GeriMedRisk, a telemedicine geriatric pharmacology consultation service to address adverse drug events in long-term care: a stepped-wedge cluster randomized feasibility trial protocol (ISRCTN17219647).

BACKGROUND: Multimorbidity, polypharmacy, and older age predispose seniors to adverse drug events (ADE). Seniors with an ADE experience greater morbidity, mortality, and health care utilization compared to their younger counterparts. To mitigate and manage ADEs among this vulnerable population, we designed a geriatric pharmacology consultation service connecting clinicians with specialist physicians and pharmacists and will investigate the feasibility and acceptability of this complex intervention in the long-term care setting, prior to conducting a larger efficacy trial. METHODS/DESIGN: We will conduct a cluster randomized feasibility trial and qualitative analysis of GeriMedRisk among four long-term care homes in the Waterloo-Wellington region from May 1 to December 31, 2017. The primary outcome is the feasibility and acceptability of GeriMedRisk and the stepped-wedge cluster randomized controlled trial design. We hypothesize that GeriMedRisk is a feasible intervention and its potential to decrease falls and drug-related hospital visits can be evaluated with a stepped-wedge cluster randomized controlled trial design. DISCUSSION: This mixed methods study will inform a larger efficacy trial of GeriMedRisk's ability to decrease adverse drug events among seniors in the long-term care setting. ETHICS AND DISSEMINATION: The Hamilton Integrated Research Ethics Board granted the approval for this study protocol 2812. We plan to disseminate the results of this study in peer-reviewed journals and also to our partners and stakeholders. TRIAL REGISTRATION: ISRCTN clinical trials registry, ISRCTN17219647 (March 27, 2017).

Discernment between deliberate and natural infectious disease outbreaks.

Public health authorities should be vigilant to the potential for outbreaks deliberately caused by biological agents (bioterrorism). Such events require a rapid response and incorporation of non-traditional partners for disease investigation and outbreak control. The astute application of infectious disease epidemiological principles can promote an enhanced index of suspicion for such events. We discuss epidemiological indicators that should be considered during outbreak investigations, and also examine their application during bioterrorism incidents, an accidental release of an agent, outbreaks of infections that were alleged to have been deliberately initiated, and a model scenario. The Grunow & Finke epidemiological assessment tool is used to examine these historical events and the model scenario. The results received from this analysis, coupled with an understanding of epidemiological clues to unnatural events, and knowledge of how to manage such events, can aid in the improved response and resolution of epidemics.

Implementation of laboratory order data in BioSense Early Event Detection and Situation Awareness System.

INTRODUCTION: Laboratory test orders constitute an early outbreak data source. CDC receives laboratory order data in HL7 format from the Laboratory Corporation of America (LabCorp) and plans to use the data in the BioSense Early Event Detection and Situation Awareness System. METHODS: These LabCorp data contain information on tests ordered and include the type of test ordered and the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-coded reasons for the order. A consensus panel was formed to group test orders on the basis of expert opinion into eight standard syndrome categories to provide an additional data source for early outbreak detection. A laboratory order taxonomy was developed and used in the mapping consolidation phase. The five main classes of this taxonomy are miscellaneous functional tests, fluid screening tests, system-specific tests, tests for specific infections (by primary manifestation), and tests for specific noninfectious diseases. RESULTS: Summary of numbers of laboratory order codes in each syndrome category are fever (53), respiratory (53), gastrointestinal (27), neurological (35), rash (37), lymphadenitis (20), localized cutaneous lesion (11), and specific infection (63). CONCLUSION: With the daily use of laboratory order data in BioSense, the actual distribution of laboratory order codes in syndrome groups can be evaluated, allowing modification of the mapping.

An evaluation model for syndromic surveillance: assessing the performance of a temporal algorithm.

