Human monoclonal antibodies against anthrax lethal factor and protective antigen act independently to protect against Bacillus anthracis infection and enhance endogenous immunity to anthrax

The unpredictable nature of bioterrorism and the absence of real-time detection systems have highlighted the need for an efficient postexposure therapy for Bacillus anthracis infection. One approach is passive immunization through the administration of antibodies that mitigate the biological action of anthrax toxin. We isolated and characterized two protective fully human monoclonal antibodies with specificity for protective antigen (PA) and lethal factor (LF). These antibodies, designated IQNPA (anti-PA) and IQNLF (anti-LF), were developed as hybridomas from individuals immunized with licensed anthrax vaccine. The effective concentration of IQNPA that neutralized 50% of the toxin in anthrax toxin neutralization assays was 0.3 nM, while 0.1 nM IQNLF neutralized the same amount of toxin. When combined, the antibodies had additive neutralization efficacy. IQNPA binds to domain IV of PA containing the host cell receptor binding site, while IQNLF recognizes domain I containing the PA binding region in LF. A single 180-mug dose of either antibody given to A/J mice 2.5 h before challenge conferred 100% protection against a lethal intraperitoneal spore challenge with 24 50% lethal doses [LD50s] of B. anthracis Sterne and against rechallenge on day 20 with a more aggressive challenge dose of 41 LD50s. Mice treated with either antibody and infected with B. anthracis Sterne developed detectable murine anti-PA and anti-LF immunoglobulin G antibody responses by day 17 that were dependent on which antibody the mice had received. Based on these results, IQNPA and IQNLF act independently during prophylactic anthrax treatment and do not interfere with the establishment of endogenous immunity.     

Malnutrition Diagnosis during Adult Inpatient Hospitalizations: Analysis of a Multi-Institutional Collaborative Database of Academic Medical Centers

Background

Malnutrition is a significant problem for hospitalized patients. However, the true prevalence of reported malnutrition diagnosis in real-world clinical practice is largely unknown. Using a large collaborative multi-institutional database, the rate of malnutrition diagnosis was assessed and used to assess institutional variables associated with higher rates of malnutrition diagnosis.

High-Risk Driving Behaviors Among 12th Grade Students: Differences Between Alcohol-Only and Alcohol Mixed With Energy Drink Users

Background: About 30% of high school students use energy drinks. Alcohol mixed with energy drinks (AmED) has been associated with higher rates of risky driving among college students. Objectives: The purpose of this study was to: (a) examine AmED-use in a sample of high school students and (b) to specifically investigate differences in risky driving behaviors between 12th grade students who engaged in AmED-use and those who consumed alcohol only. Methods: Differences in risky driving behaviors were investigated by utilizing secondary data analyses of nationally representative data from the Monitoring the Future Study (N = 1305). Results: 12th grade AmED users were significantly more likely to be in a motor vehicle accident (p <.001) and receive a ticket for a traffic violation (p <.05). Additionally, 12th grade AmED users were significantly less likely to wear a seatbelt as a driver or passenger (p <.001). Conclusions/Importance: Although this study does not link risky driving behaviors to specific drinking events, it does indicate a relationship between AmED-use and high-risk driving. Because traffic accidents are the highest cause of mortality among U.S. teenagers, drug education efforts to reduce high-risk driving behaviors should include information on the decision-making and synergistic effects of energy drinks when mixed with alcohol.     

Enhanced terminal room disinfection and acquisition and infection caused by multidrug-resistant organisms and Clostridium diffcile(the Benefits of Enhanced Terminal Room Disinfection study):a cluster-randomised,multicentre,crossover study

中文:背景患者入院后可从不当消毒的环境表面获得多药耐药菌和艰难梭菌。本文确定了3种强化的终末消毒(入住同一病房的两名患者之间的消毒)策略,对感染耐甲氧西林金黄色葡萄球菌(MRSA)、耐万古霉素肠球菌(VRE)、艰难梭菌(CD)和多重耐药不动杆菌的影响。方法本文在美国东南部的9家医院开展了一项务实的、集群-随机、交叉研究。凡曾有感染或定植目标细菌感染患者居住过的病房,患者出院后随机采取4种消毒策略中的一种方法进行终末消毒:对照(季胺盐类消毒剂消毒,但凡遇到CD采用含氯消毒剂);UV(季胺盐类+UV-C消毒,但凡遇到CD采用含氯消毒剂+UV-C);含氯消毒剂;含氯消毒剂+UV-C。凡入住目标病房的患者被列为暴露人群。这4种终末消毒方法分别在每家医院连续实施7个月的周期。本文随机设计这几种消毒策略在每家医院内的实施顺序(1:1:1:1)。主要产出的结果是,观察暴露患者中目标细菌的感染的发生或定植情况,以及ITT人群中暴露患者CD感染发生率。本研究ClinicalTrials.gov注册编号:NCT01579370。结果共有31 226名患者暴露,其中21 395(69%)符合标准,包括4 916名对照组,5 178名UV组,5 438名含氯消毒剂组,以及5 863名含氯消毒剂+UV组。在对照组中,22 426个暴露日中有115名患者发生目标细菌的感染(51.3/10000暴露日)。在标准清洁策略的基础上增加UV消毒的暴露患者,其目标细菌感染的发生率明显较低(n=76;33.9/10 000暴露日;RR:0.70,95%CI:0.50～0.988;P=0.036)。含氯消毒剂组(n=101;41.6/10 000暴露日;RR:0.85,95%CI:0.69～1.04;P=0.116),或含氯消毒剂+UV组患者(n=131;45.6/10 000暴露日;RR:0.91,95%CI:0.76～1.09;P=0.303)的目标细菌的感染率,其差异无统计学意义。同样,在含氯消毒剂的基础上增加UV消毒,暴露患者中CD感染率也没有发生改变((n=38 vs 36;30.4 vs 31.6/10 000暴露日;RR:1.0,95%CI:0.57-1.75;P=0.997)。解释污染的医疗机构环境是获得病原微生物的重要来源;强化终末消毒可以降低这一风险。     

