Robert Finn

RANCHO MIRAGE, CALIF. – In diagnosing a child with an extreme case of daytime sleepiness, there's no good substitute for the multiple sleep latency test, Dr. Timothy F. Hoban said at a conference on sleep disorders in infancy and childhood sponsored by the Annenberg Center for Health Sciences.

Although a simple clinical evaluation can provide a fairly good indication as to whether the child has daytime sleepiness, it's often difficult to estimate how severe the problem is. “The multiple sleep latency test (MSLT) can help answer that question in an objective way that's been standardized and well validated,” said Dr. Hoban of the sleep disorders center at the University of Michigan, Ann Arbor.

Unlike certain questionnaire-based assessments, the MSLT has been validated in children, and provides reliable results as long as the child is at least 6 or 7 years old. However, the test is expensive and time consuming to perform and must be conducted in a sleep lab. The MSLT may be useful when a child has excessive daytime sleepiness but the clinical history, examination, and polysomnography reveal no specific cause. Dr. Hoban recommended judicious use of the MSLT in evaluations of sleep-disordered breathing, circadian rhythm disorders, narcolepsy, and other disorders of excessive sleepiness.

Developed initially at Stanford (Calif.) University in the 1970s, the MSLT has a simple premise: People who are sleepy will fall asleep faster than those who are not.

After a night of polysomnography to screen for some sleep disrupters and to ensure that the patient has had a good night's sleep, the child is given four or five chances to nap in a dark, quiet environment, with each nap separated by about 2 hours. If the child fails to fall asleep (as measured by EEG tracings) within 20 minutes, the nap opportunity ends. Otherwise the child is allowed to sleep for 15 minutes following the first epoch of sleep.

In addition to the latency of sleep, the MSLT records the presence of sleep-onset REM periods (SOREMPs). The presence of SOREMPs correlates strongly with the presence of narcolepsy. Narcoleptic patients also typically have a sleep latency of 5 minutes or less.

Normal adults have a sleep latency of about 15 minutes, but normal latencies in children can be much longer. Detailed studies have correlated mean sleep latencies with Tanner stage. Children in Tanner stage 1 take an average of 19 minutes to fall asleep, whereas those in stage 5 take about 16.6 minutes; older adolescents take a mean 15.7 minutes to fall asleep.

“The net result of this is that in preadolescent children you can have a sleep latency of 14 or 15 minutes that would be considered solidly normal by adult standards but substantially abnormal for a child,” Dr. Hoban said.

In addition to being objective, standardized, and well validated, the MSLT has the advantage of being easily administered to school-age children and also can be used to assess the response to treatment. On the other hand, it's an expensive and time-consuming test, doubly so because it must be preceded by full-night polysomnography. It's sensitive to extraneous influences, such as certain sleep-disrupting medications like Ritalin or even excessive physical activity during the intervals between naps.

Dr. Hoban described a case that illustrated the value of the MSLT. The patient was a 16-year-old with a history of disabling sleepiness for several years. He had first been tested for what were thought to be seizures (that is, episodes characterized by staring or unresponsiveness followed by brief losses of posture from which he quickly recovered).

The patient's MSLT results were striking. “MSLTs this dramatic are very easy to score and recognize,” Dr. Hoban said. His strong suspicion that the patient had narcolepsy was confirmed by further analysis of the young man's polysomnograph, which demonstrated frequent nighttime awakenings, another characteristic sign of narcolepsy.

RANCHO MIRAGE, CALIF. – In diagnosing a child with an extreme case of daytime sleepiness, there's no good substitute for the multiple sleep latency test, Dr. Timothy F. Hoban said at a conference on sleep disorders in infancy and childhood sponsored by the Annenberg Center for Health Sciences.

Although a simple clinical evaluation can provide a fairly good indication as to whether the child has daytime sleepiness, it's often difficult to estimate how severe the problem is. “The multiple sleep latency test (MSLT) can help answer that question in an objective way that's been standardized and well validated,” said Dr. Hoban of the sleep disorders center at the University of Michigan, Ann Arbor.

Unlike certain questionnaire-based assessments, the MSLT has been validated in children, and provides reliable results as long as the child is at least 6 or 7 years old. However, the test is expensive and time consuming to perform and must be conducted in a sleep lab. The MSLT may be useful when a child has excessive daytime sleepiness but the clinical history, examination, and polysomnography reveal no specific cause. Dr. Hoban recommended judicious use of the MSLT in evaluations of sleep-disordered breathing, circadian rhythm disorders, narcolepsy, and other disorders of excessive sleepiness.

Developed initially at Stanford (Calif.) University in the 1970s, the MSLT has a simple premise: People who are sleepy will fall asleep faster than those who are not.

After a night of polysomnography to screen for some sleep disrupters and to ensure that the patient has had a good night's sleep, the child is given four or five chances to nap in a dark, quiet environment, with each nap separated by about 2 hours. If the child fails to fall asleep (as measured by EEG tracings) within 20 minutes, the nap opportunity ends. Otherwise the child is allowed to sleep for 15 minutes following the first epoch of sleep.

In addition to the latency of sleep, the MSLT records the presence of sleep-onset REM periods (SOREMPs). The presence of SOREMPs correlates strongly with the presence of narcolepsy. Narcoleptic patients also typically have a sleep latency of 5 minutes or less.

Normal adults have a sleep latency of about 15 minutes, but normal latencies in children can be much longer. Detailed studies have correlated mean sleep latencies with Tanner stage. Children in Tanner stage 1 take an average of 19 minutes to fall asleep, whereas those in stage 5 take about 16.6 minutes; older adolescents take a mean 15.7 minutes to fall asleep.

“The net result of this is that in preadolescent children you can have a sleep latency of 14 or 15 minutes that would be considered solidly normal by adult standards but substantially abnormal for a child,” Dr. Hoban said.

In addition to being objective, standardized, and well validated, the MSLT has the advantage of being easily administered to school-age children and also can be used to assess the response to treatment. On the other hand, it's an expensive and time-consuming test, doubly so because it must be preceded by full-night polysomnography. It's sensitive to extraneous influences, such as certain sleep-disrupting medications like Ritalin or even excessive physical activity during the intervals between naps.

Dr. Hoban described a case that illustrated the value of the MSLT. The patient was a 16-year-old with a history of disabling sleepiness for several years. He had first been tested for what were thought to be seizures (that is, episodes characterized by staring or unresponsiveness followed by brief losses of posture from which he quickly recovered).

The patient's MSLT results were striking. “MSLTs this dramatic are very easy to score and recognize,” Dr. Hoban said. His strong suspicion that the patient had narcolepsy was confirmed by further analysis of the young man's polysomnograph, which demonstrated frequent nighttime awakenings, another characteristic sign of narcolepsy.

RANCHO MIRAGE, CALIF. – In diagnosing a child with an extreme case of daytime sleepiness, there's no good substitute for the multiple sleep latency test, Dr. Timothy F. Hoban said at a conference on sleep disorders in infancy and childhood sponsored by the Annenberg Center for Health Sciences.

Although a simple clinical evaluation can provide a fairly good indication as to whether the child has daytime sleepiness, it's often difficult to estimate how severe the problem is. “The multiple sleep latency test (MSLT) can help answer that question in an objective way that's been standardized and well validated,” said Dr. Hoban of the sleep disorders center at the University of Michigan, Ann Arbor.

Unlike certain questionnaire-based assessments, the MSLT has been validated in children, and provides reliable results as long as the child is at least 6 or 7 years old. However, the test is expensive and time consuming to perform and must be conducted in a sleep lab. The MSLT may be useful when a child has excessive daytime sleepiness but the clinical history, examination, and polysomnography reveal no specific cause. Dr. Hoban recommended judicious use of the MSLT in evaluations of sleep-disordered breathing, circadian rhythm disorders, narcolepsy, and other disorders of excessive sleepiness.