INTRODUCTION: Syndromic surveillance offers the potential to rapidly detect outbreaks resulting from terrorism. Despite considerable experience with implementing syndromic surveillance, limited evidence exists to describe the performance of syndromic surveillance systems in detecting outbreaks. OBJECTIVES: To describe a model for simulating cases that might result from exposure to inhalational anthrax and then use the model to evaluate the ability of syndromic surveillance to detect an outbreak of inhalational anthrax after an aerosol release. METHODS: Disease progression and health-care use were simulated for persons infected with anthrax. Simulated cases were then superimposed on authentic surveillance data to create test data sets. A temporal outbreak detection algorithm was applied to each test data set, and sensitivity and timeliness of outbreak detection were calculated by using syndromic surveillance. RESULTS: The earliest detection using a temporal algorithm was 2 days after a release. Earlier detection tended to occur when more persons were infected, and performance worsened as the proportion of persons seeking care in the prodromal disease state declined. A shorter median incubation state led to earlier detection, as soon as 1 day after release when the incubation state was < or =5 days. CONCLUSION: Syndromic surveillance of a respiratory syndrome using a temporal detection algorithm tended to detect an anthrax attack within 3-4 days after exposure if >10,000 persons were infected. The performance of surveillance (i.e., timeliness and sensitivity) worsened as the number of persons infected decreased.

Evaluation of syndromic surveillance systems--design of an epidemic simulation model.

INTRODUCTION: The paucity of outbreak data from biologic terrorism and emerging infectious diseases limits the evaluation of syndromic surveillance systems. Evaluation using naturally occurring outbreaks of proxy disease (e.g., influenza) is one alternative but does not allow for rigorous evaluation. Another approach is to inject simulated outbreaks into real background data, but existing simulation models generally do not account for such factors as spatial mobility and do not explicitly incorporate knowledge of the disease agent. OBJECTIVE: The objective of this analysis was to design a simulated anthrax epidemic injection model that accounts for the complexity of the background data and enables sensitivity analyses based on uncertain disease-agent characteristics. MODEL REQUIREMENTS AND ASSUMPTIONS: Model requirements are described and used to limit the scope of model development. Major assumptions used to limit model complexity are also described. Available literature on inhalational anthrax is reviewed to ensure that the level of model detail reflects available disease knowledge. MODEL DESIGN: The model is divided into four components: 1) agent dispersion, 2) infection, 3) disease and behavior, and 4) data source. The agent-dispersion component uses a Gaussian plume model to compute spore counts on a fine grid. The infection component uses a cohort approach to identify infected persons by residential zip code, accounting for demographic covariates and spatial mobility. The disease and behavior component uses a discrete-event approach to simulate progression through disease stages and health-services utilization. The data-source component generates records to insert into background data sources. CONCLUSIONS: An epidemic simulation model was designed to enable evaluation of syndromic surveillance systems. The model addresses limitations of existing simulation approaches by accounting for such factors as spatial mobility and by explicitly modeling disease knowledge. Subsequent work entails software implementation and model validation.

Bio-ALIRT biosurveillance detection algorithm evaluation.

INTRODUCTION: Early detection of disease outbreaks by a medical biosurveillance system relies on two major components: 1) the contribution of early and reliable data sources and 2) the sensitivity, specificity, and timeliness of biosurveillance detection algorithms. This paper describes an effort to assess leading detection algorithms by arranging a common challenge problem and providing a common data set. OBJECTIVES: The objectives of this study were to determine whether automated detection algorithms can reliably and quickly identify the onset of natural disease outbreaks that are surrogates for possible terrorist pathogen releases, and do so at acceptable false-alert rates (e.g., once every 2-6 weeks). METHODS: Historic de-identified data were obtained from five metropolitan areas over 23 months; these data included International Classification of Diseases, Ninth Revision (ICD-9) codes related to respiratory and gastrointestinal illness syndromes. An outbreak detection group identified and labeled two natural disease outbreaks in these data and provided them to analysts for training of detection algorithms. All outbreaks in the remaining test data were identified but not revealed to the detection groups until after their analyses. The algorithms established a probability of outbreak for each day's counts. The probability of outbreak was assessed as an "actual" alert for different false-alert rates. RESULTS: The best algorithms were able to detect all of the outbreaks at false-alert rates of one every 2-6 weeks. They were often able to detect for the same day human investigators had identified as the true start of the outbreak. CONCLUSIONS: Because minimal data exists for an actual biologic attack, determining how quickly an algorithm might detect such an attack is difficult. However, application of these algorithms in combination with other data-analysis methods to historic outbreak data indicates that biosurveillance techniques for analyzing syndrome counts can rapidly detect seasonal respiratory and gastrointestinal illness outbreaks. Further research is needed to assess the value of electronic data sources for predictive detection. In addition, simulations need to be developed and implemented to better characterize the size and type of biologic attack that can be detected by current methods by challenging them under different projected operational conditions.

