Mary Ann Moon

Aspirin therapy should be continued at the time of hospital discharge in patients with cardiovascular comorbidities treated for peptic ulcer bleeding, researchers say.

Among patients taking low-dose aspirin therapy who were hospitalized for bleeding of peptic ulcers, those who stopped aspirin altogether were more than six times as likely to die or have a cardiovascular event in the near future as were patients who resumed aspirin therapy after discharge, according to a database analysis. Researcher Maryam Derogar of the Karolinska Institute, Stockholm, and her associates reported their findings in the January issue of Clinical Gastroenterology and Hepatology.

Video Source: American Gastroenterological Association YouTube channel

"Balancing between the cardioprotective effect of aspirin and the increased risk of rebleeding associated with aspirin use requires a careful clinical tradeoff," the investigators wrote (Clin. Gastroenterol. Hepatol. 2013;11:38-42).

They noted that all deaths or acute CV events in the study were among patients at least 64 years old. The study findings indicate that aspirin therapy should not be permanently discontinued in older patients at cardiovascular risk who develop bleeding peptic ulcer, but should resume after the bleeding episode is treated, they wrote.

Given the ulcerogenic properties of aspirin, "concomitant prescription of acid suppressants in the form of proton pump inhibitors is highly recommended," the researchers added.

Only one randomized clinical trial has examined the consequences of discontinuing aspirin therapy in this patient population, and it found a substantially higher risk of short-term mortality in patients who didn’t resume taking aspirin after treatment of the bleeding ulcer (Ann. Intern. Med. 2010;152:1-9). However, that trial had methodological flaws and a short follow-up of only 8 weeks, the investigators said.

They used an administrative database at their hospital to examine this issue, reviewing the medical records of 118 adults treated in 2007-2010 for upper GI bleeding. All the study subjects had endoscopically verified peptic ulcer and were taking low-dose aspirin therapy (75 mg or 160 mg daily) at the time of hospitalization.

Patients who had bleeding from sources other than peptic ulcer, such as esophageal varices or angiodysplasia, were excluded from the study.

Aspirin therapy was permanently discontinued in 40% (47) of the study subjects. Forty percent of patients (48) restarted aspirin therapy immediately after hospital discharge, and the remaining 20% (23) restarted aspirin therapy a median of 1 week later (range, 2 days to 2 months).

During a median follow-up of 2 years, 37% (44) of study subjects either died or had acute cardiovascular events.

The rate of death or acute CV events during the first 6 months of follow-up was more than sixfold higher in patients who discontinued aspirin therapy than in those who resumed aspirin therapy, with a hazard ratio of 6.8, the investigators said. The investigators adjusted the comparison to account for numerous potential confounders, such as alcohol abuse, chronic ischemic heart disease (angina), chronic heart failure, previous MI, atrial fibrillation, previous stroke or TIA, chronic renal failure, diabetes, COPD, and cancer.

Further analysis showed that the rate of mortality and acute CV events during the first 6 months of follow-up rose only in study subjects who had existing cardiovascular comorbidities at hospitalization, and did not rise in those who had no CV comorbidities. This rate was 31% in the 26 such patients who stopped aspirin therapy, compared with only 8% in the 50 who resumed aspirin therapy.

After 6 months of follow-up, the rate of mortality and acute CV events was not significantly different between patients who stopped and patients who resumed aspirin therapy.

Six percent of patients required rehospitalization for recurrent peptic ulcer bleeding during follow-up. No patients died from such rebleeding.

These findings confirm and extend those of the previous randomized clinical trial, which reported an eightfold increase in mortality during 2 months of follow-up for patients who permanently discontinued aspirin therapy, Ms. Derogar and her colleagues said.

No patients in their study who were under age 64 died or developed an acute CV event. "The results are therefore not fully applicable to younger patients and might imply that the elderly are more susceptible to discontinuation of aspirin therapy," they wrote.

Ms. Derogar reported no potential financial conflicts of interest. One of her associates reported receiving a scholarship from the Olle Engkvist Byggmastare Foundation.

Aspirin therapy should be continued at the time of hospital discharge in patients with cardiovascular comorbidities treated for peptic ulcer bleeding, researchers say.

Among patients taking low-dose aspirin therapy who were hospitalized for bleeding of peptic ulcers, those who stopped aspirin altogether were more than six times as likely to die or have a cardiovascular event in the near future as were patients who resumed aspirin therapy after discharge, according to a database analysis. Researcher Maryam Derogar of the Karolinska Institute, Stockholm, and her associates reported their findings in the January issue of Clinical Gastroenterology and Hepatology.

Video Source: American Gastroenterological Association YouTube channel

"Balancing between the cardioprotective effect of aspirin and the increased risk of rebleeding associated with aspirin use requires a careful clinical tradeoff," the investigators wrote (Clin. Gastroenterol. Hepatol. 2013;11:38-42).

They noted that all deaths or acute CV events in the study were among patients at least 64 years old. The study findings indicate that aspirin therapy should not be permanently discontinued in older patients at cardiovascular risk who develop bleeding peptic ulcer, but should resume after the bleeding episode is treated, they wrote.

Given the ulcerogenic properties of aspirin, "concomitant prescription of acid suppressants in the form of proton pump inhibitors is highly recommended," the researchers added.

Only one randomized clinical trial has examined the consequences of discontinuing aspirin therapy in this patient population, and it found a substantially higher risk of short-term mortality in patients who didn’t resume taking aspirin after treatment of the bleeding ulcer (Ann. Intern. Med. 2010;152:1-9). However, that trial had methodological flaws and a short follow-up of only 8 weeks, the investigators said.

They used an administrative database at their hospital to examine this issue, reviewing the medical records of 118 adults treated in 2007-2010 for upper GI bleeding. All the study subjects had endoscopically verified peptic ulcer and were taking low-dose aspirin therapy (75 mg or 160 mg daily) at the time of hospitalization.

Patients who had bleeding from sources other than peptic ulcer, such as esophageal varices or angiodysplasia, were excluded from the study.

Aspirin therapy was permanently discontinued in 40% (47) of the study subjects. Forty percent of patients (48) restarted aspirin therapy immediately after hospital discharge, and the remaining 20% (23) restarted aspirin therapy a median of 1 week later (range, 2 days to 2 months).

During a median follow-up of 2 years, 37% (44) of study subjects either died or had acute cardiovascular events.

The rate of death or acute CV events during the first 6 months of follow-up was more than sixfold higher in patients who discontinued aspirin therapy than in those who resumed aspirin therapy, with a hazard ratio of 6.8, the investigators said. The investigators adjusted the comparison to account for numerous potential confounders, such as alcohol abuse, chronic ischemic heart disease (angina), chronic heart failure, previous MI, atrial fibrillation, previous stroke or TIA, chronic renal failure, diabetes, COPD, and cancer.

Further analysis showed that the rate of mortality and acute CV events during the first 6 months of follow-up rose only in study subjects who had existing cardiovascular comorbidities at hospitalization, and did not rise in those who had no CV comorbidities. This rate was 31% in the 26 such patients who stopped aspirin therapy, compared with only 8% in the 50 who resumed aspirin therapy.

After 6 months of follow-up, the rate of mortality and acute CV events was not significantly different between patients who stopped and patients who resumed aspirin therapy.

Six percent of patients required rehospitalization for recurrent peptic ulcer bleeding during follow-up. No patients died from such rebleeding.

These findings confirm and extend those of the previous randomized clinical trial, which reported an eightfold increase in mortality during 2 months of follow-up for patients who permanently discontinued aspirin therapy, Ms. Derogar and her colleagues said.

No patients in their study who were under age 64 died or developed an acute CV event. "The results are therefore not fully applicable to younger patients and might imply that the elderly are more susceptible to discontinuation of aspirin therapy," they wrote.

Ms. Derogar reported no potential financial conflicts of interest. One of her associates reported receiving a scholarship from the Olle Engkvist Byggmastare Foundation.

Aspirin therapy should be continued at the time of hospital discharge in patients with cardiovascular comorbidities treated for peptic ulcer bleeding, researchers say.

Among patients taking low-dose aspirin therapy who were hospitalized for bleeding of peptic ulcers, those who stopped aspirin altogether were more than six times as likely to die or have a cardiovascular event in the near future as were patients who resumed aspirin therapy after discharge, according to a database analysis. Researcher Maryam Derogar of the Karolinska Institute, Stockholm, and her associates reported their findings in the January issue of Clinical Gastroenterology and Hepatology.

Video Source: American Gastroenterological Association YouTube channel

"Balancing between the cardioprotective effect of aspirin and the increased risk of rebleeding associated with aspirin use requires a careful clinical tradeoff," the investigators wrote (Clin. Gastroenterol. Hepatol. 2013;11:38-42).

They noted that all deaths or acute CV events in the study were among patients at least 64 years old. The study findings indicate that aspirin therapy should not be permanently discontinued in older patients at cardiovascular risk who develop bleeding peptic ulcer, but should resume after the bleeding episode is treated, they wrote.

Given the ulcerogenic properties of aspirin, "concomitant prescription of acid suppressants in the form of proton pump inhibitors is highly recommended," the researchers added.

Only one randomized clinical trial has examined the consequences of discontinuing aspirin therapy in this patient population, and it found a substantially higher risk of short-term mortality in patients who didn’t resume taking aspirin after treatment of the bleeding ulcer (Ann. Intern. Med. 2010;152:1-9). However, that trial had methodological flaws and a short follow-up of only 8 weeks, the investigators said.

They used an administrative database at their hospital to examine this issue, reviewing the medical records of 118 adults treated in 2007-2010 for upper GI bleeding. All the study subjects had endoscopically verified peptic ulcer and were taking low-dose aspirin therapy (75 mg or 160 mg daily) at the time of hospitalization.

Patients who had bleeding from sources other than peptic ulcer, such as esophageal varices or angiodysplasia, were excluded from the study.

Aspirin therapy was permanently discontinued in 40% (47) of the study subjects. Forty percent of patients (48) restarted aspirin therapy immediately after hospital discharge, and the remaining 20% (23) restarted aspirin therapy a median of 1 week later (range, 2 days to 2 months).

During a median follow-up of 2 years, 37% (44) of study subjects either died or had acute cardiovascular events.

The rate of death or acute CV events during the first 6 months of follow-up was more than sixfold higher in patients who discontinued aspirin therapy than in those who resumed aspirin therapy, with a hazard ratio of 6.8, the investigators said. The investigators adjusted the comparison to account for numerous potential confounders, such as alcohol abuse, chronic ischemic heart disease (angina), chronic heart failure, previous MI, atrial fibrillation, previous stroke or TIA, chronic renal failure, diabetes, COPD, and cancer.

Further analysis showed that the rate of mortality and acute CV events during the first 6 months of follow-up rose only in study subjects who had existing cardiovascular comorbidities at hospitalization, and did not rise in those who had no CV comorbidities. This rate was 31% in the 26 such patients who stopped aspirin therapy, compared with only 8% in the 50 who resumed aspirin therapy.

After 6 months of follow-up, the rate of mortality and acute CV events was not significantly different between patients who stopped and patients who resumed aspirin therapy.

