Nancy Walsh

People aged 60 years and older should receive the herpes zoster vaccine to prevent the development of shingles, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommends.

A single dose of the vaccine can be given to adults 60 years and older even if they have already had an episode of shingles, which is characterized by the development of blisters and severe pain that can persist for months or even years. The vaccine, made by Merck & Co., is not indicated to treat acute zoster, to prevent patients with zoster from developing postherpetic neuralgia, or to treat ongoing postherpetic neuralgia. It does not compromise the immunogenicity of trivalent inactivated influenza vaccine if given simultaneously.

The new recommendation, published in an early-release electronic edition of Morbidity and Mortality Weekly Report last month, replaces a provisional recommendation made the CDC's Advisory Committee on Immunization Practices after licensure of the vaccine in 2006 by the Food and Drug Administration. The report also addresses other aspects of treating herpes zoster, such as oral antiviral agents acyclovir, valacyclovir, and famciclovir, which reduce the severity and duration of acute pain from zoster.

The zoster vaccine is not licensed for persons under age 60 years or for persons of any age who have received varicella vaccine.

Zoster vaccine is contraindicated for those with a history of anaphylactic reaction to any component of the vaccine; those with primary or acquired immunodeficiency; and pregnant women, though that is not likely in this age group.

The most common side effects associated with the vaccine are redness, pain, and swelling at the injection site, as well as pruritus and headache.

People aged 60 years and older should receive the herpes zoster vaccine to prevent the development of shingles, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommends.

A single dose of the vaccine can be given to adults 60 years and older even if they have already had an episode of shingles, which is characterized by the development of blisters and severe pain that can persist for months or even years. The vaccine, made by Merck & Co., is not indicated to treat acute zoster, to prevent patients with zoster from developing postherpetic neuralgia, or to treat ongoing postherpetic neuralgia. It does not compromise the immunogenicity of trivalent inactivated influenza vaccine if given simultaneously.

The new recommendation, published in an early-release electronic edition of Morbidity and Mortality Weekly Report last month, replaces a provisional recommendation made the CDC's Advisory Committee on Immunization Practices after licensure of the vaccine in 2006 by the Food and Drug Administration. The report also addresses other aspects of treating herpes zoster, such as oral antiviral agents acyclovir, valacyclovir, and famciclovir, which reduce the severity and duration of acute pain from zoster.

The zoster vaccine is not licensed for persons under age 60 years or for persons of any age who have received varicella vaccine.

Zoster vaccine is contraindicated for those with a history of anaphylactic reaction to any component of the vaccine; those with primary or acquired immunodeficiency; and pregnant women, though that is not likely in this age group.

The most common side effects associated with the vaccine are redness, pain, and swelling at the injection site, as well as pruritus and headache.

People aged 60 years and older should receive the herpes zoster vaccine to prevent the development of shingles, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommends.

A single dose of the vaccine can be given to adults 60 years and older even if they have already had an episode of shingles, which is characterized by the development of blisters and severe pain that can persist for months or even years. The vaccine, made by Merck & Co., is not indicated to treat acute zoster, to prevent patients with zoster from developing postherpetic neuralgia, or to treat ongoing postherpetic neuralgia. It does not compromise the immunogenicity of trivalent inactivated influenza vaccine if given simultaneously.

The new recommendation, published in an early-release electronic edition of Morbidity and Mortality Weekly Report last month, replaces a provisional recommendation made the CDC's Advisory Committee on Immunization Practices after licensure of the vaccine in 2006 by the Food and Drug Administration. The report also addresses other aspects of treating herpes zoster, such as oral antiviral agents acyclovir, valacyclovir, and famciclovir, which reduce the severity and duration of acute pain from zoster.

The zoster vaccine is not licensed for persons under age 60 years or for persons of any age who have received varicella vaccine.

Zoster vaccine is contraindicated for those with a history of anaphylactic reaction to any component of the vaccine; those with primary or acquired immunodeficiency; and pregnant women, though that is not likely in this age group.

The most common side effects associated with the vaccine are redness, pain, and swelling at the injection site, as well as pruritus and headache.

TORONTO – The impact of stressful life events on alcohol relapse varied depending on personality disorder subtype and history of alcohol use in an analysis of data from the Collaborative Longitudinal Study of Personality Disorders, Dr. Christina M. Delos-Reyes said at the annual conference of the American Society of Addiction Medicine.

Theoretical models of alcohol relapse have suggested that stress is a major contributor and this relationship is mediated, at least in part, by characteristics such as personality disorders and onset of alcohol use. Previous studies have attempted to evaluate the effects of stress on relapse, but have been limited by retrospective design and brevity of follow-up.

To more clearly determine the ability of history and type of personality disorder to predict the clinical course of alcohol relapse as it relates to stress, a large, multicenter prospective study enrolled 573 patients with schizotypal personality disorder (STPD), borderline personality disorder (BPD), antisocial personality disorder (ASPD), or obsessive-compulsive personality disorder (OCPD), and followed them for 6 years.

Two-thirds of the sample were women, and the average age was 33 years. A total of 40% were self-referred and 76% were white. On average, they had 13 years of education, said Dr. Delos-Reyes of the department of psychiatry, Case Western Reserve University, Cleveland.

Stressful life events and the onset of alcohol relapse were assessed on a monthly basis, with relapse being defined as meeting the full criteria for alcohol use disorder for 2 consecutive weeks.

Life events were evaluated on the Life Events Assessment (LEA), which includes 82 stressful events, of which 59 are negative and 23 are positive. “A negative event would be losing your job, while a positive event could be having a baby,” she said.

Stressful events in the LEA are assessed over six domains: work/school, family, love relationships, crime/legal matters, money matters, and health issues.

“Over the course of 6 years, as you could imagine, 85% of the sample said they had at least one positive event, and 96% said they had at least one negative event,” she said.

Negative life events significantly predicted relapse in all patients, with a hazard ratio (HR) of 1.95. For patients with a history of alcoholism, the risk tripled for both positive (HR 3.13) and negative (HR 3.02) stressful events.

When risk was looked at in terms of personality disorder subtype, it appeared that a history of OCPD decreased the risk of relapse by 50% for both positive and negative (HR 0.57) stressful events.

“It was interesting to find what looks like a protective effect of OCD on relapse in a prospective study,” Dr. Delos-Reyes said. In contrast, patients with ASPD had double the risk for relapse with positive (HR 1.94) and negative (HR 1.92) stressful events.

Patients with a history of alcoholism had double the risk of relapse with positive stressful events. When the analysis included history of alcoholism and specific LEA domain, patients without a history of alcohol use disorder were five times more likely to relapse in response to a romantic problem (HR 4.91). Those with a history of alcoholism were almost six times more likely to relapse with a financial stressful event (HR 5.51).

Further analysis revealed that patients with OCPD and no history of alcoholism were almost 10 times more likely to relapse in the face of a stressful romantic problem, while those with ASPD and no history of alcoholism were six times more likely to relapse in the event of a stressful financial event, Dr. Delos-Reyes observed.

“These findings have implications for treatment providers who are designing relapse prevention programs,” she said. “As we are trying to improve our use of limited resources, we may want to screen for personality disorders and target prevention strategies based on personality disorder subtypes.”

TORONTO – The impact of stressful life events on alcohol relapse varied depending on personality disorder subtype and history of alcohol use in an analysis of data from the Collaborative Longitudinal Study of Personality Disorders, Dr. Christina M. Delos-Reyes said at the annual conference of the American Society of Addiction Medicine.

Theoretical models of alcohol relapse have suggested that stress is a major contributor and this relationship is mediated, at least in part, by characteristics such as personality disorders and onset of alcohol use. Previous studies have attempted to evaluate the effects of stress on relapse, but have been limited by retrospective design and brevity of follow-up.

To more clearly determine the ability of history and type of personality disorder to predict the clinical course of alcohol relapse as it relates to stress, a large, multicenter prospective study enrolled 573 patients with schizotypal personality disorder (STPD), borderline personality disorder (BPD), antisocial personality disorder (ASPD), or obsessive-compulsive personality disorder (OCPD), and followed them for 6 years.

Two-thirds of the sample were women, and the average age was 33 years. A total of 40% were self-referred and 76% were white. On average, they had 13 years of education, said Dr. Delos-Reyes of the department of psychiatry, Case Western Reserve University, Cleveland.

Stressful life events and the onset of alcohol relapse were assessed on a monthly basis, with relapse being defined as meeting the full criteria for alcohol use disorder for 2 consecutive weeks.

Life events were evaluated on the Life Events Assessment (LEA), which includes 82 stressful events, of which 59 are negative and 23 are positive. “A negative event would be losing your job, while a positive event could be having a baby,” she said.

Stressful events in the LEA are assessed over six domains: work/school, family, love relationships, crime/legal matters, money matters, and health issues.

“Over the course of 6 years, as you could imagine, 85% of the sample said they had at least one positive event, and 96% said they had at least one negative event,” she said.

Negative life events significantly predicted relapse in all patients, with a hazard ratio (HR) of 1.95. For patients with a history of alcoholism, the risk tripled for both positive (HR 3.13) and negative (HR 3.02) stressful events.

When risk was looked at in terms of personality disorder subtype, it appeared that a history of OCPD decreased the risk of relapse by 50% for both positive and negative (HR 0.57) stressful events.

“It was interesting to find what looks like a protective effect of OCD on relapse in a prospective study,” Dr. Delos-Reyes said. In contrast, patients with ASPD had double the risk for relapse with positive (HR 1.94) and negative (HR 1.92) stressful events.

Patients with a history of alcoholism had double the risk of relapse with positive stressful events. When the analysis included history of alcoholism and specific LEA domain, patients without a history of alcohol use disorder were five times more likely to relapse in response to a romantic problem (HR 4.91). Those with a history of alcoholism were almost six times more likely to relapse with a financial stressful event (HR 5.51).

Further analysis revealed that patients with OCPD and no history of alcoholism were almost 10 times more likely to relapse in the face of a stressful romantic problem, while those with ASPD and no history of alcoholism were six times more likely to relapse in the event of a stressful financial event, Dr. Delos-Reyes observed.

“These findings have implications for treatment providers who are designing relapse prevention programs,” she said. “As we are trying to improve our use of limited resources, we may want to screen for personality disorders and target prevention strategies based on personality disorder subtypes.”

TORONTO – The impact of stressful life events on alcohol relapse varied depending on personality disorder subtype and history of alcohol use in an analysis of data from the Collaborative Longitudinal Study of Personality Disorders, Dr. Christina M. Delos-Reyes said at the annual conference of the American Society of Addiction Medicine.

Theoretical models of alcohol relapse have suggested that stress is a major contributor and this relationship is mediated, at least in part, by characteristics such as personality disorders and onset of alcohol use. Previous studies have attempted to evaluate the effects of stress on relapse, but have been limited by retrospective design and brevity of follow-up.

To more clearly determine the ability of history and type of personality disorder to predict the clinical course of alcohol relapse as it relates to stress, a large, multicenter prospective study enrolled 573 patients with schizotypal personality disorder (STPD), borderline personality disorder (BPD), antisocial personality disorder (ASPD), or obsessive-compulsive personality disorder (OCPD), and followed them for 6 years.

