Diana Mahoney

BOSTON — The increased risk of disease progression, AIDS, and death associated with structured treatment interruptions in HIV-positive patients is diminished but not fully reversed when continuous therapy is resumed, according to the final results of the largest HIV therapy trial to date.

A treatment strategy that includes interruptions in antiretroviral therapy (ART) guided by patients' CD4 cell counts was deemed detrimental in 2006 by investigators in the Strategies for Management of Antiretroviral Therapies (SMART) trial. The trial was halted and all patients were encouraged to resume therapy, based on interim data showing that patients who used ART only when their CD4 cell counts fell below a threshold had higher rates of AIDS-related opportunistic illnesses, serious nonopportunistic events, and all-cause mortality than patients who stayed on continuous therapy.

“Following the recommendation to reinitiate antiretroviral therapy for patients in the treatment interruption group, the risk of opportunistic disease or death was significantly reduced, but the [risk reduction] was less than complete,” Dr. Wafaa El-Sadr of New York's Harlem Hospital Center reported at the 15th Conference on Retroviruses and Opportunistic Infections. Patients who resumed treatment and were on continuous therapy for at least 85% of the 18 months following study modification reaped the most benefit from treatment reinitiation, she said.

The SMART trial enrolled 5,472 HIV-positive adults with CD4 cell counts of at least 350 cells/mm

Before the study was modified, patients in the conservation arm had spent 36% of the trial on treatment, with a median of three treatment interruptions over an 18-month period, while patients in the viral suppression arm spent 94% of the time on treatment, Dr. El-Sadr noted.

At the time of modification, 35% of the conservation patients and 82% of the suppression patients had an undetectable viral load (less than 400 copies/mL), and the respective median CD4 counts were 425 and 625 cells/mm

After the study modification, patients who had been in the conservation group spent 71% of the follow-up time on treatment, compared with 91% in the suppression group, Dr. El-Sadr said. At the end of the study, 83% and 95% of the conservation and suppression patients, respectively, were on treatment, she said.

With respect to CD4 cells, the percentage of time the conservation group spent with counts lower than 350 cells/mm

Before the study was altered, the outcome rates of opportunistic disease or death per 100 person-years were 3.4 in the conservation arm and 1.4 in the suppression arm. The respective rates per 100 person-years for death due to any cause and a composite outcome of serious cardiovascular, kidney, and liver events were 1.5 and 1.8 in the conservation arm, compared with 0.8 and 1.1 in the suppression group.

At final follow-up, the rates for all three outcomes declined significantly in the conservation arm and remained stable in the suppression arm. For example, the rate per 100 person-years of opportunistic disease or death among those who reinitiated treatment was 2.1, compared with 1.4 for the suppression group. The rates per 100 person-years of death from any cause and of composite serious events were 1.3 and 1.1 in the conservation group, vs. 0.9 and 0.9 in the suppression group, she said.

Patients who had developed a nonfatal opportunistic disease or cardiovascular disease and those who had a renal or liver event prior to study modification had a nearly sixfold increased risk of death after the study was altered, she reported.

The “less than full” risk reversal following treatment reinitiation in the drug conservation group could be a consequence of a lower average CD4 cell count and the increased number of patients with detectable viral load, which was likely associated with a failure to resume continuous therapy as recommended, Dr. El-Sadr said. The findings, she said, support the recommendation against antiretroviral therapy interruption based on CD4 cell threshold.

BOSTON — The increased risk of disease progression, AIDS, and death associated with structured treatment interruptions in HIV-positive patients is diminished but not fully reversed when continuous therapy is resumed, according to the final results of the largest HIV therapy trial to date.

A treatment strategy that includes interruptions in antiretroviral therapy (ART) guided by patients' CD4 cell counts was deemed detrimental in 2006 by investigators in the Strategies for Management of Antiretroviral Therapies (SMART) trial. The trial was halted and all patients were encouraged to resume therapy, based on interim data showing that patients who used ART only when their CD4 cell counts fell below a threshold had higher rates of AIDS-related opportunistic illnesses, serious nonopportunistic events, and all-cause mortality than patients who stayed on continuous therapy.

“Following the recommendation to reinitiate antiretroviral therapy for patients in the treatment interruption group, the risk of opportunistic disease or death was significantly reduced, but the [risk reduction] was less than complete,” Dr. Wafaa El-Sadr of New York's Harlem Hospital Center reported at the 15th Conference on Retroviruses and Opportunistic Infections. Patients who resumed treatment and were on continuous therapy for at least 85% of the 18 months following study modification reaped the most benefit from treatment reinitiation, she said.

The SMART trial enrolled 5,472 HIV-positive adults with CD4 cell counts of at least 350 cells/mm

Before the study was modified, patients in the conservation arm had spent 36% of the trial on treatment, with a median of three treatment interruptions over an 18-month period, while patients in the viral suppression arm spent 94% of the time on treatment, Dr. El-Sadr noted.

At the time of modification, 35% of the conservation patients and 82% of the suppression patients had an undetectable viral load (less than 400 copies/mL), and the respective median CD4 counts were 425 and 625 cells/mm

After the study modification, patients who had been in the conservation group spent 71% of the follow-up time on treatment, compared with 91% in the suppression group, Dr. El-Sadr said. At the end of the study, 83% and 95% of the conservation and suppression patients, respectively, were on treatment, she said.

With respect to CD4 cells, the percentage of time the conservation group spent with counts lower than 350 cells/mm

Before the study was altered, the outcome rates of opportunistic disease or death per 100 person-years were 3.4 in the conservation arm and 1.4 in the suppression arm. The respective rates per 100 person-years for death due to any cause and a composite outcome of serious cardiovascular, kidney, and liver events were 1.5 and 1.8 in the conservation arm, compared with 0.8 and 1.1 in the suppression group.

At final follow-up, the rates for all three outcomes declined significantly in the conservation arm and remained stable in the suppression arm. For example, the rate per 100 person-years of opportunistic disease or death among those who reinitiated treatment was 2.1, compared with 1.4 for the suppression group. The rates per 100 person-years of death from any cause and of composite serious events were 1.3 and 1.1 in the conservation group, vs. 0.9 and 0.9 in the suppression group, she said.

Patients who had developed a nonfatal opportunistic disease or cardiovascular disease and those who had a renal or liver event prior to study modification had a nearly sixfold increased risk of death after the study was altered, she reported.

The “less than full” risk reversal following treatment reinitiation in the drug conservation group could be a consequence of a lower average CD4 cell count and the increased number of patients with detectable viral load, which was likely associated with a failure to resume continuous therapy as recommended, Dr. El-Sadr said. The findings, she said, support the recommendation against antiretroviral therapy interruption based on CD4 cell threshold.

BOSTON — The increased risk of disease progression, AIDS, and death associated with structured treatment interruptions in HIV-positive patients is diminished but not fully reversed when continuous therapy is resumed, according to the final results of the largest HIV therapy trial to date.

A treatment strategy that includes interruptions in antiretroviral therapy (ART) guided by patients' CD4 cell counts was deemed detrimental in 2006 by investigators in the Strategies for Management of Antiretroviral Therapies (SMART) trial. The trial was halted and all patients were encouraged to resume therapy, based on interim data showing that patients who used ART only when their CD4 cell counts fell below a threshold had higher rates of AIDS-related opportunistic illnesses, serious nonopportunistic events, and all-cause mortality than patients who stayed on continuous therapy.

“Following the recommendation to reinitiate antiretroviral therapy for patients in the treatment interruption group, the risk of opportunistic disease or death was significantly reduced, but the [risk reduction] was less than complete,” Dr. Wafaa El-Sadr of New York's Harlem Hospital Center reported at the 15th Conference on Retroviruses and Opportunistic Infections. Patients who resumed treatment and were on continuous therapy for at least 85% of the 18 months following study modification reaped the most benefit from treatment reinitiation, she said.

The SMART trial enrolled 5,472 HIV-positive adults with CD4 cell counts of at least 350 cells/mm

Before the study was modified, patients in the conservation arm had spent 36% of the trial on treatment, with a median of three treatment interruptions over an 18-month period, while patients in the viral suppression arm spent 94% of the time on treatment, Dr. El-Sadr noted.

At the time of modification, 35% of the conservation patients and 82% of the suppression patients had an undetectable viral load (less than 400 copies/mL), and the respective median CD4 counts were 425 and 625 cells/mm

After the study modification, patients who had been in the conservation group spent 71% of the follow-up time on treatment, compared with 91% in the suppression group, Dr. El-Sadr said. At the end of the study, 83% and 95% of the conservation and suppression patients, respectively, were on treatment, she said.

With respect to CD4 cells, the percentage of time the conservation group spent with counts lower than 350 cells/mm

Before the study was altered, the outcome rates of opportunistic disease or death per 100 person-years were 3.4 in the conservation arm and 1.4 in the suppression arm. The respective rates per 100 person-years for death due to any cause and a composite outcome of serious cardiovascular, kidney, and liver events were 1.5 and 1.8 in the conservation arm, compared with 0.8 and 1.1 in the suppression group.

At final follow-up, the rates for all three outcomes declined significantly in the conservation arm and remained stable in the suppression arm. For example, the rate per 100 person-years of opportunistic disease or death among those who reinitiated treatment was 2.1, compared with 1.4 for the suppression group. The rates per 100 person-years of death from any cause and of composite serious events were 1.3 and 1.1 in the conservation group, vs. 0.9 and 0.9 in the suppression group, she said.

Patients who had developed a nonfatal opportunistic disease or cardiovascular disease and those who had a renal or liver event prior to study modification had a nearly sixfold increased risk of death after the study was altered, she reported.

The “less than full” risk reversal following treatment reinitiation in the drug conservation group could be a consequence of a lower average CD4 cell count and the increased number of patients with detectable viral load, which was likely associated with a failure to resume continuous therapy as recommended, Dr. El-Sadr said. The findings, she said, support the recommendation against antiretroviral therapy interruption based on CD4 cell threshold.

BOSTON — Long-term exposure to antiretroviral therapy appears to convey substantial metabolic risk to adolescents and young adults with HIV infection, according to a National Institutes of Health study.

