Mary Ann Moon

Kidney measures such as low estimated glomerular filtration rate and high albuminuria are strongly associated with mortality and end-stage renal disease across all age groups – even in the elderly, according to a collaborative meta-analysis reported online Oct. 30 in JAMA and presented simultaneously at Kidney Week.

The risk for chronic kidney disease, which in turn is closely allied with the risk for cardiovascular disease and all-cause mortality, typically is gauged by assessing estimated GFR (eGFR) and albuminuria levels. But there has been substantial controversy regarding the accuracy of these measures for predicting mortality and CKD risk in the elderly, because kidney function appears to decline markedly even in apparently healthy people as they age, said Dr. Stein I. Hallan and his associates in the Chronic Kidney Disease Prognosis Consortium.

Some experts even hold that reduced GFR might simply be part of the natural aging process and that the kidneys undergo an inevitable senescence, rendering "normal" markers of kidney function unusable in the elderly, said Dr. Hallan, of St. Olav University Hospital and the Norwegian University of Science and Technology, both in Trondheim, and his colleagues.

To examine whether aging modifies the usefulness of estimated GFR and albuminuria in assessing the risks for mortality and CKD, Dr. Hallan and his associates analyzed data from 46 different cohorts worldwide that included the entire adult age range (18-108 years). The Chronic Kidney Disease Prognosis Consortium includes data on 20 North American, 12 European, 10 Asian, 1 Australian, and 3 multinational cohorts comprising more than 2 million study subjects followed for a mean of 6 years.

Among the study cohorts, 26 involved people from the general population, 8 involved patients at high risk for vascular disease, and the remaining 12 involved patients with CKD.

During follow-up there were 112,325 deaths in the general population and the high-risk cohorts, as well as 9,037 deaths in the CKD cohorts. There were 2,766 end-stage renal disease (ESRD) events in the general population and high-risk cohorts, as well as 5,962 ESRD events in the CKD cohorts.

Both mortality risk and the risk of ESRD events strongly increased with decreasing GFR across all age groups, even though the study populations had widely divergent demographic and clinical characteristics, the investigators said. These risks declined with increasing age (JAMA 2012 Oct. 30 [doi: 10.1001/jama.2012.16817]).

This correlation remained robust when the data were adjusted to account for patient sex, race, history of cardiovascular disease, blood pressure, serum cholesterol levels, body mass index, smoking status, and diabetes status. For example, the adjusted hazard ratio for all-cause mortality in subjects with an eGFR of 45 (compared with 80) mL/min per 1.73 m² was 3.50 in those aged 18-54 years, and declined with age to 1.35 in those aged at least 75 years.

The findings were similar for albuminuria levels, with high levels predicting mortality and ESRD events across all age groups.

"Although some variation in management of CKD should be considered by age, based on cost and benefits, with respect to risk of mortality and ESRD, our data support a common definition and staging of CKD based on eGFR and albuminuria for all age groups," they said.

These results contradict the concern "that CKD guidelines should be used with caution in older individuals and that low eGFR reflects only natural aging." They also support recommendations that CKD measures be added to mortality risk equations.

In addition, "the strong increase in mortality along with kidney measures at older ages suggests that older adults should not be left out from management strategies of CKD. Previous data show that low eGFR in the very old is associated with classical CKD complications like anemia, acidosis, hyperparathyroidism, and hyperphosphatemia," the researchers said.

This study was supported by a variety of government agencies, medical research councils, and industry sponsors. The 16 authors reported numerous ties to industry sources.

Kidney measures such as low estimated glomerular filtration rate and high albuminuria are strongly associated with mortality and end-stage renal disease across all age groups – even in the elderly, according to a collaborative meta-analysis reported online Oct. 30 in JAMA and presented simultaneously at Kidney Week.

The risk for chronic kidney disease, which in turn is closely allied with the risk for cardiovascular disease and all-cause mortality, typically is gauged by assessing estimated GFR (eGFR) and albuminuria levels. But there has been substantial controversy regarding the accuracy of these measures for predicting mortality and CKD risk in the elderly, because kidney function appears to decline markedly even in apparently healthy people as they age, said Dr. Stein I. Hallan and his associates in the Chronic Kidney Disease Prognosis Consortium.

Some experts even hold that reduced GFR might simply be part of the natural aging process and that the kidneys undergo an inevitable senescence, rendering "normal" markers of kidney function unusable in the elderly, said Dr. Hallan, of St. Olav University Hospital and the Norwegian University of Science and Technology, both in Trondheim, and his colleagues.

To examine whether aging modifies the usefulness of estimated GFR and albuminuria in assessing the risks for mortality and CKD, Dr. Hallan and his associates analyzed data from 46 different cohorts worldwide that included the entire adult age range (18-108 years). The Chronic Kidney Disease Prognosis Consortium includes data on 20 North American, 12 European, 10 Asian, 1 Australian, and 3 multinational cohorts comprising more than 2 million study subjects followed for a mean of 6 years.

Among the study cohorts, 26 involved people from the general population, 8 involved patients at high risk for vascular disease, and the remaining 12 involved patients with CKD.

During follow-up there were 112,325 deaths in the general population and the high-risk cohorts, as well as 9,037 deaths in the CKD cohorts. There were 2,766 end-stage renal disease (ESRD) events in the general population and high-risk cohorts, as well as 5,962 ESRD events in the CKD cohorts.

Both mortality risk and the risk of ESRD events strongly increased with decreasing GFR across all age groups, even though the study populations had widely divergent demographic and clinical characteristics, the investigators said. These risks declined with increasing age (JAMA 2012 Oct. 30 [doi: 10.1001/jama.2012.16817]).

This correlation remained robust when the data were adjusted to account for patient sex, race, history of cardiovascular disease, blood pressure, serum cholesterol levels, body mass index, smoking status, and diabetes status. For example, the adjusted hazard ratio for all-cause mortality in subjects with an eGFR of 45 (compared with 80) mL/min per 1.73 m² was 3.50 in those aged 18-54 years, and declined with age to 1.35 in those aged at least 75 years.

The findings were similar for albuminuria levels, with high levels predicting mortality and ESRD events across all age groups.

"Although some variation in management of CKD should be considered by age, based on cost and benefits, with respect to risk of mortality and ESRD, our data support a common definition and staging of CKD based on eGFR and albuminuria for all age groups," they said.

These results contradict the concern "that CKD guidelines should be used with caution in older individuals and that low eGFR reflects only natural aging." They also support recommendations that CKD measures be added to mortality risk equations.

In addition, "the strong increase in mortality along with kidney measures at older ages suggests that older adults should not be left out from management strategies of CKD. Previous data show that low eGFR in the very old is associated with classical CKD complications like anemia, acidosis, hyperparathyroidism, and hyperphosphatemia," the researchers said.

This study was supported by a variety of government agencies, medical research councils, and industry sponsors. The 16 authors reported numerous ties to industry sources.

Kidney measures such as low estimated glomerular filtration rate and high albuminuria are strongly associated with mortality and end-stage renal disease across all age groups – even in the elderly, according to a collaborative meta-analysis reported online Oct. 30 in JAMA and presented simultaneously at Kidney Week.

The risk for chronic kidney disease, which in turn is closely allied with the risk for cardiovascular disease and all-cause mortality, typically is gauged by assessing estimated GFR (eGFR) and albuminuria levels. But there has been substantial controversy regarding the accuracy of these measures for predicting mortality and CKD risk in the elderly, because kidney function appears to decline markedly even in apparently healthy people as they age, said Dr. Stein I. Hallan and his associates in the Chronic Kidney Disease Prognosis Consortium.

Some experts even hold that reduced GFR might simply be part of the natural aging process and that the kidneys undergo an inevitable senescence, rendering "normal" markers of kidney function unusable in the elderly, said Dr. Hallan, of St. Olav University Hospital and the Norwegian University of Science and Technology, both in Trondheim, and his colleagues.

To examine whether aging modifies the usefulness of estimated GFR and albuminuria in assessing the risks for mortality and CKD, Dr. Hallan and his associates analyzed data from 46 different cohorts worldwide that included the entire adult age range (18-108 years). The Chronic Kidney Disease Prognosis Consortium includes data on 20 North American, 12 European, 10 Asian, 1 Australian, and 3 multinational cohorts comprising more than 2 million study subjects followed for a mean of 6 years.

Among the study cohorts, 26 involved people from the general population, 8 involved patients at high risk for vascular disease, and the remaining 12 involved patients with CKD.

During follow-up there were 112,325 deaths in the general population and the high-risk cohorts, as well as 9,037 deaths in the CKD cohorts. There were 2,766 end-stage renal disease (ESRD) events in the general population and high-risk cohorts, as well as 5,962 ESRD events in the CKD cohorts.

Both mortality risk and the risk of ESRD events strongly increased with decreasing GFR across all age groups, even though the study populations had widely divergent demographic and clinical characteristics, the investigators said. These risks declined with increasing age (JAMA 2012 Oct. 30 [doi: 10.1001/jama.2012.16817]).

This correlation remained robust when the data were adjusted to account for patient sex, race, history of cardiovascular disease, blood pressure, serum cholesterol levels, body mass index, smoking status, and diabetes status. For example, the adjusted hazard ratio for all-cause mortality in subjects with an eGFR of 45 (compared with 80) mL/min per 1.73 m² was 3.50 in those aged 18-54 years, and declined with age to 1.35 in those aged at least 75 years.

