Recent human genetic studies suggest that allelic variants of leukotriene pathway genes influence the risk of clinical and subclinical atherosclerosis. We sequenced the promoter, exonic, and splice site regions of ALOX5 and ALOX5AP and then genotyped 7 SNPs in ALOX5 and 6 SNPs in ALOX5AP in 1,552 cases with clinically significant coronary artery disease (CAD) and 1,583 controls from Kaiser Permanente including a subset of participants of the coronary artery risk development in young adults study. A nominally significant association was detected between a promoter SNP in ALOX5 (rs12762303) and CAD in our subset of white/European subjects (adjusted odds ratio per minor allele, log-additive model, 1.32; P = 0.002). In this race/ethnic group, rs12762303 has a minor allele frequency of 15% and is tightly linked to variation at the SP1 variable tandem repeat promoter polymorphism. However, the association between CAD and rs12762303 could not be reproduced in the atherosclerosis risk in communities study (hazard rate ratio per minor allele; 1.08, P = 0.1). Assuming a recessive mode of inheritance, the association was not significant in either population study but our power to detect modest effects was limited. No significant associations were observed between all other SNPs and the risk of CAD. Overall, our findings do not support a link between common allelic variation in or near ALOX5 or ALOX5AP and the risk of CAD. However, additional studies are needed to exclude modest effects of promoter variation in ALOX5 on the risk of CAD assuming a recessive mode of inheritance.

OBJECTIVE: To identify communication needs and evaluate the effectiveness of alternative communication strategies for bioterrorism responses. METHODS: We provide a framework for evaluating communication needs during a bioterrorism response. Then, using a simulation model of a hypothetical response to anthrax bioterrorism in a large metropolitan area, we evaluate the costs and benefits of alternative strategies for communication during a response. RESULTS: Expected mortality increases significantly with increases in the time for attack detection and announcement; decreases in the rate at which exposed individuals seek and receive prophylaxis; increases in the number of unexposed people seeking prophylaxis; and increases in workload imbalances at dispensing centers. Thus, the timeliness, accuracy, and precision of communications about the mechanisms of exposure and instructions for obtaining prophylaxis and treatment are critical. Investment in strategies that improve adherence to prophylaxis is likely to be highly cost effective, even if the improvement in adherence is modest, and even if such strategies reduce the prophylaxis dispensing rate. CONCLUSIONS: Communication during the response to a bioterror attack must involve the right information delivered at the appropriate time in an effective manner from trusted sources. Because the response system for bioterror communication is only fully operationalized once an attack has occurred, tabletop planning and simulation exercises, and other up-front investments in the design of an effective communication strategy, are critical for effective response planning.

Background: The United States (U.S.) Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) has implemented economic analyses in single-site and multi-site clinical trials. To date, no one has reviewed whether the QUERI Centers are taking an optimal approach to doing so. Consistent with the continuous learning culture of the QUERI Program, this paper provides such a reflection.

Methods: We present a case study of QUERI as an example of how economic considerations can and should be integrated into implementation research within both single and multi-site studies. We review theoretical and applied cost research in implementation studies outside and within VA. We also present a critique of the use of economic research within the QUERI program.

Results: Economic evaluation is a key element of implementation research. QUERI has contributed many developments in the field of implementation but has only recently begun multi-site implementation trials across multiple regions within the national VA healthcare system. These trials are unusual in their emphasis on developing detailed costs of implementation, as well as in the use of business case analyses (budget impact analyses).

Conclusion: Economics appears to play an important role in QUERI implementation studies, only after implementation has reached the stage of multi-site trials. Economic analysis could better inform the choice of which clinical best practices to implement and the choice of implementation interventions to employ. QUERI economics also would benefit from research on costing methods and development of widely accepted international standards for implementation economics.

This issue of CHP/PCOR's Quarterly Update covers news from the Fall 2007 quarter and includes articles about:

• the 2007 Eisenberg Legacy Lecture event, featuring CHP/PCOR core faculty member Victor R. Fuchs;
• annual meeting and conference coverage, including the Society for Medical Decision Meeting's Annual Meeting, and the Freeman Spogli Institute for International Studies conference;
• two Research in Brief selections -- one highlights differences in gender use care in the VA system, and the second examines health risk assessment tools;
• how the Geriatrics Research team at the VA is using informatics to improve quality of health care;
• international health features from the field and from a research perspective;
• a Q & A with senior scholar Dena M. Bravata, who led a popular pedometer that received lots of media attention in past months.

The newsletter also contains various other news items that may be of interest to our readers.