In a cross-sectional investigation of 40 HIV-infected patients aged 11–27 years who acquired HIV in infancy or childhood and had been exposed to antiretroviral therapy (ART), a majority of study participants had impaired glucose tolerance and other metabolic abnormalities, said Dr. Colleen M. Hadigan of the National Institute of Allergy and Infectious Diseases and her colleagues.

While the medical literature is replete with studies linking such metabolic complications as dyslipidemia, lipodystrophy, and insulin resistance to long-term ART in HIV-infected adults, the pediatric literature is relatively sparse, and comprehensive reviews of metabolic consequences of ART in children are rare, Dr. Hadigan reported at the 15th Conference on Retroviruses and Opportunistic Infections.

The current study was designed to characterize the extent of metabolic abnormalities in a cohort of adolescents who acquired HIV infection perinatally or in childhood, she said.

All study subjects were ART experienced, with a mean treatment duration of 14 years, and all had current or past protease inhibitor and stavudine exposure. At the time of the investigation, 88% of the patients were receiving a protease inhibitor. At enrollment, approximately half of the patients had an HIV RNA of less than 50 copies/mL; the mean CD4 count was 665.

According to the study protocol, all of the subjects completed oral glucose tolerance testing and fasting insulin and lipid studies, and all underwent anthropometric assessments including whole body dual-energy x-ray absorptiometry (DXA) scans.

An analysis of the results showed impaired glucose tolerance in 20% of the subjects. The mean fasting insulin level for the group was 18 IU/mL, the mean glucose level was 86 mg/dL, and the mean homeostatic model for assessment of insulin resistance (HOMA) was 3.9, Dr. Hadigan reported at the conference, which was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.

Approximately 38% of the subjects had a HOMA value greater than 4.0, and thus met the criteria for insulin resistance, Dr. Hadigan said. In addition, 50% had elevated triglyceride levels (greater than 150 mg/dL), 53% had low levels of HDL cholesterol (less than 50 mg/dL for females and less than 40 mg/dL for males), and 24% had an elevated total cholesterol level (greater than 200 mg/dL).

With respect to body mass index (BMI) and body fat, the mean BMI was 22 kg/m

Approximately 15% of the subjects were overweight, with a BMI greater than 25 kg/m

Of interest, Dr. Hadigan noted, was the fact that insulin resistance by HOMA was significantly positively correlated with waist-to-hip ratio in this mostly nonobese population.

Although none of the subjects had type 2 diabetes, the results suggest that long-term exposure to ART may substantially increase their risk for that outcome as well as for cardiovascular disease, Dr. Hadigan warned.

As such, “these findings warrant careful monitoring in this population, as well as further research,” she added.

BOSTON — Long-term exposure to antiretroviral therapy appears to convey substantial metabolic risk to adolescents and young adults with HIV infection, according to a National Institutes of Health study.

In a cross-sectional investigation of 40 HIV-infected patients aged 11–27 years who acquired HIV in infancy or childhood and had been exposed to antiretroviral therapy (ART), a majority of study participants had impaired glucose tolerance and other metabolic abnormalities, said Dr. Colleen M. Hadigan of the National Institute of Allergy and Infectious Diseases and her colleagues.

While the medical literature is replete with studies linking such metabolic complications as dyslipidemia, lipodystrophy, and insulin resistance to long-term ART in HIV-infected adults, the pediatric literature is relatively sparse, and comprehensive reviews of metabolic consequences of ART in children are rare, Dr. Hadigan reported at the 15th Conference on Retroviruses and Opportunistic Infections.

The current study was designed to characterize the extent of metabolic abnormalities in a cohort of adolescents who acquired HIV infection perinatally or in childhood, she said.

All study subjects were ART experienced, with a mean treatment duration of 14 years, and all had current or past protease inhibitor and stavudine exposure. At the time of the investigation, 88% of the patients were receiving a protease inhibitor. At enrollment, approximately half of the patients had an HIV RNA of less than 50 copies/mL; the mean CD4 count was 665.

According to the study protocol, all of the subjects completed oral glucose tolerance testing and fasting insulin and lipid studies, and all underwent anthropometric assessments including whole body dual-energy x-ray absorptiometry (DXA) scans.

An analysis of the results showed impaired glucose tolerance in 20% of the subjects. The mean fasting insulin level for the group was 18 IU/mL, the mean glucose level was 86 mg/dL, and the mean homeostatic model for assessment of insulin resistance (HOMA) was 3.9, Dr. Hadigan reported at the conference, which was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.

Approximately 38% of the subjects had a HOMA value greater than 4.0, and thus met the criteria for insulin resistance, Dr. Hadigan said. In addition, 50% had elevated triglyceride levels (greater than 150 mg/dL), 53% had low levels of HDL cholesterol (less than 50 mg/dL for females and less than 40 mg/dL for males), and 24% had an elevated total cholesterol level (greater than 200 mg/dL).

With respect to body mass index (BMI) and body fat, the mean BMI was 22 kg/m

Approximately 15% of the subjects were overweight, with a BMI greater than 25 kg/m

Of interest, Dr. Hadigan noted, was the fact that insulin resistance by HOMA was significantly positively correlated with waist-to-hip ratio in this mostly nonobese population.

Although none of the subjects had type 2 diabetes, the results suggest that long-term exposure to ART may substantially increase their risk for that outcome as well as for cardiovascular disease, Dr. Hadigan warned.

As such, “these findings warrant careful monitoring in this population, as well as further research,” she added.

BOSTON — Long-term exposure to antiretroviral therapy appears to convey substantial metabolic risk to adolescents and young adults with HIV infection, according to a National Institutes of Health study.

In a cross-sectional investigation of 40 HIV-infected patients aged 11–27 years who acquired HIV in infancy or childhood and had been exposed to antiretroviral therapy (ART), a majority of study participants had impaired glucose tolerance and other metabolic abnormalities, said Dr. Colleen M. Hadigan of the National Institute of Allergy and Infectious Diseases and her colleagues.

While the medical literature is replete with studies linking such metabolic complications as dyslipidemia, lipodystrophy, and insulin resistance to long-term ART in HIV-infected adults, the pediatric literature is relatively sparse, and comprehensive reviews of metabolic consequences of ART in children are rare, Dr. Hadigan reported at the 15th Conference on Retroviruses and Opportunistic Infections.

The current study was designed to characterize the extent of metabolic abnormalities in a cohort of adolescents who acquired HIV infection perinatally or in childhood, she said.

All study subjects were ART experienced, with a mean treatment duration of 14 years, and all had current or past protease inhibitor and stavudine exposure. At the time of the investigation, 88% of the patients were receiving a protease inhibitor. At enrollment, approximately half of the patients had an HIV RNA of less than 50 copies/mL; the mean CD4 count was 665.

According to the study protocol, all of the subjects completed oral glucose tolerance testing and fasting insulin and lipid studies, and all underwent anthropometric assessments including whole body dual-energy x-ray absorptiometry (DXA) scans.

An analysis of the results showed impaired glucose tolerance in 20% of the subjects. The mean fasting insulin level for the group was 18 IU/mL, the mean glucose level was 86 mg/dL, and the mean homeostatic model for assessment of insulin resistance (HOMA) was 3.9, Dr. Hadigan reported at the conference, which was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.

Approximately 38% of the subjects had a HOMA value greater than 4.0, and thus met the criteria for insulin resistance, Dr. Hadigan said. In addition, 50% had elevated triglyceride levels (greater than 150 mg/dL), 53% had low levels of HDL cholesterol (less than 50 mg/dL for females and less than 40 mg/dL for males), and 24% had an elevated total cholesterol level (greater than 200 mg/dL).

With respect to body mass index (BMI) and body fat, the mean BMI was 22 kg/m

Approximately 15% of the subjects were overweight, with a BMI greater than 25 kg/m

Of interest, Dr. Hadigan noted, was the fact that insulin resistance by HOMA was significantly positively correlated with waist-to-hip ratio in this mostly nonobese population.

Although none of the subjects had type 2 diabetes, the results suggest that long-term exposure to ART may substantially increase their risk for that outcome as well as for cardiovascular disease, Dr. Hadigan warned.

As such, “these findings warrant careful monitoring in this population, as well as further research,” she added.

BOSTON — Recent use of the nucleoside analogues abacavir and didanosine is associated with a significantly increased risk of myocardial infarction in HIV-infected individuals, whereas treatment with the thymidine analogues appears to convey no such risk, according to findings presented at the 15th Conference on Retroviruses and Opportunistic Infections.

Using data from the DAD (Data Collection of Adverse Effects of Anti-HIV Drugs) study, a prospective study of more than 33,000 patients from 11 existing cohorts in Europe, Australia, and the United States, Dr. Caroline Sabin of the Royal Free Hospital, London, and her colleagues determined previously that antiretroviral treatment as a whole and protease inhibitor use specifically were associated with an increased risk of cardiovascular disease.

In the current study, 517 myocardial infarctions occurred during the approximately 7 years of follow-up. The study, which looked at the effect of five individual nucleoside reverse transcriptase inhibitors (NRTIs), showed that treatment with abacavir (Ziagen) was associated with a 90% increased risk of MI, and didanosine was associated with a 49% increased risk. Neither of the thymidine analogues—zidovudine or stavudine—nor the nucleoside analogue lamivudine was associated with increased MI risk, Dr. Sabin said. She reported no conflicts of interest pertaining to the study drugs.

The findings were unexpected, she noted, in that the current investigation was undertaken to test the hypothesis that thymidine analogues, because of their known association with dyslipidemia and insulin resistance, might also be associated with an increased risk of heart attack in HIV-infected individuals. “The primary hypothesis focused on exposure to stavudine and zidovudine. For completeness, the same analyses were performed for the other NRTIs” because there was sufficient exposure in the DAD cohort.

To assess the effect of cumulative, recent (defined as current or within the past 6 months), and past (defined as outside the past 6 months) use of the five NRTIs, the investigators generated Poisson regression models, adjusting for demographic factors including age, sex, HIV risk, and ethnicity; calendar year; cohort; cardiovascular risk factors not modified by antiretroviral therapy; and cumulative exposure to other antiretroviral drugs.