Developed initially at Stanford (Calif.) University in the 1970s, the MSLT has a simple premise: People who are sleepy will fall asleep faster than those who are not.

After a night of polysomnography to screen for some sleep disrupters and to ensure that the patient has had a good night's sleep, the child is given four or five chances to nap in a dark, quiet environment, with each nap separated by about 2 hours. If the child fails to fall asleep (as measured by EEG tracings) within 20 minutes, the nap opportunity ends. Otherwise the child is allowed to sleep for 15 minutes following the first epoch of sleep.

In addition to the latency of sleep, the MSLT records the presence of sleep-onset REM periods (SOREMPs). The presence of SOREMPs correlates strongly with the presence of narcolepsy. Narcoleptic patients also typically have a sleep latency of 5 minutes or less.

Normal adults have a sleep latency of about 15 minutes, but normal latencies in children can be much longer. Detailed studies have correlated mean sleep latencies with Tanner stage. Children in Tanner stage 1 take an average of 19 minutes to fall asleep, whereas those in stage 5 take about 16.6 minutes; older adolescents take a mean 15.7 minutes to fall asleep.

“The net result of this is that in preadolescent children you can have a sleep latency of 14 or 15 minutes that would be considered solidly normal by adult standards but substantially abnormal for a child,” Dr. Hoban said.

In addition to being objective, standardized, and well validated, the MSLT has the advantage of being easily administered to school-age children and also can be used to assess the response to treatment. On the other hand, it's an expensive and time-consuming test, doubly so because it must be preceded by full-night polysomnography. It's sensitive to extraneous influences, such as certain sleep-disrupting medications like Ritalin or even excessive physical activity during the intervals between naps.

Dr. Hoban described a case that illustrated the value of the MSLT. The patient was a 16-year-old with a history of disabling sleepiness for several years. He had first been tested for what were thought to be seizures (that is, episodes characterized by staring or unresponsiveness followed by brief losses of posture from which he quickly recovered).

The patient's MSLT results were striking. “MSLTs this dramatic are very easy to score and recognize,” Dr. Hoban said. His strong suspicion that the patient had narcolepsy was confirmed by further analysis of the young man's polysomnograph, which demonstrated frequent nighttime awakenings, another characteristic sign of narcolepsy.

SAN FRANCISCO – In assessing an adolescent newly diagnosed with HIV, establishing a productive doctor-patient relationship can be every bit as important as determining viral loads, Dr. Andrew T. Pavia said at a meeting on HIV management sponsored by the University of California, San Francisco.

With adolescents, “one of the difficulties is getting to the point where the conversation starts,” said Dr. Pavia of the University of Utah, Salt Lake City. “Sometimes a lot of the visit is spent while the kid is examining her shoes and not answering questions and speaking in monosyllables. And as you reach the end of the visit and you're running out of time, suddenly the floodgates open.”

Few clinicians have the luxury of the five-visit assessment model pioneered by Children's Hospital of Philadelphia. There, the initial visit is entirely devoted to relationship building and to determining the teen's psychological profile. Only at the second visit does the initial medical intake examination begin, including blood draws for STD testing and HIV staging.

The third visit involves mental health screening, including cognitive testing and screening for depression. During the fourth visit the physician reviews the patient's CD4 counts and viral loads, and at the fifth visit those tests are repeated.

“We don't have the luxury of doing a five-visit evaluation, but it's actually been very surprising how much tests like the Beck Depression Inventory can help open up a range of conversations,” Dr. Pavia said. Starting the visit with this and discussing the results with the patient immediately can be a shortcut to developing a productive therapeutic relationship.

The physician should try to understand the patient's psychosocial situation. It's important to know whether the teen's basic needs for housing, food, clothing, child care, and education are being met.

It's important to know whether the adolescent has mental health issues or is a substance abuser. It's also important to know what legal issues the teen may be facing.

For example, Dr. Pavia discovered that after he sent them off for referrals, some adolescents simply failed to show up. When he questioned them, some mentioned that they were on probation or had outstanding warrants, and while they trusted him not to turn them in, they couldn't be so sure about other health care workers.

It's important to determine whether the adolescent has an adequate support system, and if so, how to engage it. It's important to determine whether the adolescent has any special needs, such as language translation, hearing impairment, reading impairment, and the like.

And it's important to determine where the patient stands on disclosing his or her HIV status or sexual orientation to parents or guardians.

SAN FRANCISCO – In assessing an adolescent newly diagnosed with HIV, establishing a productive doctor-patient relationship can be every bit as important as determining viral loads, Dr. Andrew T. Pavia said at a meeting on HIV management sponsored by the University of California, San Francisco.

With adolescents, “one of the difficulties is getting to the point where the conversation starts,” said Dr. Pavia of the University of Utah, Salt Lake City. “Sometimes a lot of the visit is spent while the kid is examining her shoes and not answering questions and speaking in monosyllables. And as you reach the end of the visit and you're running out of time, suddenly the floodgates open.”

Few clinicians have the luxury of the five-visit assessment model pioneered by Children's Hospital of Philadelphia. There, the initial visit is entirely devoted to relationship building and to determining the teen's psychological profile. Only at the second visit does the initial medical intake examination begin, including blood draws for STD testing and HIV staging.

The third visit involves mental health screening, including cognitive testing and screening for depression. During the fourth visit the physician reviews the patient's CD4 counts and viral loads, and at the fifth visit those tests are repeated.

“We don't have the luxury of doing a five-visit evaluation, but it's actually been very surprising how much tests like the Beck Depression Inventory can help open up a range of conversations,” Dr. Pavia said. Starting the visit with this and discussing the results with the patient immediately can be a shortcut to developing a productive therapeutic relationship.

The physician should try to understand the patient's psychosocial situation. It's important to know whether the teen's basic needs for housing, food, clothing, child care, and education are being met.

It's important to know whether the adolescent has mental health issues or is a substance abuser. It's also important to know what legal issues the teen may be facing.

For example, Dr. Pavia discovered that after he sent them off for referrals, some adolescents simply failed to show up. When he questioned them, some mentioned that they were on probation or had outstanding warrants, and while they trusted him not to turn them in, they couldn't be so sure about other health care workers.

It's important to determine whether the adolescent has an adequate support system, and if so, how to engage it. It's important to determine whether the adolescent has any special needs, such as language translation, hearing impairment, reading impairment, and the like.

And it's important to determine where the patient stands on disclosing his or her HIV status or sexual orientation to parents or guardians.

SAN FRANCISCO – In assessing an adolescent newly diagnosed with HIV, establishing a productive doctor-patient relationship can be every bit as important as determining viral loads, Dr. Andrew T. Pavia said at a meeting on HIV management sponsored by the University of California, San Francisco.

With adolescents, “one of the difficulties is getting to the point where the conversation starts,” said Dr. Pavia of the University of Utah, Salt Lake City. “Sometimes a lot of the visit is spent while the kid is examining her shoes and not answering questions and speaking in monosyllables. And as you reach the end of the visit and you're running out of time, suddenly the floodgates open.”

Few clinicians have the luxury of the five-visit assessment model pioneered by Children's Hospital of Philadelphia. There, the initial visit is entirely devoted to relationship building and to determining the teen's psychological profile. Only at the second visit does the initial medical intake examination begin, including blood draws for STD testing and HIV staging.

The third visit involves mental health screening, including cognitive testing and screening for depression. During the fourth visit the physician reviews the patient's CD4 counts and viral loads, and at the fifth visit those tests are repeated.

“We don't have the luxury of doing a five-visit evaluation, but it's actually been very surprising how much tests like the Beck Depression Inventory can help open up a range of conversations,” Dr. Pavia said. Starting the visit with this and discussing the results with the patient immediately can be a shortcut to developing a productive therapeutic relationship.

The physician should try to understand the patient's psychosocial situation. It's important to know whether the teen's basic needs for housing, food, clothing, child care, and education are being met.

It's important to know whether the adolescent has mental health issues or is a substance abuser. It's also important to know what legal issues the teen may be facing.