Two-thirds of the sample were women, and the average age was 33 years. A total of 40% were self-referred and 76% were white. On average, they had 13 years of education, said Dr. Delos-Reyes of the department of psychiatry, Case Western Reserve University, Cleveland.

Stressful life events and the onset of alcohol relapse were assessed on a monthly basis, with relapse being defined as meeting the full criteria for alcohol use disorder for 2 consecutive weeks.

Life events were evaluated on the Life Events Assessment (LEA), which includes 82 stressful events, of which 59 are negative and 23 are positive. “A negative event would be losing your job, while a positive event could be having a baby,” she said.

Stressful events in the LEA are assessed over six domains: work/school, family, love relationships, crime/legal matters, money matters, and health issues.

“Over the course of 6 years, as you could imagine, 85% of the sample said they had at least one positive event, and 96% said they had at least one negative event,” she said.

Negative life events significantly predicted relapse in all patients, with a hazard ratio (HR) of 1.95. For patients with a history of alcoholism, the risk tripled for both positive (HR 3.13) and negative (HR 3.02) stressful events.

When risk was looked at in terms of personality disorder subtype, it appeared that a history of OCPD decreased the risk of relapse by 50% for both positive and negative (HR 0.57) stressful events.

“It was interesting to find what looks like a protective effect of OCD on relapse in a prospective study,” Dr. Delos-Reyes said. In contrast, patients with ASPD had double the risk for relapse with positive (HR 1.94) and negative (HR 1.92) stressful events.

Patients with a history of alcoholism had double the risk of relapse with positive stressful events. When the analysis included history of alcoholism and specific LEA domain, patients without a history of alcohol use disorder were five times more likely to relapse in response to a romantic problem (HR 4.91). Those with a history of alcoholism were almost six times more likely to relapse with a financial stressful event (HR 5.51).

Further analysis revealed that patients with OCPD and no history of alcoholism were almost 10 times more likely to relapse in the face of a stressful romantic problem, while those with ASPD and no history of alcoholism were six times more likely to relapse in the event of a stressful financial event, Dr. Delos-Reyes observed.

“These findings have implications for treatment providers who are designing relapse prevention programs,” she said. “As we are trying to improve our use of limited resources, we may want to screen for personality disorders and target prevention strategies based on personality disorder subtypes.”

BOSTON — The adolescent HIV-1 epidemic as reflected in a multisite cohort of U.S. youth is changing from one of vertically transmitted infection to one where infection is acquired through risk behaviors, posing new challenges for providers and the health care system, Dr. Allison L. Agwu reported in a poster session at the 15th Conference on Retroviruses and Opportunistic Infections.

The HIV Research Network, a consortium of 21 clinical sites that provide primary HIV care, includes 684 patients aged 12–24 years. Vertical transmission was the source of infection in 227 patients, while risk behaviors account for 457 cases, according to Dr. Agwu of Johns Hopkins University, Baltimore.

Analysis of data from this cohort showed that patients infected through risk behaviors are older, with a median age of 22 years, compared with a median age of 15 years among vertical-transmission patients.

They also are more likely to be male. A total of 292 (64%) of the risk-behavior patients are male, as are 108 (48%) of the vertical-transmission patients.

Risk behaviors comprised men having sex with men (51%), unprotected heterosexual activity (45%), and intravenous drug use (4%).

The median CD4 count in the risk-behavior group was 492 cells/mm

Despite this worse immune suppression and higher levels of viremia among the risk-behavior patients, they were less likely to be on highly active antiretroviral therapy (HAART) (43% versus 88%), Dr. Agwu found.

Those infected through risk behaviors also had significantly fewer outpatient visits, averaging five visits per year, while vertical-transmission patients averaged seven visits.

The rates of hospitalization did not differ, at 19 per 100 patient-years for the risk-behavior group and 17 per 100 patient-years for the group infected through vertical transmission, Dr. Agwu reported at the meeting, which was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.

Other aspects of treatment also did not differ significantly between the two groups. For example, 89% of patients meeting the criteria for prophylaxis against Pneumocystis carinii pneumonia in the risk-behavior group received prophylaxis, as did 80% of vertical-transmission patients.

Prophylaxis against Mycobacterium avium complex recommendations were followed by 83% and 75% of those in the risk-behavior and vertical-transmission groups, respectively.

"We suspect that there may be differences in psychosocial risk factors between the two groups that may account for the varying rates of HAART utilization," Dr. Agwu said in an interview. "Our future questions will focus on deciphering both patient and provider barriers to HAART initiation in the risk behavior group in order to institute appropriate interventions," she said.

She added that this group of patients in need of treatment is likely to grow in number as the Centers for Disease Control and Prevention's recommendation of universal opt-out testing is implemented.

ELSEVIER GLOBAL MEDICAL NEWS

BOSTON — The adolescent HIV-1 epidemic as reflected in a multisite cohort of U.S. youth is changing from one of vertically transmitted infection to one where infection is acquired through risk behaviors, posing new challenges for providers and the health care system, Dr. Allison L. Agwu reported in a poster session at the 15th Conference on Retroviruses and Opportunistic Infections.

The HIV Research Network, a consortium of 21 clinical sites that provide primary HIV care, includes 684 patients aged 12–24 years. Vertical transmission was the source of infection in 227 patients, while risk behaviors account for 457 cases, according to Dr. Agwu of Johns Hopkins University, Baltimore.

Analysis of data from this cohort showed that patients infected through risk behaviors are older, with a median age of 22 years, compared with a median age of 15 years among vertical-transmission patients.

They also are more likely to be male. A total of 292 (64%) of the risk-behavior patients are male, as are 108 (48%) of the vertical-transmission patients.

Risk behaviors comprised men having sex with men (51%), unprotected heterosexual activity (45%), and intravenous drug use (4%).

The median CD4 count in the risk-behavior group was 492 cells/mm

Despite this worse immune suppression and higher levels of viremia among the risk-behavior patients, they were less likely to be on highly active antiretroviral therapy (HAART) (43% versus 88%), Dr. Agwu found.

Those infected through risk behaviors also had significantly fewer outpatient visits, averaging five visits per year, while vertical-transmission patients averaged seven visits.

The rates of hospitalization did not differ, at 19 per 100 patient-years for the risk-behavior group and 17 per 100 patient-years for the group infected through vertical transmission, Dr. Agwu reported at the meeting, which was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.

Other aspects of treatment also did not differ significantly between the two groups. For example, 89% of patients meeting the criteria for prophylaxis against Pneumocystis carinii pneumonia in the risk-behavior group received prophylaxis, as did 80% of vertical-transmission patients.

Prophylaxis against Mycobacterium avium complex recommendations were followed by 83% and 75% of those in the risk-behavior and vertical-transmission groups, respectively.

"We suspect that there may be differences in psychosocial risk factors between the two groups that may account for the varying rates of HAART utilization," Dr. Agwu said in an interview. "Our future questions will focus on deciphering both patient and provider barriers to HAART initiation in the risk behavior group in order to institute appropriate interventions," she said.

She added that this group of patients in need of treatment is likely to grow in number as the Centers for Disease Control and Prevention's recommendation of universal opt-out testing is implemented.

ELSEVIER GLOBAL MEDICAL NEWS

BOSTON — The adolescent HIV-1 epidemic as reflected in a multisite cohort of U.S. youth is changing from one of vertically transmitted infection to one where infection is acquired through risk behaviors, posing new challenges for providers and the health care system, Dr. Allison L. Agwu reported in a poster session at the 15th Conference on Retroviruses and Opportunistic Infections.

The HIV Research Network, a consortium of 21 clinical sites that provide primary HIV care, includes 684 patients aged 12–24 years. Vertical transmission was the source of infection in 227 patients, while risk behaviors account for 457 cases, according to Dr. Agwu of Johns Hopkins University, Baltimore.

Analysis of data from this cohort showed that patients infected through risk behaviors are older, with a median age of 22 years, compared with a median age of 15 years among vertical-transmission patients.

They also are more likely to be male. A total of 292 (64%) of the risk-behavior patients are male, as are 108 (48%) of the vertical-transmission patients.

Risk behaviors comprised men having sex with men (51%), unprotected heterosexual activity (45%), and intravenous drug use (4%).

The median CD4 count in the risk-behavior group was 492 cells/mm

Despite this worse immune suppression and higher levels of viremia among the risk-behavior patients, they were less likely to be on highly active antiretroviral therapy (HAART) (43% versus 88%), Dr. Agwu found.

Those infected through risk behaviors also had significantly fewer outpatient visits, averaging five visits per year, while vertical-transmission patients averaged seven visits.

The rates of hospitalization did not differ, at 19 per 100 patient-years for the risk-behavior group and 17 per 100 patient-years for the group infected through vertical transmission, Dr. Agwu reported at the meeting, which was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.

Other aspects of treatment also did not differ significantly between the two groups. For example, 89% of patients meeting the criteria for prophylaxis against Pneumocystis carinii pneumonia in the risk-behavior group received prophylaxis, as did 80% of vertical-transmission patients.

Prophylaxis against Mycobacterium avium complex recommendations were followed by 83% and 75% of those in the risk-behavior and vertical-transmission groups, respectively.

"We suspect that there may be differences in psychosocial risk factors between the two groups that may account for the varying rates of HAART utilization," Dr. Agwu said in an interview. "Our future questions will focus on deciphering both patient and provider barriers to HAART initiation in the risk behavior group in order to institute appropriate interventions," she said.

She added that this group of patients in need of treatment is likely to grow in number as the Centers for Disease Control and Prevention's recommendation of universal opt-out testing is implemented.

ELSEVIER GLOBAL MEDICAL NEWS

BOSTON — The increased survival among HIV-infected children seen with effective prevention of perinatal transmission and the widespread adoption of highly active antiretroviral therapy has been accompanied by the emergence of a new generation of clinical, public health, and social challenges.

The median age of more than 3,500 infected children followed at U.S. clinical trial sites is now 15 years, and some patients are in their early 20s. The median age at death—9 years in 1994—had risen to 18 years by 2006, said Dr. Lynne Mofenson, chief of the Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md.

Although mortality has decreased, it remains 30 times higher for HIV-infected children than for uninfected children. There also has been a shift in causes of death, with fewer children dying from AIDS-related opportunistic infections and central nervous system disease and more succumbing to end-stage AIDS with multiple organ failure, or to sepsis or renal failure, Dr. Mofenson said at the 15th Conference on Retroviruses and Opportunistic Infections.

Aside from the disease itself, these young patients and their caregivers today face multiple challenges including drug resistance, complications of therapy, and issues related to adherence and mental health, Dr. Mofenson said.

Several studies have found an increase in primary drug resistance among newly infected infants.

For instance, data from New York State showed a 58% increase in resistance between 1998 and 2002, reaching 19%. This was primarily accounted for by mutations conferring resistance to the nonnucleoside reverse transcriptase inhibitors (J. Acquir. Immune Defic. Syndr. 2006;42:614–9).

Another series found resistance among 24% of infected children, with 10% being resistant to at least two classes of antiretroviral drugs, Dr. Mofenson said at the meeting, which was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.

Multidrug resistance is a particular problem for older children who were treated with monotherapy or dual therapy before triple therapy became the standard of care. Few choices remain for these children, particularly because many drugs available for adult patients have no pediatric formulations or dosing guidelines. "Without additional drugs, some HIV-infected children will run out of treatment options at a very early age," Dr. Mofenson said.

