Mary Ann Moon

Early-stage HER2-positive breast cancers that overexpress a subset of genes involved in the regulation of immune function are much more likely to respond to adjuvant trastuzumab therapy than breast cancers that do not express those genes, according to a report published online Jan. 19 in Journal of Clinical Oncology.

This finding from a secondary analysis of tumor samples obtained in a phase III clinical trial represents “the first demonstration of a cohort of immune function genes that seem to predict benefit from adjuvant trastuzumab,” said Dr. Edith A. Perez of Mayo Clinic, Jacksonville, Fla., and her associates.

The original trial “was one of several large studies that helped define the standard of care for patients with early-stage HER2-positive breast cancer,” demonstrating that adding trastuzumab to adjuvant chemotherapy was effective at preventing recurrences. However, 20%-25% of women with these tumors still relapse despite this targeted approach, and a biomarker to identify this subset of nonresponders is urgently needed, the investigators said (J. Clin. Oncol. 2015 Jan. 19. [doi:10.1200/JCO.2014.57.6298]).

To identify such a biomarker, they performed whole transcriptome analysis of 1,282 breast cancer samples collected in the trial that were evaluable for gene expression profiling. A total of 433 of the cancers had been treated with anthracycline plus cyclophosphamide, followed by paclitaxel. The remaining cancers had been treated with anthracycline plus cyclophosphamide followed by paclitaxel, then trastuzumab (477 tumors) or anthracycline plus cyclophosphamide followed by concurrent paclitaxel plus trastuzumab (372 tumors). There were 204 cancer recurrences overall.

The investigators identified 485 genes expressed by the cancers that were significantly associated with recurrence-free survival and discovered that certain genes linked to immune functions – including T- and B-cell responses, chemokine signaling, chemotaxis, and inflammation – predicted higher recurrence-free survival only in women treated with trastuzumab. They then built a predictive genetic signature comprising 14 genes related to immune function, which was used to designate which tumors were immune response enriched (IRE) and which were non–immune response enriched (NIRE).

Recurrence-free survival was significantly better for women with IRE tumors who received trastuzumab, compared with those who received chemotherapy alone, with a hazard ratio of 0.36. In contrast, recurrence-free survival was no different between women with NIRE tumors who received trastuzumab and those who received chemotherapy alone.

“Our data indicate that a subset of HER2-positive tumors likely manifests a high level of immunologic activity, as evidenced by expression of a diverse cohort of immune function genes.” Thus, the study results suggest that “benefit from adjuvant trastuzumab, beyond the benefit conveyed by chemotherapy alone, may reside largely within this cohort of immune-enriched tumors,” Dr. Perez and her associates said.

It is hoped that these findings, if confirmed in larger studies, can be used to predict which patients would most benefit from trastuzumab. More important, other approaches could be devised for treating patients with NIRE tumors who wouldn’t respond to trastuzumab and who are at high risk for recurrence. Perhaps enhancing the decreased immune activity of their cancers could sensitize the tumors to further biologic therapy, the investigators added.

Early-stage HER2-positive breast cancers that overexpress a subset of genes involved in the regulation of immune function are much more likely to respond to adjuvant trastuzumab therapy than breast cancers that do not express those genes, according to a report published online Jan. 19 in Journal of Clinical Oncology.

This finding from a secondary analysis of tumor samples obtained in a phase III clinical trial represents “the first demonstration of a cohort of immune function genes that seem to predict benefit from adjuvant trastuzumab,” said Dr. Edith A. Perez of Mayo Clinic, Jacksonville, Fla., and her associates.

The original trial “was one of several large studies that helped define the standard of care for patients with early-stage HER2-positive breast cancer,” demonstrating that adding trastuzumab to adjuvant chemotherapy was effective at preventing recurrences. However, 20%-25% of women with these tumors still relapse despite this targeted approach, and a biomarker to identify this subset of nonresponders is urgently needed, the investigators said (J. Clin. Oncol. 2015 Jan. 19. [doi:10.1200/JCO.2014.57.6298]).

To identify such a biomarker, they performed whole transcriptome analysis of 1,282 breast cancer samples collected in the trial that were evaluable for gene expression profiling. A total of 433 of the cancers had been treated with anthracycline plus cyclophosphamide, followed by paclitaxel. The remaining cancers had been treated with anthracycline plus cyclophosphamide followed by paclitaxel, then trastuzumab (477 tumors) or anthracycline plus cyclophosphamide followed by concurrent paclitaxel plus trastuzumab (372 tumors). There were 204 cancer recurrences overall.

The investigators identified 485 genes expressed by the cancers that were significantly associated with recurrence-free survival and discovered that certain genes linked to immune functions – including T- and B-cell responses, chemokine signaling, chemotaxis, and inflammation – predicted higher recurrence-free survival only in women treated with trastuzumab. They then built a predictive genetic signature comprising 14 genes related to immune function, which was used to designate which tumors were immune response enriched (IRE) and which were non–immune response enriched (NIRE).

Recurrence-free survival was significantly better for women with IRE tumors who received trastuzumab, compared with those who received chemotherapy alone, with a hazard ratio of 0.36. In contrast, recurrence-free survival was no different between women with NIRE tumors who received trastuzumab and those who received chemotherapy alone.

“Our data indicate that a subset of HER2-positive tumors likely manifests a high level of immunologic activity, as evidenced by expression of a diverse cohort of immune function genes.” Thus, the study results suggest that “benefit from adjuvant trastuzumab, beyond the benefit conveyed by chemotherapy alone, may reside largely within this cohort of immune-enriched tumors,” Dr. Perez and her associates said.

It is hoped that these findings, if confirmed in larger studies, can be used to predict which patients would most benefit from trastuzumab. More important, other approaches could be devised for treating patients with NIRE tumors who wouldn’t respond to trastuzumab and who are at high risk for recurrence. Perhaps enhancing the decreased immune activity of their cancers could sensitize the tumors to further biologic therapy, the investigators added.

Early-stage HER2-positive breast cancers that overexpress a subset of genes involved in the regulation of immune function are much more likely to respond to adjuvant trastuzumab therapy than breast cancers that do not express those genes, according to a report published online Jan. 19 in Journal of Clinical Oncology.

This finding from a secondary analysis of tumor samples obtained in a phase III clinical trial represents “the first demonstration of a cohort of immune function genes that seem to predict benefit from adjuvant trastuzumab,” said Dr. Edith A. Perez of Mayo Clinic, Jacksonville, Fla., and her associates.

The original trial “was one of several large studies that helped define the standard of care for patients with early-stage HER2-positive breast cancer,” demonstrating that adding trastuzumab to adjuvant chemotherapy was effective at preventing recurrences. However, 20%-25% of women with these tumors still relapse despite this targeted approach, and a biomarker to identify this subset of nonresponders is urgently needed, the investigators said (J. Clin. Oncol. 2015 Jan. 19. [doi:10.1200/JCO.2014.57.6298]).

To identify such a biomarker, they performed whole transcriptome analysis of 1,282 breast cancer samples collected in the trial that were evaluable for gene expression profiling. A total of 433 of the cancers had been treated with anthracycline plus cyclophosphamide, followed by paclitaxel. The remaining cancers had been treated with anthracycline plus cyclophosphamide followed by paclitaxel, then trastuzumab (477 tumors) or anthracycline plus cyclophosphamide followed by concurrent paclitaxel plus trastuzumab (372 tumors). There were 204 cancer recurrences overall.

The investigators identified 485 genes expressed by the cancers that were significantly associated with recurrence-free survival and discovered that certain genes linked to immune functions – including T- and B-cell responses, chemokine signaling, chemotaxis, and inflammation – predicted higher recurrence-free survival only in women treated with trastuzumab. They then built a predictive genetic signature comprising 14 genes related to immune function, which was used to designate which tumors were immune response enriched (IRE) and which were non–immune response enriched (NIRE).

Recurrence-free survival was significantly better for women with IRE tumors who received trastuzumab, compared with those who received chemotherapy alone, with a hazard ratio of 0.36. In contrast, recurrence-free survival was no different between women with NIRE tumors who received trastuzumab and those who received chemotherapy alone.