Six percent of patients required rehospitalization for recurrent peptic ulcer bleeding during follow-up. No patients died from such rebleeding.

These findings confirm and extend those of the previous randomized clinical trial, which reported an eightfold increase in mortality during 2 months of follow-up for patients who permanently discontinued aspirin therapy, Ms. Derogar and her colleagues said.

No patients in their study who were under age 64 died or developed an acute CV event. "The results are therefore not fully applicable to younger patients and might imply that the elderly are more susceptible to discontinuation of aspirin therapy," they wrote.

Ms. Derogar reported no potential financial conflicts of interest. One of her associates reported receiving a scholarship from the Olle Engkvist Byggmastare Foundation.

Among people at high risk of developing psychosis, those who will shortly convert to psychosis show cognitive impairment in comparison to those who will not convert to psychosis during the next 2 years, according to a report published online in Psychiatry Research.

This impairment affects a broad range of cognitive functions, so unfortunately there is no specific dysfunction that consistently predicts conversion to psychosis, said Mariapaola Barbato, Ph.D., of the Hotchkiss Brain Institute, the University of Calgary (Alta.), and her associates.

Several studies have examined possible precursors to the development of psychosis, but their results have been conflicting. Most have found a variety of cognitive impairments that precede psychosis, but some have not.

Dr. Barbato and her colleagues assessed the issue in a multicenter longitudinal study involving 151 young patients (aged 12-21 years) who were at clinical high risk of developing psychosis and were followed for 2 years.

At baseline all of the study subjects met the Criteria of Prodromal Syndromes (COPS), as well as one of three other sets of criteria: the attenuated positive symptom syndrome, the brief intermittent psychotic symptom syndrome, or genetic risk and deterioration. These study subjects completed a battery of cognitive tests at baseline and again 6 months later.

A total of 25 patients converted to psychosis during the study.

Compared with patients who did not develop psychosis, those who did showed significant impairment on a composite measure of cognition as well as on individual tests of attention, verbal explicit memory, verbal and spatial working memory, verbal fluency, and executive function.

In addition, over time the subjects who did not develop psychosis either had a stable or improved performance on the battery of tests. "Improvement was seen on attention, processing speed, executive function, fine motor function, and spatial working memory. Interestingly, scores on verbal memory and verbal fluency were stable," which suggests that even though they didn’t develop psychosis, these subjects "continue to have deficits on two of the tasks that are typically most impaired in schizophrenia," the investigators said (Psychiatry Res. 2012 [http://dx.doi.org/10.1016/j.psychres.2012.10.013]).

"It seems as if in a [clinically high-risk] group that most likely has some impairment, there is a tendency for those who later develop a psychotic illness to have more impairment on a range of tasks. However ... we are not seeing specific tasks or domains that are consistently impaired except perhaps for memory and fluency, similar to what is reported in the schizophrenia literature," the investigators added.

This study is limited in that about 40% of the study subjects developed psychosis before undergoing the second round of cognitive testing and thus could not complete that testing or be included in parts of the analysis, Dr. Barbato and her associates said.

The investigators added that they were unable to address the issue of whether there is a point at which cognitive performance diverges from the norm in people who will later convert to psychosis, and that this question "is clearly a target for future research."

This study was supported by the National Institute of Mental Health. No financial conflicts of interest were reported.

Among people at high risk of developing psychosis, those who will shortly convert to psychosis show cognitive impairment in comparison to those who will not convert to psychosis during the next 2 years, according to a report published online in Psychiatry Research.

This impairment affects a broad range of cognitive functions, so unfortunately there is no specific dysfunction that consistently predicts conversion to psychosis, said Mariapaola Barbato, Ph.D., of the Hotchkiss Brain Institute, the University of Calgary (Alta.), and her associates.

Several studies have examined possible precursors to the development of psychosis, but their results have been conflicting. Most have found a variety of cognitive impairments that precede psychosis, but some have not.

Dr. Barbato and her colleagues assessed the issue in a multicenter longitudinal study involving 151 young patients (aged 12-21 years) who were at clinical high risk of developing psychosis and were followed for 2 years.

At baseline all of the study subjects met the Criteria of Prodromal Syndromes (COPS), as well as one of three other sets of criteria: the attenuated positive symptom syndrome, the brief intermittent psychotic symptom syndrome, or genetic risk and deterioration. These study subjects completed a battery of cognitive tests at baseline and again 6 months later.

A total of 25 patients converted to psychosis during the study.

Compared with patients who did not develop psychosis, those who did showed significant impairment on a composite measure of cognition as well as on individual tests of attention, verbal explicit memory, verbal and spatial working memory, verbal fluency, and executive function.

In addition, over time the subjects who did not develop psychosis either had a stable or improved performance on the battery of tests. "Improvement was seen on attention, processing speed, executive function, fine motor function, and spatial working memory. Interestingly, scores on verbal memory and verbal fluency were stable," which suggests that even though they didn’t develop psychosis, these subjects "continue to have deficits on two of the tasks that are typically most impaired in schizophrenia," the investigators said (Psychiatry Res. 2012 [http://dx.doi.org/10.1016/j.psychres.2012.10.013]).

"It seems as if in a [clinically high-risk] group that most likely has some impairment, there is a tendency for those who later develop a psychotic illness to have more impairment on a range of tasks. However ... we are not seeing specific tasks or domains that are consistently impaired except perhaps for memory and fluency, similar to what is reported in the schizophrenia literature," the investigators added.

This study is limited in that about 40% of the study subjects developed psychosis before undergoing the second round of cognitive testing and thus could not complete that testing or be included in parts of the analysis, Dr. Barbato and her associates said.

The investigators added that they were unable to address the issue of whether there is a point at which cognitive performance diverges from the norm in people who will later convert to psychosis, and that this question "is clearly a target for future research."

This study was supported by the National Institute of Mental Health. No financial conflicts of interest were reported.

Among people at high risk of developing psychosis, those who will shortly convert to psychosis show cognitive impairment in comparison to those who will not convert to psychosis during the next 2 years, according to a report published online in Psychiatry Research.

This impairment affects a broad range of cognitive functions, so unfortunately there is no specific dysfunction that consistently predicts conversion to psychosis, said Mariapaola Barbato, Ph.D., of the Hotchkiss Brain Institute, the University of Calgary (Alta.), and her associates.

Several studies have examined possible precursors to the development of psychosis, but their results have been conflicting. Most have found a variety of cognitive impairments that precede psychosis, but some have not.

Dr. Barbato and her colleagues assessed the issue in a multicenter longitudinal study involving 151 young patients (aged 12-21 years) who were at clinical high risk of developing psychosis and were followed for 2 years.

At baseline all of the study subjects met the Criteria of Prodromal Syndromes (COPS), as well as one of three other sets of criteria: the attenuated positive symptom syndrome, the brief intermittent psychotic symptom syndrome, or genetic risk and deterioration. These study subjects completed a battery of cognitive tests at baseline and again 6 months later.

A total of 25 patients converted to psychosis during the study.

Compared with patients who did not develop psychosis, those who did showed significant impairment on a composite measure of cognition as well as on individual tests of attention, verbal explicit memory, verbal and spatial working memory, verbal fluency, and executive function.

In addition, over time the subjects who did not develop psychosis either had a stable or improved performance on the battery of tests. "Improvement was seen on attention, processing speed, executive function, fine motor function, and spatial working memory. Interestingly, scores on verbal memory and verbal fluency were stable," which suggests that even though they didn’t develop psychosis, these subjects "continue to have deficits on two of the tasks that are typically most impaired in schizophrenia," the investigators said (Psychiatry Res. 2012 [http://dx.doi.org/10.1016/j.psychres.2012.10.013]).

"It seems as if in a [clinically high-risk] group that most likely has some impairment, there is a tendency for those who later develop a psychotic illness to have more impairment on a range of tasks. However ... we are not seeing specific tasks or domains that are consistently impaired except perhaps for memory and fluency, similar to what is reported in the schizophrenia literature," the investigators added.

This study is limited in that about 40% of the study subjects developed psychosis before undergoing the second round of cognitive testing and thus could not complete that testing or be included in parts of the analysis, Dr. Barbato and her associates said.

The investigators added that they were unable to address the issue of whether there is a point at which cognitive performance diverges from the norm in people who will later convert to psychosis, and that this question "is clearly a target for future research."

This study was supported by the National Institute of Mental Health. No financial conflicts of interest were reported.

Patients having their first episode of psychosis receive treatment more rapidly if they present with both hallucinations and delusions than if either type of positive symptom occurs on its own, according to a report in Psychiatry Research.

This is one of several findings of an exploratory study examining patterns of symptom onset in first-episode psychosis. To date there has been "remarkably little literature" investigating the initial development of these two key symptoms, said Dr. Michael T. Compton of George Washington University, Washington, and his associates.

Dr. Compton and his colleagues used data from a relatively large sample of 159 patients hospitalized with their first episode of psychosis "to begin to address whether meaningful clinical differences exist ... based on patterns of emergence of delusions and hallucinations in the early, pretreatment course."

The study subjects were participants in two cross-sectional studies of nonaffective psychosis who were recruited from a university-affiliated public hospital, a psychiatric emergency department, and a suburban psychiatric crisis center. They were aged 18-40 years (mean age, 24 years).

Most of these study subjects were male (75%), African American (90%), single (91%), living with family members before hospitalization (65%), and unemployed (65%).

Their diagnoses included schizophrenia, paranoid type (48%); schizophreniform disorder (17%); psychotic disorder not otherwise specified (11%); schizoaffective disorder, depressive type (6%); schizophrenia, disorganized type (4%); schizophrenia, undifferentiated type (4%); brief psychotic disorder (4%); schizoaffective disorder, bipolar type (3%); delusional disorder (2%); and schizophrenia, residual type (1%).

Both the study subjects and their family members or close friends were interviewed separately to gather information on symptom onset, demographic characteristics, and family history. Both groups completed the Symptom Onset in Schizophrenia inventory. Patient’s’ insight was self-assessed using the Birchwood Insight Scale and objectively assessed by researchers using the PANSS.

Symptom severity also was assessed using the PANSS, which included evaluations of excitement, hostility, uncooperativeness, impulse control, conceptual disorganization, mannerisms, posturing, difficulty in abstract thinking, and inattention. Global functioning was assessed using the GAF scale and the Social and Occupational Functioning Assessment (SOFA) scale.

The cohort was categorized according to whether patients had delusions only (18% of subjects), delusions preceding hallucinations by at least 1 month (20%), hallucinations preceding delusions by at least 1 month (16%), or delusions emerging concomitantly with hallucinations (46%). The four patients who had hallucinations only were excluded from the analysis because that sample size was judged too small to yield reliable statistical estimates.

So the first finding of interest was that the prevalence of first-episode psychosis patients who develop hallucinations only is quite low. "The early course of psychosis is seldom characterized by hallucinations in isolation of delusions," Dr. Compton and his associates said (Psychiatry Res. 2012;200:702-7).

This finding appears to support the theory that delusions may arise as an attempt to explain hallucinatory experiences. "Thus, once an individual at imminent risk of developing a psychotic disorder experiences hallucinations, delusional interpretations of those perceptual abnormalities are likely to follow," they noted.