Neither cumulative nor recent use of the two thymidine analogues or lamivudine was associated with risk of MI, whereas recent use of abacavir and didanosine predicted risk of MI, Dr. Sabin reported. Additionally, the risks of MI associated with recent abacavir and didanosine use were independent of duration of use and remained after adjustment for HIV-RNA levels, CD4 count, dyslipidemia, and other metabolic factors, she said. Past use of both drugs was not associated with increased risk of MI, which suggests that the unknown biological mechanism for increased MI risk may be reversible upon cessation of the drugs, she added.

To determine the absolute risk of MI among nucleoside analogue users, the investigators incorporated the Framingham predicted 10-year coronary heart disease risk into the main regression model, and determined that the rate of MI was increased by 119% in patients with a moderate 10-year risk and by 222% in patients with a high 10-year risk, relative to those with a low 10-year risk, Dr. Sabin reported. As such, the clinical implications of the findings depend on an individual patient's underlying cardiovascular risk, she said.

Because of the perception that abacavir might have a safer cardiovascular profile than do the other drugs, the investigators considered the possibility that the findings might reflect a possible channeling bias, in that more patients with higher underlying risk of cardiovascular disease might receive initial treatment with abacavir. Such a bias is unlikely, however, because the adjustment for known cardiovascular risk factors had little effect on the outcomes, and because MI risk decreased after abacavir was stopped, Dr. Sabin said.

In a position statement, the DAD steering committee said that physicians should consider an individual patient's cardiovascular risk profile in determining the most appropriate anti-HIV drug regimen.

The conference was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.

BOSTON — Recent use of the nucleoside analogues abacavir and didanosine is associated with a significantly increased risk of myocardial infarction in HIV-infected individuals, whereas treatment with the thymidine analogues appears to convey no such risk, according to findings presented at the 15th Conference on Retroviruses and Opportunistic Infections.

Using data from the DAD (Data Collection of Adverse Effects of Anti-HIV Drugs) study, a prospective study of more than 33,000 patients from 11 existing cohorts in Europe, Australia, and the United States, Dr. Caroline Sabin of the Royal Free Hospital, London, and her colleagues determined previously that antiretroviral treatment as a whole and protease inhibitor use specifically were associated with an increased risk of cardiovascular disease.

In the current study, 517 myocardial infarctions occurred during the approximately 7 years of follow-up. The study, which looked at the effect of five individual nucleoside reverse transcriptase inhibitors (NRTIs), showed that treatment with abacavir (Ziagen) was associated with a 90% increased risk of MI, and didanosine was associated with a 49% increased risk. Neither of the thymidine analogues—zidovudine or stavudine—nor the nucleoside analogue lamivudine was associated with increased MI risk, Dr. Sabin said. She reported no conflicts of interest pertaining to the study drugs.

The findings were unexpected, she noted, in that the current investigation was undertaken to test the hypothesis that thymidine analogues, because of their known association with dyslipidemia and insulin resistance, might also be associated with an increased risk of heart attack in HIV-infected individuals. “The primary hypothesis focused on exposure to stavudine and zidovudine. For completeness, the same analyses were performed for the other NRTIs” because there was sufficient exposure in the DAD cohort.

To assess the effect of cumulative, recent (defined as current or within the past 6 months), and past (defined as outside the past 6 months) use of the five NRTIs, the investigators generated Poisson regression models, adjusting for demographic factors including age, sex, HIV risk, and ethnicity; calendar year; cohort; cardiovascular risk factors not modified by antiretroviral therapy; and cumulative exposure to other antiretroviral drugs.

Neither cumulative nor recent use of the two thymidine analogues or lamivudine was associated with risk of MI, whereas recent use of abacavir and didanosine predicted risk of MI, Dr. Sabin reported. Additionally, the risks of MI associated with recent abacavir and didanosine use were independent of duration of use and remained after adjustment for HIV-RNA levels, CD4 count, dyslipidemia, and other metabolic factors, she said. Past use of both drugs was not associated with increased risk of MI, which suggests that the unknown biological mechanism for increased MI risk may be reversible upon cessation of the drugs, she added.

To determine the absolute risk of MI among nucleoside analogue users, the investigators incorporated the Framingham predicted 10-year coronary heart disease risk into the main regression model, and determined that the rate of MI was increased by 119% in patients with a moderate 10-year risk and by 222% in patients with a high 10-year risk, relative to those with a low 10-year risk, Dr. Sabin reported. As such, the clinical implications of the findings depend on an individual patient's underlying cardiovascular risk, she said.

Because of the perception that abacavir might have a safer cardiovascular profile than do the other drugs, the investigators considered the possibility that the findings might reflect a possible channeling bias, in that more patients with higher underlying risk of cardiovascular disease might receive initial treatment with abacavir. Such a bias is unlikely, however, because the adjustment for known cardiovascular risk factors had little effect on the outcomes, and because MI risk decreased after abacavir was stopped, Dr. Sabin said.

In a position statement, the DAD steering committee said that physicians should consider an individual patient's cardiovascular risk profile in determining the most appropriate anti-HIV drug regimen.

The conference was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.

BOSTON — Recent use of the nucleoside analogues abacavir and didanosine is associated with a significantly increased risk of myocardial infarction in HIV-infected individuals, whereas treatment with the thymidine analogues appears to convey no such risk, according to findings presented at the 15th Conference on Retroviruses and Opportunistic Infections.

Using data from the DAD (Data Collection of Adverse Effects of Anti-HIV Drugs) study, a prospective study of more than 33,000 patients from 11 existing cohorts in Europe, Australia, and the United States, Dr. Caroline Sabin of the Royal Free Hospital, London, and her colleagues determined previously that antiretroviral treatment as a whole and protease inhibitor use specifically were associated with an increased risk of cardiovascular disease.

In the current study, 517 myocardial infarctions occurred during the approximately 7 years of follow-up. The study, which looked at the effect of five individual nucleoside reverse transcriptase inhibitors (NRTIs), showed that treatment with abacavir (Ziagen) was associated with a 90% increased risk of MI, and didanosine was associated with a 49% increased risk. Neither of the thymidine analogues—zidovudine or stavudine—nor the nucleoside analogue lamivudine was associated with increased MI risk, Dr. Sabin said. She reported no conflicts of interest pertaining to the study drugs.

The findings were unexpected, she noted, in that the current investigation was undertaken to test the hypothesis that thymidine analogues, because of their known association with dyslipidemia and insulin resistance, might also be associated with an increased risk of heart attack in HIV-infected individuals. “The primary hypothesis focused on exposure to stavudine and zidovudine. For completeness, the same analyses were performed for the other NRTIs” because there was sufficient exposure in the DAD cohort.

To assess the effect of cumulative, recent (defined as current or within the past 6 months), and past (defined as outside the past 6 months) use of the five NRTIs, the investigators generated Poisson regression models, adjusting for demographic factors including age, sex, HIV risk, and ethnicity; calendar year; cohort; cardiovascular risk factors not modified by antiretroviral therapy; and cumulative exposure to other antiretroviral drugs.

Neither cumulative nor recent use of the two thymidine analogues or lamivudine was associated with risk of MI, whereas recent use of abacavir and didanosine predicted risk of MI, Dr. Sabin reported. Additionally, the risks of MI associated with recent abacavir and didanosine use were independent of duration of use and remained after adjustment for HIV-RNA levels, CD4 count, dyslipidemia, and other metabolic factors, she said. Past use of both drugs was not associated with increased risk of MI, which suggests that the unknown biological mechanism for increased MI risk may be reversible upon cessation of the drugs, she added.

To determine the absolute risk of MI among nucleoside analogue users, the investigators incorporated the Framingham predicted 10-year coronary heart disease risk into the main regression model, and determined that the rate of MI was increased by 119% in patients with a moderate 10-year risk and by 222% in patients with a high 10-year risk, relative to those with a low 10-year risk, Dr. Sabin reported. As such, the clinical implications of the findings depend on an individual patient's underlying cardiovascular risk, she said.

Because of the perception that abacavir might have a safer cardiovascular profile than do the other drugs, the investigators considered the possibility that the findings might reflect a possible channeling bias, in that more patients with higher underlying risk of cardiovascular disease might receive initial treatment with abacavir. Such a bias is unlikely, however, because the adjustment for known cardiovascular risk factors had little effect on the outcomes, and because MI risk decreased after abacavir was stopped, Dr. Sabin said.

In a position statement, the DAD steering committee said that physicians should consider an individual patient's cardiovascular risk profile in determining the most appropriate anti-HIV drug regimen.

The conference was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.

BOSTON— Fluoxetine is not an effective treatment for depression in adolescents with comorbid substance-related disorders, suggest results of a placebo-controlled trial presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

Previous studies have suggested that—in adolescents with comorbid major depression and alcohol use disorder in particular—fluoxetine may minimize depressive symptoms and drinking.

In the current study, designed to assess the efficacy and tolerability of fluoxetine in adolescents aged 12–17 years who were diagnosed with depression and a substance use disorder, Dr. Robert L. Findling and his colleagues at University Hospitals Case Medical Center, Cleveland, showed that the effect of treatment with the selective serotonin reuptake inhibitor was comparable with placebo in alleviating depressive symptoms. Additionally, patients treated with fluoxetine did not show a significantly greater decrease in their substance use, compared with patients who received placebo.

The 34 adolescents (mean age 16.46 years) who were enrolled in the trial met DSM-IV-R (revised) criteria for major depressive disorder or dysthymic disorder, and all had depressive symptoms of at least moderate severity, Dr. Findling reported in a poster presentation.

In addition, all the patients had a comorbid substance use disorder, including cannabis use disorder (in 56%), polysubstance use disorder (39%), and alcohol use disorder (11%).

For the study, 18 patients were randomized to receive 10-mg fluoxetine for 4 weeks, after which the dose could be increased to 20 mg, and 16 patients were randomized to placebo with a matching increase after 4 weeks.

The primary study outcome was mean change from baseline to end point in depressive symptoms and psychosocial functioning, based on Children's Depression Rating Scale-Revised (CDRS-R) scores. Additional measures included the Clinical Global Impressions-Severity (CGI-S) scale, the CGI-improvement (CGI-I) scale, the Beck Depression Inventory (BDI), the Beck Hopelessness Scale (BHS), and the Children's Global Assessment of Functioning (CGAS). Rates of positive urine drug screens were calculated.

