Martha Kerr

Hippocampal and amygdalar atrophy are predictive of dementia in the cognitively intact elderly, Dutch researchers reported.

The investigators studied 511 community residents aged 60–90 years and free of dementia at baseline. The objective of the study, conducted by Dr. Tom den Heijer of Erasmus Medical Center in Rotterdam, the Netherlands, and his colleagues, was to assess whether atrophy of the hippocampus and amygdala was present before the onset of dementia. All of the participants were part of The Rotterdam Study, a prospective, population-based study launched in 1990.

In the current investigation, volumetric assessment of the hippocampus and amygdala was evaluated by MRI. The investigators also performed extensive neuropsychological testing and questioned participants about daily memory problems (Arch. Gen. Psychiatry 2006;63:57–62).

During a mean follow-up of 6 years, 35 of the participants developed dementia, 26 of whom were diagnosed with Alzheimer's disease. The investigators found that those participants who developed dementia had much smaller hippocampal and amygdalar volumes at baseline than did those without incident dementia.

Furthermore, they found that volume reduction at baseline was inversely associated with time until the onset of dementia. This was true “even in persons without memory complaints or low cognitive performance at baseline,” the investigators reported.

Dr. den Heijer and his colleagues said that MRI findings have been validated by previous autopsy studies of brain tissue showing neuronal loss and Alzheimer's disease.

Decreases in hippocampal and amygdalar volumes of 5%–17% were found, depending on how far in advance of dementia the MRI was done. For individuals with Alzheimer's disease, Dr. den Heijer's team found reductions ranging from 25% to 40%, a range that suggests that the atrophy rate accelerates in patients with Alzheimer's disease.

The investigators concluded that “structural imaging can help identify people at high risk for developing dementia, even before they have any memory complaints or measurable cognitive impairment.” They hastened to add, however, that most people with atrophy failed to develop dementia, even after 6 years.

Hippocampal and amygdalar atrophy are predictive of dementia in the cognitively intact elderly, Dutch researchers reported.

The investigators studied 511 community residents aged 60–90 years and free of dementia at baseline. The objective of the study, conducted by Dr. Tom den Heijer of Erasmus Medical Center in Rotterdam, the Netherlands, and his colleagues, was to assess whether atrophy of the hippocampus and amygdala was present before the onset of dementia. All of the participants were part of The Rotterdam Study, a prospective, population-based study launched in 1990.

In the current investigation, volumetric assessment of the hippocampus and amygdala was evaluated by MRI. The investigators also performed extensive neuropsychological testing and questioned participants about daily memory problems (Arch. Gen. Psychiatry 2006;63:57–62).

During a mean follow-up of 6 years, 35 of the participants developed dementia, 26 of whom were diagnosed with Alzheimer's disease. The investigators found that those participants who developed dementia had much smaller hippocampal and amygdalar volumes at baseline than did those without incident dementia.

Furthermore, they found that volume reduction at baseline was inversely associated with time until the onset of dementia. This was true “even in persons without memory complaints or low cognitive performance at baseline,” the investigators reported.

Dr. den Heijer and his colleagues said that MRI findings have been validated by previous autopsy studies of brain tissue showing neuronal loss and Alzheimer's disease.

Decreases in hippocampal and amygdalar volumes of 5%–17% were found, depending on how far in advance of dementia the MRI was done. For individuals with Alzheimer's disease, Dr. den Heijer's team found reductions ranging from 25% to 40%, a range that suggests that the atrophy rate accelerates in patients with Alzheimer's disease.

The investigators concluded that “structural imaging can help identify people at high risk for developing dementia, even before they have any memory complaints or measurable cognitive impairment.” They hastened to add, however, that most people with atrophy failed to develop dementia, even after 6 years.

Hippocampal and amygdalar atrophy are predictive of dementia in the cognitively intact elderly, Dutch researchers reported.

The investigators studied 511 community residents aged 60–90 years and free of dementia at baseline. The objective of the study, conducted by Dr. Tom den Heijer of Erasmus Medical Center in Rotterdam, the Netherlands, and his colleagues, was to assess whether atrophy of the hippocampus and amygdala was present before the onset of dementia. All of the participants were part of The Rotterdam Study, a prospective, population-based study launched in 1990.

In the current investigation, volumetric assessment of the hippocampus and amygdala was evaluated by MRI. The investigators also performed extensive neuropsychological testing and questioned participants about daily memory problems (Arch. Gen. Psychiatry 2006;63:57–62).

During a mean follow-up of 6 years, 35 of the participants developed dementia, 26 of whom were diagnosed with Alzheimer's disease. The investigators found that those participants who developed dementia had much smaller hippocampal and amygdalar volumes at baseline than did those without incident dementia.

Furthermore, they found that volume reduction at baseline was inversely associated with time until the onset of dementia. This was true “even in persons without memory complaints or low cognitive performance at baseline,” the investigators reported.

Dr. den Heijer and his colleagues said that MRI findings have been validated by previous autopsy studies of brain tissue showing neuronal loss and Alzheimer's disease.

Decreases in hippocampal and amygdalar volumes of 5%–17% were found, depending on how far in advance of dementia the MRI was done. For individuals with Alzheimer's disease, Dr. den Heijer's team found reductions ranging from 25% to 40%, a range that suggests that the atrophy rate accelerates in patients with Alzheimer's disease.

The investigators concluded that “structural imaging can help identify people at high risk for developing dementia, even before they have any memory complaints or measurable cognitive impairment.” They hastened to add, however, that most people with atrophy failed to develop dementia, even after 6 years.

Vaginal birth does not contribute to the development of stress urinary incontinence later in life, according to Dr. Gunhilde Buchsbaum, of the department of ob.gyn at the University of Rochester (N.Y.), and colleagues.

“Contrary to the conventional wisdom that nulliparity protects against stress urinary incontinence, we found similar rates of urinary incontinence in postmenopausal nulliparous women and their parous biological sisters,” the investigators reported (Obstet. Gynecol. 2005;106:1253–8).

Dr. Buchsbaum's team analyzed a sample of 143 pairs of nulliparous/parous postmenopausal sisters. All of the women answered a questionnaire about symptoms of pelvic floor disorders, and 101 pairs also underwent clinical evaluation of urinary incontinence and genital prolapse. The researchers found that 47.6% of nulliparous women and 49.7% of parous women reported urinary incontinence, with no difference in type and severity of urinary incontinence between the groups.

Of interest was the finding that there was “a high concordance in continence status … within biological sisters,” according to Dr. Buchsbaum. This finding suggests that there may be a genetic predisposition for urinary incontinence. If that proves to be true, it “would have great implications for the direction of basic research, treatment approaches, risk management, and potential prophylactic interventions.”

Vaginal birth does not contribute to the development of stress urinary incontinence later in life, according to Dr. Gunhilde Buchsbaum, of the department of ob.gyn at the University of Rochester (N.Y.), and colleagues.