“Our data indicate that a subset of HER2-positive tumors likely manifests a high level of immunologic activity, as evidenced by expression of a diverse cohort of immune function genes.” Thus, the study results suggest that “benefit from adjuvant trastuzumab, beyond the benefit conveyed by chemotherapy alone, may reside largely within this cohort of immune-enriched tumors,” Dr. Perez and her associates said.

It is hoped that these findings, if confirmed in larger studies, can be used to predict which patients would most benefit from trastuzumab. More important, other approaches could be devised for treating patients with NIRE tumors who wouldn’t respond to trastuzumab and who are at high risk for recurrence. Perhaps enhancing the decreased immune activity of their cancers could sensitize the tumors to further biologic therapy, the investigators added.

Adding cetuximab to standard first-line FOLFIRI chemotherapy is beneficial for patients with RAS wild-type metastatic colorectal cancers but not for such tumors with other RAS mutations, according to a report published online Jan. 19 in Journal of Clinical Oncology.

When added to infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) combination chemotherapy, cetuximab improved survival outcomes in the phase III randomized CRYSTAL trial among patients who had KRAS codon 12 and 13 wild-type metastatic colorectal cancer. The researchers now presented the results of their post hoc analysis of a subset of 430 CRYSTAL participants, assessing the treatment’s effect in patients whose tumors carried mutations at RAS loci other than KRAS 12 or 13, said Dr. Eric Van Cutsem of University Hospitals Leuven (Belgium), and his associates.

They found “a clear and significant benefit” in overall survival, progression-free survival, and the rate of objective tumor response when cetuximab was added to FOLFIRI among the 367 patients who had RAS wild-type tumors. In contrast, there was no clear benefit from the addition of cetuximab in the 63 patients who had tumors with other RAS mutations; it neither improved nor worsened outcomes, the investigators said (J. Clin. Oncol. 2015 January 19 [doi:10.1200/JCO.2014.59.4812]).

These findings indicate that molecular testing for all KRAS mutations is essential before considering anti-EGFR therapy for patients with metastatic colorectal cancer, to reserve the addition of cetuximab for those with RAS wild-type tumors, they added.

Adding cetuximab to standard first-line FOLFIRI chemotherapy is beneficial for patients with RAS wild-type metastatic colorectal cancers but not for such tumors with other RAS mutations, according to a report published online Jan. 19 in Journal of Clinical Oncology.

When added to infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) combination chemotherapy, cetuximab improved survival outcomes in the phase III randomized CRYSTAL trial among patients who had KRAS codon 12 and 13 wild-type metastatic colorectal cancer. The researchers now presented the results of their post hoc analysis of a subset of 430 CRYSTAL participants, assessing the treatment’s effect in patients whose tumors carried mutations at RAS loci other than KRAS 12 or 13, said Dr. Eric Van Cutsem of University Hospitals Leuven (Belgium), and his associates.

They found “a clear and significant benefit” in overall survival, progression-free survival, and the rate of objective tumor response when cetuximab was added to FOLFIRI among the 367 patients who had RAS wild-type tumors. In contrast, there was no clear benefit from the addition of cetuximab in the 63 patients who had tumors with other RAS mutations; it neither improved nor worsened outcomes, the investigators said (J. Clin. Oncol. 2015 January 19 [doi:10.1200/JCO.2014.59.4812]).

These findings indicate that molecular testing for all KRAS mutations is essential before considering anti-EGFR therapy for patients with metastatic colorectal cancer, to reserve the addition of cetuximab for those with RAS wild-type tumors, they added.

Adding cetuximab to standard first-line FOLFIRI chemotherapy is beneficial for patients with RAS wild-type metastatic colorectal cancers but not for such tumors with other RAS mutations, according to a report published online Jan. 19 in Journal of Clinical Oncology.

When added to infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) combination chemotherapy, cetuximab improved survival outcomes in the phase III randomized CRYSTAL trial among patients who had KRAS codon 12 and 13 wild-type metastatic colorectal cancer. The researchers now presented the results of their post hoc analysis of a subset of 430 CRYSTAL participants, assessing the treatment’s effect in patients whose tumors carried mutations at RAS loci other than KRAS 12 or 13, said Dr. Eric Van Cutsem of University Hospitals Leuven (Belgium), and his associates.

They found “a clear and significant benefit” in overall survival, progression-free survival, and the rate of objective tumor response when cetuximab was added to FOLFIRI among the 367 patients who had RAS wild-type tumors. In contrast, there was no clear benefit from the addition of cetuximab in the 63 patients who had tumors with other RAS mutations; it neither improved nor worsened outcomes, the investigators said (J. Clin. Oncol. 2015 January 19 [doi:10.1200/JCO.2014.59.4812]).

These findings indicate that molecular testing for all KRAS mutations is essential before considering anti-EGFR therapy for patients with metastatic colorectal cancer, to reserve the addition of cetuximab for those with RAS wild-type tumors, they added.

Among adults who present to the emergency department with acute heart failure, blood glucose levels may predict 30-day mortality, regardless of whether or not the patients have preexisting diabetes.

At ED presentation, patients with acute heart failure syndrome “demonstrate a wide spectrum of physiological and metabolic perturbations.” Hyperglycemia occurs in up to 40% of them, irrespective of their diabetes status. “If blood glucose measurement is prognostically useful, it may be of broad potential utility because it is a rapid, readily available, and inexpensive test that can be used in the acute setting to allow rapid risk stratification for a wide range of potential outcomes,” according to Dr. Maneesh Sud of the University of Toronto and Toronto General Hospital and his associates.

To examine whether initial glucose level correlated with later outcomes, the investigators analyzed data from two large population-based cohorts of patients hospitalized for acute HF during a 3-year period. A total of 9,275 of the 16,524 patients (median age, 79 years) did not have preexisting diabetes (56%), and the remaining 44% did (Eur. Heart J. 2015 [doi:10.1093/eurheartj/ehu462]).

Among patients with diabetes, a blood glucose level exceeding 11.1 mmol/L was associated with significantly increased all-cause 30-day mortality, compared with normal glucose levels, with a hazard ratio (HR) of 1.48. Among patients without diabetes, a blood glucose level exceeding 6.1 mmol/L was associated with significantly increased all-cause 30-day mortality, with an HR of 1.26, and that risk rose with increasing glucose levels to 1.50 at the maximum level of 11.1 mmol/L.

The risk for cardiovascular death within 30 days increased as blood glucose levels rose for both groups of patients, as did the risk for cardiovascular hospitalization. In addition, both patients who had preexisting diabetes and those who did not were at significantly increased risk for diabetes-related hospitalization if their blood glucose level exceeded the normal range at presentation to the ED. And, in patients without diabetes who had elevated blood glucose levels, the risk of developing diabetes was significantly increased, in a dose-dependent fashion. These findings suggest that determining blood glucose levels at ED presentation “may serve as a screen to identify high-risk patients who warrant formal testing for diabetes, allowing for prompt referral to prevent further morbidity and mortality,” Dr. Sud and his associates said.

Among adults who present to the emergency department with acute heart failure, blood glucose levels may predict 30-day mortality, regardless of whether or not the patients have preexisting diabetes.

At ED presentation, patients with acute heart failure syndrome “demonstrate a wide spectrum of physiological and metabolic perturbations.” Hyperglycemia occurs in up to 40% of them, irrespective of their diabetes status. “If blood glucose measurement is prognostically useful, it may be of broad potential utility because it is a rapid, readily available, and inexpensive test that can be used in the acute setting to allow rapid risk stratification for a wide range of potential outcomes,” according to Dr. Maneesh Sud of the University of Toronto and Toronto General Hospital and his associates.

To examine whether initial glucose level correlated with later outcomes, the investigators analyzed data from two large population-based cohorts of patients hospitalized for acute HF during a 3-year period. A total of 9,275 of the 16,524 patients (median age, 79 years) did not have preexisting diabetes (56%), and the remaining 44% did (Eur. Heart J. 2015 [doi:10.1093/eurheartj/ehu462]).

Among patients with diabetes, a blood glucose level exceeding 11.1 mmol/L was associated with significantly increased all-cause 30-day mortality, compared with normal glucose levels, with a hazard ratio (HR) of 1.48. Among patients without diabetes, a blood glucose level exceeding 6.1 mmol/L was associated with significantly increased all-cause 30-day mortality, with an HR of 1.26, and that risk rose with increasing glucose levels to 1.50 at the maximum level of 11.1 mmol/L.

