The Updated Mouse Universal Genotyping Array Bioinformatic Pipeline Improves Genetic QC in Laboratory Mice.

The MiniMUGA genotyping array is a popular tool for genetic QC of laboratory mice and genotyping of samples from most types of experimental crosses involving laboratory strains, particularly for reduced complexity crosses. The content of the production version of the MiniMUGA array is fixed; however, there is the opportunity to improve array's performance and the associated report's usefulness by leveraging thousands of samples genotyped since the initial description of MiniMUGA in 2020. Here we report our efforts to update and improve marker annotation, increase the number and the reliability of the consensus genotypes for inbred strains and increase the number of constructs that can reliably be detected with MiniMUGA. In addition, we have implemented key changes in the informatics pipeline to identify and quantify the contribution of specific genetic backgrounds to the makeup of a given sample, remove arbitrary thresholds, include the Y Chromosome and mitochondrial genome in the ideogram, and improve robust detection of the presence of commercially available substrains based on diagnostic alleles. Finally, we have made changes to the layout of the report, to simplify the interpretation and completeness of the analysis and added a table summarizing the ideogram. We believe that these changes will be of general interest to the mouse research community and will be instrumental in our goal of improving the rigor and reproducibility of mouse-based biomedical research.

Toxigenic Profile of Clostridium perfringens Strains Isolated from Natural Ingredient Laboratory Animal Diets.

Clostridium perfringens is an anaerobic, gram-positive, spore-forming bacterium that ubiquitously inhabits a wide variety of natural environments including the gastrointestinal tract of humans and animals. C. perfringens is an opportunistic enteropathogen capable of producing at least 20 different toxins in various combinations. Strains of C. perfringens are currently categorized into 7 toxinotypes (A, B, C, D, E, F, and G) based on the presence or absence of 6 typing-toxins (α, ß, epsilon, iota, enterotoxin, and netB). Each toxinotype is associated with specific histotoxic and enteric diseases. Spontaneous enteritis due to C. perfringens has been reported in laboratory animals; however, the source of the bacteria was unknown. The Quality Assurance Laboratory (QAL) at the National Institute of Environmental Health Sciences (NIEHS) routinely screens incoming animal feeds for aerobic, enteric pathogens, such as Salmonella spp. and E. coli. Recently, QAL incorporated anaerobic screening of incoming animal feeds. To date, the lab has isolated numerous Clostridium species, including C. perfringens, from 23 lots of natural ingredient laboratory animal diets. Published reports of C. perfringens isolation from laboratory animal feeds could not be found in the literature. Therefore, we performed a toxin profile screen of our isolated strains of C. perfringens using PCR to determine which toxinotypes were present in the laboratory animal diets. Our results showed that most C. perfringens strains we isolated from the laboratory animal feed were toxinotype A with most strains also possessing the theta toxin. Two of the C. perfringens strains also possessed the ß toxin. Our results demonstrated the presence of C. perfringens in nonsterile, natural ingredient feeds for laboratory animals which could serve as a source of this opportunistic pathogen.

Toxigenic Profile of Clostridium perfringens Strains Isolated from Natural Ingredient Laboratory Animal Diets.

Clostridium perfringens is an anaerobic, gram-positive, spore-forming bacterium that ubiquitously inhabits a wide varietyof natural environments including the gastrointestinal tract of humans and animals. C. perfringens is an opportunistic enteropathogen capable of producing at least 20 different toxins in various combinations. Strains of C. perfringens are currentlycategorized into 7 toxinotypes (A, B, C, D, E, F, and G) based on the presence or absence of 6 typing-toxins (α, ß, epsilon, iota, enterotoxin, and netB). Each toxinotype is associated with specific histotoxic and enteric diseases. Spontaneous enteritis due to C. perfringens has been reported in laboratory animals; however, the source of the bacteria was unknown. The Quality Assurance Laboratory (QAL) at the National Institute of Environmental Health Sciences (NIEHS) routinely screens incoming animal feeds for aerobic, enteric pathogens, such as Salmonella spp. and E. coli. Recently, QAL incorporated anaerobic screening of incoming animal feeds. To date, the lab has isolated numerous Clostridium species, including C. perfringens, from 23 lots ofnatural ingredient laboratory animal diets. Published reports of C. perfringens isolation from laboratory animal feeds couldnot be found in the literature. Therefore, we performed a toxin profile screen of our isolated strains of C. perfringens usingPCR to determine which toxinotypes were present in the laboratory animal diets. Our results showed that most C. perfringens strains we isolated from the laboratory animal feed were toxinotype A with most strains also possessing the theta toxin. Two of the C. perfringens strains also possessed the ß toxin. Our results demonstrated the presence of C. perfringens in nonsterile, natural ingredient feeds for laboratory animals which could serve as a source of this opportunistic pathogen.

