Mary Ann Moon

Treating subclinical hypothyroidism with levothyroxine was found to decrease the rate of ischemic heart disease in patients aged 40-70 years, the first evidence ever to be published regarding the benefit of treatment on "hard" clinical outcomes, according to a report published online April 23 in Archives of Internal Medicine

In a review of the medical records of 4,735 patients across the United Kingdom, levothyroxine therapy reduced all-cause mortality and the number of ischemic heart disease events in adults up to 70 years of age, but did not benefit those older than 70, said Dr. Salman Razvi of the Institutes of Human Genetics, Newcastle (U.K.) University, and his associates.

Subclinical hypothyroidism has been believed to predispose patients to cardiovascular disease for decades, but no adequately powered randomized controlled intervention trials have been performed to determine whether treatment of the condition actually improves the risk for ischemic heart disease. Nevertheless, many patients with subclinical hypothyroidism are treated with levothyroxine for symptoms of the condition as well as for the perceived amelioration of CV risk factors such as dyslipidemia, the investigators said.

They examined the issue using data from the General Practitioner Research Database, which contains the longitudinal medical records of a representative sample of more than 10 million British patients (about 16% of the U.K. population). The researchers identified 4,735 adults diagnosed as having subclinical hypothyroidism in 2001 and tracked their records for a median of 8 years for the development of cardiovascular morbidity and mortality.

The study cohort was divided into younger and older groups, with 3,093 subjects aged 40-70 years and 1,642 subjects aged over 70 years. Previous studies have established that subclinical hypothyroidism does not have the same adverse cardiovascular effects in elderly patients as in younger patients, and may even be cardioprotective, Dr. Razvi and his colleagues noted.

During follow-up, both fatal and nonfatal ischemic heart disease events occurred in 165 patients in the younger group (5.3%) and 192 in the older group (11.7%).

In the younger group, the number of such events was 39% lower among patients taking levothyroxine than in untreated patients, a significant difference. All-cause mortality also was lower in the treated younger patients, by 64% (Arch. Int. Med. 2012 April 23 [doi:10.1001/archinternmed.2012.1159].

However, in the older patients, there were no significant differences between treated and untreated patients in the rate of ischemic heart disease events or all-cause mortality.

In addition, the incidence of atrial fibrillation showed no association with treatment of subclinical hypothyroidism in either study group.

"Our data suggest that physicians can be reassured that levothyroxine treatment of subclinical hypothyroidism in patients aged 40-70 years is not harmful and may be associated with modestly improved medium-term health outcomes," the investigators said.

They added that their findings "may provide the best evidence about the management of subclinical hypotension for some time," given that no prospective randomized controlled trials of the issue have yet begun.

This study was funded in part by the Medical Research Council. One of Dr. Razvi’s associates reported receiving speakers’ fees from Merck Serono, and no other financial conflicts of interest were reported.

Treating subclinical hypothyroidism with levothyroxine was found to decrease the rate of ischemic heart disease in patients aged 40-70 years, the first evidence ever to be published regarding the benefit of treatment on "hard" clinical outcomes, according to a report published online April 23 in Archives of Internal Medicine

In a review of the medical records of 4,735 patients across the United Kingdom, levothyroxine therapy reduced all-cause mortality and the number of ischemic heart disease events in adults up to 70 years of age, but did not benefit those older than 70, said Dr. Salman Razvi of the Institutes of Human Genetics, Newcastle (U.K.) University, and his associates.

Subclinical hypothyroidism has been believed to predispose patients to cardiovascular disease for decades, but no adequately powered randomized controlled intervention trials have been performed to determine whether treatment of the condition actually improves the risk for ischemic heart disease. Nevertheless, many patients with subclinical hypothyroidism are treated with levothyroxine for symptoms of the condition as well as for the perceived amelioration of CV risk factors such as dyslipidemia, the investigators said.

They examined the issue using data from the General Practitioner Research Database, which contains the longitudinal medical records of a representative sample of more than 10 million British patients (about 16% of the U.K. population). The researchers identified 4,735 adults diagnosed as having subclinical hypothyroidism in 2001 and tracked their records for a median of 8 years for the development of cardiovascular morbidity and mortality.

The study cohort was divided into younger and older groups, with 3,093 subjects aged 40-70 years and 1,642 subjects aged over 70 years. Previous studies have established that subclinical hypothyroidism does not have the same adverse cardiovascular effects in elderly patients as in younger patients, and may even be cardioprotective, Dr. Razvi and his colleagues noted.

During follow-up, both fatal and nonfatal ischemic heart disease events occurred in 165 patients in the younger group (5.3%) and 192 in the older group (11.7%).

In the younger group, the number of such events was 39% lower among patients taking levothyroxine than in untreated patients, a significant difference. All-cause mortality also was lower in the treated younger patients, by 64% (Arch. Int. Med. 2012 April 23 [doi:10.1001/archinternmed.2012.1159].

However, in the older patients, there were no significant differences between treated and untreated patients in the rate of ischemic heart disease events or all-cause mortality.

In addition, the incidence of atrial fibrillation showed no association with treatment of subclinical hypothyroidism in either study group.

"Our data suggest that physicians can be reassured that levothyroxine treatment of subclinical hypothyroidism in patients aged 40-70 years is not harmful and may be associated with modestly improved medium-term health outcomes," the investigators said.

They added that their findings "may provide the best evidence about the management of subclinical hypotension for some time," given that no prospective randomized controlled trials of the issue have yet begun.

This study was funded in part by the Medical Research Council. One of Dr. Razvi’s associates reported receiving speakers’ fees from Merck Serono, and no other financial conflicts of interest were reported.

Treating subclinical hypothyroidism with levothyroxine was found to decrease the rate of ischemic heart disease in patients aged 40-70 years, the first evidence ever to be published regarding the benefit of treatment on "hard" clinical outcomes, according to a report published online April 23 in Archives of Internal Medicine

In a review of the medical records of 4,735 patients across the United Kingdom, levothyroxine therapy reduced all-cause mortality and the number of ischemic heart disease events in adults up to 70 years of age, but did not benefit those older than 70, said Dr. Salman Razvi of the Institutes of Human Genetics, Newcastle (U.K.) University, and his associates.

Subclinical hypothyroidism has been believed to predispose patients to cardiovascular disease for decades, but no adequately powered randomized controlled intervention trials have been performed to determine whether treatment of the condition actually improves the risk for ischemic heart disease. Nevertheless, many patients with subclinical hypothyroidism are treated with levothyroxine for symptoms of the condition as well as for the perceived amelioration of CV risk factors such as dyslipidemia, the investigators said.

They examined the issue using data from the General Practitioner Research Database, which contains the longitudinal medical records of a representative sample of more than 10 million British patients (about 16% of the U.K. population). The researchers identified 4,735 adults diagnosed as having subclinical hypothyroidism in 2001 and tracked their records for a median of 8 years for the development of cardiovascular morbidity and mortality.

The study cohort was divided into younger and older groups, with 3,093 subjects aged 40-70 years and 1,642 subjects aged over 70 years. Previous studies have established that subclinical hypothyroidism does not have the same adverse cardiovascular effects in elderly patients as in younger patients, and may even be cardioprotective, Dr. Razvi and his colleagues noted.

During follow-up, both fatal and nonfatal ischemic heart disease events occurred in 165 patients in the younger group (5.3%) and 192 in the older group (11.7%).

In the younger group, the number of such events was 39% lower among patients taking levothyroxine than in untreated patients, a significant difference. All-cause mortality also was lower in the treated younger patients, by 64% (Arch. Int. Med. 2012 April 23 [doi:10.1001/archinternmed.2012.1159].

However, in the older patients, there were no significant differences between treated and untreated patients in the rate of ischemic heart disease events or all-cause mortality.

In addition, the incidence of atrial fibrillation showed no association with treatment of subclinical hypothyroidism in either study group.

"Our data suggest that physicians can be reassured that levothyroxine treatment of subclinical hypothyroidism in patients aged 40-70 years is not harmful and may be associated with modestly improved medium-term health outcomes," the investigators said.

They added that their findings "may provide the best evidence about the management of subclinical hypotension for some time," given that no prospective randomized controlled trials of the issue have yet begun.

This study was funded in part by the Medical Research Council. One of Dr. Razvi’s associates reported receiving speakers’ fees from Merck Serono, and no other financial conflicts of interest were reported.

Adding bevacizumab to standard first-line carboplatin and paclitaxel chemotherapy didn’t improve survival in a large retrospective cohort study of patients aged 65 and older who had advanced non–small cell lung cancer, according to a report in the April 18 issue of JAMA.

This finding is consistent with subgroup analyses of older lung cancer patients in efficacy studies of bevacizumab (Avastin), as well as with the results of a recent meta-analysis of four randomized clinical trials. Taken together, the findings demonstrate that bevacizumab should only be used "judiciously," and should not be considered the standard of care in this age group, said Junya Zhu of the Center for Patient Safety, Dana-Farber Cancer Institute, Boston, and her associates.

Approximately two-thirds of patients with lung cancer are diagnosed at age 65 or older, they noted.

Bevacizumab, a monoclonal antibody that inhibits tumor angiogenesis, was approved by the Food and Drug Administration (FDA) in 2006 as a combination therapy with carboplatin and paclitaxel for advanced nonsquamous non–small cell lung cancer (NSCLC). The pivotal Eastern Cooperative Oncology Group (ECOG 4599) trial demonstrated a statistically significant 2-month survival advantage with the addition of bevacizumab, but subset analyses did not find significant survival differences in older patients.

Ms. Zhu and her colleagues assessed the treatment in a Medicare population of 4,168 patients diagnosed with stage IIIB or IV nonsquamous NSCLC in 2002-2007, linking data from their medical records with data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) cancer registry.

The investigators compared outcomes in patients diagnosed in 2006-2007 who received bevacizumab plus carboplatin-paclitaxel (318 subjects) with outcomes in patients who received first-line carboplatin and paclitaxel alone (1,184 subjects). To mitigate any selection bias that might confound the results of the first comparison, they also compared survival outcomes with a second control group, 2,664 patients treated in 2002-2005 before bevacizumab was commercially available.

All study subjects were followed for a minimum of 2 years after diagnosis, at which point 83% were deceased.

The median unadjusted survival was 9.7 months for patients receiving the bevacizumab combination, compared with 8.9 months for those receiving carboplatin-paclitaxel only and 8.0 months for the historical controls. When the data were adjusted to control for demographic and clinical characteristics, there was no significant difference in survival among the three study groups, the investigators said (JAMA 2012;307:1593-1601).

In four further data analyses that adjusted for propensity scores, there also was no evidence to support the superiority of adding bevacizumab to standard chemotherapy in these patients. Sensitivity analyses did not change these results. And analyses of subgroups of patients such as those with the most advanced disease or those with a high burden of comorbidity also showed no benefit from adding bevacizumab to the standard chemotherapy regimen.

Perhaps as important as the clinical results was the finding that following FDA approval of bevacizumab, only 20%-22% of the subjects in this study received the drug as a component of their first-line chemotherapy. This suggests that "the medical oncology community requires therapeutic evidence specific to a particular disease prior to adoption," Ms. Zhu and her associates said.

"Medical oncologists, particularly those in private practice, may have financial incentives to administer new, expensive treatment agents if they can purchase them for less money than [Medicare] reimburses. Because bevacizumab is expensive and was covered by [Medicare], if oncologists were subject to powerful treatment incentives as some have suggested, we would have expected to observe them in this context.

"That we did not observe rapid or complete uptake of bevacizumab provides some measure of reassurance that oncologists are circumspect and judicious in their use of new agents with uncertain benefit in the Medicare population," the researchers noted.

The study also points to the need for greater representation of the elderly in relevant clinical trials, according to the authors. Less than half of patients in the pivotal ECOG trial – 44% of those given standard treatment and 42% of those given bevacizumab with standard treatment – were diagnosed at 65 years or older, compared with 100% of the population in the current analysis.

"In the future, for malignancies like NSCLC that disproportionately affect elderly patients or where [Medicare] covers a large proportion of treatment costs, negotiations with pharmaceutical sponsors of pivotal trials might mandate adequate representation of elderly patients and/or preplanned subgroup analyses relevant to the Medicare population," they added.

This study was supported by the National Cancer Institute, the U.S. Agency for Healthcare Research and Quality, the California Department of Public Health, and the Centers for Disease Control and Prevention. No relevant financial conflicts of interest were reported.

Adding bevacizumab to standard first-line carboplatin and paclitaxel chemotherapy didn’t improve survival in a large retrospective cohort study of patients aged 65 and older who had advanced non–small cell lung cancer, according to a report in the April 18 issue of JAMA.

This finding is consistent with subgroup analyses of older lung cancer patients in efficacy studies of bevacizumab (Avastin), as well as with the results of a recent meta-analysis of four randomized clinical trials. Taken together, the findings demonstrate that bevacizumab should only be used "judiciously," and should not be considered the standard of care in this age group, said Junya Zhu of the Center for Patient Safety, Dana-Farber Cancer Institute, Boston, and her associates.

Approximately two-thirds of patients with lung cancer are diagnosed at age 65 or older, they noted.

Bevacizumab, a monoclonal antibody that inhibits tumor angiogenesis, was approved by the Food and Drug Administration (FDA) in 2006 as a combination therapy with carboplatin and paclitaxel for advanced nonsquamous non–small cell lung cancer (NSCLC). The pivotal Eastern Cooperative Oncology Group (ECOG 4599) trial demonstrated a statistically significant 2-month survival advantage with the addition of bevacizumab, but subset analyses did not find significant survival differences in older patients.

