Johns Hopkins Magazine -- September 1999
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Vital Signs

Ambassadors for relief
A dramatic cap to vision loss
Doling out dollars for disease
Low-cost drug prevents HIV in infants
For prostate cancer patients, what next?

Ambassadors for relief

Last April, Michael Van Rooyen received an urgent call asking him to set up a healthcare system for a new refugee camp in Hamallaj, Albania, by May 2.

Van Rooyen, an associate professor of emergency medicine at Hopkins, had coordinated medical relief for refugees and disaster victims in India, El Salvador, Somalia, and elsewhere. He was now imparting the skills he'd acquired in the field to graduate students in his course Public Health in Disasters.

Pediatrician Maryann Robb cares for refugees.
Photo by Chayan Dey
So Van Rooyen sent e-mail to each of his students asking if any were interested in developing a real-life refugee health system in Albania. More than 20 wrote back, flooding him with ideas.

The students quickly took the project into their own hands, dividing up the necessary tasks--one taking responsibility for maternal and child health, for instance, and another for surgical services. They then researched everything they could find about the health needs of the refugees, and kept each other informed of their progress through e-mails, which they would "cc" to Van Rooyen. "Before I knew it, a grinding machine got going and I was out of the loop," he says.

The refugees would be coming from Kosovo and Macedonia. At least half, the students learned, would be children, many of whom had not been vaccinated and would be susceptible to measles and other childhood diseases. For every 10,000 refugees, the medical staff should expect between four and six births and 200 new patients each day.

The students also included strategies for preventing violence against women and children by other refugees. One recommendation: keeping the latrines and hospital entrances well lit.

Van Rooyen carried a 30-page condensed version of the students' refugee health plan to the camp, which was in southern Albania. Officials from the international relief organization Samaritan's Purse and the United Nations High Commissioner for Refugees approved the plan, and UNHCR agreed to fund it.

After setting up the health care facilities, Van Rooyen returned to Baltimore, and Hopkins emergency physician Chayan Dey replaced him. The camp at Hamallaj ended up serving roughly 4,000 refugees before fighting ended in Kosovo. --Melissa Hendricks


Photo courtesy Peter Campochiaro
A dramatic cap to vision loss

In his five years of testing experimental drugs to prevent blindness, Hopkins ophthalmologist Peter Campochiaro has never seen anything like PKC 412. While other agents have had modest success in slowing the blinding growth of blood vessels in the eye, PKC 412 halted it entirely. "This is the first [drug] that has a dramatic effect," says the retinal surgeon, who reported the results in the June American Journal of Pathology.

Campochiaro conducted his study in mice that were engineered to model either diabetic retinopathy or macular degeneration--"the two biggest problems I see," says Campochiaro. Macular degeneration is the most common cause of severe vision loss in people older than 60. Diabetic retinopathy, one of the major complications of type I and type II diabetes, is the leading cause of blindness among working-age Americans.

Campochiaro hopes to begin clinical trials in early 2000. PKC 412 is currently being tested for safety and tolerability in end-stage cancer patients. Campochiaro collaborated with scientists from Novartis Ltd. Pharmaceuticals, which developed the drug.

Doling out dollars for disease

The National Institutes of Health funds research on hundreds of diseases. How do funding levels compare to the toll each disease takes? Does the greatest amount go to illnesses with the highest mortality rates? The ones that affect the most people? Incur the greatest economic losses?

Advocacy groups and politicians have at times criticized the NIH for making arbitrary funding decisions. Some groups argue that the squeaky wheel gets the grant. But what really happens?

In the June 17 New England Journal of Medicine, School of Public Health researchers concluded that NIH funding generally reflects a comprehensive measurement of the burden of disease, though there are exceptions.

This measurement is called disability adjusted life-years (DALY). One DALY is defined as one year of healthy life lost due to disability or death. It takes into account the age of those affected, the degree of disability, and the number of deaths associated with a particular disease.

Using 1996 funding data for 29 diseases, the researchers compared the actual funding allocated for each disease to the amount each would have received if NIH used only the DALY to apportion funding.

In general, actual funding levels approximated the DALY figures, says Neil Powe, director of Public Health's Welch Center for Prevention. A few diseases, however were significantly overfunded: AIDS received $1.4 billion, compared to a DALY-based prediction of $104 million; breast cancer, with a DALY of $110 million, received $382 million.

