Neuromuscular blockers and ARDS: Thou shalt not breathe, move, or die!

Background\ud In patients undergoing mechanical ventilation for Acute Respiratory Distress Syndrome (ARDS), neuromuscular blocking agents (NMBAs) may improve oxygenation and decrease ventilator-induced lung injury but may also cause muscle weakness.\ud \ud Methods\ud Objective\ud To identify if 48 hour therapy with the NMBA cisatracurium early in the course of ARDS reduces adjusted 90-day in-hospital mortality rate.\ud \ud Design\ud Multicenter, double blind, randomized clinical trial.\ud \ud Setting\ud Twenty multidisciplinary intensive care units in France\ud \ud Subjects\ud Patients presenting with onset of severe ARDS within the previous 48 hours. Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of less than 150, with a positive end-expiratory pressure of 5 cm or more of water and a tidal volume of 6 to 8 ml per kilogram of predicted body weight.\ud \ud Intervention\ud After enrollment, 340 patients were randomized to receive either cisatracurium besylate (n = 178) or placebo (n = 162). All patients were sedated to a Ramsay sedation score of 6 using sulfentanil and midazolam prior to intervention. A dose of 15 mg cisatracurium besylate or placebo was then administered, followed by a continuous infusion of 37.5 mg/hour for 48 hours. Patients were not monitored for depth of paralysis.\ud \ud Outcomes\ud The primary outcome was the proportion of patients who died either before hospital discharge or within 90 days after study enrollment (i.e., the 90-day in-hospital mortality rate), adjusted for predefined covariates and baseline differences between groups with the use of a Cox model.\ud \ud Results\ud The crude 90-day mortality was 31.6% (95% confidence interval [CI], 25.2 to 38.8) in the cisatracurium group and 40.7% (95% CI, 33.5 to 48.4) in the placebo group (P = 0.08). The hazard ratio for death at 90 days in the cisatracurium group, as compared with the placebo group, was 0.68 (95% CI, 0.48 to 0.98; P = 0.04), after adjustment for the baseline PaO2:FIO2 ratio, plateau pressure and the Simplified Acute Physiology II score. Mortality at 28 days was 23.7% (95% CI, 18.1 to 30.5) with cisatracurium and 33.3% (95% CI, 26.5 to 40.9) with placebo (P = 0.05). The rate of ICU-acquired paresis did not differ significantly between the two groups.\ud \ud Conclusions\ud In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time o the ventilator without increasing muscle weakness.\ud \ud Trial Registration\ud NCT0029965

CLINICAL AND MICROBIOLOGICAL PROFILE OF CANDIDA ISOLATES FROM ORAL CANDIDIASIS IN PATIENTS UNDERGOING RADIOTHERAPY FOR HEAD AND NECK MALIGNANCY

ABSTRACTObjective: To study the clinico-microbiological profile of oral candidiasis in head and neck squamous cell cancer (HNSCC) patients undergoingcurative radiotherapy (cRT).Methods: Patients undergoing cRT and developing oral candidiasis were enrolled. Clinical features such as pain and xerostomia were recorded.Candida isolates from lesions were speciated using CHROMagar (Himedia Inc.), and antifungal susceptibility was determined using microbrothdilution (MBD). Patients were followed up to study the clinical course of infection.Results: Of the 100 patients undergoing cRT, 79 developed oral candidiasis. Median duration to development of infection was 4 weeks (range:1-6.5 weeks). Mucositis was observed in 76 (96.2%) and xerostomia in 53 (67.1%) patients; 61 patients (77.2%) had symptoms attributable tocandidiasis. However, there was no correlation between severity of infection and mucositis (p=0.84) or xerostomia (p=0.51). Candida albicans was themost frequent (47 patients, 59.4%) isolate, followed by Candida tropicalis (23 patients; 29.1%). All isolates were sensitive to nystatin, but fluconazoleresistance/dose-dependent susceptibility was noted in 26 (32.9%) isolates. Both Candida krusei and two of four Candida glabrata isolate exhibitedfluconazole resistance. All patients received treatment for Candidiasis. On follow-up, 1 month after cRT, oral candidiasis resolved with gradualrecovery of mucositis in all patients.Conclusion: Candida albicans was the most common cause of oral Candidiasis in HNSCC cRT, and all isolates were susceptible to nystatin in-vitro.All lesions resolved with recovery from mucositis. In addition, as no patient developed systemic candidiasis, it appears that oral candidiasis thoughtroublesome is curable with treatment.Keywords: Radiation mucositis, CHROMagar, Microbroth dilution, Antifungal susceptibility

Merck Animal Health Uses Operations Research Methods to Transform Biomanufacturing Productivity for Lifesaving Medicines

Merck Animal Health offers veterinarians, farmers, pet owners, and governments a wide range of veterinary pharmaceuticals, vaccines, health management solutions and services, and an extensive suite of connected technology that includes identification, traceability, and monitoring products. Biomanufacturing uses living organisms (i.e., viruses and bacteria) to grow the active ingredients in vaccines, pharmaceuticals, and therapeutics. This high-tech manufacturing process generates unique challenges not found in many other industries. For example, biomanufacturing operations include high levels of uncertainty and batch-to-batch variability in production yield, lead times, and costs. Additionally, the high cost of equipment and labor-intensive nature of operations preclude the ability to flexibly add capacity. Facing these challenges, we decided that harnessing the power of operations research and advanced analytics to complement our rich life sciences and biomanufacturing expertise was critical. After four years of collaboration with the Eindhoven University of Technology, we developed a portfolio of optimization models and decision support applications that substantially improved our biomanufacturing effectiveness. The implementation of the developed models had a significant impact by generating $200 million of additional revenue without the need for additional raw materials, energy resources, or new equipment. The developed models are widely adopted across the firm, thus enhancing its core function

Internet Sensor Grid: Experiences with Passive and Active Instruments

The Internet is constantly evolving with new emergent behaviours arising; some of them malicious. This paper discusses opportunities and research direction in an Internet sensor grid for malicious behaviour detection, analysis and countermeasures. We use two example sensors as a basis; firstly the honeyclient for malicious server and content identification (i.e. drive-by-downloads, the most prevalent attack vector for client systems) and secondly the network telescope for Internet Background Radiation detection (IBR - which is classified as unsolicited, non-productive traffic that traverses the Internet, often malicious in nature or origin). Large amounts of security data can be collected from such sensors for analysis and federating honeyclient and telescope data provides a worldwide picture of attacks that could enable the provision of countermeasures. In this paper we outline some experiences with these sensors and analyzing network telescope data through Grid computing as part of an “intelligence layer” within the Internet

Dielectron Cross Section Measurements in Nucleus-Nucleus Reactions at 1.0 A GeV

We present measured dielectron production cross sections for Ca+Ca, C+C, He+Ca, and d+Ca reactions at 1.0 A GeV. Statistical uncertainties and systematic effects are smaller than in previous DLS nucleus-nucleus data. For pair mass < 0.35 GeV/c2 : 1) the Ca+Ca cross section is larger than the previous DLS measurement and current model results, 2) the mass spectra suggest large contributions from pi0 and eta Dalitz decays, and 3) dsigma/dM is proportional to ApAt. For M > 0.5 GeV/c2 the Ca+Ca to C+C cross section ratio is significantly larger than the ratio of ApAt values.Comment: Submitted to Physical Review Letters. Further analysis information will be posted on our web pages -- http://macdls.lbl.gov Figure 1 has been redrawn to make more legible. Text modified to support redrawn figur