Ms. Zhu and her colleagues assessed the treatment in a Medicare population of 4,168 patients diagnosed with stage IIIB or IV nonsquamous NSCLC in 2002-2007, linking data from their medical records with data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) cancer registry.

The investigators compared outcomes in patients diagnosed in 2006-2007 who received bevacizumab plus carboplatin-paclitaxel (318 subjects) with outcomes in patients who received first-line carboplatin and paclitaxel alone (1,184 subjects). To mitigate any selection bias that might confound the results of the first comparison, they also compared survival outcomes with a second control group, 2,664 patients treated in 2002-2005 before bevacizumab was commercially available.

All study subjects were followed for a minimum of 2 years after diagnosis, at which point 83% were deceased.

The median unadjusted survival was 9.7 months for patients receiving the bevacizumab combination, compared with 8.9 months for those receiving carboplatin-paclitaxel only and 8.0 months for the historical controls. When the data were adjusted to control for demographic and clinical characteristics, there was no significant difference in survival among the three study groups, the investigators said (JAMA 2012;307:1593-1601).

In four further data analyses that adjusted for propensity scores, there also was no evidence to support the superiority of adding bevacizumab to standard chemotherapy in these patients. Sensitivity analyses did not change these results. And analyses of subgroups of patients such as those with the most advanced disease or those with a high burden of comorbidity also showed no benefit from adding bevacizumab to the standard chemotherapy regimen.

Perhaps as important as the clinical results was the finding that following FDA approval of bevacizumab, only 20%-22% of the subjects in this study received the drug as a component of their first-line chemotherapy. This suggests that "the medical oncology community requires therapeutic evidence specific to a particular disease prior to adoption," Ms. Zhu and her associates said.

"Medical oncologists, particularly those in private practice, may have financial incentives to administer new, expensive treatment agents if they can purchase them for less money than [Medicare] reimburses. Because bevacizumab is expensive and was covered by [Medicare], if oncologists were subject to powerful treatment incentives as some have suggested, we would have expected to observe them in this context.

"That we did not observe rapid or complete uptake of bevacizumab provides some measure of reassurance that oncologists are circumspect and judicious in their use of new agents with uncertain benefit in the Medicare population," the researchers noted.

The study also points to the need for greater representation of the elderly in relevant clinical trials, according to the authors. Less than half of patients in the pivotal ECOG trial – 44% of those given standard treatment and 42% of those given bevacizumab with standard treatment – were diagnosed at 65 years or older, compared with 100% of the population in the current analysis.

"In the future, for malignancies like NSCLC that disproportionately affect elderly patients or where [Medicare] covers a large proportion of treatment costs, negotiations with pharmaceutical sponsors of pivotal trials might mandate adequate representation of elderly patients and/or preplanned subgroup analyses relevant to the Medicare population," they added.

This study was supported by the National Cancer Institute, the U.S. Agency for Healthcare Research and Quality, the California Department of Public Health, and the Centers for Disease Control and Prevention. No relevant financial conflicts of interest were reported.

Adding bevacizumab to standard first-line carboplatin and paclitaxel chemotherapy didn’t improve survival in a large retrospective cohort study of patients aged 65 and older who had advanced non–small cell lung cancer, according to a report in the April 18 issue of JAMA.

This finding is consistent with subgroup analyses of older lung cancer patients in efficacy studies of bevacizumab (Avastin), as well as with the results of a recent meta-analysis of four randomized clinical trials. Taken together, the findings demonstrate that bevacizumab should only be used "judiciously," and should not be considered the standard of care in this age group, said Junya Zhu of the Center for Patient Safety, Dana-Farber Cancer Institute, Boston, and her associates.

Approximately two-thirds of patients with lung cancer are diagnosed at age 65 or older, they noted.

Bevacizumab, a monoclonal antibody that inhibits tumor angiogenesis, was approved by the Food and Drug Administration (FDA) in 2006 as a combination therapy with carboplatin and paclitaxel for advanced nonsquamous non–small cell lung cancer (NSCLC). The pivotal Eastern Cooperative Oncology Group (ECOG 4599) trial demonstrated a statistically significant 2-month survival advantage with the addition of bevacizumab, but subset analyses did not find significant survival differences in older patients.

Ms. Zhu and her colleagues assessed the treatment in a Medicare population of 4,168 patients diagnosed with stage IIIB or IV nonsquamous NSCLC in 2002-2007, linking data from their medical records with data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) cancer registry.

The investigators compared outcomes in patients diagnosed in 2006-2007 who received bevacizumab plus carboplatin-paclitaxel (318 subjects) with outcomes in patients who received first-line carboplatin and paclitaxel alone (1,184 subjects). To mitigate any selection bias that might confound the results of the first comparison, they also compared survival outcomes with a second control group, 2,664 patients treated in 2002-2005 before bevacizumab was commercially available.

All study subjects were followed for a minimum of 2 years after diagnosis, at which point 83% were deceased.

The median unadjusted survival was 9.7 months for patients receiving the bevacizumab combination, compared with 8.9 months for those receiving carboplatin-paclitaxel only and 8.0 months for the historical controls. When the data were adjusted to control for demographic and clinical characteristics, there was no significant difference in survival among the three study groups, the investigators said (JAMA 2012;307:1593-1601).

In four further data analyses that adjusted for propensity scores, there also was no evidence to support the superiority of adding bevacizumab to standard chemotherapy in these patients. Sensitivity analyses did not change these results. And analyses of subgroups of patients such as those with the most advanced disease or those with a high burden of comorbidity also showed no benefit from adding bevacizumab to the standard chemotherapy regimen.

Perhaps as important as the clinical results was the finding that following FDA approval of bevacizumab, only 20%-22% of the subjects in this study received the drug as a component of their first-line chemotherapy. This suggests that "the medical oncology community requires therapeutic evidence specific to a particular disease prior to adoption," Ms. Zhu and her associates said.

"Medical oncologists, particularly those in private practice, may have financial incentives to administer new, expensive treatment agents if they can purchase them for less money than [Medicare] reimburses. Because bevacizumab is expensive and was covered by [Medicare], if oncologists were subject to powerful treatment incentives as some have suggested, we would have expected to observe them in this context.

"That we did not observe rapid or complete uptake of bevacizumab provides some measure of reassurance that oncologists are circumspect and judicious in their use of new agents with uncertain benefit in the Medicare population," the researchers noted.

The study also points to the need for greater representation of the elderly in relevant clinical trials, according to the authors. Less than half of patients in the pivotal ECOG trial – 44% of those given standard treatment and 42% of those given bevacizumab with standard treatment – were diagnosed at 65 years or older, compared with 100% of the population in the current analysis.

"In the future, for malignancies like NSCLC that disproportionately affect elderly patients or where [Medicare] covers a large proportion of treatment costs, negotiations with pharmaceutical sponsors of pivotal trials might mandate adequate representation of elderly patients and/or preplanned subgroup analyses relevant to the Medicare population," they added.

This study was supported by the National Cancer Institute, the U.S. Agency for Healthcare Research and Quality, the California Department of Public Health, and the Centers for Disease Control and Prevention. No relevant financial conflicts of interest were reported.

High-functioning patients with schizophrenia experienced "mind-pops" significantly more often than did two control groups in a preliminary study exploring a possible connection between these benign cognitive phenomena and hallucinations, according to a report published online in Psychiatry Research.

Mind-pops is the term coined in 1997 for the involuntary semantic memories that "come to mind unexpectedly, without any attempt to recall them, and consist of isolated fragments of one’s semantic knowledge, rather than meaningful episodes from one’s personal past." They typically occur when a person is alone, involved in an everyday activity that requires little attention (such as brushing teeth), and thinking about unrelated matters (such as what to wear that day), and they consist of the sudden intrusion of a word or phrase, a name, a visual image, or a familiar snatch of music that "amazes the person with its irrelevance to the current situation," said Ia Elua, Ph.D., of the University of Herefordshire School of Psychology, Hatfield (U.K.), and her associates (Psychiatry Res. 2012 [doi:10.1016/j.psychres.2011.11.026]).

Mind-pops usually are "one-off occurrences," but occasionally they can come to mind repeatedly and be difficult to dismiss. Musical mind-pops – recurring melodies, songs, or commercial jingles – "have been recently studied under a variety of names such as ‘earworms,’ ‘stuck song syndrome,’ or involuntary musical imagery," the investigators noted.

Mind-pops are different from other involuntary cognitive phenomena described in the literature in that they have no trigger. In contrast, ordinary autobiographical memories can pop up (rather than being summoned intentionally) in response to a relevant trigger – such as remembering a holiday trip when seeing an advertisement for vacations. And more intrusive memories of negative events, such as remembering being mugged when hearing footsteps approaching in the dark, also have obvious triggers.

Mind-pops usually are "one-off occurrences," but occasionally they can come to mind repeatedly and be difficult to dismiss.

Mind-pops also differ from other cognitive intrusions such as repetitive negative thoughts, compulsions, and flashbacks of traumatic experiences in that they are benign. They usually take the form of words or phrases and less often involve visual images or music.

There are several traits common to both mind-pops and hallucinations. Both occur unexpectedly, have no triggers, and can be disruptive, hence both can sometimes be perceived as "alien" thoughts being imposed on the mind from outside. Both can sometimes occur during altered states of consciousness, such as when falling asleep or waking, but primarily occur when the individual is alone and engaged in an undemanding activity. And like mind-pops, hallucinations are primarily verbal but can also be visual or musical, Dr. Elua and her colleagues said.

These similarities led the researchers to hypothesize that mind-pops "could be the raw cognitive material from which hallucinations are constructed in schizophrenia." To test this hypothesis, they assessed the frequency and nature of mind-pops in 37 high-functioning patients with schizophrenia and 31 high-functioning patients who had major depressive disorder without psychotic features, all of whom were attending either day treatment or outpatient mental health clinics, as well as 31 nonclinical control subjects.

The 19 men and 18 women with schizophrenia had paranoid type (23 subjects), undifferentiated type (11 subjects), or residual type (3 subjects).

All the study participants with schizophrenia said they had experienced mind-pops. In contrast, six (19%) of the subjects with depression and five (16%) of the nonclinical control subjects said they had never experienced mind-pops. This difference is statistically significant, the investigators said.

Patients with schizophrenia also experienced mind-pops more frequently than did the control subjects, scoring a median of 6.05 on an 8-point scale in which 1 signified only a few mind-pops over the lifetime and 8 signified 3 or more mind-pops per day. In contrast, patients with depression scored a median of 3.74 on this scale and the nonclinical controls scores a median of 3.13.

These results were not materially changed in further analyses that controlled for subject age and years of education, nor in an analysis that excluded all subjects who had never experienced mind-pops.

The patients with schizophrenia were divided among those who were having hallucinations near the time of the assessment (22 subjects) and those who were not having hallucinations currently but had had them in the past (15 subjects). The mean frequency of mind-pops was higher among patients who had current hallucinations, but the difference did not reach statistical significance.

In addition, patients with schizophrenia reported having a significantly larger range of the different types of mind-pops than did subjects in both control groups.

Schizophrenia patients also were much more likely to provide examples of their mind-pops in answer to an optional question. However, the content of mind-pops was similar across all three study groups.

These findings suggest "a possible intriguing link between mind-pops and hallucinations." It may be that "ordinary mind-pops, experienced as benign phenomena by nonclinical individuals, will take the exaggerated and abnormal form of auditory and other types of hallucinations in patients with schizophrenia," Dr. Elua and her associates said.

Future research should attempt to ascertain "whether the content of mind-pops is more negative and distressing in patients with schizophrenia than in clinical and nonclinical controls, and whether schizophrenia patients are more likely to actively suppress and/or control the occurrence of their mind-pops. If that is the case, then these processes can be responsible for transforming ordinary mind-pops into hallucinations," the investigators said.

Alternatively, it might be that the content of mind-pops is similar between schizophrenia patients and controls, but that the schizophrenia patients interpret them as being more alien or threatening. "They may assume that something strange is happening to them ... that they are ‘going mad,’ " the researchers said.

Dr. Elua is now with the Jewish Board of Family and Children’s Services, Outpatient Mental Health Clinic, New York.

High-functioning patients with schizophrenia experienced "mind-pops" significantly more often than did two control groups in a preliminary study exploring a possible connection between these benign cognitive phenomena and hallucinations, according to a report published online in Psychiatry Research.

Mind-pops is the term coined in 1997 for the involuntary semantic memories that "come to mind unexpectedly, without any attempt to recall them, and consist of isolated fragments of one’s semantic knowledge, rather than meaningful episodes from one’s personal past." They typically occur when a person is alone, involved in an everyday activity that requires little attention (such as brushing teeth), and thinking about unrelated matters (such as what to wear that day), and they consist of the sudden intrusion of a word or phrase, a name, a visual image, or a familiar snatch of music that "amazes the person with its irrelevance to the current situation," said Ia Elua, Ph.D., of the University of Herefordshire School of Psychology, Hatfield (U.K.), and her associates (Psychiatry Res. 2012 [doi:10.1016/j.psychres.2011.11.026]).

Mind-pops usually are "one-off occurrences," but occasionally they can come to mind repeatedly and be difficult to dismiss. Musical mind-pops – recurring melodies, songs, or commercial jingles – "have been recently studied under a variety of names such as ‘earworms,’ ‘stuck song syndrome,’ or involuntary musical imagery," the investigators noted.