ESSENCE II and the framework for evaluating syndromic surveillance systems.

INTRODUCTION: The Electronic Surveillance System for the Early Notification of Community-Based Epidemics (ESSENCE II) is a prototype syndromic surveillance system for capturing and analyzing public health indicators for early detection of disease outbreaks. OBJECTIVES: This paper presents a preliminary evaluation of ESSENCE II according to a CDC framework for evaluating syndromic surveillance systems. METHODS: Each major topic of the framework is addressed in this assessment of ESSENCE II performance. RESULTS: ESSENCE captures data in multiple formats, parses text strings into syndrome groupings, and applies multiple temporal and spatio-temporal outbreak-detection algorithms. During a recent DARPA evaluation exercise, ESSENCE algorithms detected a set of health events with a median delay of 1 day after the earliest possible detection opportunity. CONCLUSIONS: ESSENCE II has provided excellent performance with respect to the framework and has proven to be a useful and cost-effective approach for providing early detection of health events.

Clinical recognition and management of patients exposed to biological warfare agents.

Concern regarding the use of biological agents (bacteria, viruses, or toxins) as tools of warfare or terrorism has led to measures to deter their use or, failing that, to deal with the consequences. Unlike chemical agents, which typically lead to severe disease syndromes within minutes at the site of exposure, diseases resulting from biological agents have incubation periods of days. Rather than a paramedic, it will likely be a physician who is first faced with evidence of the results of a biological attack. Provided here is an updated primer on 11 classic BW and potential terrorist agents to increase the likelihood of their being considered in a differential diagnosis. Although the resultant diseases are rarely seen in many countries today, accepted diagnostic and epidemiologic principles apply; if the cause is identified quickly, appropriate therapy can be initiated and the impact of a terrorist attack greatly reduced.

Bioterrorism and the importance of the public health laboratory.

Biological terrorism is a threat to the United States that public health laboratories cannot afford to ignore. With the ability to recognize unusual strains of organisms, or an increase in test requests or isolation of specific organisms, the public health laboratory can detect the beginning of an outbreak. The laboratory can also facilitate appropriate response measures with rapid diagnostic testing and by determining antibiotic resistance patterns. Public health laboratory personnel need to assess their capabilities, improve them where indicated, and know where to turn for assistance. As improvements in bioterrorism detection occur in the civilian sector, military laboratories must integrate with local, state, and federal health department systems. Laboratories are essential components in surveillance, recognition, and response for both bioterrorism and naturally occurring disease outbreaks.

The Department of Defense laboratory-based global influenza surveillance system.

Military global influenza surveillance began in 1976 as an Air Force program. In 1997, the Department of Defense (DoD) Global Emerging Infections Surveillance and Response System expanded the program to include all services. Also included were local residents in areas where DoD overseas research activities operated. This new, worldwide DoD surveillance infrastructure provides valuable information and can respond quickly to outbreaks. This was demonstrated during the current influenza season when a suspected outbreak was reported in Panama. In less than 3 weeks, specimens were collected, transported, and cultured, and isolates were subtyped and sent to the Centers for Disease Control and Prevention for further studies. This influenza surveillance initiative combines viral isolation, antigenic characterization, and molecular sequencing with clinical and public health management of information. The information obtained is shared with the Centers for Disease Control and Prevention and the World Health Organization and has contributed to important decisions in influenza vaccine composition.

Immunization against potential biological warfare agents.

The intentional release of biological agents by belligerents or terrorists is a possibility that has recently attracted increased attention. Law enforcement agencies, military planners, public health officials, and clinicians are gaining an increasing awareness of this potential threat. From a military perspective, an important component of the protective pre-exposure armamentarium against this threat is immunization. In addition, certain vaccines are an accepted component of postexposure prophylaxis against potential bioterrorist threat agents. These vaccines might, therefore, be used to respond to a terrorist attack against civilians. We review the development of vaccines against 10 of the most credible biological threats.

Propofol versus isoflurane for endoscopic sinus surgery.

