HIV/AIDS
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For 2009, SPICE has developed four new curriculum units: Examining Long-term Radiation Effects, Interactive Teaching AIDS: A Comprehensive HIV/AIDS Prevention Curriculum, China's Republican Era, 1911 to 1949, and Teacher's Guide to Wings of Defeat.

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In this op-ed, CISAC's Richard Rhodes argues that public health, a discipline that organizes science-based systems of surveillance and prevention, has been primarily responsible for controlling the effects of infectious disease. A similar campaign around public safety could help end the existential threat posed by nuclear weapons. Such a push would help create unity in common security and a fundamental transformation in relationships between nations, Rhodes argues.

Today, at the other end of the long trek down the glacier of the Cold War, the nuclear threat has seemingly calved off and fallen into the sea. In 2007, the Pew Research Center's Global Attitudes Project found that 12 countries rated the growing gap between rich and poor as the greatest danger to the world. HIV/AIDS led the list (or tied) in 16 countries, religious and ethnic hatred in another 12. Pollution was identified as the greatest menace in 19 countries, while substantial majorities in 25 countries thought global warming was a "very serious" problem. Only nine countries considered the spread of nuclear weapons to be the greatest danger to the world.

The response was very different among nuclear and national security experts when Indiana Republican Sen. Richard Lugar surveyed PDF them in 2005. This group of 85 experts judged that the possibility of a WMD attack against a city or other target somewhere in the world is real and increasing over time. The median estimate of the risk of a nuclear attack somewhere in the world by 2010 was 10 percent. The risk of an attack by 2015 doubled to 20 percent median. There was strong, though not universal, agreement that a nuclear attack is more likely to be carried out by a terrorist organization than by a government. The group was split 45 to 55 percent on whether terrorists were more likely to obtain an intact working nuclear weapon or manufacture one after obtaining weapon-grade nuclear material.

"The proliferation of weapons of mass destruction is not just a security problem," Lugar wrote in the report's introduction. "It is the economic dilemma and the moral challenge of the current age. On September 11, 2001, the world witnessed the destructive potential of international terrorism. But the September 11 attacks do not come close to approximating the destruction that would be unleashed by a nuclear weapon. Weapons of mass destruction have made it possible for a small nation, or even a sub-national group, to kill as many innocent people in a day as national armies killed in months of fighting during World War II.

"The bottom line is this," Lugar concluded: "For the foreseeable future, the United States and other nations will face an existential threat from the intersection of terrorism and weapons of mass destruction."

It's paradoxical that a diminished threat of a superpower nuclear exchange should somehow have resulted in a world where the danger of at least a single nuclear explosion in a major city has increased (and that city is as likely, or likelier, to be Moscow as it is to be Washington or New York). We tend to think that a terrorist nuclear attack would lead us to drive for the elimination of nuclear weapons. I think the opposite case is at least equally likely: A terrorist nuclear attack would almost certainly be followed by a retaliatory nuclear strike on whatever country we believed to be sheltering the perpetrators. That response would surely initiate a new round of nuclear armament and rearmament in the name of deterrence, however illogical. Think of how much 9/11 frightened us; think of how desperate our leaders were to prevent any further such attacks; think of the fact that we invaded and occupied a country, Iraq, that had nothing to do with those attacks in the name of sending a message.

Richard Butler, the former chairman of the Canberra Commission on the Elimination of Nuclear Weapons and the last chairman of UNSCOM, often makes the point that the problem with nuclear weapons is nuclear weapons. People don't always understand what he means. He means that it is the weapons themselves that are the problem, not the values of the entities that control them. U.S. nuclear weapons are just as potentially dangerous to the world as, say, North Korean nuclear weapons. More, I would say, since we have greater numbers of them and have not hesitated to brandish them--even to use them--when we thought it in our interest to do so.

That the problem with nuclear weapons is nuclear weapons may seem counterintuitive, but two centuries ago governments began to think that way about disease, with untold benefits to humanity as a result. Epidemic disease had been conceived in normative terms, as an act of God for which states bore no responsibility. The change that came when disease began to be conceived as a phenomenon of nature without a metaphysical superstructure, a public health problem, a problem for government and a measure of government's success, was revolutionary. More lives were saved, and spared, with public health measures in the twentieth century in the United States alone than were lost throughout the world in all of the twentieth century's wars.