“Contrary to the conventional wisdom that nulliparity protects against stress urinary incontinence, we found similar rates of urinary incontinence in postmenopausal nulliparous women and their parous biological sisters,” the investigators reported (Obstet. Gynecol. 2005;106:1253–8).

Dr. Buchsbaum's team analyzed a sample of 143 pairs of nulliparous/parous postmenopausal sisters. All of the women answered a questionnaire about symptoms of pelvic floor disorders, and 101 pairs also underwent clinical evaluation of urinary incontinence and genital prolapse. The researchers found that 47.6% of nulliparous women and 49.7% of parous women reported urinary incontinence, with no difference in type and severity of urinary incontinence between the groups.

Of interest was the finding that there was “a high concordance in continence status … within biological sisters,” according to Dr. Buchsbaum. This finding suggests that there may be a genetic predisposition for urinary incontinence. If that proves to be true, it “would have great implications for the direction of basic research, treatment approaches, risk management, and potential prophylactic interventions.”

Vaginal birth does not contribute to the development of stress urinary incontinence later in life, according to Dr. Gunhilde Buchsbaum, of the department of ob.gyn at the University of Rochester (N.Y.), and colleagues.

“Contrary to the conventional wisdom that nulliparity protects against stress urinary incontinence, we found similar rates of urinary incontinence in postmenopausal nulliparous women and their parous biological sisters,” the investigators reported (Obstet. Gynecol. 2005;106:1253–8).

Dr. Buchsbaum's team analyzed a sample of 143 pairs of nulliparous/parous postmenopausal sisters. All of the women answered a questionnaire about symptoms of pelvic floor disorders, and 101 pairs also underwent clinical evaluation of urinary incontinence and genital prolapse. The researchers found that 47.6% of nulliparous women and 49.7% of parous women reported urinary incontinence, with no difference in type and severity of urinary incontinence between the groups.

Of interest was the finding that there was “a high concordance in continence status … within biological sisters,” according to Dr. Buchsbaum. This finding suggests that there may be a genetic predisposition for urinary incontinence. If that proves to be true, it “would have great implications for the direction of basic research, treatment approaches, risk management, and potential prophylactic interventions.”

Women with stable systemic lupus erythematosus can use with relative safety any one of three forms of birth control—a combined oral contraceptive, a progestin-only contraceptive, or the copper intrauterine device—according to the findings of a study that showed each method had its own small degree of risk.

The safety of these forms of contraception was evaluated in a study of 162 women with mild, stable systemic lupus erythematosus (SLE), according to Dr. Jorge Sanchez-Guerrero of the Salvador Zubiran National Institute of Medical Science and Nutrition in Mexico City and his associates.

The women's mean SLE Disease Activity Index (SLEDAI) scores were 6.1 in women on combined OCs, 6.4 in women receiving progestin-only pills, and 5.0 in recipients of the copper IUD.

The primary outcome measure was global disease activity. Among the secondary outcomes were disease flares, median time to first flare, and adverse events. Disease activity was assessed at baseline and at months 1, 2, 3, 6, 9, and 12.

There were no significant differences in disease activity between the three groups (N. Engl. J. Med. 2005;353:2539–49).

Median time to disease flare was 3 months in each of the three groups. Two women in each group on hormonal contraception developed thrombosis, for a total of four cases. There were fives cases of severe infection in the IUD group, two in the OC group, and two in users of the progestin-only pill.

Although all three methods are relatively safe, women on hormonal contraceptives require close monitoring for risk of thrombosis, notes Dr. Sanchez-Guerrero and his associates.

In an accompanying editorial, Dr. Bonnie L. Bermas, of Brigham and Women's Hospital in Boston, noted that there are a number of reasons for prescribing oral contraceptives in women with stable SLE.

Among them are that pregnancies planned during remission result in better outcomes; these women are often on teratogenic medications and require a reliable form of birth control; and OCs may reduce bone loss in those on long-term glucocorticoid therapy (N. Engl. J. Med. 2005;353:2602–4).

Overall, she says the findings “support the use of combined oral contraceptives by those with inactive or moderately active, stable disease.”

Women with stable systemic lupus erythematosus can use with relative safety any one of three forms of birth control—a combined oral contraceptive, a progestin-only contraceptive, or the copper intrauterine device—according to the findings of a study that showed each method had its own small degree of risk.

The safety of these forms of contraception was evaluated in a study of 162 women with mild, stable systemic lupus erythematosus (SLE), according to Dr. Jorge Sanchez-Guerrero of the Salvador Zubiran National Institute of Medical Science and Nutrition in Mexico City and his associates.

The women's mean SLE Disease Activity Index (SLEDAI) scores were 6.1 in women on combined OCs, 6.4 in women receiving progestin-only pills, and 5.0 in recipients of the copper IUD.

The primary outcome measure was global disease activity. Among the secondary outcomes were disease flares, median time to first flare, and adverse events. Disease activity was assessed at baseline and at months 1, 2, 3, 6, 9, and 12.

There were no significant differences in disease activity between the three groups (N. Engl. J. Med. 2005;353:2539–49).

Median time to disease flare was 3 months in each of the three groups. Two women in each group on hormonal contraception developed thrombosis, for a total of four cases. There were fives cases of severe infection in the IUD group, two in the OC group, and two in users of the progestin-only pill.

Although all three methods are relatively safe, women on hormonal contraceptives require close monitoring for risk of thrombosis, notes Dr. Sanchez-Guerrero and his associates.

In an accompanying editorial, Dr. Bonnie L. Bermas, of Brigham and Women's Hospital in Boston, noted that there are a number of reasons for prescribing oral contraceptives in women with stable SLE.

Among them are that pregnancies planned during remission result in better outcomes; these women are often on teratogenic medications and require a reliable form of birth control; and OCs may reduce bone loss in those on long-term glucocorticoid therapy (N. Engl. J. Med. 2005;353:2602–4).

Overall, she says the findings “support the use of combined oral contraceptives by those with inactive or moderately active, stable disease.”

Women with stable systemic lupus erythematosus can use with relative safety any one of three forms of birth control—a combined oral contraceptive, a progestin-only contraceptive, or the copper intrauterine device—according to the findings of a study that showed each method had its own small degree of risk.

The safety of these forms of contraception was evaluated in a study of 162 women with mild, stable systemic lupus erythematosus (SLE), according to Dr. Jorge Sanchez-Guerrero of the Salvador Zubiran National Institute of Medical Science and Nutrition in Mexico City and his associates.

The women's mean SLE Disease Activity Index (SLEDAI) scores were 6.1 in women on combined OCs, 6.4 in women receiving progestin-only pills, and 5.0 in recipients of the copper IUD.

The primary outcome measure was global disease activity. Among the secondary outcomes were disease flares, median time to first flare, and adverse events. Disease activity was assessed at baseline and at months 1, 2, 3, 6, 9, and 12.

There were no significant differences in disease activity between the three groups (N. Engl. J. Med. 2005;353:2539–49).

