Amy Karon

Benzodiazepine use is associated with significantly increased risks of adverse respiratory outcomes in older adults with chronic obstructive pulmonary disease, researchers reported online April 17 in the European Respiratory Journal.

New benzodiazepine users were 45% more likely to receive outpatient respiratory medications and 92% more likely to visit the emergency department for respiratory reasons than were non–benzodiazepine users, reported Dr. Nicholas Vozoris of St. Michael’s Hospital and the University of Toronto and his associates.

"These findings are concerning, given that benzodiazepines are known to be frequently used among older adults with COPD and in suboptimal ways," the investigators wrote. "The findings suggest that the potential for adverse respiratory outcomes needs to be considered when administering benzodiazepines to older adults with COPD."

The retrospective population-based cohort study identified 177,355 adults with COPD who were at least 66 years old and lived in Ontario, Canada, during 2003-2010. The researchers used 1:1 propensity score matching without replacement to match 48,915 new benzodiazepine users with the same number of nonusers (Eur. Respir. J. 2014 April 17 [doi: 10.1183/09031936.00008014]).

New users of benzodiazepines were significantly more likely to be prescribed oral corticosteroids or respiratory antibiotics (relative risk, 1.45; 95% confidence interval, 1.36-1.54) and to visit the emergency department for COPD or pneumonia (RR, 1.92; 95% CI, 1.69-2.18).

Furthermore, in the subgroup of patients who had no exacerbation of COPD during the year before baseline, new benzodiazepine users had a significantly greater risk of receiving outpatient respiratory medications (RR, 1.63; 95% CI, 1.44-1.84), visiting an emergency department for COPD or pneumonia (RR, 2.46; 95% CI, 1.90-3.18), being hospitalized for either diagnosis (RR, 1.29; 95% CI, 1.07-1.56), or dying from any cause (RR, 1.19, 95% CI, 1.06-1.34).

The research is consistent with findings from previous smaller, shorter-duration studies, said Dr. Vozoris and his associates. They noted that their definition of COPD had a sensitivity of only 58%, which could limit the generalizability of the findings.

The Canadian Institutes of Health and the Institute for Clinical Evaluative Sciences funded the study. The investigators reported having no conflicts of interest.

Benzodiazepine use is associated with significantly increased risks of adverse respiratory outcomes in older adults with chronic obstructive pulmonary disease, researchers reported online April 17 in the European Respiratory Journal.

New benzodiazepine users were 45% more likely to receive outpatient respiratory medications and 92% more likely to visit the emergency department for respiratory reasons than were non–benzodiazepine users, reported Dr. Nicholas Vozoris of St. Michael’s Hospital and the University of Toronto and his associates.

"These findings are concerning, given that benzodiazepines are known to be frequently used among older adults with COPD and in suboptimal ways," the investigators wrote. "The findings suggest that the potential for adverse respiratory outcomes needs to be considered when administering benzodiazepines to older adults with COPD."

The retrospective population-based cohort study identified 177,355 adults with COPD who were at least 66 years old and lived in Ontario, Canada, during 2003-2010. The researchers used 1:1 propensity score matching without replacement to match 48,915 new benzodiazepine users with the same number of nonusers (Eur. Respir. J. 2014 April 17 [doi: 10.1183/09031936.00008014]).

New users of benzodiazepines were significantly more likely to be prescribed oral corticosteroids or respiratory antibiotics (relative risk, 1.45; 95% confidence interval, 1.36-1.54) and to visit the emergency department for COPD or pneumonia (RR, 1.92; 95% CI, 1.69-2.18).

Furthermore, in the subgroup of patients who had no exacerbation of COPD during the year before baseline, new benzodiazepine users had a significantly greater risk of receiving outpatient respiratory medications (RR, 1.63; 95% CI, 1.44-1.84), visiting an emergency department for COPD or pneumonia (RR, 2.46; 95% CI, 1.90-3.18), being hospitalized for either diagnosis (RR, 1.29; 95% CI, 1.07-1.56), or dying from any cause (RR, 1.19, 95% CI, 1.06-1.34).

The research is consistent with findings from previous smaller, shorter-duration studies, said Dr. Vozoris and his associates. They noted that their definition of COPD had a sensitivity of only 58%, which could limit the generalizability of the findings.

The Canadian Institutes of Health and the Institute for Clinical Evaluative Sciences funded the study. The investigators reported having no conflicts of interest.

Benzodiazepine use is associated with significantly increased risks of adverse respiratory outcomes in older adults with chronic obstructive pulmonary disease, researchers reported online April 17 in the European Respiratory Journal.

New benzodiazepine users were 45% more likely to receive outpatient respiratory medications and 92% more likely to visit the emergency department for respiratory reasons than were non–benzodiazepine users, reported Dr. Nicholas Vozoris of St. Michael’s Hospital and the University of Toronto and his associates.

"These findings are concerning, given that benzodiazepines are known to be frequently used among older adults with COPD and in suboptimal ways," the investigators wrote. "The findings suggest that the potential for adverse respiratory outcomes needs to be considered when administering benzodiazepines to older adults with COPD."

The retrospective population-based cohort study identified 177,355 adults with COPD who were at least 66 years old and lived in Ontario, Canada, during 2003-2010. The researchers used 1:1 propensity score matching without replacement to match 48,915 new benzodiazepine users with the same number of nonusers (Eur. Respir. J. 2014 April 17 [doi: 10.1183/09031936.00008014]).

New users of benzodiazepines were significantly more likely to be prescribed oral corticosteroids or respiratory antibiotics (relative risk, 1.45; 95% confidence interval, 1.36-1.54) and to visit the emergency department for COPD or pneumonia (RR, 1.92; 95% CI, 1.69-2.18).

Furthermore, in the subgroup of patients who had no exacerbation of COPD during the year before baseline, new benzodiazepine users had a significantly greater risk of receiving outpatient respiratory medications (RR, 1.63; 95% CI, 1.44-1.84), visiting an emergency department for COPD or pneumonia (RR, 2.46; 95% CI, 1.90-3.18), being hospitalized for either diagnosis (RR, 1.29; 95% CI, 1.07-1.56), or dying from any cause (RR, 1.19, 95% CI, 1.06-1.34).

The research is consistent with findings from previous smaller, shorter-duration studies, said Dr. Vozoris and his associates. They noted that their definition of COPD had a sensitivity of only 58%, which could limit the generalizability of the findings.

The Canadian Institutes of Health and the Institute for Clinical Evaluative Sciences funded the study. The investigators reported having no conflicts of interest.

Nocturnal cortisol levels explained up to 16% of changes in learning, memory, and working memory in patients with obstructive sleep apnea, a study showed.

But severity of obstructive sleep apnea (OSA) did not itself predict neurocognitive impairment, said Dr. Kate M. Edwards of the University of Sydney in Lidscombe, Australia, and her associates, who conducted the study at the University of California, San Diego.

"These findings suggest that OSA-related alterations in [hypothalamic-pituitary-adrenal] activity may play a key role in the pathophysiology of neuropsychologic impairments in OSA," the investigators wrote (Sleep Med. 2014;15:27-32).

©Silvia Jansen/iStockphoto

The researchers enrolled 55 men and women with OSA and measured blood cortisol levels every 2 hours for 24 hours. Participants underwent polysomnography the next night and took a battery of tests to assess seven cognitive domains. The oxygen desaturation index (ODI) was used as an index of OSA severity.

In univariate analyses, the mean apnea-hypopnea index, ODI, and nighttime cortisol levels were significantly associated with global deficit scores and particularly with domains of learning, memory, and working memory, said the investigators. In hierarchical linear regression analyses, nighttime cortisol levels accounted for 9%-16% of variance in the three domains, while ODI (apnea) severity did not predict additional variance, they reported.

