Erik Goldman

PHILADELPHIA — High-dose topical tretinoin is generally well tolerated for chemoprevention of basal and squamous cell carcinomas, Dr. Amy Geng said at the annual meeting of the Society for Investigative Dermatology.

Daily application of 0.1% tretinoin causes some irritation, but it is generally mild, and tolerability tends to improve over time.

“Dermatologists tend to use 0.05% concentrations or lower, in an attempt to reduce the chances of irritation or other side effects. This is especially true for young patients with acne,” said Dr. Geng of the department of dermatology at Veterans Affairs Medical Center, Providence, R.I., and Brown University in Providence. But when using retinoids for long-term prevention of skin cancers, the lower concentrations may not give the full benefit. The challenge is always to balance optimal clinical outcomes against the potential for adverse effects.

Dr. Geng presented tolerability data from the VA Topical Tretinoin Chemoprevention Trial (VATTC), a large-scale, long-term study involving 736 elderly men with histories of keratinocyte skin cancers (BCC or SCCD). The patients were randomized to treatment with a vehicle cream or a 0.1% tretinoin cream on an ongoing basis. All of the study participants, who had an average age of 71 years, had had two or more keratinocyte skin cancers in the 6 months prior to enrollment.

The patients were instructed to apply the assigned treatment once daily for the first 3 weeks and twice daily thereafter. At any time during the study they could step back down to once-daily application if the twice-daily dosing proved to be too irritating. They could also apply sunscreens and moisturizers whenever they felt the need.

Investigators at the four participating centers saw the patients for follow-up visits every 6 months. To date, the patients have been on the protocol for a range of 1.5 to 5.5 years.

There is no question that the tretinoin produced more irritation than did the placebo. At 6 months, 61% of the tretinoin-treated patients reported some sort of retinoid-associated symptoms such as burning, itching, tingling, or other localized reactions, compared with 42% of those using the vehicle alone. Burning sensations, the most common reason people discontinue retinoid therapy, were reported by 39% of the tretinoin group but only 17% of the placebo group during the first 6 months.

The prevalence of all side effects tended to drop off steadily as the patients continued with treatment. By 30 months, there was no longer any statistically significant difference between the two groups in terms of frequency or severity of burning.

Overall, the side effects were mild, and there was no difference in severity of burning sensations between the patients in the two treatment groups.

There were more treatment cessations or dosing step-downs in the tretinoin group than in the placebo group. In all, 30% of those on the retinoid maintained their twice-daily dosing schedules, compared with 42% of those on placebo. Of the tretinoin patients, 15% had stopped using the medication, compared with 9% in the placebo group.

“By 6 months, the patients in the tretinoin group were less likely than were the controls to apply the treatment twice daily, but they were more likely to be using it twice daily than not at all,” Dr. Geng said. “Overall, 0.1% tretinoin is well tolerated, even with twice-daily application. It may be better tolerated in older people who have had keratinocyte cancers than in younger acne patients.”

ELSEVIER GLOBAL MEDICAL NEWS

PHILADELPHIA — High-dose topical tretinoin is generally well tolerated for chemoprevention of basal and squamous cell carcinomas, Dr. Amy Geng said at the annual meeting of the Society for Investigative Dermatology.

Daily application of 0.1% tretinoin causes some irritation, but it is generally mild, and tolerability tends to improve over time.

“Dermatologists tend to use 0.05% concentrations or lower, in an attempt to reduce the chances of irritation or other side effects. This is especially true for young patients with acne,” said Dr. Geng of the department of dermatology at Veterans Affairs Medical Center, Providence, R.I., and Brown University in Providence. But when using retinoids for long-term prevention of skin cancers, the lower concentrations may not give the full benefit. The challenge is always to balance optimal clinical outcomes against the potential for adverse effects.

Dr. Geng presented tolerability data from the VA Topical Tretinoin Chemoprevention Trial (VATTC), a large-scale, long-term study involving 736 elderly men with histories of keratinocyte skin cancers (BCC or SCCD). The patients were randomized to treatment with a vehicle cream or a 0.1% tretinoin cream on an ongoing basis. All of the study participants, who had an average age of 71 years, had had two or more keratinocyte skin cancers in the 6 months prior to enrollment.

The patients were instructed to apply the assigned treatment once daily for the first 3 weeks and twice daily thereafter. At any time during the study they could step back down to once-daily application if the twice-daily dosing proved to be too irritating. They could also apply sunscreens and moisturizers whenever they felt the need.

Investigators at the four participating centers saw the patients for follow-up visits every 6 months. To date, the patients have been on the protocol for a range of 1.5 to 5.5 years.

There is no question that the tretinoin produced more irritation than did the placebo. At 6 months, 61% of the tretinoin-treated patients reported some sort of retinoid-associated symptoms such as burning, itching, tingling, or other localized reactions, compared with 42% of those using the vehicle alone. Burning sensations, the most common reason people discontinue retinoid therapy, were reported by 39% of the tretinoin group but only 17% of the placebo group during the first 6 months.

The prevalence of all side effects tended to drop off steadily as the patients continued with treatment. By 30 months, there was no longer any statistically significant difference between the two groups in terms of frequency or severity of burning.

Overall, the side effects were mild, and there was no difference in severity of burning sensations between the patients in the two treatment groups.

There were more treatment cessations or dosing step-downs in the tretinoin group than in the placebo group. In all, 30% of those on the retinoid maintained their twice-daily dosing schedules, compared with 42% of those on placebo. Of the tretinoin patients, 15% had stopped using the medication, compared with 9% in the placebo group.

“By 6 months, the patients in the tretinoin group were less likely than were the controls to apply the treatment twice daily, but they were more likely to be using it twice daily than not at all,” Dr. Geng said. “Overall, 0.1% tretinoin is well tolerated, even with twice-daily application. It may be better tolerated in older people who have had keratinocyte cancers than in younger acne patients.”

ELSEVIER GLOBAL MEDICAL NEWS

PHILADELPHIA — High-dose topical tretinoin is generally well tolerated for chemoprevention of basal and squamous cell carcinomas, Dr. Amy Geng said at the annual meeting of the Society for Investigative Dermatology.

Daily application of 0.1% tretinoin causes some irritation, but it is generally mild, and tolerability tends to improve over time.

“Dermatologists tend to use 0.05% concentrations or lower, in an attempt to reduce the chances of irritation or other side effects. This is especially true for young patients with acne,” said Dr. Geng of the department of dermatology at Veterans Affairs Medical Center, Providence, R.I., and Brown University in Providence. But when using retinoids for long-term prevention of skin cancers, the lower concentrations may not give the full benefit. The challenge is always to balance optimal clinical outcomes against the potential for adverse effects.

Dr. Geng presented tolerability data from the VA Topical Tretinoin Chemoprevention Trial (VATTC), a large-scale, long-term study involving 736 elderly men with histories of keratinocyte skin cancers (BCC or SCCD). The patients were randomized to treatment with a vehicle cream or a 0.1% tretinoin cream on an ongoing basis. All of the study participants, who had an average age of 71 years, had had two or more keratinocyte skin cancers in the 6 months prior to enrollment.

The patients were instructed to apply the assigned treatment once daily for the first 3 weeks and twice daily thereafter. At any time during the study they could step back down to once-daily application if the twice-daily dosing proved to be too irritating. They could also apply sunscreens and moisturizers whenever they felt the need.

Investigators at the four participating centers saw the patients for follow-up visits every 6 months. To date, the patients have been on the protocol for a range of 1.5 to 5.5 years.

There is no question that the tretinoin produced more irritation than did the placebo. At 6 months, 61% of the tretinoin-treated patients reported some sort of retinoid-associated symptoms such as burning, itching, tingling, or other localized reactions, compared with 42% of those using the vehicle alone. Burning sensations, the most common reason people discontinue retinoid therapy, were reported by 39% of the tretinoin group but only 17% of the placebo group during the first 6 months.

The prevalence of all side effects tended to drop off steadily as the patients continued with treatment. By 30 months, there was no longer any statistically significant difference between the two groups in terms of frequency or severity of burning.

Overall, the side effects were mild, and there was no difference in severity of burning sensations between the patients in the two treatment groups.

There were more treatment cessations or dosing step-downs in the tretinoin group than in the placebo group. In all, 30% of those on the retinoid maintained their twice-daily dosing schedules, compared with 42% of those on placebo. Of the tretinoin patients, 15% had stopped using the medication, compared with 9% in the placebo group.

“By 6 months, the patients in the tretinoin group were less likely than were the controls to apply the treatment twice daily, but they were more likely to be using it twice daily than not at all,” Dr. Geng said. “Overall, 0.1% tretinoin is well tolerated, even with twice-daily application. It may be better tolerated in older people who have had keratinocyte cancers than in younger acne patients.”

ELSEVIER GLOBAL MEDICAL NEWS

MADRID — European and American hypertension specialists appear to be mending their rift over the issue of “prehypertension,” and moving toward consensus on the importance of treating the earliest stages of the hypertensive disease process.

Leaders of the European Society of Hypertension (ESH) and the American Society of Hypertension (ASH) held a first-ever joint meeting during the European society's 16th Annual European Meeting on Hypertension. Despite past differences regarding prehypertension, views on both sides of the Atlantic now show far more convergence than divergence.

The concept of prehypertension, and the position that some high-risk people with blood pressures as low as 120/80 mm Hg should be treated with antihypertensive drugs, drew considerable criticism, especially from European cardiologists, when it was first articulated in the 2003 Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines. Critics on both sides of the ocean argued that JNC was doing the bidding of pharmaceutical companies by lowering the treatment threshold in a way that would suddenly render as many as 50 million more people eligible for drug therapy.

Dr. Thomas D. Giles, immediate past president of ASH, who represented the Americans in the joint meeting, defended the underlying intention of the recommendations. “JNC was calling attention to the fact that just because the blood pressure isn't over 140/90 doesn't mean there's no disease process going on.” Essentially, JNC took the 120/80 cut-point, considered “optimal” in the previous guidelines, and made it the new “normal,” with the new “optimal” being under the 120/80 mark.

Over the last 3 years, a number of studies and metaanalyses have shed light on the subject, dispelling much of the criticism but also tempering the enthusiasm of those who would treat anyone with systolic pressure over 120 mm Hg.

The Trial of Preventing Hypertension (TROPHY) showed that treatment of high-risk but normotensive patients could keep them from going into the hypertension range (Am. J. Hypertens. 2005;18:980–5). Dr. Giles pointed out that although these patients were considered normotensive under current guidelines, many of them had multiple risk factors for cardiovascular disease.

“These were not normal people. They were actually sick, and the study showed that if you give them an ARB [angiotensin receptor blocker] and get a 10-mm reduction in systolic [blood pressure], you can prevent emergence of frank hypertension. I would not want to be in the placebo group of the TROPHY study,” he said.

In aggregate, available data support the notion that the hypertensive and cardiovascular disease process begins well before blood pressure increases, and that early intervention can reduce cardiovascular risk. However, the emerging view obliterates the idea of simple blood pressure cut-points and supports the European view that blood pressure itself is only one of many variables that must be considered in a global clinical assessment of a person's cardiovascular risk.

The very same data set that gave rise to the original prehypertension concept also challenges the idea of simple clinical cut-points. JNC developed the prehypertension idea after looking at the data of Lewington and colleagues (Lancet 2002;360:1903–13), which showed that cardiovascular risk begins to rise at pressures as low as 115/75. For each 20/10 mm Hg rise in pressure, there is a doubling of cardiovascular risk. But these same data obliterate simple thresholds. “There really is no cut-point, no threshold. There's only a continuum of risk that begins after 115/75.”

The point, said Dr. Giles, is that “you cannot treat blood pressure isolated from the rest of the patient. … New definitions of hypertension should not be based on rigid numeric cut-offs, but rather on assessment of the overall state of the cardiovascular system.”

If Dr. Giles' comments seem to have a decidedly European accent, Dr. Giuseppe Mancia, executive officer of the Scientific Council for ESH, said European views are starting to move to an American beat. “There are a lot of high-risk people who have early signs of organ damage, and they need treatment regardless of the blood pressure numbers,” he said.

Dr. Peter Sleight, of the department of cardiovascular medicine at John Radcliffe Hospital, Oxford, England, said that one of the main virtues of JNC's prehypertension idea is that it called attention to the fact that the majority of strokes occur in people who would have been considered normotensive under previous guidelines. “The whole game in stroke prevention is in lowering blood pressure. A systolic of 135 carries lower risk than a systolic of 145,” said Dr. Sleight.

ESH is in the process of revising its therapeutic guidelines, which were last revised in 2003, and the new edition is expected sometime next year. Although it is too soon to know exactly what they will say, Dr. Mancia predicted they will likely move European practice standards closer to the early-intervention predilection of the Americans.

The new European guidelines will definitely underscore the general importance of lowering blood pressure. “We know that regardless of the kind of treatment you give, lowering blood pressure is protective. The magnitude of pressure reduction correlates directly with the magnitude of reduction of cardiovascular morbidity and mortality. We don't care how you do it. Get the pressure below 140/90, and you reduce risk. It should be below 130/80 if patients are at high risk. All the international guidelines agree on this.”

They will also likely support the wider use of combination therapy at the outset of treatment. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) showed that 9 of 10 high-risk hypertensive patients required more than one antihypertensive medication to achieve pressure control.

The guidelines will reinforce the general European preference for global risk assessment. “We need to look at the overall status of the cardiovascular system, not just the blood pressure measurements. The greater the risk, the more aggressive the treatment should be,” said Dr. Mancia, professor of medicine at the University of Milan-Bicocca, Italy. He stressed that total risk assessment involves consideration of subclinical organ damage such as microalbuminuria and left ventricular hypertrophy.

If patients have LVH alone or microalbuminuria alone, they do far better than if they have both (J. Hum. Hypertens. 2004;18:453–9). Early organ system damage “is prognostic, and it won't show up unless you look for it. Regression of LVH or proteinuria by treatment is associated with improved outcomes. We surmised this, but we didn't have the data in 2003,” he said.

Dr. Mancia and Dr. Giles agreed that it is these other factors that will be critical in determining if a patient with borderline high blood pressure truly needs treatment. If an otherwise healthy 65-year-old man has a pressure reading of 125/80, he probably does not need drug therapy. However, if there are elevated lipids, impaired glucose tolerance, microalbuminuria, and other indicators of risk, the rationale for treatment is much stronger.

It is important to look at blood pressure over time. A systolic measurement of 120 may seem normotensive, but if this reflects a steady and consistent increase from 90 or 100 in previous years, it is an indicator that the cardiovascular system is beginning to malfunction.

The new ESH guidelines will probably call for wider use of ambulatory and home blood pressure monitoring. Dr. Mancia stressed that office pressure measurements are limited, and cited a recent Italian study that showed progressive increase in risk if ambulatory or home pressure measurements are also increased.

Hypertension experts across the globe are beginning to question the value of brachial artery pressure measurements. “If you measure blood pressure in the brachial artery, you cannot be confident you're getting a picture of the central aortic pressures,” said Dr. Giles. He added that measurement of central aortic pressure makes a lot more sense. Currently, the technology to do so is limited to research settings, but this is a technological impediment not a conceptual one.

MADRID — European and American hypertension specialists appear to be mending their rift over the issue of “prehypertension,” and moving toward consensus on the importance of treating the earliest stages of the hypertensive disease process.

Leaders of the European Society of Hypertension (ESH) and the American Society of Hypertension (ASH) held a first-ever joint meeting during the European society's 16th Annual European Meeting on Hypertension. Despite past differences regarding prehypertension, views on both sides of the Atlantic now show far more convergence than divergence.

The concept of prehypertension, and the position that some high-risk people with blood pressures as low as 120/80 mm Hg should be treated with antihypertensive drugs, drew considerable criticism, especially from European cardiologists, when it was first articulated in the 2003 Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines. Critics on both sides of the ocean argued that JNC was doing the bidding of pharmaceutical companies by lowering the treatment threshold in a way that would suddenly render as many as 50 million more people eligible for drug therapy.

Dr. Thomas D. Giles, immediate past president of ASH, who represented the Americans in the joint meeting, defended the underlying intention of the recommendations. “JNC was calling attention to the fact that just because the blood pressure isn't over 140/90 doesn't mean there's no disease process going on.” Essentially, JNC took the 120/80 cut-point, considered “optimal” in the previous guidelines, and made it the new “normal,” with the new “optimal” being under the 120/80 mark.

Over the last 3 years, a number of studies and metaanalyses have shed light on the subject, dispelling much of the criticism but also tempering the enthusiasm of those who would treat anyone with systolic pressure over 120 mm Hg.

The Trial of Preventing Hypertension (TROPHY) showed that treatment of high-risk but normotensive patients could keep them from going into the hypertension range (Am. J. Hypertens. 2005;18:980–5). Dr. Giles pointed out that although these patients were considered normotensive under current guidelines, many of them had multiple risk factors for cardiovascular disease.

“These were not normal people. They were actually sick, and the study showed that if you give them an ARB [angiotensin receptor blocker] and get a 10-mm reduction in systolic [blood pressure], you can prevent emergence of frank hypertension. I would not want to be in the placebo group of the TROPHY study,” he said.

In aggregate, available data support the notion that the hypertensive and cardiovascular disease process begins well before blood pressure increases, and that early intervention can reduce cardiovascular risk. However, the emerging view obliterates the idea of simple blood pressure cut-points and supports the European view that blood pressure itself is only one of many variables that must be considered in a global clinical assessment of a person's cardiovascular risk.

The very same data set that gave rise to the original prehypertension concept also challenges the idea of simple clinical cut-points. JNC developed the prehypertension idea after looking at the data of Lewington and colleagues (Lancet 2002;360:1903–13), which showed that cardiovascular risk begins to rise at pressures as low as 115/75. For each 20/10 mm Hg rise in pressure, there is a doubling of cardiovascular risk. But these same data obliterate simple thresholds. “There really is no cut-point, no threshold. There's only a continuum of risk that begins after 115/75.”

The point, said Dr. Giles, is that “you cannot treat blood pressure isolated from the rest of the patient. … New definitions of hypertension should not be based on rigid numeric cut-offs, but rather on assessment of the overall state of the cardiovascular system.”

If Dr. Giles' comments seem to have a decidedly European accent, Dr. Giuseppe Mancia, executive officer of the Scientific Council for ESH, said European views are starting to move to an American beat. “There are a lot of high-risk people who have early signs of organ damage, and they need treatment regardless of the blood pressure numbers,” he said.

Dr. Peter Sleight, of the department of cardiovascular medicine at John Radcliffe Hospital, Oxford, England, said that one of the main virtues of JNC's prehypertension idea is that it called attention to the fact that the majority of strokes occur in people who would have been considered normotensive under previous guidelines. “The whole game in stroke prevention is in lowering blood pressure. A systolic of 135 carries lower risk than a systolic of 145,” said Dr. Sleight.