Investigations by the Pediatric Spectrum of Disease Project found that in 2001, 44% of children had already received two or more highly active antiretroviral treatment (HAART) regimens, and 3% had received five or more regimens. "This is only going to increase over time," she said.

These children increasingly face potentially severe complications of long-term therapy, particularly during puberty when as-yet unidentified physiologic changes appear to result in the development of hypercholesterolemia, which has been reported in up to 67% of children on therapy, and lipodystrophy, which has been reported in up to 47%.

Additionally, in one series, hyperinsulinemia was found in 60% of children, although insulin resistance was uncommon, she said.

Risk factors that have been identified for the development of these metabolic abnormalities include duration of antiretroviral therapy and the use of protease inhibitors and nucleoside reverse transcriptase inhibitors, particularly ritonavir, Dr. Mofenson said.

These findings further raise concerns about the potential for long-term cardiac complications. In one study from England, carotid intima thickness was significantly greater among 83 HIV-infected children, compared with a control group of 59 healthy children (Circulation 2005;112:103–9).

In that study, preatherosclerotic changes were particularly pronounced among patients treated with protease inhibitors. There may be roles for both HIV infection itself and intermittent antiretroviral therapy in the development of cardiovascular complications, she said.

Another area that is becoming important in pediatric HIV is mental health. "These children are born into families with multiple stresses including drug use and poverty," Dr. Mofenson said.

In one series of more than 300 children, the prevalence of attention-deficit/hyperactivity disorder was 24%, sixfold higher than in the general population of children, she said. Additionally, 29% had an anxiety disorder, which is a fourfold increase compared with healthy children, and 25% had clinical depression, which is a sevenfold increase.

"Finally, there is the overall challenge of HIV in adolescence," she said.

Many adolescents do not know they are infected, either because their perinatal infection has not been disclosed to them or they are at risk but have not been tested. And adherence to complex, lifelong therapy can present many difficulties, particularly in young patients who may appear well.

Infected adolescents also increasingly represent a high-risk population for HIV transmission. It has been estimated that 40%-60% of infected adolescents engage in unprotected sex, and there are high rates of substance abuse and smoking as well, she said.

Another disturbing finding that is emerging involves discrepancies in the use of HAART between children who were perinatally infected and those who were infected through risky sex.

"And of course HIV infection is a worldwide public health challenge that disproportionately affects children living in the poorest parts of the world. Infected children in high-resource settings such as the United States represent only 1% of the 2.3 million infected children worldwide," Dr. Mofenson commented.

BOSTON — The increased survival among HIV-infected children seen with effective prevention of perinatal transmission and the widespread adoption of highly active antiretroviral therapy has been accompanied by the emergence of a new generation of clinical, public health, and social challenges.

The median age of more than 3,500 infected children followed at U.S. clinical trial sites is now 15 years, and some patients are in their early 20s. The median age at death—9 years in 1994—had risen to 18 years by 2006, said Dr. Lynne Mofenson, chief of the Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md.

Although mortality has decreased, it remains 30 times higher for HIV-infected children than for uninfected children. There also has been a shift in causes of death, with fewer children dying from AIDS-related opportunistic infections and central nervous system disease and more succumbing to end-stage AIDS with multiple organ failure, or to sepsis or renal failure, Dr. Mofenson said at the 15th Conference on Retroviruses and Opportunistic Infections.

Aside from the disease itself, these young patients and their caregivers today face multiple challenges including drug resistance, complications of therapy, and issues related to adherence and mental health, Dr. Mofenson said.

Several studies have found an increase in primary drug resistance among newly infected infants.

For instance, data from New York State showed a 58% increase in resistance between 1998 and 2002, reaching 19%. This was primarily accounted for by mutations conferring resistance to the nonnucleoside reverse transcriptase inhibitors (J. Acquir. Immune Defic. Syndr. 2006;42:614–9).

Another series found resistance among 24% of infected children, with 10% being resistant to at least two classes of antiretroviral drugs, Dr. Mofenson said at the meeting, which was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.

Multidrug resistance is a particular problem for older children who were treated with monotherapy or dual therapy before triple therapy became the standard of care. Few choices remain for these children, particularly because many drugs available for adult patients have no pediatric formulations or dosing guidelines. "Without additional drugs, some HIV-infected children will run out of treatment options at a very early age," Dr. Mofenson said.

Investigations by the Pediatric Spectrum of Disease Project found that in 2001, 44% of children had already received two or more highly active antiretroviral treatment (HAART) regimens, and 3% had received five or more regimens. "This is only going to increase over time," she said.

These children increasingly face potentially severe complications of long-term therapy, particularly during puberty when as-yet unidentified physiologic changes appear to result in the development of hypercholesterolemia, which has been reported in up to 67% of children on therapy, and lipodystrophy, which has been reported in up to 47%.

Additionally, in one series, hyperinsulinemia was found in 60% of children, although insulin resistance was uncommon, she said.

Risk factors that have been identified for the development of these metabolic abnormalities include duration of antiretroviral therapy and the use of protease inhibitors and nucleoside reverse transcriptase inhibitors, particularly ritonavir, Dr. Mofenson said.

These findings further raise concerns about the potential for long-term cardiac complications. In one study from England, carotid intima thickness was significantly greater among 83 HIV-infected children, compared with a control group of 59 healthy children (Circulation 2005;112:103–9).

In that study, preatherosclerotic changes were particularly pronounced among patients treated with protease inhibitors. There may be roles for both HIV infection itself and intermittent antiretroviral therapy in the development of cardiovascular complications, she said.

Another area that is becoming important in pediatric HIV is mental health. "These children are born into families with multiple stresses including drug use and poverty," Dr. Mofenson said.

In one series of more than 300 children, the prevalence of attention-deficit/hyperactivity disorder was 24%, sixfold higher than in the general population of children, she said. Additionally, 29% had an anxiety disorder, which is a fourfold increase compared with healthy children, and 25% had clinical depression, which is a sevenfold increase.

"Finally, there is the overall challenge of HIV in adolescence," she said.

Many adolescents do not know they are infected, either because their perinatal infection has not been disclosed to them or they are at risk but have not been tested. And adherence to complex, lifelong therapy can present many difficulties, particularly in young patients who may appear well.

Infected adolescents also increasingly represent a high-risk population for HIV transmission. It has been estimated that 40%-60% of infected adolescents engage in unprotected sex, and there are high rates of substance abuse and smoking as well, she said.

Another disturbing finding that is emerging involves discrepancies in the use of HAART between children who were perinatally infected and those who were infected through risky sex.

"And of course HIV infection is a worldwide public health challenge that disproportionately affects children living in the poorest parts of the world. Infected children in high-resource settings such as the United States represent only 1% of the 2.3 million infected children worldwide," Dr. Mofenson commented.

BOSTON — The increased survival among HIV-infected children seen with effective prevention of perinatal transmission and the widespread adoption of highly active antiretroviral therapy has been accompanied by the emergence of a new generation of clinical, public health, and social challenges.

The median age of more than 3,500 infected children followed at U.S. clinical trial sites is now 15 years, and some patients are in their early 20s. The median age at death—9 years in 1994—had risen to 18 years by 2006, said Dr. Lynne Mofenson, chief of the Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md.

Although mortality has decreased, it remains 30 times higher for HIV-infected children than for uninfected children. There also has been a shift in causes of death, with fewer children dying from AIDS-related opportunistic infections and central nervous system disease and more succumbing to end-stage AIDS with multiple organ failure, or to sepsis or renal failure, Dr. Mofenson said at the 15th Conference on Retroviruses and Opportunistic Infections.

Aside from the disease itself, these young patients and their caregivers today face multiple challenges including drug resistance, complications of therapy, and issues related to adherence and mental health, Dr. Mofenson said.

Several studies have found an increase in primary drug resistance among newly infected infants.

For instance, data from New York State showed a 58% increase in resistance between 1998 and 2002, reaching 19%. This was primarily accounted for by mutations conferring resistance to the nonnucleoside reverse transcriptase inhibitors (J. Acquir. Immune Defic. Syndr. 2006;42:614–9).

Another series found resistance among 24% of infected children, with 10% being resistant to at least two classes of antiretroviral drugs, Dr. Mofenson said at the meeting, which was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.

Multidrug resistance is a particular problem for older children who were treated with monotherapy or dual therapy before triple therapy became the standard of care. Few choices remain for these children, particularly because many drugs available for adult patients have no pediatric formulations or dosing guidelines. "Without additional drugs, some HIV-infected children will run out of treatment options at a very early age," Dr. Mofenson said.

Investigations by the Pediatric Spectrum of Disease Project found that in 2001, 44% of children had already received two or more highly active antiretroviral treatment (HAART) regimens, and 3% had received five or more regimens. "This is only going to increase over time," she said.

These children increasingly face potentially severe complications of long-term therapy, particularly during puberty when as-yet unidentified physiologic changes appear to result in the development of hypercholesterolemia, which has been reported in up to 67% of children on therapy, and lipodystrophy, which has been reported in up to 47%.

Additionally, in one series, hyperinsulinemia was found in 60% of children, although insulin resistance was uncommon, she said.

Risk factors that have been identified for the development of these metabolic abnormalities include duration of antiretroviral therapy and the use of protease inhibitors and nucleoside reverse transcriptase inhibitors, particularly ritonavir, Dr. Mofenson said.

These findings further raise concerns about the potential for long-term cardiac complications. In one study from England, carotid intima thickness was significantly greater among 83 HIV-infected children, compared with a control group of 59 healthy children (Circulation 2005;112:103–9).

In that study, preatherosclerotic changes were particularly pronounced among patients treated with protease inhibitors. There may be roles for both HIV infection itself and intermittent antiretroviral therapy in the development of cardiovascular complications, she said.

Another area that is becoming important in pediatric HIV is mental health. "These children are born into families with multiple stresses including drug use and poverty," Dr. Mofenson said.

In one series of more than 300 children, the prevalence of attention-deficit/hyperactivity disorder was 24%, sixfold higher than in the general population of children, she said. Additionally, 29% had an anxiety disorder, which is a fourfold increase compared with healthy children, and 25% had clinical depression, which is a sevenfold increase.

"Finally, there is the overall challenge of HIV in adolescence," she said.

Many adolescents do not know they are infected, either because their perinatal infection has not been disclosed to them or they are at risk but have not been tested. And adherence to complex, lifelong therapy can present many difficulties, particularly in young patients who may appear well.

Infected adolescents also increasingly represent a high-risk population for HIV transmission. It has been estimated that 40%-60% of infected adolescents engage in unprotected sex, and there are high rates of substance abuse and smoking as well, she said.

Another disturbing finding that is emerging involves discrepancies in the use of HAART between children who were perinatally infected and those who were infected through risky sex.

"And of course HIV infection is a worldwide public health challenge that disproportionately affects children living in the poorest parts of the world. Infected children in high-resource settings such as the United States represent only 1% of the 2.3 million infected children worldwide," Dr. Mofenson commented.

NEW YORK — The greatest malignancy risk in patients receiving tumor necrosis factor antagonists is skin cancer, Dr. Jeffrey Greenberg said at a rheumatology meeting sponsored by New York University.

