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Timely detection of an inhalational anthrax outbreak is critical for clinical and public health management. Syndromic surveillance has received considerable investment, but little is known about how it will perform relative to routine clinical case finding for detection of an inhalational anthrax outbreak. We conducted a simulation study to compare clinical case finding with syndromic surveillance for detection of an outbreak of inhalational anthrax. After simulated release of 1 kg of anthrax spores, the proportion of outbreaks detected first by syndromic surveillance was 0.59 at a specificity of 0.9 and 0.28 at a specificity of 0.975. The mean detection benefit of syndromic surveillance was 1.0 day at a specificity of 0.9 and 0.32 days at a specificity of 0.975. When syndromic surveillance was sufficiently sensitive to detect a substantial proportion of outbreaks before clinical case finding, it generated frequent false alarms.

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Emerging Infectious Diseases
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Douglas K. Owens
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Objective:

To assess the effectiveness and cost-effectiveness of treating HIV-infected injection drug users (IDUs) and non-IDUs in Russia with highly active antiretroviral therapy HAART.

Design and Methods:

A dynamic HIV epidemic model was developed for a population of IDUs and non-IDUs. The location for the study was St. Petersburg, Russia. The adult population aged 15 to 49 years was subdivided on the basis of injection drug use and HIV status. HIV treatment targeted to IDUs and non-IDUs, and untargeted treatment interventions were considered. Health care costs and quality-adjusted life years (QALYs) experienced in the population were measured, and HIV prevalence, HIV infections averted, and incremental cost-effectiveness ratios of different HAART strategies were calculated.

Results:

With no incremental HAART programs, HIV prevalence reached 64% among IDUs and 1.7% among non-IDUs after 20 years. If treatment were targeted to IDUs, over 40 000 infections would be prevented (75% among non-IDUs), adding 650 000 QALYs at a cost of USD 1501 per QALY gained. If treatment were targeted to non-IDUs, fewer than 10 000 infections would be prevented, adding 400 000 QALYs at a cost of USD 2572 per QALY gained. Untargeted strategies prevented the most infections, adding 950 000 QALYs at a cost of USD 1827 per QALY gained. Our results were sensitive to HIV transmission parameters.

Conclusions:

Expanded use of antiretroviral therapy in St. Petersburg, Russia would generate enormous population-wide health benefits and be economically efficient. Exclusively treating non-IDUs provided the least health benefit, and was the least economically efficient. Our findings highlight the urgency of initiating HAART for both IDUs and non-IDUs in Russia.

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AIDS
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Margaret L. Brandeau
Douglas K. Owens
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Background: An extensive literature supports expanded HIV screening in the United States. However, the question of whom to test and how frequently remains controversial.
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Annals of Internal Medicine
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In late September, the federal Centers for Disease Control and Prevention announced new guidelines recommending that all Americans ages 13 to 64 be voluntarily screened for HIV infection. That's a significant change from the previous guidelines, which recommended testing only for high-risk individuals, such as injection drug users or those with multiple sex partners.

The new guidelines were influenced by a study published last year in the New England Journal of Medicine, led by Douglas K. Owens, a CHP/PCOR core faculty member and an investigator at the VA Palo Alto. Owens and his colleagues -- including CHP/PCOR researchers Gillian D. Sanders, Vandana Sundaram, Kristof Neukermans and Laura Lazzeroni -- found that expanding HIV screening would be a cost-effective way to increase life expectancy and decrease the transmission of HIV. Below, Owens discusses the research and the CDC's new screening guidelines.

Q. Why does this new policy matter, and whom will it help?

Owens: The policy is a profound change because it advises that all individuals ages 13 to 64 be screened for HIV. It matters because it will identify people who have HIV but don't know it. These people will benefit because they'll have access to life-prolonging drugs that they otherwise might not have received until very late in the course of HIV disease. The rest of the community will also benefit, through reduced transmission of HIV.

Q. How did your findings contribute to the CDC adopting the new guidelines?

Owens: First, we found that widespread screening provides a substantial health benefit to HIV-positive people who are identified through screening and receive anti-retroviral treatment earlier than they would have otherwise. Early treatment added about a year and a half of life expectancy for these people. Second, we found a substantial potential benefit to the community because of reduced transmission of HIV. Transmission is reduced because many people cut down on risky behaviors (such as having unprotected sex) when they're identified as having HIV, and because anti-retroviral treatment makes a person less infectious. Our key finding was that routine screening is cost-effective even if only 1 in 2,000 people who are screened have HIV. This means HIV screening is cost-effective in a much broader group than recognized previously.

Q. How and why did the CDC revise its previous guidelines? What role did you and your colleagues play in the decision-making?

Owens: CDC officials made this change because they saw mounting evidence that the prior approach to screening -- focusing on those with identifiable risk factors -- simply wasn't working. If you test people based on risk behavior, you miss many people who have HIV. Even among people who had easily identified risk behaviors, many of them weren't being tested. We also know that most people who have HIV are diagnosed very late in the disease, when they can't get the full benefit from anti-retroviral therapy.

Our involvement in the decision-making was to help assess the prevalence of HIV at which routine screening would be recommended. Through several conference calls with CDC officials, we presented our work and explained the issues related to cost-effectiveness and prevalence. Based on those results and the results of a similar study from Yale, the agency went in the direction of lowering the threshold for screening quite substantially -- to 1 in 1,000 from a prior threshold of 1 percent.