ESH is in the process of revising its therapeutic guidelines, which were last revised in 2003, and the new edition is expected sometime next year. Although it is too soon to know exactly what they will say, Dr. Mancia predicted they will likely move European practice standards closer to the early-intervention predilection of the Americans.

The new European guidelines will definitely underscore the general importance of lowering blood pressure. “We know that regardless of the kind of treatment you give, lowering blood pressure is protective. The magnitude of pressure reduction correlates directly with the magnitude of reduction of cardiovascular morbidity and mortality. We don't care how you do it. Get the pressure below 140/90, and you reduce risk. It should be below 130/80 if patients are at high risk. All the international guidelines agree on this.”

They will also likely support the wider use of combination therapy at the outset of treatment. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) showed that 9 of 10 high-risk hypertensive patients required more than one antihypertensive medication to achieve pressure control.

The guidelines will reinforce the general European preference for global risk assessment. “We need to look at the overall status of the cardiovascular system, not just the blood pressure measurements. The greater the risk, the more aggressive the treatment should be,” said Dr. Mancia, professor of medicine at the University of Milan-Bicocca, Italy. He stressed that total risk assessment involves consideration of subclinical organ damage such as microalbuminuria and left ventricular hypertrophy.

If patients have LVH alone or microalbuminuria alone, they do far better than if they have both (J. Hum. Hypertens. 2004;18:453–9). Early organ system damage “is prognostic, and it won't show up unless you look for it. Regression of LVH or proteinuria by treatment is associated with improved outcomes. We surmised this, but we didn't have the data in 2003,” he said.

Dr. Mancia and Dr. Giles agreed that it is these other factors that will be critical in determining if a patient with borderline high blood pressure truly needs treatment. If an otherwise healthy 65-year-old man has a pressure reading of 125/80, he probably does not need drug therapy. However, if there are elevated lipids, impaired glucose tolerance, microalbuminuria, and other indicators of risk, the rationale for treatment is much stronger.

It is important to look at blood pressure over time. A systolic measurement of 120 may seem normotensive, but if this reflects a steady and consistent increase from 90 or 100 in previous years, it is an indicator that the cardiovascular system is beginning to malfunction.

The new ESH guidelines will probably call for wider use of ambulatory and home blood pressure monitoring. Dr. Mancia stressed that office pressure measurements are limited, and cited a recent Italian study that showed progressive increase in risk if ambulatory or home pressure measurements are also increased.

Hypertension experts across the globe are beginning to question the value of brachial artery pressure measurements. “If you measure blood pressure in the brachial artery, you cannot be confident you're getting a picture of the central aortic pressures,” said Dr. Giles. He added that measurement of central aortic pressure makes a lot more sense. Currently, the technology to do so is limited to research settings, but this is a technological impediment not a conceptual one.

MADRID — European and American hypertension specialists appear to be mending their rift over the issue of “prehypertension,” and moving toward consensus on the importance of treating the earliest stages of the hypertensive disease process.

Leaders of the European Society of Hypertension (ESH) and the American Society of Hypertension (ASH) held a first-ever joint meeting during the European society's 16th Annual European Meeting on Hypertension. Despite past differences regarding prehypertension, views on both sides of the Atlantic now show far more convergence than divergence.

The concept of prehypertension, and the position that some high-risk people with blood pressures as low as 120/80 mm Hg should be treated with antihypertensive drugs, drew considerable criticism, especially from European cardiologists, when it was first articulated in the 2003 Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines. Critics on both sides of the ocean argued that JNC was doing the bidding of pharmaceutical companies by lowering the treatment threshold in a way that would suddenly render as many as 50 million more people eligible for drug therapy.

Dr. Thomas D. Giles, immediate past president of ASH, who represented the Americans in the joint meeting, defended the underlying intention of the recommendations. “JNC was calling attention to the fact that just because the blood pressure isn't over 140/90 doesn't mean there's no disease process going on.” Essentially, JNC took the 120/80 cut-point, considered “optimal” in the previous guidelines, and made it the new “normal,” with the new “optimal” being under the 120/80 mark.

Over the last 3 years, a number of studies and metaanalyses have shed light on the subject, dispelling much of the criticism but also tempering the enthusiasm of those who would treat anyone with systolic pressure over 120 mm Hg.

The Trial of Preventing Hypertension (TROPHY) showed that treatment of high-risk but normotensive patients could keep them from going into the hypertension range (Am. J. Hypertens. 2005;18:980–5). Dr. Giles pointed out that although these patients were considered normotensive under current guidelines, many of them had multiple risk factors for cardiovascular disease.

“These were not normal people. They were actually sick, and the study showed that if you give them an ARB [angiotensin receptor blocker] and get a 10-mm reduction in systolic [blood pressure], you can prevent emergence of frank hypertension. I would not want to be in the placebo group of the TROPHY study,” he said.

In aggregate, available data support the notion that the hypertensive and cardiovascular disease process begins well before blood pressure increases, and that early intervention can reduce cardiovascular risk. However, the emerging view obliterates the idea of simple blood pressure cut-points and supports the European view that blood pressure itself is only one of many variables that must be considered in a global clinical assessment of a person's cardiovascular risk.

The very same data set that gave rise to the original prehypertension concept also challenges the idea of simple clinical cut-points. JNC developed the prehypertension idea after looking at the data of Lewington and colleagues (Lancet 2002;360:1903–13), which showed that cardiovascular risk begins to rise at pressures as low as 115/75. For each 20/10 mm Hg rise in pressure, there is a doubling of cardiovascular risk. But these same data obliterate simple thresholds. “There really is no cut-point, no threshold. There's only a continuum of risk that begins after 115/75.”

The point, said Dr. Giles, is that “you cannot treat blood pressure isolated from the rest of the patient. … New definitions of hypertension should not be based on rigid numeric cut-offs, but rather on assessment of the overall state of the cardiovascular system.”

If Dr. Giles' comments seem to have a decidedly European accent, Dr. Giuseppe Mancia, executive officer of the Scientific Council for ESH, said European views are starting to move to an American beat. “There are a lot of high-risk people who have early signs of organ damage, and they need treatment regardless of the blood pressure numbers,” he said.

Dr. Peter Sleight, of the department of cardiovascular medicine at John Radcliffe Hospital, Oxford, England, said that one of the main virtues of JNC's prehypertension idea is that it called attention to the fact that the majority of strokes occur in people who would have been considered normotensive under previous guidelines. “The whole game in stroke prevention is in lowering blood pressure. A systolic of 135 carries lower risk than a systolic of 145,” said Dr. Sleight.

ESH is in the process of revising its therapeutic guidelines, which were last revised in 2003, and the new edition is expected sometime next year. Although it is too soon to know exactly what they will say, Dr. Mancia predicted they will likely move European practice standards closer to the early-intervention predilection of the Americans.

The new European guidelines will definitely underscore the general importance of lowering blood pressure. “We know that regardless of the kind of treatment you give, lowering blood pressure is protective. The magnitude of pressure reduction correlates directly with the magnitude of reduction of cardiovascular morbidity and mortality. We don't care how you do it. Get the pressure below 140/90, and you reduce risk. It should be below 130/80 if patients are at high risk. All the international guidelines agree on this.”

They will also likely support the wider use of combination therapy at the outset of treatment. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) showed that 9 of 10 high-risk hypertensive patients required more than one antihypertensive medication to achieve pressure control.

The guidelines will reinforce the general European preference for global risk assessment. “We need to look at the overall status of the cardiovascular system, not just the blood pressure measurements. The greater the risk, the more aggressive the treatment should be,” said Dr. Mancia, professor of medicine at the University of Milan-Bicocca, Italy. He stressed that total risk assessment involves consideration of subclinical organ damage such as microalbuminuria and left ventricular hypertrophy.

If patients have LVH alone or microalbuminuria alone, they do far better than if they have both (J. Hum. Hypertens. 2004;18:453–9). Early organ system damage “is prognostic, and it won't show up unless you look for it. Regression of LVH or proteinuria by treatment is associated with improved outcomes. We surmised this, but we didn't have the data in 2003,” he said.

Dr. Mancia and Dr. Giles agreed that it is these other factors that will be critical in determining if a patient with borderline high blood pressure truly needs treatment. If an otherwise healthy 65-year-old man has a pressure reading of 125/80, he probably does not need drug therapy. However, if there are elevated lipids, impaired glucose tolerance, microalbuminuria, and other indicators of risk, the rationale for treatment is much stronger.

It is important to look at blood pressure over time. A systolic measurement of 120 may seem normotensive, but if this reflects a steady and consistent increase from 90 or 100 in previous years, it is an indicator that the cardiovascular system is beginning to malfunction.

The new ESH guidelines will probably call for wider use of ambulatory and home blood pressure monitoring. Dr. Mancia stressed that office pressure measurements are limited, and cited a recent Italian study that showed progressive increase in risk if ambulatory or home pressure measurements are also increased.

Hypertension experts across the globe are beginning to question the value of brachial artery pressure measurements. “If you measure blood pressure in the brachial artery, you cannot be confident you're getting a picture of the central aortic pressures,” said Dr. Giles. He added that measurement of central aortic pressure makes a lot more sense. Currently, the technology to do so is limited to research settings, but this is a technological impediment not a conceptual one.

OLD GREENWICH, CONN. — Vitamin D deficiency, sometimes quite severe, is common in obese adolescents, according to a recent study by Dr. Margarita Smotkin-Tangorra and colleagues at Maimonides Medical Center, N.Y.

Speaking at a meeting of the Eastern Society for Pediatric Research, Dr. Smotkin-Tangorra, of the department of pediatric endocrinology and diabetes at the medical center, said that 55% of a cohort of 217 obese children and adolescents were deficient in serum 25-hydroxyvitamin D (25-OHD), with blood levels of less than 20 ng/mL; 22% were severely deficient, with serum levels below 10 ng/mL.

Though there are published reports showing correlations between vitamin D deficiency and obesity in adults, there are no prior studies in children or teens. “We know vitamin D deficiency is prevalent in all age groups, including healthy adolescents. In obese adults, we know that it correlates with insulin resistance, progression to diabetes mellitus, metabolic and endocrine problems, and increased risk of cancer. We wanted to see if there were similar correlations in obese kids,” she told attendees at the meeting, cosponsored by Children's Hospital of Philadelphia.

The study group included 118 females and 99 males, ranging in age from 7 to 18 years, and with a mean BMI of 32.2 kg/m

They found strong correlations between low vitamin D level and elevated BMI, increased systolic blood pressure, lower HDL, and lower alkaline phosphatase.

The correlation between vitamin D status and BMI was particularly striking. Those patients who were vitamin D deficient had a mean BMI of 36.2, compared with a mean of 30.6 among patients whose vitamin D levels were sufficient.

The association with systolic hypertension was also noteworthy; vitamin D-deficient patients had a mean systolic blood pressure of 117 mm Hg, while those with sufficient vitamin D had a mean systolic blood pressure of 111 mm Hg. Mean HDL was 40 mg/dL in the vitamin-deficient group, compared with 42 mg/dL in the vitamin-sufficient group.

There was no correlation between vitamin D status and fasting blood glucose or thyroid hormone levels. Insulin sensitivity as indicated by a quantitative insulin sensitivity check index score showed a marginally significant correlation with vitamin D, with the deficient children showing a slightly lower score than the sufficient ones.

Vitamin D deficiency is disturbingly common, even among healthy children. Best current estimates are that roughly 20% of all school-age children are deficient. If Dr. Smotkin-Tangorra's data prove to be representative of obese children nationwide, the problem may be greater than previously imagined, especially given what is now known about the long-term impact of chronic vitamin D deficiency.

Increased prevalence of deficiency reflects several general trends, most importantly the diminishing quality of children's diets and lack of outdoor exercise. How it fits into the pathophysiology and etiology of obesity is an open-ended question at this point. Lower levels of vitamin D could well be an indicator of poor overall nutritional status. Dr. Smotkin-Tangorra's team did not study blood levels of any other vitamins or minerals, but their research suggests that the more obese a child is, the more likely that the child's overall nutritional status will be poor.

Vitamin D deficiency is one of the few common correlates of childhood obesity that is easy to rectify. “We are routinely supplementing all of our obese kids with Os-Cal, 500 mg, thrice daily, and we are starting to collect data on the outcomes.” She advised clinicians working with children and adolescents to stay vigilant for vitamin D deficiency, especially in obese patients, and to supplement with vitamin D and calcium when the levels are low. There's little risk, it is inexpensive, and the potential long-term benefits could be great.

OLD GREENWICH, CONN. — Vitamin D deficiency, sometimes quite severe, is common in obese adolescents, according to a recent study by Dr. Margarita Smotkin-Tangorra and colleagues at Maimonides Medical Center, N.Y.

Speaking at a meeting of the Eastern Society for Pediatric Research, Dr. Smotkin-Tangorra, of the department of pediatric endocrinology and diabetes at the medical center, said that 55% of a cohort of 217 obese children and adolescents were deficient in serum 25-hydroxyvitamin D (25-OHD), with blood levels of less than 20 ng/mL; 22% were severely deficient, with serum levels below 10 ng/mL.

Though there are published reports showing correlations between vitamin D deficiency and obesity in adults, there are no prior studies in children or teens. “We know vitamin D deficiency is prevalent in all age groups, including healthy adolescents. In obese adults, we know that it correlates with insulin resistance, progression to diabetes mellitus, metabolic and endocrine problems, and increased risk of cancer. We wanted to see if there were similar correlations in obese kids,” she told attendees at the meeting, cosponsored by Children's Hospital of Philadelphia.

The study group included 118 females and 99 males, ranging in age from 7 to 18 years, and with a mean BMI of 32.2 kg/m

They found strong correlations between low vitamin D level and elevated BMI, increased systolic blood pressure, lower HDL, and lower alkaline phosphatase.

The correlation between vitamin D status and BMI was particularly striking. Those patients who were vitamin D deficient had a mean BMI of 36.2, compared with a mean of 30.6 among patients whose vitamin D levels were sufficient.

The association with systolic hypertension was also noteworthy; vitamin D-deficient patients had a mean systolic blood pressure of 117 mm Hg, while those with sufficient vitamin D had a mean systolic blood pressure of 111 mm Hg. Mean HDL was 40 mg/dL in the vitamin-deficient group, compared with 42 mg/dL in the vitamin-sufficient group.

There was no correlation between vitamin D status and fasting blood glucose or thyroid hormone levels. Insulin sensitivity as indicated by a quantitative insulin sensitivity check index score showed a marginally significant correlation with vitamin D, with the deficient children showing a slightly lower score than the sufficient ones.

Vitamin D deficiency is disturbingly common, even among healthy children. Best current estimates are that roughly 20% of all school-age children are deficient. If Dr. Smotkin-Tangorra's data prove to be representative of obese children nationwide, the problem may be greater than previously imagined, especially given what is now known about the long-term impact of chronic vitamin D deficiency.

Increased prevalence of deficiency reflects several general trends, most importantly the diminishing quality of children's diets and lack of outdoor exercise. How it fits into the pathophysiology and etiology of obesity is an open-ended question at this point. Lower levels of vitamin D could well be an indicator of poor overall nutritional status. Dr. Smotkin-Tangorra's team did not study blood levels of any other vitamins or minerals, but their research suggests that the more obese a child is, the more likely that the child's overall nutritional status will be poor.

Vitamin D deficiency is one of the few common correlates of childhood obesity that is easy to rectify. “We are routinely supplementing all of our obese kids with Os-Cal, 500 mg, thrice daily, and we are starting to collect data on the outcomes.” She advised clinicians working with children and adolescents to stay vigilant for vitamin D deficiency, especially in obese patients, and to supplement with vitamin D and calcium when the levels are low. There's little risk, it is inexpensive, and the potential long-term benefits could be great.

OLD GREENWICH, CONN. — Vitamin D deficiency, sometimes quite severe, is common in obese adolescents, according to a recent study by Dr. Margarita Smotkin-Tangorra and colleagues at Maimonides Medical Center, N.Y.

Speaking at a meeting of the Eastern Society for Pediatric Research, Dr. Smotkin-Tangorra, of the department of pediatric endocrinology and diabetes at the medical center, said that 55% of a cohort of 217 obese children and adolescents were deficient in serum 25-hydroxyvitamin D (25-OHD), with blood levels of less than 20 ng/mL; 22% were severely deficient, with serum levels below 10 ng/mL.

Though there are published reports showing correlations between vitamin D deficiency and obesity in adults, there are no prior studies in children or teens. “We know vitamin D deficiency is prevalent in all age groups, including healthy adolescents. In obese adults, we know that it correlates with insulin resistance, progression to diabetes mellitus, metabolic and endocrine problems, and increased risk of cancer. We wanted to see if there were similar correlations in obese kids,” she told attendees at the meeting, cosponsored by Children's Hospital of Philadelphia.

The study group included 118 females and 99 males, ranging in age from 7 to 18 years, and with a mean BMI of 32.2 kg/m

They found strong correlations between low vitamin D level and elevated BMI, increased systolic blood pressure, lower HDL, and lower alkaline phosphatase.

The correlation between vitamin D status and BMI was particularly striking. Those patients who were vitamin D deficient had a mean BMI of 36.2, compared with a mean of 30.6 among patients whose vitamin D levels were sufficient.

The association with systolic hypertension was also noteworthy; vitamin D-deficient patients had a mean systolic blood pressure of 117 mm Hg, while those with sufficient vitamin D had a mean systolic blood pressure of 111 mm Hg. Mean HDL was 40 mg/dL in the vitamin-deficient group, compared with 42 mg/dL in the vitamin-sufficient group.

There was no correlation between vitamin D status and fasting blood glucose or thyroid hormone levels. Insulin sensitivity as indicated by a quantitative insulin sensitivity check index score showed a marginally significant correlation with vitamin D, with the deficient children showing a slightly lower score than the sufficient ones.

Vitamin D deficiency is disturbingly common, even among healthy children. Best current estimates are that roughly 20% of all school-age children are deficient. If Dr. Smotkin-Tangorra's data prove to be representative of obese children nationwide, the problem may be greater than previously imagined, especially given what is now known about the long-term impact of chronic vitamin D deficiency.

Increased prevalence of deficiency reflects several general trends, most importantly the diminishing quality of children's diets and lack of outdoor exercise. How it fits into the pathophysiology and etiology of obesity is an open-ended question at this point. Lower levels of vitamin D could well be an indicator of poor overall nutritional status. Dr. Smotkin-Tangorra's team did not study blood levels of any other vitamins or minerals, but their research suggests that the more obese a child is, the more likely that the child's overall nutritional status will be poor.