The findings were similar for albuminuria levels, with high levels predicting mortality and ESRD events across all age groups.

"Although some variation in management of CKD should be considered by age, based on cost and benefits, with respect to risk of mortality and ESRD, our data support a common definition and staging of CKD based on eGFR and albuminuria for all age groups," they said.

These results contradict the concern "that CKD guidelines should be used with caution in older individuals and that low eGFR reflects only natural aging." They also support recommendations that CKD measures be added to mortality risk equations.

In addition, "the strong increase in mortality along with kidney measures at older ages suggests that older adults should not be left out from management strategies of CKD. Previous data show that low eGFR in the very old is associated with classical CKD complications like anemia, acidosis, hyperparathyroidism, and hyperphosphatemia," the researchers said.

This study was supported by a variety of government agencies, medical research councils, and industry sponsors. The 16 authors reported numerous ties to industry sources.

Symptoms of psychosis were associated with greatly increased risk for suicidal behavior in the general adolescent population as well as in adolescents who have nonpsychotic disorders, such as depression, attention-deficit/hyperactivity disorder, anxiety disorders, or obsessive compulsive disorder, according to two separate epidemiologic studies reported online Oct. 29 in the Archives of General Psychiatry.

Among adolescents in the general population, as well as the subgroup of adolescents who had nonpsychotic DSM-III diagnoses, those who reported suicidal ideation, suicide planning, or suicidal acts were 10 times more likely than those who did not to affirm on direct questioning that they had experienced psychotic symptoms – mainly auditory hallucinations, said Ian Kelleher, Ph.D., of the department of psychiatry, Royal College of Surgeons in Ireland, Dublin, and his associates.

"The immediate clinical relevance of these findings is that all patients presenting at risk for suicidal behavior should receive a thorough assessment of psychotic symptoms and not just a screening to rule out psychotic disorder," they noted.

Both primary care physicians and psychiatric clinicians must recognize that psychotic symptoms in a nonpsychotic patient signify a high suicide risk. "Research has shown that the largest increase in suicide risk in the general population occurs after there has already been contact with mental health services and that approximately half of patients who complete suicide [had] contact with primary care providers in the month preceding their death[s]," the investigators added.

Hallucinations and delusions, the classic symptoms of psychosis, are far more prevalent in the general population than are diagnosable psychotic disorders. They are "especially common in young people, with a meta-analysis of general population studies demonstrating a median prevalence of 17% in children aged 9-12 years and 7.5% in adolescents aged 13-17 years," the researchers wrote.

And psychosis is known to raise the risk of suicide dramatically. Yet no studies to date have examined the relationship between psychotic symptoms and suicidal behaviors among adolescents. Dr. Kelleher and his colleagues did so using data from two independent cross-sectional epidemiologic studies of the general Irish population.

The Adolescent Brain Development (ABD) study assessed the prevalence of psychotic symptoms among 1,131 students aged 11-13 years in 16 mainstream schools, representing more than half of the total school population in that age group. The Challenging Times (CT) study assessed the prevalence of psychiatric disorders among 743 students aged 13-15 years in eight mainstream schools.

For this study, Dr. Kelleher and his associates analyzed the results of in-depth diagnostic interviews for 212 subjects from the ABD study and 211 from the CT study, as well as the interview responses of their parents.

Overall, 22% of the ABD sample and 7% of the CT sample reported experiencing psychotic symptoms when they were specifically asked about them, almost all of them during the preceding year. "From our clinical experience, young people will rarely volunteer information on psychotic symptoms unless questioned directly about such experiences. Adolescents are usually willing to talk openly about their experiences, however, in response to direct but sensitive questioning."

Examples of such questions included: "Sometimes people when they are alone hear things or see things, and they’re not quite sure where they came from. Does that ever happen to you?" and "Was there ever a time when you thought that your imagination was playing tricks on you?"

In the two cohorts combined, 44 subjects reported suicidal ideation, 16 reported making specific suicidal plans, and 8 reported suicidal acts.

Adolescents in both studies who reported suicidal behavior were more than 10 times more likely than were those who did not report suicidal behavior to say that they had also experienced hallucinations or delusions, the investigators said (Arch. Gen. Psychiatry Oct. 29 [doi:10.1001/archgenpsychiatry.2012.164]).

"Strikingly, a majority of adolescents with suicidal plans or acts reported psychotic symptoms in both the ABD study (60%) and the CT (55%), studies," they noted.

The researchers also examined the link between psychotic symptoms and suicidal behavior in the subgroup of adolescents who had a diagnosable psychiatric disorder. These included major depressive disorder, adjustment disorder with depressed mood, ADHD, oppositional defiant disorder, conduct disorder, generalized anxiety disorder, social phobia, separation anxiety disorder, and OCD.

In these high-risk subjects, those who reported experiencing hallucinations or delusions were more than five times more likely to also report suicidal behavior than were subjects who had no psychotic symptoms.

Moreover, a further analysis of the data showed that adolescents who had psychotic symptoms were more likely to show the most serious suicidal behavior (planning and attempts) than the less serious suicidal ideation.

This study was not designed to examine the reasons for this robust association between psychotic symptoms and suicidal behavior, but there are several possible mechanisms.

"The most obvious is that hallucinations may direct the individual to harm or kill themselves." However, only one subject reported hearing a voice commanding him to do so, suggesting that the content of hallucinations is not to blame, at least not in this age group.

Indirect cognitive mechanisms may play a role. "Changes in the subjective sense of self, for example, are among the earliest recognizable symptoms of psychosis, and a sense of disintegration and fragmentation of the self resulting from intrusive voices or thoughts have been linked to suicidal thinking," Dr. Kelleher and his colleagues said.

Alternatively, "Bleuler’s concept of ‘the suicidal drive’ might not be just the most severe symptom of schizophrenia but the most severe symptom of a much broader psychosis phenotype made up of individuals in the general population who experience psychotic symptoms," they wrote.

It is also possible some common factor underlies both psychotic symptoms and suicidal behavior. For example, the symptoms may be a marker for deteriorating mental health, which in turn puts patients at high risk for suicide.

Traumatic experiences also might be an underlying factor. Adolescents who have experienced severe adverse events such as childhood physical or sexual abuse are known to be at increased risk for developing psychotic symptoms, and their psychological distress may also place them at high risk for suicidal behavior, the researchers said.

This study also could not delineate when psychotic symptoms arose in relation to suicidal behavior, because it was cross-sectional rather than longitudinal. "Further research with more temporal information will help to address this point," they added.

This study was funded by the European Community’s Seventh Framework Programme. No conflicts of interest were reported.

Symptoms of psychosis were associated with greatly increased risk for suicidal behavior in the general adolescent population as well as in adolescents who have nonpsychotic disorders, such as depression, attention-deficit/hyperactivity disorder, anxiety disorders, or obsessive compulsive disorder, according to two separate epidemiologic studies reported online Oct. 29 in the Archives of General Psychiatry.

Among adolescents in the general population, as well as the subgroup of adolescents who had nonpsychotic DSM-III diagnoses, those who reported suicidal ideation, suicide planning, or suicidal acts were 10 times more likely than those who did not to affirm on direct questioning that they had experienced psychotic symptoms – mainly auditory hallucinations, said Ian Kelleher, Ph.D., of the department of psychiatry, Royal College of Surgeons in Ireland, Dublin, and his associates.

"The immediate clinical relevance of these findings is that all patients presenting at risk for suicidal behavior should receive a thorough assessment of psychotic symptoms and not just a screening to rule out psychotic disorder," they noted.

Both primary care physicians and psychiatric clinicians must recognize that psychotic symptoms in a nonpsychotic patient signify a high suicide risk. "Research has shown that the largest increase in suicide risk in the general population occurs after there has already been contact with mental health services and that approximately half of patients who complete suicide [had] contact with primary care providers in the month preceding their death[s]," the investigators added.

Hallucinations and delusions, the classic symptoms of psychosis, are far more prevalent in the general population than are diagnosable psychotic disorders. They are "especially common in young people, with a meta-analysis of general population studies demonstrating a median prevalence of 17% in children aged 9-12 years and 7.5% in adolescents aged 13-17 years," the researchers wrote.

And psychosis is known to raise the risk of suicide dramatically. Yet no studies to date have examined the relationship between psychotic symptoms and suicidal behaviors among adolescents. Dr. Kelleher and his colleagues did so using data from two independent cross-sectional epidemiologic studies of the general Irish population.

The Adolescent Brain Development (ABD) study assessed the prevalence of psychotic symptoms among 1,131 students aged 11-13 years in 16 mainstream schools, representing more than half of the total school population in that age group. The Challenging Times (CT) study assessed the prevalence of psychiatric disorders among 743 students aged 13-15 years in eight mainstream schools.

For this study, Dr. Kelleher and his associates analyzed the results of in-depth diagnostic interviews for 212 subjects from the ABD study and 211 from the CT study, as well as the interview responses of their parents.