Median time to disease flare was 3 months in each of the three groups. Two women in each group on hormonal contraception developed thrombosis, for a total of four cases. There were fives cases of severe infection in the IUD group, two in the OC group, and two in users of the progestin-only pill.

Although all three methods are relatively safe, women on hormonal contraceptives require close monitoring for risk of thrombosis, notes Dr. Sanchez-Guerrero and his associates.

In an accompanying editorial, Dr. Bonnie L. Bermas, of Brigham and Women's Hospital in Boston, noted that there are a number of reasons for prescribing oral contraceptives in women with stable SLE.

Among them are that pregnancies planned during remission result in better outcomes; these women are often on teratogenic medications and require a reliable form of birth control; and OCs may reduce bone loss in those on long-term glucocorticoid therapy (N. Engl. J. Med. 2005;353:2602–4).

Overall, she says the findings “support the use of combined oral contraceptives by those with inactive or moderately active, stable disease.”

The addition of L-arginine to standard post-MI therapy does not decrease vascular stiffness or improve ejection fraction and may be related to increased postinfarction mortality, according to the results of the Vascular Interaction With Age in Myocardial Infarction trial.

Dr. Steven P. Schulman and colleagues randomized 153 patients following a first ST-segment elevation MI to receive L-arginine (with a goal dose of 3 g, three times daily) or placebo. Of the patients, 77 were aged 60 years or older. All the patients were followed up at 1, 3, and 6 months.

The amino acid L-arginine is a substrate for nitric oxide synthase. The results of previous studies suggest that it is associated with a reduction in vascular stiffness. As such, the investigators' objective was to establish whether the addition of the amino acid to standard treatment in post-MI patients, and especially older patients, would reduce vascular stiffness and improve left ventricular function (JAMA 2006;259:58–64).

In patients aged 60 years and older, ejection fraction and vascular stiffness did not change during the 6 months of follow-up in either group. However, six (9%) patients who had been randomized to L-arginine died, compared with none of those who received placebo. As a result, the data and safety monitoring board closed enrollment, the authors reported.

The participants had normal L-arginine levels at baseline, and Dr. Schulman, an associate professor of medicine and director of the Coronary Care Unit at Johns Hopkins University in Baltimore, and his associates speculated that the L-arginine level could explain the lack of efficacy. “The lack of any dose response in plasma L-arginine levels from 0 to 9 g suggests that higher doses of L-arginine would not have resulted in any biological effect in this population,” the authors wrote, adding that many of the patients were already taking medications such as ACE inhibitors to improve vascular function.

The authors concluded that “L-arginine therapy should not be given to patients following a myocardial infarction. It neither alters noninvasive measures of vascular stiffness nor improves left ventricular function.”

The addition of L-arginine to standard post-MI therapy does not decrease vascular stiffness or improve ejection fraction and may be related to increased postinfarction mortality, according to the results of the Vascular Interaction With Age in Myocardial Infarction trial.

Dr. Steven P. Schulman and colleagues randomized 153 patients following a first ST-segment elevation MI to receive L-arginine (with a goal dose of 3 g, three times daily) or placebo. Of the patients, 77 were aged 60 years or older. All the patients were followed up at 1, 3, and 6 months.

The amino acid L-arginine is a substrate for nitric oxide synthase. The results of previous studies suggest that it is associated with a reduction in vascular stiffness. As such, the investigators' objective was to establish whether the addition of the amino acid to standard treatment in post-MI patients, and especially older patients, would reduce vascular stiffness and improve left ventricular function (JAMA 2006;259:58–64).

In patients aged 60 years and older, ejection fraction and vascular stiffness did not change during the 6 months of follow-up in either group. However, six (9%) patients who had been randomized to L-arginine died, compared with none of those who received placebo. As a result, the data and safety monitoring board closed enrollment, the authors reported.

The participants had normal L-arginine levels at baseline, and Dr. Schulman, an associate professor of medicine and director of the Coronary Care Unit at Johns Hopkins University in Baltimore, and his associates speculated that the L-arginine level could explain the lack of efficacy. “The lack of any dose response in plasma L-arginine levels from 0 to 9 g suggests that higher doses of L-arginine would not have resulted in any biological effect in this population,” the authors wrote, adding that many of the patients were already taking medications such as ACE inhibitors to improve vascular function.

The authors concluded that “L-arginine therapy should not be given to patients following a myocardial infarction. It neither alters noninvasive measures of vascular stiffness nor improves left ventricular function.”

The addition of L-arginine to standard post-MI therapy does not decrease vascular stiffness or improve ejection fraction and may be related to increased postinfarction mortality, according to the results of the Vascular Interaction With Age in Myocardial Infarction trial.

Dr. Steven P. Schulman and colleagues randomized 153 patients following a first ST-segment elevation MI to receive L-arginine (with a goal dose of 3 g, three times daily) or placebo. Of the patients, 77 were aged 60 years or older. All the patients were followed up at 1, 3, and 6 months.

The amino acid L-arginine is a substrate for nitric oxide synthase. The results of previous studies suggest that it is associated with a reduction in vascular stiffness. As such, the investigators' objective was to establish whether the addition of the amino acid to standard treatment in post-MI patients, and especially older patients, would reduce vascular stiffness and improve left ventricular function (JAMA 2006;259:58–64).

In patients aged 60 years and older, ejection fraction and vascular stiffness did not change during the 6 months of follow-up in either group. However, six (9%) patients who had been randomized to L-arginine died, compared with none of those who received placebo. As a result, the data and safety monitoring board closed enrollment, the authors reported.

The participants had normal L-arginine levels at baseline, and Dr. Schulman, an associate professor of medicine and director of the Coronary Care Unit at Johns Hopkins University in Baltimore, and his associates speculated that the L-arginine level could explain the lack of efficacy. “The lack of any dose response in plasma L-arginine levels from 0 to 9 g suggests that higher doses of L-arginine would not have resulted in any biological effect in this population,” the authors wrote, adding that many of the patients were already taking medications such as ACE inhibitors to improve vascular function.

The authors concluded that “L-arginine therapy should not be given to patients following a myocardial infarction. It neither alters noninvasive measures of vascular stiffness nor improves left ventricular function.”

Older adults living in low-income census tracts are significantly less likely to respond to depression treatment than are their counterparts in middle- and high-income census tracts, researchers reported.

Alex Cohen, Ph.D., of Harvard Medical School, Boston, and his associates analyzed pooled data from the open-label phases of two Pittsburgh-based clinical trials funded by the National Institute of Mental Health.

In the first of these studies, nortriptyline hydrochloride combined with interpersonal psychotherapy was studied for the treatment of depression in 169 subjects aged 59 and older. The second study evaluated the combination of paroxetine and interpersonal psychotherapy among 116 subjects aged 69 and older (Arch. Gen. Psychiatry 2006;63:50–6).