Vitamin D deficiency is one of the few common correlates of childhood obesity that is easy to rectify. “We are routinely supplementing all of our obese kids with Os-Cal, 500 mg, thrice daily, and we are starting to collect data on the outcomes.” She advised clinicians working with children and adolescents to stay vigilant for vitamin D deficiency, especially in obese patients, and to supplement with vitamin D and calcium when the levels are low. There's little risk, it is inexpensive, and the potential long-term benefits could be great.

PHILADELPHIA — Patients with psoriasis who drink coffee frequently respond better to treatment with methotrexate and sulfasalazine, Dr. Yolanda Helfrich reported at the annual meeting of the Society for Investigative Dermatology.

That should be good news for patients who like to drink coffee, said Dr. Helfrich of the department of dermatology, University of Michigan, Ann Arbor. The impact of coffee and other caffeine-containing beverages on inflammatory conditions such as psoriasis has been the subject of controversy for some time. Many people consider caffeine to be proinflammatory and have suggested that patients with inflammatory diseases cut their consumption.

On face value, one would expect coffee to thwart the efficacy of drugs such as methotrexate (MTX) and sulfasalazine (SSZ). “Both of these drugs are anti-inflammatory, and they work by inhibiting an enzyme called 5-amidoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase, resulting in AICAR accumulation. This leads to increased adenosine which has anti-inflammatory properties,” explained Dr. Helfrich. “Caffeine acts as an adenosine receptor antagonist, so you'd expect it to inhibit MTX and SSZ.”

Indeed, a study published several years ago involving 91 patients with rheumatoid arthritis showed that regular coffee drinkers were more likely to discontinue MTX therapy due to perceived lack of efficacy. A second rheumatoid arthritis study involving 39 patients also showed inhibition of the drug's effects, but other published studies show no such effects.

But it appears that, at least biochemically, coffee has bivalent effects. While it is true that caffeine is an adenosine receptor antagonist, it also increases cyclic adenosine monophosphate, (cAMP) which has antiproliferative and immunosuppressive effects. It also simultaneously reduces the production of tumor necrosis factor-? (TNF-α, which is high in psoriasis. Presumably, both of these changes would be beneficial to patients with psoriasis. “We wondered which effect would be more important: the receptor antagonism or the TNF-α reduction and cAMP increase.”

Dr. Helfrich and her colleagues surveyed 21 patients with moderate to severe psoriasis who received MTX and SSZ. The patients were asked to rate the efficacy of the drug therapies on a 1–10 scale, with 1 representing “not effective” and 10 representing “highly effective.” Among other questions regarding their lifestyles, the patients were asked to estimate their weekly coffee consumption.

Plotting coffee consumption against treatment rating scores, the investigators found a weak but statistically significant correlation between coffee drinking and improved efficacy as perceived by the patients. Those who drank 10 or more cups of coffee each week had a mean 1-point improvement in treatment rating scores, compared with those who drank less. When the researchers looked at the data through a linear regression model that controlled for gender, duration of psoriasis, drug doses, and years of drug therapy, they found a much more robust correlation.

Dr. Helfrich acknowledged the limitations of this study—mainly the small population size and the exclusive reliance on patient self-reporting—for the drug efficacy data and for the estimates of caffeine intake. She also recognized the possibility that the perk-up patients experience from drinking coffee could be giving them an overall sense of well-being that colored their perception of the therapeutic efficacy. “Caffeine is an addictive drug and most addictive drugs increase endorphins, which makes us feel better. So this is an open question. We do need to do a study with investigator assessment of the drug efficacy,” she said.

That said, she noted that there is reason to think that the observation represents an objective phenomenon. “In psoriasis, the longer-term anti-inflammatory effects of increasing the adenosine receptors, increasing cAMP and reducing TNF outweigh the acute proinflammatory effects of caffeine.”

Dr. Helfrich said she believes the observed effect of coffee is due to the caffeine, so presumably other caffeinated beverages would have similar impact, but this remains to be determined by future research.

In the meantime, it seems there is no reason to counsel coffee-loving MTX/SSZ-treated psoriasis patients against making routine trips to their local coffeehouses.

PHILADELPHIA — Patients with psoriasis who drink coffee frequently respond better to treatment with methotrexate and sulfasalazine, Dr. Yolanda Helfrich reported at the annual meeting of the Society for Investigative Dermatology.

That should be good news for patients who like to drink coffee, said Dr. Helfrich of the department of dermatology, University of Michigan, Ann Arbor. The impact of coffee and other caffeine-containing beverages on inflammatory conditions such as psoriasis has been the subject of controversy for some time. Many people consider caffeine to be proinflammatory and have suggested that patients with inflammatory diseases cut their consumption.

On face value, one would expect coffee to thwart the efficacy of drugs such as methotrexate (MTX) and sulfasalazine (SSZ). “Both of these drugs are anti-inflammatory, and they work by inhibiting an enzyme called 5-amidoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase, resulting in AICAR accumulation. This leads to increased adenosine which has anti-inflammatory properties,” explained Dr. Helfrich. “Caffeine acts as an adenosine receptor antagonist, so you'd expect it to inhibit MTX and SSZ.”

Indeed, a study published several years ago involving 91 patients with rheumatoid arthritis showed that regular coffee drinkers were more likely to discontinue MTX therapy due to perceived lack of efficacy. A second rheumatoid arthritis study involving 39 patients also showed inhibition of the drug's effects, but other published studies show no such effects.

But it appears that, at least biochemically, coffee has bivalent effects. While it is true that caffeine is an adenosine receptor antagonist, it also increases cyclic adenosine monophosphate, (cAMP) which has antiproliferative and immunosuppressive effects. It also simultaneously reduces the production of tumor necrosis factor-? (TNF-α, which is high in psoriasis. Presumably, both of these changes would be beneficial to patients with psoriasis. “We wondered which effect would be more important: the receptor antagonism or the TNF-α reduction and cAMP increase.”

Dr. Helfrich and her colleagues surveyed 21 patients with moderate to severe psoriasis who received MTX and SSZ. The patients were asked to rate the efficacy of the drug therapies on a 1–10 scale, with 1 representing “not effective” and 10 representing “highly effective.” Among other questions regarding their lifestyles, the patients were asked to estimate their weekly coffee consumption.

Plotting coffee consumption against treatment rating scores, the investigators found a weak but statistically significant correlation between coffee drinking and improved efficacy as perceived by the patients. Those who drank 10 or more cups of coffee each week had a mean 1-point improvement in treatment rating scores, compared with those who drank less. When the researchers looked at the data through a linear regression model that controlled for gender, duration of psoriasis, drug doses, and years of drug therapy, they found a much more robust correlation.

Dr. Helfrich acknowledged the limitations of this study—mainly the small population size and the exclusive reliance on patient self-reporting—for the drug efficacy data and for the estimates of caffeine intake. She also recognized the possibility that the perk-up patients experience from drinking coffee could be giving them an overall sense of well-being that colored their perception of the therapeutic efficacy. “Caffeine is an addictive drug and most addictive drugs increase endorphins, which makes us feel better. So this is an open question. We do need to do a study with investigator assessment of the drug efficacy,” she said.

That said, she noted that there is reason to think that the observation represents an objective phenomenon. “In psoriasis, the longer-term anti-inflammatory effects of increasing the adenosine receptors, increasing cAMP and reducing TNF outweigh the acute proinflammatory effects of caffeine.”

Dr. Helfrich said she believes the observed effect of coffee is due to the caffeine, so presumably other caffeinated beverages would have similar impact, but this remains to be determined by future research.

In the meantime, it seems there is no reason to counsel coffee-loving MTX/SSZ-treated psoriasis patients against making routine trips to their local coffeehouses.

PHILADELPHIA — Patients with psoriasis who drink coffee frequently respond better to treatment with methotrexate and sulfasalazine, Dr. Yolanda Helfrich reported at the annual meeting of the Society for Investigative Dermatology.

That should be good news for patients who like to drink coffee, said Dr. Helfrich of the department of dermatology, University of Michigan, Ann Arbor. The impact of coffee and other caffeine-containing beverages on inflammatory conditions such as psoriasis has been the subject of controversy for some time. Many people consider caffeine to be proinflammatory and have suggested that patients with inflammatory diseases cut their consumption.

On face value, one would expect coffee to thwart the efficacy of drugs such as methotrexate (MTX) and sulfasalazine (SSZ). “Both of these drugs are anti-inflammatory, and they work by inhibiting an enzyme called 5-amidoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase, resulting in AICAR accumulation. This leads to increased adenosine which has anti-inflammatory properties,” explained Dr. Helfrich. “Caffeine acts as an adenosine receptor antagonist, so you'd expect it to inhibit MTX and SSZ.”

Indeed, a study published several years ago involving 91 patients with rheumatoid arthritis showed that regular coffee drinkers were more likely to discontinue MTX therapy due to perceived lack of efficacy. A second rheumatoid arthritis study involving 39 patients also showed inhibition of the drug's effects, but other published studies show no such effects.

But it appears that, at least biochemically, coffee has bivalent effects. While it is true that caffeine is an adenosine receptor antagonist, it also increases cyclic adenosine monophosphate, (cAMP) which has antiproliferative and immunosuppressive effects. It also simultaneously reduces the production of tumor necrosis factor-? (TNF-α, which is high in psoriasis. Presumably, both of these changes would be beneficial to patients with psoriasis. “We wondered which effect would be more important: the receptor antagonism or the TNF-α reduction and cAMP increase.”

Dr. Helfrich and her colleagues surveyed 21 patients with moderate to severe psoriasis who received MTX and SSZ. The patients were asked to rate the efficacy of the drug therapies on a 1–10 scale, with 1 representing “not effective” and 10 representing “highly effective.” Among other questions regarding their lifestyles, the patients were asked to estimate their weekly coffee consumption.

Plotting coffee consumption against treatment rating scores, the investigators found a weak but statistically significant correlation between coffee drinking and improved efficacy as perceived by the patients. Those who drank 10 or more cups of coffee each week had a mean 1-point improvement in treatment rating scores, compared with those who drank less. When the researchers looked at the data through a linear regression model that controlled for gender, duration of psoriasis, drug doses, and years of drug therapy, they found a much more robust correlation.

Dr. Helfrich acknowledged the limitations of this study—mainly the small population size and the exclusive reliance on patient self-reporting—for the drug efficacy data and for the estimates of caffeine intake. She also recognized the possibility that the perk-up patients experience from drinking coffee could be giving them an overall sense of well-being that colored their perception of the therapeutic efficacy. “Caffeine is an addictive drug and most addictive drugs increase endorphins, which makes us feel better. So this is an open question. We do need to do a study with investigator assessment of the drug efficacy,” she said.

That said, she noted that there is reason to think that the observation represents an objective phenomenon. “In psoriasis, the longer-term anti-inflammatory effects of increasing the adenosine receptors, increasing cAMP and reducing TNF outweigh the acute proinflammatory effects of caffeine.”

Dr. Helfrich said she believes the observed effect of coffee is due to the caffeine, so presumably other caffeinated beverages would have similar impact, but this remains to be determined by future research.

In the meantime, it seems there is no reason to counsel coffee-loving MTX/SSZ-treated psoriasis patients against making routine trips to their local coffeehouses.

PHILADELPHIA — Willingness-to-pay studies, widely used in managed care and health policy studies to assess patient priorities, can tell dermatologists a lot about what psoriasis patients really want from their therapies, Matthew Delfino Jr. said at the annual meeting of the Society for Investigative Dermatology.

Mr. Delfino, a medical student at Harvard Medical School, Boston, has been working with the department of dermatology at Brigham and Women's Hospital to bring the skills and methodologies he learned during his business administration training to the management of skin disease.

"Willingness-to-pay [WTP] studies elicit both stated preferences, as well as unstated preferences. Higher willingness to pay is associated with stronger desire or preference for relief or improvement in a particular aspect of life," he explained.

The concept is simple: Investigators interview patients and ask them a series of questions along the lines of "Assuming a hypothetical ideally effective therapy, how much would you be willing to pay out of pocket for complete elimination of the impact or impairment of psoriasis on this particular domain of your life?"

It is akin to asking someone how much he or she would be willing to pay for an umbrella. If it is raining, and the individual's perceived need is pressing, he or she will likely be willing to pay more than if the sun is shining. "Greater impact on quality of life correlates with greater willingness to pay," Mr. Delfino explained.

Working with dermatologists at the hospital, he designed a WTP question panel that could evaluate patients' willingness to pay for alleviation of psoriasis-related impairment in eight life domains: intimacy, sleep, physical comfort, social comfort, emotional health, ability to work or participate in volunteer efforts, ability to maintain self-care, and ability to concentrate.

They recruited 40 patients with a history of psoriasis for participation in face-to-face interviews. The subjects had a mean age of 51.5 years; 83% were white and 48% were female; 60% were college educated, and 55% had annual incomes of more than $45,000.

In addition to the WTP questions, patients were also asked to rate their overall health and their psoriasis-related health on a 1- to 10-point visual analog scale.

In general, the patients were healthy, or at least they perceived themselves to be. As a group, they had an overall health score of 7.25. On psoriasis-related issues, they had a mean score of 5.4, indicating that they rated their dermatologic health considerably lower than their total health.

In terms of WTP responses, the four most important life domains for these patients were physical comfort, social comfort, emotional health, and ability to maintain self-care. The mean amount patients would be willing to pay for total elimination of physical symptoms was $2,000, with a range from $500 (the bottom price quartile) to $5,500 (the 75th quartile). Similarly, for total emotional health, the patients would be willing to pay a mean of $2,000, with a range of $250–$5,000.

At the other end of the priority spectrum, ability to sleep and ability to concentrate seem to be little affected by psoriasis. Patients were willing to pay a mean of $625 (range $50–$5,000) for total relief of sleep problems and $875 (range $25–$3,850) for elimination of any concentration problems associated with psoriasis.

These priorities were generally consistent across gender, age, and socioeconomic parameters. In fact, the investigators were surprised that education level and income had no measurable impact on the patients' WTP responses. Mr. Delfino noted that men were slightly more likely than women to report psoriasis-associated sleep problems, but there were no gender-associated differences in WTP for relief of sleep-related issues.

In general, the patients' priorities, as indicated by their WTP responses, correlated well with their perceived psoriasis-related and total health scores.

As a methodology, WTP assessment does have its limitations. "You are, in effect, 'monetizing' health outcomes, which can be very tricky," Mr. Delfino acknowledged. Further, studies like this rely almost exclusively on patient self-evaluation, which is always somewhat questionable. That said, the WTP approach is generally accepted in health policy literature, and advocates believe it can reveal important information about patients' real-world experiences, desires, and preferences that cannot be obtained through other lines of questioning.

Mr. Delfino said that the Brigham group is continuing to explore ways to apply WTP methodology in psoriasis. The next step is to go back to the medical records of patients in the study cohort and determine if there are any correlations between disease severity, duration, body surface area involvement, or other measures of psoriasis and the patients' response to the WTP questions.

PHILADELPHIA — Willingness-to-pay studies, widely used in managed care and health policy studies to assess patient priorities, can tell dermatologists a lot about what psoriasis patients really want from their therapies, Matthew Delfino Jr. said at the annual meeting of the Society for Investigative Dermatology.

Mr. Delfino, a medical student at Harvard Medical School, Boston, has been working with the department of dermatology at Brigham and Women's Hospital to bring the skills and methodologies he learned during his business administration training to the management of skin disease.

"Willingness-to-pay [WTP] studies elicit both stated preferences, as well as unstated preferences. Higher willingness to pay is associated with stronger desire or preference for relief or improvement in a particular aspect of life," he explained.

The concept is simple: Investigators interview patients and ask them a series of questions along the lines of "Assuming a hypothetical ideally effective therapy, how much would you be willing to pay out of pocket for complete elimination of the impact or impairment of psoriasis on this particular domain of your life?"

It is akin to asking someone how much he or she would be willing to pay for an umbrella. If it is raining, and the individual's perceived need is pressing, he or she will likely be willing to pay more than if the sun is shining. "Greater impact on quality of life correlates with greater willingness to pay," Mr. Delfino explained.

Working with dermatologists at the hospital, he designed a WTP question panel that could evaluate patients' willingness to pay for alleviation of psoriasis-related impairment in eight life domains: intimacy, sleep, physical comfort, social comfort, emotional health, ability to work or participate in volunteer efforts, ability to maintain self-care, and ability to concentrate.

They recruited 40 patients with a history of psoriasis for participation in face-to-face interviews. The subjects had a mean age of 51.5 years; 83% were white and 48% were female; 60% were college educated, and 55% had annual incomes of more than $45,000.

In addition to the WTP questions, patients were also asked to rate their overall health and their psoriasis-related health on a 1- to 10-point visual analog scale.

In general, the patients were healthy, or at least they perceived themselves to be. As a group, they had an overall health score of 7.25. On psoriasis-related issues, they had a mean score of 5.4, indicating that they rated their dermatologic health considerably lower than their total health.

In terms of WTP responses, the four most important life domains for these patients were physical comfort, social comfort, emotional health, and ability to maintain self-care. The mean amount patients would be willing to pay for total elimination of physical symptoms was $2,000, with a range from $500 (the bottom price quartile) to $5,500 (the 75th quartile). Similarly, for total emotional health, the patients would be willing to pay a mean of $2,000, with a range of $250–$5,000.

At the other end of the priority spectrum, ability to sleep and ability to concentrate seem to be little affected by psoriasis. Patients were willing to pay a mean of $625 (range $50–$5,000) for total relief of sleep problems and $875 (range $25–$3,850) for elimination of any concentration problems associated with psoriasis.

These priorities were generally consistent across gender, age, and socioeconomic parameters. In fact, the investigators were surprised that education level and income had no measurable impact on the patients' WTP responses. Mr. Delfino noted that men were slightly more likely than women to report psoriasis-associated sleep problems, but there were no gender-associated differences in WTP for relief of sleep-related issues.

In general, the patients' priorities, as indicated by their WTP responses, correlated well with their perceived psoriasis-related and total health scores.

As a methodology, WTP assessment does have its limitations. "You are, in effect, 'monetizing' health outcomes, which can be very tricky," Mr. Delfino acknowledged. Further, studies like this rely almost exclusively on patient self-evaluation, which is always somewhat questionable. That said, the WTP approach is generally accepted in health policy literature, and advocates believe it can reveal important information about patients' real-world experiences, desires, and preferences that cannot be obtained through other lines of questioning.

Mr. Delfino said that the Brigham group is continuing to explore ways to apply WTP methodology in psoriasis. The next step is to go back to the medical records of patients in the study cohort and determine if there are any correlations between disease severity, duration, body surface area involvement, or other measures of psoriasis and the patients' response to the WTP questions.

