Randomized clinical trial of a customized electronic alert requiring an affirmative response compared to a control group receiving a commercial passive CPOE alert: NSAID�Cwarfarin co-prescribing as a test case

Background

Studies that have looked at the effectiveness of computerized decision support systems to prevent drug–drug interactions have reported modest results because of low response by the providers to the automated alerts.

Objective

To evaluate, within an inpatient computerized physician order entry (CPOE) system, the incremental effectiveness of an alert that required a response from the provider, intended as a stronger intervention to prevent concurrent orders of warfarin and non-steroidal anti-inflammatory drugs (NSAIDs).

Design

Randomized clinical trial of 1963 clinicians assigned to either an intervention group receiving a customized electronic alert requiring affirmative response or a control group receiving a commercially available passive alert as part of the CPOE. The study duration was 2 August 2006 to 15 December 2007.

Measurements

Alert adherence was compared between study groups.

Results

The proportion of desired ordering responses (ie, not reordering the alert-triggering drug after firing) was lower in the intervention group (114/464 (25%) customized alerts issued) than in the control group (154/560 (28%) passive alerts firing). The adjusted OR of inappropriate ordering was 1.22 (95% CI 0.69 to 2.16).

Conclusion

A customized CPOE alert that required a provider response had no effect in reducing concomitant prescribing of NSAIDs and warfarin beyond that of the commercially available passive alert received by the control group. New CPOE alerts cannot be assumed to be effective in improving prescribing, and need evaluation.     

Effectiveness of an information technology intervention to improve prophylactic antibacterial use in the postoperative period

Background

A 2005 report from the Centers for Medicare and Medicaid Services and the Centers for Disease Control Surgical Infection Prevention program indicated that only 41% of prophylactic antibacterials were correctly stopped within 24 h of the end of surgery. Electronic order sets have shown promise as a means of integrating guideline information with electronic order entry systems and facilitating safer, more effective care.

Objective

The aim was to study the effectiveness of a computer-based antibacterial order set on increasing the proportion of patients who have antibacterial wound prophylaxis discontinued in the appropriate time frame.

Design

The authors conducted a quasi-experimental interrupted time-series analysis over an 8-month study period with the implementation of a computer-based order system designed to prevent excessive duration of surgical prophylaxis antibacterials.

Measurement

The primary outcome was the proportion of surgeries with antibacterials discontinued in the appropriate time frame. Additionally, we evaluated the percent of surgeries after implementation of the electronic intervention with chart documentation of infection among surgeries where the prescriber indicated the reason for antibacterial therapy was treatment.

Results

The computer-based order intervention significantly improved the proportion of surgeries with timely discontinuation of antibacterials from 38.8% to 55.7% (p<0.001) in the intervention hospital, while the control hospital remained at 56–57% (p=0.006 for the difference between treated and control hospitals). In surgeries after intervention implementation where a prescriber indicated the reason for antibacterial therapy was treatment, the prevalence of chart documented infection was only 14%.

Conclusions

A computer-based electronic order set intervention increased timely discontinuation of postoperative antibacterials.     

A tissue reconstitution model to study cancer cell‐intrinsic and ‐extrinsic factors in mammary tumourigenesis

The contribution of cancer cell‐intrinsic and ‐extrinsic factors to metastatic breast cancer is still poorly understood, hampering development of novel therapeutic strategies that decrease breast cancer mortality. Cre/loxP‐based conditional mouse models of breast cancer present unique opportunities to study sporadic tumour formation and progression in a controlled setting. Unfortunately, the generation of mouse strains carrying multiple mutant alleles needed for such studies is very time‐consuming. Moreover, conditional mouse tumour models do not permit independent manipulation of tumour cell‐intrinsic and ‐extrinsic factors. Although the latter can be achieved by cleared fat‐pad transplantation of mouse mammary epithelial cells (MMECs) from tumour suppressor gene (TSG) knockouts into wild‐type or mutant recipients, this procedure is not possible for mutations that cause embryonic lethality or preclude mammary gland development. Here we show that cleared fat‐pad transplantations with MMECs isolated from K14cre;Cdh1^F/F; Trp53^F/F mice expressing Cre recombinase under control of the cytokeratin‐14 promoter and carrying conditional null alleles for p53 and E‐cadherin (Cdh1) first resulted in the formation of phenotypically normal mammary glands, followed by the development of invasive metastatic mammary tumours. Tumour formation in the recipients mimicked tumour latency, spectrum, morphology, immunophenotype, and metastatic characteristics of the original mammary tumour model. This transplantation system, which can be expanded to other conditional TSG knockouts, permits independent genetic analysis of stromal factors and testing of additional cancer cell‐intrinsic mutations that would otherwise be embryonic lethal or require intensive breeding. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Warfarin with fluoroquinolones, sulfonamides, or azole antifungals: interactions and the risk of hospitalization for gastrointestinal bleeding

The aim of this study was to determine whether a potential pharmacokinetic interaction between warfarin and orally administered anti-infectives increases the risk of hospitalization for gastrointestinal (GI) bleeding in warfarin users. We conducted a nested case-control and case-crossover study using US Medicaid data. Logistic regression was used to determine the association between GI bleeding and prior use of ciprofloxacin, levofloxacin, gatifloxacin, co-trimoxazole, or fluconazole vs. no exposure and also vs. use of cephalexin, which would not be expected to interact with warfarin. All of the anti-infectives examined were associated with elevated odds ratios (ORs) when compared to no exposure to these drugs. With cephalexin data as the reference, the ORs for co-trimoxazole (OR: 1.68 (95% confidence interval (CI): 1.21-2.33) in the prior 6-10 days) and fluconazole (OR: 2.09 (95% CI: 1.34-3.26) in the prior 11-15 days) were significantly elevated. Warfarin users who had received an anti-infective agent showed a substantially increased risk of GI bleeding. However, a drug-drug interaction with warfarin was evident only for co-trimoxazole and fluconazole.     

Impairment in associative memory in healthy aging is distinct from that in other types of episodic memory

There is evidence that age related changes in episodic memory are heterogeneous and result from diverse pathologies. To test this, we examined performance of healthy high-functioning younger (N=41, ages 18-60 y) and older (N=58, ages 61-83 y) individuals in tests of associative memory, logical memory and memory in executive and object-recognition domains. We compared their relationships to each other and to other cognitive functions, including, psychomotor speed and verbal and spatial working memory. Older individuals showed significantly greater reduction in an index of the ability to learn new associations (NAL) than for memory in executive and object-recognition domains. Age-related reduction in NAL and in logical memory was of similar severity, but the two measures showed only moderate correlation when age and other cognitive functions were controlled for. NAL shows an age-related pattern of change distinct from memory in executive and object-recognition domains and from logical (item) memory. We propose that in healthy well-functioning individuals, NAL taps processes which support binding of newly learned association in context of accumulating information, a key function of the hippocampus. NAL may thus serve as a selective marker of complex, hippocampus-based, cognitive functions in studies of normal cognitive aging and of its possible relationship to early dementia.