Using the 17-item Hamilton Rating Scale for Depression, the investigators found that subjects living in low-income census tracts were less likely to respond to treatment. For example, participants in the higher-income tracts were far less likely to report suicidal ideation. The investigators found no association between socioeconomic status and remission.

One possible explanation for the gap between low- and middle-income subjects, the researchers said, is that “the persistence of depressive episodes was more pronounced among individuals with lower socioeconomic status.” Comorbid conditions also had some effect on antidepressant response, but they did not negate the effects of socioeconomic status when investigators adjusted for that variable.

Dr. Cohen and his colleagues also pointed to the “nonlinearity” of the findings. Educational level is usually a principal component of socioeconomic status, but in this study, higher educational status did not correlate with better treatment outcome. Subjects in the higher-income census tracts were not always the most likely to respond.

In an interview, Dr. Cohen said he would be cautious about drawing clinical implications from this research for two reasons: The work needs to be replicated, and he is not a psychiatrist. However, he said he would assume that research showing predictors of response to treatment does have clinical implications.

“If it is true that residents of low-income neighborhoods are relatively less likely to respond to efficacious interventions and more likely to experience suicidal ideation during treatment, then it would follow that treatment for such patients might need to be more intense, of longer duration, or possibly, augmented with other psychosocial interventions,” he said.

Dr. Cohen, an anthropologist, is affiliated with the Harvard Medical School's department of social medicine.

Older adults living in low-income census tracts are significantly less likely to respond to depression treatment than are their counterparts in middle- and high-income census tracts, researchers reported.

Alex Cohen, Ph.D., of Harvard Medical School, Boston, and his associates analyzed pooled data from the open-label phases of two Pittsburgh-based clinical trials funded by the National Institute of Mental Health.

In the first of these studies, nortriptyline hydrochloride combined with interpersonal psychotherapy was studied for the treatment of depression in 169 subjects aged 59 and older. The second study evaluated the combination of paroxetine and interpersonal psychotherapy among 116 subjects aged 69 and older (Arch. Gen. Psychiatry 2006;63:50–6).

Using the 17-item Hamilton Rating Scale for Depression, the investigators found that subjects living in low-income census tracts were less likely to respond to treatment. For example, participants in the higher-income tracts were far less likely to report suicidal ideation. The investigators found no association between socioeconomic status and remission.

One possible explanation for the gap between low- and middle-income subjects, the researchers said, is that “the persistence of depressive episodes was more pronounced among individuals with lower socioeconomic status.” Comorbid conditions also had some effect on antidepressant response, but they did not negate the effects of socioeconomic status when investigators adjusted for that variable.

Dr. Cohen and his colleagues also pointed to the “nonlinearity” of the findings. Educational level is usually a principal component of socioeconomic status, but in this study, higher educational status did not correlate with better treatment outcome. Subjects in the higher-income census tracts were not always the most likely to respond.

In an interview, Dr. Cohen said he would be cautious about drawing clinical implications from this research for two reasons: The work needs to be replicated, and he is not a psychiatrist. However, he said he would assume that research showing predictors of response to treatment does have clinical implications.

“If it is true that residents of low-income neighborhoods are relatively less likely to respond to efficacious interventions and more likely to experience suicidal ideation during treatment, then it would follow that treatment for such patients might need to be more intense, of longer duration, or possibly, augmented with other psychosocial interventions,” he said.

Dr. Cohen, an anthropologist, is affiliated with the Harvard Medical School's department of social medicine.

Older adults living in low-income census tracts are significantly less likely to respond to depression treatment than are their counterparts in middle- and high-income census tracts, researchers reported.

Alex Cohen, Ph.D., of Harvard Medical School, Boston, and his associates analyzed pooled data from the open-label phases of two Pittsburgh-based clinical trials funded by the National Institute of Mental Health.

In the first of these studies, nortriptyline hydrochloride combined with interpersonal psychotherapy was studied for the treatment of depression in 169 subjects aged 59 and older. The second study evaluated the combination of paroxetine and interpersonal psychotherapy among 116 subjects aged 69 and older (Arch. Gen. Psychiatry 2006;63:50–6).

Using the 17-item Hamilton Rating Scale for Depression, the investigators found that subjects living in low-income census tracts were less likely to respond to treatment. For example, participants in the higher-income tracts were far less likely to report suicidal ideation. The investigators found no association between socioeconomic status and remission.

One possible explanation for the gap between low- and middle-income subjects, the researchers said, is that “the persistence of depressive episodes was more pronounced among individuals with lower socioeconomic status.” Comorbid conditions also had some effect on antidepressant response, but they did not negate the effects of socioeconomic status when investigators adjusted for that variable.

Dr. Cohen and his colleagues also pointed to the “nonlinearity” of the findings. Educational level is usually a principal component of socioeconomic status, but in this study, higher educational status did not correlate with better treatment outcome. Subjects in the higher-income census tracts were not always the most likely to respond.

In an interview, Dr. Cohen said he would be cautious about drawing clinical implications from this research for two reasons: The work needs to be replicated, and he is not a psychiatrist. However, he said he would assume that research showing predictors of response to treatment does have clinical implications.

“If it is true that residents of low-income neighborhoods are relatively less likely to respond to efficacious interventions and more likely to experience suicidal ideation during treatment, then it would follow that treatment for such patients might need to be more intense, of longer duration, or possibly, augmented with other psychosocial interventions,” he said.

Dr. Cohen, an anthropologist, is affiliated with the Harvard Medical School's department of social medicine.

Atrial overdrive pacing proved ineffective in most cases of obstructive sleep apnea-hypopnea syndrome, while nasal continuous positive airway pressure showed strong efficacy, according to a comparison study by Greek researchers.

Dr. Emmanuel N. Simantirakis and colleagues at Heraklion (Crete) University Hospital, Greece, implanted dual chamber pacemakers in 16 patients with moderate or severe sleep apnea, documented sleep-related bradycardias, and normal ventricular function (N. Engl. J. Med. 2005;353: 2568–77).

Patients had a mean baseline apnea-hypopnea index of 49 and had at least two self-reported syncopal episodes in the preceding year. Diagnosis of obstructive sleep apnea-hypopnea syndrome was confirmed on polysomnography.

All pacemakers were initially programmed to initiate atrial pacing when the heart rate fell below 40 beats per minute. After 48 hours, half of the patients had their pacemakers programmed for atrial overdrive pacing, with pacing at a rate greater than 15 beats per minute or greater than their normal nocturnal heart rate.

The rest of the patients remained on backup atrial pacing plus nasal continuous positive airway pressure (n-CPAP).

One month later, the groups switched therapies. The researchers then followed the patients for another month.

Atrial overdrive pacing had virtually no effect on the average apnea-hypopnea index at 1 month, which rose from 49 at baseline to 49.2. The increase was not statistically significant. In contrast, n-CPAP significantly improved the average apnea-hypopnea index after 1 month of therapy, which fell from 49 at baseline to 2.7.