For example, Dr. Pavia discovered that after he sent them off for referrals, some adolescents simply failed to show up. When he questioned them, some mentioned that they were on probation or had outstanding warrants, and while they trusted him not to turn them in, they couldn't be so sure about other health care workers.

It's important to determine whether the adolescent has an adequate support system, and if so, how to engage it. It's important to determine whether the adolescent has any special needs, such as language translation, hearing impairment, reading impairment, and the like.

And it's important to determine where the patient stands on disclosing his or her HIV status or sexual orientation to parents or guardians.

SAN FRANCISCO — Using nitrite inhalants, being uncircumcised, and engaging in certain sexual practices all increase the risk of HIV seroconversion among HIV-negative men who have sex with men, Dr. Susan P. Buchbinder reported at a meeting on HIV management sponsored by the University of California, San Francisco.

The results of her published study, along with related unpublished data, suggest a number of behavioral strategies to reduce the risk of HIV transmission among men who have sex with men (MSM).

“Some people say, 'We know what causes HIV [transmission], so why don't men change behavior?'” said Dr. Buchbinder, director of the university's HIV research section. “This is a response that one of my colleagues gave many years ago: She said, 'If behavior change were easy, I'd be thin.' I think we all recognize that behavior change is difficult. It's difficult to sustain over time.”

Dr. Buchbinder's study involved 3,257 MSM from six U.S. cities who were HIV negative when they enrolled in the study in 1995. Participants were seen every 6 months for an 18-month period. During that time, 72 men became infected with HIV, yielding an annualized HIV seroincidence of 1.55 per 100 person-years (J. Acquir. Immune Defic. Syndr. 2005;39:82–9).

Taking into account the odds ratios of various risk factors (adjusted for sexual behaviors), as well as the prevalence of those risk factors in the population studied, Dr. Buchbinder and her colleagues calculated the population-attributable risks (PARs) of various behaviors and characteristics. (See table.)

The highest PARs were seen in men who had greater numbers of HIV-negative sex partners. The risk of seroconversion increased by 14% with each additional HIV-negative partner reported in the prior 6 months. If one has a lot of HIV-negative partners, the chances increase that one of those partners may have recently become infected and is unaware of this, she explained.

These findings suggest that “we need to further develop new HIV-testing strategies, [such as] the implementation of rapid testing to allow people to know their serostatus more quickly,” she said.

The use of nitrite inhalants (known as poppers) also carried a high PAR in Dr. Buchbinder's published study. She mentioned other unpublished data that implicated other drugs, including crystal methamphetamine and sildenafil (Viagra).

“In this study, we found that these three drugs were associated not just with having an increase in anal sex, and not even just having an increase in unprotected anal sex. [These men are] having an increase in unprotected anal sex with a partner whose serostatus was different.”

Furthermore, there are probably ways in which these drugs may enhance transmission biologically. For example, limited animal, in vitro, and human studies suggest that crystal methamphetamine is associated with increased HIV replication and perturbations in immune function.

Poppers are also associated with an effect on immune function as well as vasodilation in mucosal surfaces. And crystal methamphetamine, poppers, and Viagra may additionally be associated with more prolonged sexual activities.

It's difficult to know what to do about substance use in this population, Dr. Buchbinder said. Most studies on substance use address people who are addicted, and that model may not apply in a population that uses these drugs intermittently to enhance sexual pleasure.

Seroconversion was significantly higher in uncircumcised men, a finding that Dr. Buchbinder and her colleagues described as biologically plausible, with several possible mechanisms.

One surprising finding was the significant risk associated with receptive oral sex, even after controlling for anal sex practices. Other studies have failed to find an independent contribution of receptive oral sex to HIV transmission. The investigators could not rule out the possibility that this apparent association may simply be a marker for riskier sex practices in general, or that it may reflect unmeasured confounders.

SAN FRANCISCO — Using nitrite inhalants, being uncircumcised, and engaging in certain sexual practices all increase the risk of HIV seroconversion among HIV-negative men who have sex with men, Dr. Susan P. Buchbinder reported at a meeting on HIV management sponsored by the University of California, San Francisco.

The results of her published study, along with related unpublished data, suggest a number of behavioral strategies to reduce the risk of HIV transmission among men who have sex with men (MSM).

“Some people say, 'We know what causes HIV [transmission], so why don't men change behavior?'” said Dr. Buchbinder, director of the university's HIV research section. “This is a response that one of my colleagues gave many years ago: She said, 'If behavior change were easy, I'd be thin.' I think we all recognize that behavior change is difficult. It's difficult to sustain over time.”

Dr. Buchbinder's study involved 3,257 MSM from six U.S. cities who were HIV negative when they enrolled in the study in 1995. Participants were seen every 6 months for an 18-month period. During that time, 72 men became infected with HIV, yielding an annualized HIV seroincidence of 1.55 per 100 person-years (J. Acquir. Immune Defic. Syndr. 2005;39:82–9).

Taking into account the odds ratios of various risk factors (adjusted for sexual behaviors), as well as the prevalence of those risk factors in the population studied, Dr. Buchbinder and her colleagues calculated the population-attributable risks (PARs) of various behaviors and characteristics. (See table.)

The highest PARs were seen in men who had greater numbers of HIV-negative sex partners. The risk of seroconversion increased by 14% with each additional HIV-negative partner reported in the prior 6 months. If one has a lot of HIV-negative partners, the chances increase that one of those partners may have recently become infected and is unaware of this, she explained.

These findings suggest that “we need to further develop new HIV-testing strategies, [such as] the implementation of rapid testing to allow people to know their serostatus more quickly,” she said.

The use of nitrite inhalants (known as poppers) also carried a high PAR in Dr. Buchbinder's published study. She mentioned other unpublished data that implicated other drugs, including crystal methamphetamine and sildenafil (Viagra).

“In this study, we found that these three drugs were associated not just with having an increase in anal sex, and not even just having an increase in unprotected anal sex. [These men are] having an increase in unprotected anal sex with a partner whose serostatus was different.”

Furthermore, there are probably ways in which these drugs may enhance transmission biologically. For example, limited animal, in vitro, and human studies suggest that crystal methamphetamine is associated with increased HIV replication and perturbations in immune function.

Poppers are also associated with an effect on immune function as well as vasodilation in mucosal surfaces. And crystal methamphetamine, poppers, and Viagra may additionally be associated with more prolonged sexual activities.

It's difficult to know what to do about substance use in this population, Dr. Buchbinder said. Most studies on substance use address people who are addicted, and that model may not apply in a population that uses these drugs intermittently to enhance sexual pleasure.

Seroconversion was significantly higher in uncircumcised men, a finding that Dr. Buchbinder and her colleagues described as biologically plausible, with several possible mechanisms.

One surprising finding was the significant risk associated with receptive oral sex, even after controlling for anal sex practices. Other studies have failed to find an independent contribution of receptive oral sex to HIV transmission. The investigators could not rule out the possibility that this apparent association may simply be a marker for riskier sex practices in general, or that it may reflect unmeasured confounders.

SAN FRANCISCO — Using nitrite inhalants, being uncircumcised, and engaging in certain sexual practices all increase the risk of HIV seroconversion among HIV-negative men who have sex with men, Dr. Susan P. Buchbinder reported at a meeting on HIV management sponsored by the University of California, San Francisco.

The results of her published study, along with related unpublished data, suggest a number of behavioral strategies to reduce the risk of HIV transmission among men who have sex with men (MSM).

“Some people say, 'We know what causes HIV [transmission], so why don't men change behavior?'” said Dr. Buchbinder, director of the university's HIV research section. “This is a response that one of my colleagues gave many years ago: She said, 'If behavior change were easy, I'd be thin.' I think we all recognize that behavior change is difficult. It's difficult to sustain over time.”