"Our data are in line with the literature reporting that chronic exposure to elevated physiologic cortisol levels is associated with a decline in neurocognitive function and hippocampal structure," the investigators said. "The functional effects of cortisol on reduced memory function have been demonstrated by experimental cortisol treatment and stress-induced cortisol level increases."

"The treatment of OSA with CPAP [continuous positive airway pressure] has been reported to show improvements in some aspects of neuropsychologic function, though findings are inconsistent," the investigators wrote.

"It may yield interesting data if future studies address the possibility that CPAP treatment effects on neurocognitive function are mediated by alterations in [hypothalamic-pituitary-adrenal] function, specifically reductions in nighttime cortisol levels."

The work was funded by University of California, San Diego, grants. The authors disclosed no relevant financial conflicts of interest.

Nocturnal cortisol levels explained up to 16% of changes in learning, memory, and working memory in patients with obstructive sleep apnea, a study showed.

But severity of obstructive sleep apnea (OSA) did not itself predict neurocognitive impairment, said Dr. Kate M. Edwards of the University of Sydney in Lidscombe, Australia, and her associates, who conducted the study at the University of California, San Diego.

"These findings suggest that OSA-related alterations in [hypothalamic-pituitary-adrenal] activity may play a key role in the pathophysiology of neuropsychologic impairments in OSA," the investigators wrote (Sleep Med. 2014;15:27-32).

©Silvia Jansen/iStockphoto

The researchers enrolled 55 men and women with OSA and measured blood cortisol levels every 2 hours for 24 hours. Participants underwent polysomnography the next night and took a battery of tests to assess seven cognitive domains. The oxygen desaturation index (ODI) was used as an index of OSA severity.

In univariate analyses, the mean apnea-hypopnea index, ODI, and nighttime cortisol levels were significantly associated with global deficit scores and particularly with domains of learning, memory, and working memory, said the investigators. In hierarchical linear regression analyses, nighttime cortisol levels accounted for 9%-16% of variance in the three domains, while ODI (apnea) severity did not predict additional variance, they reported.

"Our data are in line with the literature reporting that chronic exposure to elevated physiologic cortisol levels is associated with a decline in neurocognitive function and hippocampal structure," the investigators said. "The functional effects of cortisol on reduced memory function have been demonstrated by experimental cortisol treatment and stress-induced cortisol level increases."

"The treatment of OSA with CPAP [continuous positive airway pressure] has been reported to show improvements in some aspects of neuropsychologic function, though findings are inconsistent," the investigators wrote.

"It may yield interesting data if future studies address the possibility that CPAP treatment effects on neurocognitive function are mediated by alterations in [hypothalamic-pituitary-adrenal] function, specifically reductions in nighttime cortisol levels."

The work was funded by University of California, San Diego, grants. The authors disclosed no relevant financial conflicts of interest.

Nocturnal cortisol levels explained up to 16% of changes in learning, memory, and working memory in patients with obstructive sleep apnea, a study showed.

But severity of obstructive sleep apnea (OSA) did not itself predict neurocognitive impairment, said Dr. Kate M. Edwards of the University of Sydney in Lidscombe, Australia, and her associates, who conducted the study at the University of California, San Diego.

"These findings suggest that OSA-related alterations in [hypothalamic-pituitary-adrenal] activity may play a key role in the pathophysiology of neuropsychologic impairments in OSA," the investigators wrote (Sleep Med. 2014;15:27-32).

©Silvia Jansen/iStockphoto

The researchers enrolled 55 men and women with OSA and measured blood cortisol levels every 2 hours for 24 hours. Participants underwent polysomnography the next night and took a battery of tests to assess seven cognitive domains. The oxygen desaturation index (ODI) was used as an index of OSA severity.

In univariate analyses, the mean apnea-hypopnea index, ODI, and nighttime cortisol levels were significantly associated with global deficit scores and particularly with domains of learning, memory, and working memory, said the investigators. In hierarchical linear regression analyses, nighttime cortisol levels accounted for 9%-16% of variance in the three domains, while ODI (apnea) severity did not predict additional variance, they reported.

"Our data are in line with the literature reporting that chronic exposure to elevated physiologic cortisol levels is associated with a decline in neurocognitive function and hippocampal structure," the investigators said. "The functional effects of cortisol on reduced memory function have been demonstrated by experimental cortisol treatment and stress-induced cortisol level increases."

"The treatment of OSA with CPAP [continuous positive airway pressure] has been reported to show improvements in some aspects of neuropsychologic function, though findings are inconsistent," the investigators wrote.

"It may yield interesting data if future studies address the possibility that CPAP treatment effects on neurocognitive function are mediated by alterations in [hypothalamic-pituitary-adrenal] function, specifically reductions in nighttime cortisol levels."

The work was funded by University of California, San Diego, grants. The authors disclosed no relevant financial conflicts of interest.

The experimental targeted agent panitumumab failed to improve progression-free survival over bevacizumab when added to first-line chemotherapy for wild-type KRAS exon 2 colorectal cancer, investigators reported online in the Journal of Clinical Oncology.

But patients treated with panitumumab lived a median of 10 months longer than those who received bevacizumab, said Dr. Lee Schwartzberg of West Clinic, Memphis, and his associates.

Panitumumab is an experimental monoclonal antibody that targets epidermal growth factor receptor (EGFR), while bevacizumab is an anti–vascular endothelial growth factor (anti-VEGF) antibody. The randomized, multicenter, phase II PEAK trial compared the agents head-to-head when added on to modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) for patients with previously untreated, unresectable wild-type KRAS exon 2 metastatic colorectal cancer. The investigators treated 278 patients with mFOLFOX6 plus biweekly panitumumab (6 mg/kg) or bevacizumab (5 mg/kg).

The primary endpoint, progression-free survival (PFS), was similar between treatment groups (10.9 vs. 10.1 months, respectively; hazard ratio, 0.87; 95% confidence interval, 0.65-1.17; P = .353), the investigators said. However, median overall survival (OS) was 10 months longer with panitumumab than bevacizumab (34.2 vs. 24.3 months; HR, 0.62; 95% CI, 0.44-0.89; P = .009), they reported (J. Clin. Oncol. 2014 March 31 [doi: 10.1200/jco.2013.53.2473]).

In an extended analysis of a wild-type RAS subgroup, PFS was 3.5 months longer for panitumumab (13.0 vs. 9.5 months for bevacizumab; HR, 0.65; 95% CI, 0.44-0.96; P = .029), the researchers reported. They added that patients experienced more skin toxicity and hypomagnesemia on panitumumab and more hypertension on bevacizumab.

Confounding could have caused the discrepancy between PFS and OS in the primary analysis, said Dr. Schwartzberg and his associates. "One possibility is that OS results were confounded by subsequent therapies. Alternatively, because the OS Kaplan-Meier curves separated before 6 months, PFS results may have been confounded by the negative contribution from the 23% of patients with RAS mutations beyond KRAS exon 2."

Nonetheless, they said, the OS benefit seen for panitumumab in the PEAK trial mirrors results for cetuximab, compared with bevacizumab, in the FIRE-3 trial. They added that the two head-to-head trials suggest that anti-EGFR therapy improves OS compared with antiangiogenesis therapy in this population, particularly in patients with wild-type RAS tumors.

Amgen sponsored the study and makes panitumumab (Vectibix). The investigators reported financial and advisory or consulting relationships with Amgen, Roche, and Merck, and three of them work for Amgen.

