Sharon Worcester

Depression was associated with accelerated cognitive decline among patients with type 2 diabetes in the prospective ACCORD-MIND study.

Of 2,977 adults with type 2 diabetes and a high risk of cardiovascular events who participated in the 40-month cohort ACCORD-MIND (Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes) study, 531 (18%) were considered to have depression based on a score of 10 or greater on the 9-item Patient Health Questionnaire (PHQ-9). Those patients showed greater cognitive decline than did nondepressed patients on a rigorous battery of cognitive tests, Dr. Mark D. Sullivan of the University of Washington, Seattle, and his colleagues reported online Aug. 14 in JAMA Psychiatry.

For example, estimated least squares means for decline in cognitive function were consistently greater among the depressed patients, compared with nondepressed patients, for the Digit Symbol Substitution Test (DSST), which is an omnibus test of psychomotor speed (0.72); the Rey Auditory Verbal Learning Test, which assesses memory (0.18); and the modified Stroop Test, which assesses executive function (–1.06).

"Adjustment for progressively more extensive lists of demographic and clinical covariates did little to change the differences in means or statistical significance," the investigators said, noting that when the PHQ-9 score was entered into the models as a continuous variable, the score remained significantly associated with cognitive decline on all three tests (JAMA Psychiatry 2013 Aug. 14 [doi:10.1001/jamapsychiatry.2013.1965]).

The effect of depression on cognitive decline did not differ based on insulin levels, previous cardiovascular disease, baseline cognition or age, intensive vs. standard glucose-lowering treatment, blood pressure treatment, or lipid treatment, the investigators said.

Furthermore, the effects of depression on cognitive decline were greater when the initial cognition level was included in the models for change.

"Additional exploratory analyses revealed that subjects with PHQ-9 scores 10 or more at both baseline and 20 months showed the greatest cognitive decline on the DSST during both the 0- to 20-month (mean decline, –2.0) and 20- to 40-month (mean decline, –2.7) intervals. The group with a PHQ-9 score less than 10 at baseline but 10 or more at 20 months showed nearly as large a decline (mean decline, –2.5) in the 20- to 40-month interval," Dr. Sullivan and his associates wrote.

Patients included in the study were middle-aged and older adults who had type 2 diabetes for a mean duration of 9 years and who were at high risk for cardiovascular disease.

The findings support those of prior studies that also showed a link between depression and dementia in patients with type 2 diabetes and expand those findings to show that the association exists across cognitive domains and patient groups.

"To our knowledge, this is the clearest demonstration to date that depression constitutes a risk factor for cognitive decline in the population of patients with type 2 diabetes. It also demonstrates that this effect is not limited to specific cognitive tests or specific subgroups," the investigators said.

The findings also suggest that the interaction between cognition and depression develops over relatively short periods, as it was apparent in this study in the first 40 months of follow-up, they added, noting that the interaction needs monitoring over time.

As for why depression is associated with cognitive decline in type 2 diabetes, the authors suggested several possible mechanisms, including the association between depression and poor adherence to recommendations regarding diet, exercise, smoking and medication, as well as between depression and poor glycemic control in patients with diabetes – all of which can contribute to the increased risk of dementia.

Additionally, both depression and type 2 diabetes are associated with signs of systemic inflammation, decreased insulin sensitivity, and autonomic dysfunction. These also might mediate the effects of depression on dementia risk.

Depression also is associated with "an array of biologic abnormalities that may mediate the effect of depression on cognitive decline," Dr. Sullivan and his colleagues said.

The findings are limited by numerous factors, such as the lack of a control population of patients without diabetes and the use of a self-report measure for assessing depression.

Also, since the study was observational, the investigators were not able to determine whether treatment of depression would reduce the risk of cognitive decline among patients with type 2 diabetes – a possibility that should be addressed in future studies, they said.

Despite the limitations, the findings suggest that "a potentially reversible factor may be promoting general cognitive decline in the broad population of patients with type 2 diabetes," the investigators said.

"Since dementia is one of the fastest growing and most dreaded complications of diabetes, our findings may be important for public health," they concluded.

The ACCORD-MIND study was funded through an intra-agency agreement between the National Institute on Aging; the National Heart, Lung, and Blood Institute; and the National Institute on Aging Intramural Research Program. Study drugs, equipment, and/or supplies were provided by Abbott Laboratories, Amylin Pharmaceuticals, AstraZeneca, Bayer HealthCare, Closer Healthcare, GlaxoSmithKline, King Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare, Sanofi-Aventis, and Schering-Plough.

Depression was associated with accelerated cognitive decline among patients with type 2 diabetes in the prospective ACCORD-MIND study.

Of 2,977 adults with type 2 diabetes and a high risk of cardiovascular events who participated in the 40-month cohort ACCORD-MIND (Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes) study, 531 (18%) were considered to have depression based on a score of 10 or greater on the 9-item Patient Health Questionnaire (PHQ-9). Those patients showed greater cognitive decline than did nondepressed patients on a rigorous battery of cognitive tests, Dr. Mark D. Sullivan of the University of Washington, Seattle, and his colleagues reported online Aug. 14 in JAMA Psychiatry.

For example, estimated least squares means for decline in cognitive function were consistently greater among the depressed patients, compared with nondepressed patients, for the Digit Symbol Substitution Test (DSST), which is an omnibus test of psychomotor speed (0.72); the Rey Auditory Verbal Learning Test, which assesses memory (0.18); and the modified Stroop Test, which assesses executive function (–1.06).

"Adjustment for progressively more extensive lists of demographic and clinical covariates did little to change the differences in means or statistical significance," the investigators said, noting that when the PHQ-9 score was entered into the models as a continuous variable, the score remained significantly associated with cognitive decline on all three tests (JAMA Psychiatry 2013 Aug. 14 [doi:10.1001/jamapsychiatry.2013.1965]).

The effect of depression on cognitive decline did not differ based on insulin levels, previous cardiovascular disease, baseline cognition or age, intensive vs. standard glucose-lowering treatment, blood pressure treatment, or lipid treatment, the investigators said.

Furthermore, the effects of depression on cognitive decline were greater when the initial cognition level was included in the models for change.

"Additional exploratory analyses revealed that subjects with PHQ-9 scores 10 or more at both baseline and 20 months showed the greatest cognitive decline on the DSST during both the 0- to 20-month (mean decline, –2.0) and 20- to 40-month (mean decline, –2.7) intervals. The group with a PHQ-9 score less than 10 at baseline but 10 or more at 20 months showed nearly as large a decline (mean decline, –2.5) in the 20- to 40-month interval," Dr. Sullivan and his associates wrote.

Patients included in the study were middle-aged and older adults who had type 2 diabetes for a mean duration of 9 years and who were at high risk for cardiovascular disease.

The findings support those of prior studies that also showed a link between depression and dementia in patients with type 2 diabetes and expand those findings to show that the association exists across cognitive domains and patient groups.

"To our knowledge, this is the clearest demonstration to date that depression constitutes a risk factor for cognitive decline in the population of patients with type 2 diabetes. It also demonstrates that this effect is not limited to specific cognitive tests or specific subgroups," the investigators said.

The findings also suggest that the interaction between cognition and depression develops over relatively short periods, as it was apparent in this study in the first 40 months of follow-up, they added, noting that the interaction needs monitoring over time.

As for why depression is associated with cognitive decline in type 2 diabetes, the authors suggested several possible mechanisms, including the association between depression and poor adherence to recommendations regarding diet, exercise, smoking and medication, as well as between depression and poor glycemic control in patients with diabetes – all of which can contribute to the increased risk of dementia.

Additionally, both depression and type 2 diabetes are associated with signs of systemic inflammation, decreased insulin sensitivity, and autonomic dysfunction. These also might mediate the effects of depression on dementia risk.

Depression also is associated with "an array of biologic abnormalities that may mediate the effect of depression on cognitive decline," Dr. Sullivan and his colleagues said.

The findings are limited by numerous factors, such as the lack of a control population of patients without diabetes and the use of a self-report measure for assessing depression.

Also, since the study was observational, the investigators were not able to determine whether treatment of depression would reduce the risk of cognitive decline among patients with type 2 diabetes – a possibility that should be addressed in future studies, they said.

Despite the limitations, the findings suggest that "a potentially reversible factor may be promoting general cognitive decline in the broad population of patients with type 2 diabetes," the investigators said.

"Since dementia is one of the fastest growing and most dreaded complications of diabetes, our findings may be important for public health," they concluded.

The ACCORD-MIND study was funded through an intra-agency agreement between the National Institute on Aging; the National Heart, Lung, and Blood Institute; and the National Institute on Aging Intramural Research Program. Study drugs, equipment, and/or supplies were provided by Abbott Laboratories, Amylin Pharmaceuticals, AstraZeneca, Bayer HealthCare, Closer Healthcare, GlaxoSmithKline, King Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare, Sanofi-Aventis, and Schering-Plough.

Depression was associated with accelerated cognitive decline among patients with type 2 diabetes in the prospective ACCORD-MIND study.

Of 2,977 adults with type 2 diabetes and a high risk of cardiovascular events who participated in the 40-month cohort ACCORD-MIND (Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes) study, 531 (18%) were considered to have depression based on a score of 10 or greater on the 9-item Patient Health Questionnaire (PHQ-9). Those patients showed greater cognitive decline than did nondepressed patients on a rigorous battery of cognitive tests, Dr. Mark D. Sullivan of the University of Washington, Seattle, and his colleagues reported online Aug. 14 in JAMA Psychiatry.

For example, estimated least squares means for decline in cognitive function were consistently greater among the depressed patients, compared with nondepressed patients, for the Digit Symbol Substitution Test (DSST), which is an omnibus test of psychomotor speed (0.72); the Rey Auditory Verbal Learning Test, which assesses memory (0.18); and the modified Stroop Test, which assesses executive function (–1.06).

"Adjustment for progressively more extensive lists of demographic and clinical covariates did little to change the differences in means or statistical significance," the investigators said, noting that when the PHQ-9 score was entered into the models as a continuous variable, the score remained significantly associated with cognitive decline on all three tests (JAMA Psychiatry 2013 Aug. 14 [doi:10.1001/jamapsychiatry.2013.1965]).

The effect of depression on cognitive decline did not differ based on insulin levels, previous cardiovascular disease, baseline cognition or age, intensive vs. standard glucose-lowering treatment, blood pressure treatment, or lipid treatment, the investigators said.

Furthermore, the effects of depression on cognitive decline were greater when the initial cognition level was included in the models for change.

"Additional exploratory analyses revealed that subjects with PHQ-9 scores 10 or more at both baseline and 20 months showed the greatest cognitive decline on the DSST during both the 0- to 20-month (mean decline, –2.0) and 20- to 40-month (mean decline, –2.7) intervals. The group with a PHQ-9 score less than 10 at baseline but 10 or more at 20 months showed nearly as large a decline (mean decline, –2.5) in the 20- to 40-month interval," Dr. Sullivan and his associates wrote.

Patients included in the study were middle-aged and older adults who had type 2 diabetes for a mean duration of 9 years and who were at high risk for cardiovascular disease.

The findings support those of prior studies that also showed a link between depression and dementia in patients with type 2 diabetes and expand those findings to show that the association exists across cognitive domains and patient groups.

"To our knowledge, this is the clearest demonstration to date that depression constitutes a risk factor for cognitive decline in the population of patients with type 2 diabetes. It also demonstrates that this effect is not limited to specific cognitive tests or specific subgroups," the investigators said.

The findings also suggest that the interaction between cognition and depression develops over relatively short periods, as it was apparent in this study in the first 40 months of follow-up, they added, noting that the interaction needs monitoring over time.

As for why depression is associated with cognitive decline in type 2 diabetes, the authors suggested several possible mechanisms, including the association between depression and poor adherence to recommendations regarding diet, exercise, smoking and medication, as well as between depression and poor glycemic control in patients with diabetes – all of which can contribute to the increased risk of dementia.

Additionally, both depression and type 2 diabetes are associated with signs of systemic inflammation, decreased insulin sensitivity, and autonomic dysfunction. These also might mediate the effects of depression on dementia risk.

Depression also is associated with "an array of biologic abnormalities that may mediate the effect of depression on cognitive decline," Dr. Sullivan and his colleagues said.

The findings are limited by numerous factors, such as the lack of a control population of patients without diabetes and the use of a self-report measure for assessing depression.

Also, since the study was observational, the investigators were not able to determine whether treatment of depression would reduce the risk of cognitive decline among patients with type 2 diabetes – a possibility that should be addressed in future studies, they said.

Despite the limitations, the findings suggest that "a potentially reversible factor may be promoting general cognitive decline in the broad population of patients with type 2 diabetes," the investigators said.

"Since dementia is one of the fastest growing and most dreaded complications of diabetes, our findings may be important for public health," they concluded.

The ACCORD-MIND study was funded through an intra-agency agreement between the National Institute on Aging; the National Heart, Lung, and Blood Institute; and the National Institute on Aging Intramural Research Program. Study drugs, equipment, and/or supplies were provided by Abbott Laboratories, Amylin Pharmaceuticals, AstraZeneca, Bayer HealthCare, Closer Healthcare, GlaxoSmithKline, King Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare, Sanofi-Aventis, and Schering-Plough.