Dr. Buchbinder's study involved 3,257 MSM from six U.S. cities who were HIV negative when they enrolled in the study in 1995. Participants were seen every 6 months for an 18-month period. During that time, 72 men became infected with HIV, yielding an annualized HIV seroincidence of 1.55 per 100 person-years (J. Acquir. Immune Defic. Syndr. 2005;39:82–9).

Taking into account the odds ratios of various risk factors (adjusted for sexual behaviors), as well as the prevalence of those risk factors in the population studied, Dr. Buchbinder and her colleagues calculated the population-attributable risks (PARs) of various behaviors and characteristics. (See table.)

The highest PARs were seen in men who had greater numbers of HIV-negative sex partners. The risk of seroconversion increased by 14% with each additional HIV-negative partner reported in the prior 6 months. If one has a lot of HIV-negative partners, the chances increase that one of those partners may have recently become infected and is unaware of this, she explained.

These findings suggest that “we need to further develop new HIV-testing strategies, [such as] the implementation of rapid testing to allow people to know their serostatus more quickly,” she said.

The use of nitrite inhalants (known as poppers) also carried a high PAR in Dr. Buchbinder's published study. She mentioned other unpublished data that implicated other drugs, including crystal methamphetamine and sildenafil (Viagra).

“In this study, we found that these three drugs were associated not just with having an increase in anal sex, and not even just having an increase in unprotected anal sex. [These men are] having an increase in unprotected anal sex with a partner whose serostatus was different.”

Furthermore, there are probably ways in which these drugs may enhance transmission biologically. For example, limited animal, in vitro, and human studies suggest that crystal methamphetamine is associated with increased HIV replication and perturbations in immune function.

Poppers are also associated with an effect on immune function as well as vasodilation in mucosal surfaces. And crystal methamphetamine, poppers, and Viagra may additionally be associated with more prolonged sexual activities.

It's difficult to know what to do about substance use in this population, Dr. Buchbinder said. Most studies on substance use address people who are addicted, and that model may not apply in a population that uses these drugs intermittently to enhance sexual pleasure.

Seroconversion was significantly higher in uncircumcised men, a finding that Dr. Buchbinder and her colleagues described as biologically plausible, with several possible mechanisms.

One surprising finding was the significant risk associated with receptive oral sex, even after controlling for anal sex practices. Other studies have failed to find an independent contribution of receptive oral sex to HIV transmission. The investigators could not rule out the possibility that this apparent association may simply be a marker for riskier sex practices in general, or that it may reflect unmeasured confounders.

SAN FRANCISCO — The optimal time to initiate antiretroviral therapy during pregnancy depends on a balance of factors, Dr. Deborah Cohan said at a meeting on HIV management sponsored by the University of California, San Francisco.

The primary goal is viral suppression by the third trimester to minimize the chances of HIV transmission to the fetus. At least one study shows that the median time to viral suppression is about 50 days in pregnant women, although 10% fail to achieve total suppression within 6.5 months.

“In the United States we tend to start antiretrovirals between 12 and 14 weeks or beyond,” said Dr. Cohan of the University of California, San Francisco. “[Many women] feel pretty bad in the first trimester, and the last thing we want is for them to … attribute their nausea and vomiting to the antiretrovirals.”

Fortunately the weight of the evidence is that transmission does not occur in the first trimester, so antiretroviral therapy may not be crucial during that time.

There are situations in which antiretroviral therapy would be appropriate during the first trimester. For example, if the woman is continuing her preconception regimen, and the regimen includes only nonteratogenic medications that are well tolerated, it need not be discontinued.

First-trimester antiretrovirals also are indicated in patients who need them immediately for their own health.

For women who fail to tolerate their preconception regimen during the first trimester despite the use of antiemetics, the advice is to discontinue all medications at once. The one exception is if the patient is on a regimen containing nonnucleoside reverse transcription inhibitors. In that case, discontinuation should be staggered.

The principles of determining a proper antiretroviral regimen are similar in pregnant and nonpregnant women, except for one major consideration: Is this for her own health, and is it going to be a long-term regimen, or is it strictly chemoprophylaxis to prevent transmission?

If it's chemoprophylaxis, less potent regimens may be acceptable. These could include triple nucleoside reverse transcriptase inhibitors. “Triple nukes really have fallen out of favor in terms of chronic use in adults,” Dr. Cohan said. “In this setting it may be appropriate. If someone comes to you with a CD4 count of 600 [cells/mm

Nelfinavir, a less potent protease inhibitor that has fallen out of favor, also is an option. It tends to be quite well tolerated in pregnancy, and in fact can counter the constipation that pregnant women frequently experience.

Another question concerns whether antiretroviral therapy is needed in pregnant women with viral loads less than 1,000 copies/mL. One as yet unpublished study of more than 1,200 woman-infant pairs determined the transmission rate to be 9.8% among women with low viral loads who don't get antiretroviral therapy, compared with 1.0% for women who do, yielding a highly significant odds ratio of 0.10.

Finally, there's the question of what one should do for women who are unlikely to comply with an antiretroviral regimen because of their life circumstances. Another unpublished study looked at the cost-effectiveness of directly observed therapy, which requires keeping women in the hospital during the third trimester. This resulted in a greatly reduced transmission rate and a cost saving of $3,200 per pregnancy.

Dr. Cohan routinely orders directly observed therapy for women in difficult circumstances. “It drives the nurses crazy and the patients often go kind of stir crazy, but we've had remarkable success at keeping these women in the hospital and getting their virus suppressed,” Dr. Cohan said.

SAN FRANCISCO — The optimal time to initiate antiretroviral therapy during pregnancy depends on a balance of factors, Dr. Deborah Cohan said at a meeting on HIV management sponsored by the University of California, San Francisco.

The primary goal is viral suppression by the third trimester to minimize the chances of HIV transmission to the fetus. At least one study shows that the median time to viral suppression is about 50 days in pregnant women, although 10% fail to achieve total suppression within 6.5 months.

“In the United States we tend to start antiretrovirals between 12 and 14 weeks or beyond,” said Dr. Cohan of the University of California, San Francisco. “[Many women] feel pretty bad in the first trimester, and the last thing we want is for them to … attribute their nausea and vomiting to the antiretrovirals.”

Fortunately the weight of the evidence is that transmission does not occur in the first trimester, so antiretroviral therapy may not be crucial during that time.

There are situations in which antiretroviral therapy would be appropriate during the first trimester. For example, if the woman is continuing her preconception regimen, and the regimen includes only nonteratogenic medications that are well tolerated, it need not be discontinued.

First-trimester antiretrovirals also are indicated in patients who need them immediately for their own health.

For women who fail to tolerate their preconception regimen during the first trimester despite the use of antiemetics, the advice is to discontinue all medications at once. The one exception is if the patient is on a regimen containing nonnucleoside reverse transcription inhibitors. In that case, discontinuation should be staggered.

The principles of determining a proper antiretroviral regimen are similar in pregnant and nonpregnant women, except for one major consideration: Is this for her own health, and is it going to be a long-term regimen, or is it strictly chemoprophylaxis to prevent transmission?

If it's chemoprophylaxis, less potent regimens may be acceptable. These could include triple nucleoside reverse transcriptase inhibitors. “Triple nukes really have fallen out of favor in terms of chronic use in adults,” Dr. Cohan said. “In this setting it may be appropriate. If someone comes to you with a CD4 count of 600 [cells/mm

Nelfinavir, a less potent protease inhibitor that has fallen out of favor, also is an option. It tends to be quite well tolerated in pregnancy, and in fact can counter the constipation that pregnant women frequently experience.

Another question concerns whether antiretroviral therapy is needed in pregnant women with viral loads less than 1,000 copies/mL. One as yet unpublished study of more than 1,200 woman-infant pairs determined the transmission rate to be 9.8% among women with low viral loads who don't get antiretroviral therapy, compared with 1.0% for women who do, yielding a highly significant odds ratio of 0.10.