However, data conflict as to how great malignancy risk is overall for these patients.

Two years ago, a widely noted systematic review and meta-analysis found a threefold increased risk for malignancy in patients with rheumatoid arthritis (RA) treated with infliximab or adalimumab (JAMA 2006;295:2275–85). The meta-analysis included nine randomized, placebo-controlled trials, with 3,493 RA patients who received an active drug and 1,512 RA patients who received placebo.

In the anti-tumor necrosis factor (TNF) arms of this analysis, there were 10 lymphomas, nine nonmelanoma skin cancers, and 12 assorted other cancers, Dr. Greenberg said. "What was most interesting was the cancers that weren't found in the placebo arms—there were two basal cell cancers and one solid tumor—and that's it," he said, adding that in a group of 1,500 RA patients, 8–10 malignancies would be expected.

Aside from the lower-than-expected rates of malignancy in the placebo arms, the meta-analysis had other limitations, according to Dr. Greenberg of New York University, New York, who is chief scientific officer of the Consortium of Rheumatology Researchers of North America (CORRONA).

Among these limitations were the exclusion of etanercept; the association of higher-than-usual doses of infliximab with most malignancies; and the fact that the investigators used a per-patient analysis rather than person-years of drug exposure. Their approach assumes equal time exposure for placebo and the anti-TNF drugs, and four of the nine trials had higher placebo dropout rates.

"Patients on placebo who drop out are not followed for long periods of time looking for malignancies, so of course they are going to have fewer events," he added.

However, a different picture is emerging from observational studies and RA registries in the United States and Europe. In three Swedish registries—one prevalent cohort that included 53,067 patients, one incident cohort that included 3,703 patients, and one TNF antagonist-treated cohort of 4,160 patients—RA patients treated with TNF blockers had a tripled lymphoma risk, compared with the general population. However, after adjustment for sex, age, and disease duration, the lymphoma risk among TNF antagonist-treated patients was no higher than in the other RA cohorts (Ann. Rheum. Dis. 2005;64:1414–20).

In a report from the National Data Bank for Rheumatic Diseases, when RA patients were compared with the general population from the National Cancer Institute's Surveillance, Epidemiology, and End Results database, there was no increased rate of cancer overall, but lymphoma and melanoma were increased, with both having standardized incidence ratios of 1.7. However, only nonmelanoma skin cancer and melanoma were increased among patients on biologics, with odds ratios of 1.5 and 2.3, respectively. No other malignancy was significantly associated with biologic use (Arthritis Rheum. 2007;56:2886–95).

Data from the British Biologics Register also found no increase in malignancy rate, with an adjusted incidence rate ratio (IRR) of 0.7 for patients treated with anti-TNF agents, compared with those treated with nonbiologic disease-modifying antirheumatic drugs.

And in CORRONA, which includes 15,000 RA patients, the adjusted IRR for skin cancer was 2.10, whereas that for lymphoma was 0.74 and that for all cancers was 1.05, according to Dr. Greenberg.

"I think the take-home message of the observational studies is that it's the nonmelanoma skin cancers and possibly the melanomas that are the greatest concern, not the lymphomas," he said.

However, the discrepancy between the findings of the meta-analysis and those of the observational studies remains to be explained, Dr. Greenberg said.

"Frankly, I think they could not be more conflicting. It may be that there is a group of patients with subclinical neoplasms, including lymphomas, that any immunosuppressive or immunomodulatory treatment may unmask or accelerate. We probably should be screening for these cancers more aggressively regardless of treatment," he said.

NEW YORK — The greatest malignancy risk in patients receiving tumor necrosis factor antagonists is skin cancer, Dr. Jeffrey Greenberg said at a rheumatology meeting sponsored by New York University.

However, data conflict as to how great malignancy risk is overall for these patients.

Two years ago, a widely noted systematic review and meta-analysis found a threefold increased risk for malignancy in patients with rheumatoid arthritis (RA) treated with infliximab or adalimumab (JAMA 2006;295:2275–85). The meta-analysis included nine randomized, placebo-controlled trials, with 3,493 RA patients who received an active drug and 1,512 RA patients who received placebo.

In the anti-tumor necrosis factor (TNF) arms of this analysis, there were 10 lymphomas, nine nonmelanoma skin cancers, and 12 assorted other cancers, Dr. Greenberg said. "What was most interesting was the cancers that weren't found in the placebo arms—there were two basal cell cancers and one solid tumor—and that's it," he said, adding that in a group of 1,500 RA patients, 8–10 malignancies would be expected.

Aside from the lower-than-expected rates of malignancy in the placebo arms, the meta-analysis had other limitations, according to Dr. Greenberg of New York University, New York, who is chief scientific officer of the Consortium of Rheumatology Researchers of North America (CORRONA).

Among these limitations were the exclusion of etanercept; the association of higher-than-usual doses of infliximab with most malignancies; and the fact that the investigators used a per-patient analysis rather than person-years of drug exposure. Their approach assumes equal time exposure for placebo and the anti-TNF drugs, and four of the nine trials had higher placebo dropout rates.

"Patients on placebo who drop out are not followed for long periods of time looking for malignancies, so of course they are going to have fewer events," he added.

However, a different picture is emerging from observational studies and RA registries in the United States and Europe. In three Swedish registries—one prevalent cohort that included 53,067 patients, one incident cohort that included 3,703 patients, and one TNF antagonist-treated cohort of 4,160 patients—RA patients treated with TNF blockers had a tripled lymphoma risk, compared with the general population. However, after adjustment for sex, age, and disease duration, the lymphoma risk among TNF antagonist-treated patients was no higher than in the other RA cohorts (Ann. Rheum. Dis. 2005;64:1414–20).

In a report from the National Data Bank for Rheumatic Diseases, when RA patients were compared with the general population from the National Cancer Institute's Surveillance, Epidemiology, and End Results database, there was no increased rate of cancer overall, but lymphoma and melanoma were increased, with both having standardized incidence ratios of 1.7. However, only nonmelanoma skin cancer and melanoma were increased among patients on biologics, with odds ratios of 1.5 and 2.3, respectively. No other malignancy was significantly associated with biologic use (Arthritis Rheum. 2007;56:2886–95).

Data from the British Biologics Register also found no increase in malignancy rate, with an adjusted incidence rate ratio (IRR) of 0.7 for patients treated with anti-TNF agents, compared with those treated with nonbiologic disease-modifying antirheumatic drugs.

And in CORRONA, which includes 15,000 RA patients, the adjusted IRR for skin cancer was 2.10, whereas that for lymphoma was 0.74 and that for all cancers was 1.05, according to Dr. Greenberg.

"I think the take-home message of the observational studies is that it's the nonmelanoma skin cancers and possibly the melanomas that are the greatest concern, not the lymphomas," he said.

However, the discrepancy between the findings of the meta-analysis and those of the observational studies remains to be explained, Dr. Greenberg said.

"Frankly, I think they could not be more conflicting. It may be that there is a group of patients with subclinical neoplasms, including lymphomas, that any immunosuppressive or immunomodulatory treatment may unmask or accelerate. We probably should be screening for these cancers more aggressively regardless of treatment," he said.

NEW YORK — The greatest malignancy risk in patients receiving tumor necrosis factor antagonists is skin cancer, Dr. Jeffrey Greenberg said at a rheumatology meeting sponsored by New York University.

However, data conflict as to how great malignancy risk is overall for these patients.

Two years ago, a widely noted systematic review and meta-analysis found a threefold increased risk for malignancy in patients with rheumatoid arthritis (RA) treated with infliximab or adalimumab (JAMA 2006;295:2275–85). The meta-analysis included nine randomized, placebo-controlled trials, with 3,493 RA patients who received an active drug and 1,512 RA patients who received placebo.

In the anti-tumor necrosis factor (TNF) arms of this analysis, there were 10 lymphomas, nine nonmelanoma skin cancers, and 12 assorted other cancers, Dr. Greenberg said. "What was most interesting was the cancers that weren't found in the placebo arms—there were two basal cell cancers and one solid tumor—and that's it," he said, adding that in a group of 1,500 RA patients, 8–10 malignancies would be expected.

Aside from the lower-than-expected rates of malignancy in the placebo arms, the meta-analysis had other limitations, according to Dr. Greenberg of New York University, New York, who is chief scientific officer of the Consortium of Rheumatology Researchers of North America (CORRONA).

Among these limitations were the exclusion of etanercept; the association of higher-than-usual doses of infliximab with most malignancies; and the fact that the investigators used a per-patient analysis rather than person-years of drug exposure. Their approach assumes equal time exposure for placebo and the anti-TNF drugs, and four of the nine trials had higher placebo dropout rates.

"Patients on placebo who drop out are not followed for long periods of time looking for malignancies, so of course they are going to have fewer events," he added.

However, a different picture is emerging from observational studies and RA registries in the United States and Europe. In three Swedish registries—one prevalent cohort that included 53,067 patients, one incident cohort that included 3,703 patients, and one TNF antagonist-treated cohort of 4,160 patients—RA patients treated with TNF blockers had a tripled lymphoma risk, compared with the general population. However, after adjustment for sex, age, and disease duration, the lymphoma risk among TNF antagonist-treated patients was no higher than in the other RA cohorts (Ann. Rheum. Dis. 2005;64:1414–20).

In a report from the National Data Bank for Rheumatic Diseases, when RA patients were compared with the general population from the National Cancer Institute's Surveillance, Epidemiology, and End Results database, there was no increased rate of cancer overall, but lymphoma and melanoma were increased, with both having standardized incidence ratios of 1.7. However, only nonmelanoma skin cancer and melanoma were increased among patients on biologics, with odds ratios of 1.5 and 2.3, respectively. No other malignancy was significantly associated with biologic use (Arthritis Rheum. 2007;56:2886–95).

Data from the British Biologics Register also found no increase in malignancy rate, with an adjusted incidence rate ratio (IRR) of 0.7 for patients treated with anti-TNF agents, compared with those treated with nonbiologic disease-modifying antirheumatic drugs.

And in CORRONA, which includes 15,000 RA patients, the adjusted IRR for skin cancer was 2.10, whereas that for lymphoma was 0.74 and that for all cancers was 1.05, according to Dr. Greenberg.

"I think the take-home message of the observational studies is that it's the nonmelanoma skin cancers and possibly the melanomas that are the greatest concern, not the lymphomas," he said.

However, the discrepancy between the findings of the meta-analysis and those of the observational studies remains to be explained, Dr. Greenberg said.

"Frankly, I think they could not be more conflicting. It may be that there is a group of patients with subclinical neoplasms, including lymphomas, that any immunosuppressive or immunomodulatory treatment may unmask or accelerate. We probably should be screening for these cancers more aggressively regardless of treatment," he said.

TORONTO — The number of pregnant women entering court-mandated substance abuse programs has increased in the years since the advent of the crack cocaine epidemic, Dr. Mishka Terplan said at the annual conference of the American Society of Addiction Medicine.

Among the more than 6 million women admitted for drug and alcohol abuse treatment between the years 1994 and 2005, about 220,000 were pregnant. By the end of that period, the annual number of pregnant women entering treatment via the criminal justice system had risen 30%, according to an analysis of data from the Treatment Episode Data Set.