As my Scottish friend Gil Elliot wrote in his seminal book Twentieth Century Book of the Dead, "[These lives] are not saved by accident or goodwill. Human life is daily deliberately protected from nature by accepted practices of hygiene and medical care, by the control of living conditions and the guidance of human relationships. Mortality statistics are constantly examined to see if the causes of death reveal any areas needing special attention. Because of the success of these practices, the area of public death has, in advanced societies, been taken over by man-made death--once an insignificant or 'merged' part of the spectrum, now almost the whole.

"When politicians, in tones of grave wonder, characterize our age as one of vast effort in saving human life, and enormous vigor in destroying it, they seem to feel they are indicating some mysterious paradox of the human spirit. There is no paradox and no mystery. The difference is that one area of public death has been tackled and secured by the forces of reason; the other has not. The pioneers of public health did not change nature, or men, but adjusted the active relationship of men to certain aspects of nature so that the relationship became one of watchful and healthy respect. In doing so they had to contend with and struggle against the suspicious opposition of those who believed that to interfere with nature was sinful, and even that disease and plague were the result of something sinful in the nature of man himself."

Elliot goes on to compare what he calls "public death," meaning biological death, death from disease, to man-made death: "[I do not wish] to claim mystical authority for the comparison I have made between two kinds of public death--that which results from disease and that which we call man-made. The irreducible virtue of the analogy is that the problem of man-made death, like that of disease, can be tackled only by reason. It contains the same elements as the problem of disease--the need to locate the sources of the pest, to devise preventive measures, and to maintain systematic vigilance in their execution. But it is a much wider problem, and for obvious reasons cannot be dealt with by scientific methods to the same extent as can disease."

To advance the cause of public health it was necessary to depoliticize disease, to remove it from the realm of value and install it in the realm of fact. Today we have advanced to the point where international cooperation toward the prevention, control, and even elimination of disease is possible among nations that hardly cooperate with each other in any other way. No one any longer considers disease a political issue, except to the extent that its control measures a nation's quality of life, and only modern primitives consider it a judgment of God.

In 1999, for the first time in human history, infectious diseases no longer ranked first among causes of death worldwide. Public health, a discipline which organizes science-based systems of surveillance and prevention, was primarily responsible for that millennial change in human mortality. One-half of all the increases in life expectancy in recorded history occurred within the twentieth century. Most of the worldwide increase was accomplished in the first half of the century, and it was almost entirely the result of public health measures directed to primary prevention. Better nutrition, sewage treatment, water purification, the pasteurization of milk, and the immunization of children extended human life--not surgeons cutting or doctors dispensing pills.

Public health is medicine's greatest success story and a powerful model for a parallel discipline, which I propose to call public safety.

Where nuclear weapons--the largest-scale instruments of man-made death--are concerned, the elements of that discipline of public safety have already begun to assemble themselves: materials control and accounting, cooperative threat reduction, security guarantees, agreements and treaties, surveillance and inspection, sanctions, forceful disarming if all else fails.

Reducing and finally eliminating the world's increasingly vestigial nuclear arsenals may be delayed by extremists of the right or the left, as progress was stalled during the George W. Bush administration by rigid Manichaean ideologues who imagined that there might be good nuclear powers and evil nuclear powers and sought to disarm only those they considered evil. Nuclear weapons operate beyond good and evil. They destroy without discrimination or mercy: Whether one lives or dies in their operation is entirely a question of distance from ground zero. In Elliot's eloquent words, they create nations of the dead, and collectively have the capacity to create a world of the dead. But as Niels Bohr, the great Danish physicist and philosopher, was the first to realize, the complement of that utter destructiveness must then be unity in common security, just as it was with smallpox, a fundamental transformation in relationships between nations, nondiscrimination in unity not on the dark side but by the light of day.

Violence originates in vulnerability brutalized: It is vulnerability's corruption, but also its revenge. "Perhaps everything terrible," the poet Rainer Maria Rilke once wrote, "is in its deepest being something helpless that wants help from us." As we extend our commitment to common security, as we work to master man-made death, we will need to recognize that terrible helplessness and relieve it--in others, but also in ourselves.

