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A permethrin metabolite is associated with adaptive immune responses in Gulf War IllnessGulf War Illness (GWI), affecting 30% of veterans from the 1991 Gulf War (GW), is a multi-symptom illness with features similar to those of patients with autoimmune diseases. The objective of the current work is to determine if exposure to GW-related pesticides, such as permethrin (PER), activates peripheral and central nervous system (CNS) adaptive immune responses. In the current study, we focused on a PER metabolite, 3-phenoxybenzoic acid (3-PBA), as this is a common metabolite previously shown to form adducts with endogenous proteins. We observed the presence of 3-PBA and 3-PBA modified lysine of protein peptides in the brain, blood and liver of pyridostigmine bromide (PB)and PER (PB+PER) exposed mice at acute and chronic post-exposure timepoints. We tested whether 3-PBA-haptenated albumin (3-PBA-albumin) can activate immune cells since it is known that chemically haptenated proteins can stimulate immune responses. We detected autoantibodies against 3-PBA-albumin in plasma from PB+PER exposed mice and veterans with GWI at chronic post-exposure timepoints. We also observed that in vitro treatment of blood with 3-PBA-albumin resulted in the activation of B- and T-helper lymphocytes and that these immune cells were also increased in blood of PB+PER exposed mice and veterans with GWI. These immune changes corresponded with elevated levels of infiltrating monocytes in the brain and blood of PB+PER exposed mice which coincided with alterations in the markers of blood-brain barrier disruption, brain macrophages and neuroinflammation. These studies suggest that pesticide exposure associated with GWI may have resulted in the activation of the peripheral and CNS adaptive immune responses, possibly contributing to an autoimmune-type phenotype in veterans with GWI.
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Prescribers' responses to alerts during medication ordering in the long term care settingOBJECTIVE: Computerized physician order entry with clinical decision support has been shown to improve medication safety in adult inpatients, but few data are available regarding its usefulness in the long-term care setting. The objective of this study was to examine opportunities for improving medication safety in that clinical setting by determining the proportion of medication orders that would generate a warning message to the prescriber via a computerized clinical decision support system and assessing the extent to which these alerts would affect prescribers' actions. DESIGN: The study was set within a randomized controlled trial of computerized clinical decision support conducted in the long-stay units of a large, academically-affiliated long-term care facility. In March 2002, a computer-based clinical decision support system (CDSS) was added to an existing computerized physician order entry (CPOE) system. Over a subsequent one-year study period, prescribers ordering drugs for residents on three resident-care units of the facility were presented with alerts; these alerts were not displayed to prescribers in the four control units. MEASUREMENTS: We assessed the frequency of drug orders associated with various categories of alerts across all participating units of the facility. To assess the impact of actually receiving an alert on prescriber behavior during drug ordering, we calculated separately for the intervention and control units the proportion of the alerts, within each category, that were followed by an appropriate action and estimated the relative risk of an appropriate action in the intervention units compared to the control units. RESULTS: During the 12 months of the study, there were 445 residents on the participating units of the facility, contributing 3,726 resident-months of observation time. During this period, 47,997 medication orders were entered through the CPOE system-approximately 9 medication orders per resident per month. 9,414 alerts were triggered (2.5 alerts per resident-month). The alert categories most often triggered were related to risks of central nervous system side-effects such as over-sedation (20%). Alerts for risk of drug-associated constipation (13%) or renal insufficiency/electrolyte imbalance (12%) were also common. Twelve percent of the alerts were related to orders for warfarin. Overall, prescribers who received alerts were only slightly more likely to take an appropriate action (relative risk 1.11, 95% confidence interval 1.00, 1.22). Alerts related to orders for warfarin or central nervous system side effects were most likely to engender an appropriate action, such as ordering a recommended laboratory test or canceling an ordered drug. CONCLUSION: Long-term care facilities must implement new system-level approaches with the potential to improve medication safety for their residents. The number of medication orders that triggered a warning message in this study suggests that CPOE with a clinical decision support system may represent one such tool. However, the relatively low rate of response to these alerts suggests that further refinements to such systems are required, and that their impact on medication errors and adverse drug events must be carefully assessed.
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Computerized physician order entry with clinical decision support in the long-term care setting: insights from the Baycrest Centre for Geriatric Care.Although computerized physician order entry (CPOE) has been successfully implemented in many acute care hospitals, few descriptions of its use in the long-term care (LTC) setting are available. This report describes the experiences of one LTC facility in developing and implementing a CPOE system with clinical decision support (CDS). Even when a facility has the necessary resources and "institutional will," many challenges are associated with the implementation of this application. The system was designed to meet the needs of healthcare providers in the LTC setting, in particular by informing prescribing decisions, reducing the frequency of prescribing and monitoring errors, and reducing adverse drug event rates. Based on experience adopting this technology early, 10 insights are offered that it is hoped will assist others who are considering the implementation of CPOE systems with CDS in the LTC setting.