Finally, there's the question of what one should do for women who are unlikely to comply with an antiretroviral regimen because of their life circumstances. Another unpublished study looked at the cost-effectiveness of directly observed therapy, which requires keeping women in the hospital during the third trimester. This resulted in a greatly reduced transmission rate and a cost saving of $3,200 per pregnancy.

Dr. Cohan routinely orders directly observed therapy for women in difficult circumstances. “It drives the nurses crazy and the patients often go kind of stir crazy, but we've had remarkable success at keeping these women in the hospital and getting their virus suppressed,” Dr. Cohan said.

SAN FRANCISCO — The optimal time to initiate antiretroviral therapy during pregnancy depends on a balance of factors, Dr. Deborah Cohan said at a meeting on HIV management sponsored by the University of California, San Francisco.

The primary goal is viral suppression by the third trimester to minimize the chances of HIV transmission to the fetus. At least one study shows that the median time to viral suppression is about 50 days in pregnant women, although 10% fail to achieve total suppression within 6.5 months.

“In the United States we tend to start antiretrovirals between 12 and 14 weeks or beyond,” said Dr. Cohan of the University of California, San Francisco. “[Many women] feel pretty bad in the first trimester, and the last thing we want is for them to … attribute their nausea and vomiting to the antiretrovirals.”

Fortunately the weight of the evidence is that transmission does not occur in the first trimester, so antiretroviral therapy may not be crucial during that time.

There are situations in which antiretroviral therapy would be appropriate during the first trimester. For example, if the woman is continuing her preconception regimen, and the regimen includes only nonteratogenic medications that are well tolerated, it need not be discontinued.

First-trimester antiretrovirals also are indicated in patients who need them immediately for their own health.

For women who fail to tolerate their preconception regimen during the first trimester despite the use of antiemetics, the advice is to discontinue all medications at once. The one exception is if the patient is on a regimen containing nonnucleoside reverse transcription inhibitors. In that case, discontinuation should be staggered.

The principles of determining a proper antiretroviral regimen are similar in pregnant and nonpregnant women, except for one major consideration: Is this for her own health, and is it going to be a long-term regimen, or is it strictly chemoprophylaxis to prevent transmission?

If it's chemoprophylaxis, less potent regimens may be acceptable. These could include triple nucleoside reverse transcriptase inhibitors. “Triple nukes really have fallen out of favor in terms of chronic use in adults,” Dr. Cohan said. “In this setting it may be appropriate. If someone comes to you with a CD4 count of 600 [cells/mm

Nelfinavir, a less potent protease inhibitor that has fallen out of favor, also is an option. It tends to be quite well tolerated in pregnancy, and in fact can counter the constipation that pregnant women frequently experience.

Another question concerns whether antiretroviral therapy is needed in pregnant women with viral loads less than 1,000 copies/mL. One as yet unpublished study of more than 1,200 woman-infant pairs determined the transmission rate to be 9.8% among women with low viral loads who don't get antiretroviral therapy, compared with 1.0% for women who do, yielding a highly significant odds ratio of 0.10.

Finally, there's the question of what one should do for women who are unlikely to comply with an antiretroviral regimen because of their life circumstances. Another unpublished study looked at the cost-effectiveness of directly observed therapy, which requires keeping women in the hospital during the third trimester. This resulted in a greatly reduced transmission rate and a cost saving of $3,200 per pregnancy.

Dr. Cohan routinely orders directly observed therapy for women in difficult circumstances. “It drives the nurses crazy and the patients often go kind of stir crazy, but we've had remarkable success at keeping these women in the hospital and getting their virus suppressed,” Dr. Cohan said.

SAN FRANCISCO — Acute hepatitis C infections among individuals who are HIV positive have been documented in four countries, and treatment of this coinfection remains controversial, Dr. Marion G. Peters said at a meeting on HIV management sponsored by the University of California, San Francisco.

The largest outbreak was documented in the United Kingdom, where 210 individuals from London and surrounding cities were found to be infected. Cases also have been reported in Germany, France, and the United States.

Dr. Peters of the University of California, San Francisco, and her colleagues documented 11 cases of acute HCV infection in the San Francisco Bay Area among men who have sex with men. Presentations varied greatly, ranging from incidental elevations of aspartate aminotransferase and alanine aminotransferase levels to severe liver dysfunction.

Ten of the 11 patients had adequate CD4 counts. Five patients were treated with interferon and ribavirin, and four of them achieved sustained virologic responses. Six patients were untreated; three of them developed chronic hepatitis C and three seroconverted spontaneously, losing their hepatitis C RNA.

Among the 210 patients with acute hepatitis C documented in London, 64% were on antiretroviral therapy, and their mean CD4 count was 552 cells/mm3, which Dr. Peters described as “perfectly adequate.”

Subtyping identified five clusters of patients. The patients in each of the clusters apparently acquired the virus from a single individual or small set of individuals. One of the clusters contained 43 patients. Genotype 1a was found in 78% of the cases overall.

A case-control study involving 60 of the 210 patients documented significant levels of high-risk behavior. Patients with acute hepatitis C were more likely than were controls to be users of intravenous drugs, and they reported a larger median number of sexual partners.

Studies of monogamous couples in which both partners have hepatitis C show that their viruses are rarely identical, and that sexual transmission occurs in only 1 case in 500. This suggests that blood-to-blood transmission, perhaps due to traumatic sexual practices, is likely to account for the transmission of hepatitis C in patients who are HIV positive.

Most authorities recommend treating these coinfected patients with interferon and ribavirin, but controversy remains over when to begin that treatment. Many patients seroconvert on their own, so the question is how long to wait.

“There's a big argument in the world literature [over] whether you should wait 12 weeks, 24 weeks, [or some other length of time],” Dr. Peters said. “We know that if you wait too long the patient will become chronic and then [his or her] chances of responding are very low. So we are fairly aggressive, and if we have a pinpoint of when they acquired [the infection], I would wait 12 weeks. If we don't have a pinpoint, it's doctor-patient preference.”

SAN FRANCISCO — Acute hepatitis C infections among individuals who are HIV positive have been documented in four countries, and treatment of this coinfection remains controversial, Dr. Marion G. Peters said at a meeting on HIV management sponsored by the University of California, San Francisco.

The largest outbreak was documented in the United Kingdom, where 210 individuals from London and surrounding cities were found to be infected. Cases also have been reported in Germany, France, and the United States.

Dr. Peters of the University of California, San Francisco, and her colleagues documented 11 cases of acute HCV infection in the San Francisco Bay Area among men who have sex with men. Presentations varied greatly, ranging from incidental elevations of aspartate aminotransferase and alanine aminotransferase levels to severe liver dysfunction.

Ten of the 11 patients had adequate CD4 counts. Five patients were treated with interferon and ribavirin, and four of them achieved sustained virologic responses. Six patients were untreated; three of them developed chronic hepatitis C and three seroconverted spontaneously, losing their hepatitis C RNA.

Among the 210 patients with acute hepatitis C documented in London, 64% were on antiretroviral therapy, and their mean CD4 count was 552 cells/mm3, which Dr. Peters described as “perfectly adequate.”

Subtyping identified five clusters of patients. The patients in each of the clusters apparently acquired the virus from a single individual or small set of individuals. One of the clusters contained 43 patients. Genotype 1a was found in 78% of the cases overall.

A case-control study involving 60 of the 210 patients documented significant levels of high-risk behavior. Patients with acute hepatitis C were more likely than were controls to be users of intravenous drugs, and they reported a larger median number of sexual partners.

Studies of monogamous couples in which both partners have hepatitis C show that their viruses are rarely identical, and that sexual transmission occurs in only 1 case in 500. This suggests that blood-to-blood transmission, perhaps due to traumatic sexual practices, is likely to account for the transmission of hepatitis C in patients who are HIV positive.

Most authorities recommend treating these coinfected patients with interferon and ribavirin, but controversy remains over when to begin that treatment. Many patients seroconvert on their own, so the question is how long to wait.