Methotrexate plus infliximab was not superior to methotrexate plus intravenous corticosteroid for inducing remission in treatment-naïve patients in the Infliximab as Induction Therapy in Early Rheumatoid Arthritis (IDEA) Trial.

Participants in the 18-month, phase IV, randomized, controlled, superiority trial were treated using a rapid remission strategy followed by a treat-to-target approach. At week 50 after the start of treatment, the mean change in modified total Sharp-van der Heijde score (mTSS) was 1.20 in 55 patients in the infliximab group, compared with 2.81 in 57 patients in the intravenous corticosteroid group, Dr. Jackie L. Nam of the University of Leeds (England) and her colleagues reported (Ann. Rheum. Dis. 2013 Aug. 2 [doi:10.1136/annrheumdis-2013-203440]).

An mTSS score of less than 2.0, indicating radiographic nonprogression, was achieved by week 78 in 80.6% of patients who received infliximab and in 71% of those who received steroid (odds ratio, 1.77), and an mTSS of less than 0.5 was achieved by week 78 in 61.9% and 46.7% of patients in the groups, respectively.

The clinical and radiographic findings of this study "support the call to treat to target. They confirm benefit of methotrexate and biologic combination therapies in early DMARD [disease-modifying antirheumatic drugs]–naive RA with the potential for drug de-escalation. Additionally, they demonstrate the benefit of combination therapy with methotrexate and steroid given here initially as a single intravenous dose," Dr. Nam and her associates wrote. However, longer-term outcomes could refine the conclusions drawn thus far from the study, and some effects of the treatments remain to be determined, particularly on bone and cardiovascular risk.

An exploratory analysis suggested that more patients in the infliximab group had early remission, which was defined as a Disease Activity Score 44 (DAS44) of less than 1.6 for 6 months. Although early remission occurred in 18.3% of infliximab-treated patients and 7.1% of steroid-treated patients (OR, 5.02), the proportion of patients achieving DAS44 remission did not differ significantly between the groups at weeks 26, 50, or 78. At week 78, for example, 47.7% and 50% in the infliximab and steroid groups, respectively, achieved DAS44 remission (OR, 1.12), the investigators said.

No substantive differences in adverse events were seen between the two groups: 98.2% of patients in the infliximab group and 94.7% in the steroid group reported adverse events. The most common were noninfectious gastrointestinal events and pulmonary/upper respiratory infections. A total of 20 serious AEs occurred in 13 patients in the infliximab group and 9 occurred in 9 patients in the steroid group, and two serious infections occurred in each group, they noted.

Patients in the multicenter trial were adults aged 18-80 years with a DAS44 of 2.4 or greater and symptom duration that ranged from 3 to 12 months. They were recruited from five sites in West Yorkshire, England, from September 2006 to July 2009, and were blinded to their treatment assignment until week 26. Patients in both groups received 10 mg methotrexate weekly, increasing to 20 mg or the maximum tolerated dose by week 6, along with 5 mg folic acid daily except on the methotrexate administration day.

Additionally, the infliximab group received infusions from 250-mL bags over a 2-hour period, receiving 3 mg/kg to a maximum dose of 1,000 mg at weeks 0, 2, 6, 14, and 22. The steroid group received 250 mg intravenous methylprednisolone at week 0, and placebo infusions at weeks 2, 6, 14, and 22.

"Disease activity was measured at weeks 0, 6, 14, 22, 26, 38, 50, 68, and 78. From week 26, during an open label observation period, patients continued therapy according to a pragmatic predetermined study escalation protocol with dose adjustment or DMARD change in the infliximab group, and DMARD escalation in the intravenous steroid group if DAS44 was greater than 2.4," the investigators wrote.

Infliximab was discontinued for sustained remission, defined as DAS44 less than 1.6 for 6 months.

This study was supported by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme. Dr. Nam reported receiving speakers bureau fees from UCB. Several other study authors reported receiving grant funding, consultancy fees, and/or honoraria, and also serving on speakers bureaus or advisory boards for numerous pharmaceutical companies, including AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Chugai, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Roche-Chugai, Sanofi-Aventis, Schering-Plough, UCB, and Vertex.

Methotrexate plus infliximab was not superior to methotrexate plus intravenous corticosteroid for inducing remission in treatment-naïve patients in the Infliximab as Induction Therapy in Early Rheumatoid Arthritis (IDEA) Trial.

Participants in the 18-month, phase IV, randomized, controlled, superiority trial were treated using a rapid remission strategy followed by a treat-to-target approach. At week 50 after the start of treatment, the mean change in modified total Sharp-van der Heijde score (mTSS) was 1.20 in 55 patients in the infliximab group, compared with 2.81 in 57 patients in the intravenous corticosteroid group, Dr. Jackie L. Nam of the University of Leeds (England) and her colleagues reported (Ann. Rheum. Dis. 2013 Aug. 2 [doi:10.1136/annrheumdis-2013-203440]).

An mTSS score of less than 2.0, indicating radiographic nonprogression, was achieved by week 78 in 80.6% of patients who received infliximab and in 71% of those who received steroid (odds ratio, 1.77), and an mTSS of less than 0.5 was achieved by week 78 in 61.9% and 46.7% of patients in the groups, respectively.

The clinical and radiographic findings of this study "support the call to treat to target. They confirm benefit of methotrexate and biologic combination therapies in early DMARD [disease-modifying antirheumatic drugs]–naive RA with the potential for drug de-escalation. Additionally, they demonstrate the benefit of combination therapy with methotrexate and steroid given here initially as a single intravenous dose," Dr. Nam and her associates wrote. However, longer-term outcomes could refine the conclusions drawn thus far from the study, and some effects of the treatments remain to be determined, particularly on bone and cardiovascular risk.

An exploratory analysis suggested that more patients in the infliximab group had early remission, which was defined as a Disease Activity Score 44 (DAS44) of less than 1.6 for 6 months. Although early remission occurred in 18.3% of infliximab-treated patients and 7.1% of steroid-treated patients (OR, 5.02), the proportion of patients achieving DAS44 remission did not differ significantly between the groups at weeks 26, 50, or 78. At week 78, for example, 47.7% and 50% in the infliximab and steroid groups, respectively, achieved DAS44 remission (OR, 1.12), the investigators said.

No substantive differences in adverse events were seen between the two groups: 98.2% of patients in the infliximab group and 94.7% in the steroid group reported adverse events. The most common were noninfectious gastrointestinal events and pulmonary/upper respiratory infections. A total of 20 serious AEs occurred in 13 patients in the infliximab group and 9 occurred in 9 patients in the steroid group, and two serious infections occurred in each group, they noted.

Patients in the multicenter trial were adults aged 18-80 years with a DAS44 of 2.4 or greater and symptom duration that ranged from 3 to 12 months. They were recruited from five sites in West Yorkshire, England, from September 2006 to July 2009, and were blinded to their treatment assignment until week 26. Patients in both groups received 10 mg methotrexate weekly, increasing to 20 mg or the maximum tolerated dose by week 6, along with 5 mg folic acid daily except on the methotrexate administration day.

Additionally, the infliximab group received infusions from 250-mL bags over a 2-hour period, receiving 3 mg/kg to a maximum dose of 1,000 mg at weeks 0, 2, 6, 14, and 22. The steroid group received 250 mg intravenous methylprednisolone at week 0, and placebo infusions at weeks 2, 6, 14, and 22.

"Disease activity was measured at weeks 0, 6, 14, 22, 26, 38, 50, 68, and 78. From week 26, during an open label observation period, patients continued therapy according to a pragmatic predetermined study escalation protocol with dose adjustment or DMARD change in the infliximab group, and DMARD escalation in the intravenous steroid group if DAS44 was greater than 2.4," the investigators wrote.

Infliximab was discontinued for sustained remission, defined as DAS44 less than 1.6 for 6 months.

This study was supported by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme. Dr. Nam reported receiving speakers bureau fees from UCB. Several other study authors reported receiving grant funding, consultancy fees, and/or honoraria, and also serving on speakers bureaus or advisory boards for numerous pharmaceutical companies, including AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Chugai, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Roche-Chugai, Sanofi-Aventis, Schering-Plough, UCB, and Vertex.

Methotrexate plus infliximab was not superior to methotrexate plus intravenous corticosteroid for inducing remission in treatment-naïve patients in the Infliximab as Induction Therapy in Early Rheumatoid Arthritis (IDEA) Trial.

Participants in the 18-month, phase IV, randomized, controlled, superiority trial were treated using a rapid remission strategy followed by a treat-to-target approach. At week 50 after the start of treatment, the mean change in modified total Sharp-van der Heijde score (mTSS) was 1.20 in 55 patients in the infliximab group, compared with 2.81 in 57 patients in the intravenous corticosteroid group, Dr. Jackie L. Nam of the University of Leeds (England) and her colleagues reported (Ann. Rheum. Dis. 2013 Aug. 2 [doi:10.1136/annrheumdis-2013-203440]).

An mTSS score of less than 2.0, indicating radiographic nonprogression, was achieved by week 78 in 80.6% of patients who received infliximab and in 71% of those who received steroid (odds ratio, 1.77), and an mTSS of less than 0.5 was achieved by week 78 in 61.9% and 46.7% of patients in the groups, respectively.

The clinical and radiographic findings of this study "support the call to treat to target. They confirm benefit of methotrexate and biologic combination therapies in early DMARD [disease-modifying antirheumatic drugs]–naive RA with the potential for drug de-escalation. Additionally, they demonstrate the benefit of combination therapy with methotrexate and steroid given here initially as a single intravenous dose," Dr. Nam and her associates wrote. However, longer-term outcomes could refine the conclusions drawn thus far from the study, and some effects of the treatments remain to be determined, particularly on bone and cardiovascular risk.

An exploratory analysis suggested that more patients in the infliximab group had early remission, which was defined as a Disease Activity Score 44 (DAS44) of less than 1.6 for 6 months. Although early remission occurred in 18.3% of infliximab-treated patients and 7.1% of steroid-treated patients (OR, 5.02), the proportion of patients achieving DAS44 remission did not differ significantly between the groups at weeks 26, 50, or 78. At week 78, for example, 47.7% and 50% in the infliximab and steroid groups, respectively, achieved DAS44 remission (OR, 1.12), the investigators said.

No substantive differences in adverse events were seen between the two groups: 98.2% of patients in the infliximab group and 94.7% in the steroid group reported adverse events. The most common were noninfectious gastrointestinal events and pulmonary/upper respiratory infections. A total of 20 serious AEs occurred in 13 patients in the infliximab group and 9 occurred in 9 patients in the steroid group, and two serious infections occurred in each group, they noted.

Patients in the multicenter trial were adults aged 18-80 years with a DAS44 of 2.4 or greater and symptom duration that ranged from 3 to 12 months. They were recruited from five sites in West Yorkshire, England, from September 2006 to July 2009, and were blinded to their treatment assignment until week 26. Patients in both groups received 10 mg methotrexate weekly, increasing to 20 mg or the maximum tolerated dose by week 6, along with 5 mg folic acid daily except on the methotrexate administration day.

Additionally, the infliximab group received infusions from 250-mL bags over a 2-hour period, receiving 3 mg/kg to a maximum dose of 1,000 mg at weeks 0, 2, 6, 14, and 22. The steroid group received 250 mg intravenous methylprednisolone at week 0, and placebo infusions at weeks 2, 6, 14, and 22.

"Disease activity was measured at weeks 0, 6, 14, 22, 26, 38, 50, 68, and 78. From week 26, during an open label observation period, patients continued therapy according to a pragmatic predetermined study escalation protocol with dose adjustment or DMARD change in the infliximab group, and DMARD escalation in the intravenous steroid group if DAS44 was greater than 2.4," the investigators wrote.

Infliximab was discontinued for sustained remission, defined as DAS44 less than 1.6 for 6 months.

This study was supported by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme. Dr. Nam reported receiving speakers bureau fees from UCB. Several other study authors reported receiving grant funding, consultancy fees, and/or honoraria, and also serving on speakers bureaus or advisory boards for numerous pharmaceutical companies, including AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Chugai, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Roche-Chugai, Sanofi-Aventis, Schering-Plough, UCB, and Vertex.

Patients with hypertensive retinopathy have an increased long-term risk of stroke, according to findings from the Atherosclerosis Risk in Communities study.

Of a subset of 2,907 participants with hypertension who were part of the prospective population-based study, 1,354 had mild hypertensive retinopathy, 146 had moderate hypertensive retinopathy, and 1 had severe hypertensive retinopathy; 165 developed incident stroke, including 146 with cerebral infarction and 15 with hemorrhagic stroke, during a mean of 13 years of follow-up. After adjustment for age, sex, blood pressure, and other risk factors such as body mass index, smoking, and alcohol consumption, those with moderate hypertensive retinopathy were found to have a significantly greater risk of stroke than those without retinopathy (adjusted hazard ratio, 2.37), Yi-Ting Ong of the National University of Singapore and colleagues reported online Aug. 12 in Hypertension.