PHILADELPHIA — Willingness-to-pay studies, widely used in managed care and health policy studies to assess patient priorities, can tell dermatologists a lot about what psoriasis patients really want from their therapies, Matthew Delfino Jr. said at the annual meeting of the Society for Investigative Dermatology.

Mr. Delfino, a medical student at Harvard Medical School, Boston, has been working with the department of dermatology at Brigham and Women's Hospital to bring the skills and methodologies he learned during his business administration training to the management of skin disease.

"Willingness-to-pay [WTP] studies elicit both stated preferences, as well as unstated preferences. Higher willingness to pay is associated with stronger desire or preference for relief or improvement in a particular aspect of life," he explained.

The concept is simple: Investigators interview patients and ask them a series of questions along the lines of "Assuming a hypothetical ideally effective therapy, how much would you be willing to pay out of pocket for complete elimination of the impact or impairment of psoriasis on this particular domain of your life?"

It is akin to asking someone how much he or she would be willing to pay for an umbrella. If it is raining, and the individual's perceived need is pressing, he or she will likely be willing to pay more than if the sun is shining. "Greater impact on quality of life correlates with greater willingness to pay," Mr. Delfino explained.

Working with dermatologists at the hospital, he designed a WTP question panel that could evaluate patients' willingness to pay for alleviation of psoriasis-related impairment in eight life domains: intimacy, sleep, physical comfort, social comfort, emotional health, ability to work or participate in volunteer efforts, ability to maintain self-care, and ability to concentrate.

They recruited 40 patients with a history of psoriasis for participation in face-to-face interviews. The subjects had a mean age of 51.5 years; 83% were white and 48% were female; 60% were college educated, and 55% had annual incomes of more than $45,000.

In addition to the WTP questions, patients were also asked to rate their overall health and their psoriasis-related health on a 1- to 10-point visual analog scale.

In general, the patients were healthy, or at least they perceived themselves to be. As a group, they had an overall health score of 7.25. On psoriasis-related issues, they had a mean score of 5.4, indicating that they rated their dermatologic health considerably lower than their total health.

In terms of WTP responses, the four most important life domains for these patients were physical comfort, social comfort, emotional health, and ability to maintain self-care. The mean amount patients would be willing to pay for total elimination of physical symptoms was $2,000, with a range from $500 (the bottom price quartile) to $5,500 (the 75th quartile). Similarly, for total emotional health, the patients would be willing to pay a mean of $2,000, with a range of $250–$5,000.

At the other end of the priority spectrum, ability to sleep and ability to concentrate seem to be little affected by psoriasis. Patients were willing to pay a mean of $625 (range $50–$5,000) for total relief of sleep problems and $875 (range $25–$3,850) for elimination of any concentration problems associated with psoriasis.

These priorities were generally consistent across gender, age, and socioeconomic parameters. In fact, the investigators were surprised that education level and income had no measurable impact on the patients' WTP responses. Mr. Delfino noted that men were slightly more likely than women to report psoriasis-associated sleep problems, but there were no gender-associated differences in WTP for relief of sleep-related issues.

In general, the patients' priorities, as indicated by their WTP responses, correlated well with their perceived psoriasis-related and total health scores.

As a methodology, WTP assessment does have its limitations. "You are, in effect, 'monetizing' health outcomes, which can be very tricky," Mr. Delfino acknowledged. Further, studies like this rely almost exclusively on patient self-evaluation, which is always somewhat questionable. That said, the WTP approach is generally accepted in health policy literature, and advocates believe it can reveal important information about patients' real-world experiences, desires, and preferences that cannot be obtained through other lines of questioning.

Mr. Delfino said that the Brigham group is continuing to explore ways to apply WTP methodology in psoriasis. The next step is to go back to the medical records of patients in the study cohort and determine if there are any correlations between disease severity, duration, body surface area involvement, or other measures of psoriasis and the patients' response to the WTP questions.

WASHINGTON — Genomic science is advancing rapidly on many fronts, but without solid federal policy to prevent genetic discrimination, it will be very difficult for physicians and patients to harvest the fruits of researchers' labors, said Dr. Francis S. Collins, director of the National Human Genomic Research Institute, National Institutes of Health.

“All of the original goals of the Human Genome Project have been achieved,” the nation's Gene Dean said at the World Health Care Congress, a health policy conference sponsored by the Wall Street Journal. Genomic researchers are making clinically relevant and potentially cost-saving discoveries in early disease detection, pharmacogenomics, nutrigenomics, and rational gene-based drug design.

But widespread clinical application of these advances will remain a dream without adequate antidiscrimination safeguards.

“We really need this kind of protection to forward genomic medicine. The single greatest inhibition that people have about genomic medicine is the fear that the genetic information will be used against them. We've known about this hang-up for 10 years now,” Dr. Collins said. He and other leaders in the genomics field have repeatedly pushed for federal legislation that would guarantee nondiscrimination in employment or health insurance coverage decisions. Though such a bill has repeatedly been introduced, Congress has failed to come through.

One particular bill (S. 1053) died in the last Congress; and was reintroduced in the current Congress as S. 306 and HR. 1227, Dr. Collins said. Though it is technically still alive, he expressed doubt that either branch of Congress will move on it this year.

The hang-up? Dr. Collins said that many in the business community are concerned that this type of legislation would provide further chum for already voracious antidiscrimination attorneys, leading to an avalanche of spurious genetic discrimination lawsuits that could paralyze corporate America.

“Some of us are concerned that if someone doesn't start to move this soon, nothing will happen,” Dr. Collins said.

Dr. Elias Zerhouni, director of the National Institutes of Health, agreed. In a separate address at the conference, he said he shares Dr. Collins concern. “We really need antidiscrimination legislation.” Stasis on the policy front would be a tragedy, he continued, because genomic researchers are coming up with some pretty nifty clinical stuff these days.

Among the new advances, Dr. Zerhouni and Dr. Collins cited the evolution of the Hereditary Non-Polyposis Colon Cancer (HNPCC) screening panel that allows clinicians to predict the risk of colon cancer in families that have members with this type of colon cancer. According to a cost analysis published in 2001, HNPCC screening of individuals with the cancer costs roughly $42,000 per life-year gained. Not exactly a bargain, Dr. Collins admitted.

“But remember that each patient has relatives, and each first-degree relative has a 50% risk of developing the cancer,” he added. If you look at screening of parents, siblings and children of index cases, the cost drops dramatically to $7,556 per life-year gained (Ann. Intern. Med. 2001;135: 577). “This is much more cost effective, and it should be reimbursed.”

A multigene assay for predicting risk of recurrence in women with node-negative, tamoxifen-treated breast cancer is another bright light on the clinical genomics horizon. This assay can accurately identify which women are most and least likely to have positive long-term recurrence-free responses to tamoxifen chemotherapy (N. Engl. J. Med. 2004;351:2817–26). Its main virtue is that it allows patients who are unlikely to respond to tamoxifen to avoid undergoing the often unpleasant chemotherapy regimen.

The assay “has been widely adopted by many oncologists, and it has a big patient satisfaction benefit,” Dr. Collins said. But he acknowledged that the test is marginally cost efficient.

Another example from Dr. Collins: The emergence of assays to evaluate warfarin metabolism based on genetic variations in the function of the hepatic cytochrome P-450 (CYP-450) enzyme system has tremendous everyday potential for routine clinical practice. Assessment of the gene coding for CYP 2C9 can help physicians tailor warfarin doses to prevent bleeding episodes in patients with genetic propensities for higher-than-average responsiveness to the drug.

The test costs roughly $135 per patient, and can prevent one major bleeding episode for every 44 patients on warfarin (Am. J. Man. Care. 2003;9:493–500). Prevention of a single severe hemorrhage using the genetic test would cost roughly $6,000, the approximate cost of managing a bleeding episode. So this test, by itself, is cost neutral, “but it is a major improvement in terms of patient outcomes,” said Dr. Collins, who called for a prospective trial on the subject.

According to Dr. Zerhouni, early detection of disease susceptibility years, if not decades, before symptoms emerge, and genomically guided drug therapy are the future of American medicine. “DNA sequencing costs are plummeting. This is opening up a new vista regarding our ability to understand disease.”

He said he believes genomic medicine is at a critical inflection point. “We have a lot of information. We need to exploit it to intervene, not at the most costly advanced stages of symptoms, but at early pre-symptomatic stages where we can truly prevent diseases from manifesting.”

Dr. Reed Tuckson, senior vice president for consumer health and medical care advancement at UnitedHealth Group, said there's a lot of public and physician education work that needs to be done before anyone will be able to make good on Dr. Zerhouni's vision.

WASHINGTON — Genomic science is advancing rapidly on many fronts, but without solid federal policy to prevent genetic discrimination, it will be very difficult for physicians and patients to harvest the fruits of researchers' labors, said Dr. Francis S. Collins, director of the National Human Genomic Research Institute, National Institutes of Health.

“All of the original goals of the Human Genome Project have been achieved,” the nation's Gene Dean said at the World Health Care Congress, a health policy conference sponsored by the Wall Street Journal. Genomic researchers are making clinically relevant and potentially cost-saving discoveries in early disease detection, pharmacogenomics, nutrigenomics, and rational gene-based drug design.

But widespread clinical application of these advances will remain a dream without adequate antidiscrimination safeguards.

“We really need this kind of protection to forward genomic medicine. The single greatest inhibition that people have about genomic medicine is the fear that the genetic information will be used against them. We've known about this hang-up for 10 years now,” Dr. Collins said. He and other leaders in the genomics field have repeatedly pushed for federal legislation that would guarantee nondiscrimination in employment or health insurance coverage decisions. Though such a bill has repeatedly been introduced, Congress has failed to come through.

One particular bill (S. 1053) died in the last Congress; and was reintroduced in the current Congress as S. 306 and HR. 1227, Dr. Collins said. Though it is technically still alive, he expressed doubt that either branch of Congress will move on it this year.

The hang-up? Dr. Collins said that many in the business community are concerned that this type of legislation would provide further chum for already voracious antidiscrimination attorneys, leading to an avalanche of spurious genetic discrimination lawsuits that could paralyze corporate America.

“Some of us are concerned that if someone doesn't start to move this soon, nothing will happen,” Dr. Collins said.

Dr. Elias Zerhouni, director of the National Institutes of Health, agreed. In a separate address at the conference, he said he shares Dr. Collins concern. “We really need antidiscrimination legislation.” Stasis on the policy front would be a tragedy, he continued, because genomic researchers are coming up with some pretty nifty clinical stuff these days.

Among the new advances, Dr. Zerhouni and Dr. Collins cited the evolution of the Hereditary Non-Polyposis Colon Cancer (HNPCC) screening panel that allows clinicians to predict the risk of colon cancer in families that have members with this type of colon cancer. According to a cost analysis published in 2001, HNPCC screening of individuals with the cancer costs roughly $42,000 per life-year gained. Not exactly a bargain, Dr. Collins admitted.

“But remember that each patient has relatives, and each first-degree relative has a 50% risk of developing the cancer,” he added. If you look at screening of parents, siblings and children of index cases, the cost drops dramatically to $7,556 per life-year gained (Ann. Intern. Med. 2001;135: 577). “This is much more cost effective, and it should be reimbursed.”

A multigene assay for predicting risk of recurrence in women with node-negative, tamoxifen-treated breast cancer is another bright light on the clinical genomics horizon. This assay can accurately identify which women are most and least likely to have positive long-term recurrence-free responses to tamoxifen chemotherapy (N. Engl. J. Med. 2004;351:2817–26). Its main virtue is that it allows patients who are unlikely to respond to tamoxifen to avoid undergoing the often unpleasant chemotherapy regimen.

The assay “has been widely adopted by many oncologists, and it has a big patient satisfaction benefit,” Dr. Collins said. But he acknowledged that the test is marginally cost efficient.

Another example from Dr. Collins: The emergence of assays to evaluate warfarin metabolism based on genetic variations in the function of the hepatic cytochrome P-450 (CYP-450) enzyme system has tremendous everyday potential for routine clinical practice. Assessment of the gene coding for CYP 2C9 can help physicians tailor warfarin doses to prevent bleeding episodes in patients with genetic propensities for higher-than-average responsiveness to the drug.

The test costs roughly $135 per patient, and can prevent one major bleeding episode for every 44 patients on warfarin (Am. J. Man. Care. 2003;9:493–500). Prevention of a single severe hemorrhage using the genetic test would cost roughly $6,000, the approximate cost of managing a bleeding episode. So this test, by itself, is cost neutral, “but it is a major improvement in terms of patient outcomes,” said Dr. Collins, who called for a prospective trial on the subject.

According to Dr. Zerhouni, early detection of disease susceptibility years, if not decades, before symptoms emerge, and genomically guided drug therapy are the future of American medicine. “DNA sequencing costs are plummeting. This is opening up a new vista regarding our ability to understand disease.”

He said he believes genomic medicine is at a critical inflection point. “We have a lot of information. We need to exploit it to intervene, not at the most costly advanced stages of symptoms, but at early pre-symptomatic stages where we can truly prevent diseases from manifesting.”

Dr. Reed Tuckson, senior vice president for consumer health and medical care advancement at UnitedHealth Group, said there's a lot of public and physician education work that needs to be done before anyone will be able to make good on Dr. Zerhouni's vision.

WASHINGTON — Genomic science is advancing rapidly on many fronts, but without solid federal policy to prevent genetic discrimination, it will be very difficult for physicians and patients to harvest the fruits of researchers' labors, said Dr. Francis S. Collins, director of the National Human Genomic Research Institute, National Institutes of Health.

“All of the original goals of the Human Genome Project have been achieved,” the nation's Gene Dean said at the World Health Care Congress, a health policy conference sponsored by the Wall Street Journal. Genomic researchers are making clinically relevant and potentially cost-saving discoveries in early disease detection, pharmacogenomics, nutrigenomics, and rational gene-based drug design.

But widespread clinical application of these advances will remain a dream without adequate antidiscrimination safeguards.

“We really need this kind of protection to forward genomic medicine. The single greatest inhibition that people have about genomic medicine is the fear that the genetic information will be used against them. We've known about this hang-up for 10 years now,” Dr. Collins said. He and other leaders in the genomics field have repeatedly pushed for federal legislation that would guarantee nondiscrimination in employment or health insurance coverage decisions. Though such a bill has repeatedly been introduced, Congress has failed to come through.

One particular bill (S. 1053) died in the last Congress; and was reintroduced in the current Congress as S. 306 and HR. 1227, Dr. Collins said. Though it is technically still alive, he expressed doubt that either branch of Congress will move on it this year.

The hang-up? Dr. Collins said that many in the business community are concerned that this type of legislation would provide further chum for already voracious antidiscrimination attorneys, leading to an avalanche of spurious genetic discrimination lawsuits that could paralyze corporate America.

“Some of us are concerned that if someone doesn't start to move this soon, nothing will happen,” Dr. Collins said.

Dr. Elias Zerhouni, director of the National Institutes of Health, agreed. In a separate address at the conference, he said he shares Dr. Collins concern. “We really need antidiscrimination legislation.” Stasis on the policy front would be a tragedy, he continued, because genomic researchers are coming up with some pretty nifty clinical stuff these days.

Among the new advances, Dr. Zerhouni and Dr. Collins cited the evolution of the Hereditary Non-Polyposis Colon Cancer (HNPCC) screening panel that allows clinicians to predict the risk of colon cancer in families that have members with this type of colon cancer. According to a cost analysis published in 2001, HNPCC screening of individuals with the cancer costs roughly $42,000 per life-year gained. Not exactly a bargain, Dr. Collins admitted.

“But remember that each patient has relatives, and each first-degree relative has a 50% risk of developing the cancer,” he added. If you look at screening of parents, siblings and children of index cases, the cost drops dramatically to $7,556 per life-year gained (Ann. Intern. Med. 2001;135: 577). “This is much more cost effective, and it should be reimbursed.”

A multigene assay for predicting risk of recurrence in women with node-negative, tamoxifen-treated breast cancer is another bright light on the clinical genomics horizon. This assay can accurately identify which women are most and least likely to have positive long-term recurrence-free responses to tamoxifen chemotherapy (N. Engl. J. Med. 2004;351:2817–26). Its main virtue is that it allows patients who are unlikely to respond to tamoxifen to avoid undergoing the often unpleasant chemotherapy regimen.

The assay “has been widely adopted by many oncologists, and it has a big patient satisfaction benefit,” Dr. Collins said. But he acknowledged that the test is marginally cost efficient.

Another example from Dr. Collins: The emergence of assays to evaluate warfarin metabolism based on genetic variations in the function of the hepatic cytochrome P-450 (CYP-450) enzyme system has tremendous everyday potential for routine clinical practice. Assessment of the gene coding for CYP 2C9 can help physicians tailor warfarin doses to prevent bleeding episodes in patients with genetic propensities for higher-than-average responsiveness to the drug.

The test costs roughly $135 per patient, and can prevent one major bleeding episode for every 44 patients on warfarin (Am. J. Man. Care. 2003;9:493–500). Prevention of a single severe hemorrhage using the genetic test would cost roughly $6,000, the approximate cost of managing a bleeding episode. So this test, by itself, is cost neutral, “but it is a major improvement in terms of patient outcomes,” said Dr. Collins, who called for a prospective trial on the subject.

According to Dr. Zerhouni, early detection of disease susceptibility years, if not decades, before symptoms emerge, and genomically guided drug therapy are the future of American medicine. “DNA sequencing costs are plummeting. This is opening up a new vista regarding our ability to understand disease.”

He said he believes genomic medicine is at a critical inflection point. “We have a lot of information. We need to exploit it to intervene, not at the most costly advanced stages of symptoms, but at early pre-symptomatic stages where we can truly prevent diseases from manifesting.”

Dr. Reed Tuckson, senior vice president for consumer health and medical care advancement at UnitedHealth Group, said there's a lot of public and physician education work that needs to be done before anyone will be able to make good on Dr. Zerhouni's vision.

PHILADELPHIA — There is mounting evidence that patients with psoriasis are at increased risk of cardiovascular disease, according to several large epidemiologic surveys presented at the annual meeting of the Society for Investigative Dermatology.

Over the last decade, several studies have shown that people with psoriasis often have comorbidities including depression, hypertension, and diabetes. The new studies confirm these earlier findings, and indicate clearly that psoriasis patients are at increased risk for myocardial infarction.

The big question now is whether the skin condition itself is an independent risk factor or if the increase in heart disease is because of adverse effects from psoriasis therapies or to increased likelihood of smoking, depression, or overweight, which are also more prevalent in psoriatic patients than in the general population. These questions will require further research, but in the meantime, the clinical message is clear: Physicians need to pay closer attention to the cardiovascular health of this population.

The largest study of the psoriasis-heart disease link comes from epidemiologists at Centocor Inc., the pharmaceutical company that manufactures infliximab and other immune-system modulating drugs.