Medication errors and adverse drug events in an intensive care unit: direct observation approach for detection.

OBJECTIVE: To determine the incidence and preventability of medication errors and potential/actual adverse drug events. To evaluate system failures leading to error occurrence. DESIGN: Prospective, direct observation study. SETTING: Tertiary care academic medical center. PATIENTS: Patients in a medical/surgical intensive care unit. INTERVENTIONS: Observers would intervene only in the event that the medication error would cause substantial patient harm or discomfort. MEASUREMENTS AND MAIN RESULTS: The observers identified 185 incidents during a pilot period and four phases totaling 16.5 days (33 12-hr shifts). Two independent evaluators concluded that 13 of 35 (37%) actual adverse drug events were nonpreventable (i.e., not medication errors). An additional 40 of the remaining 172 medication errors were judged not to be clinically important. Of the 132 medication errors classified as clinically important, 110 (83%) led to potential adverse drug events and 22 (17%) led to actual, preventable adverse drug events. There was one error (i.e., resulting in a potential or actual, preventable adverse drug event) for every five doses of medication administered. The potential adverse drug events mostly occurred in the administration and dispensing stages of the medication use process (34% in each); all of the actual, preventable adverse drug events occurred in the prescribing (77%) and administration (23%) stages. Errors of omission accounted for the majority of potential and actual, preventable adverse drug events (23%), followed by errors due to wrong dose (20%), wrong drug (16%), wrong administration technique (15%), and drug-drug interaction (10%). CONCLUSIONS: Using a direct observation approach, we found a higher incidence of potential and actual, preventable adverse drug events and an increased ratio of potential to actual, preventable adverse drug events compared with studies that used chart reviews and solicited incident reporting. All of the potential adverse drug events and approximately two thirds of the actual adverse drug events were judged to be preventable. There was one preventable error for every five doses of medication administered; most errors were due to dose omission, wrong dose, wrong drug, wrong technique, or interactions.

Stress ulcer prophylaxis in the postoperative period.

PURPOSE: The implications of recent studies for guidelines that pertain to stress ulcer prophylaxis in the postoperative period are discussed. SUMMARY: The therapeutic guidelines on stress ulcer prophylaxis published by the American Society of Health-System Pharmacists (ASHP) provided clinicians with recommendations regarding appropriate candidates for stress ulcer prophylaxis and selection of a pharmacologic agent. Since these guidelines were published in 1999, additional research has been completed to resolve some of the controversial issues surrounding stress ulcer prophylaxis. The frequency of stress-induced bleeding in recent investigations continues to be highly variable, depending on the definition used to describe bleeding. In general, investigations that evaluate overt bleeding or bleeding without hemodynamic changes or blood transfusion report higher frequencies of bleeding than those that evaluate clinically important bleeding. Similar to that reported in the initial ASHP guidelines, the frequency of clinically important bleeding in recent investigations is low. In addition, the majority of recently published prospective studies and a meta-analysis have been unable to demonstrate a reduction in clinically important bleeding with pharmacologic agents. As a result, some experts have suggested that advances in critical care are more influential in the development of stress-induced bleeding than the use of pharmacologic agents. Recently published investigations support the effectiveness of institution-specific guidelines to help clinicians identify appropriate candidates for stress ulcer prophylaxis. The selection of an optimal pharmacologic agent for stress ulcer prophylaxis continues to be debated. The majority of recent studies have involved the administration of proton-pump inhibitors (PPIs). In general, these studies have demonstrated that PPIs are at least as effective as histamine H2-receptor antagonists at increasing gastric pH, but adequately powered studies investigating the endpoint of clinically important bleeding are needed. Similar to the initial ASHP guidelines, the development of institution-specific guidelines is recommended to identify the most appropriate pharmacologic treatment. CONCLUSION: The frequency of clinically important bleeding reported in recent studies is low. The majority of recently published prospective studies and meta-analyses found little significant reduction in bleeding with pharmacologic prophylaxis.