The experimental targeted agent panitumumab failed to improve progression-free survival over bevacizumab when added to first-line chemotherapy for wild-type KRAS exon 2 colorectal cancer, investigators reported online in the Journal of Clinical Oncology.

But patients treated with panitumumab lived a median of 10 months longer than those who received bevacizumab, said Dr. Lee Schwartzberg of West Clinic, Memphis, and his associates.

Panitumumab is an experimental monoclonal antibody that targets epidermal growth factor receptor (EGFR), while bevacizumab is an anti–vascular endothelial growth factor (anti-VEGF) antibody. The randomized, multicenter, phase II PEAK trial compared the agents head-to-head when added on to modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) for patients with previously untreated, unresectable wild-type KRAS exon 2 metastatic colorectal cancer. The investigators treated 278 patients with mFOLFOX6 plus biweekly panitumumab (6 mg/kg) or bevacizumab (5 mg/kg).

The primary endpoint, progression-free survival (PFS), was similar between treatment groups (10.9 vs. 10.1 months, respectively; hazard ratio, 0.87; 95% confidence interval, 0.65-1.17; P = .353), the investigators said. However, median overall survival (OS) was 10 months longer with panitumumab than bevacizumab (34.2 vs. 24.3 months; HR, 0.62; 95% CI, 0.44-0.89; P = .009), they reported (J. Clin. Oncol. 2014 March 31 [doi: 10.1200/jco.2013.53.2473]).

In an extended analysis of a wild-type RAS subgroup, PFS was 3.5 months longer for panitumumab (13.0 vs. 9.5 months for bevacizumab; HR, 0.65; 95% CI, 0.44-0.96; P = .029), the researchers reported. They added that patients experienced more skin toxicity and hypomagnesemia on panitumumab and more hypertension on bevacizumab.

Confounding could have caused the discrepancy between PFS and OS in the primary analysis, said Dr. Schwartzberg and his associates. "One possibility is that OS results were confounded by subsequent therapies. Alternatively, because the OS Kaplan-Meier curves separated before 6 months, PFS results may have been confounded by the negative contribution from the 23% of patients with RAS mutations beyond KRAS exon 2."

Nonetheless, they said, the OS benefit seen for panitumumab in the PEAK trial mirrors results for cetuximab, compared with bevacizumab, in the FIRE-3 trial. They added that the two head-to-head trials suggest that anti-EGFR therapy improves OS compared with antiangiogenesis therapy in this population, particularly in patients with wild-type RAS tumors.

Amgen sponsored the study and makes panitumumab (Vectibix). The investigators reported financial and advisory or consulting relationships with Amgen, Roche, and Merck, and three of them work for Amgen.

The experimental targeted agent panitumumab failed to improve progression-free survival over bevacizumab when added to first-line chemotherapy for wild-type KRAS exon 2 colorectal cancer, investigators reported online in the Journal of Clinical Oncology.

But patients treated with panitumumab lived a median of 10 months longer than those who received bevacizumab, said Dr. Lee Schwartzberg of West Clinic, Memphis, and his associates.

Panitumumab is an experimental monoclonal antibody that targets epidermal growth factor receptor (EGFR), while bevacizumab is an anti–vascular endothelial growth factor (anti-VEGF) antibody. The randomized, multicenter, phase II PEAK trial compared the agents head-to-head when added on to modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) for patients with previously untreated, unresectable wild-type KRAS exon 2 metastatic colorectal cancer. The investigators treated 278 patients with mFOLFOX6 plus biweekly panitumumab (6 mg/kg) or bevacizumab (5 mg/kg).

The primary endpoint, progression-free survival (PFS), was similar between treatment groups (10.9 vs. 10.1 months, respectively; hazard ratio, 0.87; 95% confidence interval, 0.65-1.17; P = .353), the investigators said. However, median overall survival (OS) was 10 months longer with panitumumab than bevacizumab (34.2 vs. 24.3 months; HR, 0.62; 95% CI, 0.44-0.89; P = .009), they reported (J. Clin. Oncol. 2014 March 31 [doi: 10.1200/jco.2013.53.2473]).

In an extended analysis of a wild-type RAS subgroup, PFS was 3.5 months longer for panitumumab (13.0 vs. 9.5 months for bevacizumab; HR, 0.65; 95% CI, 0.44-0.96; P = .029), the researchers reported. They added that patients experienced more skin toxicity and hypomagnesemia on panitumumab and more hypertension on bevacizumab.

Confounding could have caused the discrepancy between PFS and OS in the primary analysis, said Dr. Schwartzberg and his associates. "One possibility is that OS results were confounded by subsequent therapies. Alternatively, because the OS Kaplan-Meier curves separated before 6 months, PFS results may have been confounded by the negative contribution from the 23% of patients with RAS mutations beyond KRAS exon 2."

Nonetheless, they said, the OS benefit seen for panitumumab in the PEAK trial mirrors results for cetuximab, compared with bevacizumab, in the FIRE-3 trial. They added that the two head-to-head trials suggest that anti-EGFR therapy improves OS compared with antiangiogenesis therapy in this population, particularly in patients with wild-type RAS tumors.

Amgen sponsored the study and makes panitumumab (Vectibix). The investigators reported financial and advisory or consulting relationships with Amgen, Roche, and Merck, and three of them work for Amgen.

Girls with childhood cancers who received whole-lung irradiation had a 43-fold increase in subsequent risk of breast cancer, compared with the general population, a study showed.

The risk exceeded previous reports and resembled that of BRCA mutation carriers, said Dr. Chaya S. Moskowitz of Memorial Sloan-Kettering Cancer Center, New York, and her associates.

The results show the importance of radiation volume as well as dose in subsequent cancer risk, the investigators said. Whole-lung irradiation (WLI) involves high volumes of breast tissue, but doses were less than 20 Gy, so the patients would not meet annual mammogram and MRI screening recommendations for girls and young women who receive chest irradiation (J. Clin. Oncol. 2014 [doi:10.1200/JCO.2013.54.4601]).

The investigators studied 1,230 women who had received chest radiation therapy for childhood Hodgkin lymphoma, Wilm’s tumor, non-Hodgkin lymphoma, neuroblastoma, leukemia, and other cancers. The women were participants in the Childhood Cancer Survivor Study, a retrospective cohort study with longitudinal follow-up of patients treated at 26 centers in the United States and Canada.

By age 50 years, 30% of patients had developed breast cancer (95% confidence interval, 25%-34%), including 35% of Hodgkin lymphoma survivors (95% CI, 29%-40%), the investigators reported. In comparison, 31% of BRCA1 mutation carriers and 10% of BRCA2 carriers in the WECARE (Women’s Environmental Cancer and Radiation Epidemiology) study developed breast cancer by age 50 years (95% CI, 15%-48% and 1%-23%, respectively), the researchers said.

"The cumulative risk is remarkably similar between BRCA1 carriers and Hodgkin lymphoma survivors," Dr. Moscowitz and her associates wrote.

Furthermore, WLI involved lower radiation doses (median, 14 Gy, vs. 40 Gy for mantle field and 30 Gy for mediastinal field irradiation), but was linked to the highest incidence of breast cancer, compared with the risk in the general population (standardized incidence ratio, 43.6; 95% confidence interval, 27.1-70.1), the researchers reported. Cumulative breast cancer incidence in WLI recipients resembled that for mantle field radiation (incidence rate ratio, 1.9; 95% CI, 0.9-3.7; P = .07) and exceeded that for mediastinal field irradiation (IRR, 3.4; 95% CI, 1.6-7.2; P = .001), they added.

Median time from diagnosis of childhood cancer to onset of breast cancer was only 23 years, the researchers reported. "This is a relatively young cohort, with a median age of 37 years," they added. "As the participants age, breast cancer incidence may increase."

