Moving Towards Common Data Elements and Core Outcome Measures in Frailty Research.

With aging populations around the world, frailty is becoming more prevalent increasing the need for health systems and social systems to deliver optimal evidence based care. However, in spite of the growing number of frailty publications, high-quality evidence for decision making is often lacking. Inadequate descriptions of the populations enrolled including frailty severity and frailty conceptualization, lack of use of validated frailty assessment tools, utilization of different frailty instruments between studies, and variation in reported outcomes impairs the ability to interpret, generalize and implement the research findings. The utilization of common data elements (CDEs) and core outcome measures (COMs) in clinical trials is increasingly being adopted to address such concerns. To catalyze the development and use of CDEs and COMs for future frailty studies, the Canadian Frailty Network (www.cfn-nce.ca; CFN), a not-for-profit pan-Canadian nationally-funded research network, convened an international group of experts to examine the issue and plan the path forward. The meeting was structured to allow for an examination of current frailty evidence, ability to learn from other COMs and CDEs initiatives, discussions about specific considerations for frailty COMs and CDEs and finally the identification of the necessary steps for a COMs and CDEs consensus initiative going forward. It was agreed at the onset of the meeting that a statement based on the meeting would be published and herein we report the statement.

Utilization of computerized clinical decision support for potentially inappropriate medications.

Background: Electronic medical record (EMR) alerts may inform point of care decisions, including the decision to prescribe potentially inappropriate medications (PIM) identified in the Beers criteria. EMR alerts may not be considered relevant or informative in the clinician context, leading to a phenomenon colloquially known as "alert fatigue." Objective: To assess the frequency of clinical interaction with EMR alerts and associated deprescribing behaviors in ambulatory settings. Methods: This is a retrospective observational study in two ambulatory clinics (the Kaye Edmonton Clinic Senior's Clinic and the Lynnwood Family Practice Clinic) in Edmonton over an observational period of 30 months. Statistical analysis was done using descriptive statistics, chi-square and regression analysis. Results: The reminder performance for interactions with the alert was 17.2% across the two clinics. The Number Needed to Remind (NNR) or mean number of alerts shown on clinician screens prior to a single interaction of any kind with the alert was 5.8. When actions were defined as a deprescribing (ie discontinuation) event that was related to the alert and that particular interaction in the EMR, the reminder performance was 1.2%, for an NNR of 82.8. Conclusion: The configuration of alerts in the EMR was not associated with a clinically detectable increase in the uptake of the Beers criteria for high hazard medications.

Implementing Frailty Measures in the Canadian Healthcare System.

Canadian healthcare is changing to include individuals living with frailty, but frailty must be better operationalized and better framed by sound data standards and policy. Frailty results from deficit accumulation in multiple body systems, with exaggerated vulnerability to external stressors. A growing consensus on defining frailty sets the stage for consensus on operationalization and widespread implementation in care settings. Frailty measurement is not yet integrated into daily clinical practice in Canada. Here, we will present how this integration might occur. We hope to demonstrate that implementation must appeal to inter-professional practice needs in different settings or circumstances. In some settings, methods for frailty case finding are expected to evolve as deemed to be most appropriate to the front-line users. In this "hands-off" approach, care providers, supported by emerging knowledge translation on frailty operationalization, would be informed by their setting and local practices to establish patterns of ad hoc case finding and component definition of frailty. This more nimble case finding strategy would be opportunistic, and would appeal to expert clinicians and self-directed teams who emphasize an individualized health care experience for their patients. In other settings, we can shape frailty case finding by building care algorithms around existing standardized practices and data repositories, leading to a systematic application of frailty measures and a more coordinated process of component definition and care protocols. Here, recommended instruments and data standards must be endorsed by health networks locally, provincially and nationally. The interRAI suite of assessment instruments has pan-Canadian standards in place and its pervasiveness makes it the most obvious starting point, especially in home care and long-term care. We anticipate the evolution of an integrated model informed by stakeholders and settings, where policy makers focus on system supports for frailty case finding, while front-line clinicians use case finding strategies to pinpoint and act on key frailty components.

Incidence and risk factors for delirium and other adverse outcomes in older adults after coronary artery bypass graft surgery.

OBJECTIVE: To determine the incidence and risk factors for delirium after coronary artery bypass graft (CABG) surgery. DESIGN: Prospective cohort. SETTING: Cardiac surgery units of a tertiary care hospital. PARTICIPANTS: Consecutive patients over age 65 years undergoing elective CABG surgery. Exclusion criteria included preoperative sensory or language barriers. INTERVENTIONS: Each patient was assessed within 24 h before surgery for baseline demographic, medical and functional data. Incident delirium (within four postoperative days) was diagnosed by a study physician. Nine potential risk factors for delirium were subjected to univariate and multivariate analysis. MAIN RESULTS: Of 75 consenting patients, three died during or soon after surgery and one was still comatose at follow-up. Of the remaining 71 participants, 23 (32%) experienced delirium. Those with delirium were more likely than those without delirium to have a history of a stroke (21% versus 4%, respectively, P=0.032) and to have had a longer duration of cardiopulmonary bypass (CPB) (113 mins versus 95 mins, respectively, P=0.025). A tendency to have experienced low cardiac output (83% versus 58%, respectively, P=0.061) postoperatively was also noted. Multivariate analysis confirmed past stroke and duration of cardiopulmonary bypass as risk factors. CONCLUSIONS: Delirium in the elderly after CABG surgery is common. Its occurrence may be predisposed by a history of a stroke and precipitated by a longer duration of CPB.