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Infectious diseases, though largely preventable, are a major cause of death and disability around the world. This curriculum was developed for students to: learn about the biological basis of infectious disease; understand how diseases can spread and affect whole populations; explore the public health response to such threats; and get involved in their own communities. Case studies and multimedia activities are designed to debunk myths, stimulate creative thinking, and inspire the next generation of public health advocates.
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It is commonly believed that America and Europe are very different societies, and growing apart. A look at the data shows that the anecdotes are misleading and that the differences across the Atlantic have been overstated.

Peter Baldwin, Professor of History at UCLA, is author of several books on the comparative history of European and American state building, most recently, Disease and Democracy: The Industrialized World Faces AIDS.

Introduction by FSI Senior Fellow Josef Joffe.

Encina Ground Floor Conference Room

Peter Baldwin Professor of History, UCLA Speaker
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An equilibrium search model of the Malawian HIV/AIDS epidemic is presented. Individuals engage in di¤erent types of sexual activity, which vary in their riskiness. When choosing a sexual activity, such as short-term sex without a condom, a person rationally considers its risk. A simulated version of the model is parameterized to match some salient facts about the Malawian epidemic. Some topical policies (e.g., male circumcision, treatment of other STDs, and promoting marriage) are studied and found to have potential to back…re: Moderate interventions may actually increase the prevalence of HIV/AIDS, due to shifts in human behavior and equilibrium e¤ects.

Assistant Professor Michele Tertilt is one of three Stanford scholars awarded a two-year Sloan Research Fellowship.  The Sloan Research Fellowships support the work of exceptional young researchers early in their academic careers.  Michele's research focuses on  family economics, consumer credit, growth and development, and demography.  The Economics department congratulates Michele on the prestigious fellowship.

Encina Ground Floor Conference Room

Michele Tertilt Assistant Professor Speaker the Department of Economics, Stanford University
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Despite recommendations for voluntary HIV screening, few medical centres have implemented screening programmes. The objective of the study was to determine whether an intervention with computer-based reminders and feedback would increase screening for HIV in a Department of Veterans Affairs (VA) health-care system. The design of the study was a randomized controlled trial at five primary care clinics at the VA Palo Alto Health Care System. All primary care providers were eligible to participate in the study. The study intervention was computer-based reminders to either assess HIV risk behaviours or to offer HIV testing; feedback on adherence to reminders was provided. The main outcome measure was the difference in HIV testing rates between intervention and control group providers. The control group providers tested 1.0% (n = 67) and 1.4% (n = 106) of patients in the preintervention and intervention period, respectively; intervention providers tested 1.8% (n = 98) and 1.9% (n = 114), respectively (P = 0.75).In our random sample of 753 untested patients, 204 (27%) had documented risk behaviours. Providers were more likely to adhere to reminders to test rather than with reminders to perform risk assessment (11% versus 5%, P < 0.01). Sixty-one percent of providers felt that lack of time prevented risk assessment. In conclusion, in primary care clinics in our setting, HIV testing rates were low. Providers were unaware of the high rates of risky behaviour in their patient population and perceived important barriers to testing. Low-intensity clinical reminders and feedback did not increase rates of screening.

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International Journal of STDs and AIDS
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Douglas K. Owens
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Estimating the potential health benefits and expenditures of a partially effective HIV vaccine is an important consideration in the debate about whether HIV vaccine research should continue. We developed an epidemic model to estimate HIV prevalence, new infections, and the cost-effectiveness of vaccination strategies in the U.S. Vaccines with modest efficacy could prevent 300,000-700,000 HIV infections and save $30 billion in healthcare expenditures over 20 years. Targeted vaccination of high-risk individuals is economically efficient, but difficulty in reaching these groups may mitigate these benefits. Universal vaccination is cost-effective for vaccines with 50% efficacy and price similar to other infectious disease vaccines.

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Vaccine
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Douglas K. Owens
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Objectives To assess the concurrent validity and responsiveness of the Health Utility Index 3 (HUI3) in patients with advanced HIV/AIDS, and to determine the responsiveness of this measure, the MOS-HIV and EQ-5D to HIV-related clinical events.

Methods Data from the OPTIMA (OPTions In Management with Antiretrovirals) trial was analyzed. Two aspects of the validity of the HUI3 were considered: concurrent validity was evaluated using Spearman correlations with MOS-HIV component and summary scores. Responsiveness to AIDS-defining events (ADE) and all adverse events (our external change criterion) was assessed using area under the receiver operating characteristic (AUROC) curves.