The increased stroke risk persisted even when the patients’ hypertension was well controlled medically. In the subset of all patients with well-controlled hypertension, the stroke risk in those with mild and moderate/severe hypertensive retinopathy was significantly increased compared with patients without retinopathy (adjusted HR for mild retinopathy, 1.96, and for moderate/severe retinopathy, 2.98), the investigators reported (Hypertension 2013 Aug. 12 [doi: 10.1161/hypertensionaha.113.01414]).

Atherosclerosis Risk in Communities (ARIC) study participants were aged 49-73 years at a baseline examination between 1993 and 1996. Those with prevalent hypertension in the absence of prevalent stroke or coronary heart disease for whom gradable retinal photographs were available were included in the current analysis. Excluded were people with diabetes mellitus at the time of the photographs.

The findings suggest that "the presence of these retinal microvascular changes is indicative of additional vascular risk beyond that conferred by traditional cardiovascular risk factors," the investigators said.

The findings also suggest that retinal photography – which is widely available in clinics, hospitals, and optical shops – is a potential clinical tool for stroke risk assessment.

"Histopathologic studies suggest that these hypertensive retinopathy lesions result from small vessel arteriosclerosis, and continued elevated blood pressure results in retinal ischemia and breakdown of the blood-retina barrier. They parallel hypertensive microvascular changes described in the brain, such as concentric thickening of the arterial wall, intimal thickening, medial hyperplasia, and increased vessel permeability attributable to blood-brain barrier breakdown, suggesting that retinal photography is a potential clinical tool to indirectly assess potential microvascular damage in the cerebral vasculature," they explained.

The simplified three-grade system used in this study to classify hypertensive retinopathy (mild, moderate, severe) also appears useful, as it is easily implementable in both clinical and research settings, they said.

Of note, while clinical guidelines strongly recommend the lowering of blood pressure to reduce stroke risk, patients with retinal hypertension in this study remained at increased risk of stroke despite good blood pressure control.

"This suggests that closely monitoring blood pressures and medication compliance may not be sufficient for stroke prevention in patients with hypertension. Retinal assessment may be useful especially in those with good control of hypertension," they said.

In a press statement, lead author Dr. Mohammad Kamran Ikram, also of the National University of Singapore, said it would be premature to recommend changes in clinical practice based on the findings.

"Other studies need to confirm our findings and examine whether retinal imaging can be useful in providing additional information about stroke risk in people with high blood pressure," he said.

ARIC is supported by the National Heart, Lung, and Blood Institute. Dr. Ikram received funding from the Singapore Ministry of Education Academic Research Fund and the Singapore Ministry of Health’s National Medical Research Council. The authors reported having no other disclosures.

Patients with hypertensive retinopathy have an increased long-term risk of stroke, according to findings from the Atherosclerosis Risk in Communities study.

Of a subset of 2,907 participants with hypertension who were part of the prospective population-based study, 1,354 had mild hypertensive retinopathy, 146 had moderate hypertensive retinopathy, and 1 had severe hypertensive retinopathy; 165 developed incident stroke, including 146 with cerebral infarction and 15 with hemorrhagic stroke, during a mean of 13 years of follow-up. After adjustment for age, sex, blood pressure, and other risk factors such as body mass index, smoking, and alcohol consumption, those with moderate hypertensive retinopathy were found to have a significantly greater risk of stroke than those without retinopathy (adjusted hazard ratio, 2.37), Yi-Ting Ong of the National University of Singapore and colleagues reported online Aug. 12 in Hypertension.

The increased stroke risk persisted even when the patients’ hypertension was well controlled medically. In the subset of all patients with well-controlled hypertension, the stroke risk in those with mild and moderate/severe hypertensive retinopathy was significantly increased compared with patients without retinopathy (adjusted HR for mild retinopathy, 1.96, and for moderate/severe retinopathy, 2.98), the investigators reported (Hypertension 2013 Aug. 12 [doi: 10.1161/hypertensionaha.113.01414]).

Atherosclerosis Risk in Communities (ARIC) study participants were aged 49-73 years at a baseline examination between 1993 and 1996. Those with prevalent hypertension in the absence of prevalent stroke or coronary heart disease for whom gradable retinal photographs were available were included in the current analysis. Excluded were people with diabetes mellitus at the time of the photographs.

The findings suggest that "the presence of these retinal microvascular changes is indicative of additional vascular risk beyond that conferred by traditional cardiovascular risk factors," the investigators said.

The findings also suggest that retinal photography – which is widely available in clinics, hospitals, and optical shops – is a potential clinical tool for stroke risk assessment.

"Histopathologic studies suggest that these hypertensive retinopathy lesions result from small vessel arteriosclerosis, and continued elevated blood pressure results in retinal ischemia and breakdown of the blood-retina barrier. They parallel hypertensive microvascular changes described in the brain, such as concentric thickening of the arterial wall, intimal thickening, medial hyperplasia, and increased vessel permeability attributable to blood-brain barrier breakdown, suggesting that retinal photography is a potential clinical tool to indirectly assess potential microvascular damage in the cerebral vasculature," they explained.

The simplified three-grade system used in this study to classify hypertensive retinopathy (mild, moderate, severe) also appears useful, as it is easily implementable in both clinical and research settings, they said.

Of note, while clinical guidelines strongly recommend the lowering of blood pressure to reduce stroke risk, patients with retinal hypertension in this study remained at increased risk of stroke despite good blood pressure control.

"This suggests that closely monitoring blood pressures and medication compliance may not be sufficient for stroke prevention in patients with hypertension. Retinal assessment may be useful especially in those with good control of hypertension," they said.

In a press statement, lead author Dr. Mohammad Kamran Ikram, also of the National University of Singapore, said it would be premature to recommend changes in clinical practice based on the findings.

"Other studies need to confirm our findings and examine whether retinal imaging can be useful in providing additional information about stroke risk in people with high blood pressure," he said.

ARIC is supported by the National Heart, Lung, and Blood Institute. Dr. Ikram received funding from the Singapore Ministry of Education Academic Research Fund and the Singapore Ministry of Health’s National Medical Research Council. The authors reported having no other disclosures.

Patients with hypertensive retinopathy have an increased long-term risk of stroke, according to findings from the Atherosclerosis Risk in Communities study.

Of a subset of 2,907 participants with hypertension who were part of the prospective population-based study, 1,354 had mild hypertensive retinopathy, 146 had moderate hypertensive retinopathy, and 1 had severe hypertensive retinopathy; 165 developed incident stroke, including 146 with cerebral infarction and 15 with hemorrhagic stroke, during a mean of 13 years of follow-up. After adjustment for age, sex, blood pressure, and other risk factors such as body mass index, smoking, and alcohol consumption, those with moderate hypertensive retinopathy were found to have a significantly greater risk of stroke than those without retinopathy (adjusted hazard ratio, 2.37), Yi-Ting Ong of the National University of Singapore and colleagues reported online Aug. 12 in Hypertension.

The increased stroke risk persisted even when the patients’ hypertension was well controlled medically. In the subset of all patients with well-controlled hypertension, the stroke risk in those with mild and moderate/severe hypertensive retinopathy was significantly increased compared with patients without retinopathy (adjusted HR for mild retinopathy, 1.96, and for moderate/severe retinopathy, 2.98), the investigators reported (Hypertension 2013 Aug. 12 [doi: 10.1161/hypertensionaha.113.01414]).

Atherosclerosis Risk in Communities (ARIC) study participants were aged 49-73 years at a baseline examination between 1993 and 1996. Those with prevalent hypertension in the absence of prevalent stroke or coronary heart disease for whom gradable retinal photographs were available were included in the current analysis. Excluded were people with diabetes mellitus at the time of the photographs.

The findings suggest that "the presence of these retinal microvascular changes is indicative of additional vascular risk beyond that conferred by traditional cardiovascular risk factors," the investigators said.

The findings also suggest that retinal photography – which is widely available in clinics, hospitals, and optical shops – is a potential clinical tool for stroke risk assessment.

"Histopathologic studies suggest that these hypertensive retinopathy lesions result from small vessel arteriosclerosis, and continued elevated blood pressure results in retinal ischemia and breakdown of the blood-retina barrier. They parallel hypertensive microvascular changes described in the brain, such as concentric thickening of the arterial wall, intimal thickening, medial hyperplasia, and increased vessel permeability attributable to blood-brain barrier breakdown, suggesting that retinal photography is a potential clinical tool to indirectly assess potential microvascular damage in the cerebral vasculature," they explained.

The simplified three-grade system used in this study to classify hypertensive retinopathy (mild, moderate, severe) also appears useful, as it is easily implementable in both clinical and research settings, they said.

Of note, while clinical guidelines strongly recommend the lowering of blood pressure to reduce stroke risk, patients with retinal hypertension in this study remained at increased risk of stroke despite good blood pressure control.

"This suggests that closely monitoring blood pressures and medication compliance may not be sufficient for stroke prevention in patients with hypertension. Retinal assessment may be useful especially in those with good control of hypertension," they said.

In a press statement, lead author Dr. Mohammad Kamran Ikram, also of the National University of Singapore, said it would be premature to recommend changes in clinical practice based on the findings.

"Other studies need to confirm our findings and examine whether retinal imaging can be useful in providing additional information about stroke risk in people with high blood pressure," he said.

ARIC is supported by the National Heart, Lung, and Blood Institute. Dr. Ikram received funding from the Singapore Ministry of Education Academic Research Fund and the Singapore Ministry of Health’s National Medical Research Council. The authors reported having no other disclosures.

Children who experience functional abdominal pain are at increased risk of anxiety that persists into early adulthood, findings from a prospective case-control study suggest.

The lifetime risk of an anxiety disorder in 332 patients who were diagnosed with functional abdominal pain (FAP) during childhood was 51.2%, compared with 20.4% in 147 control subjects. After controlling for age and gender, those who experienced FAP in childhood had a nearly fivefold increased lifetime anxiety disorder risk (odds ratio, 4.59), Grace D. Shelby, Ph.D., of Vanderbilt University, Nashville, Tenn., and her colleagues reported online Aug. 12 in Pediatrics.

"Similarly, a significantly higher proportion of the FAP group met criteria for [one or more] current anxiety disorders at follow-up, compared with the control group (30.4% vs. 11.6%). The odds ratio for any current anxiety disorder was 3.57 times greater for FAP, compared with controls," the investigators said (Pediatrics 2013 Aug. 12[doi:10.1542/peds.2012-2191]).

The most common anxiety disorder in the FAP group was social anxiety disorder, which was diagnosed in 25.9% of the patients, whose lifetime risk of social anxiety was nearly six times greater than the risk among controls (OR, 5.84) and whose risk for current social anxiety disorder at follow-up was more than eight times greater than the risk among controls (OR, 8.14), they said.

Patients with functional abdominal pain also were at increased lifetime risk of depressive disorders, compared with controls (40.1% vs. 16.3%; OR, 2.62), although current depression risk was low and did not differ between the groups.

The risk of both anxiety disorders and depressive disorders was greatest among those with FAP who met Rome III Diagnostic Questionnaire for Functional Gastrointestinal Disorders criteria for an abdominal pain-related functional gastrointestinal disorder (FGID) at follow-up.

In most study participants who met criteria for a lifetime anxiety disorder, onset occurred during childhood and the age of onset did not differ between the cases and controls (mean age of onset, 7.78 years and 8.97 years, respectively). Conversely, the onset of depressive disorders was usually during adolescence; the mean age of onset for depression also did not differ between cases and controls (mean of 15.96 and 14.92 years, respectively).

Most FAP patients with a lifetime anxiety disorder (72.62%) reported onset before their FAP evaluation, and most of those with lifetime depressive disorders (77.27%) reported onset after their FAP evaluation, the investigators said.

Patients in this study were consecutive new patients, aged 8-17 years, who were evaluated between 1993 and 2007 at the Vanderbilt pediatric gastroenterology service for abdominal pain lasting 3 or more months. Control subjects were children without abdominal pain who were recruited from area schools and who participated in a health survey in the same time period. Those who had reached at least age 12 years, and who were initially evaluated at least 4 years prior, were included in the follow-up study and were followed prospectively for a mean of 8.49 years; subjects were re-evaluated at a mean age of 20.01 years.

The findings support those of a smaller study published in 2001 (Pediatrics 2001;108:e1) that also showed a link between recurrent abdominal pain in childhood and increased likelihood of meeting diagnostic criteria for lifetime and current anxiety disorders in adulthood. The current findings "underscore the importance of a biopsychosocial approach to FAP that includes screening for anxiety and depression," the investigators said, adding that future research should assess whether interventions for mental health conditions in FAP also improve abdominal pain outcomes.

This study was supported by grants from the National Institute on Child Health and Development, Vanderbilt Kennedy Center, Vanderbilt Digestive Disease Research Center, and the Vanderbilt Clinical and Translational Science Award from the National Institutes of Health. Dr. Shelby was supported by a training grant from the National Institute of Mental Health. The authors reported having no other disclosures.