The arousal index, desaturation index, and all other variables measured except total sleep time showed improvements with n-CPAP, while atrial overdrive pacing had no measurable effect on the variables, the researchers said.

“We were unable to show any beneficial effect of pacing in reducing the number of episodes of apnea or hypopnea per hour,” the investigators wrote.

The findings of the study, however, may not apply in general to all patients with the obstructive sleep apnea-hypopnea syndrome, they cautioned.

The failure of atrial overdrive pacing to improve symptoms “suggests that overdrive pacing is likely to have a very limited role in this setting,” Dr. Daniel J. Gottlieb of Boston University said in an accompanying editorial (N. Engl. J. Med. 2005;353:2604–6).

“Phenotypes will be identified in which modification of neuromuscular factors will play a useful therapeutic role,” he added.

Atrial overdrive pacing proved ineffective in most cases of obstructive sleep apnea-hypopnea syndrome, while nasal continuous positive airway pressure showed strong efficacy, according to a comparison study by Greek researchers.

Dr. Emmanuel N. Simantirakis and colleagues at Heraklion (Crete) University Hospital, Greece, implanted dual chamber pacemakers in 16 patients with moderate or severe sleep apnea, documented sleep-related bradycardias, and normal ventricular function (N. Engl. J. Med. 2005;353: 2568–77).

Patients had a mean baseline apnea-hypopnea index of 49 and had at least two self-reported syncopal episodes in the preceding year. Diagnosis of obstructive sleep apnea-hypopnea syndrome was confirmed on polysomnography.

All pacemakers were initially programmed to initiate atrial pacing when the heart rate fell below 40 beats per minute. After 48 hours, half of the patients had their pacemakers programmed for atrial overdrive pacing, with pacing at a rate greater than 15 beats per minute or greater than their normal nocturnal heart rate.

The rest of the patients remained on backup atrial pacing plus nasal continuous positive airway pressure (n-CPAP).

One month later, the groups switched therapies. The researchers then followed the patients for another month.

Atrial overdrive pacing had virtually no effect on the average apnea-hypopnea index at 1 month, which rose from 49 at baseline to 49.2. The increase was not statistically significant. In contrast, n-CPAP significantly improved the average apnea-hypopnea index after 1 month of therapy, which fell from 49 at baseline to 2.7.

The arousal index, desaturation index, and all other variables measured except total sleep time showed improvements with n-CPAP, while atrial overdrive pacing had no measurable effect on the variables, the researchers said.

“We were unable to show any beneficial effect of pacing in reducing the number of episodes of apnea or hypopnea per hour,” the investigators wrote.

The findings of the study, however, may not apply in general to all patients with the obstructive sleep apnea-hypopnea syndrome, they cautioned.

The failure of atrial overdrive pacing to improve symptoms “suggests that overdrive pacing is likely to have a very limited role in this setting,” Dr. Daniel J. Gottlieb of Boston University said in an accompanying editorial (N. Engl. J. Med. 2005;353:2604–6).

“Phenotypes will be identified in which modification of neuromuscular factors will play a useful therapeutic role,” he added.

Atrial overdrive pacing proved ineffective in most cases of obstructive sleep apnea-hypopnea syndrome, while nasal continuous positive airway pressure showed strong efficacy, according to a comparison study by Greek researchers.

Dr. Emmanuel N. Simantirakis and colleagues at Heraklion (Crete) University Hospital, Greece, implanted dual chamber pacemakers in 16 patients with moderate or severe sleep apnea, documented sleep-related bradycardias, and normal ventricular function (N. Engl. J. Med. 2005;353: 2568–77).

Patients had a mean baseline apnea-hypopnea index of 49 and had at least two self-reported syncopal episodes in the preceding year. Diagnosis of obstructive sleep apnea-hypopnea syndrome was confirmed on polysomnography.

All pacemakers were initially programmed to initiate atrial pacing when the heart rate fell below 40 beats per minute. After 48 hours, half of the patients had their pacemakers programmed for atrial overdrive pacing, with pacing at a rate greater than 15 beats per minute or greater than their normal nocturnal heart rate.

The rest of the patients remained on backup atrial pacing plus nasal continuous positive airway pressure (n-CPAP).

One month later, the groups switched therapies. The researchers then followed the patients for another month.

Atrial overdrive pacing had virtually no effect on the average apnea-hypopnea index at 1 month, which rose from 49 at baseline to 49.2. The increase was not statistically significant. In contrast, n-CPAP significantly improved the average apnea-hypopnea index after 1 month of therapy, which fell from 49 at baseline to 2.7.

The arousal index, desaturation index, and all other variables measured except total sleep time showed improvements with n-CPAP, while atrial overdrive pacing had no measurable effect on the variables, the researchers said.

“We were unable to show any beneficial effect of pacing in reducing the number of episodes of apnea or hypopnea per hour,” the investigators wrote.

The findings of the study, however, may not apply in general to all patients with the obstructive sleep apnea-hypopnea syndrome, they cautioned.

The failure of atrial overdrive pacing to improve symptoms “suggests that overdrive pacing is likely to have a very limited role in this setting,” Dr. Daniel J. Gottlieb of Boston University said in an accompanying editorial (N. Engl. J. Med. 2005;353:2604–6).

“Phenotypes will be identified in which modification of neuromuscular factors will play a useful therapeutic role,” he added.

The addition of L-arginine to standard post-MI therapy does not decrease vascular stiffness or improve ejection fraction and may be related to an increase in postinfarction mortality, according to the results of the Vascular Interaction With Age in Myocardial Infarction trial.

Dr. Steven P. Schulman and colleagues randomized 153 patients following a first ST-segment elevation MI to receive L-arginine (with a goal dose of 3 g, three times daily) or placebo. Of the patients, 77 were aged 60 years or older. All the patients were followed up at 1, 3, and 6 months.

The amino acid L-arginine is a substrate for nitric oxide synthase. The results of previous studies suggest that it is associated with a reduction in vascular stiffness. As such, the investigators' objective was to establish whether the addition of the amino acid to standard treatment in post-MI patients, and especially older patients, would reduce vascular stiffness and improve left ventricular function (JAMA 2006;259:58–64).

In patients aged 60 years and older, ejection fraction and vascular stiffness did not change during the 6 months of follow-up in either group. However, six (9%) patients who had been randomized to L-arginine died, compared with none of those who received placebo. As a result, the data and safety monitoring board closed enrollment, the authors reported.

The participants had normal L-arginine levels at baseline, and Dr. Schulman, an associate professor of medicine and director of the Coronary Care Unit at Johns Hopkins University in Baltimore, and his associates speculated that the L-arginine level could explain the lack of efficacy.

“The lack of any dose response in plasma L-arginine levels from 0 to 9 g suggests that higher doses of L-arginine would not have resulted in any biological effect in this population,” the authors wrote, adding that many of the patients were already taking medications such as ACE to improve vascular function.

The authors attributed the absence of change in ejection fraction and of remodeling possibly to the large proportion of patients who had received “early percutaneous coronary intervention with establishments of coronary patency.”