“There's a big argument in the world literature [over] whether you should wait 12 weeks, 24 weeks, [or some other length of time],” Dr. Peters said. “We know that if you wait too long the patient will become chronic and then [his or her] chances of responding are very low. So we are fairly aggressive, and if we have a pinpoint of when they acquired [the infection], I would wait 12 weeks. If we don't have a pinpoint, it's doctor-patient preference.”

SAN FRANCISCO — Acute hepatitis C infections among individuals who are HIV positive have been documented in four countries, and treatment of this coinfection remains controversial, Dr. Marion G. Peters said at a meeting on HIV management sponsored by the University of California, San Francisco.

The largest outbreak was documented in the United Kingdom, where 210 individuals from London and surrounding cities were found to be infected. Cases also have been reported in Germany, France, and the United States.

Dr. Peters of the University of California, San Francisco, and her colleagues documented 11 cases of acute HCV infection in the San Francisco Bay Area among men who have sex with men. Presentations varied greatly, ranging from incidental elevations of aspartate aminotransferase and alanine aminotransferase levels to severe liver dysfunction.

Ten of the 11 patients had adequate CD4 counts. Five patients were treated with interferon and ribavirin, and four of them achieved sustained virologic responses. Six patients were untreated; three of them developed chronic hepatitis C and three seroconverted spontaneously, losing their hepatitis C RNA.

Among the 210 patients with acute hepatitis C documented in London, 64% were on antiretroviral therapy, and their mean CD4 count was 552 cells/mm3, which Dr. Peters described as “perfectly adequate.”

Subtyping identified five clusters of patients. The patients in each of the clusters apparently acquired the virus from a single individual or small set of individuals. One of the clusters contained 43 patients. Genotype 1a was found in 78% of the cases overall.

A case-control study involving 60 of the 210 patients documented significant levels of high-risk behavior. Patients with acute hepatitis C were more likely than were controls to be users of intravenous drugs, and they reported a larger median number of sexual partners.

Studies of monogamous couples in which both partners have hepatitis C show that their viruses are rarely identical, and that sexual transmission occurs in only 1 case in 500. This suggests that blood-to-blood transmission, perhaps due to traumatic sexual practices, is likely to account for the transmission of hepatitis C in patients who are HIV positive.

Most authorities recommend treating these coinfected patients with interferon and ribavirin, but controversy remains over when to begin that treatment. Many patients seroconvert on their own, so the question is how long to wait.

“There's a big argument in the world literature [over] whether you should wait 12 weeks, 24 weeks, [or some other length of time],” Dr. Peters said. “We know that if you wait too long the patient will become chronic and then [his or her] chances of responding are very low. So we are fairly aggressive, and if we have a pinpoint of when they acquired [the infection], I would wait 12 weeks. If we don't have a pinpoint, it's doctor-patient preference.”

SAN FRANCISCO — The longer infants experience hyperglycemia following cardiac surgery, the greater their morbidity and mortality, Dr. Andrew R. Yates reported in a poster presentation at the annual congress of the Society of Critical Care Medicine.

Infants who have hyperglycemia for 7 days or more have close to a 100% chance of morbidity and a 50%–60% chance of mortality, according to Dr. Yates and his colleagues from Ohio State University, Columbus.

Their retrospective chart review involved 184 patients younger than 1 year who underwent cardiac surgery requiring cardiopulmonary bypass. At baseline, infants who weighed less than 2 kg; those with liver or renal insufficiency, or diabetes; or those requiring extracorporeal circulation membrane oxygenation (ECMO) were excluded.

The average age of the infants was 4.3 months, and their average weight was 4.9 kg. Of the 184 patients, 21 (11.4%) died. Duration of hyperglycemia was significantly associated with liver insufficiency, renal insufficiency, infection, CNS events, the need for dialysis, the need for ECMO, and a composite measure of morbidity.

Two other measures of hyperglycemia—initial glucose level and peak glucose level—had somewhat weaker associations with various forms of morbidity. Both measures were significantly associated with the composite morbidity measure.

SAN FRANCISCO — The longer infants experience hyperglycemia following cardiac surgery, the greater their morbidity and mortality, Dr. Andrew R. Yates reported in a poster presentation at the annual congress of the Society of Critical Care Medicine.

Infants who have hyperglycemia for 7 days or more have close to a 100% chance of morbidity and a 50%–60% chance of mortality, according to Dr. Yates and his colleagues from Ohio State University, Columbus.

Their retrospective chart review involved 184 patients younger than 1 year who underwent cardiac surgery requiring cardiopulmonary bypass. At baseline, infants who weighed less than 2 kg; those with liver or renal insufficiency, or diabetes; or those requiring extracorporeal circulation membrane oxygenation (ECMO) were excluded.

The average age of the infants was 4.3 months, and their average weight was 4.9 kg. Of the 184 patients, 21 (11.4%) died. Duration of hyperglycemia was significantly associated with liver insufficiency, renal insufficiency, infection, CNS events, the need for dialysis, the need for ECMO, and a composite measure of morbidity.

Two other measures of hyperglycemia—initial glucose level and peak glucose level—had somewhat weaker associations with various forms of morbidity. Both measures were significantly associated with the composite morbidity measure.

SAN FRANCISCO — The longer infants experience hyperglycemia following cardiac surgery, the greater their morbidity and mortality, Dr. Andrew R. Yates reported in a poster presentation at the annual congress of the Society of Critical Care Medicine.

Infants who have hyperglycemia for 7 days or more have close to a 100% chance of morbidity and a 50%–60% chance of mortality, according to Dr. Yates and his colleagues from Ohio State University, Columbus.

Their retrospective chart review involved 184 patients younger than 1 year who underwent cardiac surgery requiring cardiopulmonary bypass. At baseline, infants who weighed less than 2 kg; those with liver or renal insufficiency, or diabetes; or those requiring extracorporeal circulation membrane oxygenation (ECMO) were excluded.

The average age of the infants was 4.3 months, and their average weight was 4.9 kg. Of the 184 patients, 21 (11.4%) died. Duration of hyperglycemia was significantly associated with liver insufficiency, renal insufficiency, infection, CNS events, the need for dialysis, the need for ECMO, and a composite measure of morbidity.

Two other measures of hyperglycemia—initial glucose level and peak glucose level—had somewhat weaker associations with various forms of morbidity. Both measures were significantly associated with the composite morbidity measure.

The risk of transmission of hepatitis C from mother to infant is increased by concomitant HIV infection.

The study turned up the surprising result that girl babies are at twice the risk of vertical transmission as are boys (J. Infect. Dis. 2005;192:1872–9). The study, by the European Paediatric Hepatitis C Virus Network, involved 1,479 pregnant women with confirmed hepatitis C infections from 33 sites across Europe. They and their babies were followed prospectively over at least 24 months.

Infants were counted as being infected only if they tested positive (by an RNA polymerase chain reaction test and/or by the presence of anti-hepatitis C antibodies) after the age of 18 months. This is the age by which passively acquired maternal antibodies have almost always disappeared.

The overall hepatitis C vertical transmission rate was 6.2%. Among mothers who were coinfected with HIV, the transmission rate was 8.7%, significantly higher than the 5.5% rate seen among mothers who were infected only with hepatitis C.

After adjusting for maternal HIV infection status, mode of delivery, prematurity, and infant feeding type, the study showed that female infants had 2.07 times the risk of vertical transmission as males, a statistically significant increase.

The risk of transmission of hepatitis C from mother to infant is increased by concomitant HIV infection.

The study turned up the surprising result that girl babies are at twice the risk of vertical transmission as are boys (J. Infect. Dis. 2005;192:1872–9). The study, by the European Paediatric Hepatitis C Virus Network, involved 1,479 pregnant women with confirmed hepatitis C infections from 33 sites across Europe. They and their babies were followed prospectively over at least 24 months.

Infants were counted as being infected only if they tested positive (by an RNA polymerase chain reaction test and/or by the presence of anti-hepatitis C antibodies) after the age of 18 months. This is the age by which passively acquired maternal antibodies have almost always disappeared.