Mind-pops are different from other involuntary cognitive phenomena described in the literature in that they have no trigger. In contrast, ordinary autobiographical memories can pop up (rather than being summoned intentionally) in response to a relevant trigger – such as remembering a holiday trip when seeing an advertisement for vacations. And more intrusive memories of negative events, such as remembering being mugged when hearing footsteps approaching in the dark, also have obvious triggers.

Mind-pops usually are "one-off occurrences," but occasionally they can come to mind repeatedly and be difficult to dismiss.

Mind-pops also differ from other cognitive intrusions such as repetitive negative thoughts, compulsions, and flashbacks of traumatic experiences in that they are benign. They usually take the form of words or phrases and less often involve visual images or music.

There are several traits common to both mind-pops and hallucinations. Both occur unexpectedly, have no triggers, and can be disruptive, hence both can sometimes be perceived as "alien" thoughts being imposed on the mind from outside. Both can sometimes occur during altered states of consciousness, such as when falling asleep or waking, but primarily occur when the individual is alone and engaged in an undemanding activity. And like mind-pops, hallucinations are primarily verbal but can also be visual or musical, Dr. Elua and her colleagues said.

These similarities led the researchers to hypothesize that mind-pops "could be the raw cognitive material from which hallucinations are constructed in schizophrenia." To test this hypothesis, they assessed the frequency and nature of mind-pops in 37 high-functioning patients with schizophrenia and 31 high-functioning patients who had major depressive disorder without psychotic features, all of whom were attending either day treatment or outpatient mental health clinics, as well as 31 nonclinical control subjects.

The 19 men and 18 women with schizophrenia had paranoid type (23 subjects), undifferentiated type (11 subjects), or residual type (3 subjects).

All the study participants with schizophrenia said they had experienced mind-pops. In contrast, six (19%) of the subjects with depression and five (16%) of the nonclinical control subjects said they had never experienced mind-pops. This difference is statistically significant, the investigators said.

Patients with schizophrenia also experienced mind-pops more frequently than did the control subjects, scoring a median of 6.05 on an 8-point scale in which 1 signified only a few mind-pops over the lifetime and 8 signified 3 or more mind-pops per day. In contrast, patients with depression scored a median of 3.74 on this scale and the nonclinical controls scores a median of 3.13.

These results were not materially changed in further analyses that controlled for subject age and years of education, nor in an analysis that excluded all subjects who had never experienced mind-pops.

The patients with schizophrenia were divided among those who were having hallucinations near the time of the assessment (22 subjects) and those who were not having hallucinations currently but had had them in the past (15 subjects). The mean frequency of mind-pops was higher among patients who had current hallucinations, but the difference did not reach statistical significance.

In addition, patients with schizophrenia reported having a significantly larger range of the different types of mind-pops than did subjects in both control groups.

Schizophrenia patients also were much more likely to provide examples of their mind-pops in answer to an optional question. However, the content of mind-pops was similar across all three study groups.

These findings suggest "a possible intriguing link between mind-pops and hallucinations." It may be that "ordinary mind-pops, experienced as benign phenomena by nonclinical individuals, will take the exaggerated and abnormal form of auditory and other types of hallucinations in patients with schizophrenia," Dr. Elua and her associates said.

Future research should attempt to ascertain "whether the content of mind-pops is more negative and distressing in patients with schizophrenia than in clinical and nonclinical controls, and whether schizophrenia patients are more likely to actively suppress and/or control the occurrence of their mind-pops. If that is the case, then these processes can be responsible for transforming ordinary mind-pops into hallucinations," the investigators said.

Alternatively, it might be that the content of mind-pops is similar between schizophrenia patients and controls, but that the schizophrenia patients interpret them as being more alien or threatening. "They may assume that something strange is happening to them ... that they are ‘going mad,’ " the researchers said.

Dr. Elua is now with the Jewish Board of Family and Children’s Services, Outpatient Mental Health Clinic, New York.

High-functioning patients with schizophrenia experienced "mind-pops" significantly more often than did two control groups in a preliminary study exploring a possible connection between these benign cognitive phenomena and hallucinations, according to a report published online in Psychiatry Research.

Mind-pops is the term coined in 1997 for the involuntary semantic memories that "come to mind unexpectedly, without any attempt to recall them, and consist of isolated fragments of one’s semantic knowledge, rather than meaningful episodes from one’s personal past." They typically occur when a person is alone, involved in an everyday activity that requires little attention (such as brushing teeth), and thinking about unrelated matters (such as what to wear that day), and they consist of the sudden intrusion of a word or phrase, a name, a visual image, or a familiar snatch of music that "amazes the person with its irrelevance to the current situation," said Ia Elua, Ph.D., of the University of Herefordshire School of Psychology, Hatfield (U.K.), and her associates (Psychiatry Res. 2012 [doi:10.1016/j.psychres.2011.11.026]).

Mind-pops usually are "one-off occurrences," but occasionally they can come to mind repeatedly and be difficult to dismiss. Musical mind-pops – recurring melodies, songs, or commercial jingles – "have been recently studied under a variety of names such as ‘earworms,’ ‘stuck song syndrome,’ or involuntary musical imagery," the investigators noted.

Mind-pops are different from other involuntary cognitive phenomena described in the literature in that they have no trigger. In contrast, ordinary autobiographical memories can pop up (rather than being summoned intentionally) in response to a relevant trigger – such as remembering a holiday trip when seeing an advertisement for vacations. And more intrusive memories of negative events, such as remembering being mugged when hearing footsteps approaching in the dark, also have obvious triggers.

Mind-pops usually are "one-off occurrences," but occasionally they can come to mind repeatedly and be difficult to dismiss.

Mind-pops also differ from other cognitive intrusions such as repetitive negative thoughts, compulsions, and flashbacks of traumatic experiences in that they are benign. They usually take the form of words or phrases and less often involve visual images or music.

There are several traits common to both mind-pops and hallucinations. Both occur unexpectedly, have no triggers, and can be disruptive, hence both can sometimes be perceived as "alien" thoughts being imposed on the mind from outside. Both can sometimes occur during altered states of consciousness, such as when falling asleep or waking, but primarily occur when the individual is alone and engaged in an undemanding activity. And like mind-pops, hallucinations are primarily verbal but can also be visual or musical, Dr. Elua and her colleagues said.

These similarities led the researchers to hypothesize that mind-pops "could be the raw cognitive material from which hallucinations are constructed in schizophrenia." To test this hypothesis, they assessed the frequency and nature of mind-pops in 37 high-functioning patients with schizophrenia and 31 high-functioning patients who had major depressive disorder without psychotic features, all of whom were attending either day treatment or outpatient mental health clinics, as well as 31 nonclinical control subjects.

The 19 men and 18 women with schizophrenia had paranoid type (23 subjects), undifferentiated type (11 subjects), or residual type (3 subjects).

All the study participants with schizophrenia said they had experienced mind-pops. In contrast, six (19%) of the subjects with depression and five (16%) of the nonclinical control subjects said they had never experienced mind-pops. This difference is statistically significant, the investigators said.

Patients with schizophrenia also experienced mind-pops more frequently than did the control subjects, scoring a median of 6.05 on an 8-point scale in which 1 signified only a few mind-pops over the lifetime and 8 signified 3 or more mind-pops per day. In contrast, patients with depression scored a median of 3.74 on this scale and the nonclinical controls scores a median of 3.13.

These results were not materially changed in further analyses that controlled for subject age and years of education, nor in an analysis that excluded all subjects who had never experienced mind-pops.

The patients with schizophrenia were divided among those who were having hallucinations near the time of the assessment (22 subjects) and those who were not having hallucinations currently but had had them in the past (15 subjects). The mean frequency of mind-pops was higher among patients who had current hallucinations, but the difference did not reach statistical significance.

In addition, patients with schizophrenia reported having a significantly larger range of the different types of mind-pops than did subjects in both control groups.

Schizophrenia patients also were much more likely to provide examples of their mind-pops in answer to an optional question. However, the content of mind-pops was similar across all three study groups.

These findings suggest "a possible intriguing link between mind-pops and hallucinations." It may be that "ordinary mind-pops, experienced as benign phenomena by nonclinical individuals, will take the exaggerated and abnormal form of auditory and other types of hallucinations in patients with schizophrenia," Dr. Elua and her associates said.

Future research should attempt to ascertain "whether the content of mind-pops is more negative and distressing in patients with schizophrenia than in clinical and nonclinical controls, and whether schizophrenia patients are more likely to actively suppress and/or control the occurrence of their mind-pops. If that is the case, then these processes can be responsible for transforming ordinary mind-pops into hallucinations," the investigators said.

Alternatively, it might be that the content of mind-pops is similar between schizophrenia patients and controls, but that the schizophrenia patients interpret them as being more alien or threatening. "They may assume that something strange is happening to them ... that they are ‘going mad,’ " the researchers said.

Dr. Elua is now with the Jewish Board of Family and Children’s Services, Outpatient Mental Health Clinic, New York.

Intravenous cangrelor may prove to be a useful "bridge" in patients awaiting nonemergency CABG who must first discontinue their regular antiplatelet therapy, according to the results of the Maintenance of Platelet Inhibition With Cangrelor (BRIDGE) trial.

The practice of discontinuation of antiplatelet therapy is associated with significant morbidity and mortality; in patients who have coronary stents, it raises the risk of stent thrombosis that often leads to myocardial infarction and death. "Cessation of thienopyridine treatment for nearly a week before surgery, with patients not hospitalized or monitored but carrying an excess risk of major ischemic events, has been a troubling and not infrequent problem for clinicians, because it is estimated that approximately 5% of patients will require some type of surgery within the first 12 months after stent implant or [acute coronary syndrome] diagnosis," said Dr. Dominick J. Angiolillo of the department of cardiology, University of Florida, Jacksonville, and his associates.

In this multicenter clinical trial sponsored by the drug’s maker, cangrelor "achieved and maintained target levels of platelet inhibition known to be associated with a low risk of thrombotic events compared with placebo, without a significant excess in bleeding complications," the investigators noted.

Cangrelor is an investigational nonthienopyridine adenosine triphosphate analogue that acts as an antagonist of the P2Y12 receptor. It is characterized by "rapid, potent, predictable, and reversible platelet inhibition," and its extremely short half-life (3-6 minutes) allows "rapid offset of effect."

The investigators hypothesized that cangrelor would allow patients who must discontinue antiplatelet therapy prior to cardiac surgery, especially if they’re taking a P2Y12 inhibitor such as ticlopidine, clopidogrel, or prasugrel, to go off their usual drug without raising their risk for thrombotic events. They tested this hypothesis in a two-part trial.

The first part was an open-label dose-finding study involving 11 adults and concluded that the optimal intravenous dose needed to maintain antiplatelet activity without raising bleeding risks was 0.75 mcg/kg per minute. In the second part of the trial, 210 patients awaiting CABG at 34 medical centers around the world were randomly assigned to receive either cangrelor (106 subjects) or placebo (104 subjects) after thienopyridines were discontinued and throughout the preoperative period – that is, until 1-6 hours before surgical incision.

The mean interval between discontinuation of thienopyridines and infusion of the study drug was 29 hours, and the mean duration of the infusion was approximately 3 days. The primary end point was the percentage of patients who showed platelet reactivity of less than 240 P2Y12 Reaction Units (PRUs) throughout the infusion of the study drug.

"This level approximated the levels of platelet reactivity expected to be maintained if a thienopyridine had not been discontinued," the investigators explained.

This end point was met by 99% of the cangrelor group but only 19% of the placebo group (JAMA 2012;307:265-74).

Moreover, cangrelor did not raise the rate of excessive bleeding related to CABG surgery. This safety end point occurred in 22 patients: 11.8% of the cangrelor group and 10.4% of the placebo group, a nonsignificant difference.

The number of minor bleeding events was numerically higher with cangrelor but did not reach statistical significance. This favorable safety profile, even with prolonged infusion of up to 7 days, was "reassuring," the researchers noted.

Ischemic end points prior to surgery were low, occurring in 2.8% (3 of 106) and 4.0% (4 of 101) of patients in the cangrelor and placebo groups.

"These observations support the hypothesis that intravenous cangrelor is a feasible management strategy, providing prolonged platelet P2Y12 inhibition in patients who must wait for cardiac surgery after thienopyridine discontinuation," they said.

The study was sponsored by the Medicines Company. Dr. Angiolillo reported ties to various pharmaceutical companies.

Intravenous cangrelor may prove to be a useful "bridge" in patients awaiting nonemergency CABG who must first discontinue their regular antiplatelet therapy, according to the results of the Maintenance of Platelet Inhibition With Cangrelor (BRIDGE) trial.

The practice of discontinuation of antiplatelet therapy is associated with significant morbidity and mortality; in patients who have coronary stents, it raises the risk of stent thrombosis that often leads to myocardial infarction and death. "Cessation of thienopyridine treatment for nearly a week before surgery, with patients not hospitalized or monitored but carrying an excess risk of major ischemic events, has been a troubling and not infrequent problem for clinicians, because it is estimated that approximately 5% of patients will require some type of surgery within the first 12 months after stent implant or [acute coronary syndrome] diagnosis," said Dr. Dominick J. Angiolillo of the department of cardiology, University of Florida, Jacksonville, and his associates.

In this multicenter clinical trial sponsored by the drug’s maker, cangrelor "achieved and maintained target levels of platelet inhibition known to be associated with a low risk of thrombotic events compared with placebo, without a significant excess in bleeding complications," the investigators noted.

Cangrelor is an investigational nonthienopyridine adenosine triphosphate analogue that acts as an antagonist of the P2Y12 receptor. It is characterized by "rapid, potent, predictable, and reversible platelet inhibition," and its extremely short half-life (3-6 minutes) allows "rapid offset of effect."