Children who experience functional abdominal pain are at increased risk of anxiety that persists into early adulthood, findings from a prospective case-control study suggest.

The lifetime risk of an anxiety disorder in 332 patients who were diagnosed with functional abdominal pain (FAP) during childhood was 51.2%, compared with 20.4% in 147 control subjects. After controlling for age and gender, those who experienced FAP in childhood had a nearly fivefold increased lifetime anxiety disorder risk (odds ratio, 4.59), Grace D. Shelby, Ph.D., of Vanderbilt University, Nashville, Tenn., and her colleagues reported online Aug. 12 in Pediatrics.

"Similarly, a significantly higher proportion of the FAP group met criteria for [one or more] current anxiety disorders at follow-up, compared with the control group (30.4% vs. 11.6%). The odds ratio for any current anxiety disorder was 3.57 times greater for FAP, compared with controls," the investigators said (Pediatrics 2013 Aug. 12[doi:10.1542/peds.2012-2191]).

The most common anxiety disorder in the FAP group was social anxiety disorder, which was diagnosed in 25.9% of the patients, whose lifetime risk of social anxiety was nearly six times greater than the risk among controls (OR, 5.84) and whose risk for current social anxiety disorder at follow-up was more than eight times greater than the risk among controls (OR, 8.14), they said.

Patients with functional abdominal pain also were at increased lifetime risk of depressive disorders, compared with controls (40.1% vs. 16.3%; OR, 2.62), although current depression risk was low and did not differ between the groups.

The risk of both anxiety disorders and depressive disorders was greatest among those with FAP who met Rome III Diagnostic Questionnaire for Functional Gastrointestinal Disorders criteria for an abdominal pain-related functional gastrointestinal disorder (FGID) at follow-up.

In most study participants who met criteria for a lifetime anxiety disorder, onset occurred during childhood and the age of onset did not differ between the cases and controls (mean age of onset, 7.78 years and 8.97 years, respectively). Conversely, the onset of depressive disorders was usually during adolescence; the mean age of onset for depression also did not differ between cases and controls (mean of 15.96 and 14.92 years, respectively).

Most FAP patients with a lifetime anxiety disorder (72.62%) reported onset before their FAP evaluation, and most of those with lifetime depressive disorders (77.27%) reported onset after their FAP evaluation, the investigators said.

Patients in this study were consecutive new patients, aged 8-17 years, who were evaluated between 1993 and 2007 at the Vanderbilt pediatric gastroenterology service for abdominal pain lasting 3 or more months. Control subjects were children without abdominal pain who were recruited from area schools and who participated in a health survey in the same time period. Those who had reached at least age 12 years, and who were initially evaluated at least 4 years prior, were included in the follow-up study and were followed prospectively for a mean of 8.49 years; subjects were re-evaluated at a mean age of 20.01 years.

The findings support those of a smaller study published in 2001 (Pediatrics 2001;108:e1) that also showed a link between recurrent abdominal pain in childhood and increased likelihood of meeting diagnostic criteria for lifetime and current anxiety disorders in adulthood. The current findings "underscore the importance of a biopsychosocial approach to FAP that includes screening for anxiety and depression," the investigators said, adding that future research should assess whether interventions for mental health conditions in FAP also improve abdominal pain outcomes.

This study was supported by grants from the National Institute on Child Health and Development, Vanderbilt Kennedy Center, Vanderbilt Digestive Disease Research Center, and the Vanderbilt Clinical and Translational Science Award from the National Institutes of Health. Dr. Shelby was supported by a training grant from the National Institute of Mental Health. The authors reported having no other disclosures.

Children who experience functional abdominal pain are at increased risk of anxiety that persists into early adulthood, findings from a prospective case-control study suggest.

The lifetime risk of an anxiety disorder in 332 patients who were diagnosed with functional abdominal pain (FAP) during childhood was 51.2%, compared with 20.4% in 147 control subjects. After controlling for age and gender, those who experienced FAP in childhood had a nearly fivefold increased lifetime anxiety disorder risk (odds ratio, 4.59), Grace D. Shelby, Ph.D., of Vanderbilt University, Nashville, Tenn., and her colleagues reported online Aug. 12 in Pediatrics.

"Similarly, a significantly higher proportion of the FAP group met criteria for [one or more] current anxiety disorders at follow-up, compared with the control group (30.4% vs. 11.6%). The odds ratio for any current anxiety disorder was 3.57 times greater for FAP, compared with controls," the investigators said (Pediatrics 2013 Aug. 12[doi:10.1542/peds.2012-2191]).

The most common anxiety disorder in the FAP group was social anxiety disorder, which was diagnosed in 25.9% of the patients, whose lifetime risk of social anxiety was nearly six times greater than the risk among controls (OR, 5.84) and whose risk for current social anxiety disorder at follow-up was more than eight times greater than the risk among controls (OR, 8.14), they said.

Patients with functional abdominal pain also were at increased lifetime risk of depressive disorders, compared with controls (40.1% vs. 16.3%; OR, 2.62), although current depression risk was low and did not differ between the groups.

The risk of both anxiety disorders and depressive disorders was greatest among those with FAP who met Rome III Diagnostic Questionnaire for Functional Gastrointestinal Disorders criteria for an abdominal pain-related functional gastrointestinal disorder (FGID) at follow-up.

In most study participants who met criteria for a lifetime anxiety disorder, onset occurred during childhood and the age of onset did not differ between the cases and controls (mean age of onset, 7.78 years and 8.97 years, respectively). Conversely, the onset of depressive disorders was usually during adolescence; the mean age of onset for depression also did not differ between cases and controls (mean of 15.96 and 14.92 years, respectively).

Most FAP patients with a lifetime anxiety disorder (72.62%) reported onset before their FAP evaluation, and most of those with lifetime depressive disorders (77.27%) reported onset after their FAP evaluation, the investigators said.

Patients in this study were consecutive new patients, aged 8-17 years, who were evaluated between 1993 and 2007 at the Vanderbilt pediatric gastroenterology service for abdominal pain lasting 3 or more months. Control subjects were children without abdominal pain who were recruited from area schools and who participated in a health survey in the same time period. Those who had reached at least age 12 years, and who were initially evaluated at least 4 years prior, were included in the follow-up study and were followed prospectively for a mean of 8.49 years; subjects were re-evaluated at a mean age of 20.01 years.

The findings support those of a smaller study published in 2001 (Pediatrics 2001;108:e1) that also showed a link between recurrent abdominal pain in childhood and increased likelihood of meeting diagnostic criteria for lifetime and current anxiety disorders in adulthood. The current findings "underscore the importance of a biopsychosocial approach to FAP that includes screening for anxiety and depression," the investigators said, adding that future research should assess whether interventions for mental health conditions in FAP also improve abdominal pain outcomes.

This study was supported by grants from the National Institute on Child Health and Development, Vanderbilt Kennedy Center, Vanderbilt Digestive Disease Research Center, and the Vanderbilt Clinical and Translational Science Award from the National Institutes of Health. Dr. Shelby was supported by a training grant from the National Institute of Mental Health. The authors reported having no other disclosures.

ORLANDO – Mid- and long-term esophageal cancer–free survival rates are similar in patients with early esophageal adenocarcinoma who undergo endoscopic eradication therapy and those who undergo surgical resection, according to findings from a large population-based study.

Of 1,087 patients with early esophageal adenocarcinoma (EAC) who were included in the Surveillance, Epidemiology and End Results (SEER) database, 283 underwent endoscopic eradication therapy (EET), and 804 underwent surgical resection. No significant differences were seen between the groups with respect to 2-year esophageal cancer–free survival (93.5% and 89.6% in the EET and surgery groups, respectively) or 5-year survival (69.3% and 75.8%, respectively), Dr. Sachin Wani reported during a late-breaking abstract session at the annual Digestive Disease Week.

However, the EET group had higher mortality than the surgery group due to non-EAC causes (12.8% vs. 5.7% at 2 years, and 34.8% vs. 12.9% at 5 years), he said. Cardiovascular disease was the most common cause of non-EAC mortality.

Variables significantly associated with mortality were older age (hazard ratio, 1.02), stage T1a disease (compared with T0 disease; HR, 2.71), year of diagnosis (HR, 0.93), and radiation therapy (HR, 5.29), said Dr. Wani of the University of Colorado, Aurora.

Treatment arm was not a predictor of overall survival.

A time-trend analysis showed a significant increase in the proportion of patients with T0 disease undergoing endoscopic eradication therapy. A similar significant increase was noted in patients with stage T1a disease, as well, he said.

Notably, patients undergoing EET were significantly older than those undergoing surgery (70 vs. 63 years), and more likely to be diagnosed with T0 disease (32.5% vs. 23.1% of patients) with well-differentiated histology (33% vs. 24%). They also were less likely to be men, and less likely to receive radiation therapy.

"However, the overall follow-up in the endoscopy arm was shorter than for their surgical counterparts," Dr. Wani noted.

Regional variations were observed in the proportions of patients undergoing EET and surgery, he said.

The differences between the groups, along with the significant differences in non–EAC-related mortality between the treatment groups, highlight selection bias with respect to the therapies offered to patients with EAC, he said.

Patients included in this analysis were adults who had EAC between 1998 and 2009. EAC was defined as carcinoma in situ (T0 disease), or invasive tumor confined to the mucosa, lamina propria, and muscularis mucosae (T1a disease).

The vast majority of patients in the endoscopy arm underwent endoscopic mucosal resection alone; the vast majority in the surgery arm underwent esophagectomy plus partial or total gastrectomy, Dr. Wani said.

Though limited by the use of population-based data that lacked details on recurrences, pathology, staging modalities, and complications and morbidity, this study analyzed one of the largest cohorts of patients with EAC undergoing endoscopic therapy.

The findings are important, because EETs for EAC have gained wide acceptance, and have been endorsed by society guidelines despite a paucity of long-term data examining the differences in outcomes between EET and the gold standard of surgical resection, he said.

Indeed, esophagectomy has traditionally been considered the treatment of choice for EAC, but it is also associated with high morbidity and mortality, even in expert centers, he noted.

"The implications of our study? It really provides a greater degree of confidence in what we do on a daily basis and this whole concept of endoscopic eradication therapy for patients with early esophageal cancer. However we need long-term data – i.e., 5-year data, at least – with newer ablative therapies, such as radiofrequency ablation in combination with endoscopy mucosal resection," he said. Future studies should focus on identifying patient and provider determinants of optimal outcomes, he added.

Dr. Wani reported having no disclosures.

ORLANDO – Mid- and long-term esophageal cancer–free survival rates are similar in patients with early esophageal adenocarcinoma who undergo endoscopic eradication therapy and those who undergo surgical resection, according to findings from a large population-based study.

Of 1,087 patients with early esophageal adenocarcinoma (EAC) who were included in the Surveillance, Epidemiology and End Results (SEER) database, 283 underwent endoscopic eradication therapy (EET), and 804 underwent surgical resection. No significant differences were seen between the groups with respect to 2-year esophageal cancer–free survival (93.5% and 89.6% in the EET and surgery groups, respectively) or 5-year survival (69.3% and 75.8%, respectively), Dr. Sachin Wani reported during a late-breaking abstract session at the annual Digestive Disease Week.

However, the EET group had higher mortality than the surgery group due to non-EAC causes (12.8% vs. 5.7% at 2 years, and 34.8% vs. 12.9% at 5 years), he said. Cardiovascular disease was the most common cause of non-EAC mortality.

Variables significantly associated with mortality were older age (hazard ratio, 1.02), stage T1a disease (compared with T0 disease; HR, 2.71), year of diagnosis (HR, 0.93), and radiation therapy (HR, 5.29), said Dr. Wani of the University of Colorado, Aurora.

Treatment arm was not a predictor of overall survival.

A time-trend analysis showed a significant increase in the proportion of patients with T0 disease undergoing endoscopic eradication therapy. A similar significant increase was noted in patients with stage T1a disease, as well, he said.

Notably, patients undergoing EET were significantly older than those undergoing surgery (70 vs. 63 years), and more likely to be diagnosed with T0 disease (32.5% vs. 23.1% of patients) with well-differentiated histology (33% vs. 24%). They also were less likely to be men, and less likely to receive radiation therapy.

"However, the overall follow-up in the endoscopy arm was shorter than for their surgical counterparts," Dr. Wani noted.

Regional variations were observed in the proportions of patients undergoing EET and surgery, he said.

The differences between the groups, along with the significant differences in non–EAC-related mortality between the treatment groups, highlight selection bias with respect to the therapies offered to patients with EAC, he said.

Patients included in this analysis were adults who had EAC between 1998 and 2009. EAC was defined as carcinoma in situ (T0 disease), or invasive tumor confined to the mucosa, lamina propria, and muscularis mucosae (T1a disease).

The vast majority of patients in the endoscopy arm underwent endoscopic mucosal resection alone; the vast majority in the surgery arm underwent esophagectomy plus partial or total gastrectomy, Dr. Wani said.