Comparison of the primary outcome via mixture model analysis demonstrated no treatment difference in mean change in CDRS-R total score, said Dr. Findling, who also noted that no significant treatment-by-visit interaction was observed in the random effects regression model, “suggesting there was no difference between treatment groups [in mean CDRS-R] change over time.”

No statistically significant differences in mean change from baseline were observed in any of the measures of depressive symptoms and psychosocial functioning, and an analysis of urine drug-screen results showed no difference in the rates of positive screens between treatment groups, he said.

Treatment was discontinued before 8 weeks by three patients in the placebo arm and six in the fluoxetine arm because of lack of efficacy, Dr. Findling said. Enrollment in the trial was stopped after the 8-week analysis based on the prespecified futility stopping rule.

Funding was provided by the American Foundation for Suicide Prevention and St. Luke's Foundation of Cleveland; medications were provided, in part, by Eli Lilly & Co.

The data suggest that there was no difference between the groups in terms of change in depression scores. DR. FINDLING

BOSTON— Fluoxetine is not an effective treatment for depression in adolescents with comorbid substance-related disorders, suggest results of a placebo-controlled trial presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

Previous studies have suggested that—in adolescents with comorbid major depression and alcohol use disorder in particular—fluoxetine may minimize depressive symptoms and drinking.

In the current study, designed to assess the efficacy and tolerability of fluoxetine in adolescents aged 12–17 years who were diagnosed with depression and a substance use disorder, Dr. Robert L. Findling and his colleagues at University Hospitals Case Medical Center, Cleveland, showed that the effect of treatment with the selective serotonin reuptake inhibitor was comparable with placebo in alleviating depressive symptoms. Additionally, patients treated with fluoxetine did not show a significantly greater decrease in their substance use, compared with patients who received placebo.

The 34 adolescents (mean age 16.46 years) who were enrolled in the trial met DSM-IV-R (revised) criteria for major depressive disorder or dysthymic disorder, and all had depressive symptoms of at least moderate severity, Dr. Findling reported in a poster presentation.

In addition, all the patients had a comorbid substance use disorder, including cannabis use disorder (in 56%), polysubstance use disorder (39%), and alcohol use disorder (11%).

For the study, 18 patients were randomized to receive 10-mg fluoxetine for 4 weeks, after which the dose could be increased to 20 mg, and 16 patients were randomized to placebo with a matching increase after 4 weeks.

The primary study outcome was mean change from baseline to end point in depressive symptoms and psychosocial functioning, based on Children's Depression Rating Scale-Revised (CDRS-R) scores. Additional measures included the Clinical Global Impressions-Severity (CGI-S) scale, the CGI-improvement (CGI-I) scale, the Beck Depression Inventory (BDI), the Beck Hopelessness Scale (BHS), and the Children's Global Assessment of Functioning (CGAS). Rates of positive urine drug screens were calculated.

Comparison of the primary outcome via mixture model analysis demonstrated no treatment difference in mean change in CDRS-R total score, said Dr. Findling, who also noted that no significant treatment-by-visit interaction was observed in the random effects regression model, “suggesting there was no difference between treatment groups [in mean CDRS-R] change over time.”

No statistically significant differences in mean change from baseline were observed in any of the measures of depressive symptoms and psychosocial functioning, and an analysis of urine drug-screen results showed no difference in the rates of positive screens between treatment groups, he said.

Treatment was discontinued before 8 weeks by three patients in the placebo arm and six in the fluoxetine arm because of lack of efficacy, Dr. Findling said. Enrollment in the trial was stopped after the 8-week analysis based on the prespecified futility stopping rule.

Funding was provided by the American Foundation for Suicide Prevention and St. Luke's Foundation of Cleveland; medications were provided, in part, by Eli Lilly & Co.

The data suggest that there was no difference between the groups in terms of change in depression scores. DR. FINDLING

BOSTON— Fluoxetine is not an effective treatment for depression in adolescents with comorbid substance-related disorders, suggest results of a placebo-controlled trial presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

Previous studies have suggested that—in adolescents with comorbid major depression and alcohol use disorder in particular—fluoxetine may minimize depressive symptoms and drinking.

In the current study, designed to assess the efficacy and tolerability of fluoxetine in adolescents aged 12–17 years who were diagnosed with depression and a substance use disorder, Dr. Robert L. Findling and his colleagues at University Hospitals Case Medical Center, Cleveland, showed that the effect of treatment with the selective serotonin reuptake inhibitor was comparable with placebo in alleviating depressive symptoms. Additionally, patients treated with fluoxetine did not show a significantly greater decrease in their substance use, compared with patients who received placebo.

The 34 adolescents (mean age 16.46 years) who were enrolled in the trial met DSM-IV-R (revised) criteria for major depressive disorder or dysthymic disorder, and all had depressive symptoms of at least moderate severity, Dr. Findling reported in a poster presentation.

In addition, all the patients had a comorbid substance use disorder, including cannabis use disorder (in 56%), polysubstance use disorder (39%), and alcohol use disorder (11%).

For the study, 18 patients were randomized to receive 10-mg fluoxetine for 4 weeks, after which the dose could be increased to 20 mg, and 16 patients were randomized to placebo with a matching increase after 4 weeks.

The primary study outcome was mean change from baseline to end point in depressive symptoms and psychosocial functioning, based on Children's Depression Rating Scale-Revised (CDRS-R) scores. Additional measures included the Clinical Global Impressions-Severity (CGI-S) scale, the CGI-improvement (CGI-I) scale, the Beck Depression Inventory (BDI), the Beck Hopelessness Scale (BHS), and the Children's Global Assessment of Functioning (CGAS). Rates of positive urine drug screens were calculated.

Comparison of the primary outcome via mixture model analysis demonstrated no treatment difference in mean change in CDRS-R total score, said Dr. Findling, who also noted that no significant treatment-by-visit interaction was observed in the random effects regression model, “suggesting there was no difference between treatment groups [in mean CDRS-R] change over time.”

No statistically significant differences in mean change from baseline were observed in any of the measures of depressive symptoms and psychosocial functioning, and an analysis of urine drug-screen results showed no difference in the rates of positive screens between treatment groups, he said.

Treatment was discontinued before 8 weeks by three patients in the placebo arm and six in the fluoxetine arm because of lack of efficacy, Dr. Findling said. Enrollment in the trial was stopped after the 8-week analysis based on the prespecified futility stopping rule.

Funding was provided by the American Foundation for Suicide Prevention and St. Luke's Foundation of Cleveland; medications were provided, in part, by Eli Lilly & Co.

The data suggest that there was no difference between the groups in terms of change in depression scores. DR. FINDLING

BOSTON – Vitamin D deficiency is prevalent in rheumatoid arthritis patients and may influence patient disability, which makes a periodic assessment of vitamin D status a crucial part of their management, according to Dr. Uzma J. Haque of Johns Hopkins University in Baltimore.

Of 62 rheumatoid arthritis patients followed at the Johns Hopkins Arthritis Center, Baltimore, from December 2003 through November 2006, those patients with vitamin D deficiency (defined as a serum 25-hydroxyvitamin D [25(OH)D] level below 30 ng/mL) were significantly more likely to report major difficulties in performing activities of daily living than were patients with normal levels of vitamin D, Dr. Haque reported in a poster presentation at the annual meeting of the American College of Rheumatology. Vitamin D deficiency was not, however, significantly associated with markers of rheumatoid arthritis, she said.

The mean age of the predominantly white, female (82%) study population was 57.6 years, and the mean disease duration was 11.6 years.

In addition to the serum concentration of 25(OH)D, the analysis included joint count, disease activity score, health assessment questionnaire (HAQ), and pain scores, Dr. Haque noted.

The investigators identified vitamin D deficiency in 37 of the 62 patients and observed that 25(OH)D levels fluctuated, ebbing lowest between April and June and highest between July and September, according to Dr. Haque.

Vitamin D deficiency was not significantly associated with any demographic or rheumatoid arthritis characteristics, nor were there any significant associations between vitamin D levels and disease activity score, joint counts, morning stiffness, or rheumatologist global assessments, she said.

“In contrast, [vitamin D] levels were significantly and inversely associated with HAQ, even after controlling for disease duration,” Dr. Haque reported.

Dr. Haque reported no conflicts of interest relative to her presentation.

BOSTON – Vitamin D deficiency is prevalent in rheumatoid arthritis patients and may influence patient disability, which makes a periodic assessment of vitamin D status a crucial part of their management, according to Dr. Uzma J. Haque of Johns Hopkins University in Baltimore.

Of 62 rheumatoid arthritis patients followed at the Johns Hopkins Arthritis Center, Baltimore, from December 2003 through November 2006, those patients with vitamin D deficiency (defined as a serum 25-hydroxyvitamin D [25(OH)D] level below 30 ng/mL) were significantly more likely to report major difficulties in performing activities of daily living than were patients with normal levels of vitamin D, Dr. Haque reported in a poster presentation at the annual meeting of the American College of Rheumatology. Vitamin D deficiency was not, however, significantly associated with markers of rheumatoid arthritis, she said.

The mean age of the predominantly white, female (82%) study population was 57.6 years, and the mean disease duration was 11.6 years.

In addition to the serum concentration of 25(OH)D, the analysis included joint count, disease activity score, health assessment questionnaire (HAQ), and pain scores, Dr. Haque noted.

The investigators identified vitamin D deficiency in 37 of the 62 patients and observed that 25(OH)D levels fluctuated, ebbing lowest between April and June and highest between July and September, according to Dr. Haque.

Vitamin D deficiency was not significantly associated with any demographic or rheumatoid arthritis characteristics, nor were there any significant associations between vitamin D levels and disease activity score, joint counts, morning stiffness, or rheumatologist global assessments, she said.

“In contrast, [vitamin D] levels were significantly and inversely associated with HAQ, even after controlling for disease duration,” Dr. Haque reported.

Dr. Haque reported no conflicts of interest relative to her presentation.

BOSTON – Vitamin D deficiency is prevalent in rheumatoid arthritis patients and may influence patient disability, which makes a periodic assessment of vitamin D status a crucial part of their management, according to Dr. Uzma J. Haque of Johns Hopkins University in Baltimore.