The overall hepatitis C vertical transmission rate was 6.2%. Among mothers who were coinfected with HIV, the transmission rate was 8.7%, significantly higher than the 5.5% rate seen among mothers who were infected only with hepatitis C.

After adjusting for maternal HIV infection status, mode of delivery, prematurity, and infant feeding type, the study showed that female infants had 2.07 times the risk of vertical transmission as males, a statistically significant increase.

The risk of transmission of hepatitis C from mother to infant is increased by concomitant HIV infection.

The study turned up the surprising result that girl babies are at twice the risk of vertical transmission as are boys (J. Infect. Dis. 2005;192:1872–9). The study, by the European Paediatric Hepatitis C Virus Network, involved 1,479 pregnant women with confirmed hepatitis C infections from 33 sites across Europe. They and their babies were followed prospectively over at least 24 months.

Infants were counted as being infected only if they tested positive (by an RNA polymerase chain reaction test and/or by the presence of anti-hepatitis C antibodies) after the age of 18 months. This is the age by which passively acquired maternal antibodies have almost always disappeared.

The overall hepatitis C vertical transmission rate was 6.2%. Among mothers who were coinfected with HIV, the transmission rate was 8.7%, significantly higher than the 5.5% rate seen among mothers who were infected only with hepatitis C.

After adjusting for maternal HIV infection status, mode of delivery, prematurity, and infant feeding type, the study showed that female infants had 2.07 times the risk of vertical transmission as males, a statistically significant increase.

SAN FRANCISCO — Elderly individuals who have metabolic syndrome are about twice as likely to become frail as those who are healthy, Dr. Joshua I. Barzilay reported in a poster presentation at the Third World Congress on Insulin Resistance Syndrome.

The study involved 2,376 individuals aged 69–74 who were followed prospectively for 7–9 years. At baseline none of the participants were frail, nor did they have other illnesses that increase inflammation markers or mimic frailty, reported Dr. Barzilay, of Emory University, Atlanta, and his colleagues.

At the end of follow-up, 169 participants qualified as frail and another 1,082 qualified as prefrail. The three most commonly seen components of frailty were diminished walking speed, diminished strength, and diminished activity, all of which are consistent with sarcopenia.

Participants who developed frailty or prefrailty had significantly higher fasting insulin levels, higher white blood cell counts, higher C-reactive protein levels, and higher factor VII levels than those who didn't.

Participants were 30%–100% more likely to have metabolic syndrome at baseline, compared with those who did not develop frailty or prefrailty.

SAN FRANCISCO — Elderly individuals who have metabolic syndrome are about twice as likely to become frail as those who are healthy, Dr. Joshua I. Barzilay reported in a poster presentation at the Third World Congress on Insulin Resistance Syndrome.

The study involved 2,376 individuals aged 69–74 who were followed prospectively for 7–9 years. At baseline none of the participants were frail, nor did they have other illnesses that increase inflammation markers or mimic frailty, reported Dr. Barzilay, of Emory University, Atlanta, and his colleagues.

At the end of follow-up, 169 participants qualified as frail and another 1,082 qualified as prefrail. The three most commonly seen components of frailty were diminished walking speed, diminished strength, and diminished activity, all of which are consistent with sarcopenia.

Participants who developed frailty or prefrailty had significantly higher fasting insulin levels, higher white blood cell counts, higher C-reactive protein levels, and higher factor VII levels than those who didn't.

Participants were 30%–100% more likely to have metabolic syndrome at baseline, compared with those who did not develop frailty or prefrailty.

SAN FRANCISCO — Elderly individuals who have metabolic syndrome are about twice as likely to become frail as those who are healthy, Dr. Joshua I. Barzilay reported in a poster presentation at the Third World Congress on Insulin Resistance Syndrome.

The study involved 2,376 individuals aged 69–74 who were followed prospectively for 7–9 years. At baseline none of the participants were frail, nor did they have other illnesses that increase inflammation markers or mimic frailty, reported Dr. Barzilay, of Emory University, Atlanta, and his colleagues.

At the end of follow-up, 169 participants qualified as frail and another 1,082 qualified as prefrail. The three most commonly seen components of frailty were diminished walking speed, diminished strength, and diminished activity, all of which are consistent with sarcopenia.

Participants who developed frailty or prefrailty had significantly higher fasting insulin levels, higher white blood cell counts, higher C-reactive protein levels, and higher factor VII levels than those who didn't.

Participants were 30%–100% more likely to have metabolic syndrome at baseline, compared with those who did not develop frailty or prefrailty.

SAN FRANCISCO — For at least one medical condition, it's low and not high BMI that predicts mortality, a study has shown.

Patients admitted to the ICU for septic shock had a significantly greater risk of death if they had a lower-than-normal BMI, according to a poster presented by Dr. Almothana Shanaah at the annual congress of the Society of Critical Care Medicine. Patients with BMIs in the overweight or obese ranges had no significantly increased risk of dying.

Dr. Shanaah of Cooper University Hospital, Camden, N.J., and colleagues used a multicenter database to extract data on patients admitted with septic shock. A total of 1,745 patients were included. The researchers considered patients with BMIs of 18.5–24.9 kg/m

The groups did not differ significantly in age or APACHE II (Acute Physiology and Chronic Health Evaluation) severity of disease score. Ventilator dependency and chronic renal failure also were associated with mortality.

SAN FRANCISCO — For at least one medical condition, it's low and not high BMI that predicts mortality, a study has shown.

Patients admitted to the ICU for septic shock had a significantly greater risk of death if they had a lower-than-normal BMI, according to a poster presented by Dr. Almothana Shanaah at the annual congress of the Society of Critical Care Medicine. Patients with BMIs in the overweight or obese ranges had no significantly increased risk of dying.

Dr. Shanaah of Cooper University Hospital, Camden, N.J., and colleagues used a multicenter database to extract data on patients admitted with septic shock. A total of 1,745 patients were included. The researchers considered patients with BMIs of 18.5–24.9 kg/m

The groups did not differ significantly in age or APACHE II (Acute Physiology and Chronic Health Evaluation) severity of disease score. Ventilator dependency and chronic renal failure also were associated with mortality.

SAN FRANCISCO — For at least one medical condition, it's low and not high BMI that predicts mortality, a study has shown.

Patients admitted to the ICU for septic shock had a significantly greater risk of death if they had a lower-than-normal BMI, according to a poster presented by Dr. Almothana Shanaah at the annual congress of the Society of Critical Care Medicine. Patients with BMIs in the overweight or obese ranges had no significantly increased risk of dying.

Dr. Shanaah of Cooper University Hospital, Camden, N.J., and colleagues used a multicenter database to extract data on patients admitted with septic shock. A total of 1,745 patients were included. The researchers considered patients with BMIs of 18.5–24.9 kg/m

The groups did not differ significantly in age or APACHE II (Acute Physiology and Chronic Health Evaluation) severity of disease score. Ventilator dependency and chronic renal failure also were associated with mortality.

SAN FRANCISCO — Recent research indicates that liver disease independently drives cardiovascular disease, Dr. Arun J. Sanyal said at the Third World Congress on Insulin Resistance Syndrome.

This relationship is so striking that Dr. Sanyal maintained, only half in jest, that “the liver is the boss of the heart.”

“The chicken-and-egg relationship between insulin resistance and hepatic steatosis can have potential effects at the level of the endothelium, platelet aggregability, and atherosclerosis, all of which combine to produce cardiovascular disease,” said Dr. Sanyal of Virginia Commonwealth University, Richmond.

One longitudinal study demonstrated that altered liver enzymes predict the development of metabolic syndrome (Diabetes 2005;54:3140–7).

Among 633 subjects who were free of metabolic syndrome at baseline, 127 developed metabolic syndrome within 5 years.