Though limited by the use of population-based data that lacked details on recurrences, pathology, staging modalities, and complications and morbidity, this study analyzed one of the largest cohorts of patients with EAC undergoing endoscopic therapy.

The findings are important, because EETs for EAC have gained wide acceptance, and have been endorsed by society guidelines despite a paucity of long-term data examining the differences in outcomes between EET and the gold standard of surgical resection, he said.

Indeed, esophagectomy has traditionally been considered the treatment of choice for EAC, but it is also associated with high morbidity and mortality, even in expert centers, he noted.

"The implications of our study? It really provides a greater degree of confidence in what we do on a daily basis and this whole concept of endoscopic eradication therapy for patients with early esophageal cancer. However we need long-term data – i.e., 5-year data, at least – with newer ablative therapies, such as radiofrequency ablation in combination with endoscopy mucosal resection," he said. Future studies should focus on identifying patient and provider determinants of optimal outcomes, he added.

Dr. Wani reported having no disclosures.

ORLANDO – Mid- and long-term esophageal cancer–free survival rates are similar in patients with early esophageal adenocarcinoma who undergo endoscopic eradication therapy and those who undergo surgical resection, according to findings from a large population-based study.

Of 1,087 patients with early esophageal adenocarcinoma (EAC) who were included in the Surveillance, Epidemiology and End Results (SEER) database, 283 underwent endoscopic eradication therapy (EET), and 804 underwent surgical resection. No significant differences were seen between the groups with respect to 2-year esophageal cancer–free survival (93.5% and 89.6% in the EET and surgery groups, respectively) or 5-year survival (69.3% and 75.8%, respectively), Dr. Sachin Wani reported during a late-breaking abstract session at the annual Digestive Disease Week.

However, the EET group had higher mortality than the surgery group due to non-EAC causes (12.8% vs. 5.7% at 2 years, and 34.8% vs. 12.9% at 5 years), he said. Cardiovascular disease was the most common cause of non-EAC mortality.

Variables significantly associated with mortality were older age (hazard ratio, 1.02), stage T1a disease (compared with T0 disease; HR, 2.71), year of diagnosis (HR, 0.93), and radiation therapy (HR, 5.29), said Dr. Wani of the University of Colorado, Aurora.

Treatment arm was not a predictor of overall survival.

A time-trend analysis showed a significant increase in the proportion of patients with T0 disease undergoing endoscopic eradication therapy. A similar significant increase was noted in patients with stage T1a disease, as well, he said.

Notably, patients undergoing EET were significantly older than those undergoing surgery (70 vs. 63 years), and more likely to be diagnosed with T0 disease (32.5% vs. 23.1% of patients) with well-differentiated histology (33% vs. 24%). They also were less likely to be men, and less likely to receive radiation therapy.

"However, the overall follow-up in the endoscopy arm was shorter than for their surgical counterparts," Dr. Wani noted.

Regional variations were observed in the proportions of patients undergoing EET and surgery, he said.

The differences between the groups, along with the significant differences in non–EAC-related mortality between the treatment groups, highlight selection bias with respect to the therapies offered to patients with EAC, he said.

Patients included in this analysis were adults who had EAC between 1998 and 2009. EAC was defined as carcinoma in situ (T0 disease), or invasive tumor confined to the mucosa, lamina propria, and muscularis mucosae (T1a disease).

The vast majority of patients in the endoscopy arm underwent endoscopic mucosal resection alone; the vast majority in the surgery arm underwent esophagectomy plus partial or total gastrectomy, Dr. Wani said.

Though limited by the use of population-based data that lacked details on recurrences, pathology, staging modalities, and complications and morbidity, this study analyzed one of the largest cohorts of patients with EAC undergoing endoscopic therapy.

The findings are important, because EETs for EAC have gained wide acceptance, and have been endorsed by society guidelines despite a paucity of long-term data examining the differences in outcomes between EET and the gold standard of surgical resection, he said.

Indeed, esophagectomy has traditionally been considered the treatment of choice for EAC, but it is also associated with high morbidity and mortality, even in expert centers, he noted.

"The implications of our study? It really provides a greater degree of confidence in what we do on a daily basis and this whole concept of endoscopic eradication therapy for patients with early esophageal cancer. However we need long-term data – i.e., 5-year data, at least – with newer ablative therapies, such as radiofrequency ablation in combination with endoscopy mucosal resection," he said. Future studies should focus on identifying patient and provider determinants of optimal outcomes, he added.

Dr. Wani reported having no disclosures.

DESTIN, FLA. – The optimal rituximab dose and dosing intervals for maintenance treatment of granulomatosis with polyangiitis and microscopic polyangiitis are unknown, but the available data do provide some guidance for rituximab use in these diseases, according to Dr. Gary Hoffman.

Findings from the Rituximab in ANCA-Associated Vasculitis (RAVE) trial, for example, suggest that rituximab is an alternative to cyclophosphamide-based therapy. Steroid-free remission induction at 6 months in 197 participants with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) was similar at 64% and 53% in those treated with rituximab or cyclophosphamide/azathioprine, respectively; and 86% of patients overall achieved remission at 6 months when steroid dose was not taken into consideration (N. Engl. J. Med. 2010;363:221-32), said Dr. Hoffman, chairman of the department of rheumatic and immunologic diseases at the Cleveland Clinic and professor of medicine at the Cleveland Clinic’s Lerner College of Medicine.

The recently published 18-month results of the RAVE study indicate that a single, 4-week course of rituximab is similar to a continuous immunosuppression regimen of cyclophosphamide followed by azathioprine in inducing and maintaining remission (N. Engl. J. Med. 2013 Aug. 1 [doi:10.1056/NEJMoa1213277]).

In a retrospective study of 65 patients with various types of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis who experienced remission with either four once-weekly 375-mg treatments or two biweekly 1-g treatments of rituximab, 80% of patients relapsed within 2 years without maintenance therapy (Arthritis Rheum. 2009;60:2156-68).

"So that begs the question, what if you were to give rituximab repeatedly to prevent relapse?" Dr. Hoffman asked.

In another retrospective study of 73 patients with GPA or MPA, the relapse rate was 12% in 45 patients treated with rituximab every 6 months, compared with 73% in 28 patients treated as needed for relapse (Arthritis Rheum. 2012;64:3760-9).

The groups did not differ with respect to the rate of serious infections (18% and 14%, respectively) or mortality. The rate of malignancy was higher in the regular dosing group (4% vs. 0%) but the numbers were too small to conclude that treatment increases cancer risk, he said at the Congress of Clinical Rheumatology.

On the basis of these data, a large international, randomized controlled trial is now underway to better answer the question about repeat dosing, Dr. Hoffman noted.

In addition, interim findings from a French phase III study (MAINRITSAN), also presented at the annual meeting of the American College of Rheumatology last year as well as at the International Vasculitis and ANCA Workshop in Paris in April, show that a 500-mg dose of rituximab every 6 months is associated with a greater likelihood of staying in remission, compared with maintenance treatment with azathioprine at 2 mg/kg per day for 22 months.

The major relapse rate was 5% vs. 25%, the serious adverse event rate was 51% vs. 50%, and the mortality rate was 5% vs. 0% in the rituximab and azathioprine groups, respectively.

"Pretty compelling," Dr. Hoffman commented.

Based on all of these data, he said he uses rituximab for induction of remission in young women of reproductive age as an alternative to chronic cyclophosphamide, which can cause infertility.

"I don’t think we need to do that anymore, when we have an alternative effective agent," he said, adding: "I would apply the same rule to men who are planning a family, because the risk of infertility in men is also known to be significant."

Dr. Hoffman also uses rituximab to induce remission in patients in whom cyclophosphamide was used in the past for disease with severe relapses, and in those who have had a rituximab-mediated complete remission lasting at least 6 months if they experience relapse with critical organ system involvement for which cyclophosphamide would otherwise be considered.

"It’s the cumulative dose of cyclophosphamide that buys you that long-term toxicity, whether it’s infertility, marrow failure, increased risk of malignancy, cystitis, and so on. We try not to ever give people large cumulative doses of cyclophosphamide anymore," he said.

Patients in whom he would consider automatic maintenance rituximab include those previously treated with cyclophosphamide who have severe critical organ damage that is likely to lead to profound disability or death if the patient is exposed again to cyclophosphamide.

Conversely, he uses methotrexate or azathioprine, if well tolerated, for maintenance in those who have done extremely well on rituximab or cyclophosphamide, he said.

He typically tries to use cyclophosphamide for 3 months followed by the appropriate maintenance therapy. The available data suggest that once a patient is in remission and doing well, treatment should be maintained at a steady dose to prevent relapse unless toxicity mandates a change.

However, rituximab has not been adequately evaluated in cases of immediately life-threatening disease, while cyclophosphamide in this setting has both avoided organ damage and been lifesaving, he said.

Other areas that require further study are the effective dose and dosing intervals for rituximab maintenance, although some data suggest that both 500-mg and 1,000-mg doses every 6 months are effective, he noted.

Data are needed with respect to the long-term risks, as well. Some longer-term data in patients with rheumatoid arthritis suggest that serious infusion reactions are rare, and mortality is not increased, but GPA and MPA are very different diseases from RA, and additional study is needed. GPA and MPA, as well as other types of ANCA-associated vasculitis, are also very different from each other, and should be studied separately, he said.

Dr. Hoffman is a member of the data safety monitoring board for Roche and sanofi-aventis and is a consultant for Genentech and sanofi-aventis.

DESTIN, FLA. – The optimal rituximab dose and dosing intervals for maintenance treatment of granulomatosis with polyangiitis and microscopic polyangiitis are unknown, but the available data do provide some guidance for rituximab use in these diseases, according to Dr. Gary Hoffman.

Findings from the Rituximab in ANCA-Associated Vasculitis (RAVE) trial, for example, suggest that rituximab is an alternative to cyclophosphamide-based therapy. Steroid-free remission induction at 6 months in 197 participants with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) was similar at 64% and 53% in those treated with rituximab or cyclophosphamide/azathioprine, respectively; and 86% of patients overall achieved remission at 6 months when steroid dose was not taken into consideration (N. Engl. J. Med. 2010;363:221-32), said Dr. Hoffman, chairman of the department of rheumatic and immunologic diseases at the Cleveland Clinic and professor of medicine at the Cleveland Clinic’s Lerner College of Medicine.

The recently published 18-month results of the RAVE study indicate that a single, 4-week course of rituximab is similar to a continuous immunosuppression regimen of cyclophosphamide followed by azathioprine in inducing and maintaining remission (N. Engl. J. Med. 2013 Aug. 1 [doi:10.1056/NEJMoa1213277]).

In a retrospective study of 65 patients with various types of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis who experienced remission with either four once-weekly 375-mg treatments or two biweekly 1-g treatments of rituximab, 80% of patients relapsed within 2 years without maintenance therapy (Arthritis Rheum. 2009;60:2156-68).

"So that begs the question, what if you were to give rituximab repeatedly to prevent relapse?" Dr. Hoffman asked.

In another retrospective study of 73 patients with GPA or MPA, the relapse rate was 12% in 45 patients treated with rituximab every 6 months, compared with 73% in 28 patients treated as needed for relapse (Arthritis Rheum. 2012;64:3760-9).

The groups did not differ with respect to the rate of serious infections (18% and 14%, respectively) or mortality. The rate of malignancy was higher in the regular dosing group (4% vs. 0%) but the numbers were too small to conclude that treatment increases cancer risk, he said at the Congress of Clinical Rheumatology.

On the basis of these data, a large international, randomized controlled trial is now underway to better answer the question about repeat dosing, Dr. Hoffman noted.

In addition, interim findings from a French phase III study (MAINRITSAN), also presented at the annual meeting of the American College of Rheumatology last year as well as at the International Vasculitis and ANCA Workshop in Paris in April, show that a 500-mg dose of rituximab every 6 months is associated with a greater likelihood of staying in remission, compared with maintenance treatment with azathioprine at 2 mg/kg per day for 22 months.

The major relapse rate was 5% vs. 25%, the serious adverse event rate was 51% vs. 50%, and the mortality rate was 5% vs. 0% in the rituximab and azathioprine groups, respectively.

"Pretty compelling," Dr. Hoffman commented.

Based on all of these data, he said he uses rituximab for induction of remission in young women of reproductive age as an alternative to chronic cyclophosphamide, which can cause infertility.

"I don’t think we need to do that anymore, when we have an alternative effective agent," he said, adding: "I would apply the same rule to men who are planning a family, because the risk of infertility in men is also known to be significant."

Dr. Hoffman also uses rituximab to induce remission in patients in whom cyclophosphamide was used in the past for disease with severe relapses, and in those who have had a rituximab-mediated complete remission lasting at least 6 months if they experience relapse with critical organ system involvement for which cyclophosphamide would otherwise be considered.

"It’s the cumulative dose of cyclophosphamide that buys you that long-term toxicity, whether it’s infertility, marrow failure, increased risk of malignancy, cystitis, and so on. We try not to ever give people large cumulative doses of cyclophosphamide anymore," he said.