The investigators hypothesized that cangrelor would allow patients who must discontinue antiplatelet therapy prior to cardiac surgery, especially if they’re taking a P2Y12 inhibitor such as ticlopidine, clopidogrel, or prasugrel, to go off their usual drug without raising their risk for thrombotic events. They tested this hypothesis in a two-part trial.

The first part was an open-label dose-finding study involving 11 adults and concluded that the optimal intravenous dose needed to maintain antiplatelet activity without raising bleeding risks was 0.75 mcg/kg per minute. In the second part of the trial, 210 patients awaiting CABG at 34 medical centers around the world were randomly assigned to receive either cangrelor (106 subjects) or placebo (104 subjects) after thienopyridines were discontinued and throughout the preoperative period – that is, until 1-6 hours before surgical incision.

The mean interval between discontinuation of thienopyridines and infusion of the study drug was 29 hours, and the mean duration of the infusion was approximately 3 days. The primary end point was the percentage of patients who showed platelet reactivity of less than 240 P2Y12 Reaction Units (PRUs) throughout the infusion of the study drug.

"This level approximated the levels of platelet reactivity expected to be maintained if a thienopyridine had not been discontinued," the investigators explained.

This end point was met by 99% of the cangrelor group but only 19% of the placebo group (JAMA 2012;307:265-74).

Moreover, cangrelor did not raise the rate of excessive bleeding related to CABG surgery. This safety end point occurred in 22 patients: 11.8% of the cangrelor group and 10.4% of the placebo group, a nonsignificant difference.

The number of minor bleeding events was numerically higher with cangrelor but did not reach statistical significance. This favorable safety profile, even with prolonged infusion of up to 7 days, was "reassuring," the researchers noted.

Ischemic end points prior to surgery were low, occurring in 2.8% (3 of 106) and 4.0% (4 of 101) of patients in the cangrelor and placebo groups.

"These observations support the hypothesis that intravenous cangrelor is a feasible management strategy, providing prolonged platelet P2Y12 inhibition in patients who must wait for cardiac surgery after thienopyridine discontinuation," they said.

The study was sponsored by the Medicines Company. Dr. Angiolillo reported ties to various pharmaceutical companies.

Intravenous cangrelor may prove to be a useful "bridge" in patients awaiting nonemergency CABG who must first discontinue their regular antiplatelet therapy, according to the results of the Maintenance of Platelet Inhibition With Cangrelor (BRIDGE) trial.

The practice of discontinuation of antiplatelet therapy is associated with significant morbidity and mortality; in patients who have coronary stents, it raises the risk of stent thrombosis that often leads to myocardial infarction and death. "Cessation of thienopyridine treatment for nearly a week before surgery, with patients not hospitalized or monitored but carrying an excess risk of major ischemic events, has been a troubling and not infrequent problem for clinicians, because it is estimated that approximately 5% of patients will require some type of surgery within the first 12 months after stent implant or [acute coronary syndrome] diagnosis," said Dr. Dominick J. Angiolillo of the department of cardiology, University of Florida, Jacksonville, and his associates.

In this multicenter clinical trial sponsored by the drug’s maker, cangrelor "achieved and maintained target levels of platelet inhibition known to be associated with a low risk of thrombotic events compared with placebo, without a significant excess in bleeding complications," the investigators noted.

Cangrelor is an investigational nonthienopyridine adenosine triphosphate analogue that acts as an antagonist of the P2Y12 receptor. It is characterized by "rapid, potent, predictable, and reversible platelet inhibition," and its extremely short half-life (3-6 minutes) allows "rapid offset of effect."

The investigators hypothesized that cangrelor would allow patients who must discontinue antiplatelet therapy prior to cardiac surgery, especially if they’re taking a P2Y12 inhibitor such as ticlopidine, clopidogrel, or prasugrel, to go off their usual drug without raising their risk for thrombotic events. They tested this hypothesis in a two-part trial.

The first part was an open-label dose-finding study involving 11 adults and concluded that the optimal intravenous dose needed to maintain antiplatelet activity without raising bleeding risks was 0.75 mcg/kg per minute. In the second part of the trial, 210 patients awaiting CABG at 34 medical centers around the world were randomly assigned to receive either cangrelor (106 subjects) or placebo (104 subjects) after thienopyridines were discontinued and throughout the preoperative period – that is, until 1-6 hours before surgical incision.

The mean interval between discontinuation of thienopyridines and infusion of the study drug was 29 hours, and the mean duration of the infusion was approximately 3 days. The primary end point was the percentage of patients who showed platelet reactivity of less than 240 P2Y12 Reaction Units (PRUs) throughout the infusion of the study drug.

"This level approximated the levels of platelet reactivity expected to be maintained if a thienopyridine had not been discontinued," the investigators explained.

This end point was met by 99% of the cangrelor group but only 19% of the placebo group (JAMA 2012;307:265-74).

Moreover, cangrelor did not raise the rate of excessive bleeding related to CABG surgery. This safety end point occurred in 22 patients: 11.8% of the cangrelor group and 10.4% of the placebo group, a nonsignificant difference.

The number of minor bleeding events was numerically higher with cangrelor but did not reach statistical significance. This favorable safety profile, even with prolonged infusion of up to 7 days, was "reassuring," the researchers noted.

Ischemic end points prior to surgery were low, occurring in 2.8% (3 of 106) and 4.0% (4 of 101) of patients in the cangrelor and placebo groups.

"These observations support the hypothesis that intravenous cangrelor is a feasible management strategy, providing prolonged platelet P2Y12 inhibition in patients who must wait for cardiac surgery after thienopyridine discontinuation," they said.

The study was sponsored by the Medicines Company. Dr. Angiolillo reported ties to various pharmaceutical companies.

In patients with chronic hepatitis B who are negative for hepatitis B e antigen and have low viral loads, serum levels of hepatitis B surface antigen can be used to predict risk for hepatocellular carcinoma (HCC), Dr. Tai-Chung Tseng and colleagues reported in the May issue of Gastroenterology.

In such patients, high levels of hepatitis B surface antigen (HBsAg) indicate higher risk for liver cancer, regardless of low hepatitis B DNA levels, said Dr. Tseng of the Buddhist Tzu Chi General Hospital Taipei, and associates.

HBV DNA levels are considered the major driver of disease progression in patients with chronic hepatitis B, and those with low viral loads are usually considered to be at low risk for developing HCC. However, even these patients still carry some risk for the malignancy, with an estimated annual incidence of 0.06%.

"Therefore, identification of factors predictive of HCC other than viral load in these ‘low-risk’ patients remains [imperative]," the investigators wrote (Gastroenterology 2012 Feb. 13 [doi:10.1053/j.gastro.2012.02.007]).

"Recently, HBsAg quantification has become increasingly recognized as a marker for evaluating viral replication and possible host immune control over HBV infection. A lower HBsAg level is associated with ... a lower risk of hepatitis activity," they noted.

So Dr. Tseng and colleagues assessed a large cohort of treatment-naive patients who had chronic HBV infection with genotypes B or C, but no cirrhosis. The study subjects and had been enrolled in a study of HBsAg loss in 1985-1995, and study enrollment later was extended until 2000.

The study population comprised 2,688 HBV carriers aged 28 and older at baseline who underwent frequent liver function tests, serum sampling, and abdominal ultrasonography for HCC surveillance. Approximately 61% of them were men.

The average duration of follow-up was 14.7 years (range, 2.5 to 25.8 years). A total of 191 patients developed HCC during that time, with an overall incidence of 4.8 cases per 1,000 person-years.

The average interval between baseline and development of HCC was 11 years (range, 2.5 to 24.5 years).

As expected, HBeAg positivity, higher levels of HBV DNA, and higher levels of alanine aminotransferase all were associated with a higher rate of HCC. Other factors known to raise the risk of HCC did so in this study, including older age, male gender, and infection with genotype C.

HBsAg level also was found to correlate with HCC risk, in a dose-response manner. However, it was not as strong as the other predictors in the study population as a whole or in the subgroup of patients who were HBeAg positive.

But the researchers were particularly interested in patients who were HBeAg-negative and had low viral loads, and thus were lacking the two risk factors that best predicted HCC risk.

In a univariate analysis, the hazard ratio (HR) for developing HCC was 5.4 in such patients who had a high (1,000 IU/mL or greater) HBsAg level, compared with those who had an HBsAg level lower than 1,000 IU/mL.

Further multivariate analysis showed that a high HBsAg level remained an independent risk factor for HCC, with an HR of 13.7.

"These data suggest that HBsAg level may complement HBV DNA level in predicting HCC development," especially in patients with low viral loads, Dr. Tseng and colleagues said.

They proposed that patients with low viral loads but high HBsAg levels "may harbor more hepatocytes with HBV integration than those who have a low HbsAg level. Therefore, the higher risk of HCC ... may be attributed to the increased genomic instability as a result of integrated viral sequences, which play an important role in hepatocarcinogenesis."

In this study population, the subgroup of patients who had both a low HBV DNA level and a low HBsAg level showed a cumulative incidence of HCC of only 0.2%, which is similar to the level reported in control subjects in previous studies. Thus, a low HbsAg level accompanied by a low HBV DNA level appears to reflect adequate host immune control against HBV infection and can be used to identify patients at low risk for developing HCC.

Clinicians "urgently require a good indictor to stop nucleotide analogue therapy in HBeAg-negative patients. If an HbsAg level of less than 1000 IU/mL could be reliably used to define low-risk or inactive HBV carriers, we may adopt this cutoff level as the intermediate treatment goal," assuming that the results of this study are confirmed in future research, the authors wrote.

This study was supported by the Buddhist Tzu-Chi General Hospital Taipei Branch, the National Taiwan University Hospital, the Department of Health, and the National Science Council. Dr. Tseng’s associates reported ties to Abbott, Bayer, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, and Roche.

In patients with chronic hepatitis B who are negative for hepatitis B e antigen and have low viral loads, serum levels of hepatitis B surface antigen can be used to predict risk for hepatocellular carcinoma (HCC), Dr. Tai-Chung Tseng and colleagues reported in the May issue of Gastroenterology.

In such patients, high levels of hepatitis B surface antigen (HBsAg) indicate higher risk for liver cancer, regardless of low hepatitis B DNA levels, said Dr. Tseng of the Buddhist Tzu Chi General Hospital Taipei, and associates.

HBV DNA levels are considered the major driver of disease progression in patients with chronic hepatitis B, and those with low viral loads are usually considered to be at low risk for developing HCC. However, even these patients still carry some risk for the malignancy, with an estimated annual incidence of 0.06%.

"Therefore, identification of factors predictive of HCC other than viral load in these ‘low-risk’ patients remains [imperative]," the investigators wrote (Gastroenterology 2012 Feb. 13 [doi:10.1053/j.gastro.2012.02.007]).

"Recently, HBsAg quantification has become increasingly recognized as a marker for evaluating viral replication and possible host immune control over HBV infection. A lower HBsAg level is associated with ... a lower risk of hepatitis activity," they noted.

So Dr. Tseng and colleagues assessed a large cohort of treatment-naive patients who had chronic HBV infection with genotypes B or C, but no cirrhosis. The study subjects and had been enrolled in a study of HBsAg loss in 1985-1995, and study enrollment later was extended until 2000.

The study population comprised 2,688 HBV carriers aged 28 and older at baseline who underwent frequent liver function tests, serum sampling, and abdominal ultrasonography for HCC surveillance. Approximately 61% of them were men.

The average duration of follow-up was 14.7 years (range, 2.5 to 25.8 years). A total of 191 patients developed HCC during that time, with an overall incidence of 4.8 cases per 1,000 person-years.

The average interval between baseline and development of HCC was 11 years (range, 2.5 to 24.5 years).

As expected, HBeAg positivity, higher levels of HBV DNA, and higher levels of alanine aminotransferase all were associated with a higher rate of HCC. Other factors known to raise the risk of HCC did so in this study, including older age, male gender, and infection with genotype C.

HBsAg level also was found to correlate with HCC risk, in a dose-response manner. However, it was not as strong as the other predictors in the study population as a whole or in the subgroup of patients who were HBeAg positive.

But the researchers were particularly interested in patients who were HBeAg-negative and had low viral loads, and thus were lacking the two risk factors that best predicted HCC risk.

In a univariate analysis, the hazard ratio (HR) for developing HCC was 5.4 in such patients who had a high (1,000 IU/mL or greater) HBsAg level, compared with those who had an HBsAg level lower than 1,000 IU/mL.

Further multivariate analysis showed that a high HBsAg level remained an independent risk factor for HCC, with an HR of 13.7.

"These data suggest that HBsAg level may complement HBV DNA level in predicting HCC development," especially in patients with low viral loads, Dr. Tseng and colleagues said.

They proposed that patients with low viral loads but high HBsAg levels "may harbor more hepatocytes with HBV integration than those who have a low HbsAg level. Therefore, the higher risk of HCC ... may be attributed to the increased genomic instability as a result of integrated viral sequences, which play an important role in hepatocarcinogenesis."

In this study population, the subgroup of patients who had both a low HBV DNA level and a low HBsAg level showed a cumulative incidence of HCC of only 0.2%, which is similar to the level reported in control subjects in previous studies. Thus, a low HbsAg level accompanied by a low HBV DNA level appears to reflect adequate host immune control against HBV infection and can be used to identify patients at low risk for developing HCC.