The risk for cardiovascular death within 30 days increased as blood glucose levels rose for both groups of patients, as did the risk for cardiovascular hospitalization. In addition, both patients who had preexisting diabetes and those who did not were at significantly increased risk for diabetes-related hospitalization if their blood glucose level exceeded the normal range at presentation to the ED. And, in patients without diabetes who had elevated blood glucose levels, the risk of developing diabetes was significantly increased, in a dose-dependent fashion. These findings suggest that determining blood glucose levels at ED presentation “may serve as a screen to identify high-risk patients who warrant formal testing for diabetes, allowing for prompt referral to prevent further morbidity and mortality,” Dr. Sud and his associates said.

Among adults who present to the emergency department with acute heart failure, blood glucose levels may predict 30-day mortality, regardless of whether or not the patients have preexisting diabetes.

At ED presentation, patients with acute heart failure syndrome “demonstrate a wide spectrum of physiological and metabolic perturbations.” Hyperglycemia occurs in up to 40% of them, irrespective of their diabetes status. “If blood glucose measurement is prognostically useful, it may be of broad potential utility because it is a rapid, readily available, and inexpensive test that can be used in the acute setting to allow rapid risk stratification for a wide range of potential outcomes,” according to Dr. Maneesh Sud of the University of Toronto and Toronto General Hospital and his associates.

To examine whether initial glucose level correlated with later outcomes, the investigators analyzed data from two large population-based cohorts of patients hospitalized for acute HF during a 3-year period. A total of 9,275 of the 16,524 patients (median age, 79 years) did not have preexisting diabetes (56%), and the remaining 44% did (Eur. Heart J. 2015 [doi:10.1093/eurheartj/ehu462]).

Among patients with diabetes, a blood glucose level exceeding 11.1 mmol/L was associated with significantly increased all-cause 30-day mortality, compared with normal glucose levels, with a hazard ratio (HR) of 1.48. Among patients without diabetes, a blood glucose level exceeding 6.1 mmol/L was associated with significantly increased all-cause 30-day mortality, with an HR of 1.26, and that risk rose with increasing glucose levels to 1.50 at the maximum level of 11.1 mmol/L.

The risk for cardiovascular death within 30 days increased as blood glucose levels rose for both groups of patients, as did the risk for cardiovascular hospitalization. In addition, both patients who had preexisting diabetes and those who did not were at significantly increased risk for diabetes-related hospitalization if their blood glucose level exceeded the normal range at presentation to the ED. And, in patients without diabetes who had elevated blood glucose levels, the risk of developing diabetes was significantly increased, in a dose-dependent fashion. These findings suggest that determining blood glucose levels at ED presentation “may serve as a screen to identify high-risk patients who warrant formal testing for diabetes, allowing for prompt referral to prevent further morbidity and mortality,” Dr. Sud and his associates said.

The abuse of prescription opioids plateaued and began to decline in recent years, after its alarming rise to epidemic levels in 2002-2010, according to a report published online Jan. 15 in the New England Journal of Medicine.

Hundreds of programs have been implemented by local, state, and federal governments to limit opioid prescribing, reduce doctor shopping, improve questionable practices by pain clinics, and close “pill mills.” Other organizations also have taken steps to stem the epidemic, such as formulating guidelines for responsible opioid prescribing, and new opioid formulations have been devised to resist tampering. “The impressive response to the epidemic is heartening, but the effect of these programs is not yet known,” wrote Dr. Richard C. Dart of the Rocky Mountain Poison and Drug Center, Denver, and his associates (N. Engl. J. Med. 2015 Jan. 15 [doi:10.1056/NEJM.sa1406143]).

To assess such effects, the investigators analyzed data from five programs in the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) database for the years 2002 through 2013. One program tracked cases reported to poison control centers that were classified as intentional abuse, another tracked investigations into prescription-drug diversion by law enforcement agencies, two more surveyed new patients entering substance abuse treatment about their recent drug use, and the fifth compiled college students’ anonymous reporting of their recent use of prescription drugs. The investigators focused on data regarding oxycodone, hydrocodone, hydromorphone, fentanyl, morphine, and tramadol.

According to all five RADARS measures, opioid abuse continued to greatly increase through 2010 but then plateaued and began to decline in 2011-2013. The rate of opioid-related deaths paralleled this pattern, rising precipitously through 2010 but then flattening and falling off in 2011-2013.

“Our results suggest that the United States is making progress in combating the abuse of prescription opioid analgesics. If our observation of decreased abuse is confirmed, changes in public health policy and strategy will be needed” Dr. Dart and his associates wrote.

This study was supported by the Denver Health and Hospital Authority, which owns the RADARS system. Dr. Dart and his associates reported having no relevant financial disclosures.

The abuse of prescription opioids plateaued and began to decline in recent years, after its alarming rise to epidemic levels in 2002-2010, according to a report published online Jan. 15 in the New England Journal of Medicine.

Hundreds of programs have been implemented by local, state, and federal governments to limit opioid prescribing, reduce doctor shopping, improve questionable practices by pain clinics, and close “pill mills.” Other organizations also have taken steps to stem the epidemic, such as formulating guidelines for responsible opioid prescribing, and new opioid formulations have been devised to resist tampering. “The impressive response to the epidemic is heartening, but the effect of these programs is not yet known,” wrote Dr. Richard C. Dart of the Rocky Mountain Poison and Drug Center, Denver, and his associates (N. Engl. J. Med. 2015 Jan. 15 [doi:10.1056/NEJM.sa1406143]).

To assess such effects, the investigators analyzed data from five programs in the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) database for the years 2002 through 2013. One program tracked cases reported to poison control centers that were classified as intentional abuse, another tracked investigations into prescription-drug diversion by law enforcement agencies, two more surveyed new patients entering substance abuse treatment about their recent drug use, and the fifth compiled college students’ anonymous reporting of their recent use of prescription drugs. The investigators focused on data regarding oxycodone, hydrocodone, hydromorphone, fentanyl, morphine, and tramadol.

According to all five RADARS measures, opioid abuse continued to greatly increase through 2010 but then plateaued and began to decline in 2011-2013. The rate of opioid-related deaths paralleled this pattern, rising precipitously through 2010 but then flattening and falling off in 2011-2013.

“Our results suggest that the United States is making progress in combating the abuse of prescription opioid analgesics. If our observation of decreased abuse is confirmed, changes in public health policy and strategy will be needed” Dr. Dart and his associates wrote.

This study was supported by the Denver Health and Hospital Authority, which owns the RADARS system. Dr. Dart and his associates reported having no relevant financial disclosures.

The abuse of prescription opioids plateaued and began to decline in recent years, after its alarming rise to epidemic levels in 2002-2010, according to a report published online Jan. 15 in the New England Journal of Medicine.

Hundreds of programs have been implemented by local, state, and federal governments to limit opioid prescribing, reduce doctor shopping, improve questionable practices by pain clinics, and close “pill mills.” Other organizations also have taken steps to stem the epidemic, such as formulating guidelines for responsible opioid prescribing, and new opioid formulations have been devised to resist tampering. “The impressive response to the epidemic is heartening, but the effect of these programs is not yet known,” wrote Dr. Richard C. Dart of the Rocky Mountain Poison and Drug Center, Denver, and his associates (N. Engl. J. Med. 2015 Jan. 15 [doi:10.1056/NEJM.sa1406143]).

To assess such effects, the investigators analyzed data from five programs in the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) database for the years 2002 through 2013. One program tracked cases reported to poison control centers that were classified as intentional abuse, another tracked investigations into prescription-drug diversion by law enforcement agencies, two more surveyed new patients entering substance abuse treatment about their recent drug use, and the fifth compiled college students’ anonymous reporting of their recent use of prescription drugs. The investigators focused on data regarding oxycodone, hydrocodone, hydromorphone, fentanyl, morphine, and tramadol.

According to all five RADARS measures, opioid abuse continued to greatly increase through 2010 but then plateaued and began to decline in 2011-2013. The rate of opioid-related deaths paralleled this pattern, rising precipitously through 2010 but then flattening and falling off in 2011-2013.

“Our results suggest that the United States is making progress in combating the abuse of prescription opioid analgesics. If our observation of decreased abuse is confirmed, changes in public health policy and strategy will be needed” Dr. Dart and his associates wrote.

