were recalculated using the tool and compared to submitted measurement data as a test of the models’ robustness. Results: The average percentage of data passing a ±2%/2mm gamma criterion during validation testing was 99.5%, 99.6%, 98.1%, and 98.1% for Elekta 6MV, 10MV, Varian TrueBeam FFF 6MV, and FFF 10MV beams, respectively. The percentage of data passing the benchmarking evaluation criterion of ±3%/2mm was 87.4%, 89.9%, 90.1%, and 90.8% for Elekta 6MV, Elekta 10MV, Varian TrueBeam FFF 6MV, and Varian TrueBeam FFF 10MV beams, respectively. Conclusions: Elekta 6MV and 10MV and Varian TrueBeam FFF 6MV and FFF 10MV multiple source models based on dose calculations using the DPM Monte Carlo code were successfully developed, validated, and benchmarked against measurements. A recalculation of TPS dose from archived phantom credentialing audits was performed as a proof of concept for the models’ utility as a quality assurance tool for use in clinical trial audits

Pharmacokinetic studies in children: recommendations for practice and research.

Optimising the dosing of medicines for neonates and children remains a challenge. The importance of pharmacokinetic (PK) and pharmacodynamic (PD) research is recognised both in medicines regulation and paediatric clinical pharmacology, yet there remain barriers to undertaking high-quality PK and PD studies. While these studies are essential in understanding the dose-concentration-effect relationship and should underpin dosing recommendations, this review examines how challenges affecting the design and conduct of paediatric pharmacological studies can be overcome using targeted pharmacometric strategies. Model-based approaches confer benefits at all stages of the drug life-cycle, from identifying the first dose to be used in children, to clinical trial design, and optimising the dosing regimens of older, off-patent medications. To benefit patients, strategies to ensure that new PK, PD and trial data are incorporated into evidence-based dosing recommendations are needed. This review summarises practical strategies to address current challenges, particularly the use of model-based (pharmacometric) approaches in study design and analysis. Recommendations for practice and directions for future paediatric pharmacological research are given, based on current literature and our joint international experience. Success of PK research in children requires a robust infrastructure, with sustainable funding mechanisms at its core, supported by political and regulatory initiatives, and international collaborations. There is a unique opportunity to advance paediatric medicines research at an unprecedented pace, bringing the age of evidence-based paediatric pharmacotherapy into sight

A 2-year-old boy with hemolytic uremic syndrome and pneumocephalus

Clostridium septicum infection following hemolytic uremic syndrome is rare and carries a poor prognosis, especially when the brain is involved. We report a case of a previously healthy 2-year-old boy who presented with two days of anuria and bloody diarrhea. He was admitted to the local children's hospital with a diagnosis of hemolytic uremic syndrome, presumably secondary to E. coli O157. He soon required intubation and was noted to have fixed and dilated pupils. Head CT revealed left frontal subcortical white matter vasogenic edema and scattered pockets of pneumocephalus. The patient expired 14 hours after admission. Antemortem blood cultures grew C. septicum. Gross pathologic examination of the brain revealed a large intraparenchymal cerebral hemorrhage in the left frontal and parietal lobes. There was extensive cystic changes as well. Microscopic examination revealed vacuolization and diffuse colonization with rod-shaped bacteria, but without the expected tissue response. There have been only six previously reported cases of C. septicum infection following hemolytic uremic syndrome, four of which had brain involvement. Mortality rate is high, with the only known survivor among those with brain involvement having a brain abscess rather than diffuse pneumocephalus

Correction: Faught et al. “Socioeconomic Disadvantage across the Life Course is associated with Diet Quality in Young Adulthood” Nutrients, 2019, 11(2), 242

We noticed an error in the text that requires correcting as it may contribute to an incorrect understanding of our study’s scientific conclusions. In the text accompanying Table 4 (Section 3.3: Mediation Analysis (Pathways Hypothesis), page 11), the third sentence in the paragraph reads: “Adult SEP at the level of university education mediated associations between childhood SEP and mean adult HEI-2015 score (p < 0.001).” This should in fact read: “Adult SEP at the level of high school or less mediated associations between childhood SEP and mean adult HEI-2015 score (p < 0.001).” This correction is consistent with the results presented in Table 4, and in line with the scientific conclusions discussed in the article that a low socioeconomic position (SEP) in adulthood mediates associations between childhood SEP and adult diet quality. SEP at the level of university education was the reference group in this analysis