Second, the pattern of symptom onset predicted the length of the delay before patients sought treatment. This interval was significantly shorter for patients with concurrent hallucinations and delusions than for any other group.

This finding makes sense, because the simultaneous emergence of two such symptoms "is likely more readily noticeable and alarming to the individual and others around him or her, being perceived as requiring more immediate treatment," the researchers said.

Efforts at early detection would benefit from the knowledge that treatment is delayed significantly longer for patients who develop only delusions or only hallucinations.

Third, scores on the PANSS and on measures of social/occupational functioning varied widely across the study groups; patients who had delusions only consistently showed less severe symptoms, less impairment, and greater function than did the other groups. It thus appears that patients who develop only delusions in their first psychotic episode may have a better overall prognosis than those who develop both delusions and hallucinations.

And fourth, despite distinct differences in symptom profiles and in function, level of insight was remarkably similar across the study groups. Measures of insight also were quite similar whether gauged by the patients themselves or by trained researchers.

This "suggests the possibility that insight is inherently related to delusional thought content," the investigators said.

Overall, this study demonstrates that the onset of positive symptoms "is a complex and varied process about which remarkably little is definitively known. Further elucidation of specific patterns of symptom emergence would deepen the field’s understanding of early-course phenomenology, and may inform efforts to improve upon nosology, prognostication, and treatment selection," Dr. Compton and his colleagues said.

This study was supported by the National Institute of Mental Health. No financial conflicts of interest were reported.

Patients having their first episode of psychosis receive treatment more rapidly if they present with both hallucinations and delusions than if either type of positive symptom occurs on its own, according to a report in Psychiatry Research.

This is one of several findings of an exploratory study examining patterns of symptom onset in first-episode psychosis. To date there has been "remarkably little literature" investigating the initial development of these two key symptoms, said Dr. Michael T. Compton of George Washington University, Washington, and his associates.

Dr. Compton and his colleagues used data from a relatively large sample of 159 patients hospitalized with their first episode of psychosis "to begin to address whether meaningful clinical differences exist ... based on patterns of emergence of delusions and hallucinations in the early, pretreatment course."

The study subjects were participants in two cross-sectional studies of nonaffective psychosis who were recruited from a university-affiliated public hospital, a psychiatric emergency department, and a suburban psychiatric crisis center. They were aged 18-40 years (mean age, 24 years).

Most of these study subjects were male (75%), African American (90%), single (91%), living with family members before hospitalization (65%), and unemployed (65%).

Their diagnoses included schizophrenia, paranoid type (48%); schizophreniform disorder (17%); psychotic disorder not otherwise specified (11%); schizoaffective disorder, depressive type (6%); schizophrenia, disorganized type (4%); schizophrenia, undifferentiated type (4%); brief psychotic disorder (4%); schizoaffective disorder, bipolar type (3%); delusional disorder (2%); and schizophrenia, residual type (1%).

Both the study subjects and their family members or close friends were interviewed separately to gather information on symptom onset, demographic characteristics, and family history. Both groups completed the Symptom Onset in Schizophrenia inventory. Patient’s’ insight was self-assessed using the Birchwood Insight Scale and objectively assessed by researchers using the PANSS.

Symptom severity also was assessed using the PANSS, which included evaluations of excitement, hostility, uncooperativeness, impulse control, conceptual disorganization, mannerisms, posturing, difficulty in abstract thinking, and inattention. Global functioning was assessed using the GAF scale and the Social and Occupational Functioning Assessment (SOFA) scale.

The cohort was categorized according to whether patients had delusions only (18% of subjects), delusions preceding hallucinations by at least 1 month (20%), hallucinations preceding delusions by at least 1 month (16%), or delusions emerging concomitantly with hallucinations (46%). The four patients who had hallucinations only were excluded from the analysis because that sample size was judged too small to yield reliable statistical estimates.

So the first finding of interest was that the prevalence of first-episode psychosis patients who develop hallucinations only is quite low. "The early course of psychosis is seldom characterized by hallucinations in isolation of delusions," Dr. Compton and his associates said (Psychiatry Res. 2012;200:702-7).

This finding appears to support the theory that delusions may arise as an attempt to explain hallucinatory experiences. "Thus, once an individual at imminent risk of developing a psychotic disorder experiences hallucinations, delusional interpretations of those perceptual abnormalities are likely to follow," they noted.

Second, the pattern of symptom onset predicted the length of the delay before patients sought treatment. This interval was significantly shorter for patients with concurrent hallucinations and delusions than for any other group.

This finding makes sense, because the simultaneous emergence of two such symptoms "is likely more readily noticeable and alarming to the individual and others around him or her, being perceived as requiring more immediate treatment," the researchers said.

Efforts at early detection would benefit from the knowledge that treatment is delayed significantly longer for patients who develop only delusions or only hallucinations.

Third, scores on the PANSS and on measures of social/occupational functioning varied widely across the study groups; patients who had delusions only consistently showed less severe symptoms, less impairment, and greater function than did the other groups. It thus appears that patients who develop only delusions in their first psychotic episode may have a better overall prognosis than those who develop both delusions and hallucinations.

And fourth, despite distinct differences in symptom profiles and in function, level of insight was remarkably similar across the study groups. Measures of insight also were quite similar whether gauged by the patients themselves or by trained researchers.

This "suggests the possibility that insight is inherently related to delusional thought content," the investigators said.

Overall, this study demonstrates that the onset of positive symptoms "is a complex and varied process about which remarkably little is definitively known. Further elucidation of specific patterns of symptom emergence would deepen the field’s understanding of early-course phenomenology, and may inform efforts to improve upon nosology, prognostication, and treatment selection," Dr. Compton and his colleagues said.

This study was supported by the National Institute of Mental Health. No financial conflicts of interest were reported.

Patients having their first episode of psychosis receive treatment more rapidly if they present with both hallucinations and delusions than if either type of positive symptom occurs on its own, according to a report in Psychiatry Research.

This is one of several findings of an exploratory study examining patterns of symptom onset in first-episode psychosis. To date there has been "remarkably little literature" investigating the initial development of these two key symptoms, said Dr. Michael T. Compton of George Washington University, Washington, and his associates.

Dr. Compton and his colleagues used data from a relatively large sample of 159 patients hospitalized with their first episode of psychosis "to begin to address whether meaningful clinical differences exist ... based on patterns of emergence of delusions and hallucinations in the early, pretreatment course."

The study subjects were participants in two cross-sectional studies of nonaffective psychosis who were recruited from a university-affiliated public hospital, a psychiatric emergency department, and a suburban psychiatric crisis center. They were aged 18-40 years (mean age, 24 years).

Most of these study subjects were male (75%), African American (90%), single (91%), living with family members before hospitalization (65%), and unemployed (65%).

Their diagnoses included schizophrenia, paranoid type (48%); schizophreniform disorder (17%); psychotic disorder not otherwise specified (11%); schizoaffective disorder, depressive type (6%); schizophrenia, disorganized type (4%); schizophrenia, undifferentiated type (4%); brief psychotic disorder (4%); schizoaffective disorder, bipolar type (3%); delusional disorder (2%); and schizophrenia, residual type (1%).

Both the study subjects and their family members or close friends were interviewed separately to gather information on symptom onset, demographic characteristics, and family history. Both groups completed the Symptom Onset in Schizophrenia inventory. Patient’s’ insight was self-assessed using the Birchwood Insight Scale and objectively assessed by researchers using the PANSS.

Symptom severity also was assessed using the PANSS, which included evaluations of excitement, hostility, uncooperativeness, impulse control, conceptual disorganization, mannerisms, posturing, difficulty in abstract thinking, and inattention. Global functioning was assessed using the GAF scale and the Social and Occupational Functioning Assessment (SOFA) scale.

The cohort was categorized according to whether patients had delusions only (18% of subjects), delusions preceding hallucinations by at least 1 month (20%), hallucinations preceding delusions by at least 1 month (16%), or delusions emerging concomitantly with hallucinations (46%). The four patients who had hallucinations only were excluded from the analysis because that sample size was judged too small to yield reliable statistical estimates.

So the first finding of interest was that the prevalence of first-episode psychosis patients who develop hallucinations only is quite low. "The early course of psychosis is seldom characterized by hallucinations in isolation of delusions," Dr. Compton and his associates said (Psychiatry Res. 2012;200:702-7).

This finding appears to support the theory that delusions may arise as an attempt to explain hallucinatory experiences. "Thus, once an individual at imminent risk of developing a psychotic disorder experiences hallucinations, delusional interpretations of those perceptual abnormalities are likely to follow," they noted.

Second, the pattern of symptom onset predicted the length of the delay before patients sought treatment. This interval was significantly shorter for patients with concurrent hallucinations and delusions than for any other group.

This finding makes sense, because the simultaneous emergence of two such symptoms "is likely more readily noticeable and alarming to the individual and others around him or her, being perceived as requiring more immediate treatment," the researchers said.

Efforts at early detection would benefit from the knowledge that treatment is delayed significantly longer for patients who develop only delusions or only hallucinations.

Third, scores on the PANSS and on measures of social/occupational functioning varied widely across the study groups; patients who had delusions only consistently showed less severe symptoms, less impairment, and greater function than did the other groups. It thus appears that patients who develop only delusions in their first psychotic episode may have a better overall prognosis than those who develop both delusions and hallucinations.

And fourth, despite distinct differences in symptom profiles and in function, level of insight was remarkably similar across the study groups. Measures of insight also were quite similar whether gauged by the patients themselves or by trained researchers.

This "suggests the possibility that insight is inherently related to delusional thought content," the investigators said.

Overall, this study demonstrates that the onset of positive symptoms "is a complex and varied process about which remarkably little is definitively known. Further elucidation of specific patterns of symptom emergence would deepen the field’s understanding of early-course phenomenology, and may inform efforts to improve upon nosology, prognostication, and treatment selection," Dr. Compton and his colleagues said.

This study was supported by the National Institute of Mental Health. No financial conflicts of interest were reported.

Tocilizumab, a monoclonal antibody that blocks interleukin-6 receptors, was found effective against severe, persistent systemic juvenile idiopathic arthritis that had been unresponsive to all previous treatments in a phase III clinical trial.

A total of 85% of the 112 study subjects achieved the primary outcome of a juvenile idiopathic arthritis (JIA) ACR 30 response, most of them after receiving only one dose of tocilizumab (Actemra). In addition, control of systemic and laboratory features of JIA was sustained throughout 1-year of follow-up using open-label therapy, "with a progressive decrease in joint involvement and clinically relevant improvement in physical function," Dr. Fabrizio De Benedetti of Ospedale Pediatrico Bambino Gesù, Rome, and his associates reported Dec. 20 in the New England Journal of Medicine.

"Almost one-third of patients had clinically inactive disease at week 52. Glucocorticoid sparing, with maintenance of disease control, was also achieved: 52% of the patients discontinued oral glucocorticoids, with the remaining patients receiving doses in the range associated with minimal toxicity," the investigators wrote.