Of 62 rheumatoid arthritis patients followed at the Johns Hopkins Arthritis Center, Baltimore, from December 2003 through November 2006, those patients with vitamin D deficiency (defined as a serum 25-hydroxyvitamin D [25(OH)D] level below 30 ng/mL) were significantly more likely to report major difficulties in performing activities of daily living than were patients with normal levels of vitamin D, Dr. Haque reported in a poster presentation at the annual meeting of the American College of Rheumatology. Vitamin D deficiency was not, however, significantly associated with markers of rheumatoid arthritis, she said.

The mean age of the predominantly white, female (82%) study population was 57.6 years, and the mean disease duration was 11.6 years.

In addition to the serum concentration of 25(OH)D, the analysis included joint count, disease activity score, health assessment questionnaire (HAQ), and pain scores, Dr. Haque noted.

The investigators identified vitamin D deficiency in 37 of the 62 patients and observed that 25(OH)D levels fluctuated, ebbing lowest between April and June and highest between July and September, according to Dr. Haque.

Vitamin D deficiency was not significantly associated with any demographic or rheumatoid arthritis characteristics, nor were there any significant associations between vitamin D levels and disease activity score, joint counts, morning stiffness, or rheumatologist global assessments, she said.

“In contrast, [vitamin D] levels were significantly and inversely associated with HAQ, even after controlling for disease duration,” Dr. Haque reported.

Dr. Haque reported no conflicts of interest relative to her presentation.

BOSTON – Heart failure appears to be treated less aggressively in people with concomitant rheumatoid arthritis, based on the results of a community-based cohort study.

The findings, which were reported at the annual meeting of the American College of Rheumatology, showed that treatment disparities may account for some of the excess cardiovascular mortality in RA patients.

Optimizing the treatment of heart failure in RA could lead to improved survival and should be a priority, according to one of the study's investigators, Dr. John M Davis III of the Mayo Clinic in Rochester, Minn.

“The clinical implication is that we need to maintain a high index of suspicion for signs and symptoms of heart failure, order appropriate work-up, and consider cardiovascular referral and/or therapies,” he said in an interview.

Dr. Davis and his colleagues studied 309 patients, 103 with and 206 without RA. Their mean age was 78 years, and all had heart failure as defined by Framingham criteria. Medical charts were reviewed for data on the use of echocardiograms and the prescription of cardiovascular drugs, including ACE inhibitors, β-blockers, and diuretics, both before and after heart failure diagnosis. The researchers used chi-square tests and logistic regression models to examine the differences between the two groups.

The prevalence of ischemic heart disease was 24% in those with RA and 40% in those without. Hypertension was less prevalent in the RA patients (60% vs. 70%), but smoking was more prevalent (55% vs. 44%).

Fewer than half (47%) of the RA patients and 61% of those without RA received an echocardiogram within 90 days of their heart failure diagnosis, a significant difference. The difference persisted after adjusting for ischemic heart disease, hypertension, and smoking, Dr. Davis stated, noting that the odds ratio for receiving an echocardiogram among RA patients, compared with those without RA, was 0.53. In addition, 40% of the heart failure patients with RA and 84% of those without RA received cardiovascular medications within 60 days following diagnosis.

“The signs and symptoms of heart failure appear to be more subtle in the RA population, so there may be some difficulty in terms of recognition,” he said in an interview. Other disease factors might mask heart failure symptoms. “[Arthritis] patients' sedentary status limits the ability to develop exertional symptoms; interstitial lung changes can confound the pulmonary exam for edema; and swelling in the ankles could be interpreted as arthritis and not edema,” he said. In addition, long medication lists might discourage adding cardiovascular treatments and introduce compliance issues in patients.

BOSTON – Heart failure appears to be treated less aggressively in people with concomitant rheumatoid arthritis, based on the results of a community-based cohort study.

The findings, which were reported at the annual meeting of the American College of Rheumatology, showed that treatment disparities may account for some of the excess cardiovascular mortality in RA patients.

Optimizing the treatment of heart failure in RA could lead to improved survival and should be a priority, according to one of the study's investigators, Dr. John M Davis III of the Mayo Clinic in Rochester, Minn.

“The clinical implication is that we need to maintain a high index of suspicion for signs and symptoms of heart failure, order appropriate work-up, and consider cardiovascular referral and/or therapies,” he said in an interview.

Dr. Davis and his colleagues studied 309 patients, 103 with and 206 without RA. Their mean age was 78 years, and all had heart failure as defined by Framingham criteria. Medical charts were reviewed for data on the use of echocardiograms and the prescription of cardiovascular drugs, including ACE inhibitors, β-blockers, and diuretics, both before and after heart failure diagnosis. The researchers used chi-square tests and logistic regression models to examine the differences between the two groups.

The prevalence of ischemic heart disease was 24% in those with RA and 40% in those without. Hypertension was less prevalent in the RA patients (60% vs. 70%), but smoking was more prevalent (55% vs. 44%).

Fewer than half (47%) of the RA patients and 61% of those without RA received an echocardiogram within 90 days of their heart failure diagnosis, a significant difference. The difference persisted after adjusting for ischemic heart disease, hypertension, and smoking, Dr. Davis stated, noting that the odds ratio for receiving an echocardiogram among RA patients, compared with those without RA, was 0.53. In addition, 40% of the heart failure patients with RA and 84% of those without RA received cardiovascular medications within 60 days following diagnosis.

“The signs and symptoms of heart failure appear to be more subtle in the RA population, so there may be some difficulty in terms of recognition,” he said in an interview. Other disease factors might mask heart failure symptoms. “[Arthritis] patients' sedentary status limits the ability to develop exertional symptoms; interstitial lung changes can confound the pulmonary exam for edema; and swelling in the ankles could be interpreted as arthritis and not edema,” he said. In addition, long medication lists might discourage adding cardiovascular treatments and introduce compliance issues in patients.

BOSTON – Heart failure appears to be treated less aggressively in people with concomitant rheumatoid arthritis, based on the results of a community-based cohort study.

The findings, which were reported at the annual meeting of the American College of Rheumatology, showed that treatment disparities may account for some of the excess cardiovascular mortality in RA patients.

Optimizing the treatment of heart failure in RA could lead to improved survival and should be a priority, according to one of the study's investigators, Dr. John M Davis III of the Mayo Clinic in Rochester, Minn.

“The clinical implication is that we need to maintain a high index of suspicion for signs and symptoms of heart failure, order appropriate work-up, and consider cardiovascular referral and/or therapies,” he said in an interview.

Dr. Davis and his colleagues studied 309 patients, 103 with and 206 without RA. Their mean age was 78 years, and all had heart failure as defined by Framingham criteria. Medical charts were reviewed for data on the use of echocardiograms and the prescription of cardiovascular drugs, including ACE inhibitors, β-blockers, and diuretics, both before and after heart failure diagnosis. The researchers used chi-square tests and logistic regression models to examine the differences between the two groups.

The prevalence of ischemic heart disease was 24% in those with RA and 40% in those without. Hypertension was less prevalent in the RA patients (60% vs. 70%), but smoking was more prevalent (55% vs. 44%).

Fewer than half (47%) of the RA patients and 61% of those without RA received an echocardiogram within 90 days of their heart failure diagnosis, a significant difference. The difference persisted after adjusting for ischemic heart disease, hypertension, and smoking, Dr. Davis stated, noting that the odds ratio for receiving an echocardiogram among RA patients, compared with those without RA, was 0.53. In addition, 40% of the heart failure patients with RA and 84% of those without RA received cardiovascular medications within 60 days following diagnosis.

“The signs and symptoms of heart failure appear to be more subtle in the RA population, so there may be some difficulty in terms of recognition,” he said in an interview. Other disease factors might mask heart failure symptoms. “[Arthritis] patients' sedentary status limits the ability to develop exertional symptoms; interstitial lung changes can confound the pulmonary exam for edema; and swelling in the ankles could be interpreted as arthritis and not edema,” he said. In addition, long medication lists might discourage adding cardiovascular treatments and introduce compliance issues in patients.

BOSTON — Streamlining the preappointment assessment and management of new patients in clinical rheumatology settings can boost efficiency and improve care, according to Dr. J. Timothy Harrington Jr. of the University of Wisconsin, Madison.

Reviewing prospective patients' medical records, laboratory results, and imaging studies prior to scheduling an appointment ensures the most productive use of clinic time, Dr. Harrington said at the annual meeting of the American College of Rheumatology. The goal, he said, “is to distinguish between those patients who really need to see a rheumatologist and those who might be best served by seeing another specialist, such as an orthopedist, or who might be able to get the care they need from their primary care physician.”

Limiting “unnecessary” appointments—which can be as many as half of all appointment requests, said Dr. Harrington—substantially minimizes the wait time for new rheumatology appointments. By further classifying patients with appropriate rheumatologic indications as “routine” or “urgent,” and allocating the earliest available appointments to those with the most pressing conditions, rheumatologists are able to see new arthritis patients earlier in the disease process, when preventive interventions for joint damage are likely to have the most benefit, he said. The preappointment review of patient data also enables rheumatologists to determine how long an appointment to schedule for a given patient and reduces the likelihood of duplicity in terms of laboratory testing and imaging after the appointment, he added.

Another strategy is distributing the workload whenever possible “so the rheumatologist is not responsible for tasks that can easily be completed by support staff or even the patients themselves,” said Dr. Harrington. “This represents an enormous opportunity for us to transfer our resource use and efforts from low-value care to high-value care.”

For example, in a busy practice, rheumatologists should not be conducting narrative patient histories themselves, stressed Dr. Harrington. Instead, practices should implement a standardized data collection process with a history form that uses branching logic. “Typically, the top portion of these forms can be completed by patients while they are in the waiting room—that alone can save perhaps 40% of the time rheumatologists might spend just finding out what is going on,” he said. Physician assistants or nurse practitioners, when available, can help the patients with these forms and can provide the rheumatologist with a summary of the patients' history, he added.

The patient information can be used to generate an immediate disease activity score, such as the Global Arthritis Score, “which offers the rheumatologist an immediate sense of the patient's status and insight into optimal management,” Dr. Harrington noted.

