Safety and immunogenicity of a mutagenized, live attenuated Rift Valley fever vaccine, MP-12, in a Phase 1 dose escalation and route comparison study in humans.

Rift Valley fever (RVF) poses a risk as a potential agent in bioterrorism or agroterrorism. A live attenuated RVF vaccine (RVF MP-12) has been shown to be safe and protective in animals and showed promise in two initial clinical trials. In the present study, healthy adult human volunteers (N=56) received a single injection of (a) RVF MP-12, administered subcutaneously (SQ) at a concentration of 10(4.7) plaque-forming units (pfu) (SQ Group); (b) RVF MP-12, administered intramuscularly (IM) at 10(3.4)pfu (IM Group 1); (c) RVF MP-12, administered IM at 10(4.4)pfu (IM Group 2); or (d) saline (Placebo Group). The vaccine was well tolerated by volunteers in all dose and route groups. Infrequent and minor adverse events were seen among recipients of both placebo and RVF MP-12. One subject had viremia detectable by direct plaque assay, and six subjects from IM Group 2 had transient low-titer viremia detectable only by nucleic acid amplification. Of the 43 vaccine recipients, 40 (93%) achieved neutralizing antibodies (measured as an 80% plaque reduction neutralization titer [PRNT80]) as well as RVF-specific IgM and IgG. The highest peak geometric mean PRNT80 titers were observed in IM Group 2. Of 34 RVF MP-12 recipients available for testing 1 year following inoculation, 28 (82%) remained seropositive (PRNT80≥1:20); this included 20 of 23 vaccinees (87%) from IM Group 2. The live attenuated RVF MP-12 vaccine was safe and immunogenic at the doses and routes studied. Given the need for an effective vaccine against RVF virus, further evaluation in humans is warranted.

An assessment of health status among medical research volunteers who served in the Project Whitecoat program at Fort Detrick, Maryland.

Between 1954 and 1973, more than 2000 men entering military service as conscientious objectors participated in Project Whitecoat as medical research volunteers for the Army's biological warfare defense program. An assessment of self-reported, current health status among 358 "exposed" individuals and 164 unexposed control subjects found no conclusive evidence that receipt of investigational agents was related to adverse health outcomes. No differences in current overall health, current exercise levels, self-reported symptoms, and self-reported medical conditions were seen between the study groups. Possible associations were seen between exposure to antibiotics or other biological agents and self-reported asthma (13.0% vs. 2.4%, relative risk [RR] = 6.00, 95% confidence interval [CI] = 1.03-34.90, p = 0.050), as well as between receipt of tularemia vaccine(s) and self-reported asthma (13.3% vs. 2.4%, RR = 6.15, 95% CI = 1.03-36.70, p = 0.049) and increased frequency/severity of headaches (35.6% vs. 18.3%, RR = 2.46, 95% CI = 0.99-6.15, p = 0.074). However, the size of the population under study was insufficient to assert with confidence that these statistical associations are real.

Medical informatics standards applicable to emergency department information systems: making sense of the jumble.

The adoption of medical informatics standards by emergency department information systems (EDISs) is not universal, despite obvious benefits. Clinicians and administrators looking to obtain an EDIS need to know exactly what the various standards can do for them and how the systems they depend on can be integrated and extended. In addition to the standard methods for systems to communicate (chiefly Health Level 7 [HL7]) and those required for submission of claims (Current Procedural Terminology [CPT]-4, International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM], and X12N), there are several other available standards that are clinically useful and can greatly improve the ability to access and exchange patient information. Major advances in the Unified Medical Language System of the National Library of Medicine have made the patient medical record information standards (Systematized Nomenclature of Medicine [SNOMED], Logical Observation Identifiers, Names, and Codes [LOINC], RxNorm) easily accessible. Detailed knowledge of the arcana associated with the technical aspects of the standards is not needed (or desired) by clinicians to use standards-based systems. However, some knowledge about the commonly used standards is helpful in choosing an EDIS, interfacing the EDIS with the other hospital information systems, extending or upgrading systems, and adopting decision support technologies.

Disparate systems, disparate data: integration, interfaces, and standards in emergency medicine information technology.

As part of the broader informatics consensus initiative sponsored by Academic Emergency Medicine, this report addresses the issues of integration, interfaces, and data standards and how they are relevant to information management in emergency medicine. The purpose of this report, and the workgroup that contributed to its content, is to provide emergency physicians and other stakeholders in the emergency informatics community a sense of direction as they design, build, and/or choose systems. Problems are identified, strategies to address these problems are discussed, and consensus recommendations are provided.

Computerized physician order entry and online decision support.