In undertaking an analysis of women treated with “compassionate coercion,” for which Dr. Terplan was given the society's young investigator award, he presumed he would find disparities between pregnant women who enter treatment via the criminal justice system and those who enter treatment voluntarily.

The concept of coercive treatment is not new. Therapeutic prison farms were established by the U.S. Public Health Service in the 1930s, but criminal justice referrals for substance abuse in general have increased across all segments of the population in recent years. The proportional increase has been greater for women than men, and even greater for pregnant women. In a speech on the occasion of the unveiling of the 2006 National Drug Control Strategy, President Bush said, “Getting people into treatment will require us to create a new climate of compassionate coercion, which begins with family, friends, employers, and the community, and uses the criminal justice system.”

Dr. Terplan said that he expected to uncover disparities in terms of the unequal application of a system of social control, and that women of color, those who use hard drugs, those with psychiatric problems, and those with less education and of lower socioeconomic class would preferentially enter mandatory rather than voluntary treatment.

It turned out that black women were only half as likely to be referred through the criminal justice system as were white or Hispanic women, and women with psychiatric diagnoses other than substance abuse also were less likely to enter treatment via the criminal justice system. “This was probably because they are already hooked up with care for their mental illness,” he said.

Pregnant women who enter court-ordered treatment after an event such as an arrest for driving while intoxicated were likely to be in their 20s or 30s, and about half had at least a high school education.

“A whopping 87% were unemployed, 46% were receiving Medicaid, 41% said they had no insurance, and 6% said they had private insurance,” said Dr. Terplan of the department of obstetrics and gynecology, University of Chicago.

The analysis also showed that there had been a shift in the substances being abused over the time period of the study. Alcohol and cocaine were the primary substances reported in 1994, but by 2005 use of methamphetamine and marijuana were most likely to result in mandatory admission, with adjusted odds ratios of 1.9 and 1.5, respectively.

Another shift over time has been an increase in the number of Hispanic women entering court-ordered treatment. In 1994 they were 20% less likely than white women to enter treatment via the criminal justice system, but by 2005 they were just as likely to enter treatment via criminal justice as white women.

“No other group of mothers lays claim to the unspeakable in quite the same way as pregnant drug users,” he said. “Even when they make substantial strides during pregnancy to reduce the risk of drug use to their babies, the image of the ideal mythical mother looms over their shoulders and over the shoulders of people who have the power to determine their futures,” Dr. Terplan said.

TORONTO — The number of pregnant women entering court-mandated substance abuse programs has increased in the years since the advent of the crack cocaine epidemic, Dr. Mishka Terplan said at the annual conference of the American Society of Addiction Medicine.

Among the more than 6 million women admitted for drug and alcohol abuse treatment between the years 1994 and 2005, about 220,000 were pregnant. By the end of that period, the annual number of pregnant women entering treatment via the criminal justice system had risen 30%, according to an analysis of data from the Treatment Episode Data Set.

In undertaking an analysis of women treated with “compassionate coercion,” for which Dr. Terplan was given the society's young investigator award, he presumed he would find disparities between pregnant women who enter treatment via the criminal justice system and those who enter treatment voluntarily.

The concept of coercive treatment is not new. Therapeutic prison farms were established by the U.S. Public Health Service in the 1930s, but criminal justice referrals for substance abuse in general have increased across all segments of the population in recent years. The proportional increase has been greater for women than men, and even greater for pregnant women. In a speech on the occasion of the unveiling of the 2006 National Drug Control Strategy, President Bush said, “Getting people into treatment will require us to create a new climate of compassionate coercion, which begins with family, friends, employers, and the community, and uses the criminal justice system.”

Dr. Terplan said that he expected to uncover disparities in terms of the unequal application of a system of social control, and that women of color, those who use hard drugs, those with psychiatric problems, and those with less education and of lower socioeconomic class would preferentially enter mandatory rather than voluntary treatment.

It turned out that black women were only half as likely to be referred through the criminal justice system as were white or Hispanic women, and women with psychiatric diagnoses other than substance abuse also were less likely to enter treatment via the criminal justice system. “This was probably because they are already hooked up with care for their mental illness,” he said.

Pregnant women who enter court-ordered treatment after an event such as an arrest for driving while intoxicated were likely to be in their 20s or 30s, and about half had at least a high school education.

“A whopping 87% were unemployed, 46% were receiving Medicaid, 41% said they had no insurance, and 6% said they had private insurance,” said Dr. Terplan of the department of obstetrics and gynecology, University of Chicago.

The analysis also showed that there had been a shift in the substances being abused over the time period of the study. Alcohol and cocaine were the primary substances reported in 1994, but by 2005 use of methamphetamine and marijuana were most likely to result in mandatory admission, with adjusted odds ratios of 1.9 and 1.5, respectively.

Another shift over time has been an increase in the number of Hispanic women entering court-ordered treatment. In 1994 they were 20% less likely than white women to enter treatment via the criminal justice system, but by 2005 they were just as likely to enter treatment via criminal justice as white women.

“No other group of mothers lays claim to the unspeakable in quite the same way as pregnant drug users,” he said. “Even when they make substantial strides during pregnancy to reduce the risk of drug use to their babies, the image of the ideal mythical mother looms over their shoulders and over the shoulders of people who have the power to determine their futures,” Dr. Terplan said.

TORONTO — The number of pregnant women entering court-mandated substance abuse programs has increased in the years since the advent of the crack cocaine epidemic, Dr. Mishka Terplan said at the annual conference of the American Society of Addiction Medicine.

Among the more than 6 million women admitted for drug and alcohol abuse treatment between the years 1994 and 2005, about 220,000 were pregnant. By the end of that period, the annual number of pregnant women entering treatment via the criminal justice system had risen 30%, according to an analysis of data from the Treatment Episode Data Set.

In undertaking an analysis of women treated with “compassionate coercion,” for which Dr. Terplan was given the society's young investigator award, he presumed he would find disparities between pregnant women who enter treatment via the criminal justice system and those who enter treatment voluntarily.

The concept of coercive treatment is not new. Therapeutic prison farms were established by the U.S. Public Health Service in the 1930s, but criminal justice referrals for substance abuse in general have increased across all segments of the population in recent years. The proportional increase has been greater for women than men, and even greater for pregnant women. In a speech on the occasion of the unveiling of the 2006 National Drug Control Strategy, President Bush said, “Getting people into treatment will require us to create a new climate of compassionate coercion, which begins with family, friends, employers, and the community, and uses the criminal justice system.”

Dr. Terplan said that he expected to uncover disparities in terms of the unequal application of a system of social control, and that women of color, those who use hard drugs, those with psychiatric problems, and those with less education and of lower socioeconomic class would preferentially enter mandatory rather than voluntary treatment.

It turned out that black women were only half as likely to be referred through the criminal justice system as were white or Hispanic women, and women with psychiatric diagnoses other than substance abuse also were less likely to enter treatment via the criminal justice system. “This was probably because they are already hooked up with care for their mental illness,” he said.

Pregnant women who enter court-ordered treatment after an event such as an arrest for driving while intoxicated were likely to be in their 20s or 30s, and about half had at least a high school education.

“A whopping 87% were unemployed, 46% were receiving Medicaid, 41% said they had no insurance, and 6% said they had private insurance,” said Dr. Terplan of the department of obstetrics and gynecology, University of Chicago.

The analysis also showed that there had been a shift in the substances being abused over the time period of the study. Alcohol and cocaine were the primary substances reported in 1994, but by 2005 use of methamphetamine and marijuana were most likely to result in mandatory admission, with adjusted odds ratios of 1.9 and 1.5, respectively.

Another shift over time has been an increase in the number of Hispanic women entering court-ordered treatment. In 1994 they were 20% less likely than white women to enter treatment via the criminal justice system, but by 2005 they were just as likely to enter treatment via criminal justice as white women.

“No other group of mothers lays claim to the unspeakable in quite the same way as pregnant drug users,” he said. “Even when they make substantial strides during pregnancy to reduce the risk of drug use to their babies, the image of the ideal mythical mother looms over their shoulders and over the shoulders of people who have the power to determine their futures,” Dr. Terplan said.

NEW YORK — The contemporary use of minocycline for acne and hydralazine for heart failure is expanding the spectrum of drug-induced lupus, and physicians need to heighten their index of suspicion for these as well as for other types of drug-induced lupus.

Minocycline-induced lupus was first reported in the early 1990s, and more than 250 cases have now been reported to the World Health Organization. There is a 5:1 female- to-male predominance. The clinical features include fever, morning stiffness, myalgias, polyarthralgias, and symmetric arthritis.

It is also characterized by large vessel vasculitis, and in more than 60% of patients, antineutrophil cytoplasmic antibodies are present and antihistone antibodies are not. This is in contrast to “classic” drug-induced lupus, in which antihistone antibodies are prominent.

Other autoantibodies also can be seen in minocycline-induced lupus, including antinuclear antibody (ANA) and anti-double-stranded DNA, said Dr. Andrew G. Franks Jr., of the department of dermatology at New York University Medical Center, New York.

“The likelihood of developing a lupus-like syndrome is elevated 8.5-fold with minocycline, so many clinicians are moving away from using minocycline for acne and rosacea and switching to doxycycline, which doesn't have this effect. I haven't used minocycline for 5 years,” he said.

Hydralazine, which had fallen out of favor as an antihypertensive, has regained popularity as part of combination therapy for heart failure in African Americans following the benefits seen in the African-American Heart Failure Trial (N. Engl. J. Med. 2004;351:2049-57).

Younger physicians might not be familiar with the association of hydralazine with drug-induced lupus, Dr. Franks said. The drug is one of the “big five” causes of classic drug-induced lupus, along with procainamide, isoniazid, quinidine, and phenytoin, but more than 100 drugs have been implicated in the 15,000-20,000 cases reported in the United States annually.

Classic drug-induced lupus is characterized by flulike symptoms and significant musculoskeletal involvement, with most patients being ANA and antihistone antibody positive. “Patients starting hydralazine or any drug in the big five should have a baseline test for ANA, although that is somewhat controversial,” Dr. Franks said.

The third main type of drug-induced lupus is subacute cutaneous lupus erythematosus (SCLE), which also is associated with an ever-widening variety of agents, including the thiazide diuretics, antifungals, calcium channel blockers, and ACE inhibitors. There also have been reports involving statins, leflunomide, and tumor necrosis factor inhibitors.

Clinically, SCLE can be difficult to sort out, he said, with targetoid lesions mixed with papulosquamous or annular lesions. The presentation can also resemble erythema multiforme or toxic epidermal necrolysis, with disadhesion of the epidermal layer and sloughing of the skin. “Patients with this subtype have very high morbidity and mortality.”

An audience member asked what happens when the offending drug is withdrawn. Dr. Franks explained that the situation is different from that with an allergic reaction, where the process should resolve in a week or two. “It can sometimes take months for this to remit, and some patients require additional therapy, but 95% of patients ultimately do remit,” he said at a rheumatology meeting sponsored by New York University.

Another audience member asked what to do if a patient's baseline ANA is positive, and whether that represents a contraindication to hydralazine therapy, for example. “That is why I said doing a baseline ANA is controversial,” Dr. Franks replied. “A number of groups do not suggest doing this, but clearly autoantibodies and a loss of tolerance precede the development of lupus, so one could be prudent and repeat the ANA yearly and see if it turns positive and the titer starts rising.”