One possible explanation for L-arginine's harmful effects is that instead of generating nitric oxide, it may actually produce reactive oxygen species that create pressure overload. L-arginine also increases homocysteine production.

The authors concluded that “L-arginine therapy should not be given to patients following a myocardial infarction. It neither alters noninvasive measures of vascular stiffness nor improves left ventricular function. L-arginine therapy in older patients with diffuse atherosclerosis may worsen clinical outcomes.”

The addition of L-arginine to standard post-MI therapy does not decrease vascular stiffness or improve ejection fraction and may be related to an increase in postinfarction mortality, according to the results of the Vascular Interaction With Age in Myocardial Infarction trial.

Dr. Steven P. Schulman and colleagues randomized 153 patients following a first ST-segment elevation MI to receive L-arginine (with a goal dose of 3 g, three times daily) or placebo. Of the patients, 77 were aged 60 years or older. All the patients were followed up at 1, 3, and 6 months.

The amino acid L-arginine is a substrate for nitric oxide synthase. The results of previous studies suggest that it is associated with a reduction in vascular stiffness. As such, the investigators' objective was to establish whether the addition of the amino acid to standard treatment in post-MI patients, and especially older patients, would reduce vascular stiffness and improve left ventricular function (JAMA 2006;259:58–64).

In patients aged 60 years and older, ejection fraction and vascular stiffness did not change during the 6 months of follow-up in either group. However, six (9%) patients who had been randomized to L-arginine died, compared with none of those who received placebo. As a result, the data and safety monitoring board closed enrollment, the authors reported.

The participants had normal L-arginine levels at baseline, and Dr. Schulman, an associate professor of medicine and director of the Coronary Care Unit at Johns Hopkins University in Baltimore, and his associates speculated that the L-arginine level could explain the lack of efficacy.

“The lack of any dose response in plasma L-arginine levels from 0 to 9 g suggests that higher doses of L-arginine would not have resulted in any biological effect in this population,” the authors wrote, adding that many of the patients were already taking medications such as ACE to improve vascular function.

The authors attributed the absence of change in ejection fraction and of remodeling possibly to the large proportion of patients who had received “early percutaneous coronary intervention with establishments of coronary patency.”

One possible explanation for L-arginine's harmful effects is that instead of generating nitric oxide, it may actually produce reactive oxygen species that create pressure overload. L-arginine also increases homocysteine production.

The authors concluded that “L-arginine therapy should not be given to patients following a myocardial infarction. It neither alters noninvasive measures of vascular stiffness nor improves left ventricular function. L-arginine therapy in older patients with diffuse atherosclerosis may worsen clinical outcomes.”

The addition of L-arginine to standard post-MI therapy does not decrease vascular stiffness or improve ejection fraction and may be related to an increase in postinfarction mortality, according to the results of the Vascular Interaction With Age in Myocardial Infarction trial.

Dr. Steven P. Schulman and colleagues randomized 153 patients following a first ST-segment elevation MI to receive L-arginine (with a goal dose of 3 g, three times daily) or placebo. Of the patients, 77 were aged 60 years or older. All the patients were followed up at 1, 3, and 6 months.

The amino acid L-arginine is a substrate for nitric oxide synthase. The results of previous studies suggest that it is associated with a reduction in vascular stiffness. As such, the investigators' objective was to establish whether the addition of the amino acid to standard treatment in post-MI patients, and especially older patients, would reduce vascular stiffness and improve left ventricular function (JAMA 2006;259:58–64).

In patients aged 60 years and older, ejection fraction and vascular stiffness did not change during the 6 months of follow-up in either group. However, six (9%) patients who had been randomized to L-arginine died, compared with none of those who received placebo. As a result, the data and safety monitoring board closed enrollment, the authors reported.

The participants had normal L-arginine levels at baseline, and Dr. Schulman, an associate professor of medicine and director of the Coronary Care Unit at Johns Hopkins University in Baltimore, and his associates speculated that the L-arginine level could explain the lack of efficacy.

“The lack of any dose response in plasma L-arginine levels from 0 to 9 g suggests that higher doses of L-arginine would not have resulted in any biological effect in this population,” the authors wrote, adding that many of the patients were already taking medications such as ACE to improve vascular function.

The authors attributed the absence of change in ejection fraction and of remodeling possibly to the large proportion of patients who had received “early percutaneous coronary intervention with establishments of coronary patency.”

One possible explanation for L-arginine's harmful effects is that instead of generating nitric oxide, it may actually produce reactive oxygen species that create pressure overload. L-arginine also increases homocysteine production.

The authors concluded that “L-arginine therapy should not be given to patients following a myocardial infarction. It neither alters noninvasive measures of vascular stiffness nor improves left ventricular function. L-arginine therapy in older patients with diffuse atherosclerosis may worsen clinical outcomes.”

Vaginal birth does not contribute to the development of stress urinary incontinence later in life, according to Dr. Gunhilde M. Buchsbaum, of the department of ob.gyn at the University of Rochester (N.Y.), and colleagues.

“Contrary to the conventional wisdom that nulliparity protects against stress urinary incontinence, we found similar rates of urinary incontinence in postmenopausal nulliparous women and their parous biological sisters,” the investigators reported (Obstet. Gynecol. 2005;106:1253–8).

Dr. Buchsbaum's team analyzed a sample of 143 pairs of nulliparous and parous postmenopausal sisters. All of the women answered a questionnaire about symptoms of pelvic floor disorders, and 101 pairs also underwent clinical evaluation of urinary incontinence and genital prolapse.

The researchers found that 47.6% of nulliparous women and 49.7% of parous women reported urinary incontinence, with no difference in type and severity of urinary incontinence between the groups.

Of interest was the finding that there was “a high concordance in continence status … within biological sisters,” according to Dr. Buchsbaum. This finding suggests that there may be a genetic predisposition for urinary incontinence. If that proves to be true, it “would have great implications for the direction of basic research, treatment approaches, risk management, and potential prophylactic interventions.”

Vaginal birth does not contribute to the development of stress urinary incontinence later in life, according to Dr. Gunhilde M. Buchsbaum, of the department of ob.gyn at the University of Rochester (N.Y.), and colleagues.

“Contrary to the conventional wisdom that nulliparity protects against stress urinary incontinence, we found similar rates of urinary incontinence in postmenopausal nulliparous women and their parous biological sisters,” the investigators reported (Obstet. Gynecol. 2005;106:1253–8).

Dr. Buchsbaum's team analyzed a sample of 143 pairs of nulliparous and parous postmenopausal sisters. All of the women answered a questionnaire about symptoms of pelvic floor disorders, and 101 pairs also underwent clinical evaluation of urinary incontinence and genital prolapse.

The researchers found that 47.6% of nulliparous women and 49.7% of parous women reported urinary incontinence, with no difference in type and severity of urinary incontinence between the groups.

