Glucose Hypometabolism Prompts RAN Translation and Exacerbates C9orf72-related ALS/FTD Phenotypes.

The most prevalent genetic cause of both amyotrophic lateral sclerosis and frontotemporal dementia is a (GGGGCC)n nucleotide repeat expansion (NRE) occurring in the first intron of the C9orf72 gene (C9). Brain glucose hypometabolism is consistently observed in C9-NRE carriers, even at pre-symptomatic stages, although its potential role in disease pathogenesis is unknown. Here, we identified alterations in glucose metabolic pathways and ATP levels in the brain of asymptomatic C9-BAC mice. We found that, through activation of the GCN2 kinase, glucose hypometabolism drives the production of dipeptide repeat proteins (DPRs), impairs the survival of C9 patient-derived neurons, and triggers motor dysfunction in C9-BAC mice. We also found that one of the arginine-rich DPRs (PR) can directly contribute to glucose metabolism and metabolic stress. These findings provide a mechanistic link between energy imbalances and C9-ALS/FTD pathogenesis and support a feedforward loop model that opens several opportunities for therapeutic intervention.

A knowledge-based decision support system for prevention and treatment of pressure ulcers.

As part of a research project intended to provide problem-based knowledge to clinicians at the point of care, we have developed a system that supports the nurse's development of patient-specific, guideline-based treatment plans for patients who have pressure ulcers or are at risk for developing them. The system captures coded data about assessment, diagnosis and interventions using a point-and-click interface. Knowledge is accessible to the user via: 1) hypertext links from the data entry screens; 2) explicit entry into an indexed version of the guideline; 3) imbedded knowledge-based rules that critique the diagnosis and offer guidance for treatment; and 4) explicit entry into interactive algorithms. The system has been implemented experimentally on one care unit at our hospital, where its impact will be assessed in comparison with a control unit. Data on 113 patients were entered during the 21-week experimental period. The system is being evaluated for its instructional adequacy, its impact on clinicians' decision-making and knowledge, and on processes of care. Users' perceptions of the system are also being evaluated. Dissemination issues in the context of today's health care environment are addressed.

Development of the Leapfrog methodology for evaluating hospital implemented inpatient computerized physician order entry systems.

The 1999 Institute of Medicine report raised public awareness of the frequency and cost of adverse drug events in medicine. In response, in November 2000 a coalition of healthcare purchasers announced the formation of the Leapfrog Group, an organization dedicated to making "great leaps forward" in the safety and quality of health care in America. Their first target-computerized physician order entry (CPOE)-was selected specifically for its potential to reduce harm to patients from medications. The Leapfrog inpatient CPOE standard included a requirement that the organization operating CPOE should demonstrate via a test that their inpatient CPOE system can alert physicians to at least 50% of common serious prescribing errors. This paper outlines the development of this test which evaluates the ability of implemented CPOE systems to prevent the occurrence of medication errors that have a high likelihood of leading to adverse drug events. A framework was developed to include 12 different categories of CPOE based decision support that could prevent prescribing errors leading to adverse drug events. A scoring system was developed based on the known frequency and severity of adverse drug events. Simulated test patients and accompanying simulated test medication orders were developed to evaluate the ability of a CPOE system to intercept prescribing errors in all 12 decision support categories. The test was validated at a number of inpatient sites using both commercially available and custom developed CPOE systems. A web based application was developed to allow hospitals to self-administer the evaluation.

End-user satisfaction of a patient education tool manual versus computer-generated tool.

This article reports a nonexperimental comparative study of end-user satisfaction before and after implementation of a vendor supplied computerized system (Micromedex, Inc) for providing up-to-date patient instructions regarding diseases, injuries, procedures, and medications. The purpose of this research was to measure the satisfaction of nurses who directly interact with a specific patient educational software application and to compare user satisfaction with manual versus computer generated materials. A computing satisfaction questionnaire that uses a scale of 1 to 5 (1 being the lowest) was used to measure end-user computing satisfaction in five constructs: content, accuracy, format, ease of use, and timeliness. Summary statistics were used to calculate mean ratings for each of the questionnaire's 12 items and for each of the five constructs. Mean differences between the ratings before and after implementation of the five constructs were significant by paired t test. Total user satisfaction improved with the computerized system, and the computer generated materials were given a higher rating than were the manual materials. Implications of these findings are discussed.