Q. Will most physicians follow the new guidelines? What can be done to make sure they do?

Owens: That's the big question. The CDC's previous screening guidelines were not widely adopted. The new recommendations are much easier to adopt, because they don't depend on clinicians determining the prevalence of HIV in their patient population. Still, it will take a lot of follow-up to make sure physicians implement the guidelines. One key obstacle will be getting payers to reimburse for HIV testing. That's a critical issue, which the CDC is well aware of.

Q. Some HIV/AIDS advocates object to the new guidelines because they recommend removing two requirements that some states now have: mandatory signed consent forms and counseling before testing. Does removing these requirements pose a big problem?

Owens: It's important to emphasize that the new guidelines say people should always be informed before testing and should be able to decline. Informed consent and pretest counseling had become significant barriers that were preventing people from being tested who should have been tested. Everyone agrees that no one should be tested without their knowledge, but that doesn't mean you need a separate consent form. Of course, the confidentiality of the test results should continue to be carefully protected. I would point out that some states have laws requiring informed consent, but whether they will now change those laws isn't clear.

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This issue of CHP/PCOR's quarterly newsletter, which covers news from the summer 2006 quarter, includes articles about:

  • research by CHP/PCOR investigators that influenced the Centers for Disease Control and Prevention to recommend widespread voluntary HIV screening for all Americans ages 13 to 64 -- a significant change from the CDC's previous HIV screening guidelines;
  • a CHP/PCOR study on patient safety culture in U.S. hospitals -- the largest effort to date to measure hospitals' safety culture and seek to improve it through an intervention that gets hospital executives out of their offices and on to the hospital floors;
  • an early-stage project in which CHP/PCOR is collaborating with the Center on Democracy, Development and the Rule of Law to study the relationship between health interventions, governance and development;
  • an evidence report examining the challenges of diagnosing and treating anthrax in children, prepared by the Stanford-UCSF Evidence-based Practice Center; and
  • a study by CHP/PCOR fellow Kate Bundorf which found that depending on the definition of "affordability" that is used, health insurance is "affordable" to between one-quarter and three-quarters of the uninsured -- and many of those who can't afford insurance purchase it anyway.
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The U.S. Food and Drug Administration (FDA) is considering approval of an over-the-counter, rapid HIV test for home use. To date, testimony presented before the FDA has been overwhelmingly supportive. Advocates have argued enthusiastically that there is value in empowering individuals to manage their HIV risks and have suggested that the availability of a rapid home HIV test will dramatically increase rates of disease detection in communities that have proven difficult to reach and to link to appropriate care. The authors offer a more cautious perspective.

According to what is already known about the market demand for over-the-counter HIV testing kits, their costs, and the performance of rapid HIV tests in that market, the authors do not anticipate that the rapid home test will have a profound impact either on the HIV public health crisis or on the populations in greatest need. Home HIV testing will attract a predominantly affluent clientele, composed disproportionately of HIV-uninfected new couples and "worried well" persons, as well as very recently infected persons with undetectable disease. The authors illustrate how testing in these populations may have the perverse effect of increasing both false-positive and false-negative results. A poorly functioning home HIV test may thereby undermine confidence in the reliability of HIV testing more generally and weaken critical efforts to expand HIV detection and linkage to lifesaving care for the estimated 300 000 U.S. citizens with unidentified HIV infection.

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Annals of Internal Medicine
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Outcomes research often requires estimating the impact of a binary treatment on a binary outcome in a non-randomized setting, such as the effect of taking a drug on mortality. The data often come from self-selected samples, leading to a spurious correlation between the treatment and outcome when standard binary dependent variable techniques, like logit or probit, are used. Intuition suggests that a two-step procedure (analogous to two-stage least squares) might be sufficient to deal with this problem if variables are available that are correlated with the treatment choice but not the outcome.

This paper demonstrates the limitations of such a two-step procedure. We show that such estimators will not generally be consistent. We conduct a Monte Carlo exercise to compare the performance of the two-step probit estimator, the two-stage least squares linear probability model estimator, and the multivariate probit. The results from this exercise argue in favour of using the multivariate probit rather than the two-step or linear probability model estimators, especially when there is more than one treatment, when the average probability of the dependent variable is close to 0 or 1, or when the data generating process is not normal. We demonstrate how these different methods perform in an empirical example examining the effect of private and public insurance coverage on the mortality of HIV+ patients.

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Statistics in Medicine
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We sought to understand how diagnosis with HIV affects health-related quality of life. We assessed health-related quality of life using utility-based measures in a Department of Veterans Affairs (VA) clinic and a University-based clinic. Respondents assessed health-related quality of life regarding their current health, and retrospectively assessed their health 1 month prior to and 2 months after diagnosis with HIV infection. Sixty-six patients completed the study. The overall mean utilities for health 1 month before and 2 months after diagnosis were 0.87 (standard error 0.037), and 0.80 (0.043) (p0.005 by rank sign test), but the effect of diagnosis differed between the two clinics, with a substantial decrease in the university clinic and a small non-significant decrease in the VA clinic. The overall mean utility for current health was 0.85 (0.034), assessed on average 7.5 years after diagnosis. When asked directly whether diagnosis of HIV decreased health-related quality of life, 47% agreed, but 35% stated that HIV diagnosis positively affected health-related quality of life. Diagnosis with HIV decreased health-related quality of life at 2 months on average, but this effect diminished over time, and differed among patient populations. Years after diagnosis, although half of the patients believed that diagnosis reduced health-related quality of life, one-third reported improved health-related quality of life.

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Quality of Life Research
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Douglas K. Owens
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