Of interest was the finding that there was “a high concordance in continence status … within biological sisters,” according to Dr. Buchsbaum. This finding suggests that there may be a genetic predisposition for urinary incontinence. If that proves to be true, it “would have great implications for the direction of basic research, treatment approaches, risk management, and potential prophylactic interventions.”

Vaginal birth does not contribute to the development of stress urinary incontinence later in life, according to Dr. Gunhilde M. Buchsbaum, of the department of ob.gyn at the University of Rochester (N.Y.), and colleagues.

“Contrary to the conventional wisdom that nulliparity protects against stress urinary incontinence, we found similar rates of urinary incontinence in postmenopausal nulliparous women and their parous biological sisters,” the investigators reported (Obstet. Gynecol. 2005;106:1253–8).

Dr. Buchsbaum's team analyzed a sample of 143 pairs of nulliparous and parous postmenopausal sisters. All of the women answered a questionnaire about symptoms of pelvic floor disorders, and 101 pairs also underwent clinical evaluation of urinary incontinence and genital prolapse.

The researchers found that 47.6% of nulliparous women and 49.7% of parous women reported urinary incontinence, with no difference in type and severity of urinary incontinence between the groups.

Of interest was the finding that there was “a high concordance in continence status … within biological sisters,” according to Dr. Buchsbaum. This finding suggests that there may be a genetic predisposition for urinary incontinence. If that proves to be true, it “would have great implications for the direction of basic research, treatment approaches, risk management, and potential prophylactic interventions.”

Oral contraceptive use does not increase the number or severity of flares of inactive or mild, stable systemic lupus erythematosus, according to investigators with the Safety of Estrogens in Lupus Erythematosus—National Assessment (SELENA): Oral Contraceptives trial.

Dr. Michelle Petri, of Johns Hopkins University, Baltimore, and her associates randomized 183 women with inactive (76%) or stable active (24%) disease to receive either placebo or an oral contraceptive (OC).

The OC regimen used involved a 35-mcg triphasic ethinyl estradiol plus norethindrone 0.5–1.0 mg for 12 cycles, each 7 days long.

All women used an alternate form of birth control during the study period. The primary end point of the study was a severe lupus flare.

During the first year of follow-up, 7 of the 91 women on OCs (8%) had at least one severe flare of their SLE as did 7 of 92 women (8%) taking placebo.

Rates of severe flare were similar in the two groups, with a rate of 0.084 severe flares per person-year for the study group and 0.087 severe flares per person-year for the placebo group.

Rates of flares per person-year were 1.40 for OC users and 1.44 for placebo patients.

Serious adverse events requiring hospitalization occurred in 15 patients on OCs and 13 placebo patients.

Thrombosis occurred in two OC users and three women on placebo. Two OC users had abnormal liver function tests, and one developed hypertension.

None of these events occurred among women on placebo.

Seven women on OCs had to discontinue treatment, and 12 women on placebo withdrew from the study (N. Engl. J. Med. 2005; 353:2550–8).

In an accompanying editorial, Dr. Bonnie L. Bermas of Brigham and Women's Hospital in Boston commented that the study “supports the use of combined oral contraceptives by those with inactive or moderately active, stable disease.…”

“[T]he option to use combined oral contraceptives in antiphospholipid antibody-negative patients with mild disease appears worth considering in the appropriate clinical setting” (N. Engl. J. Med. 2005;353:2602–4).

Oral contraceptive use does not increase the number or severity of flares of inactive or mild, stable systemic lupus erythematosus, according to investigators with the Safety of Estrogens in Lupus Erythematosus—National Assessment (SELENA): Oral Contraceptives trial.

Dr. Michelle Petri, of Johns Hopkins University, Baltimore, and her associates randomized 183 women with inactive (76%) or stable active (24%) disease to receive either placebo or an oral contraceptive (OC).

The OC regimen used involved a 35-mcg triphasic ethinyl estradiol plus norethindrone 0.5–1.0 mg for 12 cycles, each 7 days long.

All women used an alternate form of birth control during the study period. The primary end point of the study was a severe lupus flare.

During the first year of follow-up, 7 of the 91 women on OCs (8%) had at least one severe flare of their SLE as did 7 of 92 women (8%) taking placebo.

Rates of severe flare were similar in the two groups, with a rate of 0.084 severe flares per person-year for the study group and 0.087 severe flares per person-year for the placebo group.

Rates of flares per person-year were 1.40 for OC users and 1.44 for placebo patients.

Serious adverse events requiring hospitalization occurred in 15 patients on OCs and 13 placebo patients.

Thrombosis occurred in two OC users and three women on placebo. Two OC users had abnormal liver function tests, and one developed hypertension.

None of these events occurred among women on placebo.

Seven women on OCs had to discontinue treatment, and 12 women on placebo withdrew from the study (N. Engl. J. Med. 2005; 353:2550–8).

In an accompanying editorial, Dr. Bonnie L. Bermas of Brigham and Women's Hospital in Boston commented that the study “supports the use of combined oral contraceptives by those with inactive or moderately active, stable disease.…”

“[T]he option to use combined oral contraceptives in antiphospholipid antibody-negative patients with mild disease appears worth considering in the appropriate clinical setting” (N. Engl. J. Med. 2005;353:2602–4).

Oral contraceptive use does not increase the number or severity of flares of inactive or mild, stable systemic lupus erythematosus, according to investigators with the Safety of Estrogens in Lupus Erythematosus—National Assessment (SELENA): Oral Contraceptives trial.

Dr. Michelle Petri, of Johns Hopkins University, Baltimore, and her associates randomized 183 women with inactive (76%) or stable active (24%) disease to receive either placebo or an oral contraceptive (OC).

The OC regimen used involved a 35-mcg triphasic ethinyl estradiol plus norethindrone 0.5–1.0 mg for 12 cycles, each 7 days long.

All women used an alternate form of birth control during the study period. The primary end point of the study was a severe lupus flare.

During the first year of follow-up, 7 of the 91 women on OCs (8%) had at least one severe flare of their SLE as did 7 of 92 women (8%) taking placebo.

Rates of severe flare were similar in the two groups, with a rate of 0.084 severe flares per person-year for the study group and 0.087 severe flares per person-year for the placebo group.

Rates of flares per person-year were 1.40 for OC users and 1.44 for placebo patients.

Serious adverse events requiring hospitalization occurred in 15 patients on OCs and 13 placebo patients.

Thrombosis occurred in two OC users and three women on placebo. Two OC users had abnormal liver function tests, and one developed hypertension.

None of these events occurred among women on placebo.

Seven women on OCs had to discontinue treatment, and 12 women on placebo withdrew from the study (N. Engl. J. Med. 2005; 353:2550–8).

In an accompanying editorial, Dr. Bonnie L. Bermas of Brigham and Women's Hospital in Boston commented that the study “supports the use of combined oral contraceptives by those with inactive or moderately active, stable disease.…”

“[T]he option to use combined oral contraceptives in antiphospholipid antibody-negative patients with mild disease appears worth considering in the appropriate clinical setting” (N. Engl. J. Med. 2005;353:2602–4).