This study was supported by the Denver Health and Hospital Authority, which owns the RADARS system. Dr. Dart and his associates reported having no relevant financial disclosures.

The abuse of prescription opioids plateaued and began to decline in recent years, after its alarming rise to epidemic levels in 2002-2010, according to a report published online Jan. 15 in the New England Journal of Medicine.

Hundreds of programs have been implemented by local, state, and federal governments to limit opioid prescribing, reduce doctor shopping, improve questionable practices by pain clinics, and close “pill mills.” Other organizations also have taken steps to stem the epidemic, such as formulating guidelines for responsible opioid prescribing, and new opioid formulations have been devised to resist tampering. “The impressive response to the epidemic is heartening, but the effect of these programs is not yet known,” wrote Dr. Richard C. Dart of the Rocky Mountain Poison and Drug Center, Denver, and his associates (N. Engl. J. Med. 2015 Jan. 15 [doi:10.1056/NEJM.sa1406143]).

©eriksvoboda/Thinkstock.com

To assess such effects, the investigators analyzed data from five programs in the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) database for the years 2002 through 2013. One program tracked cases reported to poison control centers that were classified as intentional abuse, another tracked investigations into prescription-drug diversion by law enforcement agencies, two more surveyed new patients entering substance abuse treatment about their recent drug use, and the fifth compiled college students’ anonymous reporting of their recent use of prescription drugs. The investigators focused on data regarding oxycodone, hydrocodone, hydromorphone, fentanyl, morphine, and tramadol.

According to all five RADARS measures, opioid abuse continued to greatly increase through 2010 but then plateaued and began to decline in 2011-2013. The rate of opioid-related deaths paralleled this pattern, rising precipitously through 2010 but then flattening and falling off in 2011-2013.

“Our results suggest that the United States is making progress in combating the abuse of prescription opioid analgesics. If our observation of decreased abuse is confirmed, changes in public health policy and strategy will be needed” Dr. Dart and his associates wrote.

This study was supported by the Denver Health and Hospital Authority, which owns the RADARS system. Dr. Dart and his associates reported having no relevant financial disclosures.

The abuse of prescription opioids plateaued and began to decline in recent years, after its alarming rise to epidemic levels in 2002-2010, according to a report published online Jan. 15 in the New England Journal of Medicine.

Hundreds of programs have been implemented by local, state, and federal governments to limit opioid prescribing, reduce doctor shopping, improve questionable practices by pain clinics, and close “pill mills.” Other organizations also have taken steps to stem the epidemic, such as formulating guidelines for responsible opioid prescribing, and new opioid formulations have been devised to resist tampering. “The impressive response to the epidemic is heartening, but the effect of these programs is not yet known,” wrote Dr. Richard C. Dart of the Rocky Mountain Poison and Drug Center, Denver, and his associates (N. Engl. J. Med. 2015 Jan. 15 [doi:10.1056/NEJM.sa1406143]).

©eriksvoboda/Thinkstock.com

To assess such effects, the investigators analyzed data from five programs in the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) database for the years 2002 through 2013. One program tracked cases reported to poison control centers that were classified as intentional abuse, another tracked investigations into prescription-drug diversion by law enforcement agencies, two more surveyed new patients entering substance abuse treatment about their recent drug use, and the fifth compiled college students’ anonymous reporting of their recent use of prescription drugs. The investigators focused on data regarding oxycodone, hydrocodone, hydromorphone, fentanyl, morphine, and tramadol.

According to all five RADARS measures, opioid abuse continued to greatly increase through 2010 but then plateaued and began to decline in 2011-2013. The rate of opioid-related deaths paralleled this pattern, rising precipitously through 2010 but then flattening and falling off in 2011-2013.

“Our results suggest that the United States is making progress in combating the abuse of prescription opioid analgesics. If our observation of decreased abuse is confirmed, changes in public health policy and strategy will be needed” Dr. Dart and his associates wrote.

This study was supported by the Denver Health and Hospital Authority, which owns the RADARS system. Dr. Dart and his associates reported having no relevant financial disclosures.

The abuse of prescription opioids plateaued and began to decline in recent years, after its alarming rise to epidemic levels in 2002-2010, according to a report published online Jan. 15 in the New England Journal of Medicine.

Hundreds of programs have been implemented by local, state, and federal governments to limit opioid prescribing, reduce doctor shopping, improve questionable practices by pain clinics, and close “pill mills.” Other organizations also have taken steps to stem the epidemic, such as formulating guidelines for responsible opioid prescribing, and new opioid formulations have been devised to resist tampering. “The impressive response to the epidemic is heartening, but the effect of these programs is not yet known,” wrote Dr. Richard C. Dart of the Rocky Mountain Poison and Drug Center, Denver, and his associates (N. Engl. J. Med. 2015 Jan. 15 [doi:10.1056/NEJM.sa1406143]).

©eriksvoboda/Thinkstock.com

To assess such effects, the investigators analyzed data from five programs in the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) database for the years 2002 through 2013. One program tracked cases reported to poison control centers that were classified as intentional abuse, another tracked investigations into prescription-drug diversion by law enforcement agencies, two more surveyed new patients entering substance abuse treatment about their recent drug use, and the fifth compiled college students’ anonymous reporting of their recent use of prescription drugs. The investigators focused on data regarding oxycodone, hydrocodone, hydromorphone, fentanyl, morphine, and tramadol.

According to all five RADARS measures, opioid abuse continued to greatly increase through 2010 but then plateaued and began to decline in 2011-2013. The rate of opioid-related deaths paralleled this pattern, rising precipitously through 2010 but then flattening and falling off in 2011-2013.

“Our results suggest that the United States is making progress in combating the abuse of prescription opioid analgesics. If our observation of decreased abuse is confirmed, changes in public health policy and strategy will be needed” Dr. Dart and his associates wrote.

This study was supported by the Denver Health and Hospital Authority, which owns the RADARS system. Dr. Dart and his associates reported having no relevant financial disclosures.

Adults who have asthma are at significantly greater risk than are those who don’t for developing obstructive sleep apnea, according to a report published Jan. 13 in JAMA.

“Accumulating evidence suggests a bidirectional relationship between asthma and obstructive sleep apnea, whereby each disorder deleteriously influences the other,” said Dr. Mihaela Teodorescu of the University of Wisconsin, Madison, and her colleagues.

To understand the “initiating processes of a potentially self-enforcing asthma-apnea cycle,” the investigators analyzed data from the Wisconsin Sleep Cohort Study, a population-based longitudinal epidemiologic investigation of the natural history of obstructive sleep apnea that began in 1988 and followed participants at 4-year intervals for up to 24 years. For their analysis, Dr. Teodorescu and her colleagues focused on a subset of 547 participants.

©moodboard/thinkstockphotos.com

In their first 4-year follow-up intervals, 22 of 81 participants with preexisting asthma (27%) developed incident obstructive sleep apnea, compared with 75 of 466 participants who didn’t have asthma (16%). When all the interval observations were considered, there were 45 cases of obstructive sleep apnea among 167 possible intervals in participants who had preexisting asthma, for a rate of 27%, and 160 cases among 938 possible intervals in participants without asthma, for a rate of 17%. Compared with people who didn’t have asthma, those who did showed a relative risk of 1.39 for developing apnea, regardless of potentially confounding factors such as body mass index, the investigators said (JAMA 2015 Jan. 13 [doi:10.1001/jama.2014.17822]).

This association showed a dose-response pattern when cases were categorized according to the duration of asthma, with the highest risk for obstructive sleep apnea occurring among people who had asthma of 10 or more years’ duration. The association also remained robust in numerous additional analyses, including one involving only the subset of 220 participants who had spirometry results, another involving only participants who used asthma controller medications, and a third that accounted for participants’ neck girth, waist girth, and waist-to-hip ratio.

The mechanism(s) by which asthma may predispose patients to obstructive sleep apnea is not known, but could pertain to the disease itself, its treatment, or its common comorbidities. Nighttime asthma attacks could increase pressure in pharyngeal airway tissues, or pharyngeal airway stiffness could decrease because asthma causes abrupt drops in lung volumes during sleep, or a “spillover” of systemic inflammation could weaken the respiratory muscles or trigger CNS inflammatory responses. Corticosteroid therapy could alter the architecture of the pharyngeal airway by raising or redistributing pressures in the tissues there, or it could diminish the contractility of the dilator muscles. And coexisting gastroesophageal reflux could trigger pharyngeal spasms and induce mucosal exudative neurogenic inflammation, Dr. Teodorescu and her associates said.

