Safety of local anesthetics

Local anesthetics are essential medications for the conduction of dermatological procedures. They stop the depolarization of nerve fibers and are divided into two main categories, the amide and ester types. Systemic toxicity with reflex on the central nervous and cardiovascular systems is their most feared adverse reactions, and the anaphylactic reaction is the most concerning one. Although potentially fatal, these events are extremely rare, so local anesthetics are considered safe for use in in-office procedures.     

Prediction of skin sensitization potency using machine learning approaches

The replacement of animal use in testing for regulatory classification of skin sensitizers is a priority for US federal agencies that use data from such testing. Machine learning models that classify substances as sensitizers or non‐sensitizers without using animal data have been developed and evaluated. Because some regulatory agencies require that sensitizers be further classified into potency categories, we developed statistical models to predict skin sensitization potency for murine local lymph node assay (LLNA) and human outcomes. Input variables for our models included six physicochemical properties and data from three non‐animal test methods: direct peptide reactivity assay; human cell line activation test; and KeratinoSens™ assay. Models were built to predict three potency categories using four machine learning approaches and were validated using external test sets and leave‐one‐out cross‐validation. A one‐tiered strategy modeled all three categories of response together while a two‐tiered strategy modeled sensitizer/non‐sensitizer responses and then classified the sensitizers as strong or weak sensitizers. The two‐tiered model using the support vector machine with all assay and physicochemical data inputs provided the best performance, yielding accuracy of 88% for prediction of LLNA outcomes (120 substances) and 81% for prediction of human test outcomes (87 substances). The best one‐tiered model predicted LLNA outcomes with 78% accuracy and human outcomes with 75% accuracy. By comparison, the LLNA predicts human potency categories with 69% accuracy (60 of 87 substances correctly categorized). These results suggest that computational models using non‐animal methods may provide valuable information for assessing skin sensitization potency. Copyright © 2017 John Wiley & Sons, Ltd.     

Obstetric emergencies

For more than 60 years the Confidential Enquiries into Maternal Deaths triennial reports have helped build a picture of maternity care within the UK, highlighting not only our successes but failures in caring for women within the puerperal period. Despite most obstetric emergencies being well described and having clear management strategies and guidance, there continues to be substandard management with poor outcomes recorded and this has been highlighted within the latest triennium report. This article describes some common obstetric emergencies with which the anaesthetist will become involved. It emphasizes management related to some deficiencies identified in the Centre for Maternal and Child Enquiries report as well as highlighting a multidisciplinary approach throughout. Good communication between team members is paramount in all aspects of medical care, but this approach should be fostered routinely to ensure that rapid and appropriate decisions are made in a safe and timely manner.     

局部麻醉下经腹膜前无张力疝修补术20例的疗效

目的:探讨局麻下腹膜前腹股沟疝修补术的技术要点和临床疗效。方法:对20例局部麻醉下行腹膜前腹股沟疝修补术患者的资料进行回顾性分析。结果:20例患者术后恢复快,随访时间6～14个月,无复发。结论:局麻下腹膜前腹股沟疝修补术是一种操作较简便,术后复发率低的一种疝修补术,尤其适合于合并多种慢性疾病的老年患者,为腹股沟疝患者提供了一种理想的治疗方法。     

An Approach to Bioactivity Assessment for Critical Quality Attribute Identification Based on Antibody-Antigen Complex Structure

Identification of critical quality attributes (CQAs) is an important step for development of biopharmaceuticals with intended performance. An accurate CQA assessment is needed to ensure product quality and focusing on development efforts where control is needed. The assignment of criticality is based on safety and efficacy. Efficacy is related to PK and bioactivity. Here, we developed a novel approach based on antibody-antigen complex structure and modeling as a complementary method for bioactivity assessment. To validate this approach, common product related quality attributes and mutagenesis data from several IgGs were assessed using available antibody-antigen complex structures, and results were compared with experimental data from bioactivity or binding affinity measurements. A stepwise evaluation scheme for structural based analysis is proposed; based on systematic assessment following the scheme, good correlation has been observed between structural analysis and experimental data. This demonstrates that such an approach can be applied as a complementary tool for bioactivity assessment. Main applications are 1) To decouple multiple attributes to achieve amino acid resolution for bioactivity assessment, 2) To assess bioactivity of attributes that cannot be experimentally generated, 3) To provide molecular mechanism for experimental observation and understand structure function relationship. Examples are provided to illustrate these applications.     

Trends in Binge and Heavy Drinking,Alcohol-Related Problems,and Combat Exposure in the U.S. Military

Population-based Department of Defense health behavior surveys were examined for binge and heavy drinking among U.S. active duty personnel. From 1998–2008, personnel showed significant increases in heavy drinking (15% to 20%) and binge drinking (35% to 47%). The rate of alcohol-related serious consequences was 4% for nonbinge drinkers, 9% for binge drinkers, and 19% for heavy drinkers. Personnel with high combat exposure had significantly higher rates of heavy (26.8%) and binge (54.8%) drinking than their counterparts (17% and 45%, respectively). Heavy and binge drinking put service members at high risk for problems that diminish force readiness and psychological fitness.