Overall, 22% of the ABD sample and 7% of the CT sample reported experiencing psychotic symptoms when they were specifically asked about them, almost all of them during the preceding year. "From our clinical experience, young people will rarely volunteer information on psychotic symptoms unless questioned directly about such experiences. Adolescents are usually willing to talk openly about their experiences, however, in response to direct but sensitive questioning."

Examples of such questions included: "Sometimes people when they are alone hear things or see things, and they’re not quite sure where they came from. Does that ever happen to you?" and "Was there ever a time when you thought that your imagination was playing tricks on you?"

In the two cohorts combined, 44 subjects reported suicidal ideation, 16 reported making specific suicidal plans, and 8 reported suicidal acts.

Adolescents in both studies who reported suicidal behavior were more than 10 times more likely than were those who did not report suicidal behavior to say that they had also experienced hallucinations or delusions, the investigators said (Arch. Gen. Psychiatry Oct. 29 [doi:10.1001/archgenpsychiatry.2012.164]).

"Strikingly, a majority of adolescents with suicidal plans or acts reported psychotic symptoms in both the ABD study (60%) and the CT (55%), studies," they noted.

The researchers also examined the link between psychotic symptoms and suicidal behavior in the subgroup of adolescents who had a diagnosable psychiatric disorder. These included major depressive disorder, adjustment disorder with depressed mood, ADHD, oppositional defiant disorder, conduct disorder, generalized anxiety disorder, social phobia, separation anxiety disorder, and OCD.

In these high-risk subjects, those who reported experiencing hallucinations or delusions were more than five times more likely to also report suicidal behavior than were subjects who had no psychotic symptoms.

Moreover, a further analysis of the data showed that adolescents who had psychotic symptoms were more likely to show the most serious suicidal behavior (planning and attempts) than the less serious suicidal ideation.

This study was not designed to examine the reasons for this robust association between psychotic symptoms and suicidal behavior, but there are several possible mechanisms.

"The most obvious is that hallucinations may direct the individual to harm or kill themselves." However, only one subject reported hearing a voice commanding him to do so, suggesting that the content of hallucinations is not to blame, at least not in this age group.

Indirect cognitive mechanisms may play a role. "Changes in the subjective sense of self, for example, are among the earliest recognizable symptoms of psychosis, and a sense of disintegration and fragmentation of the self resulting from intrusive voices or thoughts have been linked to suicidal thinking," Dr. Kelleher and his colleagues said.

Alternatively, "Bleuler’s concept of ‘the suicidal drive’ might not be just the most severe symptom of schizophrenia but the most severe symptom of a much broader psychosis phenotype made up of individuals in the general population who experience psychotic symptoms," they wrote.

It is also possible some common factor underlies both psychotic symptoms and suicidal behavior. For example, the symptoms may be a marker for deteriorating mental health, which in turn puts patients at high risk for suicide.

Traumatic experiences also might be an underlying factor. Adolescents who have experienced severe adverse events such as childhood physical or sexual abuse are known to be at increased risk for developing psychotic symptoms, and their psychological distress may also place them at high risk for suicidal behavior, the researchers said.

This study also could not delineate when psychotic symptoms arose in relation to suicidal behavior, because it was cross-sectional rather than longitudinal. "Further research with more temporal information will help to address this point," they added.

This study was funded by the European Community’s Seventh Framework Programme. No conflicts of interest were reported.

Symptoms of psychosis were associated with greatly increased risk for suicidal behavior in the general adolescent population as well as in adolescents who have nonpsychotic disorders, such as depression, attention-deficit/hyperactivity disorder, anxiety disorders, or obsessive compulsive disorder, according to two separate epidemiologic studies reported online Oct. 29 in the Archives of General Psychiatry.

Among adolescents in the general population, as well as the subgroup of adolescents who had nonpsychotic DSM-III diagnoses, those who reported suicidal ideation, suicide planning, or suicidal acts were 10 times more likely than those who did not to affirm on direct questioning that they had experienced psychotic symptoms – mainly auditory hallucinations, said Ian Kelleher, Ph.D., of the department of psychiatry, Royal College of Surgeons in Ireland, Dublin, and his associates.

"The immediate clinical relevance of these findings is that all patients presenting at risk for suicidal behavior should receive a thorough assessment of psychotic symptoms and not just a screening to rule out psychotic disorder," they noted.

Both primary care physicians and psychiatric clinicians must recognize that psychotic symptoms in a nonpsychotic patient signify a high suicide risk. "Research has shown that the largest increase in suicide risk in the general population occurs after there has already been contact with mental health services and that approximately half of patients who complete suicide [had] contact with primary care providers in the month preceding their death[s]," the investigators added.

Hallucinations and delusions, the classic symptoms of psychosis, are far more prevalent in the general population than are diagnosable psychotic disorders. They are "especially common in young people, with a meta-analysis of general population studies demonstrating a median prevalence of 17% in children aged 9-12 years and 7.5% in adolescents aged 13-17 years," the researchers wrote.

And psychosis is known to raise the risk of suicide dramatically. Yet no studies to date have examined the relationship between psychotic symptoms and suicidal behaviors among adolescents. Dr. Kelleher and his colleagues did so using data from two independent cross-sectional epidemiologic studies of the general Irish population.

The Adolescent Brain Development (ABD) study assessed the prevalence of psychotic symptoms among 1,131 students aged 11-13 years in 16 mainstream schools, representing more than half of the total school population in that age group. The Challenging Times (CT) study assessed the prevalence of psychiatric disorders among 743 students aged 13-15 years in eight mainstream schools.

For this study, Dr. Kelleher and his associates analyzed the results of in-depth diagnostic interviews for 212 subjects from the ABD study and 211 from the CT study, as well as the interview responses of their parents.

Overall, 22% of the ABD sample and 7% of the CT sample reported experiencing psychotic symptoms when they were specifically asked about them, almost all of them during the preceding year. "From our clinical experience, young people will rarely volunteer information on psychotic symptoms unless questioned directly about such experiences. Adolescents are usually willing to talk openly about their experiences, however, in response to direct but sensitive questioning."

Examples of such questions included: "Sometimes people when they are alone hear things or see things, and they’re not quite sure where they came from. Does that ever happen to you?" and "Was there ever a time when you thought that your imagination was playing tricks on you?"

In the two cohorts combined, 44 subjects reported suicidal ideation, 16 reported making specific suicidal plans, and 8 reported suicidal acts.

Adolescents in both studies who reported suicidal behavior were more than 10 times more likely than were those who did not report suicidal behavior to say that they had also experienced hallucinations or delusions, the investigators said (Arch. Gen. Psychiatry Oct. 29 [doi:10.1001/archgenpsychiatry.2012.164]).

"Strikingly, a majority of adolescents with suicidal plans or acts reported psychotic symptoms in both the ABD study (60%) and the CT (55%), studies," they noted.

The researchers also examined the link between psychotic symptoms and suicidal behavior in the subgroup of adolescents who had a diagnosable psychiatric disorder. These included major depressive disorder, adjustment disorder with depressed mood, ADHD, oppositional defiant disorder, conduct disorder, generalized anxiety disorder, social phobia, separation anxiety disorder, and OCD.

In these high-risk subjects, those who reported experiencing hallucinations or delusions were more than five times more likely to also report suicidal behavior than were subjects who had no psychotic symptoms.

Moreover, a further analysis of the data showed that adolescents who had psychotic symptoms were more likely to show the most serious suicidal behavior (planning and attempts) than the less serious suicidal ideation.

This study was not designed to examine the reasons for this robust association between psychotic symptoms and suicidal behavior, but there are several possible mechanisms.

"The most obvious is that hallucinations may direct the individual to harm or kill themselves." However, only one subject reported hearing a voice commanding him to do so, suggesting that the content of hallucinations is not to blame, at least not in this age group.

Indirect cognitive mechanisms may play a role. "Changes in the subjective sense of self, for example, are among the earliest recognizable symptoms of psychosis, and a sense of disintegration and fragmentation of the self resulting from intrusive voices or thoughts have been linked to suicidal thinking," Dr. Kelleher and his colleagues said.

Alternatively, "Bleuler’s concept of ‘the suicidal drive’ might not be just the most severe symptom of schizophrenia but the most severe symptom of a much broader psychosis phenotype made up of individuals in the general population who experience psychotic symptoms," they wrote.

It is also possible some common factor underlies both psychotic symptoms and suicidal behavior. For example, the symptoms may be a marker for deteriorating mental health, which in turn puts patients at high risk for suicide.

Traumatic experiences also might be an underlying factor. Adolescents who have experienced severe adverse events such as childhood physical or sexual abuse are known to be at increased risk for developing psychotic symptoms, and their psychological distress may also place them at high risk for suicidal behavior, the researchers said.

This study also could not delineate when psychotic symptoms arose in relation to suicidal behavior, because it was cross-sectional rather than longitudinal. "Further research with more temporal information will help to address this point," they added.

This study was funded by the European Community’s Seventh Framework Programme. No conflicts of interest were reported.

The rate of myocardial infarction dropped by one-third after laws prohibiting smoking in public places and workplaces were enacted in Olmsted County, Minnesota, according to a report published online Oct. 29 in Archives of Internal Medicine.

