Managing multiple-casualty incidents: a rural medical preparedness training assessment.

OBJECTIVE: The objectives of this study were to develop a novel training model for using mass-casualty incident (MCI) scenarios that trained hospital and prehospital staff together using Microsoft Visio, images from Google Earth and icons representing first responders, equipment resources, local hospital emergency department bed capacity, and trauma victims. The authors also tested participants' knowledge in the areas of communications, incident command systems (ICS), and triage. METHODS: Participants attended Managing Multiple-Casualty Incidents (MCIs), a one-day training which offered pre- and post-tests, two one-hour functional exercises, and four distinct, one-hour didactic instructional periods. Two MCI functional exercises were conducted. The one-hour trainings focused on communications, National Incident Management Systems/Incident Command Systems (NIMS/ICS) and professional roles and responsibilities in NIMS and triage. The trainings were offered throughout communities in western Montana. First response resource inventories and general manpower statistics for fire, police, Emergency Medical Services (EMS), and emergency department hospital bed capacity were determined prior to MCI scenario construction. A test was given prior to and after the training activities. RESULTS: A total of 175 firefighters, EMS, law enforcement, hospital personnel or other first-responders completed the pre- and post-test. Firefighters produced higher baseline scores than all other disciplines during pre-test analysis. At the end of the training all disciplines demonstrated significantly higher scores on the post-test when compared with their respective baseline averages. Improvements in post-test scores were noted for participants from all disciplines and in all didactic areas: communications, NIMS/ICS, and triage. CONCLUSIONS: Mass-casualty incidents offer significant challenges for prehospital and emergency room workers. Fire, Police and EMS personnel must secure the scene, establish communications, define individuals' roles and responsibilities, allocate resources, triage patients, and assign transport priorities. After emergency department notification and in advance of arrival, emergency department personnel must assess available physical resources and availability and type of manpower, all while managing patients already under their care. Mass-casualty incident trainings should strengthen the key, individual elements essential to well-coordinated response such as communications, incident management system and triage. The practice scenarios should be matched to the specific resources of the community. The authors also believe that these trainings should be provided with all disciplines represented to eliminate training "silos," to allow for discussion of overlapping jurisdictional or organizational responsibilities, and to facilitate team building.

Vitamin D and multiple sclerosis: review of a possible association.

There has been growing interest in determining environmental risk factors that may play a role in the development or progression of multiple sclerosis (MS). Epidemiological evidence and data from human and animal studies have shown an association between low serum vitamin D levels and an increased incidence of MS and that supplementation with vitamin D may protect against MS development and/or disease relapses. The most appropriate vitamin D dosage for patients with MS is unclear, but investigator shave proposed that serum vitamin D concentrations between 75 and 100 nmol/L (30-40 ng/mL) are optimal to achieve favor able clinical outcomes. Vitamin D supplemented in doses up to 3000 International Units (IU) daily may be necessary to achieve these levels in many patients, and doses of 500 to 800 IU daily appear to be necessary to maintain desired serum vitamin D levels.Short-term supplementation with doses up to 40 000 IU daily has been found to be safe. However, larger and longer clinical studies are needed to assess whether a true relationship exists between serum vitamin D concentrations and MS and to determine a safe and effective amount of vitamin D supplementation.

Emerging oral immunomodulating agents - focus on teriflunomide for the treatment of multiple sclerosis.

Treatment for multiple sclerosis (MS), a chronic disease of the central nervous system, has historically relied exclusively on the use of injectable therapies. As the disease requires lifelong therapy, the development of oral therapies that are safe and effective would provide a more convenient dosage form that may improve patient compliance. One oral medication (fingolimod) was recently approved for treatment of MS. Teriflunomide, an immunomodulator, is one of four oral therapies currently undergoing Phase III trials. Teriflunomide exerts its clinical effects via selective inhibition of de novo pyrimidine synthesis, primarily targeting proliferating T and B lymphocytes in the periphery. Teriflunomide was effective as monotherapy in reducing magnetic resonance imaging lesions and annual relapse rates in Phase II and Phase III trials. When teriflunomide was added to interferon or glatiramer acetate therapy in Phase II trials, teriflunomide reduced magnetic resonance imaging lesions significantly more than either interferon or glatiramer acetate alone. Treatment-emergent adverse events occurred at similar rates among all groups in teriflunomide studies, with a trend towards a higher treatment emergent adverse events rate in the higher dosage group of teriflunomide (14 mg daily). Treatment discontinuations in teriflunomide trials were relatively low, suggesting that teriflunomide monotherapy is well tolerated. This article reviews the mode of action of teriflunomide, its pharmacokinetic, clinical efficacy, and safety profiles.

New approaches in the management of multiple sclerosis.