Computerized physician order entry (CPOE) and decision support systems (DSS) can reduce certain types of error but often slow clinicians and may increase other types of error. The net effect of these systems on an emergency department (ED) is unknown. The consensus participants combined published evidence with expert opinion to outline recommendations for success. These include seamless integration of CPOE and DSS into systems and workflow; ensuring access to Internet-based and other online support material in the clinical arena; designing systems specifically for the ED and measuring their impact to ensure an overall benefit; ensuring that CPOE systems provide error and interaction checking and facilitate weight- and physiology-based dosing; using interruptive alerts only for the highest-severity events; providing a simple, vendor-independent interface for institutional customization of CPOE alert thresholds; maximizing the use of automated systems and passive data capture; and ensuring the widespread availability of CPOE and DSS using secure wireless and portable technologies where appropriate. Decisions regarding CPOE and DSS in the ED should be guided by the ED chair or designee. Much of what is believed to be true regarding CPOE and DSS has not been adequately studied. Additional CPOE and DSS research is needed quickly, and this research should receive funding priority. DSS and CPOE hold great promise to improve patient care, but not all systems are equal. Evidence must guide these efforts, and the measured outcomes must consider the many factors of quality care.

Toward vocabulary control for chief complaint.

The chief complaint (CC) is the data element that documents the patient's reason for visiting the emergency department (ED). The need for a CC vocabulary has been acknowledged at national meetings and in multiple publications, but to our knowledge no groups have specifically focused on the requirements and development plans for a CC vocabulary. The national consensus meeting "Towards Vocabulary Control for Chief Complaint" was convened to identify the potential uses for ED CC and to develop the framework for CC vocabulary control. The 10-point consensus recommendations for action were 1) begin to develop a controlled vocabulary for CC, 2) obtain funding, 3) establish an infrastructure, 4) work with standards organizations, 5) address CC vocabulary characteristics for all user communities, 6) create a collection of CC for research, 7) identify the best candidate vocabulary for ED CCs, 8) conduct vocabulary validation studies, 9) establish beta test sites, and 10) plan publicity and marketing for the vocabulary.

Long-term health effects of repeated exposure to multiple vaccines.

The health of 155 former workers in a US military research program who had received multiple vaccines and 265 matched community controls was assessed. The study population was mostly male (83%) and elderly (median age, 69 years). Multiply immunized (MIP) subjects received vaccines and/or skin tests (median = 154) over a median of 17.3 years; interval from start of immunizations to survey completion was 15-55 years (mean = 43.1 years). MIP subjects characterized themselves as slightly less healthy than controls (P = 0.057). Fatigue (but no other symptom) was reported more frequently in the MIP group (P = 0.011), but was not associated with number of injections, number of vaccines, or time in program. No differences between MIP and control groups were seen for numerous self-reported medical conditions. Several statistically significant abnormalities were seen in clinical laboratory tests among MIP subjects, but none appeared to be clinically significant. A significant difference in frequency of monoclonal spikes and/or paraprotein peaks between MIP (12.5%) and control (4.5%) groups (RR = 2.7, P < 0.003) was observed; no associations with lifestyle, vaccine exposure, or medical conditions were found.

Anthrax vaccine: immunogenicity and safety of a dose-reduction, route-change comparison study in humans.

Anthrax vaccine adsorbed (AVA), an effective countermeasure against anthrax, is administered as six subcutaneous (SQ) doses over 18 months. To optimize the vaccination schedule and route of administration, we performed a prospective pilot study comparing the use of fewer AVA doses administered intramuscularly (IM) or SQ with the current schedule and route. We enrolled 173 volunteers, randomized to seven groups, who were given AVA once IM or SQ; two doses, 2 or 4 weeks apart, IM or SQ; or six doses at 0, 2, 4 weeks and 6, 12, and 18 months (control group, licensed schedule and route). IM administration of AVA was associated with fewer injection site reactions than SQ administration. Following the first SQ dose of AVA, compared to males, females had a significantly higher rate of injection site reactions such as erythema, induration and subcutaneous nodules (P<0.001). Reaction rates decreased with a longer dose interval between the first two doses. The peak anti-PA IgG antibody response of subjects given two doses of AVA 4 weeks apart IM or SQ was comparable to that seen among subjects who received three doses of AVA at 2-week intervals. The IM route of administering this aluminum hydroxide adsorbed vaccine is safe and has comparable peak anti-PA IgG antibody levels when two doses are administered 4 weeks apart compared to the licensed initial dose schedule of three doses administered 2 weeks apart. A large pivotal study is being planned by the Centers for Disease Control and Prevention to confirm these results.