The researchers analyzed incidence of cardiovascular events and presence of heart disease risk factors among psoriatic patients and healthy age-matched control subjects from two massive databases. The first (“Database A”) was a proprietary database consisting of more than 6 million active or retired employees at Fortune 500 corporations, and their covered dependents; the second (“Database B”) was a health insurance claims database comprising more than 11 million people.

By using ICD-9 codes, the researchers were able to select out all patients with psoriasis, as well as all who had atherosclerosis, diabetes, and hypertension. They used a 4:1 match between control subjects and those with psoriasis during the year 2001–2002.The findings were presented at the meeting by Dr. Y. Wu from the Centocor team.

From Database A, there were 23,897 patients with psoriasis, which were compared with 95,558 age- and gender-matched control subjects. Those with psoriasis had a 24% increased odds ratio of having atherosclerosis, a 12% increased odds ratio for hypertension, and a 17% increased odds ratio for type 2 diabetes.

From Database B, they identified 30,558 psoriasis patients and compared them with 121,469 age- and gender-matched control subjects. In this data set, the psoriatic individuals had a 34% increased odds ratio of having atherosclerosis, an 18% increased odds for hypertension, and a 22% increased likelihood of diabetes.

“These are very significant data showing increased prevalence rates for cardiovascular comorbidities and risk factors. The risk was statistically significant in both databases, and the findings are in line with earlier data. We really need to understand the underlying biological mechanisms,” Dr. Wu said. In response to a question from the audience, he acknowledged that the data had not been controlled for smoking, which given its increased prevalence among psoriatic patients, could in part explain the increased cardiovascular risk. “This is something we really need to do.”

In a separate presentation, Dr. Joel Gelfand of the department of dermatology, University of Pennsylvania, Philadelphia, reviewed the data from their analysis of psoriasis and heart disease in the General Practice Research Database (GPRD), which contains electronic medical records information from more than 9 million people in the United Kingdom, during 1987–2002. They categorized the psoriasis patients who received no systemic therapy as mild (127,139) and those who received at least one systemic drug therapy or psoralen plus ultraviolet A as severe (3,837), and compared them with up to 556,995 age- and gender-matched control subjects.

The findings in the Penn study were similar to those in the Centocor study, but in the Penn analysis, heart disease risk correlated clearly with severity of psoriasis. There were 11,194 myocardial infarctions in the control group, for an incidence of 3.58 per 1,000 person-years. Among the 127,139 with mild psoriasis, there were 2,319 myocardial infarctions, for an incidence rate of 4.04 per 1,000 person-years. In the roughly 3,400 with severe psoriasis, there were 112 MIs, or 5.13 per 1,000 person-years.

The data show that those with psoriasis were more likely to have had a prior history of MI (1.4% in the control group, 1.8% in the mild group, and 2.0% in the severe psoriasis group).

Type 2 diabetes, hyperlipidemia, and hypertension all tracked with psoriasis, and the incidence of all of these was higher in the severe than in the mild psoriasis patients.

Dr. Gelfand's group did assess smoking and body mass index, and found that while the latter was relatively comparable between controls and psoriasis patients (mean BMI of 25.27 in the controls, 25.77 in the patients with mild psoriasis, and 26.55 in the patients with severe psoriasis), smoking was clearly more common among the psoriasis patients (21% of the controls were smokers, versus 28% of the mild psoriasis patients, and 30% of the severe psoriasis patients).

Still, according to Dr. Gelfand, psoriasis does seem to be an independent risk factor for heart disease. Using a Cox proportional hazard model, he found that mild psoriasis itself carries a hazard ratio of 1.54 and severe psoriasis confers an alarming hazard ratio of 7.04. By way of comparison, hyperlipidemia carries a hazard ratio of 3.08 for the patients with mild psoriasis, and 3.18 for the patients with severe psoriasis. Hypertension carries a hazard ratio of 1.11 for patients with mild psoriasis and 1.12 for those with severe disease.

Dr. Gelfand underscored a noteworthy inverse age trend in the associated risk of MI. Patients with severe psoriasis in their 20s had a hazard ratio of 4 for myocardial infarction. The risk showed a steady downward trend with age; for those in their 60s, severe psoriasis had a hazard ratio of around 1.5. Mild psoriasis showed the same hazard ratio curve, though the amplitude was lower across the age spectrum.

In a separate poster presentation, Dr. Andrea Neimann, a member of Dr. Gelfand's research team, calculated the odds ratios for various cardiovascular risk factors in the psoriatic population in the GPRD.

Patients with mild psoriasis were 27% more likely than were controls to have diabetes, 16% more likely to have hypertension, 28% more likely to have dyslipidemia, 40% more likely to be smokers, and 29% more likely to have a BMI greater than 30. Those with severe psoriasis were 86% more likely than controls to have diabetes, 25% more likely to have hypertension, 31% more likely to be dyslipidemic, 31% more likely to be smokers, and 84% more likely to be obese.

“Diabetes, smoking, and BMI are independently associated with mild and severe psoriasis, and the association between diabetes and BMI is stronger in patients with severe psoriasis than with mild psoriasis,” Dr. Neimann reported.

Studies are needed to determine the extent to which the increased heart disease burden is attributable to the psoriasis disease process itself, or whether it can be fully explained by secondary risk factors such as smoking, overeating, depression, and other psychosocial factors.

According to Dr. Gelfand, there's certainly a plausible reason to believe the skin disease itself is playing a major role. “Psoriasis is a Th-1 mediated inflammatory disease, and increasing evidence has linked chronic Th-1 inflammation with atherosclerosis and MI.”

PHILADELPHIA — There is mounting evidence that patients with psoriasis are at increased risk of cardiovascular disease, according to several large epidemiologic surveys presented at the annual meeting of the Society for Investigative Dermatology.

Over the last decade, several studies have shown that people with psoriasis often have comorbidities including depression, hypertension, and diabetes. The new studies confirm these earlier findings, and indicate clearly that psoriasis patients are at increased risk for myocardial infarction.

The big question now is whether the skin condition itself is an independent risk factor or if the increase in heart disease is because of adverse effects from psoriasis therapies or to increased likelihood of smoking, depression, or overweight, which are also more prevalent in psoriatic patients than in the general population. These questions will require further research, but in the meantime, the clinical message is clear: Physicians need to pay closer attention to the cardiovascular health of this population.

The largest study of the psoriasis-heart disease link comes from epidemiologists at Centocor Inc., the pharmaceutical company that manufactures infliximab and other immune-system modulating drugs.

The researchers analyzed incidence of cardiovascular events and presence of heart disease risk factors among psoriatic patients and healthy age-matched control subjects from two massive databases. The first (“Database A”) was a proprietary database consisting of more than 6 million active or retired employees at Fortune 500 corporations, and their covered dependents; the second (“Database B”) was a health insurance claims database comprising more than 11 million people.

By using ICD-9 codes, the researchers were able to select out all patients with psoriasis, as well as all who had atherosclerosis, diabetes, and hypertension. They used a 4:1 match between control subjects and those with psoriasis during the year 2001–2002.The findings were presented at the meeting by Dr. Y. Wu from the Centocor team.

From Database A, there were 23,897 patients with psoriasis, which were compared with 95,558 age- and gender-matched control subjects. Those with psoriasis had a 24% increased odds ratio of having atherosclerosis, a 12% increased odds ratio for hypertension, and a 17% increased odds ratio for type 2 diabetes.

From Database B, they identified 30,558 psoriasis patients and compared them with 121,469 age- and gender-matched control subjects. In this data set, the psoriatic individuals had a 34% increased odds ratio of having atherosclerosis, an 18% increased odds for hypertension, and a 22% increased likelihood of diabetes.

“These are very significant data showing increased prevalence rates for cardiovascular comorbidities and risk factors. The risk was statistically significant in both databases, and the findings are in line with earlier data. We really need to understand the underlying biological mechanisms,” Dr. Wu said. In response to a question from the audience, he acknowledged that the data had not been controlled for smoking, which given its increased prevalence among psoriatic patients, could in part explain the increased cardiovascular risk. “This is something we really need to do.”

In a separate presentation, Dr. Joel Gelfand of the department of dermatology, University of Pennsylvania, Philadelphia, reviewed the data from their analysis of psoriasis and heart disease in the General Practice Research Database (GPRD), which contains electronic medical records information from more than 9 million people in the United Kingdom, during 1987–2002. They categorized the psoriasis patients who received no systemic therapy as mild (127,139) and those who received at least one systemic drug therapy or psoralen plus ultraviolet A as severe (3,837), and compared them with up to 556,995 age- and gender-matched control subjects.

The findings in the Penn study were similar to those in the Centocor study, but in the Penn analysis, heart disease risk correlated clearly with severity of psoriasis. There were 11,194 myocardial infarctions in the control group, for an incidence of 3.58 per 1,000 person-years. Among the 127,139 with mild psoriasis, there were 2,319 myocardial infarctions, for an incidence rate of 4.04 per 1,000 person-years. In the roughly 3,400 with severe psoriasis, there were 112 MIs, or 5.13 per 1,000 person-years.

The data show that those with psoriasis were more likely to have had a prior history of MI (1.4% in the control group, 1.8% in the mild group, and 2.0% in the severe psoriasis group).

Type 2 diabetes, hyperlipidemia, and hypertension all tracked with psoriasis, and the incidence of all of these was higher in the severe than in the mild psoriasis patients.

Dr. Gelfand's group did assess smoking and body mass index, and found that while the latter was relatively comparable between controls and psoriasis patients (mean BMI of 25.27 in the controls, 25.77 in the patients with mild psoriasis, and 26.55 in the patients with severe psoriasis), smoking was clearly more common among the psoriasis patients (21% of the controls were smokers, versus 28% of the mild psoriasis patients, and 30% of the severe psoriasis patients).

Still, according to Dr. Gelfand, psoriasis does seem to be an independent risk factor for heart disease. Using a Cox proportional hazard model, he found that mild psoriasis itself carries a hazard ratio of 1.54 and severe psoriasis confers an alarming hazard ratio of 7.04. By way of comparison, hyperlipidemia carries a hazard ratio of 3.08 for the patients with mild psoriasis, and 3.18 for the patients with severe psoriasis. Hypertension carries a hazard ratio of 1.11 for patients with mild psoriasis and 1.12 for those with severe disease.

Dr. Gelfand underscored a noteworthy inverse age trend in the associated risk of MI. Patients with severe psoriasis in their 20s had a hazard ratio of 4 for myocardial infarction. The risk showed a steady downward trend with age; for those in their 60s, severe psoriasis had a hazard ratio of around 1.5. Mild psoriasis showed the same hazard ratio curve, though the amplitude was lower across the age spectrum.

In a separate poster presentation, Dr. Andrea Neimann, a member of Dr. Gelfand's research team, calculated the odds ratios for various cardiovascular risk factors in the psoriatic population in the GPRD.

Patients with mild psoriasis were 27% more likely than were controls to have diabetes, 16% more likely to have hypertension, 28% more likely to have dyslipidemia, 40% more likely to be smokers, and 29% more likely to have a BMI greater than 30. Those with severe psoriasis were 86% more likely than controls to have diabetes, 25% more likely to have hypertension, 31% more likely to be dyslipidemic, 31% more likely to be smokers, and 84% more likely to be obese.

“Diabetes, smoking, and BMI are independently associated with mild and severe psoriasis, and the association between diabetes and BMI is stronger in patients with severe psoriasis than with mild psoriasis,” Dr. Neimann reported.

Studies are needed to determine the extent to which the increased heart disease burden is attributable to the psoriasis disease process itself, or whether it can be fully explained by secondary risk factors such as smoking, overeating, depression, and other psychosocial factors.

According to Dr. Gelfand, there's certainly a plausible reason to believe the skin disease itself is playing a major role. “Psoriasis is a Th-1 mediated inflammatory disease, and increasing evidence has linked chronic Th-1 inflammation with atherosclerosis and MI.”

PHILADELPHIA — There is mounting evidence that patients with psoriasis are at increased risk of cardiovascular disease, according to several large epidemiologic surveys presented at the annual meeting of the Society for Investigative Dermatology.

Over the last decade, several studies have shown that people with psoriasis often have comorbidities including depression, hypertension, and diabetes. The new studies confirm these earlier findings, and indicate clearly that psoriasis patients are at increased risk for myocardial infarction.

The big question now is whether the skin condition itself is an independent risk factor or if the increase in heart disease is because of adverse effects from psoriasis therapies or to increased likelihood of smoking, depression, or overweight, which are also more prevalent in psoriatic patients than in the general population. These questions will require further research, but in the meantime, the clinical message is clear: Physicians need to pay closer attention to the cardiovascular health of this population.

The largest study of the psoriasis-heart disease link comes from epidemiologists at Centocor Inc., the pharmaceutical company that manufactures infliximab and other immune-system modulating drugs.

The researchers analyzed incidence of cardiovascular events and presence of heart disease risk factors among psoriatic patients and healthy age-matched control subjects from two massive databases. The first (“Database A”) was a proprietary database consisting of more than 6 million active or retired employees at Fortune 500 corporations, and their covered dependents; the second (“Database B”) was a health insurance claims database comprising more than 11 million people.

By using ICD-9 codes, the researchers were able to select out all patients with psoriasis, as well as all who had atherosclerosis, diabetes, and hypertension. They used a 4:1 match between control subjects and those with psoriasis during the year 2001–2002.The findings were presented at the meeting by Dr. Y. Wu from the Centocor team.

From Database A, there were 23,897 patients with psoriasis, which were compared with 95,558 age- and gender-matched control subjects. Those with psoriasis had a 24% increased odds ratio of having atherosclerosis, a 12% increased odds ratio for hypertension, and a 17% increased odds ratio for type 2 diabetes.

From Database B, they identified 30,558 psoriasis patients and compared them with 121,469 age- and gender-matched control subjects. In this data set, the psoriatic individuals had a 34% increased odds ratio of having atherosclerosis, an 18% increased odds for hypertension, and a 22% increased likelihood of diabetes.

“These are very significant data showing increased prevalence rates for cardiovascular comorbidities and risk factors. The risk was statistically significant in both databases, and the findings are in line with earlier data. We really need to understand the underlying biological mechanisms,” Dr. Wu said. In response to a question from the audience, he acknowledged that the data had not been controlled for smoking, which given its increased prevalence among psoriatic patients, could in part explain the increased cardiovascular risk. “This is something we really need to do.”

In a separate presentation, Dr. Joel Gelfand of the department of dermatology, University of Pennsylvania, Philadelphia, reviewed the data from their analysis of psoriasis and heart disease in the General Practice Research Database (GPRD), which contains electronic medical records information from more than 9 million people in the United Kingdom, during 1987–2002. They categorized the psoriasis patients who received no systemic therapy as mild (127,139) and those who received at least one systemic drug therapy or psoralen plus ultraviolet A as severe (3,837), and compared them with up to 556,995 age- and gender-matched control subjects.

The findings in the Penn study were similar to those in the Centocor study, but in the Penn analysis, heart disease risk correlated clearly with severity of psoriasis. There were 11,194 myocardial infarctions in the control group, for an incidence of 3.58 per 1,000 person-years. Among the 127,139 with mild psoriasis, there were 2,319 myocardial infarctions, for an incidence rate of 4.04 per 1,000 person-years. In the roughly 3,400 with severe psoriasis, there were 112 MIs, or 5.13 per 1,000 person-years.

The data show that those with psoriasis were more likely to have had a prior history of MI (1.4% in the control group, 1.8% in the mild group, and 2.0% in the severe psoriasis group).

Type 2 diabetes, hyperlipidemia, and hypertension all tracked with psoriasis, and the incidence of all of these was higher in the severe than in the mild psoriasis patients.

Dr. Gelfand's group did assess smoking and body mass index, and found that while the latter was relatively comparable between controls and psoriasis patients (mean BMI of 25.27 in the controls, 25.77 in the patients with mild psoriasis, and 26.55 in the patients with severe psoriasis), smoking was clearly more common among the psoriasis patients (21% of the controls were smokers, versus 28% of the mild psoriasis patients, and 30% of the severe psoriasis patients).

Still, according to Dr. Gelfand, psoriasis does seem to be an independent risk factor for heart disease. Using a Cox proportional hazard model, he found that mild psoriasis itself carries a hazard ratio of 1.54 and severe psoriasis confers an alarming hazard ratio of 7.04. By way of comparison, hyperlipidemia carries a hazard ratio of 3.08 for the patients with mild psoriasis, and 3.18 for the patients with severe psoriasis. Hypertension carries a hazard ratio of 1.11 for patients with mild psoriasis and 1.12 for those with severe disease.

Dr. Gelfand underscored a noteworthy inverse age trend in the associated risk of MI. Patients with severe psoriasis in their 20s had a hazard ratio of 4 for myocardial infarction. The risk showed a steady downward trend with age; for those in their 60s, severe psoriasis had a hazard ratio of around 1.5. Mild psoriasis showed the same hazard ratio curve, though the amplitude was lower across the age spectrum.

In a separate poster presentation, Dr. Andrea Neimann, a member of Dr. Gelfand's research team, calculated the odds ratios for various cardiovascular risk factors in the psoriatic population in the GPRD.

Patients with mild psoriasis were 27% more likely than were controls to have diabetes, 16% more likely to have hypertension, 28% more likely to have dyslipidemia, 40% more likely to be smokers, and 29% more likely to have a BMI greater than 30. Those with severe psoriasis were 86% more likely than controls to have diabetes, 25% more likely to have hypertension, 31% more likely to be dyslipidemic, 31% more likely to be smokers, and 84% more likely to be obese.

“Diabetes, smoking, and BMI are independently associated with mild and severe psoriasis, and the association between diabetes and BMI is stronger in patients with severe psoriasis than with mild psoriasis,” Dr. Neimann reported.

Studies are needed to determine the extent to which the increased heart disease burden is attributable to the psoriasis disease process itself, or whether it can be fully explained by secondary risk factors such as smoking, overeating, depression, and other psychosocial factors.

According to Dr. Gelfand, there's certainly a plausible reason to believe the skin disease itself is playing a major role. “Psoriasis is a Th-1 mediated inflammatory disease, and increasing evidence has linked chronic Th-1 inflammation with atherosclerosis and MI.”

WASHINGTON — Genomic science is advancing rapidly on many fronts, but without solid federal policy to prevent genetic discrimination, it will be very difficult for physicians and patients to harvest the fruits of researchers' labors, said Dr. Francis S. Collins, director of the National Human Genomic Research Institute, National Institutes of Health.

“All of the original goals of the Human Genome Project have been achieved,” the nation's gene dean said at the World Health Care Congress, a health policy conference sponsored by the Wall Street Journal. Genomic researchers are making significant, clinically relevant, and potentially cost-saving discoveries in early disease detection, pharmacogenomics, nutrigenomics, and rational gene-based drug design.

