Development and application of acute exposure guideline levels (AEGLs) for chemical warfare nerve and sulfur mustard agents

Acute exposure guideline levels (AEGLs) have been developed for the chemical warfare agents GB, GA, GD, GF, VX, and sulfur mustard. These AEGLs were approved by the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances after Federal Register publication and comment, and judged as scientifically valid by the National Research Council Committee on Toxicology Subcommittee on AEGLs. AEGLs represent general public exposure limits for durations ranging from 10 min to 8 h, and for three levels of severity (AEGL-1, AEGL-2, AEGL-3). Mild effects are possible at concentrations greater than AEGL-1, while life-threatening effects are expected at concentrations greater than AEGL-3. AEGLs can be applied to various civilian and national defense purposes, including evacuation and shelter-in-place protocols, reentry levels, protective clothing specifications, and analytical monitoring requirements. This report documents development and derivation of AEGL values for six key chemical warfare agents, and makes recommendations for their application to various potential exposure scenarios.     

Efficacy and safety of gefitinib in chemonaive patients with advanced non-small cell lung cancer treated in an Expanded Access Program

Chemotherapy (CT) is recommended in numerous clinical guidelines for advanced non-small cell lung cancer (NSCLC) and offers improved survival over best supportive care. However, many patients with advanced NSCLC never receive CT because of advanced age, poor performance status, comorbidities, or patient refusal. The epidermal growth factor receptor tyrosine kinase inhibitor gefitinib has shown antitumor activity and a favorable toxicity profile in pretreated patients with recurrent advanced NSCLC and was made available in a worldwide Expanded Access Program (EAP) to >37,000 patients who did not respond to standard treatment or were ineligible for or refused CT. A retrospective chart review of 1671 consecutive patients enrolled at 11 sites in the US arm of the EAP identified 198 patients with advanced NSCLC who had not received previous CT. All patients were treated with gefitinib 250 mg/d until treatment failure or toxicity occurred. Patients were treated for a mean of 4.7 months. The most common adverse events were diarrhea (31.3%) and rash (31.3%). Complete and partial response rates were 0.7 and 5.6%, respectively, and 40.6% had stable disease. Median survival was 6 months, and estimated 1-year survival was 29.7%. The majority of patients did not receive subsequent CT.     

Ketamine: new indications for an old drug

Ketamine is a non-competitive antagonist to the phencyclidine site of N-methyl-d-aspartate (NMDA) receptor for glutamate, though its effects are mediated by interaction with many others receptors. It has been introduced in clinical use since 1960's but today it is not largely employed as a general anaesthetic for its undesired psychic effects (emergence reactions) occurring in approximately 12% of patients. In the last decade, there has been a renewed interest in the use of subanaesthetic doses of ketamine for the treatment of acute and chronic pain. In the late 1990's, multiple prospective, randomised, controlled study has shown the efficacy of low dose of ketamine for postoperative pain relief, for analgesia during regional or local anaesthesia, and for opioid-sparing effect. At present, non-definitive conclusion can be drawn. More data are needed to define the possible long term effects and the clinical goal of ketamine use.     

Identity of rumen fluke in deer

As evidence is growing that in many temperate areas paramphistome infections are becoming more common and widespread, this study was undertaken to determine the role of deer as reservoirs for rumen fluke infections in livestock. A total of 144 deer faecal samples (88 from fallow deer, 32 from red deer and 24 samples from sika, sika/red deer hybrids) were screened for the presence of fluke eggs. Based on the ITS-2 rDNA locus plus flanking 5.8S and 28S sequences (ITS-2+), fluke eggs were identified to species level. Our results indicate that, of the 3 deer species, fallow deer had the highest fluke infection rates. Two rumen fluke species, Calicophoron daubneyi and Paramphistomum leydeni, with morphologically distinct eggs, were identified. Concurrent infections of the two paramphistome species and liver fluke, Fasciola hepatica, were common. Considering the comparatively low egg burdens observed in this study, it is unlikely that deer represent a significant source of infection for Irish livestock.     

A cohort study comparing a single-incision sling with a retropubic midurethral sling

Introduction and hypothesis

Despite established comparable efficacy between retropubic midurethral (RMUS) and transobturator slings, there are conflicting data regarding single-incision mini-slings (SIMS). This study tests the null hypothesis that the MiniArc® Single-Incision Sling is equivalent to the ALIGN® Urethral Support System for treatment of stress urinary incontinence (SUI).