They performed this multicenter trial in patients with "severe, persistent systemic JIA for whom no effective treatment was available, as reflected by the long duration of disease, large number of active joints, and high frequency of previous exposure to biologic agents at baseline." The ongoing 5-year study is being conducted at 43 medical centers, all members of PRINTO (the Paediatric Rheumatology International Trials Organisation) and PRCSG (the Pediatric Rheumatology Collaborative Study Group).

There were two parts to the study: a randomized double-blind placebo-controlled 12-week first phase, followed by an open-label extension in which all the subjects were eligible for active treatment for up to 5 years.

During the first phase of the study, 75 patients were randomly assigned to receive tocilizumab and 37 to receive placebo intravenously every 2 weeks. Concomitant therapy with stable doses of NSAIDs, oral glucocorticoids, and methotrexate was allowed. The study subjects were aged 2-17 years.

Study subjects were assessed every 2 weeks for the number of joints with active arthritis, the number of joints with limited range of motion, a global assessment of disease activity by a physician, the patient’s or the parent’s assessment of the patient’s overall well-being, and physical function using the Disability Index of the Childhood Health Assessment Questionnaire.

The primary outcome of this first phase was the proportion of patients who achieved a JIA American College of Rheumatology 30 response, defined as an improvement of 30% or more in three or more of the six variables of the ACR core set for JIA, plus no more than one variable worsening by more than 30%, plus the absence of fever.

At week 12, significantly more patients receiving tocilizumab met this primary outcome (85%) than patients receiving placebo (24%). Moreover, significantly more patients receiving tocilizumab achieved a JIA ACR 70 response (71% vs. 8%) or a JIA ACR 90 response (37% vs. 5%).

Systemic symptoms (fever and rash) as well as laboratory abnormalities (anemia, thrombocytosis, and hyperferritinemia) also improved significantly with tocilizumab, Dr. De Benedetti and his colleagues said (N. Engl. J. Med. 2012 Dec. 20 [doi:10.1056/NEJMoa1112802]).

Systemic JIA progressively improved in the 110 patients who continued into the extension phase of the study. At 1 year, 59% of them had a JIA ACR 90 response. Nearly half of the entire group had no actively affected joints, and 28% met the criteria for inactive disease.

A total of 82% of these patients had had moderate or severe functional impairment at baseline, but this percentage dropped to 38% at 1 year. A total of 52% of the cohort discontinued glucocorticoids altogether, and the remainder decreased their dose markedly.

"Cumulatively, 39 serious adverse events (including 18 serious infections) occurred in patients who received tocilizumab. Patients treated with tocilizumab appeared to have a 25% risk of a serious adverse event and an 11% risk of serious infection per year of treatment," the investigators wrote.

Six patients died: three who were receiving tocilizumab and three who had withdrawn from the study. Two died from pulmonary hypertension at 6 and 13 months after withdrawal, while one died from probable macrophage activation syndrome 13 months after withdrawal due to inefficacy. Of the three patients who died while taking the agent, one had suspected tension pneumothorax, one had probable streptococcal sepsis, and one died from trauma in a traffic accident.

The background mortality for patients with systemic JIA "as severe as that in our study population" is not known, the researchers noted.

Transient neutropenia occurred in 19 patients and transient increases in aminotransferase levels occurred in 21.

Data on longer-term safety are still needed, they added.

This study was sponsored and designed by Hoffmann-La Roche, which performed the data processing, data management, statistical analysis, and reporting of the results. Dr. De Benedetti and his associates reported numerous ties to industry sources.

Tocilizumab, a monoclonal antibody that blocks interleukin-6 receptors, was found effective against severe, persistent systemic juvenile idiopathic arthritis that had been unresponsive to all previous treatments in a phase III clinical trial.

A total of 85% of the 112 study subjects achieved the primary outcome of a juvenile idiopathic arthritis (JIA) ACR 30 response, most of them after receiving only one dose of tocilizumab (Actemra). In addition, control of systemic and laboratory features of JIA was sustained throughout 1-year of follow-up using open-label therapy, "with a progressive decrease in joint involvement and clinically relevant improvement in physical function," Dr. Fabrizio De Benedetti of Ospedale Pediatrico Bambino Gesù, Rome, and his associates reported Dec. 20 in the New England Journal of Medicine.

"Almost one-third of patients had clinically inactive disease at week 52. Glucocorticoid sparing, with maintenance of disease control, was also achieved: 52% of the patients discontinued oral glucocorticoids, with the remaining patients receiving doses in the range associated with minimal toxicity," the investigators wrote.

They performed this multicenter trial in patients with "severe, persistent systemic JIA for whom no effective treatment was available, as reflected by the long duration of disease, large number of active joints, and high frequency of previous exposure to biologic agents at baseline." The ongoing 5-year study is being conducted at 43 medical centers, all members of PRINTO (the Paediatric Rheumatology International Trials Organisation) and PRCSG (the Pediatric Rheumatology Collaborative Study Group).

There were two parts to the study: a randomized double-blind placebo-controlled 12-week first phase, followed by an open-label extension in which all the subjects were eligible for active treatment for up to 5 years.

During the first phase of the study, 75 patients were randomly assigned to receive tocilizumab and 37 to receive placebo intravenously every 2 weeks. Concomitant therapy with stable doses of NSAIDs, oral glucocorticoids, and methotrexate was allowed. The study subjects were aged 2-17 years.

Study subjects were assessed every 2 weeks for the number of joints with active arthritis, the number of joints with limited range of motion, a global assessment of disease activity by a physician, the patient’s or the parent’s assessment of the patient’s overall well-being, and physical function using the Disability Index of the Childhood Health Assessment Questionnaire.

The primary outcome of this first phase was the proportion of patients who achieved a JIA American College of Rheumatology 30 response, defined as an improvement of 30% or more in three or more of the six variables of the ACR core set for JIA, plus no more than one variable worsening by more than 30%, plus the absence of fever.

At week 12, significantly more patients receiving tocilizumab met this primary outcome (85%) than patients receiving placebo (24%). Moreover, significantly more patients receiving tocilizumab achieved a JIA ACR 70 response (71% vs. 8%) or a JIA ACR 90 response (37% vs. 5%).

Systemic symptoms (fever and rash) as well as laboratory abnormalities (anemia, thrombocytosis, and hyperferritinemia) also improved significantly with tocilizumab, Dr. De Benedetti and his colleagues said (N. Engl. J. Med. 2012 Dec. 20 [doi:10.1056/NEJMoa1112802]).

Systemic JIA progressively improved in the 110 patients who continued into the extension phase of the study. At 1 year, 59% of them had a JIA ACR 90 response. Nearly half of the entire group had no actively affected joints, and 28% met the criteria for inactive disease.

A total of 82% of these patients had had moderate or severe functional impairment at baseline, but this percentage dropped to 38% at 1 year. A total of 52% of the cohort discontinued glucocorticoids altogether, and the remainder decreased their dose markedly.

"Cumulatively, 39 serious adverse events (including 18 serious infections) occurred in patients who received tocilizumab. Patients treated with tocilizumab appeared to have a 25% risk of a serious adverse event and an 11% risk of serious infection per year of treatment," the investigators wrote.

Six patients died: three who were receiving tocilizumab and three who had withdrawn from the study. Two died from pulmonary hypertension at 6 and 13 months after withdrawal, while one died from probable macrophage activation syndrome 13 months after withdrawal due to inefficacy. Of the three patients who died while taking the agent, one had suspected tension pneumothorax, one had probable streptococcal sepsis, and one died from trauma in a traffic accident.

The background mortality for patients with systemic JIA "as severe as that in our study population" is not known, the researchers noted.

Transient neutropenia occurred in 19 patients and transient increases in aminotransferase levels occurred in 21.

Data on longer-term safety are still needed, they added.

This study was sponsored and designed by Hoffmann-La Roche, which performed the data processing, data management, statistical analysis, and reporting of the results. Dr. De Benedetti and his associates reported numerous ties to industry sources.

Tocilizumab, a monoclonal antibody that blocks interleukin-6 receptors, was found effective against severe, persistent systemic juvenile idiopathic arthritis that had been unresponsive to all previous treatments in a phase III clinical trial.

A total of 85% of the 112 study subjects achieved the primary outcome of a juvenile idiopathic arthritis (JIA) ACR 30 response, most of them after receiving only one dose of tocilizumab (Actemra). In addition, control of systemic and laboratory features of JIA was sustained throughout 1-year of follow-up using open-label therapy, "with a progressive decrease in joint involvement and clinically relevant improvement in physical function," Dr. Fabrizio De Benedetti of Ospedale Pediatrico Bambino Gesù, Rome, and his associates reported Dec. 20 in the New England Journal of Medicine.

"Almost one-third of patients had clinically inactive disease at week 52. Glucocorticoid sparing, with maintenance of disease control, was also achieved: 52% of the patients discontinued oral glucocorticoids, with the remaining patients receiving doses in the range associated with minimal toxicity," the investigators wrote.

They performed this multicenter trial in patients with "severe, persistent systemic JIA for whom no effective treatment was available, as reflected by the long duration of disease, large number of active joints, and high frequency of previous exposure to biologic agents at baseline." The ongoing 5-year study is being conducted at 43 medical centers, all members of PRINTO (the Paediatric Rheumatology International Trials Organisation) and PRCSG (the Pediatric Rheumatology Collaborative Study Group).

There were two parts to the study: a randomized double-blind placebo-controlled 12-week first phase, followed by an open-label extension in which all the subjects were eligible for active treatment for up to 5 years.

During the first phase of the study, 75 patients were randomly assigned to receive tocilizumab and 37 to receive placebo intravenously every 2 weeks. Concomitant therapy with stable doses of NSAIDs, oral glucocorticoids, and methotrexate was allowed. The study subjects were aged 2-17 years.

Study subjects were assessed every 2 weeks for the number of joints with active arthritis, the number of joints with limited range of motion, a global assessment of disease activity by a physician, the patient’s or the parent’s assessment of the patient’s overall well-being, and physical function using the Disability Index of the Childhood Health Assessment Questionnaire.

The primary outcome of this first phase was the proportion of patients who achieved a JIA American College of Rheumatology 30 response, defined as an improvement of 30% or more in three or more of the six variables of the ACR core set for JIA, plus no more than one variable worsening by more than 30%, plus the absence of fever.

At week 12, significantly more patients receiving tocilizumab met this primary outcome (85%) than patients receiving placebo (24%). Moreover, significantly more patients receiving tocilizumab achieved a JIA ACR 70 response (71% vs. 8%) or a JIA ACR 90 response (37% vs. 5%).

Systemic symptoms (fever and rash) as well as laboratory abnormalities (anemia, thrombocytosis, and hyperferritinemia) also improved significantly with tocilizumab, Dr. De Benedetti and his colleagues said (N. Engl. J. Med. 2012 Dec. 20 [doi:10.1056/NEJMoa1112802]).

Systemic JIA progressively improved in the 110 patients who continued into the extension phase of the study. At 1 year, 59% of them had a JIA ACR 90 response. Nearly half of the entire group had no actively affected joints, and 28% met the criteria for inactive disease.