But widespread clinical application of these advances will remain a dream without adequate antidiscrimination safeguards.

“We really need this kind of protection to forward genomic medicine. The single greatest inhibition that people have about genomic medicine is the fear that the genetic information will be used against them. We've known about this hang-up for 10 years now,” Dr. Collins said. He and other leaders in the genomics field have repeatedly pushed for federal legislation that would guarantee nondiscrimination in employment or health insurance coverage decisions. Though such a bill has repeatedly been introduced, Congress has failed to come through.

One particular bill (S. 1053) died in the last Congress and was reintroduced in the current Congress as S. 306 and HR. 1227, Dr. Collins said. Though it is technically still alive, he expressed doubt that either branch of Congress will move on it this year.

The hang-up? Dr. Collins said that many in the business community are concerned that this type of legislation would provide further chum for already voracious antidiscrimination attorneys, leading to an avalanche of spurious genetic discrimination lawsuits that could paralyze corporate America.

“Some of us are concerned that if someone doesn't start to move this soon, nothing will happen,” Dr. Collins said.

Dr. Elias Zerhouni, director of the National Institutes of Health, agreed. In a separate address at the conference, he said he shares Dr. Collins' concern. “We really need antidiscrimination legislation.” Stasis on the policy front would be a tragedy, he continued, because genomic researchers are “coming up with some pretty nifty clinical stuff these days.”

Among the new advances Dr. Zerhouni and Dr. Collins cited is the evolution of the Hereditary Non-Polyposis Colon Cancer (HNPCC) screening panel that allows clinicians to predict the risk of colon cancer in families that have members with this type of colon cancer. According to a cost-analysis published in 2001, HNPCC screening of individuals with the cancer costs roughly $42,000 per life-year gained. Not exactly a bargain, Dr. Collins admitted.

“But remember that each patient has relatives, and each first-degree relative has a 50% risk of developing the cancer,” he added. If you look at screening of parents, siblings, and children of index cases, the cost drops dramatically to $7,556 per life-year gained (Ann. Intern. Med. 2001;135: 577). “This is much more cost effective, and it should be reimbursed.”

A multigene assay for predicting risk of recurrence in women with node-negative, tamoxifen-treated breast cancer is another bright light on the clinical genomics horizon. This assay can accurately identify which women are most and least likely to have positive long-term recurrence-free responses to tamoxifen chemotherapy (N. Engl. J. Med. 2004;351:2817–26). Its main virtue is that it allows patients who are unlikely to respond to tamoxifen to avoid undergoing the often unpleasant chemotherapy regimen.

The assay “has been widely adopted by many oncologists, and it has a big patient satisfaction benefit,” Dr. Collins said. But he acknowledged that the test is marginally cost efficient.

Another example from Dr. Collins: The emergence of assays to evaluate warfarin metabolism based on genetic variations in the function of the hepatic cytochrome P-450 (CYP-450) enzyme system has tremendous everyday potential for routine clinical practice. Assessment of the gene coding for CYP 2C9 can help physicians tailor warfarin doses to prevent bleeding episodes in patients with genetic propensities for higher-than-average responsiveness to the drug.

The test costs roughly $135 per patient and can prevent one major bleeding episode for every 44 patients on warfarin (Am. J. Man. Care. 2003;9:493–500). Prevention of a single severe hemorrhage using the genetic test would cost roughly $6,000, the approximate cost of managing a bleeding episode. So this test, by itself, is cost neutral, “but it is a major improvement in terms of patient outcomes,” said Dr. Collins, who called for a prospective trial on the subject.

According to Dr. Zerhouni, early detection of disease susceptibility years, if not decades, before symptoms emerge and genomically guided drug therapy are the future of American medicine. “DNA sequencing costs are plummeting. This is opening up a new vista regarding our ability to understand disease.”

He said he believes genomic medicine is at a critical inflection point. “We have a lot of information. We need to exploit it to intervene, not at the most costly advanced stages of symptoms, but at early pre-symptomatic stages where we can truly prevent diseases from manifesting.”

Dr. Reed Tuckson, senior vice president for consumer health and medical care advancement at UnitedHealth Group, said there's a lot of public and physician education work that needs to be done before anyone will be able to make good on Dr. Zerhouni's vision.

“Physicians do not have time for abstract theoretical discourses on the genomics revolution. They want practical answers on how it applies to patient care and how it pertains to their daily practices. The learning systems need to meet these needs,” Dr. Tuckson said. He added that by and large, physicians and the health care system are not prepared to deal with the challenges of genomics.

“What if a doctor detects a breast cancer susceptibility gene in a patient? Does he then try to track down the patient's daughters or her sisters? This brings up some very real patient-doctor communications issues.”

The public is even further behind in terms of understanding the implications and value of genomic medicine. Dr. Tuckson called for intensive public education efforts, pointing out that the science curricula in many school systems are being decimated, leaving young people at a significant disadvantage in their ability to understand genetics. He also said that integration of genomic developments into routine practice requires many more qualified genetics counselors than are now available.

Then there's the matter of reimbursement. Dr. Tuckson noted that health plans have been slow to cover genetic testing on a wider basis because administrators have yet to be convinced that the tests, and the courses of action after testing, are ultimately cost effective.

“We need to make sure that the tests work, and then get them covered. But we really need predictive tests, not just diagnostic tests. We need a robust database to answer the question of whether this adds value, because we really need supplantive technology, not just additive technology,” Dr. Tuckson said.

The future of genomic medicine hinges on further research and development, and that requires funding. “You need to fight like hell to increase the budgets for the National Institutes of Health, the Agency for Healthcare Research and Quality, the Centers for Disease Control, the FDA, and other agencies. If we don't get the research, we can't make the choices,” Dr. Tuckson added.

WASHINGTON — Genomic science is advancing rapidly on many fronts, but without solid federal policy to prevent genetic discrimination, it will be very difficult for physicians and patients to harvest the fruits of researchers' labors, said Dr. Francis S. Collins, director of the National Human Genomic Research Institute, National Institutes of Health.

“All of the original goals of the Human Genome Project have been achieved,” the nation's gene dean said at the World Health Care Congress, a health policy conference sponsored by the Wall Street Journal. Genomic researchers are making significant, clinically relevant, and potentially cost-saving discoveries in early disease detection, pharmacogenomics, nutrigenomics, and rational gene-based drug design.

But widespread clinical application of these advances will remain a dream without adequate antidiscrimination safeguards.

“We really need this kind of protection to forward genomic medicine. The single greatest inhibition that people have about genomic medicine is the fear that the genetic information will be used against them. We've known about this hang-up for 10 years now,” Dr. Collins said. He and other leaders in the genomics field have repeatedly pushed for federal legislation that would guarantee nondiscrimination in employment or health insurance coverage decisions. Though such a bill has repeatedly been introduced, Congress has failed to come through.

One particular bill (S. 1053) died in the last Congress and was reintroduced in the current Congress as S. 306 and HR. 1227, Dr. Collins said. Though it is technically still alive, he expressed doubt that either branch of Congress will move on it this year.

The hang-up? Dr. Collins said that many in the business community are concerned that this type of legislation would provide further chum for already voracious antidiscrimination attorneys, leading to an avalanche of spurious genetic discrimination lawsuits that could paralyze corporate America.

“Some of us are concerned that if someone doesn't start to move this soon, nothing will happen,” Dr. Collins said.

Dr. Elias Zerhouni, director of the National Institutes of Health, agreed. In a separate address at the conference, he said he shares Dr. Collins' concern. “We really need antidiscrimination legislation.” Stasis on the policy front would be a tragedy, he continued, because genomic researchers are “coming up with some pretty nifty clinical stuff these days.”

Among the new advances Dr. Zerhouni and Dr. Collins cited is the evolution of the Hereditary Non-Polyposis Colon Cancer (HNPCC) screening panel that allows clinicians to predict the risk of colon cancer in families that have members with this type of colon cancer. According to a cost-analysis published in 2001, HNPCC screening of individuals with the cancer costs roughly $42,000 per life-year gained. Not exactly a bargain, Dr. Collins admitted.

“But remember that each patient has relatives, and each first-degree relative has a 50% risk of developing the cancer,” he added. If you look at screening of parents, siblings, and children of index cases, the cost drops dramatically to $7,556 per life-year gained (Ann. Intern. Med. 2001;135: 577). “This is much more cost effective, and it should be reimbursed.”

A multigene assay for predicting risk of recurrence in women with node-negative, tamoxifen-treated breast cancer is another bright light on the clinical genomics horizon. This assay can accurately identify which women are most and least likely to have positive long-term recurrence-free responses to tamoxifen chemotherapy (N. Engl. J. Med. 2004;351:2817–26). Its main virtue is that it allows patients who are unlikely to respond to tamoxifen to avoid undergoing the often unpleasant chemotherapy regimen.

The assay “has been widely adopted by many oncologists, and it has a big patient satisfaction benefit,” Dr. Collins said. But he acknowledged that the test is marginally cost efficient.

Another example from Dr. Collins: The emergence of assays to evaluate warfarin metabolism based on genetic variations in the function of the hepatic cytochrome P-450 (CYP-450) enzyme system has tremendous everyday potential for routine clinical practice. Assessment of the gene coding for CYP 2C9 can help physicians tailor warfarin doses to prevent bleeding episodes in patients with genetic propensities for higher-than-average responsiveness to the drug.

The test costs roughly $135 per patient and can prevent one major bleeding episode for every 44 patients on warfarin (Am. J. Man. Care. 2003;9:493–500). Prevention of a single severe hemorrhage using the genetic test would cost roughly $6,000, the approximate cost of managing a bleeding episode. So this test, by itself, is cost neutral, “but it is a major improvement in terms of patient outcomes,” said Dr. Collins, who called for a prospective trial on the subject.

According to Dr. Zerhouni, early detection of disease susceptibility years, if not decades, before symptoms emerge and genomically guided drug therapy are the future of American medicine. “DNA sequencing costs are plummeting. This is opening up a new vista regarding our ability to understand disease.”

He said he believes genomic medicine is at a critical inflection point. “We have a lot of information. We need to exploit it to intervene, not at the most costly advanced stages of symptoms, but at early pre-symptomatic stages where we can truly prevent diseases from manifesting.”

Dr. Reed Tuckson, senior vice president for consumer health and medical care advancement at UnitedHealth Group, said there's a lot of public and physician education work that needs to be done before anyone will be able to make good on Dr. Zerhouni's vision.

“Physicians do not have time for abstract theoretical discourses on the genomics revolution. They want practical answers on how it applies to patient care and how it pertains to their daily practices. The learning systems need to meet these needs,” Dr. Tuckson said. He added that by and large, physicians and the health care system are not prepared to deal with the challenges of genomics.

“What if a doctor detects a breast cancer susceptibility gene in a patient? Does he then try to track down the patient's daughters or her sisters? This brings up some very real patient-doctor communications issues.”

The public is even further behind in terms of understanding the implications and value of genomic medicine. Dr. Tuckson called for intensive public education efforts, pointing out that the science curricula in many school systems are being decimated, leaving young people at a significant disadvantage in their ability to understand genetics. He also said that integration of genomic developments into routine practice requires many more qualified genetics counselors than are now available.

Then there's the matter of reimbursement. Dr. Tuckson noted that health plans have been slow to cover genetic testing on a wider basis because administrators have yet to be convinced that the tests, and the courses of action after testing, are ultimately cost effective.

“We need to make sure that the tests work, and then get them covered. But we really need predictive tests, not just diagnostic tests. We need a robust database to answer the question of whether this adds value, because we really need supplantive technology, not just additive technology,” Dr. Tuckson said.

The future of genomic medicine hinges on further research and development, and that requires funding. “You need to fight like hell to increase the budgets for the National Institutes of Health, the Agency for Healthcare Research and Quality, the Centers for Disease Control, the FDA, and other agencies. If we don't get the research, we can't make the choices,” Dr. Tuckson added.

WASHINGTON — Genomic science is advancing rapidly on many fronts, but without solid federal policy to prevent genetic discrimination, it will be very difficult for physicians and patients to harvest the fruits of researchers' labors, said Dr. Francis S. Collins, director of the National Human Genomic Research Institute, National Institutes of Health.

“All of the original goals of the Human Genome Project have been achieved,” the nation's gene dean said at the World Health Care Congress, a health policy conference sponsored by the Wall Street Journal. Genomic researchers are making significant, clinically relevant, and potentially cost-saving discoveries in early disease detection, pharmacogenomics, nutrigenomics, and rational gene-based drug design.

But widespread clinical application of these advances will remain a dream without adequate antidiscrimination safeguards.

“We really need this kind of protection to forward genomic medicine. The single greatest inhibition that people have about genomic medicine is the fear that the genetic information will be used against them. We've known about this hang-up for 10 years now,” Dr. Collins said. He and other leaders in the genomics field have repeatedly pushed for federal legislation that would guarantee nondiscrimination in employment or health insurance coverage decisions. Though such a bill has repeatedly been introduced, Congress has failed to come through.

One particular bill (S. 1053) died in the last Congress and was reintroduced in the current Congress as S. 306 and HR. 1227, Dr. Collins said. Though it is technically still alive, he expressed doubt that either branch of Congress will move on it this year.

The hang-up? Dr. Collins said that many in the business community are concerned that this type of legislation would provide further chum for already voracious antidiscrimination attorneys, leading to an avalanche of spurious genetic discrimination lawsuits that could paralyze corporate America.

“Some of us are concerned that if someone doesn't start to move this soon, nothing will happen,” Dr. Collins said.

Dr. Elias Zerhouni, director of the National Institutes of Health, agreed. In a separate address at the conference, he said he shares Dr. Collins' concern. “We really need antidiscrimination legislation.” Stasis on the policy front would be a tragedy, he continued, because genomic researchers are “coming up with some pretty nifty clinical stuff these days.”

Among the new advances Dr. Zerhouni and Dr. Collins cited is the evolution of the Hereditary Non-Polyposis Colon Cancer (HNPCC) screening panel that allows clinicians to predict the risk of colon cancer in families that have members with this type of colon cancer. According to a cost-analysis published in 2001, HNPCC screening of individuals with the cancer costs roughly $42,000 per life-year gained. Not exactly a bargain, Dr. Collins admitted.

“But remember that each patient has relatives, and each first-degree relative has a 50% risk of developing the cancer,” he added. If you look at screening of parents, siblings, and children of index cases, the cost drops dramatically to $7,556 per life-year gained (Ann. Intern. Med. 2001;135: 577). “This is much more cost effective, and it should be reimbursed.”

A multigene assay for predicting risk of recurrence in women with node-negative, tamoxifen-treated breast cancer is another bright light on the clinical genomics horizon. This assay can accurately identify which women are most and least likely to have positive long-term recurrence-free responses to tamoxifen chemotherapy (N. Engl. J. Med. 2004;351:2817–26). Its main virtue is that it allows patients who are unlikely to respond to tamoxifen to avoid undergoing the often unpleasant chemotherapy regimen.

The assay “has been widely adopted by many oncologists, and it has a big patient satisfaction benefit,” Dr. Collins said. But he acknowledged that the test is marginally cost efficient.

Another example from Dr. Collins: The emergence of assays to evaluate warfarin metabolism based on genetic variations in the function of the hepatic cytochrome P-450 (CYP-450) enzyme system has tremendous everyday potential for routine clinical practice. Assessment of the gene coding for CYP 2C9 can help physicians tailor warfarin doses to prevent bleeding episodes in patients with genetic propensities for higher-than-average responsiveness to the drug.

The test costs roughly $135 per patient and can prevent one major bleeding episode for every 44 patients on warfarin (Am. J. Man. Care. 2003;9:493–500). Prevention of a single severe hemorrhage using the genetic test would cost roughly $6,000, the approximate cost of managing a bleeding episode. So this test, by itself, is cost neutral, “but it is a major improvement in terms of patient outcomes,” said Dr. Collins, who called for a prospective trial on the subject.

According to Dr. Zerhouni, early detection of disease susceptibility years, if not decades, before symptoms emerge and genomically guided drug therapy are the future of American medicine. “DNA sequencing costs are plummeting. This is opening up a new vista regarding our ability to understand disease.”

He said he believes genomic medicine is at a critical inflection point. “We have a lot of information. We need to exploit it to intervene, not at the most costly advanced stages of symptoms, but at early pre-symptomatic stages where we can truly prevent diseases from manifesting.”

Dr. Reed Tuckson, senior vice president for consumer health and medical care advancement at UnitedHealth Group, said there's a lot of public and physician education work that needs to be done before anyone will be able to make good on Dr. Zerhouni's vision.

“Physicians do not have time for abstract theoretical discourses on the genomics revolution. They want practical answers on how it applies to patient care and how it pertains to their daily practices. The learning systems need to meet these needs,” Dr. Tuckson said. He added that by and large, physicians and the health care system are not prepared to deal with the challenges of genomics.

“What if a doctor detects a breast cancer susceptibility gene in a patient? Does he then try to track down the patient's daughters or her sisters? This brings up some very real patient-doctor communications issues.”

The public is even further behind in terms of understanding the implications and value of genomic medicine. Dr. Tuckson called for intensive public education efforts, pointing out that the science curricula in many school systems are being decimated, leaving young people at a significant disadvantage in their ability to understand genetics. He also said that integration of genomic developments into routine practice requires many more qualified genetics counselors than are now available.

Then there's the matter of reimbursement. Dr. Tuckson noted that health plans have been slow to cover genetic testing on a wider basis because administrators have yet to be convinced that the tests, and the courses of action after testing, are ultimately cost effective.

“We need to make sure that the tests work, and then get them covered. But we really need predictive tests, not just diagnostic tests. We need a robust database to answer the question of whether this adds value, because we really need supplantive technology, not just additive technology,” Dr. Tuckson said.

The future of genomic medicine hinges on further research and development, and that requires funding. “You need to fight like hell to increase the budgets for the National Institutes of Health, the Agency for Healthcare Research and Quality, the Centers for Disease Control, the FDA, and other agencies. If we don't get the research, we can't make the choices,” Dr. Tuckson added.

OLD GREENWICH, CONN. — A small cohort of young people who were born infected with HIV is alive and well, and struggling to come to grips with an adulthood no one ever thought they'd live to reach.

“We first saw some of these kids when they were 4 or 5 years old, and it is so heartening to see them now as young adults. We never expected them to live this long,” said Dr. Katlyne Lubin of the Albert Einstein College of Medicine's Rose F. Kennedy Center for Excellence in Developmental Disabilities, Bronx, N.Y. Since the early 1990s, the Kennedy Center has had a special program to help young children born with HIV, many of whom have significant HIV-related neurologic and developmental problems.