Multiple sclerosis (MS) is a central nervous system chronic inflammatory disease that is characterized by an extensive and complex immune response. Scientific advances have occurred in immunology, pathophysiology, and diagnostic and clinical assessment tools, and recent discovery of unique therapeutic targets has spurred numerous Phase II and Phase III clinical trials. Reductions in MS relapse rates and improvements in T2 or gadolinium-enhancing lesion burdens have been reported from Phase III trials that include fingolimod, alemtuzumab, cladribine, and rituximab. Promising Phase II trial data exist for teriflunomide, daclizumab, laquinimod, and fumarate. The optimism created by these favorable findings must be tempered with evaluation of the adverse effect profile produced by these new agents. Given the discovery of progressive multifocal leukoencephalopathy with the use of natalizumab, ongoing vigilance for rare and life-threatening reactions due to new agents should be paramount. Patients with MS often experience difficulty with ambulation, spasticity, and cognition. Recent clinical trial data from two Phase III dalfampridine-SR trials indicate certain patients receive benefits in ambulation. This article provides an overview of data from clinical trials of newer agents of potential benefit in MS.

Sustained-release fampridine for symptomatic treatment of multiple sclerosis.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical trials, and adverse effects of sustained-release (SR) fampridine in patients with multiple sclerosis (MS). DATA SOURCES: An English-language human data search was done using PubMed/MEDLINE (1966-August 2008) to retrieve relevant material using the search terms fampridine-SR, 4-aminopyridine, and multiple sclerosis. References of selected articles and information from the drug developer were used to further identify pertinent trials. STUDY SELECTION AND DATA EXTRACTION: Article selection was based primarily on studies that evaluated the pharmacokinetics, safety, and efficacy of fampridine-SR in patients with MS. Relevant meeting abstracts were also included as part of the analysis. DATA SYNTHESIS: Fampridine-SR is a sustained-release, orally administered potassium-channel blocker acting in the central nervous system to enhance conduction in demyelinated axons. Several small trials have evaluated the safety and efficacy of fampridine-SR in patients with MS to improve their walking ability. Data from a recent large Phase 3 trial indicated that walking speed improved in 42.9% of patients with MS who were treated with fampridine-SR compared with 9.3% of those who received placebo (p < 0.001). Treatment-related adverse events associated with the use of fampridine-SR include dizziness, insomnia, nausea, and paresthesia. More severe adverse events, such as seizure, have occurred in patients receiving doses higher than those currently recommended. CONCLUSIONS: Positive results from 2 Phase 3 clinical trials have put fampridine-SR on the path toward approval as a medication for improving walking speed and lower extremity strength in patients with MS.

Acute renal failure associated with vancomycin- and tobramycin-laden cement in total hip arthroplasty.

OBJECTIVE: To describe 2 cases of acute renal failure (ARF) associated with the use of antibiotic-laden cement incorporated in total hip arthroplasties (THA). CASE SUMMARIES: An 82-year-old female received a right THA with antibiotic-laden cement spacers. She developed ARF 5 months following implantation, concurrent with an elevated serum tobramycin concentration of 5.5 microg/mL. After explantation of the prosthesis and spacers, serum creatinine and antibiotic concentrations decreased to within normal limits. A 79-year-old male received antibiotic-laden cement spacers in a revision of his right THA due to infection. ARF developed 1 1/2 months after the revision; a serum tobramycin concentration was 2.9 microg/mL. Serum creatinine and antibiotic serum concentrations decreased to within normal limits with explantation. DISCUSSION: More than 250 000 joint replacements are performed yearly in the US. A common complication is infection, which occurs in 1-2% of primary replacements and 3-4% of revisions of previously infected prostheses. Antibiotic-laden cement is used for prosthesis placement to prevent or treat infection, while minimizing systemic drug exposure. Both patients described here received antibiotic-laden spacers during THA and subsequently developed ARF in conjunction with elevated serum tobramycin concentrations. Use of the Naranjo probability scale and consideration of possible contributing factors suggest a probable association of the antibiotic-laden cement and the development of ARF in these patients. CONCLUSIONS: Antibiotic-laden cement with aminoglycosides and/or vancomycin has the potential for systemic toxicity and should be used according to guidelines and with increased vigilance and prudent monitoring in patients at increased risk for nephrotoxicity.

Natalizumab for the treatment of multiple sclerosis and Crohn's disease.

OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and pivotal clinical trials for natalizumab in the treatment of multiple sclerosis (MS) and inflammatory bowel disease. DATA SOURCES: A PubMed/MEDLINE search was conducted (1966-June 2005), and information was obtained from Iowa Drug Information Services. Additional data sources included meeting abstracts, bibliographies from identified articles, and information from the manufacturer. STUDY SELECTION AND DATA EXTRACTION: Studies and review articles examining natalizumab were evaluated. All published, randomized clinical trials evaluating natalizumab in MS and IBD were included in this review. DATA SYNTHESIS: Natalizumab is the first drug in a new class of agents called selective adhesion molecule inhibitors. It has shown promising results in MS and inflammatory bowel disease and appears superior compared with current therapies in reducing relapse rates. However, 3 recent, confirmed case reports of progressive multifocal leukoencephalopathy (PML) create concern about natalizumab's use in combination with existing therapies or in undefined patient subgroups. Natalizumab was voluntarily withdrawn from the market in March 2005 while the drug's safety is further evaluated. CONCLUSIONS: Although long-term efficacy and safety of natalizumab have not been established, available data indicate that it is a novel drug for patients with MS or inflammatory bowel disease. Analysis of its possible association with PML will determine the risk-benefit evaluation and eventual place in therapy for natalizumab.