A total of 82% of these patients had had moderate or severe functional impairment at baseline, but this percentage dropped to 38% at 1 year. A total of 52% of the cohort discontinued glucocorticoids altogether, and the remainder decreased their dose markedly.

"Cumulatively, 39 serious adverse events (including 18 serious infections) occurred in patients who received tocilizumab. Patients treated with tocilizumab appeared to have a 25% risk of a serious adverse event and an 11% risk of serious infection per year of treatment," the investigators wrote.

Six patients died: three who were receiving tocilizumab and three who had withdrawn from the study. Two died from pulmonary hypertension at 6 and 13 months after withdrawal, while one died from probable macrophage activation syndrome 13 months after withdrawal due to inefficacy. Of the three patients who died while taking the agent, one had suspected tension pneumothorax, one had probable streptococcal sepsis, and one died from trauma in a traffic accident.

The background mortality for patients with systemic JIA "as severe as that in our study population" is not known, the researchers noted.

Transient neutropenia occurred in 19 patients and transient increases in aminotransferase levels occurred in 21.

Data on longer-term safety are still needed, they added.

This study was sponsored and designed by Hoffmann-La Roche, which performed the data processing, data management, statistical analysis, and reporting of the results. Dr. De Benedetti and his associates reported numerous ties to industry sources.

Canakinumab, a monoclonal antibody that selectively inactivates interleukin-1 signaling, was effective in controlling symptoms and preventing flare-ups of systemic juvenile idiopathic arthritis in two phase III clinical trials reported online Dec. 20 in the New England Journal of Medicine.

The agent inactivated JIA in one-third of the patients in the first trial within 2 weeks, and it maintained inactive status for 2 years in 62% of the patients in the second trial. "These findings confirm, in a controlled setting, previous observations with anakinra [another anti-interleukin-1 agent], which suggested that about 40% of patients with systemic JIA have a dramatic and persistent response to anti-interleukin-1 therapy," said Dr. Nicolino Ruperto of the Istituto Giannina Gaslini, Genoa, Italy, and his associates.

"This is similar to response rates observed in some autoinflammatory diseases and in trials with anti-interleukin-6 medications," they noted.

Dr. Ruperto and his colleagues evaluated the efficacy and safety of canakinumab in the two trials, drawing study subjects from 63 medical centers that were members of PRINTO (the Paediatric Rheumatology International Trials Organisation) and PRCSG (the Pediatric Rheumatology Collaborative Study). Both trials were funded by Novartis Pharma, which also designed and managed the current study and the data analysis.

Trial 1 was a 1-month single-dose study in which 84 patients aged 2-19 years who had active systemic JIA were randomly assigned to receive either subcutaneous canakinumab (43 subjects) or a matching placebo (41 subjects) in a double-blind fashion. At 15 days, the primary outcome was assessed: an adapted JIA American College of Rheumatology 30 (JIA ACR 30) response, defined as improvement of 30% or more in three or more of the six variables in the JIA core set, with no more than one variable worsening by more than 30%, plus an absence of fever.

Thirty-six patients (84%) of the canakinumab group achieved this endpoint, compared with only four patients (10%) in the placebo group. The responders were automatically enrolled in the second, longer-term clinical trial. In addition, subjects in the placebo group who had persistent fever after day 3 were allowed to immediately enroll in trial 2 at the discretion of their treating physicians.

In trial 2, the first phase involved 177 patients who received open-label canakinumab injections every 4 weeks for 12-32 weeks. The second phase involved randomly assigning treatment responders, who had either discontinued or tapered their glucocorticoid dose, to either continued treatment (50 patients) or placebo injections (50 patients) in a double-blind fashion. In this withdrawal phase, patients who had a disease flare were switched to open-label canakinumab.

In addition, all patients who were unable to taper glucocorticoids or who had not responded to the open-label phase were permitted to enter the open-label extension of trial 2. Clinical assessments were performed monthly.

At the end of the open-label phase of trial 2, when subjects had participated for a median of 113 days and had received a median of 4 injections of canakinumab, 73% achieved an adapted JIA ACR 50 response, including 31% who had inactive disease.

During the withdrawal phase, the median time to a disease flare was 236 days for the placebo group but was "not observable" in the canakinumab group because less than half of the patients experienced a disease flare.

During extended follow-up, 74% of the canakinumab group had no disease flares, compared with only 25% of the placebo group. This represents a significant relative risk reduction of 64% regarding disease flares.

Approximately one-third of the study subjects were able to discontinue glucocorticoids completely within 7 months of beginning canakinumab, and approximately half were able to taper their dose markedly. This greatly decreased the burden of glucocorticoid toxicity, the investigators said (N. Engl. J. Med. 2012;367:2396-406).

The most common adverse effects were infections, which occurred at a similar rate between patients receiving active treatment and those receiving placebo. Neutropenia and thrombocytopenia were mostly transient and were not associated with an increase in infection or bleeding complications, the researchers said.

One patient, a 13-year-old boy who had previously been treated with anakinra and tocilizumab, was hospitalized for adenovirus gastroenteritis, which resolved. Four days later, after he received his third dose of canakinumab, he required rehospitalization for macrophage activation syndrome. He developed severe pulmonary hypertension and died 3 weeks later.

These trials were limited in their ability to assess safety, given the short duration of exposure to placebo in both trials and the use of a withdrawal design. Longer-term safety data are needed, Dr. Ruperto and his associates said.

Canakinumab, a monoclonal antibody that selectively inactivates interleukin-1 signaling, was effective in controlling symptoms and preventing flare-ups of systemic juvenile idiopathic arthritis in two phase III clinical trials reported online Dec. 20 in the New England Journal of Medicine.

The agent inactivated JIA in one-third of the patients in the first trial within 2 weeks, and it maintained inactive status for 2 years in 62% of the patients in the second trial. "These findings confirm, in a controlled setting, previous observations with anakinra [another anti-interleukin-1 agent], which suggested that about 40% of patients with systemic JIA have a dramatic and persistent response to anti-interleukin-1 therapy," said Dr. Nicolino Ruperto of the Istituto Giannina Gaslini, Genoa, Italy, and his associates.

"This is similar to response rates observed in some autoinflammatory diseases and in trials with anti-interleukin-6 medications," they noted.

Dr. Ruperto and his colleagues evaluated the efficacy and safety of canakinumab in the two trials, drawing study subjects from 63 medical centers that were members of PRINTO (the Paediatric Rheumatology International Trials Organisation) and PRCSG (the Pediatric Rheumatology Collaborative Study). Both trials were funded by Novartis Pharma, which also designed and managed the current study and the data analysis.

Trial 1 was a 1-month single-dose study in which 84 patients aged 2-19 years who had active systemic JIA were randomly assigned to receive either subcutaneous canakinumab (43 subjects) or a matching placebo (41 subjects) in a double-blind fashion. At 15 days, the primary outcome was assessed: an adapted JIA American College of Rheumatology 30 (JIA ACR 30) response, defined as improvement of 30% or more in three or more of the six variables in the JIA core set, with no more than one variable worsening by more than 30%, plus an absence of fever.

Thirty-six patients (84%) of the canakinumab group achieved this endpoint, compared with only four patients (10%) in the placebo group. The responders were automatically enrolled in the second, longer-term clinical trial. In addition, subjects in the placebo group who had persistent fever after day 3 were allowed to immediately enroll in trial 2 at the discretion of their treating physicians.

In trial 2, the first phase involved 177 patients who received open-label canakinumab injections every 4 weeks for 12-32 weeks. The second phase involved randomly assigning treatment responders, who had either discontinued or tapered their glucocorticoid dose, to either continued treatment (50 patients) or placebo injections (50 patients) in a double-blind fashion. In this withdrawal phase, patients who had a disease flare were switched to open-label canakinumab.

In addition, all patients who were unable to taper glucocorticoids or who had not responded to the open-label phase were permitted to enter the open-label extension of trial 2. Clinical assessments were performed monthly.

At the end of the open-label phase of trial 2, when subjects had participated for a median of 113 days and had received a median of 4 injections of canakinumab, 73% achieved an adapted JIA ACR 50 response, including 31% who had inactive disease.

During the withdrawal phase, the median time to a disease flare was 236 days for the placebo group but was "not observable" in the canakinumab group because less than half of the patients experienced a disease flare.

During extended follow-up, 74% of the canakinumab group had no disease flares, compared with only 25% of the placebo group. This represents a significant relative risk reduction of 64% regarding disease flares.

Approximately one-third of the study subjects were able to discontinue glucocorticoids completely within 7 months of beginning canakinumab, and approximately half were able to taper their dose markedly. This greatly decreased the burden of glucocorticoid toxicity, the investigators said (N. Engl. J. Med. 2012;367:2396-406).

The most common adverse effects were infections, which occurred at a similar rate between patients receiving active treatment and those receiving placebo. Neutropenia and thrombocytopenia were mostly transient and were not associated with an increase in infection or bleeding complications, the researchers said.

One patient, a 13-year-old boy who had previously been treated with anakinra and tocilizumab, was hospitalized for adenovirus gastroenteritis, which resolved. Four days later, after he received his third dose of canakinumab, he required rehospitalization for macrophage activation syndrome. He developed severe pulmonary hypertension and died 3 weeks later.

These trials were limited in their ability to assess safety, given the short duration of exposure to placebo in both trials and the use of a withdrawal design. Longer-term safety data are needed, Dr. Ruperto and his associates said.

Canakinumab, a monoclonal antibody that selectively inactivates interleukin-1 signaling, was effective in controlling symptoms and preventing flare-ups of systemic juvenile idiopathic arthritis in two phase III clinical trials reported online Dec. 20 in the New England Journal of Medicine.

The agent inactivated JIA in one-third of the patients in the first trial within 2 weeks, and it maintained inactive status for 2 years in 62% of the patients in the second trial. "These findings confirm, in a controlled setting, previous observations with anakinra [another anti-interleukin-1 agent], which suggested that about 40% of patients with systemic JIA have a dramatic and persistent response to anti-interleukin-1 therapy," said Dr. Nicolino Ruperto of the Istituto Giannina Gaslini, Genoa, Italy, and his associates.

"This is similar to response rates observed in some autoinflammatory diseases and in trials with anti-interleukin-6 medications," they noted.

Dr. Ruperto and his colleagues evaluated the efficacy and safety of canakinumab in the two trials, drawing study subjects from 63 medical centers that were members of PRINTO (the Paediatric Rheumatology International Trials Organisation) and PRCSG (the Pediatric Rheumatology Collaborative Study). Both trials were funded by Novartis Pharma, which also designed and managed the current study and the data analysis.

Trial 1 was a 1-month single-dose study in which 84 patients aged 2-19 years who had active systemic JIA were randomly assigned to receive either subcutaneous canakinumab (43 subjects) or a matching placebo (41 subjects) in a double-blind fashion. At 15 days, the primary outcome was assessed: an adapted JIA American College of Rheumatology 30 (JIA ACR 30) response, defined as improvement of 30% or more in three or more of the six variables in the JIA core set, with no more than one variable worsening by more than 30%, plus an absence of fever.