Adults who have asthma are at significantly greater risk than are those who don’t for developing obstructive sleep apnea, according to a report published Jan. 13 in JAMA.

“Accumulating evidence suggests a bidirectional relationship between asthma and obstructive sleep apnea, whereby each disorder deleteriously influences the other,” said Dr. Mihaela Teodorescu of the University of Wisconsin, Madison, and her colleagues.

To understand the “initiating processes of a potentially self-enforcing asthma-apnea cycle,” the investigators analyzed data from the Wisconsin Sleep Cohort Study, a population-based longitudinal epidemiologic investigation of the natural history of obstructive sleep apnea that began in 1988 and followed participants at 4-year intervals for up to 24 years. For their analysis, Dr. Teodorescu and her colleagues focused on a subset of 547 participants.

©moodboard/thinkstockphotos.com

In their first 4-year follow-up intervals, 22 of 81 participants with preexisting asthma (27%) developed incident obstructive sleep apnea, compared with 75 of 466 participants who didn’t have asthma (16%). When all the interval observations were considered, there were 45 cases of obstructive sleep apnea among 167 possible intervals in participants who had preexisting asthma, for a rate of 27%, and 160 cases among 938 possible intervals in participants without asthma, for a rate of 17%. Compared with people who didn’t have asthma, those who did showed a relative risk of 1.39 for developing apnea, regardless of potentially confounding factors such as body mass index, the investigators said (JAMA 2015 Jan. 13 [doi:10.1001/jama.2014.17822]).

This association showed a dose-response pattern when cases were categorized according to the duration of asthma, with the highest risk for obstructive sleep apnea occurring among people who had asthma of 10 or more years’ duration. The association also remained robust in numerous additional analyses, including one involving only the subset of 220 participants who had spirometry results, another involving only participants who used asthma controller medications, and a third that accounted for participants’ neck girth, waist girth, and waist-to-hip ratio.

The mechanism(s) by which asthma may predispose patients to obstructive sleep apnea is not known, but could pertain to the disease itself, its treatment, or its common comorbidities. Nighttime asthma attacks could increase pressure in pharyngeal airway tissues, or pharyngeal airway stiffness could decrease because asthma causes abrupt drops in lung volumes during sleep, or a “spillover” of systemic inflammation could weaken the respiratory muscles or trigger CNS inflammatory responses. Corticosteroid therapy could alter the architecture of the pharyngeal airway by raising or redistributing pressures in the tissues there, or it could diminish the contractility of the dilator muscles. And coexisting gastroesophageal reflux could trigger pharyngeal spasms and induce mucosal exudative neurogenic inflammation, Dr. Teodorescu and her associates said.

Adults who have asthma are at significantly greater risk than are those who don’t for developing obstructive sleep apnea, according to a report published Jan. 13 in JAMA.

“Accumulating evidence suggests a bidirectional relationship between asthma and obstructive sleep apnea, whereby each disorder deleteriously influences the other,” said Dr. Mihaela Teodorescu of the University of Wisconsin, Madison, and her colleagues.

To understand the “initiating processes of a potentially self-enforcing asthma-apnea cycle,” the investigators analyzed data from the Wisconsin Sleep Cohort Study, a population-based longitudinal epidemiologic investigation of the natural history of obstructive sleep apnea that began in 1988 and followed participants at 4-year intervals for up to 24 years. For their analysis, Dr. Teodorescu and her colleagues focused on a subset of 547 participants.

©moodboard/thinkstockphotos.com

In their first 4-year follow-up intervals, 22 of 81 participants with preexisting asthma (27%) developed incident obstructive sleep apnea, compared with 75 of 466 participants who didn’t have asthma (16%). When all the interval observations were considered, there were 45 cases of obstructive sleep apnea among 167 possible intervals in participants who had preexisting asthma, for a rate of 27%, and 160 cases among 938 possible intervals in participants without asthma, for a rate of 17%. Compared with people who didn’t have asthma, those who did showed a relative risk of 1.39 for developing apnea, regardless of potentially confounding factors such as body mass index, the investigators said (JAMA 2015 Jan. 13 [doi:10.1001/jama.2014.17822]).

This association showed a dose-response pattern when cases were categorized according to the duration of asthma, with the highest risk for obstructive sleep apnea occurring among people who had asthma of 10 or more years’ duration. The association also remained robust in numerous additional analyses, including one involving only the subset of 220 participants who had spirometry results, another involving only participants who used asthma controller medications, and a third that accounted for participants’ neck girth, waist girth, and waist-to-hip ratio.

The mechanism(s) by which asthma may predispose patients to obstructive sleep apnea is not known, but could pertain to the disease itself, its treatment, or its common comorbidities. Nighttime asthma attacks could increase pressure in pharyngeal airway tissues, or pharyngeal airway stiffness could decrease because asthma causes abrupt drops in lung volumes during sleep, or a “spillover” of systemic inflammation could weaken the respiratory muscles or trigger CNS inflammatory responses. Corticosteroid therapy could alter the architecture of the pharyngeal airway by raising or redistributing pressures in the tissues there, or it could diminish the contractility of the dilator muscles. And coexisting gastroesophageal reflux could trigger pharyngeal spasms and induce mucosal exudative neurogenic inflammation, Dr. Teodorescu and her associates said.

Sunitinib elicited an “exceptional” treatment response from refractory thymic carcinoma in an open-label phase II clinical trial involving 40 patients, investigators reported online in Lancet Oncology.

The oral tyrosine kinase inhibitor produced a 26% rate of complete or partial response for thymic epithelial tumors overall and a 91% response rate in the subset of patients with thymic carcinoma. That response was rapid and durable with continued administration of the agent. This is particularly important because most of the study participants had failed on two or more previous treatments including platinum-based chemotherapy, and no other standard treatments are available for patients who have this aggressive cancer. “Our trial is the first to show robust and durable clinical activity of a targeted agent in previously treated patients with thymic carcinoma,” said Dr. Anish Thomas of the Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, Bethesda, Md., and his associates.

The trial, performed at two U.S. cancer centers during an 18-month period, involved 24 patients with thymic carcinoma and 16 with advanced thymoma whose disease had progressed despite at least one line of platinum-based chemotherapy. All the participants were given oral sunitinib once daily in 6-week cycles until further progression or unacceptable adverse events occurred. A total of 21 of the 23 assessable patients with thymic carcinoma (91%) achieved disease control (partial response or stable disease), as did 13 of the 16 patients who had thymoma (81%), and the median duration of response was 16.4 months. Median progression-free survival was 7.2 months for thymic carcinoma and 8.5 months for thymoma, and 1-year estimated survival was 78% and 86%, respectively.

Sunitinib was generally well tolerated, though many patients required dose reductions. “Considering concurrent cardiac risk factors in patients with thymic epithelial tumors – e.g., previous exposure to anthracyclines, radiation, and high rates of subclinical cardiac tumor involvement – careful monitoring of cardiac function is needed,” Dr. Thomas and his associates said (Lancet Oncol. 2015 Jan. 13 [doi:10.1016/S1470-2045(14)71181-7]).

They noted that these exploratory findings should be viewed with caution and must be confirmed in larger cohorts. At least one such trial (NCT01621568) is currently underway.

Sunitinib elicited an “exceptional” treatment response from refractory thymic carcinoma in an open-label phase II clinical trial involving 40 patients, investigators reported online in Lancet Oncology.

The oral tyrosine kinase inhibitor produced a 26% rate of complete or partial response for thymic epithelial tumors overall and a 91% response rate in the subset of patients with thymic carcinoma. That response was rapid and durable with continued administration of the agent. This is particularly important because most of the study participants had failed on two or more previous treatments including platinum-based chemotherapy, and no other standard treatments are available for patients who have this aggressive cancer. “Our trial is the first to show robust and durable clinical activity of a targeted agent in previously treated patients with thymic carcinoma,” said Dr. Anish Thomas of the Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, Bethesda, Md., and his associates.