Clinicians "urgently require a good indictor to stop nucleotide analogue therapy in HBeAg-negative patients. If an HbsAg level of less than 1000 IU/mL could be reliably used to define low-risk or inactive HBV carriers, we may adopt this cutoff level as the intermediate treatment goal," assuming that the results of this study are confirmed in future research, the authors wrote.

This study was supported by the Buddhist Tzu-Chi General Hospital Taipei Branch, the National Taiwan University Hospital, the Department of Health, and the National Science Council. Dr. Tseng’s associates reported ties to Abbott, Bayer, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, and Roche.

In patients with chronic hepatitis B who are negative for hepatitis B e antigen and have low viral loads, serum levels of hepatitis B surface antigen can be used to predict risk for hepatocellular carcinoma (HCC), Dr. Tai-Chung Tseng and colleagues reported in the May issue of Gastroenterology.

In such patients, high levels of hepatitis B surface antigen (HBsAg) indicate higher risk for liver cancer, regardless of low hepatitis B DNA levels, said Dr. Tseng of the Buddhist Tzu Chi General Hospital Taipei, and associates.

HBV DNA levels are considered the major driver of disease progression in patients with chronic hepatitis B, and those with low viral loads are usually considered to be at low risk for developing HCC. However, even these patients still carry some risk for the malignancy, with an estimated annual incidence of 0.06%.

"Therefore, identification of factors predictive of HCC other than viral load in these ‘low-risk’ patients remains [imperative]," the investigators wrote (Gastroenterology 2012 Feb. 13 [doi:10.1053/j.gastro.2012.02.007]).

"Recently, HBsAg quantification has become increasingly recognized as a marker for evaluating viral replication and possible host immune control over HBV infection. A lower HBsAg level is associated with ... a lower risk of hepatitis activity," they noted.

So Dr. Tseng and colleagues assessed a large cohort of treatment-naive patients who had chronic HBV infection with genotypes B or C, but no cirrhosis. The study subjects and had been enrolled in a study of HBsAg loss in 1985-1995, and study enrollment later was extended until 2000.

The study population comprised 2,688 HBV carriers aged 28 and older at baseline who underwent frequent liver function tests, serum sampling, and abdominal ultrasonography for HCC surveillance. Approximately 61% of them were men.

The average duration of follow-up was 14.7 years (range, 2.5 to 25.8 years). A total of 191 patients developed HCC during that time, with an overall incidence of 4.8 cases per 1,000 person-years.

The average interval between baseline and development of HCC was 11 years (range, 2.5 to 24.5 years).

As expected, HBeAg positivity, higher levels of HBV DNA, and higher levels of alanine aminotransferase all were associated with a higher rate of HCC. Other factors known to raise the risk of HCC did so in this study, including older age, male gender, and infection with genotype C.

HBsAg level also was found to correlate with HCC risk, in a dose-response manner. However, it was not as strong as the other predictors in the study population as a whole or in the subgroup of patients who were HBeAg positive.

But the researchers were particularly interested in patients who were HBeAg-negative and had low viral loads, and thus were lacking the two risk factors that best predicted HCC risk.

In a univariate analysis, the hazard ratio (HR) for developing HCC was 5.4 in such patients who had a high (1,000 IU/mL or greater) HBsAg level, compared with those who had an HBsAg level lower than 1,000 IU/mL.

Further multivariate analysis showed that a high HBsAg level remained an independent risk factor for HCC, with an HR of 13.7.

"These data suggest that HBsAg level may complement HBV DNA level in predicting HCC development," especially in patients with low viral loads, Dr. Tseng and colleagues said.

They proposed that patients with low viral loads but high HBsAg levels "may harbor more hepatocytes with HBV integration than those who have a low HbsAg level. Therefore, the higher risk of HCC ... may be attributed to the increased genomic instability as a result of integrated viral sequences, which play an important role in hepatocarcinogenesis."

In this study population, the subgroup of patients who had both a low HBV DNA level and a low HBsAg level showed a cumulative incidence of HCC of only 0.2%, which is similar to the level reported in control subjects in previous studies. Thus, a low HbsAg level accompanied by a low HBV DNA level appears to reflect adequate host immune control against HBV infection and can be used to identify patients at low risk for developing HCC.

Clinicians "urgently require a good indictor to stop nucleotide analogue therapy in HBeAg-negative patients. If an HbsAg level of less than 1000 IU/mL could be reliably used to define low-risk or inactive HBV carriers, we may adopt this cutoff level as the intermediate treatment goal," assuming that the results of this study are confirmed in future research, the authors wrote.

This study was supported by the Buddhist Tzu-Chi General Hospital Taipei Branch, the National Taiwan University Hospital, the Department of Health, and the National Science Council. Dr. Tseng’s associates reported ties to Abbott, Bayer, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, and Roche.

Telbivudine taken during the second or third trimester of pregnancy reduced the mother-to-infant transmission of hepatitis B to zero in an open-label trial of 88 women who had high viral loads and elevated alanine aminotransferase levels, Dr. Calvin Q. Pan and his colleagues reported in the May issue of Clinical Gastroenterology and Hepatology.

The authors described their study as the first to examine telbivudine therapy in such patients. They found that the vertical transmission rate was 0% with active treatment and 9% in a control group, despite appropriate immunoprophylaxis of the neonate, said Dr. Pan of the division of liver diseases at Mount Sinai Medical Center, New York, and his associates (Clin. Gastroenterol. Hepatol. 2012 Feb. 16 [doi:10.1016/j.cgh.2012.01.019]).

These results support the idea of using antiviral drugs during pregnancy in women who have chronic hepatitis B virus (HBV) infection to reduce rates of immunoprophylaxis failure in their infants, the investigators noted.

The prospective study involved women treated at a single tertiary-care hospital in Nanjing, China, during 2008-2009. The subjects comprised women at 12-30 weeks’ gestation who had high viral loads, high ALT levels, and were positive for both hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg).

The women were not randomly assigned to study groups but instead chose whether to enroll in the antiviral therapy group (53 subjects) or the control group that received only clinical observation (35 subjects). Those in the active treatment group were to receive 600 mg oral telbivudine daily until 28 weeks postpartum.

Mothers who intended to breastfeed were instructed to discontinue the drug before doing so.

The mean duration of exposure to telbivudine was 15 weeks before delivery and 23 weeks postpartum. In all, 13 of the 52 treated mothers (29%) decided to discontinue the antiviral therapy during the first month after delivery, and the rest continued to take it until the study ended at 28 weeks postpartum.

Mean serum HBV DNA levels declined markedly in the treated women but remained steady in the control group. In the intention-to-treat analysis, HBV DNA dropped to undetectable levels in 58% of the telbivudine group but 0% of the control group.

Similarly, ALT levels normalized in 77% of the telbivudine group at 1 month postpartum and in 92% by the end of the study. In comparison, ALT levels normalized in only 49% of the control group at 1 month postpartum and in 71% by the end of the study.

All the infants in the study received hepatitis B immunoglobulin with the HBV vaccine within 6 hours of birth and completed the remainder of the HBV immunizations according to the standard vaccine schedule.

At birth, all infants were HBeAg-positive. Two in the telbivudine group and eight in the control group were HBsAg-positive. And only three infants, all in the control group, had detectable serum levels of HBV DNA.

By week 28, all the infants in the telbivudine group were negative for HBeAg, HBsAg, and HBV DNA. In the control group, three infants remained positive for HBsAg, HBeAg, and HBV DNA, and another five remained positive for HBsAg only.

The primary end point of the study – the rate of mother-to-infant transmission – was 0% (0 of 52 infants) with active treatment and 9% (3 of 32 infants) with no treatment.

In the intention-to-treat analysis, HBV was transmitted to two infants in the telbivudine group (1.9%) and six in the control group (17%).

With regard to safety, there were no significant differences between the two study groups in gestational age at delivery, incidence of maternal peripartum hemorrhage, incidence of premature rupture of membranes, or rate of cesarean delivery. None of the mothers developed hepatitis flares.

The incidence and nature of minor adverse effects among the infants were similar between the two study groups, with no significant differences in birth weight, height, or Apgar scores. There were no congenital deformities and no major adverse effects. All the infants showed normal development through the completion of the study.

During follow-up there were three cases of pneumonia in the telbivudine group and one in the control group. It was not clear whether this difference may have been related to antiviral therapy, the authors said.

They noted that approximately 6% of Asian-American women are HBsAg-positive at perinatal screening, similar to the 7% rate of HBsAg positivity in China. There is no consensus as to the management of these patients because data on antiviral therapy are so limited.

This study lends support to the concept of using antiviral therapy in the second or third trimester in these women, to reduce the failure rate of immunoprophylaxis in their newborns, the researchers said.

Limitations included the relatively small study cohort treated at a single center. A multicenter trial with a larger sample size is warranted, they added.

The study was funded by the Jiangsu Province Department of Health. Dr. Pan reported ties to Gilead, Bristol Myers Squibb, Novartis, Idenix, Roche, Schering Plough, Onyx, Three Rivers, Salix, Genentech, Vertex, and Pharmasset.

Telbivudine taken during the second or third trimester of pregnancy reduced the mother-to-infant transmission of hepatitis B to zero in an open-label trial of 88 women who had high viral loads and elevated alanine aminotransferase levels, Dr. Calvin Q. Pan and his colleagues reported in the May issue of Clinical Gastroenterology and Hepatology.

The authors described their study as the first to examine telbivudine therapy in such patients. They found that the vertical transmission rate was 0% with active treatment and 9% in a control group, despite appropriate immunoprophylaxis of the neonate, said Dr. Pan of the division of liver diseases at Mount Sinai Medical Center, New York, and his associates (Clin. Gastroenterol. Hepatol. 2012 Feb. 16 [doi:10.1016/j.cgh.2012.01.019]).

These results support the idea of using antiviral drugs during pregnancy in women who have chronic hepatitis B virus (HBV) infection to reduce rates of immunoprophylaxis failure in their infants, the investigators noted.

The prospective study involved women treated at a single tertiary-care hospital in Nanjing, China, during 2008-2009. The subjects comprised women at 12-30 weeks’ gestation who had high viral loads, high ALT levels, and were positive for both hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg).

The women were not randomly assigned to study groups but instead chose whether to enroll in the antiviral therapy group (53 subjects) or the control group that received only clinical observation (35 subjects). Those in the active treatment group were to receive 600 mg oral telbivudine daily until 28 weeks postpartum.

Mothers who intended to breastfeed were instructed to discontinue the drug before doing so.

The mean duration of exposure to telbivudine was 15 weeks before delivery and 23 weeks postpartum. In all, 13 of the 52 treated mothers (29%) decided to discontinue the antiviral therapy during the first month after delivery, and the rest continued to take it until the study ended at 28 weeks postpartum.

Mean serum HBV DNA levels declined markedly in the treated women but remained steady in the control group. In the intention-to-treat analysis, HBV DNA dropped to undetectable levels in 58% of the telbivudine group but 0% of the control group.

Similarly, ALT levels normalized in 77% of the telbivudine group at 1 month postpartum and in 92% by the end of the study. In comparison, ALT levels normalized in only 49% of the control group at 1 month postpartum and in 71% by the end of the study.

All the infants in the study received hepatitis B immunoglobulin with the HBV vaccine within 6 hours of birth and completed the remainder of the HBV immunizations according to the standard vaccine schedule.

At birth, all infants were HBeAg-positive. Two in the telbivudine group and eight in the control group were HBsAg-positive. And only three infants, all in the control group, had detectable serum levels of HBV DNA.

By week 28, all the infants in the telbivudine group were negative for HBeAg, HBsAg, and HBV DNA. In the control group, three infants remained positive for HBsAg, HBeAg, and HBV DNA, and another five remained positive for HBsAg only.

The primary end point of the study – the rate of mother-to-infant transmission – was 0% (0 of 52 infants) with active treatment and 9% (3 of 32 infants) with no treatment.

In the intention-to-treat analysis, HBV was transmitted to two infants in the telbivudine group (1.9%) and six in the control group (17%).

With regard to safety, there were no significant differences between the two study groups in gestational age at delivery, incidence of maternal peripartum hemorrhage, incidence of premature rupture of membranes, or rate of cesarean delivery. None of the mothers developed hepatitis flares.

The incidence and nature of minor adverse effects among the infants were similar between the two study groups, with no significant differences in birth weight, height, or Apgar scores. There were no congenital deformities and no major adverse effects. All the infants showed normal development through the completion of the study.

During follow-up there were three cases of pneumonia in the telbivudine group and one in the control group. It was not clear whether this difference may have been related to antiviral therapy, the authors said.

They noted that approximately 6% of Asian-American women are HBsAg-positive at perinatal screening, similar to the 7% rate of HBsAg positivity in China. There is no consensus as to the management of these patients because data on antiviral therapy are so limited.

This study lends support to the concept of using antiviral therapy in the second or third trimester in these women, to reduce the failure rate of immunoprophylaxis in their newborns, the researchers said.

Limitations included the relatively small study cohort treated at a single center. A multicenter trial with a larger sample size is warranted, they added.

The study was funded by the Jiangsu Province Department of Health. Dr. Pan reported ties to Gilead, Bristol Myers Squibb, Novartis, Idenix, Roche, Schering Plough, Onyx, Three Rivers, Salix, Genentech, Vertex, and Pharmasset.

Telbivudine taken during the second or third trimester of pregnancy reduced the mother-to-infant transmission of hepatitis B to zero in an open-label trial of 88 women who had high viral loads and elevated alanine aminotransferase levels, Dr. Calvin Q. Pan and his colleagues reported in the May issue of Clinical Gastroenterology and Hepatology.

