The Efficacy of Crotalidae Polyvalent Immune Fab (Ovine) Antivenom Versus Placebo Plus Optional Rescue Therapy on Recovery From Copperhead Snake Envenomation: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial

Study objective: Copperhead snake (Agkistrodon contortrix) envenomation causes limb injury resulting in pain and disability. It is not known whether antivenom administration improves limb function. We determine whether administration of antivenom improves recovery from limb injury in patients envenomated by copperhead snakes. Methods: From August 2013 through November 2015, we performed a multicenter, randomized, double-blind, placebo- controlled, clinical trial to evaluate the effect of ovine Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) antivenom therapy on recovery of limb function in patients with copperhead snake envenomation at 14 days postenvenomation. The study setting was 18 emergency departments in regions of the United States where copperhead snakes are endemic. Consecutive patients aged 12 years or older with mild- to moderate-severity envenomation received either FabAV or placebo. The primary outcome was limb function 14 days after envenomation, measured by the Patient-Specific Functional Scale. Additional outcomes included the Patient-Specific Functional Scale at other points; the Disorders of the Arm, Shoulder, and Hand, Lower Extremity Functional Scale, and Patient’s Global Impression of Change instruments; grip strength; walking speed; quality of life (Patient-Reported Outcomes Measurement Information System Physical Fucntion-10); pain; and analgesic use. Results: Seventy-four patients received study drug (45 FabAV, 29 placebo). Mean age was 43 years (range 12 to 86 years). Fifty-three percent were men, 62% had lower extremity envenomation, and 88% had mild initial severity. The primary outcome, the least square mean Patient-Specific Functional Scale score at 14 days postenvenomation, was 8.6 for FabAV-treated subjects and 7.4 for placebo recipients (difference 1.2; 95% confidence interval 0.1 to 2.3; P1�4.04). Additional outcome assessments generally favored FabAV. More FabAV-treated subjects experienced treatment- emergent adverse events (56% versus 28%), but few were serious (1 in each group). Conclusion: Treatment with FabAV reduces limb disability measured by the Patient-Specific Functional Scale 14 days after copperhead envenomation. [Ann Emerg Med. 2017;70:233-244.

The validity, reliability and minimal clinically important difference of the patient specific functional scale in snake envenomation

Objective: Valid, reliable, and clinically relevant outcome measures are necessary in clinical studies of snake envenomation. The aim of this study was to evaluate the psychometric (validity and reliability) and clinimetric (minimal clinically important difference [MCID]) properties of the Patient-Specific Functional Scale (PSFS) in snakebite envenomation. Methods: We performed a secondary analysis of two existing snakebite trials that measured clinical outcomes using the PSFS as well as other quality of life and functional assessments. Data were collected at 3, 7, 10, and 17 days. Reliability was determined using Cronbach’s alpha for internal consistency and the intraclass correlation coefficient (ICC) for temporal stability at 10 and 17 days. Validity was assessed using concurrent validity correlating with the other assessments. The MCID was evaluated using the following criteria: (1) the distribution of stable patients according to both standard error of measurement (SEM) and responsiveness techniques, and (2) anchor-based methods to compare between individuals and to detect discriminant ability of a positive change with a receiver operator characteristic (ROC) curve and optimal cutoff point. Results: A total of 86 patients were evaluated in this study. The average PSFS scores were 5.37 (SD 3.23), 7.95 (SD 2.22), and 9.12 (SD 1.37) at 3, 7, and 10 days, respectively. Negligible floor effect was observed (maximum of 8% at 3 days); however, a ceiling effect was observed at 17 days (25%). The PSFS showed good reliability with an internal consistency of 0.91 (Cronbach’s alpha) (95% CI 0.88, 0.95) and a temporal stability of 0.83 (ICC) (95% CI 0.72, 0.89). The PSFS showed a strong positive correlation with quality of life and functional assessments. The MCID was approximately 1.0 for all methods. Conclusions: With an MCID of approximately 1 point, the PSFS is a valid and reliable tool to assess quality of life and functionality in patients with snake envenomation