PURPOSE: A previous retrospective study reported that propofol anesthesia decreased bleeding during endoscopic sinus surgery compared with isoflurane. We performed a prospective study to compare the effects of propofol versus isoflurane on measured blood loss and the surgeon's subjective assessment of operating conditions during endoscopic sinus surgery. PATIENTS AND METHODS: After receiving institutional review board approval and written informed consent, 56 patients undergoing endoscopic sinus surgery were randomly assigned to receive propofol (n = 30) or isoflurane (n = 26) supplemented with nitrous oxide-oxygen and alfentanil. Blood loss was calculated from the hemoglobin concentration in suction canisters. One surgeon, who was blinded to the anesthetic agent, performed every procedure and assessed bleeding as follows: 1, no bleeding; 2, modest bleeding; 3, bleeding interfering with operating conditions and cause for an agent switch; and 4, intolerable bleeding requiring a change in surgical plan. Results were compared in the two anesthetic groups using chi-squared test, unpaired t-test, Mann-Whitney Utest, and a permutation test. A P of .05 was considered significant. RESULTS: Mean bleeding scores were less over time (P = .02) with propofol anesthesia, particularly in surgery in the ethmoid and sphenoid sinuses (P = .03), and the proportion of patients with a mean score >2 was less in the propofol group (30% v 54%; P = .033). Time until discharge to home or to a limited stay in a hospital bed was also less in the propofol group (183 v 243 minutes; P = .019). CONCLUSION: In our study, surgical blood loss was the same for both anesthetic agents overall, but propofol appeared to offer an advantage in terms of subjective improvement in operating conditions, particularly in the ethmoid and sphenoid sinuses.

Clinical recognition and management of patients exposed to biological warfare agents.

Concern regarding the use of biological agents--bacteria, viruses, or toxins--as tools of warfare or terrorism has led to measures to deter their use or, failing that, to deal with the consequences. Unlike chemical agents, which typically lead to violent disease syndromes within minutes at the site of exposure, diseases resulting from biological agents have incubation periods of days. Therefore, rather than a paramedic, it will likely be a physician who is first faced with evidence of the results of a biological attack. We provide here a primer on 10 classic biological warfare agents to increase the likelihood of their being considered in a differential diagnosis. Although the resultant diseases are rarely seen in many countries today, accepted diagnostic and epidemiologic principles apply; if the cause is identified quickly, appropriate therapy can be initiated and the impact of a terrorist attack greatly reduced.

Biological warfare. A historical perspective.

The deliberate use of microorganisms and toxins as weapons has been attempted throughout history. Biological warfare has evolved from the crude use of cadavers to contaminate water supplies to the development of specialized munitions for battlefield and covert use. The modern development of biological agents as weapons has paralleled advances in basic and applied microbiology. These include the identification of virulent pathogens suitable for aerosol delivery and industrial-scale fermentation processes to produce large quantities of pathogens and toxins. The history of biological warfare is difficult to assess because of a number of confounding factors. These include difficulties in verification of alleged or attempted biological attacks, the use of allegations of biological attacks for propaganda purposes, the paucity of pertinent microbiological or epidemiologic data, and the incidence of naturally occurring endemic or epidemic diseases during hostilities. Biological warfare has been renounced by 140 nations, primarily for strategic and other pragmatic reasons. International diplomatic efforts, including the 1972 Biological Weapons Convention, have not been entirely effective in preventing the enhancement and proliferation of offensive biological warfare programs. The threats posed by biological weapons are likely to continue into the future.

Second place--Resident Clinical Science Award 1990. A porcine model of chronic endobronchial obstruction.

To elucidate the effects of both prolonged lobar atelectasis and subsequent re-expansion in a non-thoracotomized animal, we have developed a chronic, reversible porcine model of endobronchial obstruction. Eight adolescent pigs underwent the bronchoscopic placement of a left lower lobe bronchial plug. The obstruction was left in place for 24 hours. Four pigs then had the balloon bronchoscopically removed, while four controls underwent sham removal of the balloon. All animals showed significant atelectasis of the obstructed lobe compared to non-obstructed lobes at 24 hours. Pulmonary blood flow decreased significantly 24 hours after obstruction compared to pre-obstruction values in the collapsed lobe in all animals. Re-expansion was followed by arterial hypoxemia, which was accompanied by an increase in relative blood flow to the partially re-expanded lobe in the experimental group. No significant changes in lung water content occurred in the study group compared to controls.