The authors described their study as the first to examine telbivudine therapy in such patients. They found that the vertical transmission rate was 0% with active treatment and 9% in a control group, despite appropriate immunoprophylaxis of the neonate, said Dr. Pan of the division of liver diseases at Mount Sinai Medical Center, New York, and his associates (Clin. Gastroenterol. Hepatol. 2012 Feb. 16 [doi:10.1016/j.cgh.2012.01.019]).

These results support the idea of using antiviral drugs during pregnancy in women who have chronic hepatitis B virus (HBV) infection to reduce rates of immunoprophylaxis failure in their infants, the investigators noted.

The prospective study involved women treated at a single tertiary-care hospital in Nanjing, China, during 2008-2009. The subjects comprised women at 12-30 weeks’ gestation who had high viral loads, high ALT levels, and were positive for both hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg).

The women were not randomly assigned to study groups but instead chose whether to enroll in the antiviral therapy group (53 subjects) or the control group that received only clinical observation (35 subjects). Those in the active treatment group were to receive 600 mg oral telbivudine daily until 28 weeks postpartum.

Mothers who intended to breastfeed were instructed to discontinue the drug before doing so.

The mean duration of exposure to telbivudine was 15 weeks before delivery and 23 weeks postpartum. In all, 13 of the 52 treated mothers (29%) decided to discontinue the antiviral therapy during the first month after delivery, and the rest continued to take it until the study ended at 28 weeks postpartum.

Mean serum HBV DNA levels declined markedly in the treated women but remained steady in the control group. In the intention-to-treat analysis, HBV DNA dropped to undetectable levels in 58% of the telbivudine group but 0% of the control group.

Similarly, ALT levels normalized in 77% of the telbivudine group at 1 month postpartum and in 92% by the end of the study. In comparison, ALT levels normalized in only 49% of the control group at 1 month postpartum and in 71% by the end of the study.

All the infants in the study received hepatitis B immunoglobulin with the HBV vaccine within 6 hours of birth and completed the remainder of the HBV immunizations according to the standard vaccine schedule.

At birth, all infants were HBeAg-positive. Two in the telbivudine group and eight in the control group were HBsAg-positive. And only three infants, all in the control group, had detectable serum levels of HBV DNA.

By week 28, all the infants in the telbivudine group were negative for HBeAg, HBsAg, and HBV DNA. In the control group, three infants remained positive for HBsAg, HBeAg, and HBV DNA, and another five remained positive for HBsAg only.

The primary end point of the study – the rate of mother-to-infant transmission – was 0% (0 of 52 infants) with active treatment and 9% (3 of 32 infants) with no treatment.

In the intention-to-treat analysis, HBV was transmitted to two infants in the telbivudine group (1.9%) and six in the control group (17%).

With regard to safety, there were no significant differences between the two study groups in gestational age at delivery, incidence of maternal peripartum hemorrhage, incidence of premature rupture of membranes, or rate of cesarean delivery. None of the mothers developed hepatitis flares.

The incidence and nature of minor adverse effects among the infants were similar between the two study groups, with no significant differences in birth weight, height, or Apgar scores. There were no congenital deformities and no major adverse effects. All the infants showed normal development through the completion of the study.

During follow-up there were three cases of pneumonia in the telbivudine group and one in the control group. It was not clear whether this difference may have been related to antiviral therapy, the authors said.

They noted that approximately 6% of Asian-American women are HBsAg-positive at perinatal screening, similar to the 7% rate of HBsAg positivity in China. There is no consensus as to the management of these patients because data on antiviral therapy are so limited.

This study lends support to the concept of using antiviral therapy in the second or third trimester in these women, to reduce the failure rate of immunoprophylaxis in their newborns, the researchers said.

Limitations included the relatively small study cohort treated at a single center. A multicenter trial with a larger sample size is warranted, they added.

The study was funded by the Jiangsu Province Department of Health. Dr. Pan reported ties to Gilead, Bristol Myers Squibb, Novartis, Idenix, Roche, Schering Plough, Onyx, Three Rivers, Salix, Genentech, Vertex, and Pharmasset.

Patients with moderately to severely active Crohn’s disease who took adalimumab as maintenance therapy for 1 year showed improved mucosal healing compared with those who took placebo, Dr. Paul Rutgeerts and his colleagues reported in the May issue of Gastroenterology.

"Historically, clinical response and remission have been the primary treatment goals for patients with Crohn’s disease. Recently, with the availability of more potent therapies, physicians are proposing that treatment goals focus on disease-modifying outcomes such as mucosal healing," said Dr. Rutgeerts, of the University Hospital of Gasthuisberg, Leuven (Belgium), and his associates (Gastroenterology 2012 Feb. 12 [doi:10.1053/j.gastro.2012.01.035]).

The EXTEND (Extend the Safety and Efficacy of Adalimumab Through Endoscopic Healing) trial involved 135 adults who had a long disease duration and had failed to improve on conventional therapy. The authors described it as "the first prospective, placebo-controlled, double-blind study designed with mucosal healing as the primary end point." All the study subjects consented to undergo up to four endoscopies during the trial.

The study also was unique in that patients were permitted to continue taking concomitant medications such as azathioprine, 6-mercaptopurine, methotrexate, aminosalicylates, antibiotics, prednisone, or budesonide. The protocol also allowed tapering of steroid therapy as patients improved, as well as resumption of steroid therapy if they subsequently worsened, and permitted patients in the placebo group who were unresponsive to switch to open-label "rescue" therapy with the active agent.

The study was sponsored by Abbott Laboratories, maker of adalimumab, and was conducted at 19 sites in Europe, the United States, and Canada.

All the study subjects received open-label induction therapy with subcutaneous adalimumab (160 mg at baseline and 80 mg at week 2) for 1 month. At that time their clinical response was assessed and they were randomly assigned to either continue adalimumab as maintenance therapy (40 mg every other week) or to receive placebo for the remainder of the year-long study.

After week 8, patients who had Crohn’s disease flares or did not respond to treatment could switch to open-label adalimumab, 40 mg every other week, for the remainder of the year. If they continued to worsen, the dose could be escalated to 40 mg every week.

The primary efficacy end point, complete mucosal healing on endoscopy at week 12, was achieved by 27% of patients who received continuous adalimumab, compared with only 13% of those who received placebo. This difference "narrowly missed statistical significance," Dr. Rutgeerts and his associates said.

However, at 1 year the difference in rates of mucosal healing did reach statistical significance, at 24% in the adalimumab group and 0% in the placebo group, they noted.

In addition, rates of remission as defined by scores on the Crohn’s Disease Endoscopic Index of Severity (CDEIS) were significantly higher with active treatment at both 12 weeks and 1 year. And significantly more patients on active treatment achieved a 75% response in CDEIS score at both 12 weeks and 1 year.

Thus, "the ability of adalimumab to maintain mucosal healing was confirmed by two endoscopic measures," the authors noted.

The rates of mucosal healing also were significantly higher at week 12 with active therapy in the subgroup of patients who strictly complied with the study protocol. The findings at week 12 were similar across several subgroups of patients. For example, the rate of mucosal healing was 25% in patients who were using steroids at baseline and who took maintenance adalimumab vs. 13% in steroid users on placebo.

And the rate of mucosal healing was 28% in patients who didn’t use steroids at baseline but took maintenance adalimumab vs. 14% in patients who didn’t use steroids and took placebo. Mucosal healing rates also were higher with adalimumab than placebo in the subgroup of patients who had high C-reactive protein levels at baseline and in the subgroup who were taking immunosuppressants at baseline.

At 1 year, 36% of patients taking maintenance adalimumab achieved a decrease in Crohn’s Disease Activity Index (CDAI) score of at least 100 points from baseline, compared with only 14% of those taking placebo. And 41% of patients taking maintenance adalimumab achieved a CDAI decrease of at least 70 points from baseline, compared with only 14% of those taking placebo.

The most common adverse events were infections, and they were more common in the adalimumab group (55%) than in the placebo group (34%). There were five serious infections during the study: one case each of anal abscess, perianal abscess, vulvar abscess, herpes zoster, and tonsillitis.

There were no deaths and no cases of cancer, demyelinating disorder, allergic reaction, lupus-like syndrome, or tuberculosis.

This study was sponsored by Abbott Laboratories, maker of adalimumab. Dr. Rutgeerts and his associates reported numerous ties to industry sources.

Patients with moderately to severely active Crohn’s disease who took adalimumab as maintenance therapy for 1 year showed improved mucosal healing compared with those who took placebo, Dr. Paul Rutgeerts and his colleagues reported in the May issue of Gastroenterology.

"Historically, clinical response and remission have been the primary treatment goals for patients with Crohn’s disease. Recently, with the availability of more potent therapies, physicians are proposing that treatment goals focus on disease-modifying outcomes such as mucosal healing," said Dr. Rutgeerts, of the University Hospital of Gasthuisberg, Leuven (Belgium), and his associates (Gastroenterology 2012 Feb. 12 [doi:10.1053/j.gastro.2012.01.035]).

The EXTEND (Extend the Safety and Efficacy of Adalimumab Through Endoscopic Healing) trial involved 135 adults who had a long disease duration and had failed to improve on conventional therapy. The authors described it as "the first prospective, placebo-controlled, double-blind study designed with mucosal healing as the primary end point." All the study subjects consented to undergo up to four endoscopies during the trial.

The study also was unique in that patients were permitted to continue taking concomitant medications such as azathioprine, 6-mercaptopurine, methotrexate, aminosalicylates, antibiotics, prednisone, or budesonide. The protocol also allowed tapering of steroid therapy as patients improved, as well as resumption of steroid therapy if they subsequently worsened, and permitted patients in the placebo group who were unresponsive to switch to open-label "rescue" therapy with the active agent.

The study was sponsored by Abbott Laboratories, maker of adalimumab, and was conducted at 19 sites in Europe, the United States, and Canada.

All the study subjects received open-label induction therapy with subcutaneous adalimumab (160 mg at baseline and 80 mg at week 2) for 1 month. At that time their clinical response was assessed and they were randomly assigned to either continue adalimumab as maintenance therapy (40 mg every other week) or to receive placebo for the remainder of the year-long study.

After week 8, patients who had Crohn’s disease flares or did not respond to treatment could switch to open-label adalimumab, 40 mg every other week, for the remainder of the year. If they continued to worsen, the dose could be escalated to 40 mg every week.

The primary efficacy end point, complete mucosal healing on endoscopy at week 12, was achieved by 27% of patients who received continuous adalimumab, compared with only 13% of those who received placebo. This difference "narrowly missed statistical significance," Dr. Rutgeerts and his associates said.

However, at 1 year the difference in rates of mucosal healing did reach statistical significance, at 24% in the adalimumab group and 0% in the placebo group, they noted.

In addition, rates of remission as defined by scores on the Crohn’s Disease Endoscopic Index of Severity (CDEIS) were significantly higher with active treatment at both 12 weeks and 1 year. And significantly more patients on active treatment achieved a 75% response in CDEIS score at both 12 weeks and 1 year.

Thus, "the ability of adalimumab to maintain mucosal healing was confirmed by two endoscopic measures," the authors noted.

The rates of mucosal healing also were significantly higher at week 12 with active therapy in the subgroup of patients who strictly complied with the study protocol. The findings at week 12 were similar across several subgroups of patients. For example, the rate of mucosal healing was 25% in patients who were using steroids at baseline and who took maintenance adalimumab vs. 13% in steroid users on placebo.

And the rate of mucosal healing was 28% in patients who didn’t use steroids at baseline but took maintenance adalimumab vs. 14% in patients who didn’t use steroids and took placebo. Mucosal healing rates also were higher with adalimumab than placebo in the subgroup of patients who had high C-reactive protein levels at baseline and in the subgroup who were taking immunosuppressants at baseline.

At 1 year, 36% of patients taking maintenance adalimumab achieved a decrease in Crohn’s Disease Activity Index (CDAI) score of at least 100 points from baseline, compared with only 14% of those taking placebo. And 41% of patients taking maintenance adalimumab achieved a CDAI decrease of at least 70 points from baseline, compared with only 14% of those taking placebo.

The most common adverse events were infections, and they were more common in the adalimumab group (55%) than in the placebo group (34%). There were five serious infections during the study: one case each of anal abscess, perianal abscess, vulvar abscess, herpes zoster, and tonsillitis.

There were no deaths and no cases of cancer, demyelinating disorder, allergic reaction, lupus-like syndrome, or tuberculosis.

This study was sponsored by Abbott Laboratories, maker of adalimumab. Dr. Rutgeerts and his associates reported numerous ties to industry sources.

Patients with moderately to severely active Crohn’s disease who took adalimumab as maintenance therapy for 1 year showed improved mucosal healing compared with those who took placebo, Dr. Paul Rutgeerts and his colleagues reported in the May issue of Gastroenterology.

"Historically, clinical response and remission have been the primary treatment goals for patients with Crohn’s disease. Recently, with the availability of more potent therapies, physicians are proposing that treatment goals focus on disease-modifying outcomes such as mucosal healing," said Dr. Rutgeerts, of the University Hospital of Gasthuisberg, Leuven (Belgium), and his associates (Gastroenterology 2012 Feb. 12 [doi:10.1053/j.gastro.2012.01.035]).

The EXTEND (Extend the Safety and Efficacy of Adalimumab Through Endoscopic Healing) trial involved 135 adults who had a long disease duration and had failed to improve on conventional therapy. The authors described it as "the first prospective, placebo-controlled, double-blind study designed with mucosal healing as the primary end point." All the study subjects consented to undergo up to four endoscopies during the trial.