The trial, performed at two U.S. cancer centers during an 18-month period, involved 24 patients with thymic carcinoma and 16 with advanced thymoma whose disease had progressed despite at least one line of platinum-based chemotherapy. All the participants were given oral sunitinib once daily in 6-week cycles until further progression or unacceptable adverse events occurred. A total of 21 of the 23 assessable patients with thymic carcinoma (91%) achieved disease control (partial response or stable disease), as did 13 of the 16 patients who had thymoma (81%), and the median duration of response was 16.4 months. Median progression-free survival was 7.2 months for thymic carcinoma and 8.5 months for thymoma, and 1-year estimated survival was 78% and 86%, respectively.

Sunitinib was generally well tolerated, though many patients required dose reductions. “Considering concurrent cardiac risk factors in patients with thymic epithelial tumors – e.g., previous exposure to anthracyclines, radiation, and high rates of subclinical cardiac tumor involvement – careful monitoring of cardiac function is needed,” Dr. Thomas and his associates said (Lancet Oncol. 2015 Jan. 13 [doi:10.1016/S1470-2045(14)71181-7]).

They noted that these exploratory findings should be viewed with caution and must be confirmed in larger cohorts. At least one such trial (NCT01621568) is currently underway.

Sunitinib elicited an “exceptional” treatment response from refractory thymic carcinoma in an open-label phase II clinical trial involving 40 patients, investigators reported online in Lancet Oncology.

The oral tyrosine kinase inhibitor produced a 26% rate of complete or partial response for thymic epithelial tumors overall and a 91% response rate in the subset of patients with thymic carcinoma. That response was rapid and durable with continued administration of the agent. This is particularly important because most of the study participants had failed on two or more previous treatments including platinum-based chemotherapy, and no other standard treatments are available for patients who have this aggressive cancer. “Our trial is the first to show robust and durable clinical activity of a targeted agent in previously treated patients with thymic carcinoma,” said Dr. Anish Thomas of the Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, Bethesda, Md., and his associates.

The trial, performed at two U.S. cancer centers during an 18-month period, involved 24 patients with thymic carcinoma and 16 with advanced thymoma whose disease had progressed despite at least one line of platinum-based chemotherapy. All the participants were given oral sunitinib once daily in 6-week cycles until further progression or unacceptable adverse events occurred. A total of 21 of the 23 assessable patients with thymic carcinoma (91%) achieved disease control (partial response or stable disease), as did 13 of the 16 patients who had thymoma (81%), and the median duration of response was 16.4 months. Median progression-free survival was 7.2 months for thymic carcinoma and 8.5 months for thymoma, and 1-year estimated survival was 78% and 86%, respectively.

Sunitinib was generally well tolerated, though many patients required dose reductions. “Considering concurrent cardiac risk factors in patients with thymic epithelial tumors – e.g., previous exposure to anthracyclines, radiation, and high rates of subclinical cardiac tumor involvement – careful monitoring of cardiac function is needed,” Dr. Thomas and his associates said (Lancet Oncol. 2015 Jan. 13 [doi:10.1016/S1470-2045(14)71181-7]).

They noted that these exploratory findings should be viewed with caution and must be confirmed in larger cohorts. At least one such trial (NCT01621568) is currently underway.

Most older patients with diabetes who had complex or poor health status and limited life expectancy were still given insulin or sulfonylureas to achieve tight glycemic control, even though such intensive treatment likely causes more harm than good in this patient population, according to a report published online Jan. 12 in JAMA Internal Medicine.

Diabetes is highly prevalent among Americans aged 65 years and older, and tight glycemic control achieved through medication use poses significant threats to them – chiefly, hypoglycemia –without imparting the benefits seen in younger, healthier patients, said Dr. Kasia J. Lipska of Yale University, New Haven, Conn., and her associates. Hypoglycemia is associated with increased mortality, cardiovascular disease, falls and accidents, dementia, and a poor health-related quality of life in older adults.

To examine such overtreatment, the investigators analyzed National Health and Nutrition Examination Survey data during a 10-year period. They focused on 1,288 participants aged 65 years and older (mean age, 73 years) whose hemoglobin A1c levels indicated glycemic control that was categorized as poor (9% or higher), moderate (7%-8.9%), or tight (<7%); the latter category included those patients with very tight glycemic control (<6.5%).

Dr. Lipska and her associates found that 62% of the sample, representing nearly 4 million older Americans, had tight glycemic control, including 42%, representing 2.6 million older Americans, who had very tight glycemic control.

Most of those patients were taking insulin or sulfonylureas. That included the majority of patients who had complex health profiles or poor health because of such coexisting conditions as arthritis, heart failure, lung disease, chronic kidney disease, coronary heart disease, stroke, urinary incontinence, and functional impairments.

“Given incomplete information on all comorbidities in our study, it is likely that we underestimated the complexity of health status, and thus, true estimates of adults who are potentially overtreated may be even higher,” the investigators said (JAMA Intern. Med. 2015 Jan. 12 [doi:10.1001/jamainternmed.2014.7345]).

“Recognition of both the harms and the benefits of glycemic control is critical for patients and physicians and other health care professionals to make informed decisions about glucose-lowering treatment,” the investigators added.

A Pepper Center Career Development Award, the National Institute on Aging, the Yale Center for Investigation, the American Federation for Aging Research, the Paul B. Beeson Career Development Program, and the National Institutes of Health funded the study. Dr. Lipska reported having no financial conflicts. Her associates reported ties to Medtronic, Johnson & Johnson, and FAIR Health.

Most older patients with diabetes who had complex or poor health status and limited life expectancy were still given insulin or sulfonylureas to achieve tight glycemic control, even though such intensive treatment likely causes more harm than good in this patient population, according to a report published online Jan. 12 in JAMA Internal Medicine.

Diabetes is highly prevalent among Americans aged 65 years and older, and tight glycemic control achieved through medication use poses significant threats to them – chiefly, hypoglycemia –without imparting the benefits seen in younger, healthier patients, said Dr. Kasia J. Lipska of Yale University, New Haven, Conn., and her associates. Hypoglycemia is associated with increased mortality, cardiovascular disease, falls and accidents, dementia, and a poor health-related quality of life in older adults.

To examine such overtreatment, the investigators analyzed National Health and Nutrition Examination Survey data during a 10-year period. They focused on 1,288 participants aged 65 years and older (mean age, 73 years) whose hemoglobin A1c levels indicated glycemic control that was categorized as poor (9% or higher), moderate (7%-8.9%), or tight (<7%); the latter category included those patients with very tight glycemic control (<6.5%).

Dr. Lipska and her associates found that 62% of the sample, representing nearly 4 million older Americans, had tight glycemic control, including 42%, representing 2.6 million older Americans, who had very tight glycemic control.

Most of those patients were taking insulin or sulfonylureas. That included the majority of patients who had complex health profiles or poor health because of such coexisting conditions as arthritis, heart failure, lung disease, chronic kidney disease, coronary heart disease, stroke, urinary incontinence, and functional impairments.

“Given incomplete information on all comorbidities in our study, it is likely that we underestimated the complexity of health status, and thus, true estimates of adults who are potentially overtreated may be even higher,” the investigators said (JAMA Intern. Med. 2015 Jan. 12 [doi:10.1001/jamainternmed.2014.7345]).

“Recognition of both the harms and the benefits of glycemic control is critical for patients and physicians and other health care professionals to make informed decisions about glucose-lowering treatment,” the investigators added.

A Pepper Center Career Development Award, the National Institute on Aging, the Yale Center for Investigation, the American Federation for Aging Research, the Paul B. Beeson Career Development Program, and the National Institutes of Health funded the study. Dr. Lipska reported having no financial conflicts. Her associates reported ties to Medtronic, Johnson & Johnson, and FAIR Health.

Most older patients with diabetes who had complex or poor health status and limited life expectancy were still given insulin or sulfonylureas to achieve tight glycemic control, even though such intensive treatment likely causes more harm than good in this patient population, according to a report published online Jan. 12 in JAMA Internal Medicine.

Diabetes is highly prevalent among Americans aged 65 years and older, and tight glycemic control achieved through medication use poses significant threats to them – chiefly, hypoglycemia –without imparting the benefits seen in younger, healthier patients, said Dr. Kasia J. Lipska of Yale University, New Haven, Conn., and her associates. Hypoglycemia is associated with increased mortality, cardiovascular disease, falls and accidents, dementia, and a poor health-related quality of life in older adults.