There were few data on women older than 45 years who received WLI, which limited the ability to draw conclusions about older women, the investigators noted.

The National Cancer Institute, the Meg Berté Owen Foundation, and the American Lebanese-Syrian Associated Charities funded the study. The authors reported no conflicts of interest.

Girls with childhood cancers who received whole-lung irradiation had a 43-fold increase in subsequent risk of breast cancer, compared with the general population, a study showed.

The risk exceeded previous reports and resembled that of BRCA mutation carriers, said Dr. Chaya S. Moskowitz of Memorial Sloan-Kettering Cancer Center, New York, and her associates.

The results show the importance of radiation volume as well as dose in subsequent cancer risk, the investigators said. Whole-lung irradiation (WLI) involves high volumes of breast tissue, but doses were less than 20 Gy, so the patients would not meet annual mammogram and MRI screening recommendations for girls and young women who receive chest irradiation (J. Clin. Oncol. 2014 [doi:10.1200/JCO.2013.54.4601]).

The investigators studied 1,230 women who had received chest radiation therapy for childhood Hodgkin lymphoma, Wilm’s tumor, non-Hodgkin lymphoma, neuroblastoma, leukemia, and other cancers. The women were participants in the Childhood Cancer Survivor Study, a retrospective cohort study with longitudinal follow-up of patients treated at 26 centers in the United States and Canada.

By age 50 years, 30% of patients had developed breast cancer (95% confidence interval, 25%-34%), including 35% of Hodgkin lymphoma survivors (95% CI, 29%-40%), the investigators reported. In comparison, 31% of BRCA1 mutation carriers and 10% of BRCA2 carriers in the WECARE (Women’s Environmental Cancer and Radiation Epidemiology) study developed breast cancer by age 50 years (95% CI, 15%-48% and 1%-23%, respectively), the researchers said.

"The cumulative risk is remarkably similar between BRCA1 carriers and Hodgkin lymphoma survivors," Dr. Moscowitz and her associates wrote.

Furthermore, WLI involved lower radiation doses (median, 14 Gy, vs. 40 Gy for mantle field and 30 Gy for mediastinal field irradiation), but was linked to the highest incidence of breast cancer, compared with the risk in the general population (standardized incidence ratio, 43.6; 95% confidence interval, 27.1-70.1), the researchers reported. Cumulative breast cancer incidence in WLI recipients resembled that for mantle field radiation (incidence rate ratio, 1.9; 95% CI, 0.9-3.7; P = .07) and exceeded that for mediastinal field irradiation (IRR, 3.4; 95% CI, 1.6-7.2; P = .001), they added.

Median time from diagnosis of childhood cancer to onset of breast cancer was only 23 years, the researchers reported. "This is a relatively young cohort, with a median age of 37 years," they added. "As the participants age, breast cancer incidence may increase."

There were few data on women older than 45 years who received WLI, which limited the ability to draw conclusions about older women, the investigators noted.

The National Cancer Institute, the Meg Berté Owen Foundation, and the American Lebanese-Syrian Associated Charities funded the study. The authors reported no conflicts of interest.

Girls with childhood cancers who received whole-lung irradiation had a 43-fold increase in subsequent risk of breast cancer, compared with the general population, a study showed.

The risk exceeded previous reports and resembled that of BRCA mutation carriers, said Dr. Chaya S. Moskowitz of Memorial Sloan-Kettering Cancer Center, New York, and her associates.

The results show the importance of radiation volume as well as dose in subsequent cancer risk, the investigators said. Whole-lung irradiation (WLI) involves high volumes of breast tissue, but doses were less than 20 Gy, so the patients would not meet annual mammogram and MRI screening recommendations for girls and young women who receive chest irradiation (J. Clin. Oncol. 2014 [doi:10.1200/JCO.2013.54.4601]).

The investigators studied 1,230 women who had received chest radiation therapy for childhood Hodgkin lymphoma, Wilm’s tumor, non-Hodgkin lymphoma, neuroblastoma, leukemia, and other cancers. The women were participants in the Childhood Cancer Survivor Study, a retrospective cohort study with longitudinal follow-up of patients treated at 26 centers in the United States and Canada.

By age 50 years, 30% of patients had developed breast cancer (95% confidence interval, 25%-34%), including 35% of Hodgkin lymphoma survivors (95% CI, 29%-40%), the investigators reported. In comparison, 31% of BRCA1 mutation carriers and 10% of BRCA2 carriers in the WECARE (Women’s Environmental Cancer and Radiation Epidemiology) study developed breast cancer by age 50 years (95% CI, 15%-48% and 1%-23%, respectively), the researchers said.

"The cumulative risk is remarkably similar between BRCA1 carriers and Hodgkin lymphoma survivors," Dr. Moscowitz and her associates wrote.

Furthermore, WLI involved lower radiation doses (median, 14 Gy, vs. 40 Gy for mantle field and 30 Gy for mediastinal field irradiation), but was linked to the highest incidence of breast cancer, compared with the risk in the general population (standardized incidence ratio, 43.6; 95% confidence interval, 27.1-70.1), the researchers reported. Cumulative breast cancer incidence in WLI recipients resembled that for mantle field radiation (incidence rate ratio, 1.9; 95% CI, 0.9-3.7; P = .07) and exceeded that for mediastinal field irradiation (IRR, 3.4; 95% CI, 1.6-7.2; P = .001), they added.

Median time from diagnosis of childhood cancer to onset of breast cancer was only 23 years, the researchers reported. "This is a relatively young cohort, with a median age of 37 years," they added. "As the participants age, breast cancer incidence may increase."

There were few data on women older than 45 years who received WLI, which limited the ability to draw conclusions about older women, the investigators noted.

The National Cancer Institute, the Meg Berté Owen Foundation, and the American Lebanese-Syrian Associated Charities funded the study. The authors reported no conflicts of interest.

U.S. adults who take statins consumed 14.4% more fat and 9.6% more calories in 1999-2000 than a decade earlier, while the prevalence of statin use more than doubled during that time, investigators reported online April 24 in JAMA Internal Medicine.

But fat and calorie intake did not change significantly among statin nonusers during the study period, reported Dr. Takehiro Sugiyama of the University of California, Los Angeles, and the University of Tokyo, and her associates.

The findings raise questions about managing hyperlipidemia in an era of epidemic obesity, diabetes, and "soaring" health care costs, the researchers said.

Dr. Sugiyama and her colleagues performed repeated cross-sectional analyses of NHANES (National Health and Nutrition Examination Survey) data on 27,886 U.S. adults aged 20 years and older during 1999-2010 (JAMA Intern. Med. 2014 [doi:10.1001/jamainternmed.2014.1927]).

At the start of the study period, statin users consumed 179 fewer kcal/day (2,000 vs. 2,179 kcal/day; P =.007) and 9.5 fewer grams of fat/day (71.7 vs. 81.2 g/day; P = .003) than did nonusers, "as we would expect for persons attempting to control their cholesterol level and weight," the researchers said.

But the gaps between the two groups narrowed as statin users consumed more calories and fat during the next several years. By 2009-2010, statin users consumed 9.6% more calories and 14.4% more fat than they had in 1999-2000, both statistically significant differences. In fact, statin users consumed 54 more calories and 2.7 g more/day than did nonusers. Furthermore, their body mass index increased significantly, by 1.3 kg/m² during 1999-2010, compared with the BMI increase in nonusers of 0.5 kg/m², the investigators reported.