The study also was unique in that patients were permitted to continue taking concomitant medications such as azathioprine, 6-mercaptopurine, methotrexate, aminosalicylates, antibiotics, prednisone, or budesonide. The protocol also allowed tapering of steroid therapy as patients improved, as well as resumption of steroid therapy if they subsequently worsened, and permitted patients in the placebo group who were unresponsive to switch to open-label "rescue" therapy with the active agent.

The study was sponsored by Abbott Laboratories, maker of adalimumab, and was conducted at 19 sites in Europe, the United States, and Canada.

All the study subjects received open-label induction therapy with subcutaneous adalimumab (160 mg at baseline and 80 mg at week 2) for 1 month. At that time their clinical response was assessed and they were randomly assigned to either continue adalimumab as maintenance therapy (40 mg every other week) or to receive placebo for the remainder of the year-long study.

After week 8, patients who had Crohn’s disease flares or did not respond to treatment could switch to open-label adalimumab, 40 mg every other week, for the remainder of the year. If they continued to worsen, the dose could be escalated to 40 mg every week.

The primary efficacy end point, complete mucosal healing on endoscopy at week 12, was achieved by 27% of patients who received continuous adalimumab, compared with only 13% of those who received placebo. This difference "narrowly missed statistical significance," Dr. Rutgeerts and his associates said.

However, at 1 year the difference in rates of mucosal healing did reach statistical significance, at 24% in the adalimumab group and 0% in the placebo group, they noted.

In addition, rates of remission as defined by scores on the Crohn’s Disease Endoscopic Index of Severity (CDEIS) were significantly higher with active treatment at both 12 weeks and 1 year. And significantly more patients on active treatment achieved a 75% response in CDEIS score at both 12 weeks and 1 year.

Thus, "the ability of adalimumab to maintain mucosal healing was confirmed by two endoscopic measures," the authors noted.

The rates of mucosal healing also were significantly higher at week 12 with active therapy in the subgroup of patients who strictly complied with the study protocol. The findings at week 12 were similar across several subgroups of patients. For example, the rate of mucosal healing was 25% in patients who were using steroids at baseline and who took maintenance adalimumab vs. 13% in steroid users on placebo.

And the rate of mucosal healing was 28% in patients who didn’t use steroids at baseline but took maintenance adalimumab vs. 14% in patients who didn’t use steroids and took placebo. Mucosal healing rates also were higher with adalimumab than placebo in the subgroup of patients who had high C-reactive protein levels at baseline and in the subgroup who were taking immunosuppressants at baseline.

At 1 year, 36% of patients taking maintenance adalimumab achieved a decrease in Crohn’s Disease Activity Index (CDAI) score of at least 100 points from baseline, compared with only 14% of those taking placebo. And 41% of patients taking maintenance adalimumab achieved a CDAI decrease of at least 70 points from baseline, compared with only 14% of those taking placebo.

The most common adverse events were infections, and they were more common in the adalimumab group (55%) than in the placebo group (34%). There were five serious infections during the study: one case each of anal abscess, perianal abscess, vulvar abscess, herpes zoster, and tonsillitis.

There were no deaths and no cases of cancer, demyelinating disorder, allergic reaction, lupus-like syndrome, or tuberculosis.

This study was sponsored by Abbott Laboratories, maker of adalimumab. Dr. Rutgeerts and his associates reported numerous ties to industry sources.

The marked increase in the diagnosis of intraductal papillary mucinous neoplasm over the last 2 decades is primarily due to a striking rise in the number of IPMNs identified incidentally, Dr. David A. Klibansky and his colleagues reported in the May issue of Clinical Gastroenterology and Hepatology.

The researchers compared the estimated number of all IPMNs against the number of malignant IPMNs reported to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database and found that the incidence of nonmalignant IPMN is 70 times higher than that of malignant IPMN.

"It would seem likely that we are recognizing an increasing number of pancreatic cystic lesions whose natural history may not be clinically important," the authors wrote. And these lesions are being found chiefly because of the widespread use of imaging, particularly high-resolution cross-sectional imaging.

Yet identifying these benign IPMNs still "drives referral to specialists, years of surveillance imaging, invasive testing, and possibly even surgical intervention because of heightened concern over malignant potential," said Dr. Klibansky of the gastroenterology and hepatology section at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and his associates (Clin. Gastro. Hepatol. 2012 [doi: 10.1016/j.cgh.2011.12.029]).

Since there is no database from which to derive the national incidence of IPMN, the researchers attempted to estimate that incidence by using data from a previously published, well-defined population study: the Rochester Epidemiology Project index, which "includes the records of virtually all medical providers that care for the residents of Olmsted County, Minnesota."

For this study, the clinical, radiographic, and pathologic data were reviewed for all 28 cases of IPMN treated during 1984-2007. The national incidence of the disease was then calculated by dividing the number of incident cases by the number of person-years at risk for the population, standardized to the age and sex distribution of the U.S. white population in the year 2000.

The investigators found that there was a 14-fold increase in the age- and sex-adjusted incidence of IPMN between 1985 and 2005, from 0.31 to 4.35 cases per 100,000 persons. A large increase in incidence has long been suspected and has been demonstrated in some previous studies, Dr. Klibansky and his associates wrote.

These figures were then compared with rates of IPMN-related cancer as estimated by SEER data during the same time period. The first malignant IPMN was reported to the SEER database in 2000.

"Using the most recent shared data point of 2005," the researchers found that the incidence of nonmalignant IPMN was 68.5 times higher than that of malignant IPMN.

Data from the early literature on IPMN, derived predominantly from retrospective analysis of surgical series, suggested that cancerous lesions accounted for 60%-70% of resected IPMN specimens from the main duct and 25% of those from branch ducts. "This literature, while critically important and representative of some of the seminal work in the evaluation of IPMN, is potentially biased with overrepresentation of malignant disease," given that these early patients were likely to have had symptomatic disease or larger than usual lesions, Dr. Klibansky and his colleagues noted.

Their study "is not meant to undermine the importance of identifying and treating IPMN that are high risk to harbor or develop malignancy," the investigators stressed.

It does, however, highlight the need for ways to differentiate IPMN that require intervention from those that require only surveillance and those that are so low risk that they require no further follow-up.

Most incidentally identified IPMNs do not meet the criteria for surgical resection, and current guidelines recommend only frequent surveillance using high-resolution imaging. The findings of this and other studies suggest that malignant transformation of such lesions is low and that even this recommended surveillance is unnecessarily aggressive and possibly unwarranted.

But many patients as well as clinicians pursue further, invasive evaluation and even surgical removal because of concern over the malignant potential of even small, asymptomatic pancreatic cysts, Dr. Klibansky and his associates said.

Physicians can reassure patients that the 5-year survival for even invasive IPMN "is significantly better than that of traditional ductal adenocarcinoma," they suggested. Moreover, "in a patient population that is older and likely to harbor significant medical comorbidities, a careful risk-to-benefit analysis needs to be performed on a case-by-case basis, taking into consideration the likely impact IPMN will have on a given patient’s life versus morbidity and costs related to intervention or lifelong surveillance," the researchers said.

This study was funded in part by the National Institutes of Health. No financial conflicts were reported.

The marked increase in the diagnosis of intraductal papillary mucinous neoplasm over the last 2 decades is primarily due to a striking rise in the number of IPMNs identified incidentally, Dr. David A. Klibansky and his colleagues reported in the May issue of Clinical Gastroenterology and Hepatology.

The researchers compared the estimated number of all IPMNs against the number of malignant IPMNs reported to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database and found that the incidence of nonmalignant IPMN is 70 times higher than that of malignant IPMN.

"It would seem likely that we are recognizing an increasing number of pancreatic cystic lesions whose natural history may not be clinically important," the authors wrote. And these lesions are being found chiefly because of the widespread use of imaging, particularly high-resolution cross-sectional imaging.

Yet identifying these benign IPMNs still "drives referral to specialists, years of surveillance imaging, invasive testing, and possibly even surgical intervention because of heightened concern over malignant potential," said Dr. Klibansky of the gastroenterology and hepatology section at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and his associates (Clin. Gastro. Hepatol. 2012 [doi: 10.1016/j.cgh.2011.12.029]).

Since there is no database from which to derive the national incidence of IPMN, the researchers attempted to estimate that incidence by using data from a previously published, well-defined population study: the Rochester Epidemiology Project index, which "includes the records of virtually all medical providers that care for the residents of Olmsted County, Minnesota."

For this study, the clinical, radiographic, and pathologic data were reviewed for all 28 cases of IPMN treated during 1984-2007. The national incidence of the disease was then calculated by dividing the number of incident cases by the number of person-years at risk for the population, standardized to the age and sex distribution of the U.S. white population in the year 2000.

The investigators found that there was a 14-fold increase in the age- and sex-adjusted incidence of IPMN between 1985 and 2005, from 0.31 to 4.35 cases per 100,000 persons. A large increase in incidence has long been suspected and has been demonstrated in some previous studies, Dr. Klibansky and his associates wrote.

These figures were then compared with rates of IPMN-related cancer as estimated by SEER data during the same time period. The first malignant IPMN was reported to the SEER database in 2000.

"Using the most recent shared data point of 2005," the researchers found that the incidence of nonmalignant IPMN was 68.5 times higher than that of malignant IPMN.

Data from the early literature on IPMN, derived predominantly from retrospective analysis of surgical series, suggested that cancerous lesions accounted for 60%-70% of resected IPMN specimens from the main duct and 25% of those from branch ducts. "This literature, while critically important and representative of some of the seminal work in the evaluation of IPMN, is potentially biased with overrepresentation of malignant disease," given that these early patients were likely to have had symptomatic disease or larger than usual lesions, Dr. Klibansky and his colleagues noted.

Their study "is not meant to undermine the importance of identifying and treating IPMN that are high risk to harbor or develop malignancy," the investigators stressed.

It does, however, highlight the need for ways to differentiate IPMN that require intervention from those that require only surveillance and those that are so low risk that they require no further follow-up.

Most incidentally identified IPMNs do not meet the criteria for surgical resection, and current guidelines recommend only frequent surveillance using high-resolution imaging. The findings of this and other studies suggest that malignant transformation of such lesions is low and that even this recommended surveillance is unnecessarily aggressive and possibly unwarranted.

But many patients as well as clinicians pursue further, invasive evaluation and even surgical removal because of concern over the malignant potential of even small, asymptomatic pancreatic cysts, Dr. Klibansky and his associates said.

Physicians can reassure patients that the 5-year survival for even invasive IPMN "is significantly better than that of traditional ductal adenocarcinoma," they suggested. Moreover, "in a patient population that is older and likely to harbor significant medical comorbidities, a careful risk-to-benefit analysis needs to be performed on a case-by-case basis, taking into consideration the likely impact IPMN will have on a given patient’s life versus morbidity and costs related to intervention or lifelong surveillance," the researchers said.

This study was funded in part by the National Institutes of Health. No financial conflicts were reported.

The marked increase in the diagnosis of intraductal papillary mucinous neoplasm over the last 2 decades is primarily due to a striking rise in the number of IPMNs identified incidentally, Dr. David A. Klibansky and his colleagues reported in the May issue of Clinical Gastroenterology and Hepatology.

The researchers compared the estimated number of all IPMNs against the number of malignant IPMNs reported to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database and found that the incidence of nonmalignant IPMN is 70 times higher than that of malignant IPMN.

"It would seem likely that we are recognizing an increasing number of pancreatic cystic lesions whose natural history may not be clinically important," the authors wrote. And these lesions are being found chiefly because of the widespread use of imaging, particularly high-resolution cross-sectional imaging.

Yet identifying these benign IPMNs still "drives referral to specialists, years of surveillance imaging, invasive testing, and possibly even surgical intervention because of heightened concern over malignant potential," said Dr. Klibansky of the gastroenterology and hepatology section at Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and his associates (Clin. Gastro. Hepatol. 2012 [doi: 10.1016/j.cgh.2011.12.029]).

Since there is no database from which to derive the national incidence of IPMN, the researchers attempted to estimate that incidence by using data from a previously published, well-defined population study: the Rochester Epidemiology Project index, which "includes the records of virtually all medical providers that care for the residents of Olmsted County, Minnesota."

For this study, the clinical, radiographic, and pathologic data were reviewed for all 28 cases of IPMN treated during 1984-2007. The national incidence of the disease was then calculated by dividing the number of incident cases by the number of person-years at risk for the population, standardized to the age and sex distribution of the U.S. white population in the year 2000.

The investigators found that there was a 14-fold increase in the age- and sex-adjusted incidence of IPMN between 1985 and 2005, from 0.31 to 4.35 cases per 100,000 persons. A large increase in incidence has long been suspected and has been demonstrated in some previous studies, Dr. Klibansky and his associates wrote.

These figures were then compared with rates of IPMN-related cancer as estimated by SEER data during the same time period. The first malignant IPMN was reported to the SEER database in 2000.

"Using the most recent shared data point of 2005," the researchers found that the incidence of nonmalignant IPMN was 68.5 times higher than that of malignant IPMN.

Data from the early literature on IPMN, derived predominantly from retrospective analysis of surgical series, suggested that cancerous lesions accounted for 60%-70% of resected IPMN specimens from the main duct and 25% of those from branch ducts. "This literature, while critically important and representative of some of the seminal work in the evaluation of IPMN, is potentially biased with overrepresentation of malignant disease," given that these early patients were likely to have had symptomatic disease or larger than usual lesions, Dr. Klibansky and his colleagues noted.

Their study "is not meant to undermine the importance of identifying and treating IPMN that are high risk to harbor or develop malignancy," the investigators stressed.

