Faculty Bibliography

A paradoxical drug reaction constitutes an outcome that is opposite from the outcome that would be expected from the drug's known actions. There are three types: 1. A paradoxical response in a condition for which the drug is being explicitly prescribed. 2. Paradoxical precipitation of a condition for which the drug is indicated, when the drug is being used for an alternative indication. 3. Effects that are paradoxical in relation to an aspect of the pharmacology of the drug but unrelated to the usual indication. In bidirectional drug reactions, a drug may produce opposite effects, either in the same or different individuals, the effects usually being different from the expected beneficial effect. Paradoxical and bidirectional drug effects can sometimes be harnessed for benefit; some may be adverse. Such reactions arise in a wide variety of drug classes. Some are common; others are reported in single case reports. Paradoxical effects are often adverse, since they are opposite the direction of the expected effect. They may complicate the assessment of adverse drug reactions, pharmacovigilance, and clinical management. Bidirectional effects may be clinically useful or adverse. From a clinical toxicological perspective, altered pharmacokinetics or pharmacodynamics in overdose may exacerbate paradoxical and bidirectional effects. Certain antidotes have paradoxical attributes, complicating management. Apparent clinical paradoxical or bidirectional effects and reactions ensue when conflicts arise at different levels in self-regulating biological systems, as complexity increases from subcellular components, such as receptors, to cells, tissues, organs, and the whole individual. These may be incompletely understood. Mechanisms of such effects include different actions at the same receptor, owing to changes with time and downstream effects; stereochemical effects; multiple receptor targets with or without associated temporal effects; antibody-mediated reactions; three-dimensional architectural constraints; pharmacokinetic competing compartment effects; disruption and non-linear effects in oscillating systems, systemic overcompensation, and other higher-level feedback mechanisms and feedback response loops at multiple levels. Here we review and provide a compendium of multiple class effects and individual reactions, relevant mechanisms, and specific clinical toxicological considerations of antibiotics, immune modulators, antineoplastic drugs, and cardiovascular, CNS, dermal, endocrine, musculoskeletal, gastrointestinal, haematological, respiratory, and psychotropic agents.

Although wolf spider venom has been implicated in necrotic arachnidism without acceptably documented verification, limited, prospectively collected data demonstrate a lack of cutaneous necrosis. The infrequent nature of exposure and inherent difficulty in confirming wolf spider bites in humans makes it challenging to study such envenomations. We present the case of a 20 year-old man with confirmed exposure to the wolf spider who developed cutaneous erythema with ulceration following the bite. There was no evidence of skin necrosis. He was treated with aggressive wound care and systemic antibiotics for wound infection, with subsequent resolution of symptoms. This case adds to the limited knowledge regarding wolf spider envenomations and describes the clinical effects and management of wolf spider envenomation.

BACKGROUND: The recent H1N1 influenza A pandemic was marked by multiple reports of illness and hospitalization in children, suggesting that children may have played a major role in the propagation of the virus. A comprehensive detailed analysis of the attack rates among children as compared with their contacts in various settings is of great importance for understanding their unique role in influenza pandemics. METHODOLOGY/PRINCIPAL FINDINGS: We searched MEDLINE (PubMed) and Embase for published studies reporting outbreak investigations with direct measurements of attack rates of the 2009 pandemic H1N1 influenza A among children, and quantified how these compare with those of their contacts. We identified 50 articles suitable for review, which reported school, household, travel and social events. The selected reports and our meta-analysis indicated that children had significantly higher attack rates as compared to adults, and that this phenomenon was observed for both virologically confirmed and clinical cases, in various settings and locations around the world. The review also provided insight into some characteristics of transmission between children and their contacts in the various settings. CONCLUSION/SIGNIFICANCE: The consistently higher attack rates of the 2009 pandemic H1N1 influenza A among children, as compared to adults, as well as the magnitude of the difference is important for understanding the contribution of children to disease burden, for implementation of mitigation strategies directed towards children, as well as more precise mathematical modeling and simulation of future influenza pandemics.

STUDY OBJECTIVE: The ECG is an essential tool in the care of poisoned patients. This study is designed to investigate the accuracy of ECG interpretation reported to a poison center. METHODS: In this prospective study, all cases in which both an electronically faxed copy of the ECG and the caller's interpretation of the ECG were available were eligible for inclusion. ECG interpretation of callers was compared with that of a blinded electrophysiologist. In cases of disagreement, a Delphi panel of toxicologists decided whether the differences were clinically significant or would have changed recommendations. RESULTS: Two hundred cases were included, with complete agreement in 78. In 23 cases, the sole difference was nonspecific ST-T-wave changes, which were believed insignificant and classified as agreement for a total of 101. The Delphi panel reviewed the remaining 99. In 42 cases, the differences in ECG interpretations were thought to be clinically significant; 37 of these would have resulted in a change in management recommendations. Forty-five cases were thought not likely to be clinically significant and would not have resulted in a recommendation change. Twelve cases were thought not clinically significant but would still have resulted in a change in recommendations. CONCLUSION: Initial interpretation of the ECG reported by callers to the poison center is frequently inaccurate. In this study, the misinterpretation was clinically significant or would have resulted in a change in management recommendations in approximately one quarter of all calls

BACKGROUND: Agents of opportunity (AO) are potentially harmful biological, chemical, radiological, and pharmaceutical substances commonly used for health care delivery and research. AOs are present in all academic medical centers (AMC), creating vulnerability in the health care sector; AO attributes and dissemination methods likely predict risk; and AMCs are inadequately secured against a purposeful AO dissemination, with limited budgets and competing priorities. We explored health care workers' perceptions of AMC security and the impact of those perceptions on AO risk. METHODS: Qualitative methods (survey, interviews, and workshops) were used to collect opinions from staff working in a medical school and 4 AMC-affiliated hospitals concerning AOs and the risk to hospital infrastructure associated with their uncontrolled presence. Secondary to this goal, staff perception concerning security, or opinions about security behaviors of others, were extracted, analyzed, and grouped into themes. RESULTS: We provide a framework for depicting the interaction of staff behavior and access control engineering, including the tendency of staff to 'defeat' inconvenient access controls. In addition, 8 security themes emerged: staff security behavior is a significant source of AO risk; the wide range of opinions about 'open' front-door policies among AMC staff illustrates a disparity of perceptions about the need for security; interviewees expressed profound skepticism concerning the effectiveness of front-door access controls; an AO risk assessment requires reconsideration of the security levels historically assigned to areas such as the loading dock and central distribution sites, where many AOs are delivered and may remain unattended for substantial periods of time; researchers' view of AMC security is influenced by the ongoing debate within the scientific community about the wisdom of engaging in bioterrorism research; there was no agreement about which areas of the AMC should be subject to stronger access controls; security personnel play dual roles of security and customer service, creating the negative perception that neither role is done well; and budget was described as an important factor in explaining the state of security controls. CONCLUSIONS: We determined that AMCs seeking to reduce AO risk should assess their institutionally unique AO risks, understand staff security perceptions, and install access controls that are responsive to the staff's tendency to defeat them. The development of AO attribute fact sheets is desirable for AO risk assessment; new funding and administrative or legislative tools to improve AMC security are required; and security practices and methods that are convenient and effective should be engineered