Multivariate logistic regression models adjusting for age, sex, ethnicity, and alcohol consumption showed that subjects in the upper quartiles of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALK) were at significantly increased risk of incident metabolic syndrome, compared with those in the lowest quartile.

Another study looked at endothelial function in 52 patients with nonalcoholic fatty liver disease (NAFLD) and 28 age- and sex-matched controls (Hepatology 2005;42:473–80). Compared with controls, patients with NAFLD had a significantly lower vasodilatory response of the brachial artery in response to ischemia. This response was significantly worse in patients with nonalcoholic steatohepatitis (NASH) than those with pure fatty liver.

In addition, the 10-year risk of coronary events as calculated by the Framingham equation was significantly worse in patients with NAFLD than in controls.

A third, longitudinal, study examined the relationship between gamma-glutamyltransferase (GGT) and incident hypertension (Hypertension 2005;46:1186–93). Among 897 patients with normal GGT values, those in the highest quintile of normal were more than twice as likely to develop hypertension over 6 years than were those in the lowest quintile. The investigators noted that the association between GGT and hypertension was present in both current and noncurrent drinkers, but only if they were above the mean in body mass index, waist circumference, and abdominal height.

This suggests that the association between GGT and hypertension is not due solely to alcohol consumption, and that fatty liver may represent an underlying mechanism of the association.

A fourth study used 4,222 normal subjects without cirrhosis or hepatitis B or C and examined the relationship between hepatic steatosis and carotid plaques (World J. Gastroenterol. 2005;11:1848–53).

After adjusting for confounding factors, the investigators determined that individuals with fatty liver had carotid plaques more often than did those without fatty liver. They hypothesized that this phenomenon may be explained by metabolic changes from nonalcoholic fatty liver disease.

Despite this accumulating evidence, Dr. Sanyal called for more research on the underlying mechanisms of the relationship between fatty liver, metabolic syndrome, and cardiovascular disease.

“This will give us terrific targets to identify new ways of addressing this atherosclerotic disease in patients who also have fatty liver disease,” he said.

This will give us new ways of addressing atherosclerotic disease in patients who also have a fatty liver. DR. SANYAL

SAN FRANCISCO — Recent research indicates that liver disease independently drives cardiovascular disease, Dr. Arun J. Sanyal said at the Third World Congress on Insulin Resistance Syndrome.

This relationship is so striking that Dr. Sanyal maintained, only half in jest, that “the liver is the boss of the heart.”

“The chicken-and-egg relationship between insulin resistance and hepatic steatosis can have potential effects at the level of the endothelium, platelet aggregability, and atherosclerosis, all of which combine to produce cardiovascular disease,” said Dr. Sanyal of Virginia Commonwealth University, Richmond.

One longitudinal study demonstrated that altered liver enzymes predict the development of metabolic syndrome (Diabetes 2005;54:3140–7).

Among 633 subjects who were free of metabolic syndrome at baseline, 127 developed metabolic syndrome within 5 years.

Multivariate logistic regression models adjusting for age, sex, ethnicity, and alcohol consumption showed that subjects in the upper quartiles of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALK) were at significantly increased risk of incident metabolic syndrome, compared with those in the lowest quartile.

Another study looked at endothelial function in 52 patients with nonalcoholic fatty liver disease (NAFLD) and 28 age- and sex-matched controls (Hepatology 2005;42:473–80). Compared with controls, patients with NAFLD had a significantly lower vasodilatory response of the brachial artery in response to ischemia. This response was significantly worse in patients with nonalcoholic steatohepatitis (NASH) than those with pure fatty liver.

In addition, the 10-year risk of coronary events as calculated by the Framingham equation was significantly worse in patients with NAFLD than in controls.

A third, longitudinal, study examined the relationship between gamma-glutamyltransferase (GGT) and incident hypertension (Hypertension 2005;46:1186–93). Among 897 patients with normal GGT values, those in the highest quintile of normal were more than twice as likely to develop hypertension over 6 years than were those in the lowest quintile. The investigators noted that the association between GGT and hypertension was present in both current and noncurrent drinkers, but only if they were above the mean in body mass index, waist circumference, and abdominal height.

This suggests that the association between GGT and hypertension is not due solely to alcohol consumption, and that fatty liver may represent an underlying mechanism of the association.

A fourth study used 4,222 normal subjects without cirrhosis or hepatitis B or C and examined the relationship between hepatic steatosis and carotid plaques (World J. Gastroenterol. 2005;11:1848–53).

After adjusting for confounding factors, the investigators determined that individuals with fatty liver had carotid plaques more often than did those without fatty liver. They hypothesized that this phenomenon may be explained by metabolic changes from nonalcoholic fatty liver disease.

Despite this accumulating evidence, Dr. Sanyal called for more research on the underlying mechanisms of the relationship between fatty liver, metabolic syndrome, and cardiovascular disease.

“This will give us terrific targets to identify new ways of addressing this atherosclerotic disease in patients who also have fatty liver disease,” he said.

This will give us new ways of addressing atherosclerotic disease in patients who also have a fatty liver. DR. SANYAL

SAN FRANCISCO — Recent research indicates that liver disease independently drives cardiovascular disease, Dr. Arun J. Sanyal said at the Third World Congress on Insulin Resistance Syndrome.

This relationship is so striking that Dr. Sanyal maintained, only half in jest, that “the liver is the boss of the heart.”

“The chicken-and-egg relationship between insulin resistance and hepatic steatosis can have potential effects at the level of the endothelium, platelet aggregability, and atherosclerosis, all of which combine to produce cardiovascular disease,” said Dr. Sanyal of Virginia Commonwealth University, Richmond.

One longitudinal study demonstrated that altered liver enzymes predict the development of metabolic syndrome (Diabetes 2005;54:3140–7).

Among 633 subjects who were free of metabolic syndrome at baseline, 127 developed metabolic syndrome within 5 years.

Multivariate logistic regression models adjusting for age, sex, ethnicity, and alcohol consumption showed that subjects in the upper quartiles of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALK) were at significantly increased risk of incident metabolic syndrome, compared with those in the lowest quartile.

Another study looked at endothelial function in 52 patients with nonalcoholic fatty liver disease (NAFLD) and 28 age- and sex-matched controls (Hepatology 2005;42:473–80). Compared with controls, patients with NAFLD had a significantly lower vasodilatory response of the brachial artery in response to ischemia. This response was significantly worse in patients with nonalcoholic steatohepatitis (NASH) than those with pure fatty liver.

In addition, the 10-year risk of coronary events as calculated by the Framingham equation was significantly worse in patients with NAFLD than in controls.

A third, longitudinal, study examined the relationship between gamma-glutamyltransferase (GGT) and incident hypertension (Hypertension 2005;46:1186–93). Among 897 patients with normal GGT values, those in the highest quintile of normal were more than twice as likely to develop hypertension over 6 years than were those in the lowest quintile. The investigators noted that the association between GGT and hypertension was present in both current and noncurrent drinkers, but only if they were above the mean in body mass index, waist circumference, and abdominal height.

This suggests that the association between GGT and hypertension is not due solely to alcohol consumption, and that fatty liver may represent an underlying mechanism of the association.

A fourth study used 4,222 normal subjects without cirrhosis or hepatitis B or C and examined the relationship between hepatic steatosis and carotid plaques (World J. Gastroenterol. 2005;11:1848–53).

After adjusting for confounding factors, the investigators determined that individuals with fatty liver had carotid plaques more often than did those without fatty liver. They hypothesized that this phenomenon may be explained by metabolic changes from nonalcoholic fatty liver disease.

Despite this accumulating evidence, Dr. Sanyal called for more research on the underlying mechanisms of the relationship between fatty liver, metabolic syndrome, and cardiovascular disease.

“This will give us terrific targets to identify new ways of addressing this atherosclerotic disease in patients who also have fatty liver disease,” he said.

This will give us new ways of addressing atherosclerotic disease in patients who also have a fatty liver. DR. SANYAL