Powe and his colleagues also found that narrower measures of disease burden--such as incidence, prevalence, or mortality--were not associated or only weakly associated with actual NIH funding. Further, there were discrepancies among the various measures. For instance, the mortality rate for depression (8,000 deaths a year) was relatively low; But in terms of incidence, depression accounted for 21 million cases--the fourth most prevalent disease.

So, in lobbying for more funding, interest groups can select the measures of disease burden that favor their cause, says Powe.

In an editorial accompanying the report, NIH director Harold Varmus points out that the NIH considers many factors in allocating funding in addition to burden of disease, including quality of research and scientific opportunities. He also notes that a significant amount of NIH funding supports basic research, where the fruits of one endeavor often benefit progress in others.

The study was supported by the Robert Wood Johnson Clinical Scholars Program. --MH

Low-cost drug prevents HIV in infants

AIDS researchers from Hopkins and Uganda demonstrated that a new antiviral drug dramatically reduces mother-to-child transmission of the AIDS virus at a fraction of the cost of the antiviral AZT. The drug, nevirapine, costs $3 to $4 per patient, compared to about $260 for an equivalent regimen of AZT. Nevirapine also appears to have fewer side effects and last longer in the body.

Brooks Jackson
"This is probably the first study that addresses the cost barriers that have been a problem of other regimens to date," says physician Brooks Jackson, who led the Hopkins team. "Its simplicity, low cost, and safety" mean the regimen will be feasible in developing nations. Jackson and his colleagues reported their results in July at the National Institute of Allergy and Infectious Diseases, which sponsored the study.

Approximately 1,800 HIV-infected babies are born every day in developing countries, according to United Nations estimates. In subSaharan Africa, as many as 30 percent of pregnant women are HIV-positive. These women have about a one in four chance of passing the virus to their infants, a risk that increases with breastfeeding.

In the United States, doctors reduce mother-to-child transmission of HIV by giving AZT to women for the last few months of pregnancy and to the baby for six weeks after birth; this reduces the transmission rate to about 8 percent.

But this regimen's hefty pricetag for developing nations-- "millions and millions of dollars," says NIAID director Anthony Fauci--has put it out of reach. "Now we have something that is really affordable," says Fauci.

Jackson and colleagues from Makerere University, in Kampala, Uganda, compared the safety and efficacy of a short-term course of AZT and nevirapine, which was developed by Boehringer Ingelheim Pharmaceuticals. They enlisted 618 pregnant Ugandan women who were HIV-positive. Half of the women received a single nevirapine pill during labor. Their infants received a single liquid dose within three days after birth. The other half of the women received AZT every three hours during labor, and their infants received the drug twice a day for one week.

Fourteen to 16 weeks later, 13 percent of the infants who received nevirapine and 25 percent of those in the AZT group were infected with HIV.

Jackson is continuing to follow the infants until they are approximately 18 months of age. --MH

For prostate cancer patients, what next?

After a man has surgery to remove a cancerous prostate, an anxiety-ridden waiting game begins. Will cancer recur? If so, will it grow fast enough to warrant treatment? Now, thanks to an extensive study conducted by Johns Hopkins researchers, finding an answer can be as simple as following a flowchart.

The chart shows a patient's chances of remaining metastases-free as determined by three diagnostic criteria: the timing of a rise in the patient's prostate specific antigen (PSA); the patient's Gleason score, the numerical value for the aggressiveness of the tumor that was removed; and the length of time it takes the PSA value to double. The study was reported in the May 5 Journal of the American Medical Association.

It shows, for example, that a man who had a moderately severe tumor, whose PSA did not rise for two years after surgery, and whose PSA doubling rate was longer than 10 months has a 95 percent chance of remaining metastases-free for three years.

The study may help clarify previously murky areas about prostate cancer treatment, says urologist Alan Partin. "There has been a big controversy over when to give patients hormonal therapy," he says. "Until now, every [post-surgical patient] with a PSA that is rising was offered hormonal therapy." But the therapy can cause bone loss, impotence, and other side effects. So men at low risk of metastatic disease might opt to avoid the rigors of this treatment.

The latest study is based on the clinical outcome data of 2,000 men who had their prostates removed at Johns Hopkins Hospital between 1982 and 1997. --MH