Patients in whom he would consider automatic maintenance rituximab include those previously treated with cyclophosphamide who have severe critical organ damage that is likely to lead to profound disability or death if the patient is exposed again to cyclophosphamide.

Conversely, he uses methotrexate or azathioprine, if well tolerated, for maintenance in those who have done extremely well on rituximab or cyclophosphamide, he said.

He typically tries to use cyclophosphamide for 3 months followed by the appropriate maintenance therapy. The available data suggest that once a patient is in remission and doing well, treatment should be maintained at a steady dose to prevent relapse unless toxicity mandates a change.

However, rituximab has not been adequately evaluated in cases of immediately life-threatening disease, while cyclophosphamide in this setting has both avoided organ damage and been lifesaving, he said.

Other areas that require further study are the effective dose and dosing intervals for rituximab maintenance, although some data suggest that both 500-mg and 1,000-mg doses every 6 months are effective, he noted.

Data are needed with respect to the long-term risks, as well. Some longer-term data in patients with rheumatoid arthritis suggest that serious infusion reactions are rare, and mortality is not increased, but GPA and MPA are very different diseases from RA, and additional study is needed. GPA and MPA, as well as other types of ANCA-associated vasculitis, are also very different from each other, and should be studied separately, he said.

Dr. Hoffman is a member of the data safety monitoring board for Roche and sanofi-aventis and is a consultant for Genentech and sanofi-aventis.

DESTIN, FLA. – The optimal rituximab dose and dosing intervals for maintenance treatment of granulomatosis with polyangiitis and microscopic polyangiitis are unknown, but the available data do provide some guidance for rituximab use in these diseases, according to Dr. Gary Hoffman.

Findings from the Rituximab in ANCA-Associated Vasculitis (RAVE) trial, for example, suggest that rituximab is an alternative to cyclophosphamide-based therapy. Steroid-free remission induction at 6 months in 197 participants with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) was similar at 64% and 53% in those treated with rituximab or cyclophosphamide/azathioprine, respectively; and 86% of patients overall achieved remission at 6 months when steroid dose was not taken into consideration (N. Engl. J. Med. 2010;363:221-32), said Dr. Hoffman, chairman of the department of rheumatic and immunologic diseases at the Cleveland Clinic and professor of medicine at the Cleveland Clinic’s Lerner College of Medicine.

The recently published 18-month results of the RAVE study indicate that a single, 4-week course of rituximab is similar to a continuous immunosuppression regimen of cyclophosphamide followed by azathioprine in inducing and maintaining remission (N. Engl. J. Med. 2013 Aug. 1 [doi:10.1056/NEJMoa1213277]).

In a retrospective study of 65 patients with various types of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis who experienced remission with either four once-weekly 375-mg treatments or two biweekly 1-g treatments of rituximab, 80% of patients relapsed within 2 years without maintenance therapy (Arthritis Rheum. 2009;60:2156-68).

"So that begs the question, what if you were to give rituximab repeatedly to prevent relapse?" Dr. Hoffman asked.

In another retrospective study of 73 patients with GPA or MPA, the relapse rate was 12% in 45 patients treated with rituximab every 6 months, compared with 73% in 28 patients treated as needed for relapse (Arthritis Rheum. 2012;64:3760-9).

The groups did not differ with respect to the rate of serious infections (18% and 14%, respectively) or mortality. The rate of malignancy was higher in the regular dosing group (4% vs. 0%) but the numbers were too small to conclude that treatment increases cancer risk, he said at the Congress of Clinical Rheumatology.

On the basis of these data, a large international, randomized controlled trial is now underway to better answer the question about repeat dosing, Dr. Hoffman noted.

In addition, interim findings from a French phase III study (MAINRITSAN), also presented at the annual meeting of the American College of Rheumatology last year as well as at the International Vasculitis and ANCA Workshop in Paris in April, show that a 500-mg dose of rituximab every 6 months is associated with a greater likelihood of staying in remission, compared with maintenance treatment with azathioprine at 2 mg/kg per day for 22 months.

The major relapse rate was 5% vs. 25%, the serious adverse event rate was 51% vs. 50%, and the mortality rate was 5% vs. 0% in the rituximab and azathioprine groups, respectively.

"Pretty compelling," Dr. Hoffman commented.

Based on all of these data, he said he uses rituximab for induction of remission in young women of reproductive age as an alternative to chronic cyclophosphamide, which can cause infertility.

"I don’t think we need to do that anymore, when we have an alternative effective agent," he said, adding: "I would apply the same rule to men who are planning a family, because the risk of infertility in men is also known to be significant."

Dr. Hoffman also uses rituximab to induce remission in patients in whom cyclophosphamide was used in the past for disease with severe relapses, and in those who have had a rituximab-mediated complete remission lasting at least 6 months if they experience relapse with critical organ system involvement for which cyclophosphamide would otherwise be considered.

"It’s the cumulative dose of cyclophosphamide that buys you that long-term toxicity, whether it’s infertility, marrow failure, increased risk of malignancy, cystitis, and so on. We try not to ever give people large cumulative doses of cyclophosphamide anymore," he said.

Patients in whom he would consider automatic maintenance rituximab include those previously treated with cyclophosphamide who have severe critical organ damage that is likely to lead to profound disability or death if the patient is exposed again to cyclophosphamide.

Conversely, he uses methotrexate or azathioprine, if well tolerated, for maintenance in those who have done extremely well on rituximab or cyclophosphamide, he said.

He typically tries to use cyclophosphamide for 3 months followed by the appropriate maintenance therapy. The available data suggest that once a patient is in remission and doing well, treatment should be maintained at a steady dose to prevent relapse unless toxicity mandates a change.

However, rituximab has not been adequately evaluated in cases of immediately life-threatening disease, while cyclophosphamide in this setting has both avoided organ damage and been lifesaving, he said.

Other areas that require further study are the effective dose and dosing intervals for rituximab maintenance, although some data suggest that both 500-mg and 1,000-mg doses every 6 months are effective, he noted.

Data are needed with respect to the long-term risks, as well. Some longer-term data in patients with rheumatoid arthritis suggest that serious infusion reactions are rare, and mortality is not increased, but GPA and MPA are very different diseases from RA, and additional study is needed. GPA and MPA, as well as other types of ANCA-associated vasculitis, are also very different from each other, and should be studied separately, he said.

Dr. Hoffman is a member of the data safety monitoring board for Roche and sanofi-aventis and is a consultant for Genentech and sanofi-aventis.

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the post-test.

Hypoglycemia is common among patients being treated for type 2 diabetes, regardless of their level of glycemic control, according to findings from the Diabetes Study of Northern California (DISTANCE) survey.

The findings challenge the conventional wisdom that hypoglycemia occurs only among those with the lowest hemoglobin A1c levels, reported Dr. Kasia J. Lipska of Yale University, New Haven, Conn., and colleagues. The study was published online July 30 in Diabetes Care.

Among 9,094 adults with diabetes who participated in the survey, 11% reported experiencing severe hypoglycemia in the past year, with nearly 1 in 4 (24%) reporting more than three events during that time period. In an unadjusted analysis, those with HbA_1c at the highest and lowest levels were most likely to experience hypoglycemia, the investigators said (Diabetes Care 2013 July 30 [doi: 10.2337/dc13-0610]).

Compared with those with "good" HbA_1c levels of 7.0%-7.9%; the relative risk of hypoglycemia was 1.25 in those with "near normal" levels of less than 6%, 1.01 in those with "very good" levels of 6.0%-6.9%, 0.99 in those with "suboptimal" levels of 8.0%-8.9%, and 1.16 among those with "very poor" levels of 9% or greater, they explained.

However, the elevated relative risk was statistically significant only for those with HbA_1c of 9% or greater, they noted, adding that while adjustment for demographic variables did not "alter the shape of the relationship," and while the point estimates for hypoglycemia risk remained higher at the two extremes of glycemic control, the differences in risk between each HbA_1c category and the reference group did not differ significantly in the fully adjusted model.

Study participants were patients with type 2 diabetes aged 30-77 years, who were members of the Kaiser Permanente Northern California Diabetes Registry. The patients, who were using glucose-lowering therapy, were surveyed during 2005-2006 about episodes of severe hypoglycemia, such as episodes during which they passed out and/or required medical assistance.

Patients most likely to report hypoglycemic episodes were women; those taking more than four medications for chronic conditions; those using either insulin or a secretagogue during the preobservation period; and those with longer duration of disease, prior history of hypoglycemia, and multiple comorbidities, the investigators noted.

After examining the prevalence of hypoglycemia across potential effect modifiers, however, they found no significant interactions.

Prior studies have resulted in inconsistent findings about the relationship between glucose control and hypoglycemic events, but findings from the current study suggest that "hypoglycemia occurs across all levels of HbA_1c, with higher risk associated with near-normal or very poor glycemic control," the investigators said.

The findings are important, they said, because several studies have shown that patients who experience severe hypoglycemia are at increased risk for a number of unfavorable health outcomes, including dementia, falls, fall-related fractures, cardiovascular events, poor health–related quality of life, and increased mortality. The researchers noted that in addition to efforts to limit adverse effects of overtreatment and to improve patient outcomes, efforts to consider the safety of the various glucose-lowering therapies in patients with higher HbA_1c levels are needed.

"Poorly controlled diabetes appears to be associated with both higher risk of diabetic complications and higher risk of treatment-related hypoglycemia. Therefore, quality improvement efforts must balance the need to improve glucose levels with safety of antihyperglycemic therapy in this group," they said.

Though limited by a number of factors, including self-reporting of hypoglycemia without laboratory confirmation and a wide age range of participants, which limits applicability to elderly patients with diabetes, the findings in this usual-care setting nonetheless underscore the importance of directing efforts to improve the safety of glucose-lowering therapies. Such efforts must be directed not only to patients achieving intensive glucose control, but also to those with poorly controlled disease, the investigators concluded, noting that "future analyses are needed to identify management strategies and treatment factors that may mitigate hypoglycemia risk."

The DISTANCE survey was funded by numerous grants, including grants to individual authors or their employers from the National Institute on Aging and the National Heart, Lung, and Blood Institute.

To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the post-test.

Hypoglycemia is common among patients being treated for type 2 diabetes, regardless of their level of glycemic control, according to findings from the Diabetes Study of Northern California (DISTANCE) survey.

The findings challenge the conventional wisdom that hypoglycemia occurs only among those with the lowest hemoglobin A1c levels, reported Dr. Kasia J. Lipska of Yale University, New Haven, Conn., and colleagues. The study was published online July 30 in Diabetes Care.

Among 9,094 adults with diabetes who participated in the survey, 11% reported experiencing severe hypoglycemia in the past year, with nearly 1 in 4 (24%) reporting more than three events during that time period. In an unadjusted analysis, those with HbA_1c at the highest and lowest levels were most likely to experience hypoglycemia, the investigators said (Diabetes Care 2013 July 30 [doi: 10.2337/dc13-0610]).

Compared with those with "good" HbA_1c levels of 7.0%-7.9%; the relative risk of hypoglycemia was 1.25 in those with "near normal" levels of less than 6%, 1.01 in those with "very good" levels of 6.0%-6.9%, 0.99 in those with "suboptimal" levels of 8.0%-8.9%, and 1.16 among those with "very poor" levels of 9% or greater, they explained.

However, the elevated relative risk was statistically significant only for those with HbA_1c of 9% or greater, they noted, adding that while adjustment for demographic variables did not "alter the shape of the relationship," and while the point estimates for hypoglycemia risk remained higher at the two extremes of glycemic control, the differences in risk between each HbA_1c category and the reference group did not differ significantly in the fully adjusted model.

Study participants were patients with type 2 diabetes aged 30-77 years, who were members of the Kaiser Permanente Northern California Diabetes Registry. The patients, who were using glucose-lowering therapy, were surveyed during 2005-2006 about episodes of severe hypoglycemia, such as episodes during which they passed out and/or required medical assistance.

Patients most likely to report hypoglycemic episodes were women; those taking more than four medications for chronic conditions; those using either insulin or a secretagogue during the preobservation period; and those with longer duration of disease, prior history of hypoglycemia, and multiple comorbidities, the investigators noted.

After examining the prevalence of hypoglycemia across potential effect modifiers, however, they found no significant interactions.

Prior studies have resulted in inconsistent findings about the relationship between glucose control and hypoglycemic events, but findings from the current study suggest that "hypoglycemia occurs across all levels of HbA_1c, with higher risk associated with near-normal or very poor glycemic control," the investigators said.

The findings are important, they said, because several studies have shown that patients who experience severe hypoglycemia are at increased risk for a number of unfavorable health outcomes, including dementia, falls, fall-related fractures, cardiovascular events, poor health–related quality of life, and increased mortality. The researchers noted that in addition to efforts to limit adverse effects of overtreatment and to improve patient outcomes, efforts to consider the safety of the various glucose-lowering therapies in patients with higher HbA_1c levels are needed.

"Poorly controlled diabetes appears to be associated with both higher risk of diabetic complications and higher risk of treatment-related hypoglycemia. Therefore, quality improvement efforts must balance the need to improve glucose levels with safety of antihyperglycemic therapy in this group," they said.