Near-fatal pediatric asthma managed with pumpless arteriovenous carbon dioxide removal

OBJECTIVE: To describe the use of pumpless arteriovenous carbon dioxide removal in support of four pediatric patients with near-fatal asthma. DESIGN: Report of four cases. SETTING: Tertiary care university pediatric intensive care unit. PATIENTS: Four pediatric patients, ages 4, 10, 12, and 13, were intubated and initially managed with positive pressure ventilation for severe respiratory failure. Despite pharmacologic therapy with inhaled beta-agonists, inhaled anticholinergics, systemic corticosteroids, and intravenous magnesium, marked progressive hypercapnia and acidosis rapidly developed requiring high levels of positive pressure ventilation. INTERVENTIONS: Application of pumpless arteriovenous carbon dioxide removal (AVCO2R) via percutaneous femoral cannulation. MEASUREMENT AND MAIN RESULTS: Arterial or mixed venous carbon dioxide partial pressure (PCO2) and pH were measured before and at intervals following initiation of AVCO2R. Before cannulation, PCO2 was elevated to 100, 108, 90, and 186 mm Hg in the four patients, with corresponding pH of 7.07, 6.96, 7.09, and 6.80, respectively. Pco2 levels were reduced to more acceptable levels (37-57 mm Hg) within 2-4 hrs of initiation of AVCO2R, with corresponding improvements in pH despite reductions in ventilatory frequency and tidal volumes to safe levels. Duration of support ranged from 18 hrs to 5 days during resolution of bronchospasm. No red blood cell or platelet transfusions were required, and no complications resulted from AVCO2R or from mechanical ventilation. All patients were discharged from the hospital without sequelae. CONCLUSIONS: Percutaneous cannulation with a simplified pumpless extracorporeal circuit is capable of removing sufficient carbon dioxide to allow application of a protective ventilatory strategy in severe hypercapnic pediatric respiratory failure. The procedure was safely applied without complications in four pediatric patients as young as 4 yrs of age.     

Improved Radiographic Outcomes With Patient-Specific Total Knee Arthroplasty

Patient-specific guides can improve limb alignment and implant positioning in total knee arthroplasty, although not all studies have supported this benefit. We compared the radiographs of 100 consecutively-performed patient-specific total knees to a similar group that was implanted with conventional instruments instead. The patient-specific group showed more accurate reproduction of the theoretically ideal mechanical axis, with fewer outliers, but implant positioning was comparable between groups. Our odds ratio comparison showed that the patient-specific group was 1.8 times more likely to be within the desired + 3° from the neutral mechanical axis when compared to the standard control group. Our data suggest that reliable reproduction of the limb mechanical axis may accrue from patient-specific guides in total knee arthroplasty when compared to standard, intramedullary instrumentation.     

The Dynamic Relationship Between Social Support and HIV-Related Stigma in Rural Uganda

Background

Cross-sectional studies show that human immunodeficiency virus (HIV) stigma is negatively correlated with social support.

Purpose

The purpose of this study is to examine the bidirectional relationship between social support and HIV stigma.

Methods

We collected quarterly data from a cohort of 422 people living with HIV in Uganda, followed for a median of 2.1 years. We used multilevel regression to model the contemporaneous and 3-month-lagged associations between social support and both enacted and internalized stigma.

Results

Lagged enacted stigma was negatively correlated with emotional and instrumental social support, and lagged instrumental social support was negatively correlated with enacted stigma. Internalized stigma and emotional social support had reciprocal lagged associations.

Conclusions

Interventions to reduce enacted stigma may strengthen social support for people living with HIV. Improved social support may in turn have a protective influence against future enacted and internalized stigma.