Statin use "may have undermined the perceived need to follow dietary recommendations," the researchers wrote. Patients, perceiving the drastic effect of statins on LDL cholesterol levels, "may have lost the incentive" to change their diet. Physicians might have contributed to the process by shifting the focus of consultations from diet to adherence to statin therapy, the researchers added.

"Another possible mechanism is that expanded statin use occurred in people who were likely to eat more," the researcher said. "Some patients may have agreed to initiate statin therapy because they did not want to restrict their diet, whereas others who did not want to take medication may have declined the proposed pharmacotherapy in favor of following dietary recommendations."

The National Center for Global Health and Medicine in Japan, the Honjo International Scholarship Foundation in Tokyo, and the National Institutes of Health funded the study. The authors reported no conflicts of interest.

U.S. adults who take statins consumed 14.4% more fat and 9.6% more calories in 1999-2000 than a decade earlier, while the prevalence of statin use more than doubled during that time, investigators reported online April 24 in JAMA Internal Medicine.

But fat and calorie intake did not change significantly among statin nonusers during the study period, reported Dr. Takehiro Sugiyama of the University of California, Los Angeles, and the University of Tokyo, and her associates.

The findings raise questions about managing hyperlipidemia in an era of epidemic obesity, diabetes, and "soaring" health care costs, the researchers said.

Dr. Sugiyama and her colleagues performed repeated cross-sectional analyses of NHANES (National Health and Nutrition Examination Survey) data on 27,886 U.S. adults aged 20 years and older during 1999-2010 (JAMA Intern. Med. 2014 [doi:10.1001/jamainternmed.2014.1927]).

At the start of the study period, statin users consumed 179 fewer kcal/day (2,000 vs. 2,179 kcal/day; P =.007) and 9.5 fewer grams of fat/day (71.7 vs. 81.2 g/day; P = .003) than did nonusers, "as we would expect for persons attempting to control their cholesterol level and weight," the researchers said.

But the gaps between the two groups narrowed as statin users consumed more calories and fat during the next several years. By 2009-2010, statin users consumed 9.6% more calories and 14.4% more fat than they had in 1999-2000, both statistically significant differences. In fact, statin users consumed 54 more calories and 2.7 g more/day than did nonusers. Furthermore, their body mass index increased significantly, by 1.3 kg/m² during 1999-2010, compared with the BMI increase in nonusers of 0.5 kg/m², the investigators reported.

Statin use "may have undermined the perceived need to follow dietary recommendations," the researchers wrote. Patients, perceiving the drastic effect of statins on LDL cholesterol levels, "may have lost the incentive" to change their diet. Physicians might have contributed to the process by shifting the focus of consultations from diet to adherence to statin therapy, the researchers added.

"Another possible mechanism is that expanded statin use occurred in people who were likely to eat more," the researcher said. "Some patients may have agreed to initiate statin therapy because they did not want to restrict their diet, whereas others who did not want to take medication may have declined the proposed pharmacotherapy in favor of following dietary recommendations."

The National Center for Global Health and Medicine in Japan, the Honjo International Scholarship Foundation in Tokyo, and the National Institutes of Health funded the study. The authors reported no conflicts of interest.

U.S. adults who take statins consumed 14.4% more fat and 9.6% more calories in 1999-2000 than a decade earlier, while the prevalence of statin use more than doubled during that time, investigators reported online April 24 in JAMA Internal Medicine.

But fat and calorie intake did not change significantly among statin nonusers during the study period, reported Dr. Takehiro Sugiyama of the University of California, Los Angeles, and the University of Tokyo, and her associates.

The findings raise questions about managing hyperlipidemia in an era of epidemic obesity, diabetes, and "soaring" health care costs, the researchers said.

Dr. Sugiyama and her colleagues performed repeated cross-sectional analyses of NHANES (National Health and Nutrition Examination Survey) data on 27,886 U.S. adults aged 20 years and older during 1999-2010 (JAMA Intern. Med. 2014 [doi:10.1001/jamainternmed.2014.1927]).

At the start of the study period, statin users consumed 179 fewer kcal/day (2,000 vs. 2,179 kcal/day; P =.007) and 9.5 fewer grams of fat/day (71.7 vs. 81.2 g/day; P = .003) than did nonusers, "as we would expect for persons attempting to control their cholesterol level and weight," the researchers said.

But the gaps between the two groups narrowed as statin users consumed more calories and fat during the next several years. By 2009-2010, statin users consumed 9.6% more calories and 14.4% more fat than they had in 1999-2000, both statistically significant differences. In fact, statin users consumed 54 more calories and 2.7 g more/day than did nonusers. Furthermore, their body mass index increased significantly, by 1.3 kg/m² during 1999-2010, compared with the BMI increase in nonusers of 0.5 kg/m², the investigators reported.

Statin use "may have undermined the perceived need to follow dietary recommendations," the researchers wrote. Patients, perceiving the drastic effect of statins on LDL cholesterol levels, "may have lost the incentive" to change their diet. Physicians might have contributed to the process by shifting the focus of consultations from diet to adherence to statin therapy, the researchers added.

"Another possible mechanism is that expanded statin use occurred in people who were likely to eat more," the researcher said. "Some patients may have agreed to initiate statin therapy because they did not want to restrict their diet, whereas others who did not want to take medication may have declined the proposed pharmacotherapy in favor of following dietary recommendations."

The National Center for Global Health and Medicine in Japan, the Honjo International Scholarship Foundation in Tokyo, and the National Institutes of Health funded the study. The authors reported no conflicts of interest.

U.S. adults who take statins consumed 14.4% more fat and 9.6% more calories in 1999-2000 than a decade earlier, while the prevalence of statin use more than doubled during that time, investigators reported online April 24 in JAMA Internal Medicine.

But fat and calorie intake did not change significantly among statin nonusers during the study period, reported Dr. Takehiro Sugiyama of the University of California, Los Angeles, and the University of Tokyo, and her associates.

The findings raise questions about managing hyperlipidemia in an era of epidemic obesity, diabetes, and "soaring" health care costs, the researchers said.

© Jeffrey Hamilton/Thinkstock

"We need to consider if it is an acceptable public health strategy to encourage statin use without also taking measures to decrease the likelihood that its use will be associated with increased caloric and fat intake as well as weight gain," they added. "We believe that the goal of statin treatment, as with any pharmacotherapy, should be to allow patients to decrease risks that cannot be decreased without medication, not to empower them to put butter on their steaks."

Dr. Sugiyama and her colleagues performed repeated cross-sectional analyses of NHANES (National Health and Nutrition Examination Survey) data on 27,886 U.S. adults aged 20 years and older during 1999-2010 (JAMA Intern. Med. 2014 [doi:10.1001/jamainternmed.2014.1927]).

At the start of the study period, statin users consumed 179 fewer kcal/day (2,000 vs. 2,179 kcal/day; P =.007) and 9.5 fewer grams of fat/day (71.7 vs. 81.2 g/day; P = .003) than did nonusers, "as we would expect for persons attempting to control their cholesterol level and weight," the researchers said.

But the gaps between the two groups narrowed as statin users consumed more calories and fat during the next several years. By 2009-2010, statin users consumed 9.6% more calories and 14.4% more fat than they had in 1999-2000, both statistically significant differences. In fact, statin users consumed 54 more calories and 2.7 g more/day than did nonusers. Furthermore, their body mass index increased significantly, by 1.3 kg/m² during 1999-2010, compared with the BMI increase in nonusers of 0.5 kg/m², the investigators reported.

Statin use "may have undermined the perceived need to follow dietary recommendations," the researchers wrote. Patients, perceiving the drastic effect of statins on LDL cholesterol levels, "may have lost the incentive" to change their diet. Physicians might have contributed to the process by shifting the focus of consultations from diet to adherence to statin therapy, the researchers added.