No single mechanism has been identified to explain the variety of drugs associated with drug-induced lupus or the varied clinical and laboratory manifestations. Hypotheses include the possibility that the drugs can act as haptens or antigens that drive an immune response, or as immune system modulators that permit development of self-directed responses (Semin. Arthritis Rheum. 2007 Dec. 31 [doi:10.1016/j.sem arthrit.2007. 10.001]).

Dr. Franks reported having no financial relationships to disclose.

The likelihood of developing a lupus-like syndrome is elevated 8.5-fold with minocycline. DR. FRANKS

NEW YORK — The contemporary use of minocycline for acne and hydralazine for heart failure is expanding the spectrum of drug-induced lupus, and physicians need to heighten their index of suspicion for these as well as for other types of drug-induced lupus.

Minocycline-induced lupus was first reported in the early 1990s, and more than 250 cases have now been reported to the World Health Organization. There is a 5:1 female- to-male predominance. The clinical features include fever, morning stiffness, myalgias, polyarthralgias, and symmetric arthritis.

It is also characterized by large vessel vasculitis, and in more than 60% of patients, antineutrophil cytoplasmic antibodies are present and antihistone antibodies are not. This is in contrast to “classic” drug-induced lupus, in which antihistone antibodies are prominent.

Other autoantibodies also can be seen in minocycline-induced lupus, including antinuclear antibody (ANA) and anti-double-stranded DNA, said Dr. Andrew G. Franks Jr., of the department of dermatology at New York University Medical Center, New York.

“The likelihood of developing a lupus-like syndrome is elevated 8.5-fold with minocycline, so many clinicians are moving away from using minocycline for acne and rosacea and switching to doxycycline, which doesn't have this effect. I haven't used minocycline for 5 years,” he said.

Hydralazine, which had fallen out of favor as an antihypertensive, has regained popularity as part of combination therapy for heart failure in African Americans following the benefits seen in the African-American Heart Failure Trial (N. Engl. J. Med. 2004;351:2049-57).

Younger physicians might not be familiar with the association of hydralazine with drug-induced lupus, Dr. Franks said. The drug is one of the “big five” causes of classic drug-induced lupus, along with procainamide, isoniazid, quinidine, and phenytoin, but more than 100 drugs have been implicated in the 15,000-20,000 cases reported in the United States annually.

Classic drug-induced lupus is characterized by flulike symptoms and significant musculoskeletal involvement, with most patients being ANA and antihistone antibody positive. “Patients starting hydralazine or any drug in the big five should have a baseline test for ANA, although that is somewhat controversial,” Dr. Franks said.

The third main type of drug-induced lupus is subacute cutaneous lupus erythematosus (SCLE), which also is associated with an ever-widening variety of agents, including the thiazide diuretics, antifungals, calcium channel blockers, and ACE inhibitors. There also have been reports involving statins, leflunomide, and tumor necrosis factor inhibitors.

Clinically, SCLE can be difficult to sort out, he said, with targetoid lesions mixed with papulosquamous or annular lesions. The presentation can also resemble erythema multiforme or toxic epidermal necrolysis, with disadhesion of the epidermal layer and sloughing of the skin. “Patients with this subtype have very high morbidity and mortality.”

An audience member asked what happens when the offending drug is withdrawn. Dr. Franks explained that the situation is different from that with an allergic reaction, where the process should resolve in a week or two. “It can sometimes take months for this to remit, and some patients require additional therapy, but 95% of patients ultimately do remit,” he said at a rheumatology meeting sponsored by New York University.

Another audience member asked what to do if a patient's baseline ANA is positive, and whether that represents a contraindication to hydralazine therapy, for example. “That is why I said doing a baseline ANA is controversial,” Dr. Franks replied. “A number of groups do not suggest doing this, but clearly autoantibodies and a loss of tolerance precede the development of lupus, so one could be prudent and repeat the ANA yearly and see if it turns positive and the titer starts rising.”

No single mechanism has been identified to explain the variety of drugs associated with drug-induced lupus or the varied clinical and laboratory manifestations. Hypotheses include the possibility that the drugs can act as haptens or antigens that drive an immune response, or as immune system modulators that permit development of self-directed responses (Semin. Arthritis Rheum. 2007 Dec. 31 [doi:10.1016/j.sem arthrit.2007. 10.001]).

Dr. Franks reported having no financial relationships to disclose.

The likelihood of developing a lupus-like syndrome is elevated 8.5-fold with minocycline. DR. FRANKS

NEW YORK — The contemporary use of minocycline for acne and hydralazine for heart failure is expanding the spectrum of drug-induced lupus, and physicians need to heighten their index of suspicion for these as well as for other types of drug-induced lupus.

Minocycline-induced lupus was first reported in the early 1990s, and more than 250 cases have now been reported to the World Health Organization. There is a 5:1 female- to-male predominance. The clinical features include fever, morning stiffness, myalgias, polyarthralgias, and symmetric arthritis.

It is also characterized by large vessel vasculitis, and in more than 60% of patients, antineutrophil cytoplasmic antibodies are present and antihistone antibodies are not. This is in contrast to “classic” drug-induced lupus, in which antihistone antibodies are prominent.

Other autoantibodies also can be seen in minocycline-induced lupus, including antinuclear antibody (ANA) and anti-double-stranded DNA, said Dr. Andrew G. Franks Jr., of the department of dermatology at New York University Medical Center, New York.

“The likelihood of developing a lupus-like syndrome is elevated 8.5-fold with minocycline, so many clinicians are moving away from using minocycline for acne and rosacea and switching to doxycycline, which doesn't have this effect. I haven't used minocycline for 5 years,” he said.

Hydralazine, which had fallen out of favor as an antihypertensive, has regained popularity as part of combination therapy for heart failure in African Americans following the benefits seen in the African-American Heart Failure Trial (N. Engl. J. Med. 2004;351:2049-57).

Younger physicians might not be familiar with the association of hydralazine with drug-induced lupus, Dr. Franks said. The drug is one of the “big five” causes of classic drug-induced lupus, along with procainamide, isoniazid, quinidine, and phenytoin, but more than 100 drugs have been implicated in the 15,000-20,000 cases reported in the United States annually.

Classic drug-induced lupus is characterized by flulike symptoms and significant musculoskeletal involvement, with most patients being ANA and antihistone antibody positive. “Patients starting hydralazine or any drug in the big five should have a baseline test for ANA, although that is somewhat controversial,” Dr. Franks said.

The third main type of drug-induced lupus is subacute cutaneous lupus erythematosus (SCLE), which also is associated with an ever-widening variety of agents, including the thiazide diuretics, antifungals, calcium channel blockers, and ACE inhibitors. There also have been reports involving statins, leflunomide, and tumor necrosis factor inhibitors.

Clinically, SCLE can be difficult to sort out, he said, with targetoid lesions mixed with papulosquamous or annular lesions. The presentation can also resemble erythema multiforme or toxic epidermal necrolysis, with disadhesion of the epidermal layer and sloughing of the skin. “Patients with this subtype have very high morbidity and mortality.”

An audience member asked what happens when the offending drug is withdrawn. Dr. Franks explained that the situation is different from that with an allergic reaction, where the process should resolve in a week or two. “It can sometimes take months for this to remit, and some patients require additional therapy, but 95% of patients ultimately do remit,” he said at a rheumatology meeting sponsored by New York University.

Another audience member asked what to do if a patient's baseline ANA is positive, and whether that represents a contraindication to hydralazine therapy, for example. “That is why I said doing a baseline ANA is controversial,” Dr. Franks replied. “A number of groups do not suggest doing this, but clearly autoantibodies and a loss of tolerance precede the development of lupus, so one could be prudent and repeat the ANA yearly and see if it turns positive and the titer starts rising.”

No single mechanism has been identified to explain the variety of drugs associated with drug-induced lupus or the varied clinical and laboratory manifestations. Hypotheses include the possibility that the drugs can act as haptens or antigens that drive an immune response, or as immune system modulators that permit development of self-directed responses (Semin. Arthritis Rheum. 2007 Dec. 31 [doi:10.1016/j.sem arthrit.2007. 10.001]).

Dr. Franks reported having no financial relationships to disclose.

The likelihood of developing a lupus-like syndrome is elevated 8.5-fold with minocycline. DR. FRANKS

Adolescents who had televisions in their bedrooms had less physical activity, poorer dietary habits, and worse school performance than did adolescents without bedroom televisions, investigators from the University of Minnesota School of Public Health, Minneapolis, reported.

Daheia J. Barr-Anderson, Ph.D., and colleagues found that nearly two-thirds of adolescents aged 15–18 years had a television (TV) in their bedrooms, despite the fact that the American Academy of Pediatrics recommends against this.

A total of 781 ethnically and socioeconomically diverse teens participated in Project Eating Among Teens (EAT), answering questions about their TV viewing, dietary and exercise habits, and school performance.

Analysis of the data revealed that factors associated with the presence of a bedroom TV included gender, race/ethnicity, and socioeconomic status. The prevalence of a TV in the bedroom among boys was 68%, compared with 58% among girls, and was highest among black youths at 82%, and lowest among Asians at 39%.

Among those from households with highest socioeconomic status, the prevalence was 39%, compared with 61% among those from households with low socioeconomic status (Pediatrics 2008;121:718–24).

Girls with bedroom TVs spent less time in vigorous activity (4.2 hours/week vs. 5.2 hours/week, spent more time watching TV (20.7 hours/week vs. 15.2 hours/week), and had lower vegetable intake (1.7 servings/day vs. 2 servings/day) and higher sweetened beverage consumption (1.2 servings/day vs. 1 serving/day) than did girls without bedroom TVs. They also participated in fewer family meals (2.9/week vs. 3.7/week).

Boys with bedroom TVs spent more time overall watching TV (22.2 hours/week vs. 18.2 hours/week), had lower fruit intake (1.7 servings/day vs. 2.2 servings/day), and participated in fewer family meals than did those without TVs (2.9/week vs. 3.6/week). They also had lower grade point averages (2.6 compared to 2.9). These differences were all statistically significant.

The investigators suggested that “refraining from placing a TV in adolescents' bedrooms may be a first step in helping to decrease screen time and subsequent poor behaviors associated with increased TV watching.”

Girls with bedroom TVs spent less time in vigorous activity and ate fewer vegetables. ©amaxim/Fotolia.com

Adolescents who had televisions in their bedrooms had less physical activity, poorer dietary habits, and worse school performance than did adolescents without bedroom televisions, investigators from the University of Minnesota School of Public Health, Minneapolis, reported.

Daheia J. Barr-Anderson, Ph.D., and colleagues found that nearly two-thirds of adolescents aged 15–18 years had a television (TV) in their bedrooms, despite the fact that the American Academy of Pediatrics recommends against this.

A total of 781 ethnically and socioeconomically diverse teens participated in Project Eating Among Teens (EAT), answering questions about their TV viewing, dietary and exercise habits, and school performance.

Analysis of the data revealed that factors associated with the presence of a bedroom TV included gender, race/ethnicity, and socioeconomic status. The prevalence of a TV in the bedroom among boys was 68%, compared with 58% among girls, and was highest among black youths at 82%, and lowest among Asians at 39%.