Though limited by a number of factors, including self-reporting of hypoglycemia without laboratory confirmation and a wide age range of participants, which limits applicability to elderly patients with diabetes, the findings in this usual-care setting nonetheless underscore the importance of directing efforts to improve the safety of glucose-lowering therapies. Such efforts must be directed not only to patients achieving intensive glucose control, but also to those with poorly controlled disease, the investigators concluded, noting that "future analyses are needed to identify management strategies and treatment factors that may mitigate hypoglycemia risk."

The DISTANCE survey was funded by numerous grants, including grants to individual authors or their employers from the National Institute on Aging and the National Heart, Lung, and Blood Institute.

To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the post-test.

Hypoglycemia is common among patients being treated for type 2 diabetes, regardless of their level of glycemic control, according to findings from the Diabetes Study of Northern California (DISTANCE) survey.

The findings challenge the conventional wisdom that hypoglycemia occurs only among those with the lowest hemoglobin A1c levels, reported Dr. Kasia J. Lipska of Yale University, New Haven, Conn., and colleagues. The study was published online July 30 in Diabetes Care.

Among 9,094 adults with diabetes who participated in the survey, 11% reported experiencing severe hypoglycemia in the past year, with nearly 1 in 4 (24%) reporting more than three events during that time period. In an unadjusted analysis, those with HbA_1c at the highest and lowest levels were most likely to experience hypoglycemia, the investigators said (Diabetes Care 2013 July 30 [doi: 10.2337/dc13-0610]).

Compared with those with "good" HbA_1c levels of 7.0%-7.9%; the relative risk of hypoglycemia was 1.25 in those with "near normal" levels of less than 6%, 1.01 in those with "very good" levels of 6.0%-6.9%, 0.99 in those with "suboptimal" levels of 8.0%-8.9%, and 1.16 among those with "very poor" levels of 9% or greater, they explained.

However, the elevated relative risk was statistically significant only for those with HbA_1c of 9% or greater, they noted, adding that while adjustment for demographic variables did not "alter the shape of the relationship," and while the point estimates for hypoglycemia risk remained higher at the two extremes of glycemic control, the differences in risk between each HbA_1c category and the reference group did not differ significantly in the fully adjusted model.

Study participants were patients with type 2 diabetes aged 30-77 years, who were members of the Kaiser Permanente Northern California Diabetes Registry. The patients, who were using glucose-lowering therapy, were surveyed during 2005-2006 about episodes of severe hypoglycemia, such as episodes during which they passed out and/or required medical assistance.

Patients most likely to report hypoglycemic episodes were women; those taking more than four medications for chronic conditions; those using either insulin or a secretagogue during the preobservation period; and those with longer duration of disease, prior history of hypoglycemia, and multiple comorbidities, the investigators noted.

After examining the prevalence of hypoglycemia across potential effect modifiers, however, they found no significant interactions.

Prior studies have resulted in inconsistent findings about the relationship between glucose control and hypoglycemic events, but findings from the current study suggest that "hypoglycemia occurs across all levels of HbA_1c, with higher risk associated with near-normal or very poor glycemic control," the investigators said.

The findings are important, they said, because several studies have shown that patients who experience severe hypoglycemia are at increased risk for a number of unfavorable health outcomes, including dementia, falls, fall-related fractures, cardiovascular events, poor health–related quality of life, and increased mortality. The researchers noted that in addition to efforts to limit adverse effects of overtreatment and to improve patient outcomes, efforts to consider the safety of the various glucose-lowering therapies in patients with higher HbA_1c levels are needed.

"Poorly controlled diabetes appears to be associated with both higher risk of diabetic complications and higher risk of treatment-related hypoglycemia. Therefore, quality improvement efforts must balance the need to improve glucose levels with safety of antihyperglycemic therapy in this group," they said.

Though limited by a number of factors, including self-reporting of hypoglycemia without laboratory confirmation and a wide age range of participants, which limits applicability to elderly patients with diabetes, the findings in this usual-care setting nonetheless underscore the importance of directing efforts to improve the safety of glucose-lowering therapies. Such efforts must be directed not only to patients achieving intensive glucose control, but also to those with poorly controlled disease, the investigators concluded, noting that "future analyses are needed to identify management strategies and treatment factors that may mitigate hypoglycemia risk."

The DISTANCE survey was funded by numerous grants, including grants to individual authors or their employers from the National Institute on Aging and the National Heart, Lung, and Blood Institute.

To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

Hypoglycemia is common among patients being treated for type 2 diabetes, regardless of their level of glycemic control, according to findings from the Diabetes Study of Northern California (DISTANCE) survey.

The findings challenge the conventional wisdom that hypoglycemia occurs only among those with the lowest hemoglobin A1c levels, reported Dr. Kasia J. Lipska of Yale University, New Haven, Conn., and colleagues. The study was published online July 30 in Diabetes Care.

Among 9,094 adults with diabetes who participated in the survey, 11% reported experiencing severe hypoglycemia in the past year, with nearly 1 in 4 (24%) reporting more than three events during that time period. In an unadjusted analysis, those with HbA_1c at the highest and lowest levels were most likely to experience hypoglycemia, the investigators said (Diabetes Care 2013 July 30 [doi: 10.2337/dc13-0610]).

Compared with those with "good" HbA_1c levels of 7.0%-7.9%; the relative risk of hypoglycemia was 1.25 in those with "near normal" levels of less than 6%, 1.01 in those with "very good" levels of 6.0%-6.9%, 0.99 in those with "suboptimal" levels of 8.0%-8.9%, and 1.16 among those with "very poor" levels of 9% or greater, they explained.

However, the elevated relative risk was statistically significant only for those with HbA_1c of 9% or greater, they noted, adding that while adjustment for demographic variables did not "alter the shape of the relationship," and while the point estimates for hypoglycemia risk remained higher at the two extremes of glycemic control, the differences in risk between each HbA_1c category and the reference group did not differ significantly in the fully adjusted model.

Study participants were patients with type 2 diabetes aged 30-77 years, who were members of the Kaiser Permanente Northern California Diabetes Registry. The patients, who were using glucose-lowering therapy, were surveyed during 2005-2006 about episodes of severe hypoglycemia, such as episodes during which they passed out and/or required medical assistance.

Patients most likely to report hypoglycemic episodes were women; those taking more than four medications for chronic conditions; those using either insulin or a secretagogue during the preobservation period; and those with longer duration of disease, prior history of hypoglycemia, and multiple comorbidities, the investigators noted.

After examining the prevalence of hypoglycemia across potential effect modifiers, however, they found no significant interactions.

Prior studies have resulted in inconsistent findings about the relationship between glucose control and hypoglycemic events, but findings from the current study suggest that "hypoglycemia occurs across all levels of HbA_1c, with higher risk associated with near-normal or very poor glycemic control," the investigators said.

The findings are important, they said, because several studies have shown that patients who experience severe hypoglycemia are at increased risk for a number of unfavorable health outcomes, including dementia, falls, fall-related fractures, cardiovascular events, poor health–related quality of life, and increased mortality. The researchers noted that in addition to efforts to limit adverse effects of overtreatment and to improve patient outcomes, efforts to consider the safety of the various glucose-lowering therapies in patients with higher HbA_1c levels are needed.

"Poorly controlled diabetes appears to be associated with both higher risk of diabetic complications and higher risk of treatment-related hypoglycemia. Therefore, quality improvement efforts must balance the need to improve glucose levels with safety of antihyperglycemic therapy in this group," they said.

Though limited by a number of factors, including self-reporting of hypoglycemia without laboratory confirmation and a wide age range of participants, which limits applicability to elderly patients with diabetes, the findings in this usual-care setting nonetheless underscore the importance of directing efforts to improve the safety of glucose-lowering therapies. Such efforts must be directed not only to patients achieving intensive glucose control, but also to those with poorly controlled disease, the investigators concluded, noting that "future analyses are needed to identify management strategies and treatment factors that may mitigate hypoglycemia risk."

The DISTANCE survey was funded by numerous grants, including grants to individual authors or their employers from the National Institute on Aging and the National Heart, Lung, and Blood Institute.

Hypoglycemia is common among patients being treated for type 2 diabetes, regardless of their level of glycemic control, according to findings from the Diabetes Study of Northern California (DISTANCE) survey.

The findings challenge the conventional wisdom that hypoglycemia occurs only among those with the lowest hemoglobin A1c levels, reported Dr. Kasia J. Lipska of Yale University, New Haven, Conn., and colleagues. The study was published online July 30 in Diabetes Care.

Among 9,094 adults with diabetes who participated in the survey, 11% reported experiencing severe hypoglycemia in the past year, with nearly 1 in 4 (24%) reporting more than three events during that time period. In an unadjusted analysis, those with HbA_1c at the highest and lowest levels were most likely to experience hypoglycemia, the investigators said (Diabetes Care 2013 July 30 [doi: 10.2337/dc13-0610]).

Compared with those with "good" HbA_1c levels of 7.0%-7.9%; the relative risk of hypoglycemia was 1.25 in those with "near normal" levels of less than 6%, 1.01 in those with "very good" levels of 6.0%-6.9%, 0.99 in those with "suboptimal" levels of 8.0%-8.9%, and 1.16 among those with "very poor" levels of 9% or greater, they explained.

However, the elevated relative risk was statistically significant only for those with HbA_1c of 9% or greater, they noted, adding that while adjustment for demographic variables did not "alter the shape of the relationship," and while the point estimates for hypoglycemia risk remained higher at the two extremes of glycemic control, the differences in risk between each HbA_1c category and the reference group did not differ significantly in the fully adjusted model.

Study participants were patients with type 2 diabetes aged 30-77 years, who were members of the Kaiser Permanente Northern California Diabetes Registry. The patients, who were using glucose-lowering therapy, were surveyed during 2005-2006 about episodes of severe hypoglycemia, such as episodes during which they passed out and/or required medical assistance.

Patients most likely to report hypoglycemic episodes were women; those taking more than four medications for chronic conditions; those using either insulin or a secretagogue during the preobservation period; and those with longer duration of disease, prior history of hypoglycemia, and multiple comorbidities, the investigators noted.

After examining the prevalence of hypoglycemia across potential effect modifiers, however, they found no significant interactions.

Prior studies have resulted in inconsistent findings about the relationship between glucose control and hypoglycemic events, but findings from the current study suggest that "hypoglycemia occurs across all levels of HbA_1c, with higher risk associated with near-normal or very poor glycemic control," the investigators said.

The findings are important, they said, because several studies have shown that patients who experience severe hypoglycemia are at increased risk for a number of unfavorable health outcomes, including dementia, falls, fall-related fractures, cardiovascular events, poor health–related quality of life, and increased mortality. The researchers noted that in addition to efforts to limit adverse effects of overtreatment and to improve patient outcomes, efforts to consider the safety of the various glucose-lowering therapies in patients with higher HbA_1c levels are needed.

"Poorly controlled diabetes appears to be associated with both higher risk of diabetic complications and higher risk of treatment-related hypoglycemia. Therefore, quality improvement efforts must balance the need to improve glucose levels with safety of antihyperglycemic therapy in this group," they said.

Though limited by a number of factors, including self-reporting of hypoglycemia without laboratory confirmation and a wide age range of participants, which limits applicability to elderly patients with diabetes, the findings in this usual-care setting nonetheless underscore the importance of directing efforts to improve the safety of glucose-lowering therapies. Such efforts must be directed not only to patients achieving intensive glucose control, but also to those with poorly controlled disease, the investigators concluded, noting that "future analyses are needed to identify management strategies and treatment factors that may mitigate hypoglycemia risk."

The DISTANCE survey was funded by numerous grants, including grants to individual authors or their employers from the National Institute on Aging and the National Heart, Lung, and Blood Institute.

Hypoglycemia is common among patients being treated for type 2 diabetes, regardless of their level of glycemic control, according to findings from the Diabetes Study of Northern California (DISTANCE) survey.

The findings challenge the conventional wisdom that hypoglycemia occurs only among those with the lowest hemoglobin A1c levels, reported Dr. Kasia J. Lipska of Yale University, New Haven, Conn., and colleagues. The study was published online July 30 in Diabetes Care.

Among 9,094 adults with diabetes who participated in the survey, 11% reported experiencing severe hypoglycemia in the past year, with nearly 1 in 4 (24%) reporting more than three events during that time period. In an unadjusted analysis, those with HbA_1c at the highest and lowest levels were most likely to experience hypoglycemia, the investigators said (Diabetes Care 2013 July 30 [doi: 10.2337/dc13-0610]).

Compared with those with "good" HbA_1c levels of 7.0%-7.9%; the relative risk of hypoglycemia was 1.25 in those with "near normal" levels of less than 6%, 1.01 in those with "very good" levels of 6.0%-6.9%, 0.99 in those with "suboptimal" levels of 8.0%-8.9%, and 1.16 among those with "very poor" levels of 9% or greater, they explained.