"Another possible mechanism is that expanded statin use occurred in people who were likely to eat more," the researcher said. "Some patients may have agreed to initiate statin therapy because they did not want to restrict their diet, whereas others who did not want to take medication may have declined the proposed pharmacotherapy in favor of following dietary recommendations."

The National Center for Global Health and Medicine in Japan, the Honjo International Scholarship Foundation in Tokyo, and the National Institutes of Health funded the study. The authors reported no conflicts of interest.

U.S. adults who take statins consumed 14.4% more fat and 9.6% more calories in 1999-2000 than a decade earlier, while the prevalence of statin use more than doubled during that time, investigators reported online April 24 in JAMA Internal Medicine.

But fat and calorie intake did not change significantly among statin nonusers during the study period, reported Dr. Takehiro Sugiyama of the University of California, Los Angeles, and the University of Tokyo, and her associates.

The findings raise questions about managing hyperlipidemia in an era of epidemic obesity, diabetes, and "soaring" health care costs, the researchers said.

© Jeffrey Hamilton/Thinkstock

"We need to consider if it is an acceptable public health strategy to encourage statin use without also taking measures to decrease the likelihood that its use will be associated with increased caloric and fat intake as well as weight gain," they added. "We believe that the goal of statin treatment, as with any pharmacotherapy, should be to allow patients to decrease risks that cannot be decreased without medication, not to empower them to put butter on their steaks."

Dr. Sugiyama and her colleagues performed repeated cross-sectional analyses of NHANES (National Health and Nutrition Examination Survey) data on 27,886 U.S. adults aged 20 years and older during 1999-2010 (JAMA Intern. Med. 2014 [doi:10.1001/jamainternmed.2014.1927]).

At the start of the study period, statin users consumed 179 fewer kcal/day (2,000 vs. 2,179 kcal/day; P =.007) and 9.5 fewer grams of fat/day (71.7 vs. 81.2 g/day; P = .003) than did nonusers, "as we would expect for persons attempting to control their cholesterol level and weight," the researchers said.

But the gaps between the two groups narrowed as statin users consumed more calories and fat during the next several years. By 2009-2010, statin users consumed 9.6% more calories and 14.4% more fat than they had in 1999-2000, both statistically significant differences. In fact, statin users consumed 54 more calories and 2.7 g more/day than did nonusers. Furthermore, their body mass index increased significantly, by 1.3 kg/m² during 1999-2010, compared with the BMI increase in nonusers of 0.5 kg/m², the investigators reported.

Statin use "may have undermined the perceived need to follow dietary recommendations," the researchers wrote. Patients, perceiving the drastic effect of statins on LDL cholesterol levels, "may have lost the incentive" to change their diet. Physicians might have contributed to the process by shifting the focus of consultations from diet to adherence to statin therapy, the researchers added.

"Another possible mechanism is that expanded statin use occurred in people who were likely to eat more," the researcher said. "Some patients may have agreed to initiate statin therapy because they did not want to restrict their diet, whereas others who did not want to take medication may have declined the proposed pharmacotherapy in favor of following dietary recommendations."

The National Center for Global Health and Medicine in Japan, the Honjo International Scholarship Foundation in Tokyo, and the National Institutes of Health funded the study. The authors reported no conflicts of interest.

U.S. adults who take statins consumed 14.4% more fat and 9.6% more calories in 1999-2000 than a decade earlier, while the prevalence of statin use more than doubled during that time, investigators reported online April 24 in JAMA Internal Medicine.

But fat and calorie intake did not change significantly among statin nonusers during the study period, reported Dr. Takehiro Sugiyama of the University of California, Los Angeles, and the University of Tokyo, and her associates.

The findings raise questions about managing hyperlipidemia in an era of epidemic obesity, diabetes, and "soaring" health care costs, the researchers said.

© Jeffrey Hamilton/Thinkstock

"We need to consider if it is an acceptable public health strategy to encourage statin use without also taking measures to decrease the likelihood that its use will be associated with increased caloric and fat intake as well as weight gain," they added. "We believe that the goal of statin treatment, as with any pharmacotherapy, should be to allow patients to decrease risks that cannot be decreased without medication, not to empower them to put butter on their steaks."

Dr. Sugiyama and her colleagues performed repeated cross-sectional analyses of NHANES (National Health and Nutrition Examination Survey) data on 27,886 U.S. adults aged 20 years and older during 1999-2010 (JAMA Intern. Med. 2014 [doi:10.1001/jamainternmed.2014.1927]).

At the start of the study period, statin users consumed 179 fewer kcal/day (2,000 vs. 2,179 kcal/day; P =.007) and 9.5 fewer grams of fat/day (71.7 vs. 81.2 g/day; P = .003) than did nonusers, "as we would expect for persons attempting to control their cholesterol level and weight," the researchers said.

But the gaps between the two groups narrowed as statin users consumed more calories and fat during the next several years. By 2009-2010, statin users consumed 9.6% more calories and 14.4% more fat than they had in 1999-2000, both statistically significant differences. In fact, statin users consumed 54 more calories and 2.7 g more/day than did nonusers. Furthermore, their body mass index increased significantly, by 1.3 kg/m² during 1999-2010, compared with the BMI increase in nonusers of 0.5 kg/m², the investigators reported.

Statin use "may have undermined the perceived need to follow dietary recommendations," the researchers wrote. Patients, perceiving the drastic effect of statins on LDL cholesterol levels, "may have lost the incentive" to change their diet. Physicians might have contributed to the process by shifting the focus of consultations from diet to adherence to statin therapy, the researchers added.

"Another possible mechanism is that expanded statin use occurred in people who were likely to eat more," the researcher said. "Some patients may have agreed to initiate statin therapy because they did not want to restrict their diet, whereas others who did not want to take medication may have declined the proposed pharmacotherapy in favor of following dietary recommendations."

The National Center for Global Health and Medicine in Japan, the Honjo International Scholarship Foundation in Tokyo, and the National Institutes of Health funded the study. The authors reported no conflicts of interest.

Benzodiazepine use is associated with significantly increased risks of adverse respiratory outcomes in older adults with chronic obstructive pulmonary disease, researchers reported online April 17 in the European Respiratory Journal.

New benzodiazepine users were 45% more likely to receive outpatient respiratory medications and 92% more likely to visit the emergency department for respiratory reasons than were non–benzodiazepine users, reported Dr. Nicholas Vozoris of St. Michael’s Hospital and the University of Toronto and his associates.

"These findings are concerning, given that benzodiazepines are known to be frequently used among older adults with COPD and in suboptimal ways," the investigators wrote. "The findings suggest that the potential for adverse respiratory outcomes needs to be considered when administering benzodiazepines to older adults with COPD."

The retrospective population-based cohort study identified 177,355 adults with COPD who were at least 66 years old and lived in Ontario, Canada, during 2003-2010. The researchers used 1:1 propensity score matching without replacement to match 48,915 new benzodiazepine users with the same number of nonusers (Eur. Respir. J. 2014 April 17 [doi: 10.1183/09031936.00008014]).

New users of benzodiazepines were significantly more likely to be prescribed oral corticosteroids or respiratory antibiotics (relative risk, 1.45; 95% confidence interval, 1.36-1.54) and to visit the emergency department for COPD or pneumonia (RR, 1.92; 95% CI, 1.69-2.18).

Furthermore, in the subgroup of patients who had no exacerbation of COPD during the year before baseline, new benzodiazepine users had a significantly greater risk of receiving outpatient respiratory medications (RR, 1.63; 95% CI, 1.44-1.84), visiting an emergency department for COPD or pneumonia (RR, 2.46; 95% CI, 1.90-3.18), being hospitalized for either diagnosis (RR, 1.29; 95% CI, 1.07-1.56), or dying from any cause (RR, 1.19, 95% CI, 1.06-1.34).