Among those from households with highest socioeconomic status, the prevalence was 39%, compared with 61% among those from households with low socioeconomic status (Pediatrics 2008;121:718–24).

Girls with bedroom TVs spent less time in vigorous activity (4.2 hours/week vs. 5.2 hours/week, spent more time watching TV (20.7 hours/week vs. 15.2 hours/week), and had lower vegetable intake (1.7 servings/day vs. 2 servings/day) and higher sweetened beverage consumption (1.2 servings/day vs. 1 serving/day) than did girls without bedroom TVs. They also participated in fewer family meals (2.9/week vs. 3.7/week).

Boys with bedroom TVs spent more time overall watching TV (22.2 hours/week vs. 18.2 hours/week), had lower fruit intake (1.7 servings/day vs. 2.2 servings/day), and participated in fewer family meals than did those without TVs (2.9/week vs. 3.6/week). They also had lower grade point averages (2.6 compared to 2.9). These differences were all statistically significant.

The investigators suggested that “refraining from placing a TV in adolescents' bedrooms may be a first step in helping to decrease screen time and subsequent poor behaviors associated with increased TV watching.”

Girls with bedroom TVs spent less time in vigorous activity and ate fewer vegetables. ©amaxim/Fotolia.com

Adolescents who had televisions in their bedrooms had less physical activity, poorer dietary habits, and worse school performance than did adolescents without bedroom televisions, investigators from the University of Minnesota School of Public Health, Minneapolis, reported.

Daheia J. Barr-Anderson, Ph.D., and colleagues found that nearly two-thirds of adolescents aged 15–18 years had a television (TV) in their bedrooms, despite the fact that the American Academy of Pediatrics recommends against this.

A total of 781 ethnically and socioeconomically diverse teens participated in Project Eating Among Teens (EAT), answering questions about their TV viewing, dietary and exercise habits, and school performance.

Analysis of the data revealed that factors associated with the presence of a bedroom TV included gender, race/ethnicity, and socioeconomic status. The prevalence of a TV in the bedroom among boys was 68%, compared with 58% among girls, and was highest among black youths at 82%, and lowest among Asians at 39%.

Among those from households with highest socioeconomic status, the prevalence was 39%, compared with 61% among those from households with low socioeconomic status (Pediatrics 2008;121:718–24).

Girls with bedroom TVs spent less time in vigorous activity (4.2 hours/week vs. 5.2 hours/week, spent more time watching TV (20.7 hours/week vs. 15.2 hours/week), and had lower vegetable intake (1.7 servings/day vs. 2 servings/day) and higher sweetened beverage consumption (1.2 servings/day vs. 1 serving/day) than did girls without bedroom TVs. They also participated in fewer family meals (2.9/week vs. 3.7/week).

Boys with bedroom TVs spent more time overall watching TV (22.2 hours/week vs. 18.2 hours/week), had lower fruit intake (1.7 servings/day vs. 2.2 servings/day), and participated in fewer family meals than did those without TVs (2.9/week vs. 3.6/week). They also had lower grade point averages (2.6 compared to 2.9). These differences were all statistically significant.

The investigators suggested that “refraining from placing a TV in adolescents' bedrooms may be a first step in helping to decrease screen time and subsequent poor behaviors associated with increased TV watching.”

Girls with bedroom TVs spent less time in vigorous activity and ate fewer vegetables. ©amaxim/Fotolia.com

NEW YORK — Short-term moderate-dose corticosteroids might avert serious flares in clinically stable lupus patients who show elevations of certain serologic disease markers, Dr. H. Michael Belmont said at a rheumatology meeting sponsored by New York University.

“Our hypothesis was that if we had a sufficiently reliable biomarker, we could predict in a reasonable way a lupus flare and intervene with an appropriate anti-inflammatory,” said Dr. Belmont, director of the lupus clinic at Bellevue Hospital and with the department of medicine, New York University, New York.

Analysis of pooled samples from 496 women enrolled in the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) trial showed increases in anti-double-stranded DNA (anti-dsDNA) antibodies and the complement degradation product C3a predicted severe disease flare in patients with clinically quiescent disease, he said.

Based on this finding, a prospective trial was undertaken to determine whether preemptive therapy could avert severe flares and the damage that can result.

A total of 180 patients with stable disease were enrolled. Patients were eligible if anti-dsDNA antibodies had been present within the past 2 years, they required daily prednisone doses below 15 mg, had no active infection, and had been on a stable drug regimen for 2 months.

They were evaluated monthly for 12–18 months with measurements of various analytes including C3, C4, CH50, C3a, and anti-dsDNA. Clinical status was assessed according to the SELENA version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and physician global assessment.

At any point in the trial, clinically stable patients who had increases in anti-dsDNA antibodies of 25% or more and of C3a by 50% since the previous visit were randomized to placebo or an increase in prednisone to 30 mg/day for 2 weeks. The dose was then tapered to 20 mg/day for 1 week and to 10 mg/day for an additional week.

A total of 41 patients flared and were randomized, 21 to prednisone and 20 to placebo. There were no statistically significant differences between the two groups; 90% were female, mean age was 35 years, disease duration averaged 7 years, and mean SLEDAI was 4.2. Mild to moderate flares were seen in two patients receiving placebo and in four receiving prednisone within 90 days of randomization. “However, the major finding was that of 21 patients who received prednisone, none experienced a severe flare, while among the 20 who received placebo, 6 had severe flares, which was a highly significant difference,” Dr. Belmont said.

Analysis revealed that at 1 month, there were three renal and one central nervous system flare, and at 2 months, one patient developed pyoderma gangrenosum and pancytopenia. At 3 months, there was an additional case of pleural effusion with fever and dyspnea.

Prednisone also led to significant benefits on SLEDAI, anti-dsDNA, C4, and C3a after 1 month.

“What price did patients pay for receiving the preemptive prednisone? It turned out that there was a slightly greater absolute number of adverse events in the placebo group, at 13, compared with 10 events in the prednisone group,” he said. So the short-term increase in prednisone did not result in an increased risk of adverse events, and despite the fact that patients randomized to prednisone initially had greater exposure to the drug, the cumulative exposure was greater in those who flared. Three patients who flared also required initiation or increase in cytotoxic therapy.

“Consideration should be given to preemptive use of short-term moderate-dose corticosteroids in clinically stable, serologically active lupus patients to prevent severe flares and prolonged exposure to high-dose corticosteroids and additional cytotoxic agents,” he said.

NEW YORK — Short-term moderate-dose corticosteroids might avert serious flares in clinically stable lupus patients who show elevations of certain serologic disease markers, Dr. H. Michael Belmont said at a rheumatology meeting sponsored by New York University.

“Our hypothesis was that if we had a sufficiently reliable biomarker, we could predict in a reasonable way a lupus flare and intervene with an appropriate anti-inflammatory,” said Dr. Belmont, director of the lupus clinic at Bellevue Hospital and with the department of medicine, New York University, New York.

Analysis of pooled samples from 496 women enrolled in the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) trial showed increases in anti-double-stranded DNA (anti-dsDNA) antibodies and the complement degradation product C3a predicted severe disease flare in patients with clinically quiescent disease, he said.

Based on this finding, a prospective trial was undertaken to determine whether preemptive therapy could avert severe flares and the damage that can result.

A total of 180 patients with stable disease were enrolled. Patients were eligible if anti-dsDNA antibodies had been present within the past 2 years, they required daily prednisone doses below 15 mg, had no active infection, and had been on a stable drug regimen for 2 months.

They were evaluated monthly for 12–18 months with measurements of various analytes including C3, C4, CH50, C3a, and anti-dsDNA. Clinical status was assessed according to the SELENA version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and physician global assessment.

At any point in the trial, clinically stable patients who had increases in anti-dsDNA antibodies of 25% or more and of C3a by 50% since the previous visit were randomized to placebo or an increase in prednisone to 30 mg/day for 2 weeks. The dose was then tapered to 20 mg/day for 1 week and to 10 mg/day for an additional week.

A total of 41 patients flared and were randomized, 21 to prednisone and 20 to placebo. There were no statistically significant differences between the two groups; 90% were female, mean age was 35 years, disease duration averaged 7 years, and mean SLEDAI was 4.2. Mild to moderate flares were seen in two patients receiving placebo and in four receiving prednisone within 90 days of randomization. “However, the major finding was that of 21 patients who received prednisone, none experienced a severe flare, while among the 20 who received placebo, 6 had severe flares, which was a highly significant difference,” Dr. Belmont said.

Analysis revealed that at 1 month, there were three renal and one central nervous system flare, and at 2 months, one patient developed pyoderma gangrenosum and pancytopenia. At 3 months, there was an additional case of pleural effusion with fever and dyspnea.

Prednisone also led to significant benefits on SLEDAI, anti-dsDNA, C4, and C3a after 1 month.

“What price did patients pay for receiving the preemptive prednisone? It turned out that there was a slightly greater absolute number of adverse events in the placebo group, at 13, compared with 10 events in the prednisone group,” he said. So the short-term increase in prednisone did not result in an increased risk of adverse events, and despite the fact that patients randomized to prednisone initially had greater exposure to the drug, the cumulative exposure was greater in those who flared. Three patients who flared also required initiation or increase in cytotoxic therapy.

“Consideration should be given to preemptive use of short-term moderate-dose corticosteroids in clinically stable, serologically active lupus patients to prevent severe flares and prolonged exposure to high-dose corticosteroids and additional cytotoxic agents,” he said.

NEW YORK — Short-term moderate-dose corticosteroids might avert serious flares in clinically stable lupus patients who show elevations of certain serologic disease markers, Dr. H. Michael Belmont said at a rheumatology meeting sponsored by New York University.

“Our hypothesis was that if we had a sufficiently reliable biomarker, we could predict in a reasonable way a lupus flare and intervene with an appropriate anti-inflammatory,” said Dr. Belmont, director of the lupus clinic at Bellevue Hospital and with the department of medicine, New York University, New York.

Analysis of pooled samples from 496 women enrolled in the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) trial showed increases in anti-double-stranded DNA (anti-dsDNA) antibodies and the complement degradation product C3a predicted severe disease flare in patients with clinically quiescent disease, he said.

Based on this finding, a prospective trial was undertaken to determine whether preemptive therapy could avert severe flares and the damage that can result.

A total of 180 patients with stable disease were enrolled. Patients were eligible if anti-dsDNA antibodies had been present within the past 2 years, they required daily prednisone doses below 15 mg, had no active infection, and had been on a stable drug regimen for 2 months.

They were evaluated monthly for 12–18 months with measurements of various analytes including C3, C4, CH50, C3a, and anti-dsDNA. Clinical status was assessed according to the SELENA version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and physician global assessment.

At any point in the trial, clinically stable patients who had increases in anti-dsDNA antibodies of 25% or more and of C3a by 50% since the previous visit were randomized to placebo or an increase in prednisone to 30 mg/day for 2 weeks. The dose was then tapered to 20 mg/day for 1 week and to 10 mg/day for an additional week.