Note to the reader:

The newsletter is fully-navigational. Any text that is surrounded by a dashed box is clickable and will allow the reader to navigate the newsletter more efficiently. The end of each article contains a special symbol (§) that, when clicked, will take the reader back to the table of contents. Please feel free to contact Amber Hsiao with any questions.

Abstract

PURPOSE:

Given the prevalence of physical inactivity among American adults, convenient, low-cost interventions are strongly indicated. This study determined the 6- and 12-month effectiveness of telephone interventions delivered by health educators or by an automated computer system in promoting physical activity.

DESIGN:

Initially inactive men and women age 55 years and older (N = 218) in stable health participated. Participants were randomly assigned to human advice, automated advice, or health education control.

MEASURES:

The validated 7-day physical activity recall interview was used to estimate minutes of moderate to vigorous physical activity. Physical activity differences by experimental arm were verified on a random subsample via accelerometry.

RESULTS:

Using intention-to-treat analysis, at 6 months, participants in both interventions, although not differing from one another, showed significant improvements in weekly physical activity compared with controls. These differences were generally maintained at 12 months, with both intervention arms remaining above the target of 150 min per week of moderate to vigorous physical activity on average.

CONCLUSION:

Automated telephone-linked delivery systems represent an effective alternative for delivering physical activity advice to inactive older adults.

To analyze temporal patterns of antiretroviral (ARV) prescribing practices relative to nationally defined guidelines in treatment-naive patients with HIV-1 infection. DESIGN: Retrospective cohort study. METHODS: We evaluated ARV prescribing patterns among ARV treatment-naive veterans who were receiving care within the US Department of Veterans Affairs (VA) from 1992 through 2004 in comparison to evolving adult HIV-1 treatment guidelines. RESULTS: A total of 15,934 patients initiated ARV treatment. Since 1999, >94% of patients initiated at least a 3-ARV medication combination, although the percentage of patients who initiated a guideline "preferred" or "alternative" regimen never rose to greater than 72% and was significantly associated with being black and with region of care. After 1999, 20% of patients started 4 or more active ARV agents in combination, which was significantly associated with lower baseline CD4 cell count, higher viral load, and receiving care in the western United States. The proportion of patients receiving guideline "not recommended" regimens (virologically undesirable or overlapping toxicities) was <1% after 1997. VA prescribing trends generally predated guideline recommendations by 6 to 12 months. CONCLUSIONS: VA prescribing patterns for ARV initiation adhere to treatment guidelines that maximize safety. Guidelines designed to maximize efficacy were not followed as stringently. Evaluating clinical practice patterns against contemporary treatment guidelines can inform guideline development.

Methods: The current medical literature that is applicable to this issue was identified by a computerized search and was evaluated using standardized methods. Recommendations were framed using the approach described by the Health and Science Policy Committee of the American College of Chest Physicians.

Results: Patients with lung cancer usually present with multiple symptoms, both respiratory related and constitutional. There is usually a time delay between symptom recognition by the patient and the ultimate diagnosis of lung cancer by the physician. Whether this time delay impacts prognosis is unclear, but delivering timely and efficient care is an important component in its own right. Lung cancer may be accompanied by a variety of paraneoplastic syndromes. These syndromes may not necessarily preclude treatment with a curative intent.

Conclusions: The initial evaluation of the patient with known or suspected lung cancer should include an assessment of symptoms, signs, and laboratory test results in a standardized manner as a screen for identifying those patients with paraneoplastic syndromes and a higher likelihood of metastatic disease.

Two common means of controlling infectious diseases are screening and contact tracing. Which should be used, and when? We consider the problem of determining the cheapest mix of screening and contact tracing necessary to achieve a desired endemic prevalence of a disease or to identify a specified number of cases. We perform a partial equilibrium analysis of small-scale interventions, assuming that prevalence is unaffected by the intervention; we develop a full equilibrium analysis where we compare the long-term cost of various combinations of screening and contact tracing needed to achieve a given equilibrium prevalence; and we solve the problem of minimizing the total costs of identifying and treating disease cases plus the cost of untreated disease cases. Our analysis provides several insights.

First, contact tracing is only cost effective when prevalence is below a threshold value. This threshold depends on the relative cost per case found by screening versus contact tracing. Second, for a given contact tracing policy, the screening rate needed to achieve a given prevalence or identify a specified number of cases is a decreasing function of disease prevalence. As prevalence increases above the threshold (and contact tracing is discontinued), the screening rate jumps discontinuously to a higher level. Third, these qualitative results hold when we consider unchanged or changed prevalence, and short-term or long-term costs.