At a meeting of the Eastern Society for Pediatric Research, Dr. Lubin reported preliminary qualitative data gathered from the first-ever U.S. follow-up study of young adults born HIV positive. Her findings provide a window into the inspiring yet heartbreaking world of a unique generation.

“There was nobody like these kids before they were born, and because here in the United States we've been so successful in preventing maternal-fetal HIV transmission, there are hardly any others coming up behind them.” Many of the survivors of the original Albert Einstein cohort are doing surprisingly well given the daunting difficulties posed by a chronic and life-threatening disease and cognitive impairment, all against a backdrop of inner city poverty.

Today, these young people face entirely new challenges as they enter an adulthood for which neither they nor the health care system are prepared.

Dr. Lubin's study is a follow-up to work originally begun by P. Papola, M. Alvarez, and H. J. Cohen at Einstein in 1994. The team assessed the neurocognitive status of 90 children, ranging in age from 5 to 14, who were born infected with HIV. All were residents of the Bronx, and nearly all were from poor African American or Hispanic/Caribbean communities (Pediatrics 1994;94:914–8).

The original study showed that 44% of these young people were below average in intelligence for their ages, and 56% were at borderline intelligence. Half had significant language impairments, and 74% required special education services.

As the youths have aged, nearly all of them have ceased coming to the Kennedy center, and have been essentially lost to follow-up.

“We began to wonder what had happened to all of these kids, so about 2 years ago we decided to try and do a follow-up study, and track down as many of them as we could. If you know anything about doing research in inner-city communities like we have in the Bronx, you'll know this was a Herculean task,” Dr. Lubin said at the meeting, cosponsored by the Children's Hospital of Philadelphia.

Her team was able to find leads to 44 of the original 90 young people, who now range in age from 16 to 24 years, with a mean age of 19. Twenty of these were confirmed deceased, but the researchers were able to make contact with 24 of the former patients, some of whom they'd not seen in over a decade. “We sent them letters and called them asking if they would come in and fill out follow-up questionnaires.”

Nine were living with adoptive families, and six were still living with a biologic parent, some of whom were HIV positive themselves. Three were living independently, and others were living with grandparents, siblings, or other relatives. Unfortunately, a significant number were in prison or detention centers.

The cognitive and neurologic problems present during their early childhoods have persisted to some degree into young adulthood. The mean total intelligence quotient in the group was 87, which is slightly lower than average (90–110). However, 17 of the young people were within the average range, and only 3 showed evidence of mild retardation. Fourteen still had language impairments, and 9 had learning disabilities.

Many of them were working very hard to overcome their disabilities. Nine of them were currently in school, four had already graduated from high school, two had obtained a general equivalency diploma, and two had actually graduated from college. “Given all the factors against them, these are major accomplishments,” said Dr. Lubin.

Dr. Lubin attributed their survival in part to improvements in antiretroviral therapy over the last decade. She noted that 14 of the 24 patients reported taking their anti-HIV drugs every day; 9 reported poor compliance. One patient reported taking the drugs on at least 5 of every 7 days. The investigators observed an age-related trend toward noncompliance; the patients who were over 21 tended to be less compliant than those under 21.

Compliance also seemed to correlate with education; the youths who dropped out of high school were less likely to take their medications consistently. But Dr. Lubin cautioned that the sample size was not large enough to determine if these are truly meaningful observations.

Some of the young people were very actively engaged in self-management; 8 knew their T-cell counts, and 10 knew their current viral loads. Those who were most compliant with their medication regimens were less likely to abuse alcohol or street drugs, and less likely to have run afoul of the law than those who were noncompliant.

Not surprisingly, given the age range of the subjects, use of alcohol and cannabis was common, with 18 reporting use of the former, and 13 reporting use of the latter. Only 4 of the 24 reported using “hard” drugs such as heroin or cocaine.

Although most were doing fairly well, seven had major problems with the law (arrests, detention or prison), and six had already done jail time.

For Dr. Lubin and her colleagues, as well as for the patients themselves, the reunions were extremely moving and often bittersweet.

“It was so amazing to see them as big kids. We knew them as little children and now here they were, fully grown. Many of them looked absolutely wonderful. They have a sense that they're doing well, and that they're going to be around for a while. But at the same time, it is very sad because their futures are very uncertain. And they're reaching an age where they are becoming sexually active and having relationships. And no matter how open-minded you are, HIV carries a huge stigma. They're struggling with the question of to whom they should disclose their status.”

Eleven of the former patients reported disclosing their HIV status to close friends, but an equal number had not disclosed it to anyone. Sixteen of the youths were sexually active, but only 7 reported that they always disclosed their serostatus to sexual partners. Another seven said they'd never disclosed to a sexual partner, and two said their willingness to disclose was variable. Ten of the 16 said they used condoms all the time, and 4 said they used them on most occasions. Two said they had never used condoms.

Some of the youths, particularly the older ones, expressed the desire to become parents themselves but they feared having an HIV-positive child. Dr. Lubin noted that two of the girls in the cohort had already had their first babies, both of whom were HIV negative.

These youths were also struggling with the larger question of what to do with their lives—adult lives no one expected them to have.

As a group, they have a lower educational level than the average, which limits their employment prospects. “A lot of them are really pretty lost. They're having difficulty transitioning to independence. They do not know how to deal with money or pay rent or anything like that. We've identified the need for programs that help them deal with basic life skills, and teach them how to deal with the various medical and social services for which they qualify.”

Dr. Lubin acknowledged that this qualitative study had major limitations such as a small sample size, reliance on self-assessment, and selection bias. Naturally, it raises as many questions as it answers. Since these youths are no longer patients of the Einstein programs, the researchers were unable to do any medical testing. Dr. Lubin is hoping to be able to set up a study of their medical status in the near future.

Limitations aside, the study does represent the first comprehensive look at how people with congenital HIV infection are faring as they emerge into adulthood. What is clear is that these young people have unique medical, psychological, social and practical needs that are not currently being met by any existing agencies. She said that her team is actively trying to link this cohort with other, smaller groups of people born HIV positive, as well as with other HIV/AIDS service organizations.

The latter can be tricky, since these young people may not readily identify with other HIV-positive subgroups such as gay men, lesbians, IV drug users, or immigrants from countries where HIV is widely prevalent. “They really are a distinct and unique group,” Dr. Lubin said.

OLD GREENWICH, CONN. — A small cohort of young people who were born infected with HIV is alive and well, and struggling to come to grips with an adulthood no one ever thought they'd live to reach.

“We first saw some of these kids when they were 4 or 5 years old, and it is so heartening to see them now as young adults. We never expected them to live this long,” said Dr. Katlyne Lubin of the Albert Einstein College of Medicine's Rose F. Kennedy Center for Excellence in Developmental Disabilities, Bronx, N.Y. Since the early 1990s, the Kennedy Center has had a special program to help young children born with HIV, many of whom have significant HIV-related neurologic and developmental problems.

At a meeting of the Eastern Society for Pediatric Research, Dr. Lubin reported preliminary qualitative data gathered from the first-ever U.S. follow-up study of young adults born HIV positive. Her findings provide a window into the inspiring yet heartbreaking world of a unique generation.

“There was nobody like these kids before they were born, and because here in the United States we've been so successful in preventing maternal-fetal HIV transmission, there are hardly any others coming up behind them.” Many of the survivors of the original Albert Einstein cohort are doing surprisingly well given the daunting difficulties posed by a chronic and life-threatening disease and cognitive impairment, all against a backdrop of inner city poverty.

Today, these young people face entirely new challenges as they enter an adulthood for which neither they nor the health care system are prepared.

Dr. Lubin's study is a follow-up to work originally begun by P. Papola, M. Alvarez, and H. J. Cohen at Einstein in 1994. The team assessed the neurocognitive status of 90 children, ranging in age from 5 to 14, who were born infected with HIV. All were residents of the Bronx, and nearly all were from poor African American or Hispanic/Caribbean communities (Pediatrics 1994;94:914–8).

The original study showed that 44% of these young people were below average in intelligence for their ages, and 56% were at borderline intelligence. Half had significant language impairments, and 74% required special education services.

As the youths have aged, nearly all of them have ceased coming to the Kennedy center, and have been essentially lost to follow-up.

“We began to wonder what had happened to all of these kids, so about 2 years ago we decided to try and do a follow-up study, and track down as many of them as we could. If you know anything about doing research in inner-city communities like we have in the Bronx, you'll know this was a Herculean task,” Dr. Lubin said at the meeting, cosponsored by the Children's Hospital of Philadelphia.

Her team was able to find leads to 44 of the original 90 young people, who now range in age from 16 to 24 years, with a mean age of 19. Twenty of these were confirmed deceased, but the researchers were able to make contact with 24 of the former patients, some of whom they'd not seen in over a decade. “We sent them letters and called them asking if they would come in and fill out follow-up questionnaires.”

Nine were living with adoptive families, and six were still living with a biologic parent, some of whom were HIV positive themselves. Three were living independently, and others were living with grandparents, siblings, or other relatives. Unfortunately, a significant number were in prison or detention centers.

The cognitive and neurologic problems present during their early childhoods have persisted to some degree into young adulthood. The mean total intelligence quotient in the group was 87, which is slightly lower than average (90–110). However, 17 of the young people were within the average range, and only 3 showed evidence of mild retardation. Fourteen still had language impairments, and 9 had learning disabilities.

Many of them were working very hard to overcome their disabilities. Nine of them were currently in school, four had already graduated from high school, two had obtained a general equivalency diploma, and two had actually graduated from college. “Given all the factors against them, these are major accomplishments,” said Dr. Lubin.

Dr. Lubin attributed their survival in part to improvements in antiretroviral therapy over the last decade. She noted that 14 of the 24 patients reported taking their anti-HIV drugs every day; 9 reported poor compliance. One patient reported taking the drugs on at least 5 of every 7 days. The investigators observed an age-related trend toward noncompliance; the patients who were over 21 tended to be less compliant than those under 21.

Compliance also seemed to correlate with education; the youths who dropped out of high school were less likely to take their medications consistently. But Dr. Lubin cautioned that the sample size was not large enough to determine if these are truly meaningful observations.

Some of the young people were very actively engaged in self-management; 8 knew their T-cell counts, and 10 knew their current viral loads. Those who were most compliant with their medication regimens were less likely to abuse alcohol or street drugs, and less likely to have run afoul of the law than those who were noncompliant.

Not surprisingly, given the age range of the subjects, use of alcohol and cannabis was common, with 18 reporting use of the former, and 13 reporting use of the latter. Only 4 of the 24 reported using “hard” drugs such as heroin or cocaine.

Although most were doing fairly well, seven had major problems with the law (arrests, detention or prison), and six had already done jail time.

For Dr. Lubin and her colleagues, as well as for the patients themselves, the reunions were extremely moving and often bittersweet.

“It was so amazing to see them as big kids. We knew them as little children and now here they were, fully grown. Many of them looked absolutely wonderful. They have a sense that they're doing well, and that they're going to be around for a while. But at the same time, it is very sad because their futures are very uncertain. And they're reaching an age where they are becoming sexually active and having relationships. And no matter how open-minded you are, HIV carries a huge stigma. They're struggling with the question of to whom they should disclose their status.”

Eleven of the former patients reported disclosing their HIV status to close friends, but an equal number had not disclosed it to anyone. Sixteen of the youths were sexually active, but only 7 reported that they always disclosed their serostatus to sexual partners. Another seven said they'd never disclosed to a sexual partner, and two said their willingness to disclose was variable. Ten of the 16 said they used condoms all the time, and 4 said they used them on most occasions. Two said they had never used condoms.

Some of the youths, particularly the older ones, expressed the desire to become parents themselves but they feared having an HIV-positive child. Dr. Lubin noted that two of the girls in the cohort had already had their first babies, both of whom were HIV negative.

These youths were also struggling with the larger question of what to do with their lives—adult lives no one expected them to have.

As a group, they have a lower educational level than the average, which limits their employment prospects. “A lot of them are really pretty lost. They're having difficulty transitioning to independence. They do not know how to deal with money or pay rent or anything like that. We've identified the need for programs that help them deal with basic life skills, and teach them how to deal with the various medical and social services for which they qualify.”

Dr. Lubin acknowledged that this qualitative study had major limitations such as a small sample size, reliance on self-assessment, and selection bias. Naturally, it raises as many questions as it answers. Since these youths are no longer patients of the Einstein programs, the researchers were unable to do any medical testing. Dr. Lubin is hoping to be able to set up a study of their medical status in the near future.

Limitations aside, the study does represent the first comprehensive look at how people with congenital HIV infection are faring as they emerge into adulthood. What is clear is that these young people have unique medical, psychological, social and practical needs that are not currently being met by any existing agencies. She said that her team is actively trying to link this cohort with other, smaller groups of people born HIV positive, as well as with other HIV/AIDS service organizations.

The latter can be tricky, since these young people may not readily identify with other HIV-positive subgroups such as gay men, lesbians, IV drug users, or immigrants from countries where HIV is widely prevalent. “They really are a distinct and unique group,” Dr. Lubin said.

OLD GREENWICH, CONN. — A small cohort of young people who were born infected with HIV is alive and well, and struggling to come to grips with an adulthood no one ever thought they'd live to reach.

“We first saw some of these kids when they were 4 or 5 years old, and it is so heartening to see them now as young adults. We never expected them to live this long,” said Dr. Katlyne Lubin of the Albert Einstein College of Medicine's Rose F. Kennedy Center for Excellence in Developmental Disabilities, Bronx, N.Y. Since the early 1990s, the Kennedy Center has had a special program to help young children born with HIV, many of whom have significant HIV-related neurologic and developmental problems.

At a meeting of the Eastern Society for Pediatric Research, Dr. Lubin reported preliminary qualitative data gathered from the first-ever U.S. follow-up study of young adults born HIV positive. Her findings provide a window into the inspiring yet heartbreaking world of a unique generation.

“There was nobody like these kids before they were born, and because here in the United States we've been so successful in preventing maternal-fetal HIV transmission, there are hardly any others coming up behind them.” Many of the survivors of the original Albert Einstein cohort are doing surprisingly well given the daunting difficulties posed by a chronic and life-threatening disease and cognitive impairment, all against a backdrop of inner city poverty.

Today, these young people face entirely new challenges as they enter an adulthood for which neither they nor the health care system are prepared.

Dr. Lubin's study is a follow-up to work originally begun by P. Papola, M. Alvarez, and H. J. Cohen at Einstein in 1994. The team assessed the neurocognitive status of 90 children, ranging in age from 5 to 14, who were born infected with HIV. All were residents of the Bronx, and nearly all were from poor African American or Hispanic/Caribbean communities (Pediatrics 1994;94:914–8).

The original study showed that 44% of these young people were below average in intelligence for their ages, and 56% were at borderline intelligence. Half had significant language impairments, and 74% required special education services.

As the youths have aged, nearly all of them have ceased coming to the Kennedy center, and have been essentially lost to follow-up.

“We began to wonder what had happened to all of these kids, so about 2 years ago we decided to try and do a follow-up study, and track down as many of them as we could. If you know anything about doing research in inner-city communities like we have in the Bronx, you'll know this was a Herculean task,” Dr. Lubin said at the meeting, cosponsored by the Children's Hospital of Philadelphia.

Her team was able to find leads to 44 of the original 90 young people, who now range in age from 16 to 24 years, with a mean age of 19. Twenty of these were confirmed deceased, but the researchers were able to make contact with 24 of the former patients, some of whom they'd not seen in over a decade. “We sent them letters and called them asking if they would come in and fill out follow-up questionnaires.”

Nine were living with adoptive families, and six were still living with a biologic parent, some of whom were HIV positive themselves. Three were living independently, and others were living with grandparents, siblings, or other relatives. Unfortunately, a significant number were in prison or detention centers.

The cognitive and neurologic problems present during their early childhoods have persisted to some degree into young adulthood. The mean total intelligence quotient in the group was 87, which is slightly lower than average (90–110). However, 17 of the young people were within the average range, and only 3 showed evidence of mild retardation. Fourteen still had language impairments, and 9 had learning disabilities.

Many of them were working very hard to overcome their disabilities. Nine of them were currently in school, four had already graduated from high school, two had obtained a general equivalency diploma, and two had actually graduated from college. “Given all the factors against them, these are major accomplishments,” said Dr. Lubin.

Dr. Lubin attributed their survival in part to improvements in antiretroviral therapy over the last decade. She noted that 14 of the 24 patients reported taking their anti-HIV drugs every day; 9 reported poor compliance. One patient reported taking the drugs on at least 5 of every 7 days. The investigators observed an age-related trend toward noncompliance; the patients who were over 21 tended to be less compliant than those under 21.

Compliance also seemed to correlate with education; the youths who dropped out of high school were less likely to take their medications consistently. But Dr. Lubin cautioned that the sample size was not large enough to determine if these are truly meaningful observations.

Some of the young people were very actively engaged in self-management; 8 knew their T-cell counts, and 10 knew their current viral loads. Those who were most compliant with their medication regimens were less likely to abuse alcohol or street drugs, and less likely to have run afoul of the law than those who were noncompliant.

Not surprisingly, given the age range of the subjects, use of alcohol and cannabis was common, with 18 reporting use of the former, and 13 reporting use of the latter. Only 4 of the 24 reported using “hard” drugs such as heroin or cocaine.

Although most were doing fairly well, seven had major problems with the law (arrests, detention or prison), and six had already done jail time.

For Dr. Lubin and her colleagues, as well as for the patients themselves, the reunions were extremely moving and often bittersweet.

“It was so amazing to see them as big kids. We knew them as little children and now here they were, fully grown. Many of them looked absolutely wonderful. They have a sense that they're doing well, and that they're going to be around for a while. But at the same time, it is very sad because their futures are very uncertain. And they're reaching an age where they are becoming sexually active and having relationships. And no matter how open-minded you are, HIV carries a huge stigma. They're struggling with the question of to whom they should disclose their status.”

Eleven of the former patients reported disclosing their HIV status to close friends, but an equal number had not disclosed it to anyone. Sixteen of the youths were sexually active, but only 7 reported that they always disclosed their serostatus to sexual partners. Another seven said they'd never disclosed to a sexual partner, and two said their willingness to disclose was variable. Ten of the 16 said they used condoms all the time, and 4 said they used them on most occasions. Two said they had never used condoms.

Some of the youths, particularly the older ones, expressed the desire to become parents themselves but they feared having an HIV-positive child. Dr. Lubin noted that two of the girls in the cohort had already had their first babies, both of whom were HIV negative.

These youths were also struggling with the larger question of what to do with their lives—adult lives no one expected them to have.