Although this epidemiologic study could not establish causality, no other interventions during the study period could plausibly explain this community-wide reduction in the MI rate. And the only major MI risk factor that declined concurrently was the prevalence of smoking; rates of hypertension and hypercholesterolemia remained steady, and rates of diabetes and obesity increased, said Dr. Richard D. Hurt of the Nicotine Dependence Center and the department of internal medicine at the Mayo Clinic in Rochester, Minn., and his associates.

© milosluz/istockphoto.com

"We believe that secondhand smoke should be considered a major risk factor for MI, joining family history, hypertension, hyperlipidemia, diabetes mellitus, and low physical activity. Hence, all clinicians should ascertain secondhand smoke exposure and promote the elimination of secondhand smoke exposure as part of their lifestyle recommendations," they noted.

"All people should avoid secondhand smoke exposure as much as possible, and those with [coronary heart disease] should have no exposure to secondhand smoke," the investigators added.

Several studies have documented declines in hospital admissions for MI after the implementation of smoke-free laws, and the Institute of Medicine has concluded that there is a causal relationship between smoking bans and reductions in acute coronary events. To more closely examine the magnitude of that risk reduction, Dr. Hurt and his colleagues analyzed data from the Rochester Epidemiology Project, in which all cases of MI and sudden cardiac death in a well-defined community were validated using rigorous epidemiologic criteria. This project "has a long track record (more than 50 years) of robust epidemiologic studies," they said.

In Olmsted County, restaurants were required to be smoke free as of Jan. 1, 2002; bars and workplaces were required to follow suit on Oct. 1, 2007. The researchers examined rates of MI and sudden cardiac death during the 18 months before and the 18 months following implementation of each ordinance.

During the entire study period, there were 717 incident MIs and 514 cases of sudden cardiac death.

The age- and sex-adjusted rate of MI dropped from 150.8/100,000 people before the laws were implemented to 100.7/100,000 afterward – a 34% decline, the investigators said (Arch. Intern. Med. 2012 [doi:10.1001/2013.jamainternmed.46]).

Similarly, there was a 17% decline in the incidence of sudden cardiac death during this period, which indicates a trend but does not constitute a statistically significant reduction.

Smoke-free legislation is effective not only because it decreases the amount of secondhand smoke to which nonsmokers are exposed, but also because it reduces the intensity of smoking among smokers, increases quit rates, and reduces the rate of taking up smoking in the first place, Dr. Hurt and his associates said.

Other research has demonstrated that as little as 30 minutes of exposure to secondhand smoke causes an abrupt and dramatic decrease in coronary artery flow velocity reserves and vascular injury that inhibits endothelial function. Exposure also has been associated with low HDL cholesterol levels, increased markers of inflammation, increased serum levels of fibrinogen and homocysteine, decreased antioxidant levels, and increased insulin resistance, they wrote.

Taken together, these findings indicate that physicians should "become advocates for effective tobacco control policies, such as increased taxes, graphic labeling, smoke-free workplaces, and marketing and advertising restrictions," the researchers said.

One limitation of this study was that the population of Olmsted County is predominantly white. Further studies are needed "in communities of more diverse racial and ethnic composition," Dr. Hurt and his colleagues said.

This study was supported by ClearWay Minnesota; the National Heart, Lung, and Blood Institute; and the National Institute on Aging. No financial conflicts of interest were reported.

The rate of myocardial infarction dropped by one-third after laws prohibiting smoking in public places and workplaces were enacted in Olmsted County, Minnesota, according to a report published online Oct. 29 in Archives of Internal Medicine.

Although this epidemiologic study could not establish causality, no other interventions during the study period could plausibly explain this community-wide reduction in the MI rate. And the only major MI risk factor that declined concurrently was the prevalence of smoking; rates of hypertension and hypercholesterolemia remained steady, and rates of diabetes and obesity increased, said Dr. Richard D. Hurt of the Nicotine Dependence Center and the department of internal medicine at the Mayo Clinic in Rochester, Minn., and his associates.

© milosluz/istockphoto.com

"We believe that secondhand smoke should be considered a major risk factor for MI, joining family history, hypertension, hyperlipidemia, diabetes mellitus, and low physical activity. Hence, all clinicians should ascertain secondhand smoke exposure and promote the elimination of secondhand smoke exposure as part of their lifestyle recommendations," they noted.

"All people should avoid secondhand smoke exposure as much as possible, and those with [coronary heart disease] should have no exposure to secondhand smoke," the investigators added.

Several studies have documented declines in hospital admissions for MI after the implementation of smoke-free laws, and the Institute of Medicine has concluded that there is a causal relationship between smoking bans and reductions in acute coronary events. To more closely examine the magnitude of that risk reduction, Dr. Hurt and his colleagues analyzed data from the Rochester Epidemiology Project, in which all cases of MI and sudden cardiac death in a well-defined community were validated using rigorous epidemiologic criteria. This project "has a long track record (more than 50 years) of robust epidemiologic studies," they said.

In Olmsted County, restaurants were required to be smoke free as of Jan. 1, 2002; bars and workplaces were required to follow suit on Oct. 1, 2007. The researchers examined rates of MI and sudden cardiac death during the 18 months before and the 18 months following implementation of each ordinance.

During the entire study period, there were 717 incident MIs and 514 cases of sudden cardiac death.

The age- and sex-adjusted rate of MI dropped from 150.8/100,000 people before the laws were implemented to 100.7/100,000 afterward – a 34% decline, the investigators said (Arch. Intern. Med. 2012 [doi:10.1001/2013.jamainternmed.46]).

Similarly, there was a 17% decline in the incidence of sudden cardiac death during this period, which indicates a trend but does not constitute a statistically significant reduction.

Smoke-free legislation is effective not only because it decreases the amount of secondhand smoke to which nonsmokers are exposed, but also because it reduces the intensity of smoking among smokers, increases quit rates, and reduces the rate of taking up smoking in the first place, Dr. Hurt and his associates said.

Other research has demonstrated that as little as 30 minutes of exposure to secondhand smoke causes an abrupt and dramatic decrease in coronary artery flow velocity reserves and vascular injury that inhibits endothelial function. Exposure also has been associated with low HDL cholesterol levels, increased markers of inflammation, increased serum levels of fibrinogen and homocysteine, decreased antioxidant levels, and increased insulin resistance, they wrote.

Taken together, these findings indicate that physicians should "become advocates for effective tobacco control policies, such as increased taxes, graphic labeling, smoke-free workplaces, and marketing and advertising restrictions," the researchers said.

One limitation of this study was that the population of Olmsted County is predominantly white. Further studies are needed "in communities of more diverse racial and ethnic composition," Dr. Hurt and his colleagues said.

This study was supported by ClearWay Minnesota; the National Heart, Lung, and Blood Institute; and the National Institute on Aging. No financial conflicts of interest were reported.

The rate of myocardial infarction dropped by one-third after laws prohibiting smoking in public places and workplaces were enacted in Olmsted County, Minnesota, according to a report published online Oct. 29 in Archives of Internal Medicine.

Although this epidemiologic study could not establish causality, no other interventions during the study period could plausibly explain this community-wide reduction in the MI rate. And the only major MI risk factor that declined concurrently was the prevalence of smoking; rates of hypertension and hypercholesterolemia remained steady, and rates of diabetes and obesity increased, said Dr. Richard D. Hurt of the Nicotine Dependence Center and the department of internal medicine at the Mayo Clinic in Rochester, Minn., and his associates.

© milosluz/istockphoto.com

"We believe that secondhand smoke should be considered a major risk factor for MI, joining family history, hypertension, hyperlipidemia, diabetes mellitus, and low physical activity. Hence, all clinicians should ascertain secondhand smoke exposure and promote the elimination of secondhand smoke exposure as part of their lifestyle recommendations," they noted.

"All people should avoid secondhand smoke exposure as much as possible, and those with [coronary heart disease] should have no exposure to secondhand smoke," the investigators added.

Several studies have documented declines in hospital admissions for MI after the implementation of smoke-free laws, and the Institute of Medicine has concluded that there is a causal relationship between smoking bans and reductions in acute coronary events. To more closely examine the magnitude of that risk reduction, Dr. Hurt and his colleagues analyzed data from the Rochester Epidemiology Project, in which all cases of MI and sudden cardiac death in a well-defined community were validated using rigorous epidemiologic criteria. This project "has a long track record (more than 50 years) of robust epidemiologic studies," they said.

In Olmsted County, restaurants were required to be smoke free as of Jan. 1, 2002; bars and workplaces were required to follow suit on Oct. 1, 2007. The researchers examined rates of MI and sudden cardiac death during the 18 months before and the 18 months following implementation of each ordinance.

During the entire study period, there were 717 incident MIs and 514 cases of sudden cardiac death.

The age- and sex-adjusted rate of MI dropped from 150.8/100,000 people before the laws were implemented to 100.7/100,000 afterward – a 34% decline, the investigators said (Arch. Intern. Med. 2012 [doi:10.1001/2013.jamainternmed.46]).

Similarly, there was a 17% decline in the incidence of sudden cardiac death during this period, which indicates a trend but does not constitute a statistically significant reduction.

Smoke-free legislation is effective not only because it decreases the amount of secondhand smoke to which nonsmokers are exposed, but also because it reduces the intensity of smoking among smokers, increases quit rates, and reduces the rate of taking up smoking in the first place, Dr. Hurt and his associates said.