The research is consistent with findings from previous smaller, shorter-duration studies, said Dr. Vozoris and his associates. They noted that their definition of COPD had a sensitivity of only 58%, which could limit the generalizability of the findings.

The Canadian Institutes of Health and the Institute for Clinical Evaluative Sciences funded the study. The investigators reported having no conflicts of interest.

Benzodiazepine use is associated with significantly increased risks of adverse respiratory outcomes in older adults with chronic obstructive pulmonary disease, researchers reported online April 17 in the European Respiratory Journal.

New benzodiazepine users were 45% more likely to receive outpatient respiratory medications and 92% more likely to visit the emergency department for respiratory reasons than were non–benzodiazepine users, reported Dr. Nicholas Vozoris of St. Michael’s Hospital and the University of Toronto and his associates.

"These findings are concerning, given that benzodiazepines are known to be frequently used among older adults with COPD and in suboptimal ways," the investigators wrote. "The findings suggest that the potential for adverse respiratory outcomes needs to be considered when administering benzodiazepines to older adults with COPD."

The retrospective population-based cohort study identified 177,355 adults with COPD who were at least 66 years old and lived in Ontario, Canada, during 2003-2010. The researchers used 1:1 propensity score matching without replacement to match 48,915 new benzodiazepine users with the same number of nonusers (Eur. Respir. J. 2014 April 17 [doi: 10.1183/09031936.00008014]).

New users of benzodiazepines were significantly more likely to be prescribed oral corticosteroids or respiratory antibiotics (relative risk, 1.45; 95% confidence interval, 1.36-1.54) and to visit the emergency department for COPD or pneumonia (RR, 1.92; 95% CI, 1.69-2.18).

Furthermore, in the subgroup of patients who had no exacerbation of COPD during the year before baseline, new benzodiazepine users had a significantly greater risk of receiving outpatient respiratory medications (RR, 1.63; 95% CI, 1.44-1.84), visiting an emergency department for COPD or pneumonia (RR, 2.46; 95% CI, 1.90-3.18), being hospitalized for either diagnosis (RR, 1.29; 95% CI, 1.07-1.56), or dying from any cause (RR, 1.19, 95% CI, 1.06-1.34).

The research is consistent with findings from previous smaller, shorter-duration studies, said Dr. Vozoris and his associates. They noted that their definition of COPD had a sensitivity of only 58%, which could limit the generalizability of the findings.

The Canadian Institutes of Health and the Institute for Clinical Evaluative Sciences funded the study. The investigators reported having no conflicts of interest.

Benzodiazepine use is associated with significantly increased risks of adverse respiratory outcomes in older adults with chronic obstructive pulmonary disease, researchers reported online April 17 in the European Respiratory Journal.

New benzodiazepine users were 45% more likely to receive outpatient respiratory medications and 92% more likely to visit the emergency department for respiratory reasons than were non–benzodiazepine users, reported Dr. Nicholas Vozoris of St. Michael’s Hospital and the University of Toronto and his associates.

"These findings are concerning, given that benzodiazepines are known to be frequently used among older adults with COPD and in suboptimal ways," the investigators wrote. "The findings suggest that the potential for adverse respiratory outcomes needs to be considered when administering benzodiazepines to older adults with COPD."

The retrospective population-based cohort study identified 177,355 adults with COPD who were at least 66 years old and lived in Ontario, Canada, during 2003-2010. The researchers used 1:1 propensity score matching without replacement to match 48,915 new benzodiazepine users with the same number of nonusers (Eur. Respir. J. 2014 April 17 [doi: 10.1183/09031936.00008014]).

New users of benzodiazepines were significantly more likely to be prescribed oral corticosteroids or respiratory antibiotics (relative risk, 1.45; 95% confidence interval, 1.36-1.54) and to visit the emergency department for COPD or pneumonia (RR, 1.92; 95% CI, 1.69-2.18).

Furthermore, in the subgroup of patients who had no exacerbation of COPD during the year before baseline, new benzodiazepine users had a significantly greater risk of receiving outpatient respiratory medications (RR, 1.63; 95% CI, 1.44-1.84), visiting an emergency department for COPD or pneumonia (RR, 2.46; 95% CI, 1.90-3.18), being hospitalized for either diagnosis (RR, 1.29; 95% CI, 1.07-1.56), or dying from any cause (RR, 1.19, 95% CI, 1.06-1.34).

The research is consistent with findings from previous smaller, shorter-duration studies, said Dr. Vozoris and his associates. They noted that their definition of COPD had a sensitivity of only 58%, which could limit the generalizability of the findings.

The Canadian Institutes of Health and the Institute for Clinical Evaluative Sciences funded the study. The investigators reported having no conflicts of interest.

Empagliflozin was associated with dose-dependent improvements in glycemic control and weight when added to metformin in adults with type 2 diabetes, according to researchers. The study was published online in Diabetes Care.

At week 24, patients who received 25 mg daily of the investigational selective sodium glucose cotransporter 2 (SGLT2) inhibitor had an adjusted mean change in hemoglobin A_1c of –0.77%, compared with –0.70% for the 10-mg empagliflozin group and –0.13% for patients who received placebo, both highly significant differences, reported Dr. Hans-Ulrich Häring of the University of Tübingen, Germany.

Empagliflozin also significantly reduced patients’ weight and mean daily glucose level compared with placebo, and was associated with similar rates of adverse effects, noted Dr. Häring and his associates (Diabetes Care 2014 April 10 [doi: 10.2337/dc13-2105]).

The double-blind, randomized trial comprised 637 adults whose HbA_1c levels remained suboptimal (defined as 7%-10%) despite a diet and exercise program and at least 12 weeks of treatment with immediate-release metformin.

In addition to the improvements in HbA_1c, patients who took 25 mg empagliflozin lost an average of 2.46 kg, compared with 2.08 kg for patients who took 10 mg empagliflozin and 0.45 kg for the placebo group, the investigators reported. Likewise, mean daily glucose levels dropped 0.80 mmol/L from baseline in the 25 mg empagliflozin group, versus 0.54 mmol/L for the 10 mg group and 0.11 mmol/L for the placebo group. All these differences were statistically significant.

Rates of adverse events were 49.5%-58.7% with empagliflozin, and it was associated with a low risk of hypoglycemia (1.8%-1.4% vs. 0.5% for placebo), the investigators reported. The treatment groups had higher rates of mild to moderate genital infections than did the placebo group, but only two patients dropped out as a result, said the investigators.

"This trial demonstrates the potential of empagliflozin to be used as add-on therapy in patients with type 2 diabetes who fail to achieve glycemic control while receiving metformin monotherapy," the researchers wrote.

The Food and Drug Administration denied Boehringer Ingelheim (BI) approval in March, citing concerns about the facility where empagliflozin is to be manufactured. Two other SGLT2 inhibitors – canagliflozin (Invokana) and dapagliflozin (Farxiga) – have already been approved.

Eli Lilly and BI funded the study. Dr. Häring is an advisory board member with BI, and five coauthors were employed by the company.

Empagliflozin was associated with dose-dependent improvements in glycemic control and weight when added to metformin in adults with type 2 diabetes, according to researchers. The study was published online in Diabetes Care.

At week 24, patients who received 25 mg daily of the investigational selective sodium glucose cotransporter 2 (SGLT2) inhibitor had an adjusted mean change in hemoglobin A_1c of –0.77%, compared with –0.70% for the 10-mg empagliflozin group and –0.13% for patients who received placebo, both highly significant differences, reported Dr. Hans-Ulrich Häring of the University of Tübingen, Germany.