To examine such overtreatment, the investigators analyzed National Health and Nutrition Examination Survey data during a 10-year period. They focused on 1,288 participants aged 65 years and older (mean age, 73 years) whose hemoglobin A1c levels indicated glycemic control that was categorized as poor (9% or higher), moderate (7%-8.9%), or tight (<7%); the latter category included those patients with very tight glycemic control (<6.5%).

Dr. Lipska and her associates found that 62% of the sample, representing nearly 4 million older Americans, had tight glycemic control, including 42%, representing 2.6 million older Americans, who had very tight glycemic control.

Most of those patients were taking insulin or sulfonylureas. That included the majority of patients who had complex health profiles or poor health because of such coexisting conditions as arthritis, heart failure, lung disease, chronic kidney disease, coronary heart disease, stroke, urinary incontinence, and functional impairments.

“Given incomplete information on all comorbidities in our study, it is likely that we underestimated the complexity of health status, and thus, true estimates of adults who are potentially overtreated may be even higher,” the investigators said (JAMA Intern. Med. 2015 Jan. 12 [doi:10.1001/jamainternmed.2014.7345]).

“Recognition of both the harms and the benefits of glycemic control is critical for patients and physicians and other health care professionals to make informed decisions about glucose-lowering treatment,” the investigators added.

A Pepper Center Career Development Award, the National Institute on Aging, the Yale Center for Investigation, the American Federation for Aging Research, the Paul B. Beeson Career Development Program, and the National Institutes of Health funded the study. Dr. Lipska reported having no financial conflicts. Her associates reported ties to Medtronic, Johnson & Johnson, and FAIR Health.

Most older patients with diabetes who had complex or poor health status and limited life expectancy were still given insulin or sulfonylureas to achieve tight glycemic control, even though such intensive treatment likely causes more harm than good in this patient population, according to a report published online Jan. 12 in JAMA Internal Medicine.

Diabetes is highly prevalent among Americans aged 65 years and older, and tight glycemic control achieved through medication use poses significant threats to them – chiefly, hypoglycemia –without imparting the benefits seen in younger, healthier patients, said Dr. Kasia J. Lipska of Yale University, New Haven, Conn., and her associates. Hypoglycemia is associated with increased mortality, cardiovascular disease, falls and accidents, dementia, and a poor health-related quality of life in older adults.

To examine such overtreatment, the investigators analyzed National Health and Nutrition Examination Survey data during a 10-year period. They focused on 1,288 participants aged 65 years and older (mean age, 73 years) whose hemoglobin A1c levels indicated glycemic control that was categorized as poor (9% or higher), moderate (7%-8.9%), or tight (<7%); the latter category included those patients with very tight glycemic control (<6.5%).

Dr. Lipska and her associates found that 62% of the sample, representing nearly 4 million older Americans, had tight glycemic control, including 42%, representing 2.6 million older Americans, who had very tight glycemic control.

Most of those patients were taking insulin or sulfonylureas. That included the majority of patients who had complex health profiles or poor health because of such coexisting conditions as arthritis, heart failure, lung disease, chronic kidney disease, coronary heart disease, stroke, urinary incontinence, and functional impairments.

“Given incomplete information on all comorbidities in our study, it is likely that we underestimated the complexity of health status, and thus, true estimates of adults who are potentially overtreated may be even higher,” the investigators said (JAMA Intern. Med. 2015 Jan. 12 [doi:10.1001/jamainternmed.2014.7345]).

“Recognition of both the harms and the benefits of glycemic control is critical for patients and physicians and other health care professionals to make informed decisions about glucose-lowering treatment,” the investigators added.

A Pepper Center Career Development Award, the National Institute on Aging, the Yale Center for Investigation, the American Federation for Aging Research, the Paul B. Beeson Career Development Program, and the National Institutes of Health funded the study. Dr. Lipska reported having no financial conflicts. Her associates reported ties to Medtronic, Johnson & Johnson, and FAIR Health.

Most older patients with diabetes who had complex or poor health status and limited life expectancy were still given insulin or sulfonylureas to achieve tight glycemic control, even though such intensive treatment likely causes more harm than good in this patient population, according to a report published online Jan. 12 in JAMA Internal Medicine.

Diabetes is highly prevalent among Americans aged 65 years and older, and tight glycemic control achieved through medication use poses significant threats to them – chiefly, hypoglycemia –without imparting the benefits seen in younger, healthier patients, said Dr. Kasia J. Lipska of Yale University, New Haven, Conn., and her associates. Hypoglycemia is associated with increased mortality, cardiovascular disease, falls and accidents, dementia, and a poor health-related quality of life in older adults.

To examine such overtreatment, the investigators analyzed National Health and Nutrition Examination Survey data during a 10-year period. They focused on 1,288 participants aged 65 years and older (mean age, 73 years) whose hemoglobin A1c levels indicated glycemic control that was categorized as poor (9% or higher), moderate (7%-8.9%), or tight (<7%); the latter category included those patients with very tight glycemic control (<6.5%).

Dr. Lipska and her associates found that 62% of the sample, representing nearly 4 million older Americans, had tight glycemic control, including 42%, representing 2.6 million older Americans, who had very tight glycemic control.

Most of those patients were taking insulin or sulfonylureas. That included the majority of patients who had complex health profiles or poor health because of such coexisting conditions as arthritis, heart failure, lung disease, chronic kidney disease, coronary heart disease, stroke, urinary incontinence, and functional impairments.

“Given incomplete information on all comorbidities in our study, it is likely that we underestimated the complexity of health status, and thus, true estimates of adults who are potentially overtreated may be even higher,” the investigators said (JAMA Intern. Med. 2015 Jan. 12 [doi:10.1001/jamainternmed.2014.7345]).

“Recognition of both the harms and the benefits of glycemic control is critical for patients and physicians and other health care professionals to make informed decisions about glucose-lowering treatment,” the investigators added.

A Pepper Center Career Development Award, the National Institute on Aging, the Yale Center for Investigation, the American Federation for Aging Research, the Paul B. Beeson Career Development Program, and the National Institutes of Health funded the study. Dr. Lipska reported having no financial conflicts. Her associates reported ties to Medtronic, Johnson & Johnson, and FAIR Health.

Most older patients with diabetes who had complex or poor health status and limited life expectancy were still given insulin or sulfonylureas to achieve tight glycemic control, even though such intensive treatment likely causes more harm than good in this patient population, according to a report published online Jan. 12 in JAMA Internal Medicine.

Diabetes is highly prevalent among Americans aged 65 years and older, and tight glycemic control achieved through medication use poses significant threats to them – chiefly, hypoglycemia –without imparting the benefits seen in younger, healthier patients, said Dr. Kasia J. Lipska of Yale University, New Haven, Conn., and her associates. Hypoglycemia is associated with increased mortality, cardiovascular disease, falls and accidents, dementia, and a poor health-related quality of life in older adults.

To examine such overtreatment, the investigators analyzed National Health and Nutrition Examination Survey data during a 10-year period. They focused on 1,288 participants aged 65 years and older (mean age, 73 years) whose hemoglobin A1c levels indicated glycemic control that was categorized as poor (9% or higher), moderate (7%-8.9%), or tight (<7%); the latter category included those patients with very tight glycemic control (<6.5%).

Dr. Lipska and her associates found that 62% of the sample, representing nearly 4 million older Americans, had tight glycemic control, including 42%, representing 2.6 million older Americans, who had very tight glycemic control.

Most of those patients were taking insulin or sulfonylureas. That included the majority of patients who had complex health profiles or poor health because of such coexisting conditions as arthritis, heart failure, lung disease, chronic kidney disease, coronary heart disease, stroke, urinary incontinence, and functional impairments.

“Given incomplete information on all comorbidities in our study, it is likely that we underestimated the complexity of health status, and thus, true estimates of adults who are potentially overtreated may be even higher,” the investigators said (JAMA Intern. Med. 2015 Jan. 12 [doi:10.1001/jamainternmed.2014.7345]).

“Recognition of both the harms and the benefits of glycemic control is critical for patients and physicians and other health care professionals to make informed decisions about glucose-lowering treatment,” the investigators added.