The Effect of All-Terrain Vehicle Crash Location on Emergency Medical Services Time Intervals

Over 100,000 all-terrain vehicle (ATV)-related injuries are evaluated in U.S. emergency departments each year. In this study, we analyzed the time intervals for emergency medical services (EMS) providers responding to ATV crashes in different location types. Data from the Iowa State Trauma Registry and a statewide ATV crash/injury database was matched with Iowa EMS Registry records from 2004–2014. Ground ambulance responses to 270 ATV crashes were identified, and response characteristics and time intervals were analyzed. Off-road crashes had a longer median patient access interval (p < 0.001) and total on scene interval (p = 0.002) than roadway crashes. Crashes in remote locations had a longer median patient access interval (p < 0.001) and total on scene interval (p < 0.001), but also a longer median on scene with patient interval (p = 0.004) than crashes in accessible locations. Fifteen percent of remote patient access times were >6 min as compared to 3% of accessible crashes (p = 0.0004). There were no differences in en route to scene or en route to hospital time. Comparisons by location type showed no differences in injury severity score or number of total procedures performed. We concluded that responding EMS providers had an increased length of time to get to the patient after arriving on scene for off-road and remote ATV crashes relative to roadway and accessible location crashes, respectively

The Effect of a Surveillance Banner in an Attacked Computer System: Additional Evidence for the Relevance of Restrictive Deterrence in Cyberspace

Objectives: Test whether the presence of a surveillance message on an attacked computer system influences system trespassers’ active engagement with the compromised system (i.e., entering computer commands). The hypothesized restrictive deterrent effect is tested both in the context of a first system trespassing incident and in the progression of repeated trespassing incidents in an attacked computer system. Methods: We designed a randomized controlled trial and deployed a series of virtual target computers with known vulnerabilities into the computer network of a large public university in the United States. The target computers were set to either display or not display a surveillance banner once system trespassers infiltrated them. Results: We find that the presence of a surveillance banner in the attacked computer systems reduced the probability of commands being typed in the system during longer first system trespassing incidents. Further, we find that the probability of commands being typed during subsequent system trespassing incidents (on the same target computer) is conditioned by the presence of a surveillance banner and by whether commands have been entered during previous trespassing incidents. Conclusions: These findings offer modest support for the application of restrictive deterrence in the study of system trespassing

Non-invasive and invasive diagnoses of aspergillosis in a rat model by mass spectrometry

Invasive pulmonary aspergillosis results in 450,000 deaths per year and complicates cancer chemotherapy, transplantations and the treatment of other immunosuppressed patients. Using a rat model of experimental aspergillosis, the fungal siderophores ferricrocin and triacetylfusarinine C were identified as markers of aspergillosis and quantified in urine, serum and lung tissues. Biomarkers were analyzed by matrix-assisted laser desorption ionization (MALDI) and electrospray ionization mass spectrometry using a 12T SolariX Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. The limits of detection of the ferri-forms of triacetylfusarinine C and ferricrocin in the rat serum were 0.28 and 0.36 ng/mL, respectively. In the rat urine the respective limits of detection achieved 0.02 and 0.03 ng/mL. In the sera of infected animals, triacetylfusarinine C was not detected but ferricrocin concentration fluctuated in the 3-32 ng/mL range. Notably, the mean concentrations of triacetylfusarinine C and ferricrocin in the rat urine were 0.37 and 0.63 μg/mL, respectively. The MALDI FTICR mass spectrometry imaging illustrated the actual microbial ferricrocin distribution in the lung tissues and resolved the false-positive results obtained by the light microscopy and histological staining. Ferricrocin and triacetylfusarinine C detection in urine represents an innovative non-invasive indication of Aspergillus infection in a host