The reviewers were not blinded to the intent of the study. Data were entered into a LBH589 in vitro Microsoft Access database (Microsoft Access 2003®, Microsoft Corporation, Redmond, WA, 2003) and double verified to ensure accuracy of data entry. Disagreement between the abstractors was identified and resolved by consensus. Included cases were reviewed to identify duplicate publication; Inhibitors,research,lifescience,medical where necessary, study authors were contacted to determine if cases reported in different publications were one and the same. Data were analyzed using SAS (v. 9.1, SAS Institute, Cary, NC). Descriptive statistics were used; confidence intervals were not presented due

to small sample sizes. The definition of “severe” envenomation was that used in the US FDA-approved prescribing information for FabAV (Table ​(Table2).2). This standard definition contains several areas of ambiguity, which were resolved a priori as follows: Table 2 Definitions of Envenomation Inhibitors,research,lifescience,medical Severity from the FabAV Prescribing Information[3] The standard definition of local tissue effects Inhibitors,research,lifescience,medical classifies, “swelling, pain, or ecchymosis involving less than a full extremity,” as “moderate,” and, “swelling, pain or ecchymosis involving more than an entire extremity,” as “severe.” We included cases involving

swelling, pain, or ecchymosis involving exactly an entire extremity in the “severe” group. The standard definition of neurotoxicity classifies, “oral paresthesias or unusual tastes,” as “moderate,” but has no criteria for severe neurotoxicity. We considered severe muscle weakness, difficulty speaking Inhibitors,research,lifescience,medical or swallowing, and fasciculations remote from the bite site (sometimes a sign of impending paralysis) to be signs of severe neurotoxicity. The phrase, “coagulation parameters are abnormal, with serious bleeding

or severe threat of bleeding,” in the standard definition required more precise definition. Using published criteria, we considered “severe threat of bleeding” to be present if the platelet count was less than 50,000 cells/mm3, if the fibrinogen was less than Inhibitors,research,lifescience,medical 50 mg/dl (1.5 micromol/L), or if the international normalized ratio (INR) or protime ratio were > 5.0[8] If protime was reported without INR or normal range data, a protime > 50 seconds was considered to represent severe threat of bleeding. The Rolziracetam standard definition does not specify a time point at which severity is assessed. In order to mirror clinical practice, we graded the severity of envenomation based on the initial presentation, i.e. the patient’s clinical condition during the first six hours after presentation for care. Cases that were of minimal or moderate severity on initial presentation, but that developed one or more features of severe envenomation many hours or days later, were counted as “minimal” or “moderate” based on the severity of the initial presentation.