BOSTON — Entecavir, an investigational oral antiviral agent, “achieves superior histologic, virologic, and biochemical improvement” in patients with e-antigen-positive chronic hepatitis B virus infection, Robert Gish, M.D., reported at the annual meeting of the American Association for the Study of Liver Diseases.

In an international phase III study, 715 patients with chronic hepatitis B who were nucleoside naive and positive for hepatitis B e-antigen (HBeAg) were randomized to receive either entecavir 0.5 mg daily or lamivudine 100 mg daily for 1 year.

“The objective here is to prevent the progression of liver disease,” said Dr. Gish, medical director of the California Pacific Medical Center in San Francisco. The HBeAg wild-type strain accounts for 25%-40% of hepatitis B virus (HBV) cases.

At 48 weeks, histologic improvement had occurred in 72% of patients on entecavir, compared with 62% on lamivudine, a statistically significant difference. Histologic improvement was defined as a reduction in the Knodell necroinflammatory score of at least 2 points plus no worsening of Knodell fibrosis.

There was a significantly greater reduction in HBV DNA with entecavir than with lamivudine, with 70% of patients having unmeasurable virus levels (below 400 copies/mL) after 48 weeks on the investigational agent, compared with 38% on lamivudine. Mean HBV DNA viral log scores dropped 6.78 log10 copies/mL in the entecavir group and 5.46 log10 copies/mL in the control group. “This is unprecedented,” Dr. Gish commented. “I know of no other modality that suppresses the virus to this extent.”

No significant differences between the lamivudine and entecavir groups were found for the percentages of patients with seroconversion, normalization of ALT levels, or loss of HBeAg DNA.

The incidence of serious adverse events was low and equal in the two treatment arms at 7%. The most commonly reported adverse effects were headache (about 25% of both groups), upper respiratory infection (about 20% of all patients), cough in about 15%, nasopharyngitis in 14%, upper abdominal pain in 10%, fatigue in 10%, and fever in about 10%. Treatment was discontinued because of adverse events in 1% of patients on entecavir and 3% of patients on lamivudine.

Bristol-Myers Squibb Co. has submitted a new drug application to the U.S. Food and Drug Administration and a marketing authorization application to the European Medicines Evaluation Agency for entecavir that includes data from this and other phase III trials of the drug.

BOSTON — Entecavir, an investigational oral antiviral agent, “achieves superior histologic, virologic, and biochemical improvement” in patients with e-antigen-positive chronic hepatitis B virus infection, Robert Gish, M.D., reported at the annual meeting of the American Association for the Study of Liver Diseases.

In an international phase III study, 715 patients with chronic hepatitis B who were nucleoside naive and positive for hepatitis B e-antigen (HBeAg) were randomized to receive either entecavir 0.5 mg daily or lamivudine 100 mg daily for 1 year.

“The objective here is to prevent the progression of liver disease,” said Dr. Gish, medical director of the California Pacific Medical Center in San Francisco. The HBeAg wild-type strain accounts for 25%-40% of hepatitis B virus (HBV) cases.

At 48 weeks, histologic improvement had occurred in 72% of patients on entecavir, compared with 62% on lamivudine, a statistically significant difference. Histologic improvement was defined as a reduction in the Knodell necroinflammatory score of at least 2 points plus no worsening of Knodell fibrosis.

There was a significantly greater reduction in HBV DNA with entecavir than with lamivudine, with 70% of patients having unmeasurable virus levels (below 400 copies/mL) after 48 weeks on the investigational agent, compared with 38% on lamivudine. Mean HBV DNA viral log scores dropped 6.78 log10 copies/mL in the entecavir group and 5.46 log10 copies/mL in the control group. “This is unprecedented,” Dr. Gish commented. “I know of no other modality that suppresses the virus to this extent.”

No significant differences between the lamivudine and entecavir groups were found for the percentages of patients with seroconversion, normalization of ALT levels, or loss of HBeAg DNA.

The incidence of serious adverse events was low and equal in the two treatment arms at 7%. The most commonly reported adverse effects were headache (about 25% of both groups), upper respiratory infection (about 20% of all patients), cough in about 15%, nasopharyngitis in 14%, upper abdominal pain in 10%, fatigue in 10%, and fever in about 10%. Treatment was discontinued because of adverse events in 1% of patients on entecavir and 3% of patients on lamivudine.

Bristol-Myers Squibb Co. has submitted a new drug application to the U.S. Food and Drug Administration and a marketing authorization application to the European Medicines Evaluation Agency for entecavir that includes data from this and other phase III trials of the drug.

BOSTON — Entecavir, an investigational oral antiviral agent, “achieves superior histologic, virologic, and biochemical improvement” in patients with e-antigen-positive chronic hepatitis B virus infection, Robert Gish, M.D., reported at the annual meeting of the American Association for the Study of Liver Diseases.

In an international phase III study, 715 patients with chronic hepatitis B who were nucleoside naive and positive for hepatitis B e-antigen (HBeAg) were randomized to receive either entecavir 0.5 mg daily or lamivudine 100 mg daily for 1 year.

“The objective here is to prevent the progression of liver disease,” said Dr. Gish, medical director of the California Pacific Medical Center in San Francisco. The HBeAg wild-type strain accounts for 25%-40% of hepatitis B virus (HBV) cases.

At 48 weeks, histologic improvement had occurred in 72% of patients on entecavir, compared with 62% on lamivudine, a statistically significant difference. Histologic improvement was defined as a reduction in the Knodell necroinflammatory score of at least 2 points plus no worsening of Knodell fibrosis.

There was a significantly greater reduction in HBV DNA with entecavir than with lamivudine, with 70% of patients having unmeasurable virus levels (below 400 copies/mL) after 48 weeks on the investigational agent, compared with 38% on lamivudine. Mean HBV DNA viral log scores dropped 6.78 log10 copies/mL in the entecavir group and 5.46 log10 copies/mL in the control group. “This is unprecedented,” Dr. Gish commented. “I know of no other modality that suppresses the virus to this extent.”

No significant differences between the lamivudine and entecavir groups were found for the percentages of patients with seroconversion, normalization of ALT levels, or loss of HBeAg DNA.

The incidence of serious adverse events was low and equal in the two treatment arms at 7%. The most commonly reported adverse effects were headache (about 25% of both groups), upper respiratory infection (about 20% of all patients), cough in about 15%, nasopharyngitis in 14%, upper abdominal pain in 10%, fatigue in 10%, and fever in about 10%. Treatment was discontinued because of adverse events in 1% of patients on entecavir and 3% of patients on lamivudine.

Bristol-Myers Squibb Co. has submitted a new drug application to the U.S. Food and Drug Administration and a marketing authorization application to the European Medicines Evaluation Agency for entecavir that includes data from this and other phase III trials of the drug.