However, the elevated relative risk was statistically significant only for those with HbA_1c of 9% or greater, they noted, adding that while adjustment for demographic variables did not "alter the shape of the relationship," and while the point estimates for hypoglycemia risk remained higher at the two extremes of glycemic control, the differences in risk between each HbA_1c category and the reference group did not differ significantly in the fully adjusted model.

Study participants were patients with type 2 diabetes aged 30-77 years, who were members of the Kaiser Permanente Northern California Diabetes Registry. The patients, who were using glucose-lowering therapy, were surveyed during 2005-2006 about episodes of severe hypoglycemia, such as episodes during which they passed out and/or required medical assistance.

Patients most likely to report hypoglycemic episodes were women; those taking more than four medications for chronic conditions; those using either insulin or a secretagogue during the preobservation period; and those with longer duration of disease, prior history of hypoglycemia, and multiple comorbidities, the investigators noted.

After examining the prevalence of hypoglycemia across potential effect modifiers, however, they found no significant interactions.

Prior studies have resulted in inconsistent findings about the relationship between glucose control and hypoglycemic events, but findings from the current study suggest that "hypoglycemia occurs across all levels of HbA_1c, with higher risk associated with near-normal or very poor glycemic control," the investigators said.

The findings are important, they said, because several studies have shown that patients who experience severe hypoglycemia are at increased risk for a number of unfavorable health outcomes, including dementia, falls, fall-related fractures, cardiovascular events, poor health–related quality of life, and increased mortality. The researchers noted that in addition to efforts to limit adverse effects of overtreatment and to improve patient outcomes, efforts to consider the safety of the various glucose-lowering therapies in patients with higher HbA_1c levels are needed.

"Poorly controlled diabetes appears to be associated with both higher risk of diabetic complications and higher risk of treatment-related hypoglycemia. Therefore, quality improvement efforts must balance the need to improve glucose levels with safety of antihyperglycemic therapy in this group," they said.

Though limited by a number of factors, including self-reporting of hypoglycemia without laboratory confirmation and a wide age range of participants, which limits applicability to elderly patients with diabetes, the findings in this usual-care setting nonetheless underscore the importance of directing efforts to improve the safety of glucose-lowering therapies. Such efforts must be directed not only to patients achieving intensive glucose control, but also to those with poorly controlled disease, the investigators concluded, noting that "future analyses are needed to identify management strategies and treatment factors that may mitigate hypoglycemia risk."

The DISTANCE survey was funded by numerous grants, including grants to individual authors or their employers from the National Institute on Aging and the National Heart, Lung, and Blood Institute.

Low-dose computed tomography reduces lung cancer mortality and all-cause mortality when used as a screening tool in asymptomatic adults at high risk for the disease, according to the results of a systematic review conducted for the U.S. Preventive Services Task Force.

In 2004, the USPSTF deemed the evidence insufficient for recommending for or against low-dose computed tomography (LDCT) for lung cancer screening in asymptomatic individuals, but the findings of the current review suggest screening has a definite benefit for most patients, Dr. Linda L. Humphrey, of Oregon Health and Science University and the Portland Veterans Affairs Medical Center, and her colleagues reported.

A draft recommendation based on the findings, published online in the July 30 issue of Annals of Internal Medicine (2013 July 29 [doi: 10.7326/0003-4819-159-6-201309170-00690]), is available on the USPSTF website for public comment.

©kutay tanir/iStockphoto.com

The researchers conducted a review of the literature published between 2000 and May 2013 and identified four trials that reported findings on the efficacy of LDCT screening in patients with smoking exposure for both intervention and control groups. Three small trials showed varying degrees of benefit with screening, but were underpowered; one large trial – the National Lung Screening Trial (NLST) – showed a significant 20% reduction in lung cancer mortality among those screened, as well as a 6.7% reduction in all-cause mortality.

The randomized multicenter NLST compared annual LDCT scans with annual single-view posterior-anterior chest radiographs for 3 years in more than 53,000 current or former smokers aged 55-74 years with at least a 30–pack-year history of smoking (N. Engl. J. Med. 2013;368:1980-91). One cancer death was prevented for every 320 patients who completed one screening, and one death from any cause was prevented for every 219 patients screened in that study; the trial was stopped early after 6.5 years of follow-up based on the findings.

In general, the benefits of LDCT for lung cancer screening in this population outweighed the risks, Dr. Humphrey and her colleagues noted.

Harms associated with LDCT, according to findings from 7 trials and 13 cohort studies that reported on such outcomes, included radiation exposure, overdiagnosis, and a high rate of false-positive findings that were resolved by further imaging in most cases. False negatives were reported in six studies, and the rates ranged from 0% to 20%, but none of the studies evaluated the harm of false reassurance, the investigators noted. The benefits of screening must be weighed against these potential harms.

Lung cancer is the third most common cancer among men and women in the United States, but is the leading cause of cancer-related deaths, accounting for nearly 27%. Furthermore, about 85% of U.S. lung cancer cases are attributable to smoking, and since about 20% of Americans currently smoke – and many more are former smokers who remain at increased risk because of their smoking history – "lung cancer will remain a major public health problem in this country for decades," the investigators wrote.

The studies included in this review were conducted in patients at high risk for lung cancer based on current or former smoking. However, patients at an increased risk for lung cancer, including older adults and those with a family history of lung cancer, chronic obstructive pulmonary disease, pulmonary fibrosis, and certain environmental and occupational exposures, may also benefit from LDCT screening.

"Future research to identify methods for focusing LDCT screening on persons at highest risk for disease, to improve discrimination between benign and malignant pulmonary nodules, and to find early indicators of aggressive disease is warranted," the investigators noted. "If LDCT screening becomes routine, the risk for harms should be measured and methods to limit them should be identified."

The review was funded by grants from the Agency for Healthcare Research and Quality and the Portland Veterans Affairs Medical Center. Dr. Humphrey is employed by the Department of Veterans Affairs, and she and her coauthors disclosed ties with UpToDate, the USPSTF, AHRQ, the Department of Veterans Affairs, the American Lung Association, the Chest/LUNGevity Foundation, the National Lung Cancer Partnership, and/or the American College of Chest Physicians.

Low-dose computed tomography reduces lung cancer mortality and all-cause mortality when used as a screening tool in asymptomatic adults at high risk for the disease, according to the results of a systematic review conducted for the U.S. Preventive Services Task Force.

In 2004, the USPSTF deemed the evidence insufficient for recommending for or against low-dose computed tomography (LDCT) for lung cancer screening in asymptomatic individuals, but the findings of the current review suggest screening has a definite benefit for most patients, Dr. Linda L. Humphrey, of Oregon Health and Science University and the Portland Veterans Affairs Medical Center, and her colleagues reported.

A draft recommendation based on the findings, published online in the July 30 issue of Annals of Internal Medicine (2013 July 29 [doi: 10.7326/0003-4819-159-6-201309170-00690]), is available on the USPSTF website for public comment.

©kutay tanir/iStockphoto.com

The researchers conducted a review of the literature published between 2000 and May 2013 and identified four trials that reported findings on the efficacy of LDCT screening in patients with smoking exposure for both intervention and control groups. Three small trials showed varying degrees of benefit with screening, but were underpowered; one large trial – the National Lung Screening Trial (NLST) – showed a significant 20% reduction in lung cancer mortality among those screened, as well as a 6.7% reduction in all-cause mortality.

The randomized multicenter NLST compared annual LDCT scans with annual single-view posterior-anterior chest radiographs for 3 years in more than 53,000 current or former smokers aged 55-74 years with at least a 30–pack-year history of smoking (N. Engl. J. Med. 2013;368:1980-91). One cancer death was prevented for every 320 patients who completed one screening, and one death from any cause was prevented for every 219 patients screened in that study; the trial was stopped early after 6.5 years of follow-up based on the findings.

In general, the benefits of LDCT for lung cancer screening in this population outweighed the risks, Dr. Humphrey and her colleagues noted.

Harms associated with LDCT, according to findings from 7 trials and 13 cohort studies that reported on such outcomes, included radiation exposure, overdiagnosis, and a high rate of false-positive findings that were resolved by further imaging in most cases. False negatives were reported in six studies, and the rates ranged from 0% to 20%, but none of the studies evaluated the harm of false reassurance, the investigators noted. The benefits of screening must be weighed against these potential harms.

Lung cancer is the third most common cancer among men and women in the United States, but is the leading cause of cancer-related deaths, accounting for nearly 27%. Furthermore, about 85% of U.S. lung cancer cases are attributable to smoking, and since about 20% of Americans currently smoke – and many more are former smokers who remain at increased risk because of their smoking history – "lung cancer will remain a major public health problem in this country for decades," the investigators wrote.

The studies included in this review were conducted in patients at high risk for lung cancer based on current or former smoking. However, patients at an increased risk for lung cancer, including older adults and those with a family history of lung cancer, chronic obstructive pulmonary disease, pulmonary fibrosis, and certain environmental and occupational exposures, may also benefit from LDCT screening.

"Future research to identify methods for focusing LDCT screening on persons at highest risk for disease, to improve discrimination between benign and malignant pulmonary nodules, and to find early indicators of aggressive disease is warranted," the investigators noted. "If LDCT screening becomes routine, the risk for harms should be measured and methods to limit them should be identified."

The review was funded by grants from the Agency for Healthcare Research and Quality and the Portland Veterans Affairs Medical Center. Dr. Humphrey is employed by the Department of Veterans Affairs, and she and her coauthors disclosed ties with UpToDate, the USPSTF, AHRQ, the Department of Veterans Affairs, the American Lung Association, the Chest/LUNGevity Foundation, the National Lung Cancer Partnership, and/or the American College of Chest Physicians.

Low-dose computed tomography reduces lung cancer mortality and all-cause mortality when used as a screening tool in asymptomatic adults at high risk for the disease, according to the results of a systematic review conducted for the U.S. Preventive Services Task Force.

In 2004, the USPSTF deemed the evidence insufficient for recommending for or against low-dose computed tomography (LDCT) for lung cancer screening in asymptomatic individuals, but the findings of the current review suggest screening has a definite benefit for most patients, Dr. Linda L. Humphrey, of Oregon Health and Science University and the Portland Veterans Affairs Medical Center, and her colleagues reported.

A draft recommendation based on the findings, published online in the July 30 issue of Annals of Internal Medicine (2013 July 29 [doi: 10.7326/0003-4819-159-6-201309170-00690]), is available on the USPSTF website for public comment.

©kutay tanir/iStockphoto.com

The researchers conducted a review of the literature published between 2000 and May 2013 and identified four trials that reported findings on the efficacy of LDCT screening in patients with smoking exposure for both intervention and control groups. Three small trials showed varying degrees of benefit with screening, but were underpowered; one large trial – the National Lung Screening Trial (NLST) – showed a significant 20% reduction in lung cancer mortality among those screened, as well as a 6.7% reduction in all-cause mortality.

The randomized multicenter NLST compared annual LDCT scans with annual single-view posterior-anterior chest radiographs for 3 years in more than 53,000 current or former smokers aged 55-74 years with at least a 30–pack-year history of smoking (N. Engl. J. Med. 2013;368:1980-91). One cancer death was prevented for every 320 patients who completed one screening, and one death from any cause was prevented for every 219 patients screened in that study; the trial was stopped early after 6.5 years of follow-up based on the findings.

In general, the benefits of LDCT for lung cancer screening in this population outweighed the risks, Dr. Humphrey and her colleagues noted.

Harms associated with LDCT, according to findings from 7 trials and 13 cohort studies that reported on such outcomes, included radiation exposure, overdiagnosis, and a high rate of false-positive findings that were resolved by further imaging in most cases. False negatives were reported in six studies, and the rates ranged from 0% to 20%, but none of the studies evaluated the harm of false reassurance, the investigators noted. The benefits of screening must be weighed against these potential harms.

Lung cancer is the third most common cancer among men and women in the United States, but is the leading cause of cancer-related deaths, accounting for nearly 27%. Furthermore, about 85% of U.S. lung cancer cases are attributable to smoking, and since about 20% of Americans currently smoke – and many more are former smokers who remain at increased risk because of their smoking history – "lung cancer will remain a major public health problem in this country for decades," the investigators wrote.

The studies included in this review were conducted in patients at high risk for lung cancer based on current or former smoking. However, patients at an increased risk for lung cancer, including older adults and those with a family history of lung cancer, chronic obstructive pulmonary disease, pulmonary fibrosis, and certain environmental and occupational exposures, may also benefit from LDCT screening.

"Future research to identify methods for focusing LDCT screening on persons at highest risk for disease, to improve discrimination between benign and malignant pulmonary nodules, and to find early indicators of aggressive disease is warranted," the investigators noted. "If LDCT screening becomes routine, the risk for harms should be measured and methods to limit them should be identified."

The review was funded by grants from the Agency for Healthcare Research and Quality and the Portland Veterans Affairs Medical Center. Dr. Humphrey is employed by the Department of Veterans Affairs, and she and her coauthors disclosed ties with UpToDate, the USPSTF, AHRQ, the Department of Veterans Affairs, the American Lung Association, the Chest/LUNGevity Foundation, the National Lung Cancer Partnership, and/or the American College of Chest Physicians.