Thirty-six patients (84%) of the canakinumab group achieved this endpoint, compared with only four patients (10%) in the placebo group. The responders were automatically enrolled in the second, longer-term clinical trial. In addition, subjects in the placebo group who had persistent fever after day 3 were allowed to immediately enroll in trial 2 at the discretion of their treating physicians.

In trial 2, the first phase involved 177 patients who received open-label canakinumab injections every 4 weeks for 12-32 weeks. The second phase involved randomly assigning treatment responders, who had either discontinued or tapered their glucocorticoid dose, to either continued treatment (50 patients) or placebo injections (50 patients) in a double-blind fashion. In this withdrawal phase, patients who had a disease flare were switched to open-label canakinumab.

In addition, all patients who were unable to taper glucocorticoids or who had not responded to the open-label phase were permitted to enter the open-label extension of trial 2. Clinical assessments were performed monthly.

At the end of the open-label phase of trial 2, when subjects had participated for a median of 113 days and had received a median of 4 injections of canakinumab, 73% achieved an adapted JIA ACR 50 response, including 31% who had inactive disease.

During the withdrawal phase, the median time to a disease flare was 236 days for the placebo group but was "not observable" in the canakinumab group because less than half of the patients experienced a disease flare.

During extended follow-up, 74% of the canakinumab group had no disease flares, compared with only 25% of the placebo group. This represents a significant relative risk reduction of 64% regarding disease flares.

Approximately one-third of the study subjects were able to discontinue glucocorticoids completely within 7 months of beginning canakinumab, and approximately half were able to taper their dose markedly. This greatly decreased the burden of glucocorticoid toxicity, the investigators said (N. Engl. J. Med. 2012;367:2396-406).

The most common adverse effects were infections, which occurred at a similar rate between patients receiving active treatment and those receiving placebo. Neutropenia and thrombocytopenia were mostly transient and were not associated with an increase in infection or bleeding complications, the researchers said.

One patient, a 13-year-old boy who had previously been treated with anakinra and tocilizumab, was hospitalized for adenovirus gastroenteritis, which resolved. Four days later, after he received his third dose of canakinumab, he required rehospitalization for macrophage activation syndrome. He developed severe pulmonary hypertension and died 3 weeks later.

These trials were limited in their ability to assess safety, given the short duration of exposure to placebo in both trials and the use of a withdrawal design. Longer-term safety data are needed, Dr. Ruperto and his associates said.

More than 70% of women with mood disorders who become pregnant experience at least one episode of their disorder in association with the birth or, less often, the pregnancy, according to a report published online Dec. 17 in Archives of General Psychiatry.

Given that approximately 40% of all pregnancies are unplanned, the risk of perinatal episodes of mania, hypomania, psychotic depression, and nonpsychotic major depression should be discussed with all women of childbearing age who have mood disorders, even those who are not planning a pregnancy, said Dr. Ian Jones of the Institute of Psychological Medicine and Clinical Neurosciences at Cardiff (Wales) University and his associates.

In addition, "it is important that all professionals providing health care for pregnant women, including midwives, family physicians, and obstetricians, are aware of this increased risk," they wrote.

Dr. Jones and his colleagues assessed the occurrence of a range of psychological disorders associated with childbirth using data from two clinical and genetic studies of mood disorders. One study cohort included 573 women with recurrent major depression occurring in 1998-2004, and the other included 980 women with bipolar I disorder and 232 with bipolar II disorder occurring in 1991-2010.

Data were available regarding 3,017 pregnancies in 1,410 of these women. The prevalence of episodes of mania, hypomania, depression with psychosis, or nonpsychotic major depression either during pregnancy or within 1 year of childbirth was similar across the spectrum of mood disorders: 70.8% for bipolar I disorder, 70.9% for bipolar II disorder, and 73.7% for recurrent major depression.

"The importance of pregnancy and childbirth for women with mood disorders should therefore not be underestimated," the investigators said (Arch. Gen. Psychiatry 2012 Dec. 17 [doi:10.1001/jamapsychiatry.2013.279]).

In this sample, 94% of the episodes of mania or psychotic depression occurred within 4 weeks postpartum.

For women with bipolar I disorder, approximately 20% of deliveries were associated with a postpartum episode of mania or psychotic depression and an additional 25% were associated with an episode of nonpsychotic major depression. Altogether, nearly half of the deliveries in women with bipolar I disorder were associated with "an episode of a major mood disorder of some description," Dr. Jones and his associates reported.

Although the rate of such episodes was lower for both bipolar II disorder and recurrent major depression, "it would be wrong to underestimate the importance" of such episodes in these patient populations, they said. Approximately 40% of deliveries among women with bipolar II disorder or major recurrent depression were associated with episodes of these disorders.

Only a small proportion of psychotic or depressive episodes occurred during pregnancy rather than postpartum in this sample. The rate, however, was roughly twice as high in women with bipolar II disorder (18.4%) than in those with bipolar I disorder (8.6%) or recurrent major depression (11%).

The relatively few episodes of psychosis or depression that developed during pregnancy were equally distributed across the three trimesters.

Similarly, less than 4% of all episodes of psychosis or depression occurred after 6 months postpartum, and the rates were similar across the three types of mood disorder, Dr. Jones and his associates said.

This study was supported by the Wellcome Trust, the Stanley Medical Research Institute, and the Welsh Assembly Government Health Studentship. No financial conflicts were reported.

More than 70% of women with mood disorders who become pregnant experience at least one episode of their disorder in association with the birth or, less often, the pregnancy, according to a report published online Dec. 17 in Archives of General Psychiatry.

Given that approximately 40% of all pregnancies are unplanned, the risk of perinatal episodes of mania, hypomania, psychotic depression, and nonpsychotic major depression should be discussed with all women of childbearing age who have mood disorders, even those who are not planning a pregnancy, said Dr. Ian Jones of the Institute of Psychological Medicine and Clinical Neurosciences at Cardiff (Wales) University and his associates.

In addition, "it is important that all professionals providing health care for pregnant women, including midwives, family physicians, and obstetricians, are aware of this increased risk," they wrote.

Dr. Jones and his colleagues assessed the occurrence of a range of psychological disorders associated with childbirth using data from two clinical and genetic studies of mood disorders. One study cohort included 573 women with recurrent major depression occurring in 1998-2004, and the other included 980 women with bipolar I disorder and 232 with bipolar II disorder occurring in 1991-2010.

Data were available regarding 3,017 pregnancies in 1,410 of these women. The prevalence of episodes of mania, hypomania, depression with psychosis, or nonpsychotic major depression either during pregnancy or within 1 year of childbirth was similar across the spectrum of mood disorders: 70.8% for bipolar I disorder, 70.9% for bipolar II disorder, and 73.7% for recurrent major depression.

"The importance of pregnancy and childbirth for women with mood disorders should therefore not be underestimated," the investigators said (Arch. Gen. Psychiatry 2012 Dec. 17 [doi:10.1001/jamapsychiatry.2013.279]).

In this sample, 94% of the episodes of mania or psychotic depression occurred within 4 weeks postpartum.

For women with bipolar I disorder, approximately 20% of deliveries were associated with a postpartum episode of mania or psychotic depression and an additional 25% were associated with an episode of nonpsychotic major depression. Altogether, nearly half of the deliveries in women with bipolar I disorder were associated with "an episode of a major mood disorder of some description," Dr. Jones and his associates reported.

Although the rate of such episodes was lower for both bipolar II disorder and recurrent major depression, "it would be wrong to underestimate the importance" of such episodes in these patient populations, they said. Approximately 40% of deliveries among women with bipolar II disorder or major recurrent depression were associated with episodes of these disorders.

Only a small proportion of psychotic or depressive episodes occurred during pregnancy rather than postpartum in this sample. The rate, however, was roughly twice as high in women with bipolar II disorder (18.4%) than in those with bipolar I disorder (8.6%) or recurrent major depression (11%).

The relatively few episodes of psychosis or depression that developed during pregnancy were equally distributed across the three trimesters.

Similarly, less than 4% of all episodes of psychosis or depression occurred after 6 months postpartum, and the rates were similar across the three types of mood disorder, Dr. Jones and his associates said.

This study was supported by the Wellcome Trust, the Stanley Medical Research Institute, and the Welsh Assembly Government Health Studentship. No financial conflicts were reported.

More than 70% of women with mood disorders who become pregnant experience at least one episode of their disorder in association with the birth or, less often, the pregnancy, according to a report published online Dec. 17 in Archives of General Psychiatry.

Given that approximately 40% of all pregnancies are unplanned, the risk of perinatal episodes of mania, hypomania, psychotic depression, and nonpsychotic major depression should be discussed with all women of childbearing age who have mood disorders, even those who are not planning a pregnancy, said Dr. Ian Jones of the Institute of Psychological Medicine and Clinical Neurosciences at Cardiff (Wales) University and his associates.

In addition, "it is important that all professionals providing health care for pregnant women, including midwives, family physicians, and obstetricians, are aware of this increased risk," they wrote.

Dr. Jones and his colleagues assessed the occurrence of a range of psychological disorders associated with childbirth using data from two clinical and genetic studies of mood disorders. One study cohort included 573 women with recurrent major depression occurring in 1998-2004, and the other included 980 women with bipolar I disorder and 232 with bipolar II disorder occurring in 1991-2010.

Data were available regarding 3,017 pregnancies in 1,410 of these women. The prevalence of episodes of mania, hypomania, depression with psychosis, or nonpsychotic major depression either during pregnancy or within 1 year of childbirth was similar across the spectrum of mood disorders: 70.8% for bipolar I disorder, 70.9% for bipolar II disorder, and 73.7% for recurrent major depression.

"The importance of pregnancy and childbirth for women with mood disorders should therefore not be underestimated," the investigators said (Arch. Gen. Psychiatry 2012 Dec. 17 [doi:10.1001/jamapsychiatry.2013.279]).

In this sample, 94% of the episodes of mania or psychotic depression occurred within 4 weeks postpartum.

For women with bipolar I disorder, approximately 20% of deliveries were associated with a postpartum episode of mania or psychotic depression and an additional 25% were associated with an episode of nonpsychotic major depression. Altogether, nearly half of the deliveries in women with bipolar I disorder were associated with "an episode of a major mood disorder of some description," Dr. Jones and his associates reported.

Although the rate of such episodes was lower for both bipolar II disorder and recurrent major depression, "it would be wrong to underestimate the importance" of such episodes in these patient populations, they said. Approximately 40% of deliveries among women with bipolar II disorder or major recurrent depression were associated with episodes of these disorders.

Only a small proportion of psychotic or depressive episodes occurred during pregnancy rather than postpartum in this sample. The rate, however, was roughly twice as high in women with bipolar II disorder (18.4%) than in those with bipolar I disorder (8.6%) or recurrent major depression (11%).

The relatively few episodes of psychosis or depression that developed during pregnancy were equally distributed across the three trimesters.

Similarly, less than 4% of all episodes of psychosis or depression occurred after 6 months postpartum, and the rates were similar across the three types of mood disorder, Dr. Jones and his associates said.

This study was supported by the Wellcome Trust, the Stanley Medical Research Institute, and the Welsh Assembly Government Health Studentship. No financial conflicts were reported.