Other research has demonstrated that as little as 30 minutes of exposure to secondhand smoke causes an abrupt and dramatic decrease in coronary artery flow velocity reserves and vascular injury that inhibits endothelial function. Exposure also has been associated with low HDL cholesterol levels, increased markers of inflammation, increased serum levels of fibrinogen and homocysteine, decreased antioxidant levels, and increased insulin resistance, they wrote.

Taken together, these findings indicate that physicians should "become advocates for effective tobacco control policies, such as increased taxes, graphic labeling, smoke-free workplaces, and marketing and advertising restrictions," the researchers said.

One limitation of this study was that the population of Olmsted County is predominantly white. Further studies are needed "in communities of more diverse racial and ethnic composition," Dr. Hurt and his colleagues said.

This study was supported by ClearWay Minnesota; the National Heart, Lung, and Blood Institute; and the National Institute on Aging. No financial conflicts of interest were reported.

Universal testing of colorectal cancers for DNA mismatch repair genes is the strategy most likely to identify the approximately 1%-3% of patients who have Lynch syndrome, according to a report in the Oct. 17 issue of JAMA.

Correctly identifying the small subgroup of colorectal cancer (CRC) patients who have Lynch syndrome is crucial so that their presymptomatic relatives can be found and all the affected family members can consider preventive measures to limit their morbidity and mortality.

Dr. Leticia Moreira and her colleagues in the EPICOLON consortium, an international network of colon cancer cohorts, pooled data involving 10,206 probands to show that "universal tumor MMR testing followed by germline testing offers the highest sensitivity," compared with other strategies, "although the increase in the diagnostic yield is modest" (JAMA 2012;308:1555-65).

This research highlights the limitations of various methods for identifying the subgroup of colorectal cancer patients who have Lynch syndrome and should remind clinicians "that simply asking about a family history of CRC in a first-degree relative will miss the majority of patients with Lynch syndrome," because only 43% of patients with Lynch syndrome have such a family history, wrote Dr. Uri Ladabaum and Dr. James M. Ford of the gastrointestinal cancer prevention program and clinical cancer genetics program at Stanford (Calif.) University in an editorial accompanying the study (JAMA 2012;308:1581-3).

"The majority of CRC patients do not have Lynch syndrome. But in the haystack of patients with CRC, those with Lynch syndrome are more like large knitting needles than tiny sewing needles – and a systematic search can find them," they wrote.

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is the most common form of familial colorectal cancer and is caused by germline mutations in the DNA mismatch repair (MMR) genes MSH2, MLH1, MSH6, and PMS2. Dysfunction of these genes causes an accumulation of errors during DNA replication, particularly in the repetitive sequences called microsatellites.

"As a result, tumors of patients with Lynch syndrome characteristically demonstrate MMR deficiency, defined as the presence of microsatellite instability or loss of the MMR protein expression, which is the hallmark of this disorder," the investigators wrote.

Several sets of guidelines have been issued for identifying which colorectal cancer patients should undergo tumor DNA testing to reveal these traits, but none have proved sensitive and specific enough to do an optimal job, and all have been difficult to apply in clinical practice, said Dr. Moreira of the University of Barcelona and her associates.

"Unless there is strong clinical suspicion, the majority of cases remain undetected, leading to the lack of implementation of highly effective preventive measures" including intensive screening by colonoscopy and prophylactic removal of targeted organs, they noted.

By pooling the data from four large cohorts of colorectal cancer patients around the world, the researchers compared the effectiveness of different screening strategies for identifying Lynch syndrome. Universal testing of the tumors for DNA MMR abnormalities was the most effective method, with a sensitivity of 100% and a specificity of 93%.

In comparison, use of the revised Bethesda guidelines will fail to detect approximately 12% of cases, use of the Jerusalem recommendations will fail to detect approximately 15%, and use of a "selective strategy" will fail to detect approximately 5%, the investigators reported. The specificities of the strategies ranged from 95.5% with the "selective strategy" to 97.5% with the revised Bethesda guidelines. The investigators developed the "selective strategy" for screening by using the most sensitive variables in a bivariate analysis: CRC diagnosis at 70 years and fulfillment of at least 1 criterion of the revised Bethesda guidelines.

The diagnostic yield of universal MMR testing followed by germline testing was 2.2%. In comparison, the diagnostic yield of the revised Bethesda guidelines was 2.0%, that of the Jerusalem recommendations was 1.9%, and that of "selective criteria" was 2.1%.

Universal testing of colorectal cancers for DNA mismatch repair genes is the strategy most likely to identify the approximately 1%-3% of patients who have Lynch syndrome, according to a report in the Oct. 17 issue of JAMA.

Correctly identifying the small subgroup of colorectal cancer (CRC) patients who have Lynch syndrome is crucial so that their presymptomatic relatives can be found and all the affected family members can consider preventive measures to limit their morbidity and mortality.

Dr. Leticia Moreira and her colleagues in the EPICOLON consortium, an international network of colon cancer cohorts, pooled data involving 10,206 probands to show that "universal tumor MMR testing followed by germline testing offers the highest sensitivity," compared with other strategies, "although the increase in the diagnostic yield is modest" (JAMA 2012;308:1555-65).

This research highlights the limitations of various methods for identifying the subgroup of colorectal cancer patients who have Lynch syndrome and should remind clinicians "that simply asking about a family history of CRC in a first-degree relative will miss the majority of patients with Lynch syndrome," because only 43% of patients with Lynch syndrome have such a family history, wrote Dr. Uri Ladabaum and Dr. James M. Ford of the gastrointestinal cancer prevention program and clinical cancer genetics program at Stanford (Calif.) University in an editorial accompanying the study (JAMA 2012;308:1581-3).

"The majority of CRC patients do not have Lynch syndrome. But in the haystack of patients with CRC, those with Lynch syndrome are more like large knitting needles than tiny sewing needles – and a systematic search can find them," they wrote.

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is the most common form of familial colorectal cancer and is caused by germline mutations in the DNA mismatch repair (MMR) genes MSH2, MLH1, MSH6, and PMS2. Dysfunction of these genes causes an accumulation of errors during DNA replication, particularly in the repetitive sequences called microsatellites.

"As a result, tumors of patients with Lynch syndrome characteristically demonstrate MMR deficiency, defined as the presence of microsatellite instability or loss of the MMR protein expression, which is the hallmark of this disorder," the investigators wrote.

Several sets of guidelines have been issued for identifying which colorectal cancer patients should undergo tumor DNA testing to reveal these traits, but none have proved sensitive and specific enough to do an optimal job, and all have been difficult to apply in clinical practice, said Dr. Moreira of the University of Barcelona and her associates.

"Unless there is strong clinical suspicion, the majority of cases remain undetected, leading to the lack of implementation of highly effective preventive measures" including intensive screening by colonoscopy and prophylactic removal of targeted organs, they noted.

By pooling the data from four large cohorts of colorectal cancer patients around the world, the researchers compared the effectiveness of different screening strategies for identifying Lynch syndrome. Universal testing of the tumors for DNA MMR abnormalities was the most effective method, with a sensitivity of 100% and a specificity of 93%.

In comparison, use of the revised Bethesda guidelines will fail to detect approximately 12% of cases, use of the Jerusalem recommendations will fail to detect approximately 15%, and use of a "selective strategy" will fail to detect approximately 5%, the investigators reported. The specificities of the strategies ranged from 95.5% with the "selective strategy" to 97.5% with the revised Bethesda guidelines. The investigators developed the "selective strategy" for screening by using the most sensitive variables in a bivariate analysis: CRC diagnosis at 70 years and fulfillment of at least 1 criterion of the revised Bethesda guidelines.

The diagnostic yield of universal MMR testing followed by germline testing was 2.2%. In comparison, the diagnostic yield of the revised Bethesda guidelines was 2.0%, that of the Jerusalem recommendations was 1.9%, and that of "selective criteria" was 2.1%.

Universal testing of colorectal cancers for DNA mismatch repair genes is the strategy most likely to identify the approximately 1%-3% of patients who have Lynch syndrome, according to a report in the Oct. 17 issue of JAMA.

Correctly identifying the small subgroup of colorectal cancer (CRC) patients who have Lynch syndrome is crucial so that their presymptomatic relatives can be found and all the affected family members can consider preventive measures to limit their morbidity and mortality.

Dr. Leticia Moreira and her colleagues in the EPICOLON consortium, an international network of colon cancer cohorts, pooled data involving 10,206 probands to show that "universal tumor MMR testing followed by germline testing offers the highest sensitivity," compared with other strategies, "although the increase in the diagnostic yield is modest" (JAMA 2012;308:1555-65).

This research highlights the limitations of various methods for identifying the subgroup of colorectal cancer patients who have Lynch syndrome and should remind clinicians "that simply asking about a family history of CRC in a first-degree relative will miss the majority of patients with Lynch syndrome," because only 43% of patients with Lynch syndrome have such a family history, wrote Dr. Uri Ladabaum and Dr. James M. Ford of the gastrointestinal cancer prevention program and clinical cancer genetics program at Stanford (Calif.) University in an editorial accompanying the study (JAMA 2012;308:1581-3).

"The majority of CRC patients do not have Lynch syndrome. But in the haystack of patients with CRC, those with Lynch syndrome are more like large knitting needles than tiny sewing needles – and a systematic search can find them," they wrote.