A Pepper Center Career Development Award, the National Institute on Aging, the Yale Center for Investigation, the American Federation for Aging Research, the Paul B. Beeson Career Development Program, and the National Institutes of Health funded the study. Dr. Lipska reported having no financial conflicts. Her associates reported ties to Medtronic, Johnson & Johnson, and FAIR Health.

Adjuvant therapy with trastuzumab plus paclitaxel yielded a 3-year recurrence rate of < 2% in an uncontrolled, nonrandomized study involving women who had small stage I HER2-positive breast cancers, according to a report published online Jan. 8 in the New England Journal of Medicine.

Currently no standard treatment is recommended for such patients, and clinicians must weigh the generally favorable outcomes for small, stage I tumors that aren’t targeted with adjuvant chemotherapy against the potential for considerable toxic effects from adjuvant chemotherapy. Clinical trials of trastuzumab have focused on patients with more advanced cancers. “Although patients with stage I HER2-positive tumors are expected to derive a smaller absolute benefit from adjuvant therapy than those with larger or node-positive tumors, they remain at more than minimal risk for a recurrence of breast cancer,” said Dr. Sara M. Tolaney of the department of medical oncology, Dana-Farber Cancer Institute, Boston, and her associates.

Their industry-sponsored single-group study involved 406 patients with a median age of 55 years (range, 24-85 years) whose breast adenocarcinomas measured no more than 3 cm. After undergoing surgical excisions, all the study participants were assigned to receive weekly IV paclitaxel and IV trastuzumab for 12 weeks, after which trastuzumab could be continued at the same weekly dose for 40 weeks or the regimen could be changed to a slightly higher dose every 3 weeks for 40 weeks.

A total of 356 patients (87.7%) completed the full year of adjuvant trastuzumab. Women who opted for partial- or whole-breast irradiation commenced that treatment after completing paclitaxel and while taking trastuzumab, and those who chose hormonal therapy also began taking those agents after completing paclitaxel and while taking trastuzumab. Median follow-up was 4 years (maximum, 6.2 years).

At 3-year follow-up, the rate of cancer-free survival was 98.7%, which was higher than would have been predicted by historical data; there were four distant and four local or regional metastases. According to the study’s statistical design, adjuvant trastuzumab would be considered successful if the 3-year recurrence rate were 5% or lower and there were 39 or fewer metastases, Dr. Tolaney and her associates said (N. Engl. J. Med. 2015 Jan. 8 [doi:10.1056/NEJM0a1406281]).

A total of 6% of patients withdrew from the study because of treatment-related adverse effects. The most important known adverse effect of trastuzumab is left ventricular dysfunction, so cardiac function was assessed at several intervals during the year of active therapy. Two patients (0.5%) developed grade 3 LV dysfunction during treatment, and both recovered after the drug was discontinued. Thirteen patients (3.2%) showed an asymptomatic decline in ejection fraction that led to an interruption in trastuzumab therapy; this normalized in 11 of them, who then resumed the treatment. Seven patients developed grade 3 or 4 allergic reactions, and only one of them was able to resume the treatment.

Adjuvant therapy with trastuzumab plus paclitaxel yielded a 3-year recurrence rate of < 2% in an uncontrolled, nonrandomized study involving women who had small stage I HER2-positive breast cancers, according to a report published online Jan. 8 in the New England Journal of Medicine.

Currently no standard treatment is recommended for such patients, and clinicians must weigh the generally favorable outcomes for small, stage I tumors that aren’t targeted with adjuvant chemotherapy against the potential for considerable toxic effects from adjuvant chemotherapy. Clinical trials of trastuzumab have focused on patients with more advanced cancers. “Although patients with stage I HER2-positive tumors are expected to derive a smaller absolute benefit from adjuvant therapy than those with larger or node-positive tumors, they remain at more than minimal risk for a recurrence of breast cancer,” said Dr. Sara M. Tolaney of the department of medical oncology, Dana-Farber Cancer Institute, Boston, and her associates.

Their industry-sponsored single-group study involved 406 patients with a median age of 55 years (range, 24-85 years) whose breast adenocarcinomas measured no more than 3 cm. After undergoing surgical excisions, all the study participants were assigned to receive weekly IV paclitaxel and IV trastuzumab for 12 weeks, after which trastuzumab could be continued at the same weekly dose for 40 weeks or the regimen could be changed to a slightly higher dose every 3 weeks for 40 weeks.

A total of 356 patients (87.7%) completed the full year of adjuvant trastuzumab. Women who opted for partial- or whole-breast irradiation commenced that treatment after completing paclitaxel and while taking trastuzumab, and those who chose hormonal therapy also began taking those agents after completing paclitaxel and while taking trastuzumab. Median follow-up was 4 years (maximum, 6.2 years).

At 3-year follow-up, the rate of cancer-free survival was 98.7%, which was higher than would have been predicted by historical data; there were four distant and four local or regional metastases. According to the study’s statistical design, adjuvant trastuzumab would be considered successful if the 3-year recurrence rate were 5% or lower and there were 39 or fewer metastases, Dr. Tolaney and her associates said (N. Engl. J. Med. 2015 Jan. 8 [doi:10.1056/NEJM0a1406281]).

A total of 6% of patients withdrew from the study because of treatment-related adverse effects. The most important known adverse effect of trastuzumab is left ventricular dysfunction, so cardiac function was assessed at several intervals during the year of active therapy. Two patients (0.5%) developed grade 3 LV dysfunction during treatment, and both recovered after the drug was discontinued. Thirteen patients (3.2%) showed an asymptomatic decline in ejection fraction that led to an interruption in trastuzumab therapy; this normalized in 11 of them, who then resumed the treatment. Seven patients developed grade 3 or 4 allergic reactions, and only one of them was able to resume the treatment.

Adjuvant therapy with trastuzumab plus paclitaxel yielded a 3-year recurrence rate of < 2% in an uncontrolled, nonrandomized study involving women who had small stage I HER2-positive breast cancers, according to a report published online Jan. 8 in the New England Journal of Medicine.

Currently no standard treatment is recommended for such patients, and clinicians must weigh the generally favorable outcomes for small, stage I tumors that aren’t targeted with adjuvant chemotherapy against the potential for considerable toxic effects from adjuvant chemotherapy. Clinical trials of trastuzumab have focused on patients with more advanced cancers. “Although patients with stage I HER2-positive tumors are expected to derive a smaller absolute benefit from adjuvant therapy than those with larger or node-positive tumors, they remain at more than minimal risk for a recurrence of breast cancer,” said Dr. Sara M. Tolaney of the department of medical oncology, Dana-Farber Cancer Institute, Boston, and her associates.

Their industry-sponsored single-group study involved 406 patients with a median age of 55 years (range, 24-85 years) whose breast adenocarcinomas measured no more than 3 cm. After undergoing surgical excisions, all the study participants were assigned to receive weekly IV paclitaxel and IV trastuzumab for 12 weeks, after which trastuzumab could be continued at the same weekly dose for 40 weeks or the regimen could be changed to a slightly higher dose every 3 weeks for 40 weeks.

A total of 356 patients (87.7%) completed the full year of adjuvant trastuzumab. Women who opted for partial- or whole-breast irradiation commenced that treatment after completing paclitaxel and while taking trastuzumab, and those who chose hormonal therapy also began taking those agents after completing paclitaxel and while taking trastuzumab. Median follow-up was 4 years (maximum, 6.2 years).

At 3-year follow-up, the rate of cancer-free survival was 98.7%, which was higher than would have been predicted by historical data; there were four distant and four local or regional metastases. According to the study’s statistical design, adjuvant trastuzumab would be considered successful if the 3-year recurrence rate were 5% or lower and there were 39 or fewer metastases, Dr. Tolaney and her associates said (N. Engl. J. Med. 2015 Jan. 8 [doi:10.1056/NEJM0a1406281]).

A total of 6% of patients withdrew from the study because of treatment-related adverse effects. The most important known adverse effect of trastuzumab is left ventricular dysfunction, so cardiac function was assessed at several intervals during the year of active therapy. Two patients (0.5%) developed grade 3 LV dysfunction during treatment, and both recovered after the drug was discontinued. Thirteen patients (3.2%) showed an asymptomatic decline in ejection fraction that led to an interruption in trastuzumab therapy; this normalized in 11 of them, who then resumed the treatment. Seven patients developed grade 3 or 4 allergic reactions, and only one of them was able to resume the treatment.