Efficacy and safety of a rapid-sequence metaproterenol protocol in the treatment of acute adult asthma.

A 6-month prospective study was performed to examine the efficacy and safety of a rapid-sequence nebulized metaproterenol regimen for the treatment of acute asthma in adults. Patients 18 years of age or older who were not pregnant and who had not received beta 2-agonist therapy were identified and started on a rapid-sequence metaproterenol regimen (15 mg) by the triage nurse. Pretreatment and posttreatment peak flow, respiratory rate, pulse rate, and blood pressure were documented. Patients also gave a pretreatment and posttreatment rating of the clinical severity of their attack using a 1-to-10 visual analogue scale. Fifty patients were entered into the study, with an average age of 38 years (range, 19 to 87 years). Data were analyzed using the Wilcoxon matched-pairs signed rank test. Patients showed statistically significant increases in peak flow (193 to 328 L/min, P < .00001) and systolic blood pressure (136 to 143 mm Hg, P < .0054). Statistically significant decreases were shown for respiratory rate (25 to 22 beats/min, P < .0001) and clinical severity (6.2 to 3.2, P < .00001). Thirty-three patients (71%) who completed the protocol experienced an increase in pulse rate. Ten (21%) had a pulse rate increase of more than 30 beats/min. Two (4.2%) had pulse rate increases of more than 40 beats/min. Four patients were removed after one or two nebulizers because of severe side effects. One patient's pulse rate increased to more than 200 beats/min. Although effective in reversing bronchospasm, the side effects of metaproterenol when used in rapid sequence are of major concern.

Mapping nursing diagnosis nomenclatures for coordinated care.

PURPOSE: To map the problem or diagnosis terms from three nomenclatures, term to term, to determine commonalities and differences; and to determine whether it is possible to develop a single vocabulary that contains the best features of all. When different nomenclatures are used in different settings, continuity of care is hampered by the need to re-state problems and interventions. DESIGN: The sample for this descriptive analysis was 396 terms from three nursing diagnosis and problem nomenclatures recognized by the American Nurses Association: the North American Nursing Diagnosis Association (NANDA) Approved List, the Home Health Care Classification (HHCC), and the Omaha System. METHOD: Terms from each of the three nomenclatures were mapped to terms in each of the others. Consensus methods were used to resolve differences in mapping decisions. Terms were characterized as "Same," "Similar," "Broader," "Narrower," and "No Match." Validation of consistency and accuracy was done by reverse mapping, use of syllogisms, use of taxonomic groupings, and expert review. RESULTS: Of 396 terms, 21 concepts accounting for 63 terms were found to be the same or similar in all three nomenclatures; 91 terms were unique to the nomenclature in which they were found ("No Match"). The remaining 242 terms had a narrower or broader relationship to at least one term in another nomenclature. In all three nomenclatures, inconsistencies existed in level of abstractness of the diagnosis or problem terms, and in definition and placement of terms within their own taxonomic structure. CONCLUSION: Because of differences in structure and incompatible taxonomic arrangements, a master list of "preferred terms" taken from the three nomenclatures is not feasible. However, the mappings are useful for determining commonalities and the unique contributions of each nomenclature, which can facilitate the development of a uniform language for nursing diagnoses. The mapping can also form the basis for automatic translation of computer-stored nursing diagnoses from one setting to another when different nomenclatures are used.

A decision support system for prevention and treatment of pressure ulcers based on AHCPR guidelines.

We have developed a Pressure Ulcer Prevention and Management System to assist clinicians with patient-specific decision making. The system captures coded data about assessment, diagnosis and interventions using a point-and-click interface. Guideline-based knowledge is imbedded into the system, and is accessible in several ways: 1) via hypertext links from the data entry screens; 2) via explicit entry into an indexed version of the guideline; 3) via imbedded knowledge-based rules that critique the diagnosis and offer guidance for treatment; and 4) via explicit entry into interactive algorithms. The system has been implemented experimentally on one care unit at our hospital, where its impact will be assessed in comparison with a control unit. Preliminary usage data are provided. Issues with rendering guideline material useful for patient-specific decision support are discussed. In our setting, these issues had to do with a) incongruity with local standards; b) insufficient specificity; and 3) insufficient comprehensiveness. Issues of use and dissemination in the context of today's health care environment are also addressed.