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is the most common form of familial colorectal cancer and is caused by germline mutations in the DNA mismatch repair (MMR) genes MSH2, MLH1, MSH6, and PMS2. Dysfunction of these genes causes an accumulation of errors during DNA replication, particularly in the repetitive sequences called microsatellites.

"As a result, tumors of patients with Lynch syndrome characteristically demonstrate MMR deficiency, defined as the presence of microsatellite instability or loss of the MMR protein expression, which is the hallmark of this disorder," the investigators wrote.

Several sets of guidelines have been issued for identifying which colorectal cancer patients should undergo tumor DNA testing to reveal these traits, but none have proved sensitive and specific enough to do an optimal job, and all have been difficult to apply in clinical practice, said Dr. Moreira of the University of Barcelona and her associates.

"Unless there is strong clinical suspicion, the majority of cases remain undetected, leading to the lack of implementation of highly effective preventive measures" including intensive screening by colonoscopy and prophylactic removal of targeted organs, they noted.

By pooling the data from four large cohorts of colorectal cancer patients around the world, the researchers compared the effectiveness of different screening strategies for identifying Lynch syndrome. Universal testing of the tumors for DNA MMR abnormalities was the most effective method, with a sensitivity of 100% and a specificity of 93%.

In comparison, use of the revised Bethesda guidelines will fail to detect approximately 12% of cases, use of the Jerusalem recommendations will fail to detect approximately 15%, and use of a "selective strategy" will fail to detect approximately 5%, the investigators reported. The specificities of the strategies ranged from 95.5% with the "selective strategy" to 97.5% with the revised Bethesda guidelines. The investigators developed the "selective strategy" for screening by using the most sensitive variables in a bivariate analysis: CRC diagnosis at 70 years and fulfillment of at least 1 criterion of the revised Bethesda guidelines.

The diagnostic yield of universal MMR testing followed by germline testing was 2.2%. In comparison, the diagnostic yield of the revised Bethesda guidelines was 2.0%, that of the Jerusalem recommendations was 1.9%, and that of "selective criteria" was 2.1%.

Among patients with Alzheimer’s disease who develop psychosis or agitation-aggression that responds to risperidone, discontinuing the drug as advised after 3-6 months is associated with a doubling of the rate of relapse, according to a study published Oct. 17 in the New England Journal of Medicine.

"Federal regulations for nursing homes strongly urge discontinuation of antipsychotic drugs after 3-6 months of treatment" because of concern about adverse effects, even though "evidence from controlled trials in support of this long-standing regulation is very limited," said Dr. D.P. Devanand of the New York State Psychiatric Institute and Columbia University, New York, and his associates.

"Our findings suggest that patients with psychosis or agitation-aggression who have a sustained response to antipsychotic treatment for 4-8 months have a significantly increased risk of relapse for at least 4 months after discontinuation, and this finding should be weighed against the risk of adverse effects with continued antipsychotic treatment," they noted (N. Engl. J. Med. 2012 [doi:10.1056/NEJMoa1114058]).

Dr. Devanand and his colleagues presented their findings in July at the Alzheimer’s Association International Conference; read our coverage here.

This study was funded by the National Institutes of Health and the U.S. Department of Veterans Affairs. Dr. Devanand and his associates reported numerous ties to industry sources.

Among patients with Alzheimer’s disease who develop psychosis or agitation-aggression that responds to risperidone, discontinuing the drug as advised after 3-6 months is associated with a doubling of the rate of relapse, according to a study published Oct. 17 in the New England Journal of Medicine.

"Federal regulations for nursing homes strongly urge discontinuation of antipsychotic drugs after 3-6 months of treatment" because of concern about adverse effects, even though "evidence from controlled trials in support of this long-standing regulation is very limited," said Dr. D.P. Devanand of the New York State Psychiatric Institute and Columbia University, New York, and his associates.

"Our findings suggest that patients with psychosis or agitation-aggression who have a sustained response to antipsychotic treatment for 4-8 months have a significantly increased risk of relapse for at least 4 months after discontinuation, and this finding should be weighed against the risk of adverse effects with continued antipsychotic treatment," they noted (N. Engl. J. Med. 2012 [doi:10.1056/NEJMoa1114058]).

Dr. Devanand and his colleagues presented their findings in July at the Alzheimer’s Association International Conference; read our coverage here.

This study was funded by the National Institutes of Health and the U.S. Department of Veterans Affairs. Dr. Devanand and his associates reported numerous ties to industry sources.

Among patients with Alzheimer’s disease who develop psychosis or agitation-aggression that responds to risperidone, discontinuing the drug as advised after 3-6 months is associated with a doubling of the rate of relapse, according to a study published Oct. 17 in the New England Journal of Medicine.

"Federal regulations for nursing homes strongly urge discontinuation of antipsychotic drugs after 3-6 months of treatment" because of concern about adverse effects, even though "evidence from controlled trials in support of this long-standing regulation is very limited," said Dr. D.P. Devanand of the New York State Psychiatric Institute and Columbia University, New York, and his associates.

"Our findings suggest that patients with psychosis or agitation-aggression who have a sustained response to antipsychotic treatment for 4-8 months have a significantly increased risk of relapse for at least 4 months after discontinuation, and this finding should be weighed against the risk of adverse effects with continued antipsychotic treatment," they noted (N. Engl. J. Med. 2012 [doi:10.1056/NEJMoa1114058]).

Dr. Devanand and his colleagues presented their findings in July at the Alzheimer’s Association International Conference; read our coverage here.

This study was funded by the National Institutes of Health and the U.S. Department of Veterans Affairs. Dr. Devanand and his associates reported numerous ties to industry sources.

Mean serum levels of lipids have improved among American adults since the late 1980s, according to an analysis of data from three nationwide surveys, published Oct. 17 in JAMA.

Between 1988 and 2012, mean total cholesterol, non-HDL cholesterol, and LDL cholesterol levels have declined and mean HDL cholesterol levels have risen in adults overall as well as across most racial/ethnic and gender categories, said Margaret D. Carroll of the Division of Health and Nutrition Examination Surveys, National Center for Health Statistics, Hyattsville, Md., and her associates.

The investigators examined data from the National Health and Nutrition Examination Surveys (NHANES) for 1988-1994, 1999-2002, and 2007-2010 to track temporal trends in lipid levels. Each cross-sectional survey included health-related interviews and physical examinations of a nationally representative sample of tens of thousands of adults.

In the adult population as a whole, the mean total cholesterol level declined in a linear fashion from 206 mg/dL in 1988-1994 to 203 mg/dL in 1999-2002 and to 196 mg/dL in 2007-2010. This pattern remained the same in separate analyses of men and women and in all racial/ethnic subgroups, except for Mexican American men (JAMA 2012;308:1545-54).

LDL cholesterol also decreased in a linear fashion in all adults, from 128 mg/dL in the first survey to 124 mg/dL in the second and to 119 mg/dL in the final survey. LDL cholesterol levels declined in both men and women and eventually converged, so there was no longer a difference between the sexes in the latest survey.

HDL cholesterol rose in a linear fashion from 50.7 mg/dL to 52.5 mg/dL among all adults, and also rose in separate analyses of both sexes. When the data were broken down by racial/ethnic categories, HDL cholesterol rose in whites of both sexes but not in blacks or Mexican Americans.

Triglycerides showed a slightly different pattern, rising between the late 1980s (118 mg/dL) and the early 2000s (123 mg/dL), but then falling again by 2010 (110 mg/dL).

All of these temporal trends persisted when the analysis was restricted to only the oldest adults, aged 50 and older.

During the study period, the number of adults taking lipid-lowering medications also rose, from 3.4% in 1988-1994 to 9.3% in 1999-2002 and to 15.5% in 2007-2010. However, these medications did not explain the entire improvement in lipid profiles, which also improved markedly in adults who weren’t taking them.

"The Healthy People 2010 guideline of an age-adjusted mean total cholesterol level of 200 mg/dL or less has been achieved in [all] adults, in men, in women, and in all race/ethnicity and sex subgroups. However, the age-adjusted mean LDL cholesterol level in adults of 116 mg/dL [remains] higher than the optimal range of below 100 mg/dL, [which is] associated with a lower risk of CHD [coronary heart disease]," Ms. Carroll and her colleagues said.

The researchers speculated that the favorable trends in lipid profiles might be attributable in part to a decrease in the consumption of trans-fatty acids and to other healthy lifestyle changes. The changes are unlikely to have resulted from increases in physical activity or decreases in the intake of saturated fat, as other studies have demonstrated that activity has not increased and saturated fat intake has not declined during the study period, they said.

This laboratory analysis of lipids was funded by the National Heart, Lung, and Blood Institute. NHANES is conducted by the National Center for Health Statistics and the Centers for Disease Control and Prevention. No conflicts of interest were reported.

Mean serum levels of lipids have improved among American adults since the late 1980s, according to an analysis of data from three nationwide surveys, published Oct. 17 in JAMA.

Between 1988 and 2012, mean total cholesterol, non-HDL cholesterol, and LDL cholesterol levels have declined and mean HDL cholesterol levels have risen in adults overall as well as across most racial/ethnic and gender categories, said Margaret D. Carroll of the Division of Health and Nutrition Examination Surveys, National Center for Health Statistics, Hyattsville, Md., and her associates.