Switching to electronic medical records and the use of standardized dictation templates, which replace word for word narratives, can also markedly reduce documentation time per patient. The end result is that “we can get more information in a more useful format and in less time than was previously possible,” said Dr. Harrington. “These measures change our focus from being information collectors to being problem solvers.”

The continuous application of process improvement methods is one of the most practical ways to address the growing deficit in the supply of rheumatologists relative to demand, said Dr. Harrington. “It's obvious, given the numbers, that we won't be able to provide care dependably to the population that needs it if we continue doing what we're doing. We have to play an active role in the scope of our practices, and we need to negotiate and plan with colleagues and other specialists so that we are involved primarily only in those services that we alone can capably provide.”

Dr. Harrington disclosed being a member of the Consortium of Rheumatology Researchers of North America (CORRONA) and receiving honoraria and grant support from Abbott Laboratories.

BOSTON — Streamlining the preappointment assessment and management of new patients in clinical rheumatology settings can boost efficiency and improve care, according to Dr. J. Timothy Harrington Jr. of the University of Wisconsin, Madison.

Reviewing prospective patients' medical records, laboratory results, and imaging studies prior to scheduling an appointment ensures the most productive use of clinic time, Dr. Harrington said at the annual meeting of the American College of Rheumatology. The goal, he said, “is to distinguish between those patients who really need to see a rheumatologist and those who might be best served by seeing another specialist, such as an orthopedist, or who might be able to get the care they need from their primary care physician.”

Limiting “unnecessary” appointments—which can be as many as half of all appointment requests, said Dr. Harrington—substantially minimizes the wait time for new rheumatology appointments. By further classifying patients with appropriate rheumatologic indications as “routine” or “urgent,” and allocating the earliest available appointments to those with the most pressing conditions, rheumatologists are able to see new arthritis patients earlier in the disease process, when preventive interventions for joint damage are likely to have the most benefit, he said. The preappointment review of patient data also enables rheumatologists to determine how long an appointment to schedule for a given patient and reduces the likelihood of duplicity in terms of laboratory testing and imaging after the appointment, he added.

Another strategy is distributing the workload whenever possible “so the rheumatologist is not responsible for tasks that can easily be completed by support staff or even the patients themselves,” said Dr. Harrington. “This represents an enormous opportunity for us to transfer our resource use and efforts from low-value care to high-value care.”

For example, in a busy practice, rheumatologists should not be conducting narrative patient histories themselves, stressed Dr. Harrington. Instead, practices should implement a standardized data collection process with a history form that uses branching logic. “Typically, the top portion of these forms can be completed by patients while they are in the waiting room—that alone can save perhaps 40% of the time rheumatologists might spend just finding out what is going on,” he said. Physician assistants or nurse practitioners, when available, can help the patients with these forms and can provide the rheumatologist with a summary of the patients' history, he added.

The patient information can be used to generate an immediate disease activity score, such as the Global Arthritis Score, “which offers the rheumatologist an immediate sense of the patient's status and insight into optimal management,” Dr. Harrington noted.

Switching to electronic medical records and the use of standardized dictation templates, which replace word for word narratives, can also markedly reduce documentation time per patient. The end result is that “we can get more information in a more useful format and in less time than was previously possible,” said Dr. Harrington. “These measures change our focus from being information collectors to being problem solvers.”

The continuous application of process improvement methods is one of the most practical ways to address the growing deficit in the supply of rheumatologists relative to demand, said Dr. Harrington. “It's obvious, given the numbers, that we won't be able to provide care dependably to the population that needs it if we continue doing what we're doing. We have to play an active role in the scope of our practices, and we need to negotiate and plan with colleagues and other specialists so that we are involved primarily only in those services that we alone can capably provide.”

Dr. Harrington disclosed being a member of the Consortium of Rheumatology Researchers of North America (CORRONA) and receiving honoraria and grant support from Abbott Laboratories.

BOSTON — Streamlining the preappointment assessment and management of new patients in clinical rheumatology settings can boost efficiency and improve care, according to Dr. J. Timothy Harrington Jr. of the University of Wisconsin, Madison.

Reviewing prospective patients' medical records, laboratory results, and imaging studies prior to scheduling an appointment ensures the most productive use of clinic time, Dr. Harrington said at the annual meeting of the American College of Rheumatology. The goal, he said, “is to distinguish between those patients who really need to see a rheumatologist and those who might be best served by seeing another specialist, such as an orthopedist, or who might be able to get the care they need from their primary care physician.”

Limiting “unnecessary” appointments—which can be as many as half of all appointment requests, said Dr. Harrington—substantially minimizes the wait time for new rheumatology appointments. By further classifying patients with appropriate rheumatologic indications as “routine” or “urgent,” and allocating the earliest available appointments to those with the most pressing conditions, rheumatologists are able to see new arthritis patients earlier in the disease process, when preventive interventions for joint damage are likely to have the most benefit, he said. The preappointment review of patient data also enables rheumatologists to determine how long an appointment to schedule for a given patient and reduces the likelihood of duplicity in terms of laboratory testing and imaging after the appointment, he added.

Another strategy is distributing the workload whenever possible “so the rheumatologist is not responsible for tasks that can easily be completed by support staff or even the patients themselves,” said Dr. Harrington. “This represents an enormous opportunity for us to transfer our resource use and efforts from low-value care to high-value care.”

For example, in a busy practice, rheumatologists should not be conducting narrative patient histories themselves, stressed Dr. Harrington. Instead, practices should implement a standardized data collection process with a history form that uses branching logic. “Typically, the top portion of these forms can be completed by patients while they are in the waiting room—that alone can save perhaps 40% of the time rheumatologists might spend just finding out what is going on,” he said. Physician assistants or nurse practitioners, when available, can help the patients with these forms and can provide the rheumatologist with a summary of the patients' history, he added.

The patient information can be used to generate an immediate disease activity score, such as the Global Arthritis Score, “which offers the rheumatologist an immediate sense of the patient's status and insight into optimal management,” Dr. Harrington noted.

Switching to electronic medical records and the use of standardized dictation templates, which replace word for word narratives, can also markedly reduce documentation time per patient. The end result is that “we can get more information in a more useful format and in less time than was previously possible,” said Dr. Harrington. “These measures change our focus from being information collectors to being problem solvers.”

The continuous application of process improvement methods is one of the most practical ways to address the growing deficit in the supply of rheumatologists relative to demand, said Dr. Harrington. “It's obvious, given the numbers, that we won't be able to provide care dependably to the population that needs it if we continue doing what we're doing. We have to play an active role in the scope of our practices, and we need to negotiate and plan with colleagues and other specialists so that we are involved primarily only in those services that we alone can capably provide.”

Dr. Harrington disclosed being a member of the Consortium of Rheumatology Researchers of North America (CORRONA) and receiving honoraria and grant support from Abbott Laboratories.

BOSTON — The occurrence of antineutrophil cytoplasmic antibody-associated vasculitis among close relatives of individuals with the condition is low, a Swedish study has shown. The findings provide insight into the long-unanswered question of genetic susceptibility of the autoimmune vasculitis, Dr. Ann Knight reported at the annual meeting of the American College of Rheumatology.

As with rheumatoid arthritis, the etiology of ANCA-associated vasculitis is thought to harbor some interplay between genetic predisposition and environmental triggers; however, little is known about whether the disease actually aggregates in families, said Dr. Knight of Uppsala University Hospital in Sweden. While familial clustering of ANCA-associated vasculitis has been reported in multiple case reports, “our results argue strongly against a pronounced increase in familial risk,” she said, noting that the degree of familial aggregation appears to be similar in magnitude to that observed in rheumatoid arthritis.

To assess familial risk of ANCA-associated vasculitis, Dr. Knight and colleagues conducted a population-based study of the Swedish Inpatient Register, a database of all patients admitted to Swedish hospitals since 1964 identifying 1,944 patients with ANCA-associated vasculitis for 1975-2004. Slightly more than half of the patients were male, and their mean age at first hospitalization was 61 years.

Through linkage to nationwide population-based Swedish registers on morbidity, family structure, and vital status, “we compared the occurrence of [ANCA-associated vasculitis] among the 6,670 first-degree relatives and 428 spouses of the [ANCA-associated vasculitis] patients to the occurrence of the disease among 68,994 first-degree relatives and 4,812 spouses of 19,655 randomly selected general population controls,” Dr. Knight explained. The investigators used the Cox proportional hazards regression method to estimate relative risks, taking potential familial clustering into account, she said.

Among the 6,670 relatives of ANCA-associated vasculitis patients, there were two cases of the disease (one pair, consisting of a mother and son), Dr. Knight reported. There were 13 cases among the first-degree relatives of the population controls, none of which occurred in the same family, she said. None of the spouses of patients were found to have the disease.

The relative risk of ANCA-associated vasculitis in first-degree relatives was 1.56, Dr. Knight stated. The low relative risk is of clinical relevance, she noted, because patients often ask whether their own diagnosis puts their closest relatives at increased risk for the disease. Previously, clinicians' ability to answer this question rested only on case reports, which by definition do not allow for risk quantification, she said.

Dr. Knight reported having no financial disclosures relative to her presentation.

BOSTON — The occurrence of antineutrophil cytoplasmic antibody-associated vasculitis among close relatives of individuals with the condition is low, a Swedish study has shown. The findings provide insight into the long-unanswered question of genetic susceptibility of the autoimmune vasculitis, Dr. Ann Knight reported at the annual meeting of the American College of Rheumatology.

As with rheumatoid arthritis, the etiology of ANCA-associated vasculitis is thought to harbor some interplay between genetic predisposition and environmental triggers; however, little is known about whether the disease actually aggregates in families, said Dr. Knight of Uppsala University Hospital in Sweden. While familial clustering of ANCA-associated vasculitis has been reported in multiple case reports, “our results argue strongly against a pronounced increase in familial risk,” she said, noting that the degree of familial aggregation appears to be similar in magnitude to that observed in rheumatoid arthritis.

To assess familial risk of ANCA-associated vasculitis, Dr. Knight and colleagues conducted a population-based study of the Swedish Inpatient Register, a database of all patients admitted to Swedish hospitals since 1964 identifying 1,944 patients with ANCA-associated vasculitis for 1975-2004. Slightly more than half of the patients were male, and their mean age at first hospitalization was 61 years.