As a group, they have a lower educational level than the average, which limits their employment prospects. “A lot of them are really pretty lost. They're having difficulty transitioning to independence. They do not know how to deal with money or pay rent or anything like that. We've identified the need for programs that help them deal with basic life skills, and teach them how to deal with the various medical and social services for which they qualify.”

Dr. Lubin acknowledged that this qualitative study had major limitations such as a small sample size, reliance on self-assessment, and selection bias. Naturally, it raises as many questions as it answers. Since these youths are no longer patients of the Einstein programs, the researchers were unable to do any medical testing. Dr. Lubin is hoping to be able to set up a study of their medical status in the near future.

Limitations aside, the study does represent the first comprehensive look at how people with congenital HIV infection are faring as they emerge into adulthood. What is clear is that these young people have unique medical, psychological, social and practical needs that are not currently being met by any existing agencies. She said that her team is actively trying to link this cohort with other, smaller groups of people born HIV positive, as well as with other HIV/AIDS service organizations.

The latter can be tricky, since these young people may not readily identify with other HIV-positive subgroups such as gay men, lesbians, IV drug users, or immigrants from countries where HIV is widely prevalent. “They really are a distinct and unique group,” Dr. Lubin said.

OLD GREENWICH, CONN. — A small cohort of young people who were born infected with HIV is alive and well and struggling to come to grips with an adulthood no one ever thought they'd live to reach.

“We first saw some of these kids when they were 4 or 5 years old, and it is so heartening to see them now as young adults. We never expected them to live this long,” said Dr. Katlyne Lubin of the Albert Einstein College of Medicine's Rose F. Kennedy Center for Excellence in Developmental Disabilities, Bronx, N.Y. Since the early 1990s, the Kennedy Center has had a special program to help young children born with HIV, many of whom have significant HIV-related neurologic and developmental problems.

At a meeting of the Eastern Society for Pediatric Research, Dr. Lubin reported preliminary qualitative data gathered from the first-ever U.S. follow-up study of young adults born HIV positive. Her findings provide a window into the inspiring yet heartbreaking world of a unique generation.

“There was nobody like these kids before they were born, and because here in the United States we've been so successful in preventing maternal-fetal HIV transmission, there are hardly any others coming up behind them.” Many of the survivors of the original Albert Einstein cohort are doing surprisingly well given the daunting difficulties posed by a chronic and life-threatening disease and cognitive impairment, all against a backdrop of inner city poverty.

Today, these young people face entirely new challenges as they enter an adulthood for which neither they nor the health care system are prepared.

Dr. Lubin's study is a follow-up to work originally begun by P. Papola, M. Alvarez, and H. J. Cohen at Einstein in 1994. The team assessed the neurocognitive status of 90 children, ranging in age from 5 to 14, who were born infected with HIV. All were residents of the Bronx, and nearly all were from poor African American or Hispanic/Caribbean communities (Pediatrics 1994;94:914–8).

The original study showed that 44% of these young people were below average in intelligence for their ages, and 56% were at borderline intelligence. Half had significant language impairments, and 74% required special education services.

As the youths have aged, nearly all of them have ceased coming to the Kennedy center, and have been essentially lost to follow-up.

“We began to wonder what had happened to all of these kids, so about 2 years ago we decided to try and do a follow-up study, and track down as many of them as we could. If you know anything about doing research in inner city communities like we have in the Bronx, you'll know this was a Herculean task,” Dr. Lubin said at the meeting, cosponsored by the Children's Hospital of Philadelphia.

Her team was able to find leads to 44 of the original 90 young people, who now range in age from 16 to 24 years, with a mean age of 19. Twenty of these were confirmed deceased, but the researchers were able to make contact with 24 of the former patients, some of whom they'd not seen in over a decade. “We sent them letters and called them asking if they would come in and fill out follow-up questionnaires.”

Nine were living with adoptive families, and six were still living with a biologic parent, some of whom were HIV positive themselves. Three were living independently, and others were living with grandparents, siblings, or other relatives. Unfortunately, a significant number were in prison or detention centers.

The cognitive and neurologic problems present during their early childhoods have persisted to some degree into young adulthood. The mean total intelligence quotient in the group was 87, which is slightly lower than average (90–110). However, 17 of the young people were within the average range, and only 3 showed evidence of mild retardation. Fourteen still had language impairments, and 9 had learning disabilities.

Many of them were working very hard to overcome their disabilities. Nine of them were currently in school, four had already graduated from high school, two had obtained a general equivalency diploma, and two had actually graduated from college. “Given all the factors against them, these are major accomplishments,” said Dr. Lubin.

Dr. Lubin attributed their survival in part to improvements in antiretroviral therapy over the last decade. She noted that 14 of the 24 patients reported taking their anti-HIV drugs every day; 9 reported poor compliance. One patient reported taking the drugs on at least 5 of every 7 days. The investigators observed an age-related trend toward noncompliance; the patients who were over 21 tended to be less compliant than those under 21.

Compliance also seemed to correlate with education; the youths who dropped out of high school were less likely to take their medications consistently. But Dr. Lubin cautioned that the sample size was not large enough to determine if these are truly meaningful observations.

Some of the young people were very actively engaged in self-management; 8 knew their T-cell counts, and 10 knew their current viral loads. Those who were most compliant with their medication regimens were less likely to abuse alcohol or street drugs, and less likely to have run afoul of the law than those who were noncompliant.

Not surprisingly, given the age range of the subjects, use of alcohol and cannabis was common, with 18 reporting use of the former, and 13 reporting use of the latter. Only 4 of the 24 reported using “hard” drugs such as heroin or cocaine.

Although most were doing fairly well, seven had major problems with the law (arrests, detention, or prison), and six had already done jail time.

For Dr. Lubin and her colleagues, as well as for the patients themselves, the reunions were extremely moving and often bittersweet.

“It was so amazing to see them as big kids. We knew them as little children and now, here they were, fully grown. Many of them looked absolutely wonderful. They have a sense that they're doing well, and that they're going to be around for a while. But at the same time, it is very sad because their futures are very uncertain. And they're reaching an age where they are becoming sexually active and having relationships. And no matter how open-minded you are, HIV carries a huge stigma. They're struggling with the question of to whom they should disclose their status.”

Eleven of the former patients reported disclosing their HIV status to close friends, but an equal number had not disclosed it to anyone. And 16 were sexually active, but only 7 reported that they always disclosed their serostatus to sexual partners. Another 7 of the 16 said they'd never disclosed to a sexual partner, and 2 said their willingness to disclose was variable. Ten of the 16 said they used condoms all the time, and 4 said they used them on most occasions. Two said they had never used condoms.

Some of the youths, particularly the older ones, expressed the wish to become parents but feared having an HIV-positive child. Dr. Lubin noted that two of the girls in the cohort had already had their first babies, both of whom were HIV negative.

These youths were also struggling with the larger question of what to do with their lives—adult lives no one expected them to have. As a group, they have a lower educational level than the average, which limits their employment prospects. “A lot of them are really pretty lost. They're having difficulty transitioning to independence. They do not know how to deal with money or pay rent or anything like that. We've identified the need for programs that help them deal with basic life skills, and teach them how to deal with the various medical and social services for which they qualify.”

OLD GREENWICH, CONN. — A small cohort of young people who were born infected with HIV is alive and well and struggling to come to grips with an adulthood no one ever thought they'd live to reach.

“We first saw some of these kids when they were 4 or 5 years old, and it is so heartening to see them now as young adults. We never expected them to live this long,” said Dr. Katlyne Lubin of the Albert Einstein College of Medicine's Rose F. Kennedy Center for Excellence in Developmental Disabilities, Bronx, N.Y. Since the early 1990s, the Kennedy Center has had a special program to help young children born with HIV, many of whom have significant HIV-related neurologic and developmental problems.

At a meeting of the Eastern Society for Pediatric Research, Dr. Lubin reported preliminary qualitative data gathered from the first-ever U.S. follow-up study of young adults born HIV positive. Her findings provide a window into the inspiring yet heartbreaking world of a unique generation.

“There was nobody like these kids before they were born, and because here in the United States we've been so successful in preventing maternal-fetal HIV transmission, there are hardly any others coming up behind them.” Many of the survivors of the original Albert Einstein cohort are doing surprisingly well given the daunting difficulties posed by a chronic and life-threatening disease and cognitive impairment, all against a backdrop of inner city poverty.

Today, these young people face entirely new challenges as they enter an adulthood for which neither they nor the health care system are prepared.

Dr. Lubin's study is a follow-up to work originally begun by P. Papola, M. Alvarez, and H. J. Cohen at Einstein in 1994. The team assessed the neurocognitive status of 90 children, ranging in age from 5 to 14, who were born infected with HIV. All were residents of the Bronx, and nearly all were from poor African American or Hispanic/Caribbean communities (Pediatrics 1994;94:914–8).

The original study showed that 44% of these young people were below average in intelligence for their ages, and 56% were at borderline intelligence. Half had significant language impairments, and 74% required special education services.

As the youths have aged, nearly all of them have ceased coming to the Kennedy center, and have been essentially lost to follow-up.

“We began to wonder what had happened to all of these kids, so about 2 years ago we decided to try and do a follow-up study, and track down as many of them as we could. If you know anything about doing research in inner city communities like we have in the Bronx, you'll know this was a Herculean task,” Dr. Lubin said at the meeting, cosponsored by the Children's Hospital of Philadelphia.

Her team was able to find leads to 44 of the original 90 young people, who now range in age from 16 to 24 years, with a mean age of 19. Twenty of these were confirmed deceased, but the researchers were able to make contact with 24 of the former patients, some of whom they'd not seen in over a decade. “We sent them letters and called them asking if they would come in and fill out follow-up questionnaires.”

Nine were living with adoptive families, and six were still living with a biologic parent, some of whom were HIV positive themselves. Three were living independently, and others were living with grandparents, siblings, or other relatives. Unfortunately, a significant number were in prison or detention centers.

The cognitive and neurologic problems present during their early childhoods have persisted to some degree into young adulthood. The mean total intelligence quotient in the group was 87, which is slightly lower than average (90–110). However, 17 of the young people were within the average range, and only 3 showed evidence of mild retardation. Fourteen still had language impairments, and 9 had learning disabilities.

Many of them were working very hard to overcome their disabilities. Nine of them were currently in school, four had already graduated from high school, two had obtained a general equivalency diploma, and two had actually graduated from college. “Given all the factors against them, these are major accomplishments,” said Dr. Lubin.

Dr. Lubin attributed their survival in part to improvements in antiretroviral therapy over the last decade. She noted that 14 of the 24 patients reported taking their anti-HIV drugs every day; 9 reported poor compliance. One patient reported taking the drugs on at least 5 of every 7 days. The investigators observed an age-related trend toward noncompliance; the patients who were over 21 tended to be less compliant than those under 21.

Compliance also seemed to correlate with education; the youths who dropped out of high school were less likely to take their medications consistently. But Dr. Lubin cautioned that the sample size was not large enough to determine if these are truly meaningful observations.

Some of the young people were very actively engaged in self-management; 8 knew their T-cell counts, and 10 knew their current viral loads. Those who were most compliant with their medication regimens were less likely to abuse alcohol or street drugs, and less likely to have run afoul of the law than those who were noncompliant.

Not surprisingly, given the age range of the subjects, use of alcohol and cannabis was common, with 18 reporting use of the former, and 13 reporting use of the latter. Only 4 of the 24 reported using “hard” drugs such as heroin or cocaine.

Although most were doing fairly well, seven had major problems with the law (arrests, detention, or prison), and six had already done jail time.

For Dr. Lubin and her colleagues, as well as for the patients themselves, the reunions were extremely moving and often bittersweet.

“It was so amazing to see them as big kids. We knew them as little children and now, here they were, fully grown. Many of them looked absolutely wonderful. They have a sense that they're doing well, and that they're going to be around for a while. But at the same time, it is very sad because their futures are very uncertain. And they're reaching an age where they are becoming sexually active and having relationships. And no matter how open-minded you are, HIV carries a huge stigma. They're struggling with the question of to whom they should disclose their status.”

Eleven of the former patients reported disclosing their HIV status to close friends, but an equal number had not disclosed it to anyone. And 16 were sexually active, but only 7 reported that they always disclosed their serostatus to sexual partners. Another 7 of the 16 said they'd never disclosed to a sexual partner, and 2 said their willingness to disclose was variable. Ten of the 16 said they used condoms all the time, and 4 said they used them on most occasions. Two said they had never used condoms.

Some of the youths, particularly the older ones, expressed the wish to become parents but feared having an HIV-positive child. Dr. Lubin noted that two of the girls in the cohort had already had their first babies, both of whom were HIV negative.

These youths were also struggling with the larger question of what to do with their lives—adult lives no one expected them to have. As a group, they have a lower educational level than the average, which limits their employment prospects. “A lot of them are really pretty lost. They're having difficulty transitioning to independence. They do not know how to deal with money or pay rent or anything like that. We've identified the need for programs that help them deal with basic life skills, and teach them how to deal with the various medical and social services for which they qualify.”

OLD GREENWICH, CONN. — A small cohort of young people who were born infected with HIV is alive and well and struggling to come to grips with an adulthood no one ever thought they'd live to reach.

“We first saw some of these kids when they were 4 or 5 years old, and it is so heartening to see them now as young adults. We never expected them to live this long,” said Dr. Katlyne Lubin of the Albert Einstein College of Medicine's Rose F. Kennedy Center for Excellence in Developmental Disabilities, Bronx, N.Y. Since the early 1990s, the Kennedy Center has had a special program to help young children born with HIV, many of whom have significant HIV-related neurologic and developmental problems.

At a meeting of the Eastern Society for Pediatric Research, Dr. Lubin reported preliminary qualitative data gathered from the first-ever U.S. follow-up study of young adults born HIV positive. Her findings provide a window into the inspiring yet heartbreaking world of a unique generation.

“There was nobody like these kids before they were born, and because here in the United States we've been so successful in preventing maternal-fetal HIV transmission, there are hardly any others coming up behind them.” Many of the survivors of the original Albert Einstein cohort are doing surprisingly well given the daunting difficulties posed by a chronic and life-threatening disease and cognitive impairment, all against a backdrop of inner city poverty.

Today, these young people face entirely new challenges as they enter an adulthood for which neither they nor the health care system are prepared.

Dr. Lubin's study is a follow-up to work originally begun by P. Papola, M. Alvarez, and H. J. Cohen at Einstein in 1994. The team assessed the neurocognitive status of 90 children, ranging in age from 5 to 14, who were born infected with HIV. All were residents of the Bronx, and nearly all were from poor African American or Hispanic/Caribbean communities (Pediatrics 1994;94:914–8).

The original study showed that 44% of these young people were below average in intelligence for their ages, and 56% were at borderline intelligence. Half had significant language impairments, and 74% required special education services.

As the youths have aged, nearly all of them have ceased coming to the Kennedy center, and have been essentially lost to follow-up.

“We began to wonder what had happened to all of these kids, so about 2 years ago we decided to try and do a follow-up study, and track down as many of them as we could. If you know anything about doing research in inner city communities like we have in the Bronx, you'll know this was a Herculean task,” Dr. Lubin said at the meeting, cosponsored by the Children's Hospital of Philadelphia.

Her team was able to find leads to 44 of the original 90 young people, who now range in age from 16 to 24 years, with a mean age of 19. Twenty of these were confirmed deceased, but the researchers were able to make contact with 24 of the former patients, some of whom they'd not seen in over a decade. “We sent them letters and called them asking if they would come in and fill out follow-up questionnaires.”

Nine were living with adoptive families, and six were still living with a biologic parent, some of whom were HIV positive themselves. Three were living independently, and others were living with grandparents, siblings, or other relatives. Unfortunately, a significant number were in prison or detention centers.

The cognitive and neurologic problems present during their early childhoods have persisted to some degree into young adulthood. The mean total intelligence quotient in the group was 87, which is slightly lower than average (90–110). However, 17 of the young people were within the average range, and only 3 showed evidence of mild retardation. Fourteen still had language impairments, and 9 had learning disabilities.

Many of them were working very hard to overcome their disabilities. Nine of them were currently in school, four had already graduated from high school, two had obtained a general equivalency diploma, and two had actually graduated from college. “Given all the factors against them, these are major accomplishments,” said Dr. Lubin.

Dr. Lubin attributed their survival in part to improvements in antiretroviral therapy over the last decade. She noted that 14 of the 24 patients reported taking their anti-HIV drugs every day; 9 reported poor compliance. One patient reported taking the drugs on at least 5 of every 7 days. The investigators observed an age-related trend toward noncompliance; the patients who were over 21 tended to be less compliant than those under 21.

Compliance also seemed to correlate with education; the youths who dropped out of high school were less likely to take their medications consistently. But Dr. Lubin cautioned that the sample size was not large enough to determine if these are truly meaningful observations.

Some of the young people were very actively engaged in self-management; 8 knew their T-cell counts, and 10 knew their current viral loads. Those who were most compliant with their medication regimens were less likely to abuse alcohol or street drugs, and less likely to have run afoul of the law than those who were noncompliant.

Not surprisingly, given the age range of the subjects, use of alcohol and cannabis was common, with 18 reporting use of the former, and 13 reporting use of the latter. Only 4 of the 24 reported using “hard” drugs such as heroin or cocaine.

Although most were doing fairly well, seven had major problems with the law (arrests, detention, or prison), and six had already done jail time.

For Dr. Lubin and her colleagues, as well as for the patients themselves, the reunions were extremely moving and often bittersweet.

“It was so amazing to see them as big kids. We knew them as little children and now, here they were, fully grown. Many of them looked absolutely wonderful. They have a sense that they're doing well, and that they're going to be around for a while. But at the same time, it is very sad because their futures are very uncertain. And they're reaching an age where they are becoming sexually active and having relationships. And no matter how open-minded you are, HIV carries a huge stigma. They're struggling with the question of to whom they should disclose their status.”

Eleven of the former patients reported disclosing their HIV status to close friends, but an equal number had not disclosed it to anyone. And 16 were sexually active, but only 7 reported that they always disclosed their serostatus to sexual partners. Another 7 of the 16 said they'd never disclosed to a sexual partner, and 2 said their willingness to disclose was variable. Ten of the 16 said they used condoms all the time, and 4 said they used them on most occasions. Two said they had never used condoms.

Some of the youths, particularly the older ones, expressed the wish to become parents but feared having an HIV-positive child. Dr. Lubin noted that two of the girls in the cohort had already had their first babies, both of whom were HIV negative.

These youths were also struggling with the larger question of what to do with their lives—adult lives no one expected them to have. As a group, they have a lower educational level than the average, which limits their employment prospects. “A lot of them are really pretty lost. They're having difficulty transitioning to independence. They do not know how to deal with money or pay rent or anything like that. We've identified the need for programs that help them deal with basic life skills, and teach them how to deal with the various medical and social services for which they qualify.”