The investigators examined data from the National Health and Nutrition Examination Surveys (NHANES) for 1988-1994, 1999-2002, and 2007-2010 to track temporal trends in lipid levels. Each cross-sectional survey included health-related interviews and physical examinations of a nationally representative sample of tens of thousands of adults.

In the adult population as a whole, the mean total cholesterol level declined in a linear fashion from 206 mg/dL in 1988-1994 to 203 mg/dL in 1999-2002 and to 196 mg/dL in 2007-2010. This pattern remained the same in separate analyses of men and women and in all racial/ethnic subgroups, except for Mexican American men (JAMA 2012;308:1545-54).

LDL cholesterol also decreased in a linear fashion in all adults, from 128 mg/dL in the first survey to 124 mg/dL in the second and to 119 mg/dL in the final survey. LDL cholesterol levels declined in both men and women and eventually converged, so there was no longer a difference between the sexes in the latest survey.

HDL cholesterol rose in a linear fashion from 50.7 mg/dL to 52.5 mg/dL among all adults, and also rose in separate analyses of both sexes. When the data were broken down by racial/ethnic categories, HDL cholesterol rose in whites of both sexes but not in blacks or Mexican Americans.

Triglycerides showed a slightly different pattern, rising between the late 1980s (118 mg/dL) and the early 2000s (123 mg/dL), but then falling again by 2010 (110 mg/dL).

All of these temporal trends persisted when the analysis was restricted to only the oldest adults, aged 50 and older.

During the study period, the number of adults taking lipid-lowering medications also rose, from 3.4% in 1988-1994 to 9.3% in 1999-2002 and to 15.5% in 2007-2010. However, these medications did not explain the entire improvement in lipid profiles, which also improved markedly in adults who weren’t taking them.

"The Healthy People 2010 guideline of an age-adjusted mean total cholesterol level of 200 mg/dL or less has been achieved in [all] adults, in men, in women, and in all race/ethnicity and sex subgroups. However, the age-adjusted mean LDL cholesterol level in adults of 116 mg/dL [remains] higher than the optimal range of below 100 mg/dL, [which is] associated with a lower risk of CHD [coronary heart disease]," Ms. Carroll and her colleagues said.

The researchers speculated that the favorable trends in lipid profiles might be attributable in part to a decrease in the consumption of trans-fatty acids and to other healthy lifestyle changes. The changes are unlikely to have resulted from increases in physical activity or decreases in the intake of saturated fat, as other studies have demonstrated that activity has not increased and saturated fat intake has not declined during the study period, they said.

This laboratory analysis of lipids was funded by the National Heart, Lung, and Blood Institute. NHANES is conducted by the National Center for Health Statistics and the Centers for Disease Control and Prevention. No conflicts of interest were reported.

Mean serum levels of lipids have improved among American adults since the late 1980s, according to an analysis of data from three nationwide surveys, published Oct. 17 in JAMA.

Between 1988 and 2012, mean total cholesterol, non-HDL cholesterol, and LDL cholesterol levels have declined and mean HDL cholesterol levels have risen in adults overall as well as across most racial/ethnic and gender categories, said Margaret D. Carroll of the Division of Health and Nutrition Examination Surveys, National Center for Health Statistics, Hyattsville, Md., and her associates.

The investigators examined data from the National Health and Nutrition Examination Surveys (NHANES) for 1988-1994, 1999-2002, and 2007-2010 to track temporal trends in lipid levels. Each cross-sectional survey included health-related interviews and physical examinations of a nationally representative sample of tens of thousands of adults.

In the adult population as a whole, the mean total cholesterol level declined in a linear fashion from 206 mg/dL in 1988-1994 to 203 mg/dL in 1999-2002 and to 196 mg/dL in 2007-2010. This pattern remained the same in separate analyses of men and women and in all racial/ethnic subgroups, except for Mexican American men (JAMA 2012;308:1545-54).

LDL cholesterol also decreased in a linear fashion in all adults, from 128 mg/dL in the first survey to 124 mg/dL in the second and to 119 mg/dL in the final survey. LDL cholesterol levels declined in both men and women and eventually converged, so there was no longer a difference between the sexes in the latest survey.

HDL cholesterol rose in a linear fashion from 50.7 mg/dL to 52.5 mg/dL among all adults, and also rose in separate analyses of both sexes. When the data were broken down by racial/ethnic categories, HDL cholesterol rose in whites of both sexes but not in blacks or Mexican Americans.

Triglycerides showed a slightly different pattern, rising between the late 1980s (118 mg/dL) and the early 2000s (123 mg/dL), but then falling again by 2010 (110 mg/dL).

All of these temporal trends persisted when the analysis was restricted to only the oldest adults, aged 50 and older.

During the study period, the number of adults taking lipid-lowering medications also rose, from 3.4% in 1988-1994 to 9.3% in 1999-2002 and to 15.5% in 2007-2010. However, these medications did not explain the entire improvement in lipid profiles, which also improved markedly in adults who weren’t taking them.

"The Healthy People 2010 guideline of an age-adjusted mean total cholesterol level of 200 mg/dL or less has been achieved in [all] adults, in men, in women, and in all race/ethnicity and sex subgroups. However, the age-adjusted mean LDL cholesterol level in adults of 116 mg/dL [remains] higher than the optimal range of below 100 mg/dL, [which is] associated with a lower risk of CHD [coronary heart disease]," Ms. Carroll and her colleagues said.

The researchers speculated that the favorable trends in lipid profiles might be attributable in part to a decrease in the consumption of trans-fatty acids and to other healthy lifestyle changes. The changes are unlikely to have resulted from increases in physical activity or decreases in the intake of saturated fat, as other studies have demonstrated that activity has not increased and saturated fat intake has not declined during the study period, they said.

This laboratory analysis of lipids was funded by the National Heart, Lung, and Blood Institute. NHANES is conducted by the National Center for Health Statistics and the Centers for Disease Control and Prevention. No conflicts of interest were reported.

Universal testing of colorectal cancers for DNA mismatch repair genes is the strategy most likely to identify the approximately 1%-3% of patients who have Lynch syndrome, according to a report in the Oct. 17 issue of JAMA.

Correctly identifying the small subgroup of colorectal cancer (CRC) patients who have Lynch syndrome is crucial so that their presymptomatic relatives can be found and all the affected family members can consider preventive measures to limit their morbidity and mortality.

Dr. Leticia Moreira and her colleagues in the EPICOLON consortium, an international network of colon cancer cohorts, pooled data involving 10,206 probands to show that "universal tumor MMR testing followed by germline testing offers the highest sensitivity," compared with other strategies, "although the increase in the diagnostic yield is modest" (JAMA 2012;308:1555-65).

This research highlights the limitations of various methods for identifying the subgroup of colorectal cancer patients who have Lynch syndrome and should remind clinicians "that simply asking about a family history of CRC in a first-degree relative will miss the majority of patients with Lynch syndrome," because only 43% of patients with Lynch syndrome have such a family history, wrote Dr. Uri Ladabaum and Dr. James M. Ford of the gastrointestinal cancer prevention program and clinical cancer genetics program at Stanford (Calif.) University in an editorial accompanying the study (JAMA 2012;308:1581-3).

"The majority of CRC patients do not have Lynch syndrome. But in the haystack of patients with CRC, those with Lynch syndrome are more like large knitting needles than tiny sewing needles--and a systematic search can find them," they wrote.

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is the most common form of familial colorectal cancer and is caused by germline mutations in the DNA mismatch repair (MMR) genes MSH2, MLH1, MSH6, and PMS2. Dysfunction of these genes causes an accumulation of errors during DNA replication, particularly in the repetitive sequences called microsatellites.

"As a result, tumors of patients with Lynch syndrome characteristically demonstrate MMR deficiency, defined as the presence of microsatellite instability or loss of the MMR protein expression, which is the hallmark of this disorder," the investigators wrote.

Several sets of guidelines have been issued for identifying which colorectal cancer patients should undergo tumor DNA testing to reveal these traits, but none have proved sensitive and specific enough to do an optimal job, and all have been difficult to apply in clinical practice, said Dr. Moreira of the University of Barcelona and her associates.

"Unless there is strong clinical suspicion, the majority of cases remain undetected, leading to the lack of implementation of highly effective preventive measures" including intensive screening by colonoscopy and prophylactic removal of targeted organs, they noted.

By pooling the data from four large cohorts of colorectal cancer patients around the world, the researchers compared the effectiveness of different screening strategies for identifying Lynch syndrome. Universal testing of the tumors for DNA MMR abnormalities was the most effective method, with a sensitivity of 100% and a specificity of 93%.

In comparison, use of the revised Bethesda guidelines will fail to detect approximately 12% of cases, use of the Jerusalem recommendations will fail to detect approximately 15%, and use of a "selective strategy" will fail to detect approximately 5%, the investigators reported. The specificities of the strategies ranged from 95.5% with the "selective strategy" to 97.5% with the revised Bethesda guidelines. The investigators developed the "selective strategy" for screening by using the significant predictors of Lynch syndrome identified in a multivariate analysis: colorectal cancer diagnosed at 60 years or younger, one or more first-degree relatives with CRC diagnosed at 50 years or younger, or personal history of metachronous Lynch syndrome–related tumors diagnosed at 50 years or younger.