Through linkage to nationwide population-based Swedish registers on morbidity, family structure, and vital status, “we compared the occurrence of [ANCA-associated vasculitis] among the 6,670 first-degree relatives and 428 spouses of the [ANCA-associated vasculitis] patients to the occurrence of the disease among 68,994 first-degree relatives and 4,812 spouses of 19,655 randomly selected general population controls,” Dr. Knight explained. The investigators used the Cox proportional hazards regression method to estimate relative risks, taking potential familial clustering into account, she said.

Among the 6,670 relatives of ANCA-associated vasculitis patients, there were two cases of the disease (one pair, consisting of a mother and son), Dr. Knight reported. There were 13 cases among the first-degree relatives of the population controls, none of which occurred in the same family, she said. None of the spouses of patients were found to have the disease.

The relative risk of ANCA-associated vasculitis in first-degree relatives was 1.56, Dr. Knight stated. The low relative risk is of clinical relevance, she noted, because patients often ask whether their own diagnosis puts their closest relatives at increased risk for the disease. Previously, clinicians' ability to answer this question rested only on case reports, which by definition do not allow for risk quantification, she said.

Dr. Knight reported having no financial disclosures relative to her presentation.

BOSTON — The occurrence of antineutrophil cytoplasmic antibody-associated vasculitis among close relatives of individuals with the condition is low, a Swedish study has shown. The findings provide insight into the long-unanswered question of genetic susceptibility of the autoimmune vasculitis, Dr. Ann Knight reported at the annual meeting of the American College of Rheumatology.

As with rheumatoid arthritis, the etiology of ANCA-associated vasculitis is thought to harbor some interplay between genetic predisposition and environmental triggers; however, little is known about whether the disease actually aggregates in families, said Dr. Knight of Uppsala University Hospital in Sweden. While familial clustering of ANCA-associated vasculitis has been reported in multiple case reports, “our results argue strongly against a pronounced increase in familial risk,” she said, noting that the degree of familial aggregation appears to be similar in magnitude to that observed in rheumatoid arthritis.

To assess familial risk of ANCA-associated vasculitis, Dr. Knight and colleagues conducted a population-based study of the Swedish Inpatient Register, a database of all patients admitted to Swedish hospitals since 1964 identifying 1,944 patients with ANCA-associated vasculitis for 1975-2004. Slightly more than half of the patients were male, and their mean age at first hospitalization was 61 years.

Through linkage to nationwide population-based Swedish registers on morbidity, family structure, and vital status, “we compared the occurrence of [ANCA-associated vasculitis] among the 6,670 first-degree relatives and 428 spouses of the [ANCA-associated vasculitis] patients to the occurrence of the disease among 68,994 first-degree relatives and 4,812 spouses of 19,655 randomly selected general population controls,” Dr. Knight explained. The investigators used the Cox proportional hazards regression method to estimate relative risks, taking potential familial clustering into account, she said.

Among the 6,670 relatives of ANCA-associated vasculitis patients, there were two cases of the disease (one pair, consisting of a mother and son), Dr. Knight reported. There were 13 cases among the first-degree relatives of the population controls, none of which occurred in the same family, she said. None of the spouses of patients were found to have the disease.

The relative risk of ANCA-associated vasculitis in first-degree relatives was 1.56, Dr. Knight stated. The low relative risk is of clinical relevance, she noted, because patients often ask whether their own diagnosis puts their closest relatives at increased risk for the disease. Previously, clinicians' ability to answer this question rested only on case reports, which by definition do not allow for risk quantification, she said.

Dr. Knight reported having no financial disclosures relative to her presentation.

Screening for specific combinations of risk factors can significantly increase the predictive accuracy of standard prodromal criteria for psychosis in high-risk adolescents, a study has shown.

In a longitudinal investigation of 291 adolescents, median age 16, who met the criteria for prodromal psychosis based on the Structured Interview for Prodromal Syndromes (SIPS), the risk of conversion to psychosis was 35%, Tyrone D. Cannon, Ph.D., of the University of California at Los Angeles, and his colleagues reported in the Archives of General Psychiatry.

The positive predictive power of the risk assessment more than doubled, however, with the application of algorithms combining two or three out of five “uniquely predictive” baseline variables, including baseline assessments of deteriorating social function, family history of psychosis together with a recent functional decline, increase in unusual thoughts, increase in suspicion and paranoia, and past or current drug abuse, the authors wrote (Arch. Gen. Psychiatry 2008;65:28-37).

Depending on the combination of variables, the refined predictive system increased the positive predictive accuracy up to 81%, which is comparable with the accuracy of risk assessment models seen in areas of preventive medicine such as diabetes.

The prospectively identified, treatment-seeking patients recruited for the study were evaluated across eight clinical research centers over the course of 21/2 years as part of the North American Prodrome Longitudinal Study (NAPLS). All of the study sites collected information on demographics, prodromal symptom severity, family history of mental illness, schizotypal personality disorder diagnosis, social and role functioning, comorbid psychiatric diagnosis, and substance abuse.

The follow-up assessments were administered at minimum 6-month intervals to detect clinical deterioration or conversion to psychosis.

In addition to determining the rate of conversion to psychosis in a high-risk population, the investigators sought to ascertain the shape of survival function across 21/2 follow-up years and to develop a multivariate risk prediction algorithm to guide case selection for future studies.

Of the 291 patients–which represents the largest database of prodromal cases followed up longitudinally worldwide–22% developed psychosis within the first 12 months, and approximately 11% and 2% had evidence of conversion at 24 and 30 months, respectively, they reported. None of the 134 healthy, age-matched controls developed psychotic illness during the study period.

Univariate analyses uncovered 37 potential predictor variables associated with conversion to psychosis. Of these, only the five aforementioned predictors continued to be related significantly and uniquely in multivariate models, according to the authors. The investigators generated prediction statistics for the five variables, independently and in each of 26 combinations. Among the algorithms requiring the co-occurrence of two risk factors, the models were associated with positive predictive values of 69% and 61%, respectively, the authors wrote.

In addition, two of the three-factor models–specifically, those involving genetic risk with recent functional decline, unusual thought content, and either suspicion/paranoia or impaired social functioning–had positive predictive values of 74% and 81%, respectively, while no further gain in prediction was associated with any of the four- or five-factor models, according to the authors. Controlling for the use of antipsychotic medication during the follow-up period did not alter the significance or the magnitude of the results, they stated.

The results of the study “provide a benchmark for the shape and rate of conversion risk against which to compare in future studies assessing comparable populations provided with a standardized intervention program,” the authors wrote.

In an accompanying editorial, Dr. Patrick D. McGorry of the University of Melbourne, and his colleagues, stressed that the NAPLS findings apply only to an ultrahigh-risk, treatment-seeking population and not to the general population (Arch. Gen. Psychiatry 2008;65:25-7).

They also cited the limitations inherent in the study's naturalistic design and called for a “large international multicenter clinical trial” to build on the NAPLS findings.

Screening for specific combinations of risk factors can significantly increase the predictive accuracy of standard prodromal criteria for psychosis in high-risk adolescents, a study has shown.

In a longitudinal investigation of 291 adolescents, median age 16, who met the criteria for prodromal psychosis based on the Structured Interview for Prodromal Syndromes (SIPS), the risk of conversion to psychosis was 35%, Tyrone D. Cannon, Ph.D., of the University of California at Los Angeles, and his colleagues reported in the Archives of General Psychiatry.

The positive predictive power of the risk assessment more than doubled, however, with the application of algorithms combining two or three out of five “uniquely predictive” baseline variables, including baseline assessments of deteriorating social function, family history of psychosis together with a recent functional decline, increase in unusual thoughts, increase in suspicion and paranoia, and past or current drug abuse, the authors wrote (Arch. Gen. Psychiatry 2008;65:28-37).

Depending on the combination of variables, the refined predictive system increased the positive predictive accuracy up to 81%, which is comparable with the accuracy of risk assessment models seen in areas of preventive medicine such as diabetes.

The prospectively identified, treatment-seeking patients recruited for the study were evaluated across eight clinical research centers over the course of 21/2 years as part of the North American Prodrome Longitudinal Study (NAPLS). All of the study sites collected information on demographics, prodromal symptom severity, family history of mental illness, schizotypal personality disorder diagnosis, social and role functioning, comorbid psychiatric diagnosis, and substance abuse.

The follow-up assessments were administered at minimum 6-month intervals to detect clinical deterioration or conversion to psychosis.

In addition to determining the rate of conversion to psychosis in a high-risk population, the investigators sought to ascertain the shape of survival function across 21/2 follow-up years and to develop a multivariate risk prediction algorithm to guide case selection for future studies.

Of the 291 patients–which represents the largest database of prodromal cases followed up longitudinally worldwide–22% developed psychosis within the first 12 months, and approximately 11% and 2% had evidence of conversion at 24 and 30 months, respectively, they reported. None of the 134 healthy, age-matched controls developed psychotic illness during the study period.

Univariate analyses uncovered 37 potential predictor variables associated with conversion to psychosis. Of these, only the five aforementioned predictors continued to be related significantly and uniquely in multivariate models, according to the authors. The investigators generated prediction statistics for the five variables, independently and in each of 26 combinations. Among the algorithms requiring the co-occurrence of two risk factors, the models were associated with positive predictive values of 69% and 61%, respectively, the authors wrote.

In addition, two of the three-factor models–specifically, those involving genetic risk with recent functional decline, unusual thought content, and either suspicion/paranoia or impaired social functioning–had positive predictive values of 74% and 81%, respectively, while no further gain in prediction was associated with any of the four- or five-factor models, according to the authors. Controlling for the use of antipsychotic medication during the follow-up period did not alter the significance or the magnitude of the results, they stated.

The results of the study “provide a benchmark for the shape and rate of conversion risk against which to compare in future studies assessing comparable populations provided with a standardized intervention program,” the authors wrote.

In an accompanying editorial, Dr. Patrick D. McGorry of the University of Melbourne, and his colleagues, stressed that the NAPLS findings apply only to an ultrahigh-risk, treatment-seeking population and not to the general population (Arch. Gen. Psychiatry 2008;65:25-7).

They also cited the limitations inherent in the study's naturalistic design and called for a “large international multicenter clinical trial” to build on the NAPLS findings.