Validity of the confusion assessment method in detecting postoperative delirium in the elderly.

In this prospective cohort of 71 elderly patients undergoing cardiac surgery, each subject was interviewed before and after surgery to detect incident delirium using the Confusion Assessment Method (CAM), the Mini-Mental State Examination (MMSE), the Clock Test, and a health record review. The first 41 were assessed by a physician and the remaining 30 by two study nurses. Delirium was then diagnosed by a physician using DSM-III-R criteria. Delirium was present in 23 subjects (32.4%). The sensitivity of the CAM differed significantly when administered by physicians compared to nurses (1.00 vs. .13). When standard cutoffs were used, neither the MMSE nor the Clock Test were found to be sensitive markers for delirium (.30 and .09, respectively). Recognition of delirium by charting was superior in nurses compared to physicians (.83 vs. .30). We conclude that the sensitivity of markers for delirium, such as the CAM and health record documentation, is dependent on the training background of the operator.

The distribution of immunoreactive topoisomerase II Protein in human tissues and neoplasms.

Western blotting experiments with topoisomerase II antiserum were performed to measure type II topoisomerase content in human tissues. In this study, antiserum produced against the C-terminus of recombinant HeLa topoisomerase II recognized both p170 and p180 forms of the enzyme. Antisera specifically made against p180 selectively recognized that enzyme form. By using these antisera, a remarkable difference in topoisomerase content between the tissues studied was observed. Tissues with a high proportion of cycling cells contained predominantly the p170 form of the enzyme, but also smaller amounts of p180. In terminally differentiated organs or in neoplasms with a low percentage of cycling cells, topoisomerase II immunoprotein was not detected in whole tissue extracts. In term human placenta, this was because this tissue contained predominantly the p180 enzyme form, yet the concentration of this form of the enzyme was apparently in too low a concentration to be detected by the antibody in crude extracts. It was readily observed after concentration by chromatography on hydroxylapatite.

DNA topoisomerase I from human placenta.

In this study we report that human placenta is an excellent source of DNA topoisomerase I. The enzyme can be isolated in the fully intact 100 kDa form although lower molecular mass species are also observed. Occasionally, the enzyme can be resolved into two peaks of activity by chromatography on phosphocellulose. As expected, the enzyme promotes marked cleavage of DNA in response to the anticancer drug camptothecin. Because of this property and the ready availability of human placenta, the enzyme should prove to be useful in the development and testing of new anticancer drugs that target topoisomerase I.

Human DNA topoisomerase II: evaluation of enzyme activity in normal and neoplastic tissues.

We have used both a quantitative filter binding assay and a decatenation assay to measure DNA topoisomerase II activity. The filter binding assay, which measures catenating activity, is able to detect topoisomerase II activity at 50-100-fold lower protein concentrations than the decatenation assay. Because of this remarkable sensitivity, we have been able to quantitate topoisomerase II activity in a variety of normal and neoplastic human tissues. The highest level of enzyme activity in normal tissues was found in the spleen and thymus. The highest level of enzyme activity in neoplasms was found in those that clinically behave in an aggressive manner and had a high proliferative status by flow cytometry. Surprisingly, these high topoisomerase II values in the neoplastic specimens are in the same range of values found in normal nonproliferating tissue. Since much previous data indicate that the enzyme is apparently a property of only proliferating cells, this finding might suggest that human tissues contain more than one form of the enzyme. The finding that 35-65% of the topoisomerase II activity in human tissues is resistant to teniposide suggests that more than one enzyme form exists.

Phase-variation of pyelonephritis-associated pili in Escherichia coli: evidence for transcriptional regulation.

The regulation of pyelonephritis-associated pili (pap) pilin gene transcription has been examined using two operons (pap-17 and pap-21) isolated from the pyelonephritogenic Escherichia coli strain C1212. DNA sequence analysis and E. coli minicell analysis were used to map two genes (papB and papI) within the pilin regulatory regions of both pap-17 and pap-21, and the protein products of these genes were identified. Pilin transcription, initiated at the papBA promoter, was monitored by constructing single copy operon fusions with lacZYA in E. coli K-12. Inoculation of E. coli (pap'-lac) strains onto solid M9 minimal medium containing glycerol and the Lac indicator X-gal (M9-Glycerol) yielded both Lac+ and Lac- colony phenotypes. The Lac+ ("phase on') and Lac- ("phase off') phenotypes were heritable since reinoculation of M9-Glycerol with bacteria picked from Lac+ colonies gave rise to a much higher fraction of Lac+ colonies than reinoculation of M9-Glycerol with bacteria picked from Lac- colonies. Measurement of phase transition rates for E. coli (pap17'-lac) inoculated onto M9-Glycerol showed that the Lac(-)----Lac+ transition frequency (1.57 X 10(-4)/cell/generation) was reduced 35-fold when cells were inoculated onto minimal medium containing glucose (M9-Glucose). However, the Lac+----Lac-transition frequency obtained using M9-Glycerol (2.60 X 10(-2)/cell/generation) was 1.4-fold lower compared to results obtained with M9-Glucose. In contrast, lowering the incubation temperature of E. coli (pap17'-lac) cultures from 37 degrees C to 23 degrees C caused all cells to shift to the Lac- state.(ABSTRACT TRUNCATED AT 250 WORDS)