Results The study enrolled 368 patients (mean follow-up: 3.66 years); 82% had at least one severe adverse event and 27% had at least one ADE. The HUI3 scale and items showed good concurrent validity, with 85% of the expected relationships with the MOS-HIV subscales verified. The HUI3 was responsive to both adverse events (AUROC [95%CI]: 0.68 [0.57, 0.80]) and ADEs (0.62 [0.51, 0.74]). The EQ-5D was responsive to ADEs (0.66 [0.56, 0.76]), but not responsive to adverse events (0.56 [0.46, 0.68]).

Conclusion The HUI3 is a valid and responsive measure of the change in HRQoL associated with clinical events in an advanced HIV/AIDS population.

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Quality of Life Research
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Douglas K. Owens
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0962-9343
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Background: Since 2003, the President's Emergency Plan for AIDS Relief (PEPFAR) has been the most ambitious initiative to address the global HIV epidemic. However, the effect of PEPFAR on HIV-related outcomes is unknown.

Objective: To assess the effect of PEPFAR on HIV-related deaths, the number of people living with HIV, and HIV prevalence in sub-Saharan Africa.

Design: Comparison of trends before and after the initiation of PEPFAR's activities.

Setting: 12 African focus countries and 29 control countries with a generalized HIV epidemic from 1997 to 2007 (451 country-year observations).

Intervention: A 5-year, $15 billion program for HIV treatment, prevention, and care that started in late 2003.

Measurements: HIV-related deaths, the number of people living with HIV, and HIV prevalence.

Results: Between 2004 and 2007, the difference in the annual change in the number of HIV-related deaths was 10.5% lower in the focus countries than the control countries (P = 0.001). The difference in trends between the groups before 2003 was not significant. The annual growth in the number of people living with HIV was 3.7% slower in the focus countries than the control countries from 1997 to 2002 (P = 0.05), but during PEPFAR's activities, the difference was no longer significant. The difference in the change in HIV prevalence did not significantly differ throughout the study period. These estimates were stable after sensitivity analysis.

Limitation: The selection of the focus countries was not random, which limits the generalizability of the results.

Conclusion: After 4 years of PEPFAR activity, HIV-related deaths decreased in sub-Saharan African focus countries compared with control countries, but trends in adult prevalence did not differ. Assessment of epidemiologic effectiveness should be part of PEPFAR's evaluation programs.

Primary Funding Source: Agency for Healthcare Research and Quality.

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Annals of Internal Medicine
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Eran Bendavid
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Background Current World Health Organization (WHO) guidelines for treatment of HIV in resource-limited settings call for 2 antiretroviral regimens. The effectiveness and cost-effectiveness of increasing the number of antiretroviral regimens is unknown.

Methods Using a simulation model, we compared the survival and costs of current WHO regimens with two 3-regimen strategies: an initial regimen of 3 nucleoside reverse transcriptase inhibitors followed by the WHO regimens and the WHO regimens followed by a regimen with a second-generation boosted protease inhibitor (2bPI). We evaluated monitoring with CD4 counts only and with both CD4 counts and viral load. We used cost and effectiveness data from Cape Town and tested all assumptions in sensitivity analyses.

Results Over the lifetime of the cohort, 25.6% of individuals failed both WHO regimens by virologic criteria. However, when patients were monitored using CD4 counts alone, only 6.5% were prescribed additional highly active antiretroviral therapy due to missed and delayed detection of failure. The life expectancy gain for individuals who took a 2bPI was 6.7-8.9 months, depending on the monitoring strategy. When CD4 alone was available, adding a regimen with a 2bPI was associated with an incremental cost-effectiveness ratio of $2581 per year of life gained, and when viral load was available, the ratio was $6519 per year of life gained. Strategies with triple-nucleoside reverse transcriptase inhibitor regimens in initial therapy were dominated. Results were sensitive to the price of 2bPIs.

Conclusions About 1 in 4 individuals who start highly active antiretroviral therapy in sub-Saharan Africa will fail currently recommended regimens. At current prices, adding a regimen with a 2bPI is cost effective for South Africa and other middle-income countries by WHO standards.

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Journal of Acquired Immune Deficiency Syndromes
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Eran Bendavid
Douglas K. Owens
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