Screening for specific combinations of risk factors can significantly increase the predictive accuracy of standard prodromal criteria for psychosis in high-risk adolescents, a study has shown.

In a longitudinal investigation of 291 adolescents, median age 16, who met the criteria for prodromal psychosis based on the Structured Interview for Prodromal Syndromes (SIPS), the risk of conversion to psychosis was 35%, Tyrone D. Cannon, Ph.D., of the University of California at Los Angeles, and his colleagues reported in the Archives of General Psychiatry.

The positive predictive power of the risk assessment more than doubled, however, with the application of algorithms combining two or three out of five “uniquely predictive” baseline variables, including baseline assessments of deteriorating social function, family history of psychosis together with a recent functional decline, increase in unusual thoughts, increase in suspicion and paranoia, and past or current drug abuse, the authors wrote (Arch. Gen. Psychiatry 2008;65:28-37).

Depending on the combination of variables, the refined predictive system increased the positive predictive accuracy up to 81%, which is comparable with the accuracy of risk assessment models seen in areas of preventive medicine such as diabetes.

The prospectively identified, treatment-seeking patients recruited for the study were evaluated across eight clinical research centers over the course of 21/2 years as part of the North American Prodrome Longitudinal Study (NAPLS). All of the study sites collected information on demographics, prodromal symptom severity, family history of mental illness, schizotypal personality disorder diagnosis, social and role functioning, comorbid psychiatric diagnosis, and substance abuse.

The follow-up assessments were administered at minimum 6-month intervals to detect clinical deterioration or conversion to psychosis.

In addition to determining the rate of conversion to psychosis in a high-risk population, the investigators sought to ascertain the shape of survival function across 21/2 follow-up years and to develop a multivariate risk prediction algorithm to guide case selection for future studies.

Of the 291 patients–which represents the largest database of prodromal cases followed up longitudinally worldwide–22% developed psychosis within the first 12 months, and approximately 11% and 2% had evidence of conversion at 24 and 30 months, respectively, they reported. None of the 134 healthy, age-matched controls developed psychotic illness during the study period.

Univariate analyses uncovered 37 potential predictor variables associated with conversion to psychosis. Of these, only the five aforementioned predictors continued to be related significantly and uniquely in multivariate models, according to the authors. The investigators generated prediction statistics for the five variables, independently and in each of 26 combinations. Among the algorithms requiring the co-occurrence of two risk factors, the models were associated with positive predictive values of 69% and 61%, respectively, the authors wrote.

In addition, two of the three-factor models–specifically, those involving genetic risk with recent functional decline, unusual thought content, and either suspicion/paranoia or impaired social functioning–had positive predictive values of 74% and 81%, respectively, while no further gain in prediction was associated with any of the four- or five-factor models, according to the authors. Controlling for the use of antipsychotic medication during the follow-up period did not alter the significance or the magnitude of the results, they stated.

The results of the study “provide a benchmark for the shape and rate of conversion risk against which to compare in future studies assessing comparable populations provided with a standardized intervention program,” the authors wrote.

In an accompanying editorial, Dr. Patrick D. McGorry of the University of Melbourne, and his colleagues, stressed that the NAPLS findings apply only to an ultrahigh-risk, treatment-seeking population and not to the general population (Arch. Gen. Psychiatry 2008;65:25-7).

They also cited the limitations inherent in the study's naturalistic design and called for a “large international multicenter clinical trial” to build on the NAPLS findings.

BOSTON – Fluoxetine is not an effective treatment for depression in adolescents with comorbid substance-related disorders, suggest results of a placebo-controlled trial presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

Previous studies have suggested that fluoxetine may minimize depressive symptoms and drinking in adolescents with comorbid major depression and alcohol use disorder.

In the current study, designed to assess the efficacy and tolerability of fluoxetine in adolescents aged 12-17 years who were diagnosed with depression and a substance use disorder, Dr. Robert L. Findling and his colleagues at University Hospitals Case Medical Center, Cleveland, showed that the effect of treatment with the selective serotonin reuptake inhibitor was comparable with placebo in alleviating depressive symptoms. Also, patients treated with fluoxetine did not show a significantly greater decrease in their substance use, compared with patients who received placebo.

The 34 adolescents (mean age 16.46 years) who were enrolled in the trial met DSM-IV-R (revised) criteria for major depressive disorder or dysthymic disorder, and all had depressive symptoms of at least moderate severity, Dr. Findling reported in a poster presentation.

In addition, all of the patients had a comorbid substance use disorder, including cannabis use disorder (in 56%), polysubstance use disorder (39%), and alcohol use disorder (11%).

For the study, 18 patients were randomized to receive 10-mg fluoxetine for 4 weeks, after which the dose could be increased to 20 mg, and 16 patients were randomized to placebo with a matching increase after 4 weeks.

The primary study outcome was mean change from baseline to end point in depressive symptoms and psychosocial functioning, based on Children's Depression Rating Scale-Revised (CDRS-R) scores.

Rates of positive urine drug screens were calculated to assess drug use during the 8-week study period.

Comparison of the primary outcome via mixture model analysis demonstrated no treatment difference in mean change in CDRS-R total score, said Dr. Findling, who also noted that no significant treatment-by-visit interaction was observed in the random effects regression model, “suggesting there was no difference between treatment groups [in mean CDRS-R] change over time.”

Analysis of urine drug-screen results showed no difference in rates of positive screens between treatment groups, he said.

Funding for the investigation was provided by the American Foundation for Suicide Prevention and St. Luke's Foundation of Cleveland, and study medications were provided, in part, by Eli Lilly & Co., which manufactures fluoxetine.

Analysis of urine drug-screen results showedno difference inrates of positive screens between treatment groups. DR. FINDLING

BOSTON – Fluoxetine is not an effective treatment for depression in adolescents with comorbid substance-related disorders, suggest results of a placebo-controlled trial presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

Previous studies have suggested that fluoxetine may minimize depressive symptoms and drinking in adolescents with comorbid major depression and alcohol use disorder.

In the current study, designed to assess the efficacy and tolerability of fluoxetine in adolescents aged 12-17 years who were diagnosed with depression and a substance use disorder, Dr. Robert L. Findling and his colleagues at University Hospitals Case Medical Center, Cleveland, showed that the effect of treatment with the selective serotonin reuptake inhibitor was comparable with placebo in alleviating depressive symptoms. Also, patients treated with fluoxetine did not show a significantly greater decrease in their substance use, compared with patients who received placebo.

The 34 adolescents (mean age 16.46 years) who were enrolled in the trial met DSM-IV-R (revised) criteria for major depressive disorder or dysthymic disorder, and all had depressive symptoms of at least moderate severity, Dr. Findling reported in a poster presentation.

In addition, all of the patients had a comorbid substance use disorder, including cannabis use disorder (in 56%), polysubstance use disorder (39%), and alcohol use disorder (11%).

For the study, 18 patients were randomized to receive 10-mg fluoxetine for 4 weeks, after which the dose could be increased to 20 mg, and 16 patients were randomized to placebo with a matching increase after 4 weeks.

The primary study outcome was mean change from baseline to end point in depressive symptoms and psychosocial functioning, based on Children's Depression Rating Scale-Revised (CDRS-R) scores.

Rates of positive urine drug screens were calculated to assess drug use during the 8-week study period.

Comparison of the primary outcome via mixture model analysis demonstrated no treatment difference in mean change in CDRS-R total score, said Dr. Findling, who also noted that no significant treatment-by-visit interaction was observed in the random effects regression model, “suggesting there was no difference between treatment groups [in mean CDRS-R] change over time.”

Analysis of urine drug-screen results showed no difference in rates of positive screens between treatment groups, he said.

Funding for the investigation was provided by the American Foundation for Suicide Prevention and St. Luke's Foundation of Cleveland, and study medications were provided, in part, by Eli Lilly & Co., which manufactures fluoxetine.

Analysis of urine drug-screen results showedno difference inrates of positive screens between treatment groups. DR. FINDLING

BOSTON – Fluoxetine is not an effective treatment for depression in adolescents with comorbid substance-related disorders, suggest results of a placebo-controlled trial presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

Previous studies have suggested that fluoxetine may minimize depressive symptoms and drinking in adolescents with comorbid major depression and alcohol use disorder.

In the current study, designed to assess the efficacy and tolerability of fluoxetine in adolescents aged 12-17 years who were diagnosed with depression and a substance use disorder, Dr. Robert L. Findling and his colleagues at University Hospitals Case Medical Center, Cleveland, showed that the effect of treatment with the selective serotonin reuptake inhibitor was comparable with placebo in alleviating depressive symptoms. Also, patients treated with fluoxetine did not show a significantly greater decrease in their substance use, compared with patients who received placebo.

The 34 adolescents (mean age 16.46 years) who were enrolled in the trial met DSM-IV-R (revised) criteria for major depressive disorder or dysthymic disorder, and all had depressive symptoms of at least moderate severity, Dr. Findling reported in a poster presentation.

In addition, all of the patients had a comorbid substance use disorder, including cannabis use disorder (in 56%), polysubstance use disorder (39%), and alcohol use disorder (11%).

For the study, 18 patients were randomized to receive 10-mg fluoxetine for 4 weeks, after which the dose could be increased to 20 mg, and 16 patients were randomized to placebo with a matching increase after 4 weeks.

The primary study outcome was mean change from baseline to end point in depressive symptoms and psychosocial functioning, based on Children's Depression Rating Scale-Revised (CDRS-R) scores.

Rates of positive urine drug screens were calculated to assess drug use during the 8-week study period.

Comparison of the primary outcome via mixture model analysis demonstrated no treatment difference in mean change in CDRS-R total score, said Dr. Findling, who also noted that no significant treatment-by-visit interaction was observed in the random effects regression model, “suggesting there was no difference between treatment groups [in mean CDRS-R] change over time.”

Analysis of urine drug-screen results showed no difference in rates of positive screens between treatment groups, he said.

Funding for the investigation was provided by the American Foundation for Suicide Prevention and St. Luke's Foundation of Cleveland, and study medications were provided, in part, by Eli Lilly & Co., which manufactures fluoxetine.

Analysis of urine drug-screen results showedno difference inrates of positive screens between treatment groups. DR. FINDLING