Methods

Women who underwent a sling for SUI from 1 January 2008 through 31 December 2009 were identified (N?=?324). A follow-up survey was mailed. Primary outcomes were treatment failure, defined as International Consultation on Incontinence Questionnaire (ICIQ) score >0 or additional anti-incontinence procedure, and stress-specific incontinence (SSI). Secondary outcomes included Patient Global Impression of Severity and Improvement (PGI-SI), satisfaction, de novo urge, and complications.

Results

The study included 202 women who returned the survey. The SIMS group had higher body mass index (BMI) (30.7?±?6.5 vs 28.9?±?6.0 kg/m², P?=?0.052) and shorter follow-up (18.6?±?11.5 vs 22.9?±?14.6 months, P?=?0.019). Treatment failure was higher in SIMS compared with RMUS (76.3 % vs 64.2 %) with adjusted odds ratio of 1.84 (95 % CI, 1.0, 3.5). The SIMS group was more likely to have postoperative SSI, with adjusted OR of 2.4 (95 % CI; 1.3–4.5). The RMUS group reported more improvement and satisfaction. Incidence of de novo urge and complications were similar between groups. Reoperation for mesh erosion was more likely in the RMUS group, while the SIMS had a higher reoperation rate for SUI.

Conclusions

Compared with retropubic ALIGN® Slings, MiniArc® Single-Incision Slings are less effective, with more postoperative incontinence, less patient-reported improvement, satisfaction, and higher reoperation rates for SUI.     

Racemic ketamine in adult head injury patients: use in endotracheal suctioning

Introduction

Endotracheal suctioning (ETS) is essential for patient care in an ICU but may represent a cause of cerebral secondary injury. Ketamine has been historically contraindicated for its use in head injury patients, since an increase of intracranial pressure (ICP) was reported; nevertheless, its use was recently suggested in neurosurgical patients. In this prospective observational study we investigated the effect of ETS on ICP, cerebral perfusion pressure (CPP), jugular oxygen saturation (SjO₂) and cerebral blood flow velocity (mVMCA) before and after the administration of ketamine.

Methods

In the control phase, ETS was performed on patients sedated with propofol and remifentanil in continuous infusion. If a cough was present, patients were assigned to the intervention phase, and 100 γ/kg/min of racemic ketamine for 10 minutes was added before ETS.

Results

In the control group ETS stimulated the cough reflex, with a median cough score of 2 (interquartile range (IQR) 1 to 2). Furthermore, it caused an increase in mean arterial pressure (MAP) (from 89.0 ± 11.6 to 96.4 ± 13.1 mmHg; P <0.001), ICP (from 11.0 ± 6.7 to 18.5 ± 8.9 mmHg; P <0.001), SjO₂ (from 82.3 ± 7.5 to 89.1 ± 5.4; P = 0.01) and mVMCA (from 76.8 ± 20.4 to 90.2 ± 30.2 cm/sec; P = 0.04). CPP did not vary with ETS. In the intervention group, no significant variation of MAP, CPP, mVMCA, and SjO₂ were observed in any step; after ETS, ICP increased if compared with baseline (15.1 ± 9.4 vs. 11.0 ± 6.4 mmHg; P <0.05). Cough score was significantly reduced in comparison with controls (P <0.0001).

Conclusions

Ketamine did not induce any significant variation in cerebral and systemic parameters. After ETS, it maintained cerebral hemodynamics without changes in CPP, mVMCA and SjO₂, and prevented cough reflex. Nevertheless, ketamine was not completely effective when used to control ICP increase after administration of 100 γ/kg/min for 10 minutes.     

Examining human behavior in video games: The development of a computational model to measure aggression

Video games with violent content have raised considerable concern in popular media and within academia. Recently, there has been considerable attention regarding the claim of the relationship between aggression and video game play. The authors of this study propose the use of a new class of tools developed via computational models to allow examination of the question of whether there is a relationship between violent video games and aggression. The purpose of this study is to computationally model and compare the General Aggression Model with the Diathesis Mode of Aggression related to the play of violent content in video games. A secondary purpose is to provide a method of measuring and examining individual aggression arising from video game play. Total participants examined for this study are N = 1065. This study occurs in three phases. Phase 1 is the development and quantification of the profile combination of traits via latent class profile analysis. Phase 2 is the training of the artificial neural network. Phase 3 is the comparison of each model as a computational model with and without the presence of video game violence. Results suggest that a combination of environmental factors and genetic predispositions trigger aggression related to video games.