A total of 41 patients flared and were randomized, 21 to prednisone and 20 to placebo. There were no statistically significant differences between the two groups; 90% were female, mean age was 35 years, disease duration averaged 7 years, and mean SLEDAI was 4.2. Mild to moderate flares were seen in two patients receiving placebo and in four receiving prednisone within 90 days of randomization. “However, the major finding was that of 21 patients who received prednisone, none experienced a severe flare, while among the 20 who received placebo, 6 had severe flares, which was a highly significant difference,” Dr. Belmont said.

Analysis revealed that at 1 month, there were three renal and one central nervous system flare, and at 2 months, one patient developed pyoderma gangrenosum and pancytopenia. At 3 months, there was an additional case of pleural effusion with fever and dyspnea.

Prednisone also led to significant benefits on SLEDAI, anti-dsDNA, C4, and C3a after 1 month.

“What price did patients pay for receiving the preemptive prednisone? It turned out that there was a slightly greater absolute number of adverse events in the placebo group, at 13, compared with 10 events in the prednisone group,” he said. So the short-term increase in prednisone did not result in an increased risk of adverse events, and despite the fact that patients randomized to prednisone initially had greater exposure to the drug, the cumulative exposure was greater in those who flared. Three patients who flared also required initiation or increase in cytotoxic therapy.

“Consideration should be given to preemptive use of short-term moderate-dose corticosteroids in clinically stable, serologically active lupus patients to prevent severe flares and prolonged exposure to high-dose corticosteroids and additional cytotoxic agents,” he said.

NEW YORK — The marked decrease in mortality relating to renal crisis in patients with scleroderma because of the widespread use of ACE inhibitors has been accompanied by a huge increase in deaths from lung disease.

“Current treatment of scleroderma lags far behind some of the great successes we have seen in other rheumatic diseases. It has the highest mortality, with a 10-year survival of only 55%,” Dr. John Varga said at a rheumatology meeting sponsored by New York University.

Immunosuppressive therapies have been largely ineffective in scleroderma. “Steroids don't work and are probably contraindicated, and experience with methotrexate and the tumor necrosis factor inhibitors has not been very positive,” he said.

However, “we have learned a great deal about what happens with scleroderma vasculopathy,” said Dr. Varga, professor of medicine at Northwestern University, Chicago.

The most important vasculopathy in scleroderma is pulmonary arterial hypertension (PAH), Dr. Varga said. “This has always been the case, but until 2 decades ago we didn't even know how to recognize it, and because there was essentially no treatment, there was very little interest in trying to study it,” he said.

PAH develops in approximately 10%–20% of patients with scleroderma, and often manifests late in the disease. “Survival is abysmal,” he said, and although newer treatments currently in use may change this, the survival data are not yet available. In any case, because PAH is such a serious and prevalent complication, it is important for clinical rheumatologists to screen for it and to do so early, he said.

The most common screening study is Doppler echocardiography, which is easily reproducible, noninvasive, and relatively inexpensive. However, this test has many false positives and false negatives and cannot differentiate PAH from pulmonary vascular hypertension, for which the treatment is very different. Right heart catheterization is needed for anyone with suspected PAH or rapidly falling diffusing capacity, according to Dr. Varga.

Better understanding of the key signaling pathways in PAH, such as the endothelin pathway, has led to the development and approval of agents such as bosentan, sildenafil, and ambrisentan. Currently there is considerable interest in combination therapy and goal-directed therapy, in which specific target goals and time frames are set and, if not met, the drug dosages are increased.

There also is good evidence now that cyclophosphamide (Cytoxan) slows interstitial lung disease, as was shown in the Scleroderma Lung Study. In that trial, 158 patients with alveolitis were randomized to cyclophosphamide or placebo and followed for 12 months. Those on standard therapy showed marked decline in lung function, while disease stabilized among those on the active treatment (Arthritis Rheum. 2007;56:1676–84).

Small but significant benefits were seen on skin scores, and some improvements were reported on the health assessment questionnaire as well as on the symptom of breathlessness—which was very important for the patients, said Dr. Varga, who participated in the trial.

“These results were encouraging, although there was debate as to whether the risk of Cytoxan was worth these fairly modest benefits,” he said.

Further follow-up found that benefits of cyclophosphamide on forced vital capacity continued through 18 months, but thereafter began to wane and was lost at two years. “Perhaps these patients should have a second treatment,” he suggested.

Targeting the pathways and mediators involved in fibrosis is another new and exciting area of research and clinical development, Dr. Varga said.

One profibrotic mediator of interest is transforming growth factor β (TGF-β), which is a ubiquitous growth factor with pleiotropic effects that act through the Smad pathway.

Small molecules have been developed that specifically block this pathway; in animal models they look promising, but no clinical data are yet available.

Good evidence from the Scleroderma Lung Study shows Cytoxan slows interstitial lung disease. DR. VARGA

NEW YORK — The marked decrease in mortality relating to renal crisis in patients with scleroderma because of the widespread use of ACE inhibitors has been accompanied by a huge increase in deaths from lung disease.

“Current treatment of scleroderma lags far behind some of the great successes we have seen in other rheumatic diseases. It has the highest mortality, with a 10-year survival of only 55%,” Dr. John Varga said at a rheumatology meeting sponsored by New York University.

Immunosuppressive therapies have been largely ineffective in scleroderma. “Steroids don't work and are probably contraindicated, and experience with methotrexate and the tumor necrosis factor inhibitors has not been very positive,” he said.

However, “we have learned a great deal about what happens with scleroderma vasculopathy,” said Dr. Varga, professor of medicine at Northwestern University, Chicago.

The most important vasculopathy in scleroderma is pulmonary arterial hypertension (PAH), Dr. Varga said. “This has always been the case, but until 2 decades ago we didn't even know how to recognize it, and because there was essentially no treatment, there was very little interest in trying to study it,” he said.

PAH develops in approximately 10%–20% of patients with scleroderma, and often manifests late in the disease. “Survival is abysmal,” he said, and although newer treatments currently in use may change this, the survival data are not yet available. In any case, because PAH is such a serious and prevalent complication, it is important for clinical rheumatologists to screen for it and to do so early, he said.

The most common screening study is Doppler echocardiography, which is easily reproducible, noninvasive, and relatively inexpensive. However, this test has many false positives and false negatives and cannot differentiate PAH from pulmonary vascular hypertension, for which the treatment is very different. Right heart catheterization is needed for anyone with suspected PAH or rapidly falling diffusing capacity, according to Dr. Varga.

Better understanding of the key signaling pathways in PAH, such as the endothelin pathway, has led to the development and approval of agents such as bosentan, sildenafil, and ambrisentan. Currently there is considerable interest in combination therapy and goal-directed therapy, in which specific target goals and time frames are set and, if not met, the drug dosages are increased.

There also is good evidence now that cyclophosphamide (Cytoxan) slows interstitial lung disease, as was shown in the Scleroderma Lung Study. In that trial, 158 patients with alveolitis were randomized to cyclophosphamide or placebo and followed for 12 months. Those on standard therapy showed marked decline in lung function, while disease stabilized among those on the active treatment (Arthritis Rheum. 2007;56:1676–84).

Small but significant benefits were seen on skin scores, and some improvements were reported on the health assessment questionnaire as well as on the symptom of breathlessness—which was very important for the patients, said Dr. Varga, who participated in the trial.

“These results were encouraging, although there was debate as to whether the risk of Cytoxan was worth these fairly modest benefits,” he said.

Further follow-up found that benefits of cyclophosphamide on forced vital capacity continued through 18 months, but thereafter began to wane and was lost at two years. “Perhaps these patients should have a second treatment,” he suggested.

Targeting the pathways and mediators involved in fibrosis is another new and exciting area of research and clinical development, Dr. Varga said.

One profibrotic mediator of interest is transforming growth factor β (TGF-β), which is a ubiquitous growth factor with pleiotropic effects that act through the Smad pathway.

Small molecules have been developed that specifically block this pathway; in animal models they look promising, but no clinical data are yet available.

Good evidence from the Scleroderma Lung Study shows Cytoxan slows interstitial lung disease. DR. VARGA

NEW YORK — The marked decrease in mortality relating to renal crisis in patients with scleroderma because of the widespread use of ACE inhibitors has been accompanied by a huge increase in deaths from lung disease.

“Current treatment of scleroderma lags far behind some of the great successes we have seen in other rheumatic diseases. It has the highest mortality, with a 10-year survival of only 55%,” Dr. John Varga said at a rheumatology meeting sponsored by New York University.

Immunosuppressive therapies have been largely ineffective in scleroderma. “Steroids don't work and are probably contraindicated, and experience with methotrexate and the tumor necrosis factor inhibitors has not been very positive,” he said.

However, “we have learned a great deal about what happens with scleroderma vasculopathy,” said Dr. Varga, professor of medicine at Northwestern University, Chicago.

The most important vasculopathy in scleroderma is pulmonary arterial hypertension (PAH), Dr. Varga said. “This has always been the case, but until 2 decades ago we didn't even know how to recognize it, and because there was essentially no treatment, there was very little interest in trying to study it,” he said.

PAH develops in approximately 10%–20% of patients with scleroderma, and often manifests late in the disease. “Survival is abysmal,” he said, and although newer treatments currently in use may change this, the survival data are not yet available. In any case, because PAH is such a serious and prevalent complication, it is important for clinical rheumatologists to screen for it and to do so early, he said.

The most common screening study is Doppler echocardiography, which is easily reproducible, noninvasive, and relatively inexpensive. However, this test has many false positives and false negatives and cannot differentiate PAH from pulmonary vascular hypertension, for which the treatment is very different. Right heart catheterization is needed for anyone with suspected PAH or rapidly falling diffusing capacity, according to Dr. Varga.

Better understanding of the key signaling pathways in PAH, such as the endothelin pathway, has led to the development and approval of agents such as bosentan, sildenafil, and ambrisentan. Currently there is considerable interest in combination therapy and goal-directed therapy, in which specific target goals and time frames are set and, if not met, the drug dosages are increased.

There also is good evidence now that cyclophosphamide (Cytoxan) slows interstitial lung disease, as was shown in the Scleroderma Lung Study. In that trial, 158 patients with alveolitis were randomized to cyclophosphamide or placebo and followed for 12 months. Those on standard therapy showed marked decline in lung function, while disease stabilized among those on the active treatment (Arthritis Rheum. 2007;56:1676–84).

Small but significant benefits were seen on skin scores, and some improvements were reported on the health assessment questionnaire as well as on the symptom of breathlessness—which was very important for the patients, said Dr. Varga, who participated in the trial.

“These results were encouraging, although there was debate as to whether the risk of Cytoxan was worth these fairly modest benefits,” he said.

Further follow-up found that benefits of cyclophosphamide on forced vital capacity continued through 18 months, but thereafter began to wane and was lost at two years. “Perhaps these patients should have a second treatment,” he suggested.

Targeting the pathways and mediators involved in fibrosis is another new and exciting area of research and clinical development, Dr. Varga said.

One profibrotic mediator of interest is transforming growth factor β (TGF-β), which is a ubiquitous growth factor with pleiotropic effects that act through the Smad pathway.

Small molecules have been developed that specifically block this pathway; in animal models they look promising, but no clinical data are yet available.

Good evidence from the Scleroderma Lung Study shows Cytoxan slows interstitial lung disease. DR. VARGA