The prevalence of nonrefractive visual impairment rose 21% in the general U.S. adult population during the most recent decade for which statistics are available, and that increase may be related to the recent rise in the rate of diabetes, according to a report in the Dec. 12 issue of JAMA.

In what they described as the first study to have noted this increase in the visual disorder, researchers found that the overall prevalence of nonrefractive impairment among adults in the United States rose from 1.4% in 1999-2002 to 1.7% in 2005-2008.

© National Eye Institute

Notably, the largest absolute increase occurred in the youngest adults, those aged 20-39 years, across all racial and ethnic groups. The elevation also was particularly large among Mexican Americans aged 60 and older, among whom it rose from 4.6% to 8.9%, said Dr. Fang Ko of the Dana Center for Preventive Ophthalmology, Johns Hopkins University, Baltimore, and her associates.

Nonrefractive visual impairment refers to a presumably organic eye disorder that impairs vision and cannot be corrected with eyeglasses. The most common causes are age-related macular degeneration, cataracts, diabetic retinopathy, and glaucoma.

Dr. Ko and her colleagues hypothesized that the prevalence of nonrefractive visual impairment may be increasing along with the increasing prevalence of diagnosed diabetes that has been reported in the literature. Rates of any type of diabetes rose from 4.9% in 1990 to 6.5% in 1998, 7.9% in 2001, 10.7% in 2007, and 11.3% in 2010, according to epidemiologic studies.

The investigators analyzed data from the National Health and Nutrition Examination Surveys (NHANES) to compare the prevalence of nonrefractive visual impairment in U.S. adults during 1999-2002 with that during 2005-2008. Conducted by the National Center for Health Statistics, NHANES examines health-related issues in nationally representative samples of approximately 10,000 adults every 2 years.

Participants in NHANES undergo extensive physical examinations that include vision assessments. A total of 8,790 adults completed a visual acuity exam during the first study period and 9,762 did so during the second study period.

The prevalence of nonrefractive visual impairment rose from 1.4% in 1999-2002 to 1.7% in 2005-2008, a relative increase of 21%.

In a multivariate analysis, factors that were associated with the visual disorder were older age, poverty, lower educational status, and diabetes. The only one of these risk factors that increased during the study periods was diabetes. In this study population, the overall prevalence of diabetes increased from 6.5% in 1999-2002 to 8.2% in 2005-2008, and the prevalence of diabetes of at least 10 years’ duration rose from 2.8% to 3.6%.

"Other than diabetes, we were unable to identify any other reason for increasing prevalence of nonrefractive visual impairment," Dr. Ko and her associates wrote (JAMA 2012;308:2361-8).

In study subjects who didn’t have diabetes, the prevalence of nonrefractive visual impairment was 1.2% in 1999-2002 and 1.4% in 2005-2008. In contrast, the prevalence of this type of visual impairment among subjects with diabetes was 3.7% in the first study period and 5.3% in the second.

In addition, the prevalence of nonrefractive visual impairment increased with increasing duration of diabetes.

And in an additional analysis of the data, controlling for diabetes status eliminated the difference in the prevalence of nonrefractive visual impairment between the two study periods.

The largest absolute increase in the prevalence of the eye disorder occurred in the youngest adults, which "is consistent with the hypothesis that increasing prevalence of diabetes among younger U.S. residents, with subsequent increasing duration of diabetes, may be related to worsening vision," the investigators said.

If the study findings are confirmed and this trend persists, "it could result in increasing rates of disability in the U.S. population, including greater numbers of patients with end-organ diabetic damage who would require ophthalmic care," they added.

This study was supported by the Centers for Disease Control and Prevention and the David Friedman Research Grant Award. Dr. Ko reported receiving a grant from Pepose, and one of his associates reported ties to several makers of ophthalmologic products.

The prevalence of nonrefractive visual impairment rose 21% in the general U.S. adult population during the most recent decade for which statistics are available, and that increase may be related to the recent rise in the rate of diabetes, according to a report in the Dec. 12 issue of JAMA.

In what they described as the first study to have noted this increase in the visual disorder, researchers found that the overall prevalence of nonrefractive impairment among adults in the United States rose from 1.4% in 1999-2002 to 1.7% in 2005-2008.

© National Eye Institute

Notably, the largest absolute increase occurred in the youngest adults, those aged 20-39 years, across all racial and ethnic groups. The elevation also was particularly large among Mexican Americans aged 60 and older, among whom it rose from 4.6% to 8.9%, said Dr. Fang Ko of the Dana Center for Preventive Ophthalmology, Johns Hopkins University, Baltimore, and her associates.

Nonrefractive visual impairment refers to a presumably organic eye disorder that impairs vision and cannot be corrected with eyeglasses. The most common causes are age-related macular degeneration, cataracts, diabetic retinopathy, and glaucoma.

Dr. Ko and her colleagues hypothesized that the prevalence of nonrefractive visual impairment may be increasing along with the increasing prevalence of diagnosed diabetes that has been reported in the literature. Rates of any type of diabetes rose from 4.9% in 1990 to 6.5% in 1998, 7.9% in 2001, 10.7% in 2007, and 11.3% in 2010, according to epidemiologic studies.

The investigators analyzed data from the National Health and Nutrition Examination Surveys (NHANES) to compare the prevalence of nonrefractive visual impairment in U.S. adults during 1999-2002 with that during 2005-2008. Conducted by the National Center for Health Statistics, NHANES examines health-related issues in nationally representative samples of approximately 10,000 adults every 2 years.

Participants in NHANES undergo extensive physical examinations that include vision assessments. A total of 8,790 adults completed a visual acuity exam during the first study period and 9,762 did so during the second study period.

The prevalence of nonrefractive visual impairment rose from 1.4% in 1999-2002 to 1.7% in 2005-2008, a relative increase of 21%.

In a multivariate analysis, factors that were associated with the visual disorder were older age, poverty, lower educational status, and diabetes. The only one of these risk factors that increased during the study periods was diabetes. In this study population, the overall prevalence of diabetes increased from 6.5% in 1999-2002 to 8.2% in 2005-2008, and the prevalence of diabetes of at least 10 years’ duration rose from 2.8% to 3.6%.

"Other than diabetes, we were unable to identify any other reason for increasing prevalence of nonrefractive visual impairment," Dr. Ko and her associates wrote (JAMA 2012;308:2361-8).

In study subjects who didn’t have diabetes, the prevalence of nonrefractive visual impairment was 1.2% in 1999-2002 and 1.4% in 2005-2008. In contrast, the prevalence of this type of visual impairment among subjects with diabetes was 3.7% in the first study period and 5.3% in the second.

In addition, the prevalence of nonrefractive visual impairment increased with increasing duration of diabetes.

And in an additional analysis of the data, controlling for diabetes status eliminated the difference in the prevalence of nonrefractive visual impairment between the two study periods.

The largest absolute increase in the prevalence of the eye disorder occurred in the youngest adults, which "is consistent with the hypothesis that increasing prevalence of diabetes among younger U.S. residents, with subsequent increasing duration of diabetes, may be related to worsening vision," the investigators said.

If the study findings are confirmed and this trend persists, "it could result in increasing rates of disability in the U.S. population, including greater numbers of patients with end-organ diabetic damage who would require ophthalmic care," they added.

This study was supported by the Centers for Disease Control and Prevention and the David Friedman Research Grant Award. Dr. Ko reported receiving a grant from Pepose, and one of his associates reported ties to several makers of ophthalmologic products.

The prevalence of nonrefractive visual impairment rose 21% in the general U.S. adult population during the most recent decade for which statistics are available, and that increase may be related to the recent rise in the rate of diabetes, according to a report in the Dec. 12 issue of JAMA.

In what they described as the first study to have noted this increase in the visual disorder, researchers found that the overall prevalence of nonrefractive impairment among adults in the United States rose from 1.4% in 1999-2002 to 1.7% in 2005-2008.

© National Eye Institute

Notably, the largest absolute increase occurred in the youngest adults, those aged 20-39 years, across all racial and ethnic groups. The elevation also was particularly large among Mexican Americans aged 60 and older, among whom it rose from 4.6% to 8.9%, said Dr. Fang Ko of the Dana Center for Preventive Ophthalmology, Johns Hopkins University, Baltimore, and her associates.

Nonrefractive visual impairment refers to a presumably organic eye disorder that impairs vision and cannot be corrected with eyeglasses. The most common causes are age-related macular degeneration, cataracts, diabetic retinopathy, and glaucoma.

Dr. Ko and her colleagues hypothesized that the prevalence of nonrefractive visual impairment may be increasing along with the increasing prevalence of diagnosed diabetes that has been reported in the literature. Rates of any type of diabetes rose from 4.9% in 1990 to 6.5% in 1998, 7.9% in 2001, 10.7% in 2007, and 11.3% in 2010, according to epidemiologic studies.

The investigators analyzed data from the National Health and Nutrition Examination Surveys (NHANES) to compare the prevalence of nonrefractive visual impairment in U.S. adults during 1999-2002 with that during 2005-2008. Conducted by the National Center for Health Statistics, NHANES examines health-related issues in nationally representative samples of approximately 10,000 adults every 2 years.

Participants in NHANES undergo extensive physical examinations that include vision assessments. A total of 8,790 adults completed a visual acuity exam during the first study period and 9,762 did so during the second study period.

The prevalence of nonrefractive visual impairment rose from 1.4% in 1999-2002 to 1.7% in 2005-2008, a relative increase of 21%.

In a multivariate analysis, factors that were associated with the visual disorder were older age, poverty, lower educational status, and diabetes. The only one of these risk factors that increased during the study periods was diabetes. In this study population, the overall prevalence of diabetes increased from 6.5% in 1999-2002 to 8.2% in 2005-2008, and the prevalence of diabetes of at least 10 years’ duration rose from 2.8% to 3.6%.

"Other than diabetes, we were unable to identify any other reason for increasing prevalence of nonrefractive visual impairment," Dr. Ko and her associates wrote (JAMA 2012;308:2361-8).

In study subjects who didn’t have diabetes, the prevalence of nonrefractive visual impairment was 1.2% in 1999-2002 and 1.4% in 2005-2008. In contrast, the prevalence of this type of visual impairment among subjects with diabetes was 3.7% in the first study period and 5.3% in the second.

In addition, the prevalence of nonrefractive visual impairment increased with increasing duration of diabetes.

And in an additional analysis of the data, controlling for diabetes status eliminated the difference in the prevalence of nonrefractive visual impairment between the two study periods.

The largest absolute increase in the prevalence of the eye disorder occurred in the youngest adults, which "is consistent with the hypothesis that increasing prevalence of diabetes among younger U.S. residents, with subsequent increasing duration of diabetes, may be related to worsening vision," the investigators said.

If the study findings are confirmed and this trend persists, "it could result in increasing rates of disability in the U.S. population, including greater numbers of patients with end-organ diabetic damage who would require ophthalmic care," they added.

This study was supported by the Centers for Disease Control and Prevention and the David Friedman Research Grant Award. Dr. Ko reported receiving a grant from Pepose, and one of his associates reported ties to several makers of ophthalmologic products.