It does, however, highlight the need for ways to differentiate IPMN that require intervention from those that require only surveillance and those that are so low risk that they require no further follow-up.

Most incidentally identified IPMNs do not meet the criteria for surgical resection, and current guidelines recommend only frequent surveillance using high-resolution imaging. The findings of this and other studies suggest that malignant transformation of such lesions is low and that even this recommended surveillance is unnecessarily aggressive and possibly unwarranted.

But many patients as well as clinicians pursue further, invasive evaluation and even surgical removal because of concern over the malignant potential of even small, asymptomatic pancreatic cysts, Dr. Klibansky and his associates said.

Physicians can reassure patients that the 5-year survival for even invasive IPMN "is significantly better than that of traditional ductal adenocarcinoma," they suggested. Moreover, "in a patient population that is older and likely to harbor significant medical comorbidities, a careful risk-to-benefit analysis needs to be performed on a case-by-case basis, taking into consideration the likely impact IPMN will have on a given patient’s life versus morbidity and costs related to intervention or lifelong surveillance," the researchers said.

This study was funded in part by the National Institutes of Health. No financial conflicts were reported.

Both major and minor abnormalities on electrocardiogram signaled an increased risk of coronary heart disease within 8 years among elderly people in the general population, according to a report in the April 11 issue of JAMA.

Adding ECG abnormalities to traditional cardiovascular risk factors in a risk prediction model modestly but significantly improved the prediction of coronary heart disease events, said Dr. Reto Auer of the department of epidemiology and biostatistics, University of California, San Francisco, and associates.

To date, few studies have examined whether ECG abnormalities could improve risk prediction in older adults, and none have adequately adjusted for the presence of traditional cardiovascular risk factors. Predicting CHD with traditional risk factors is less accurate in the elderly than in other patient populations, the investigators noted.

Dr. Auer and colleagues examined the issue using data from the Health, Aging, and Body Composition (Health ABC) Study, a population-based cohort study of community-dwelling men and women who were aged 70-79 years at baseline in 1997-1998. For their secondary analysis of data from this study, the investigators assessed a random sample of 2,192 subjects living near Pittsburgh or Memphis, Tenn., who had no evidence of cardiovascular disease and who underwent standard ECG at baseline and again 4 years later.

The mean age of the study subjects was 73.5 years. Just over half were women, and 41% were black.

Major ECG abnormalities were defined as Q-QS wave abnormalities, left ventricular hypertrophy, Wolff-Parkinson-White syndrome, complete bundle branch block or intraventricular block, atrial fibrillation, atrial flutter, or major ST-T changes. Minor ECG abnormalities were defined as minor ST-T changes.

A total of 506 subjects (23%) showed major and 276 (13%) showed minor ECG abnormalities at baseline, for an overall incidence of 36%.

During a median follow-up of 8 years, 351 study subjects had CHD events, including 96 CHD deaths, 101 acute myocardial infarctions, and 154 hospitalizations for angina or coronary revascularization. There also were 506 deaths from non-CHD causes.

The rate of CHD events was 17.2 per 1,000 person-years among subjects with no ECG abnormalities. This was significantly lower than the rate among subjects with minor ECG abnormalities (29.3 per 1,000 person-years) and the rate among those with major ECG abnormalities (31.6 per 1,000 person-years), said Dr. Auer, who is also of the University of Lausanne (Switzerland), and associates.

After the data were adjusted to account for risk factors such as subject age, sex, total and HDL cholesterol levels, blood pressure, smoking status, and diabetes status, the hazard ratio for CHD events for subjects with minor ECG abnormalities was 1.35 and the hazard ratio for CHD events for subjects with major ECG abnormalities was 1.51, compared with subjects who had no ECG abnormalities at baseline, the researchers said (JAMA 2012;307:1497-1505).

The findings were similar when the data were analyzed by race. In both black and white participants, major and minor ECG abnormalities at baseline were associated with CHD events during follow-up.

Adding ECG data to a prediction model for the subgroup of subjects at intermediate cardiovascular risk resulted in reclassifying 8% of them as high-risk and 6% of them as low-risk.

A total of 1,670 study participants underwent a second ECG at 4 years; 416 of them had a persistent ECG abnormality and 208 had a new ECG abnormality. During a median follow-up of 6.4 years, 185 of these subjects had CHD events, including 57 who died from CHD.

Both new and persistent ECG abnormalities at 4 years were associated with an increased risk of CHD events. The absolute risk was 33.2 per 1,000 person-years in those with new abnormalities and 27.8 per 1,000 person-years in those with persistent ECG abnormalities.

The findings indicate that ECG screening may be useful in the elderly population – especially in view of the fact that 36% of the study population was found to have ECG abnormalities at baseline, a rate much higher than that in younger adults. ECG screening is already known to be safe, low cost, and widely available, Dr. Auer and associates said.

However, the benefit of such screening was small in this study, and these results must be validated in other cohorts as well as in prospective clinical trials, they added.

This study was supported by the National Institute on Aging, the National Institutes of Health, the National Institute of Nursing Research, the Swiss National Science Foundation, and the Swiss Heart Foundation. Dr. Auer’s associates reported ties to Amgen, Bayer, Boston Scientific, Cardiomems, Corthera, GE Healthcare, Medtronic, Novartis, Ono Pharmaceutical, Takeda, Trevena, and World Heart.

Both major and minor abnormalities on electrocardiogram signaled an increased risk of coronary heart disease within 8 years among elderly people in the general population, according to a report in the April 11 issue of JAMA.

Adding ECG abnormalities to traditional cardiovascular risk factors in a risk prediction model modestly but significantly improved the prediction of coronary heart disease events, said Dr. Reto Auer of the department of epidemiology and biostatistics, University of California, San Francisco, and associates.

To date, few studies have examined whether ECG abnormalities could improve risk prediction in older adults, and none have adequately adjusted for the presence of traditional cardiovascular risk factors. Predicting CHD with traditional risk factors is less accurate in the elderly than in other patient populations, the investigators noted.

Dr. Auer and colleagues examined the issue using data from the Health, Aging, and Body Composition (Health ABC) Study, a population-based cohort study of community-dwelling men and women who were aged 70-79 years at baseline in 1997-1998. For their secondary analysis of data from this study, the investigators assessed a random sample of 2,192 subjects living near Pittsburgh or Memphis, Tenn., who had no evidence of cardiovascular disease and who underwent standard ECG at baseline and again 4 years later.

The mean age of the study subjects was 73.5 years. Just over half were women, and 41% were black.

Major ECG abnormalities were defined as Q-QS wave abnormalities, left ventricular hypertrophy, Wolff-Parkinson-White syndrome, complete bundle branch block or intraventricular block, atrial fibrillation, atrial flutter, or major ST-T changes. Minor ECG abnormalities were defined as minor ST-T changes.

A total of 506 subjects (23%) showed major and 276 (13%) showed minor ECG abnormalities at baseline, for an overall incidence of 36%.

During a median follow-up of 8 years, 351 study subjects had CHD events, including 96 CHD deaths, 101 acute myocardial infarctions, and 154 hospitalizations for angina or coronary revascularization. There also were 506 deaths from non-CHD causes.

The rate of CHD events was 17.2 per 1,000 person-years among subjects with no ECG abnormalities. This was significantly lower than the rate among subjects with minor ECG abnormalities (29.3 per 1,000 person-years) and the rate among those with major ECG abnormalities (31.6 per 1,000 person-years), said Dr. Auer, who is also of the University of Lausanne (Switzerland), and associates.

After the data were adjusted to account for risk factors such as subject age, sex, total and HDL cholesterol levels, blood pressure, smoking status, and diabetes status, the hazard ratio for CHD events for subjects with minor ECG abnormalities was 1.35 and the hazard ratio for CHD events for subjects with major ECG abnormalities was 1.51, compared with subjects who had no ECG abnormalities at baseline, the researchers said (JAMA 2012;307:1497-1505).

The findings were similar when the data were analyzed by race. In both black and white participants, major and minor ECG abnormalities at baseline were associated with CHD events during follow-up.

Adding ECG data to a prediction model for the subgroup of subjects at intermediate cardiovascular risk resulted in reclassifying 8% of them as high-risk and 6% of them as low-risk.

A total of 1,670 study participants underwent a second ECG at 4 years; 416 of them had a persistent ECG abnormality and 208 had a new ECG abnormality. During a median follow-up of 6.4 years, 185 of these subjects had CHD events, including 57 who died from CHD.

Both new and persistent ECG abnormalities at 4 years were associated with an increased risk of CHD events. The absolute risk was 33.2 per 1,000 person-years in those with new abnormalities and 27.8 per 1,000 person-years in those with persistent ECG abnormalities.

The findings indicate that ECG screening may be useful in the elderly population – especially in view of the fact that 36% of the study population was found to have ECG abnormalities at baseline, a rate much higher than that in younger adults. ECG screening is already known to be safe, low cost, and widely available, Dr. Auer and associates said.

However, the benefit of such screening was small in this study, and these results must be validated in other cohorts as well as in prospective clinical trials, they added.

This study was supported by the National Institute on Aging, the National Institutes of Health, the National Institute of Nursing Research, the Swiss National Science Foundation, and the Swiss Heart Foundation. Dr. Auer’s associates reported ties to Amgen, Bayer, Boston Scientific, Cardiomems, Corthera, GE Healthcare, Medtronic, Novartis, Ono Pharmaceutical, Takeda, Trevena, and World Heart.

Both major and minor abnormalities on electrocardiogram signaled an increased risk of coronary heart disease within 8 years among elderly people in the general population, according to a report in the April 11 issue of JAMA.

Adding ECG abnormalities to traditional cardiovascular risk factors in a risk prediction model modestly but significantly improved the prediction of coronary heart disease events, said Dr. Reto Auer of the department of epidemiology and biostatistics, University of California, San Francisco, and associates.

To date, few studies have examined whether ECG abnormalities could improve risk prediction in older adults, and none have adequately adjusted for the presence of traditional cardiovascular risk factors. Predicting CHD with traditional risk factors is less accurate in the elderly than in other patient populations, the investigators noted.

Dr. Auer and colleagues examined the issue using data from the Health, Aging, and Body Composition (Health ABC) Study, a population-based cohort study of community-dwelling men and women who were aged 70-79 years at baseline in 1997-1998. For their secondary analysis of data from this study, the investigators assessed a random sample of 2,192 subjects living near Pittsburgh or Memphis, Tenn., who had no evidence of cardiovascular disease and who underwent standard ECG at baseline and again 4 years later.

The mean age of the study subjects was 73.5 years. Just over half were women, and 41% were black.

Major ECG abnormalities were defined as Q-QS wave abnormalities, left ventricular hypertrophy, Wolff-Parkinson-White syndrome, complete bundle branch block or intraventricular block, atrial fibrillation, atrial flutter, or major ST-T changes. Minor ECG abnormalities were defined as minor ST-T changes.

A total of 506 subjects (23%) showed major and 276 (13%) showed minor ECG abnormalities at baseline, for an overall incidence of 36%.

During a median follow-up of 8 years, 351 study subjects had CHD events, including 96 CHD deaths, 101 acute myocardial infarctions, and 154 hospitalizations for angina or coronary revascularization. There also were 506 deaths from non-CHD causes.

The rate of CHD events was 17.2 per 1,000 person-years among subjects with no ECG abnormalities. This was significantly lower than the rate among subjects with minor ECG abnormalities (29.3 per 1,000 person-years) and the rate among those with major ECG abnormalities (31.6 per 1,000 person-years), said Dr. Auer, who is also of the University of Lausanne (Switzerland), and associates.

After the data were adjusted to account for risk factors such as subject age, sex, total and HDL cholesterol levels, blood pressure, smoking status, and diabetes status, the hazard ratio for CHD events for subjects with minor ECG abnormalities was 1.35 and the hazard ratio for CHD events for subjects with major ECG abnormalities was 1.51, compared with subjects who had no ECG abnormalities at baseline, the researchers said (JAMA 2012;307:1497-1505).

The findings were similar when the data were analyzed by race. In both black and white participants, major and minor ECG abnormalities at baseline were associated with CHD events during follow-up.

Adding ECG data to a prediction model for the subgroup of subjects at intermediate cardiovascular risk resulted in reclassifying 8% of them as high-risk and 6% of them as low-risk.

A total of 1,670 study participants underwent a second ECG at 4 years; 416 of them had a persistent ECG abnormality and 208 had a new ECG abnormality. During a median follow-up of 6.4 years, 185 of these subjects had CHD events, including 57 who died from CHD.

Both new and persistent ECG abnormalities at 4 years were associated with an increased risk of CHD events. The absolute risk was 33.2 per 1,000 person-years in those with new abnormalities and 27.8 per 1,000 person-years in those with persistent ECG abnormalities.

The findings indicate that ECG screening may be useful in the elderly population – especially in view of the fact that 36% of the study population was found to have ECG abnormalities at baseline, a rate much higher than that in younger adults. ECG screening is already known to be safe, low cost, and widely available, Dr. Auer and associates said.

However, the benefit of such screening was small in this study, and these results must be validated in other cohorts as well as in prospective clinical trials, they added.

This study was supported by the National Institute on Aging, the National Institutes of Health, the National Institute of Nursing Research, the Swiss National Science Foundation, and the Swiss Heart Foundation. Dr. Auer’s associates reported ties to Amgen, Bayer, Boston Scientific, Cardiomems, Corthera, GE Healthcare, Medtronic, Novartis, Ono Pharmaceutical, Takeda, Trevena, and World Heart.