The diagnostic yield of universal MMR testing followed by germline testing was 2.2%. In comparison, the diagnostic yield of the revised Bethesda guidelines was 2.0%, that of the Jerusalem recommendations was 1.9%, and that of "selective criteria" was 2.1%.

This study was supported by the Ministerio de Economia y Competividad; the Agnecia de Gestio-d’Ajuts Universitaris i de Recerca; the Asociacion Espaniola contra el Cancer; the Hospital Clinic of Barcelona; and the Instituto de Salud Carlos III. No financial conflicts of interest were reported. Dr. Ladabaum reported ties to Given Imaging, GE Healthcare, Abbott Molecular, Quest Diagnostics, RA Capital, Roche, Vaxart, Endosphere, and Epigenomics. Dr. Ford reported having consulted for Bristol-Myers Squibb.

Universal testing of colorectal cancers for DNA mismatch repair genes is the strategy most likely to identify the approximately 1%-3% of patients who have Lynch syndrome, according to a report in the Oct. 17 issue of JAMA.

Correctly identifying the small subgroup of colorectal cancer (CRC) patients who have Lynch syndrome is crucial so that their presymptomatic relatives can be found and all the affected family members can consider preventive measures to limit their morbidity and mortality.

Dr. Leticia Moreira and her colleagues in the EPICOLON consortium, an international network of colon cancer cohorts, pooled data involving 10,206 probands to show that "universal tumor MMR testing followed by germline testing offers the highest sensitivity," compared with other strategies, "although the increase in the diagnostic yield is modest" (JAMA 2012;308:1555-65).

This research highlights the limitations of various methods for identifying the subgroup of colorectal cancer patients who have Lynch syndrome and should remind clinicians "that simply asking about a family history of CRC in a first-degree relative will miss the majority of patients with Lynch syndrome," because only 43% of patients with Lynch syndrome have such a family history, wrote Dr. Uri Ladabaum and Dr. James M. Ford of the gastrointestinal cancer prevention program and clinical cancer genetics program at Stanford (Calif.) University in an editorial accompanying the study (JAMA 2012;308:1581-3).

"The majority of CRC patients do not have Lynch syndrome. But in the haystack of patients with CRC, those with Lynch syndrome are more like large knitting needles than tiny sewing needles--and a systematic search can find them," they wrote.

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is the most common form of familial colorectal cancer and is caused by germline mutations in the DNA mismatch repair (MMR) genes MSH2, MLH1, MSH6, and PMS2. Dysfunction of these genes causes an accumulation of errors during DNA replication, particularly in the repetitive sequences called microsatellites.

"As a result, tumors of patients with Lynch syndrome characteristically demonstrate MMR deficiency, defined as the presence of microsatellite instability or loss of the MMR protein expression, which is the hallmark of this disorder," the investigators wrote.

Several sets of guidelines have been issued for identifying which colorectal cancer patients should undergo tumor DNA testing to reveal these traits, but none have proved sensitive and specific enough to do an optimal job, and all have been difficult to apply in clinical practice, said Dr. Moreira of the University of Barcelona and her associates.

"Unless there is strong clinical suspicion, the majority of cases remain undetected, leading to the lack of implementation of highly effective preventive measures" including intensive screening by colonoscopy and prophylactic removal of targeted organs, they noted.

By pooling the data from four large cohorts of colorectal cancer patients around the world, the researchers compared the effectiveness of different screening strategies for identifying Lynch syndrome. Universal testing of the tumors for DNA MMR abnormalities was the most effective method, with a sensitivity of 100% and a specificity of 93%.

In comparison, use of the revised Bethesda guidelines will fail to detect approximately 12% of cases, use of the Jerusalem recommendations will fail to detect approximately 15%, and use of a "selective strategy" will fail to detect approximately 5%, the investigators reported. The specificities of the strategies ranged from 95.5% with the "selective strategy" to 97.5% with the revised Bethesda guidelines. The investigators developed the "selective strategy" for screening by using the significant predictors of Lynch syndrome identified in a multivariate analysis: colorectal cancer diagnosed at 60 years or younger, one or more first-degree relatives with CRC diagnosed at 50 years or younger, or personal history of metachronous Lynch syndrome–related tumors diagnosed at 50 years or younger.

The diagnostic yield of universal MMR testing followed by germline testing was 2.2%. In comparison, the diagnostic yield of the revised Bethesda guidelines was 2.0%, that of the Jerusalem recommendations was 1.9%, and that of "selective criteria" was 2.1%.

This study was supported by the Ministerio de Economia y Competividad; the Agnecia de Gestio-d’Ajuts Universitaris i de Recerca; the Asociacion Espaniola contra el Cancer; the Hospital Clinic of Barcelona; and the Instituto de Salud Carlos III. No financial conflicts of interest were reported. Dr. Ladabaum reported ties to Given Imaging, GE Healthcare, Abbott Molecular, Quest Diagnostics, RA Capital, Roche, Vaxart, Endosphere, and Epigenomics. Dr. Ford reported having consulted for Bristol-Myers Squibb.

Universal testing of colorectal cancers for DNA mismatch repair genes is the strategy most likely to identify the approximately 1%-3% of patients who have Lynch syndrome, according to a report in the Oct. 17 issue of JAMA.

Correctly identifying the small subgroup of colorectal cancer (CRC) patients who have Lynch syndrome is crucial so that their presymptomatic relatives can be found and all the affected family members can consider preventive measures to limit their morbidity and mortality.

Dr. Leticia Moreira and her colleagues in the EPICOLON consortium, an international network of colon cancer cohorts, pooled data involving 10,206 probands to show that "universal tumor MMR testing followed by germline testing offers the highest sensitivity," compared with other strategies, "although the increase in the diagnostic yield is modest" (JAMA 2012;308:1555-65).

This research highlights the limitations of various methods for identifying the subgroup of colorectal cancer patients who have Lynch syndrome and should remind clinicians "that simply asking about a family history of CRC in a first-degree relative will miss the majority of patients with Lynch syndrome," because only 43% of patients with Lynch syndrome have such a family history, wrote Dr. Uri Ladabaum and Dr. James M. Ford of the gastrointestinal cancer prevention program and clinical cancer genetics program at Stanford (Calif.) University in an editorial accompanying the study (JAMA 2012;308:1581-3).

"The majority of CRC patients do not have Lynch syndrome. But in the haystack of patients with CRC, those with Lynch syndrome are more like large knitting needles than tiny sewing needles--and a systematic search can find them," they wrote.

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is the most common form of familial colorectal cancer and is caused by germline mutations in the DNA mismatch repair (MMR) genes MSH2, MLH1, MSH6, and PMS2. Dysfunction of these genes causes an accumulation of errors during DNA replication, particularly in the repetitive sequences called microsatellites.

"As a result, tumors of patients with Lynch syndrome characteristically demonstrate MMR deficiency, defined as the presence of microsatellite instability or loss of the MMR protein expression, which is the hallmark of this disorder," the investigators wrote.

Several sets of guidelines have been issued for identifying which colorectal cancer patients should undergo tumor DNA testing to reveal these traits, but none have proved sensitive and specific enough to do an optimal job, and all have been difficult to apply in clinical practice, said Dr. Moreira of the University of Barcelona and her associates.

"Unless there is strong clinical suspicion, the majority of cases remain undetected, leading to the lack of implementation of highly effective preventive measures" including intensive screening by colonoscopy and prophylactic removal of targeted organs, they noted.

By pooling the data from four large cohorts of colorectal cancer patients around the world, the researchers compared the effectiveness of different screening strategies for identifying Lynch syndrome. Universal testing of the tumors for DNA MMR abnormalities was the most effective method, with a sensitivity of 100% and a specificity of 93%.

In comparison, use of the revised Bethesda guidelines will fail to detect approximately 12% of cases, use of the Jerusalem recommendations will fail to detect approximately 15%, and use of a "selective strategy" will fail to detect approximately 5%, the investigators reported. The specificities of the strategies ranged from 95.5% with the "selective strategy" to 97.5% with the revised Bethesda guidelines. The investigators developed the "selective strategy" for screening by using the significant predictors of Lynch syndrome identified in a multivariate analysis: colorectal cancer diagnosed at 60 years or younger, one or more first-degree relatives with CRC diagnosed at 50 years or younger, or personal history of metachronous Lynch syndrome–related tumors diagnosed at 50 years or younger.

The diagnostic yield of universal MMR testing followed by germline testing was 2.2%. In comparison, the diagnostic yield of the revised Bethesda guidelines was 2.0%, that of the Jerusalem recommendations was 1.9%, and that of "selective criteria" was 2.1%.

This study was supported by the Ministerio de Economia y Competividad; the Agnecia de Gestio-d’Ajuts Universitaris i de Recerca; the Asociacion Espaniola contra el Cancer; the Hospital Clinic of Barcelona; and the Instituto de Salud Carlos III. No financial conflicts of interest were reported. Dr. Ladabaum reported ties to Given Imaging, GE Healthcare, Abbott Molecular, Quest Diagnostics, RA Capital, Roche, Vaxart, Endosphere, and Epigenomics. Dr. Ford reported having consulted for Bristol-Myers Squibb.