Two diabetes prevention programs delivered in a primary care setting succeeded at reducing body mass index in obese patients who had prediabetes, metabolic syndrome, or both, according to a report published online Dec. 10 in Archives of Internal Medicine.

Compared with usual care, both programs produced clinically significant reductions in body weight, as well as improvements in waist circumference and fasting plasma glucose levels, over a 15-month period, reported Dr. Jun Ma of the department of health services research, Palo Alto (Calif.) Medical Foundation Research Institute, and her associates.

However, these results may not be widely generalizable, because the study subjects were "primarily of high socioeconomic status and from a single primary care clinic located within the Silicon Valley of the San Francisco Bay Area and within a parent health system that was one of the first in the nation to adopt a fully functional EHR [electronic health records] system," the researchers noted.

They performed a randomized clinical trial to assess two primary care interventions based on the Diabetes Prevention Program. The study subjects were 241 adult patients at a primary care clinic who had a body mass index of at least 25 kg/m² and had prediabetes (54%), metabolic syndrome (87%), or both (41%).

The mean subject age was 53 years, and the mean BMI was 32. Women accounted for 47% of the subjects, and 78% of the subjects were white. Most had high educational attainment and a high annual income.

Participants were randomized to a coach-led, group-delivered intervention (79 subjects), a self-directed individual intervention delivered via DVD (81 subjects), or usual care (81 subjects). Both programs entailed a 3-month intensive intervention phase followed by a 12-month maintenance phase.

For the coach-led group intervention, subjects received program materials and attended 12 weekly in-person group classes that included food tastings and up to 45 minutes of guided physical activity. They also received personalized e-mail messages from the "coach" at least monthly.

For the self-directed DVD intervention, subjects received program materials plus weight scales and pedometers, and they were trained to set weight and physical activity goals and to monitor their progress toward those goals. They were shown the American Heart Association’s Web-based Heart360 program and received standardized biweekly e-mail messages to support their efforts. They also were encouraged to use e-mail to submit questions or concerns about the program.

The primary outcome measure was the decrease in BMI after 15 months, said Dr. Ma, who is also in the department of medicine at Stanford (Calif.) University, and her colleagues.

The mean decrease in BMI was 2.2 for the coach-lead intervention and 1.6 for the self-directed intervention, compared with 0.9 for usual care. Mean weight loss was 6.3 kg for the coach-led intervention and 4.5 kg for the self-directed intervention, compared with 2.4 kg for usual care.

This reflects clinically significant reductions for both intervention groups, compared with the control group, the researchers said (Arch. Intern. Med. 2012 Dec. 10 [doi: 10.1001/2013.jamainternmed.987]). The results remained robust in sensitivity analyses.

The Diabetes Prevention Program includes a final weight-loss goal of 7%. The percentage of study subjects who achieved this goal was 37% with the coach-led intervention and 36% with the self-directed intervention, compared with only 14% in the usual-care group.

Compared with the control group, patients in both intervention groups showed significant improvements in waist circumference and fasting plasma glucose levels. Those in the coach-led intervention also showed significant improvements in diastolic blood pressure and triglyceride profiles. In addition, patients in the self-directed group showed significantly improved total cholesterol levels, compared with the control group.

For women, weight loss was significantly greater for the coach-led group intervention than the self-directed individual intervention. In contrast, men responded equally well to the two strategies. "These sex-specific findings need to be confirmed in studies adequately powered to investigate sex differences," the investigators said.

Four patients in the coach-led group experienced five serious adverse events that may have been related to the intervention. There were three fractures and one case of subdural hematoma that required surgery several months after the patient fainted during a group session.

This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the American Heart Association, and the National Center for Research Resources. Dr. Ma reported no relevant financial conflicts of interest; one of her associates reported serving as a consultant to Mylan Pharmaceuticals.

Two diabetes prevention programs delivered in a primary care setting succeeded at reducing body mass index in obese patients who had prediabetes, metabolic syndrome, or both, according to a report published online Dec. 10 in Archives of Internal Medicine.

Compared with usual care, both programs produced clinically significant reductions in body weight, as well as improvements in waist circumference and fasting plasma glucose levels, over a 15-month period, reported Dr. Jun Ma of the department of health services research, Palo Alto (Calif.) Medical Foundation Research Institute, and her associates.

However, these results may not be widely generalizable, because the study subjects were "primarily of high socioeconomic status and from a single primary care clinic located within the Silicon Valley of the San Francisco Bay Area and within a parent health system that was one of the first in the nation to adopt a fully functional EHR [electronic health records] system," the researchers noted.

They performed a randomized clinical trial to assess two primary care interventions based on the Diabetes Prevention Program. The study subjects were 241 adult patients at a primary care clinic who had a body mass index of at least 25 kg/m² and had prediabetes (54%), metabolic syndrome (87%), or both (41%).

The mean subject age was 53 years, and the mean BMI was 32. Women accounted for 47% of the subjects, and 78% of the subjects were white. Most had high educational attainment and a high annual income.

Participants were randomized to a coach-led, group-delivered intervention (79 subjects), a self-directed individual intervention delivered via DVD (81 subjects), or usual care (81 subjects). Both programs entailed a 3-month intensive intervention phase followed by a 12-month maintenance phase.

For the coach-led group intervention, subjects received program materials and attended 12 weekly in-person group classes that included food tastings and up to 45 minutes of guided physical activity. They also received personalized e-mail messages from the "coach" at least monthly.

For the self-directed DVD intervention, subjects received program materials plus weight scales and pedometers, and they were trained to set weight and physical activity goals and to monitor their progress toward those goals. They were shown the American Heart Association’s Web-based Heart360 program and received standardized biweekly e-mail messages to support their efforts. They also were encouraged to use e-mail to submit questions or concerns about the program.

The primary outcome measure was the decrease in BMI after 15 months, said Dr. Ma, who is also in the department of medicine at Stanford (Calif.) University, and her colleagues.

The mean decrease in BMI was 2.2 for the coach-lead intervention and 1.6 for the self-directed intervention, compared with 0.9 for usual care. Mean weight loss was 6.3 kg for the coach-led intervention and 4.5 kg for the self-directed intervention, compared with 2.4 kg for usual care.

This reflects clinically significant reductions for both intervention groups, compared with the control group, the researchers said (Arch. Intern. Med. 2012 Dec. 10 [doi: 10.1001/2013.jamainternmed.987]). The results remained robust in sensitivity analyses.

The Diabetes Prevention Program includes a final weight-loss goal of 7%. The percentage of study subjects who achieved this goal was 37% with the coach-led intervention and 36% with the self-directed intervention, compared with only 14% in the usual-care group.

Compared with the control group, patients in both intervention groups showed significant improvements in waist circumference and fasting plasma glucose levels. Those in the coach-led intervention also showed significant improvements in diastolic blood pressure and triglyceride profiles. In addition, patients in the self-directed group showed significantly improved total cholesterol levels, compared with the control group.

For women, weight loss was significantly greater for the coach-led group intervention than the self-directed individual intervention. In contrast, men responded equally well to the two strategies. "These sex-specific findings need to be confirmed in studies adequately powered to investigate sex differences," the investigators said.

Four patients in the coach-led group experienced five serious adverse events that may have been related to the intervention. There were three fractures and one case of subdural hematoma that required surgery several months after the patient fainted during a group session.

This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the American Heart Association, and the National Center for Research Resources. Dr. Ma reported no relevant financial conflicts of interest; one of her associates reported serving as a consultant to Mylan Pharmaceuticals.

Two diabetes prevention programs delivered in a primary care setting succeeded at reducing body mass index in obese patients who had prediabetes, metabolic syndrome, or both, according to a report published online Dec. 10 in Archives of Internal Medicine.

Compared with usual care, both programs produced clinically significant reductions in body weight, as well as improvements in waist circumference and fasting plasma glucose levels, over a 15-month period, reported Dr. Jun Ma of the department of health services research, Palo Alto (Calif.) Medical Foundation Research Institute, and her associates.

However, these results may not be widely generalizable, because the study subjects were "primarily of high socioeconomic status and from a single primary care clinic located within the Silicon Valley of the San Francisco Bay Area and within a parent health system that was one of the first in the nation to adopt a fully functional EHR [electronic health records] system," the researchers noted.

They performed a randomized clinical trial to assess two primary care interventions based on the Diabetes Prevention Program. The study subjects were 241 adult patients at a primary care clinic who had a body mass index of at least 25 kg/m² and had prediabetes (54%), metabolic syndrome (87%), or both (41%).

The mean subject age was 53 years, and the mean BMI was 32. Women accounted for 47% of the subjects, and 78% of the subjects were white. Most had high educational attainment and a high annual income.

Participants were randomized to a coach-led, group-delivered intervention (79 subjects), a self-directed individual intervention delivered via DVD (81 subjects), or usual care (81 subjects). Both programs entailed a 3-month intensive intervention phase followed by a 12-month maintenance phase.

For the coach-led group intervention, subjects received program materials and attended 12 weekly in-person group classes that included food tastings and up to 45 minutes of guided physical activity. They also received personalized e-mail messages from the "coach" at least monthly.

For the self-directed DVD intervention, subjects received program materials plus weight scales and pedometers, and they were trained to set weight and physical activity goals and to monitor their progress toward those goals. They were shown the American Heart Association’s Web-based Heart360 program and received standardized biweekly e-mail messages to support their efforts. They also were encouraged to use e-mail to submit questions or concerns about the program.

The primary outcome measure was the decrease in BMI after 15 months, said Dr. Ma, who is also in the department of medicine at Stanford (Calif.) University, and her colleagues.

The mean decrease in BMI was 2.2 for the coach-lead intervention and 1.6 for the self-directed intervention, compared with 0.9 for usual care. Mean weight loss was 6.3 kg for the coach-led intervention and 4.5 kg for the self-directed intervention, compared with 2.4 kg for usual care.

This reflects clinically significant reductions for both intervention groups, compared with the control group, the researchers said (Arch. Intern. Med. 2012 Dec. 10 [doi: 10.1001/2013.jamainternmed.987]). The results remained robust in sensitivity analyses.

The Diabetes Prevention Program includes a final weight-loss goal of 7%. The percentage of study subjects who achieved this goal was 37% with the coach-led intervention and 36% with the self-directed intervention, compared with only 14% in the usual-care group.

Compared with the control group, patients in both intervention groups showed significant improvements in waist circumference and fasting plasma glucose levels. Those in the coach-led intervention also showed significant improvements in diastolic blood pressure and triglyceride profiles. In addition, patients in the self-directed group showed significantly improved total cholesterol levels, compared with the control group.

For women, weight loss was significantly greater for the coach-led group intervention than the self-directed individual intervention. In contrast, men responded equally well to the two strategies. "These sex-specific findings need to be confirmed in studies adequately powered to investigate sex differences," the investigators said.

Four patients in the coach-led group experienced five serious adverse events that may have been related to the intervention. There were three fractures and one case of subdural hematoma that required surgery several months after the patient fainted during a group session.

This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the American Heart Association, and the National Center for Research Resources. Dr. Ma reported no relevant financial conflicts of interest; one of her associates reported serving as a consultant to Mylan Pharmaceuticals.