International Veterinary Epilepsy Task Force Consensus Proposal: Outcome of therapeutic interventions in canine and feline epilepsy

Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered

The Prospective Association Between Electronic Device Use Before Bedtime and Academic Attainment in Adolescents

© 2018 Elsevier Ltd Purpose: To examine longitudinal associations between five commonly used technology devices prior to bedtime and real-life academic outcomes in adolescents. Methods: A total of 853 adolescents were recruited to a three-year prospective cohort study, with annual assessments. Academic grades/levels for three core subjects (English, Mathematics, and Science) were extracted from school records, and standardized (z-scores) were derived at the end of each academic year. A validated questionnaire was used to determine the frequency of using five types of technology (television viewing, video gaming, mobile telephone use, listening to music, and social networking) before bedtime. Results: After adjustment, English attainment was the subject most affected by prebedtime technology use, where three of five technologies assessed were negatively and prospectively associated (social networking [β = −.07 and p =.024], video gaming [β = −.10 and p =.008], and mobile telephone [β = −.07 and p=.017]). Social networking (β = −.07and p =.042), television viewing (β = −.08 and p =.044), and mobile telephones (β = −.07 and p =.031) were associated with significant impairment in English for girls whereas attainment in boys was most impaired by video gaming (β = −.12 and p =.014). Conclusions: The use of electronic devices by adolescents before bedtime may reduce their academic attainment, but apart from video gaming for boys, the negative impact of near bedtime technology use on academic performance is small

A Comparison of Four Treatments for Generalized Convulsive Status Epilepticus

ABSTRACT Background and Methods Although generalized convulsive status epilepticus is a life-threatening emergency, the best initial drug treatment is uncertain. We conducted a five-year randomized, doubleblind, multicenter trial of four intravenous regimens: diazepam (0.15 mg per kilogram of body weight) followed by phenytoin (18 mg per kilogram), lorazepam (0.1 mg per kilogram), phenobarbital (15 mg per kilogram), and phenytoin (18 mg per kilogram). Patients were classified as having either overt generalized status epilepticus (defined as easily visible generalized convulsions) or subtle status epilepticus (indicated by coma and ictal discharges on the electroencephalogram, with or without subtle convulsive movements such as rhythmic muscle twitches or tonic eye deviation). Treatment was considered successful when all motor and electroencephalographic seizure activity ceased within 20 minutes after the beginning of the drug infusion and there was no return of seizure activity during the next 40 minutes. Analyses were performed with data on only the 518 patients with verified generalized convulsive status epilepticus as well as with data on all 570 patients who were enrolled. Results Three hundred eighty-four patients had a verified diagnosis of overt generalized convulsive status epilepticus. In this group, lorazepam was successful in 64.9 percent of those assigned to receive it, phenobarbital in 58.2 percent, diazepam and phenytoin in 55.8 percent, and phenytoin in 43.6 percent (P=0.02 for the overall comparison among the four groups). Lorazepam was significantly superior to phenytoin in a pairwise comparison (P=0.002). Among the 134 patients with a verified diagnosis of subtle generalized convulsive status epilepticus, no significant differences among the treatments were detected (range of success rates, 7.7 to 24.2 percent). In an intention-to-treat analysis, the differences among treatment groups were not significant, either among the patients with overt status epilepticus (P=0.12) or among those with subtle status epilepticus (P=0.91). There were no differences among the treatments with respect to recurrence during the 12- hour study period, the incidence of adverse reactions, or the outcome at 30 days. Conclusions As initial intravenous treatment for overt generalized convulsive status epilepticus, lorazepam is more effective than phenytoin. Although lorazepam is no more efficacious than phenobarbital or diazepam and phenytoin, it is easier to use. (N Engl J Med 1998;339:792-8.