Empagliflozin also significantly reduced patients’ weight and mean daily glucose level compared with placebo, and was associated with similar rates of adverse effects, noted Dr. Häring and his associates (Diabetes Care 2014 April 10 [doi: 10.2337/dc13-2105]).

The double-blind, randomized trial comprised 637 adults whose HbA_1c levels remained suboptimal (defined as 7%-10%) despite a diet and exercise program and at least 12 weeks of treatment with immediate-release metformin.

In addition to the improvements in HbA_1c, patients who took 25 mg empagliflozin lost an average of 2.46 kg, compared with 2.08 kg for patients who took 10 mg empagliflozin and 0.45 kg for the placebo group, the investigators reported. Likewise, mean daily glucose levels dropped 0.80 mmol/L from baseline in the 25 mg empagliflozin group, versus 0.54 mmol/L for the 10 mg group and 0.11 mmol/L for the placebo group. All these differences were statistically significant.

Rates of adverse events were 49.5%-58.7% with empagliflozin, and it was associated with a low risk of hypoglycemia (1.8%-1.4% vs. 0.5% for placebo), the investigators reported. The treatment groups had higher rates of mild to moderate genital infections than did the placebo group, but only two patients dropped out as a result, said the investigators.

"This trial demonstrates the potential of empagliflozin to be used as add-on therapy in patients with type 2 diabetes who fail to achieve glycemic control while receiving metformin monotherapy," the researchers wrote.

The Food and Drug Administration denied Boehringer Ingelheim (BI) approval in March, citing concerns about the facility where empagliflozin is to be manufactured. Two other SGLT2 inhibitors – canagliflozin (Invokana) and dapagliflozin (Farxiga) – have already been approved.

Eli Lilly and BI funded the study. Dr. Häring is an advisory board member with BI, and five coauthors were employed by the company.

Empagliflozin was associated with dose-dependent improvements in glycemic control and weight when added to metformin in adults with type 2 diabetes, according to researchers. The study was published online in Diabetes Care.

At week 24, patients who received 25 mg daily of the investigational selective sodium glucose cotransporter 2 (SGLT2) inhibitor had an adjusted mean change in hemoglobin A_1c of –0.77%, compared with –0.70% for the 10-mg empagliflozin group and –0.13% for patients who received placebo, both highly significant differences, reported Dr. Hans-Ulrich Häring of the University of Tübingen, Germany.

Empagliflozin also significantly reduced patients’ weight and mean daily glucose level compared with placebo, and was associated with similar rates of adverse effects, noted Dr. Häring and his associates (Diabetes Care 2014 April 10 [doi: 10.2337/dc13-2105]).

The double-blind, randomized trial comprised 637 adults whose HbA_1c levels remained suboptimal (defined as 7%-10%) despite a diet and exercise program and at least 12 weeks of treatment with immediate-release metformin.

In addition to the improvements in HbA_1c, patients who took 25 mg empagliflozin lost an average of 2.46 kg, compared with 2.08 kg for patients who took 10 mg empagliflozin and 0.45 kg for the placebo group, the investigators reported. Likewise, mean daily glucose levels dropped 0.80 mmol/L from baseline in the 25 mg empagliflozin group, versus 0.54 mmol/L for the 10 mg group and 0.11 mmol/L for the placebo group. All these differences were statistically significant.

Rates of adverse events were 49.5%-58.7% with empagliflozin, and it was associated with a low risk of hypoglycemia (1.8%-1.4% vs. 0.5% for placebo), the investigators reported. The treatment groups had higher rates of mild to moderate genital infections than did the placebo group, but only two patients dropped out as a result, said the investigators.

"This trial demonstrates the potential of empagliflozin to be used as add-on therapy in patients with type 2 diabetes who fail to achieve glycemic control while receiving metformin monotherapy," the researchers wrote.

The Food and Drug Administration denied Boehringer Ingelheim (BI) approval in March, citing concerns about the facility where empagliflozin is to be manufactured. Two other SGLT2 inhibitors – canagliflozin (Invokana) and dapagliflozin (Farxiga) – have already been approved.

Eli Lilly and BI funded the study. Dr. Häring is an advisory board member with BI, and five coauthors were employed by the company.

Empagliflozin was associated with dose-dependent improvements in glycemic control and weight when added to metformin in adults with type 2 diabetes, according to researchers. The study was published online April 10 in Diabetes Care.

At week 24, patients who received 25 mg daily of the investigational selective sodium glucose cotransporter 2 (SGLT2) inhibitor had an adjusted mean change in hemoglobin A_1c of –0.77%, compared with –0.70% for the 10-mg empagliflozin group and –0.13% for patients who received placebo, both highly significant differences, reported Dr. Hans-Ulrich Häring of the University of Tübingen, Germany.

Empagliflozin also significantly reduced patients’ weight and mean daily glucose level compared with placebo, and was associated with similar rates of adverse effects, noted Dr. Häring and his associates (Diabetes Care 2014 April 10 [doi: 10.2337/dc13-2105]).

The double-blind, randomized trial comprised 637 adults whose HbA_1c levels remained suboptimal (defined as 7%-10%) despite a diet and exercise program and at least 12 weeks of treatment with immediate-release metformin.

In addition to the improvements in HbA_1c, patients who took 25 mg empagliflozin lost an average of 2.46 kg, compared with 2.08 kg for patients who took 10 mg empagliflozin and 0.45 kg for the placebo group, the investigators reported. Likewise, mean daily glucose levels dropped 0.80 mmol/L from baseline in the 25 mg empagliflozin group, versus 0.54 mmol/L for the 10 mg group and 0.11 mmol/L for the placebo group. All these differences were statistically significant.

Rates of adverse events were 49.5%-58.7% with empagliflozin, and it was associated with a low risk of hypoglycemia (1.8%-1.4% vs. 0.5% for placebo), the investigators reported. The treatment groups had higher rates of mild to moderate genital infections than did the placebo group, but only two patients dropped out as a result, said the investigators.

"This trial demonstrates the potential of empagliflozin to be used as add-on therapy in patients with type 2 diabetes who fail to achieve glycemic control while receiving metformin monotherapy," the researchers wrote.

The Food and Drug Administration denied Boehringer Ingelheim (BI) approval in March, citing concerns about the facility where empagliflozin is to be manufactured. Two other SGLT2 inhibitors – canagliflozin (Invokana) and dapagliflozin (Farxiga) – have already been approved.

Eli Lilly and BI funded the study. Dr. Häring is an advisory board member with BI, and five coauthors were employed by the company.

Empagliflozin was associated with dose-dependent improvements in glycemic control and weight when added to metformin in adults with type 2 diabetes, according to researchers. The study was published online April 10 in Diabetes Care.

At week 24, patients who received 25 mg daily of the investigational selective sodium glucose cotransporter 2 (SGLT2) inhibitor had an adjusted mean change in hemoglobin A_1c of –0.77%, compared with –0.70% for the 10-mg empagliflozin group and –0.13% for patients who received placebo, both highly significant differences, reported Dr. Hans-Ulrich Häring of the University of Tübingen, Germany.

Empagliflozin also significantly reduced patients’ weight and mean daily glucose level compared with placebo, and was associated with similar rates of adverse effects, noted Dr. Häring and his associates (Diabetes Care 2014 April 10 [doi: 10.2337/dc13-2105]).

The double-blind, randomized trial comprised 637 adults whose HbA_1c levels remained suboptimal (defined as 7%-10%) despite a diet and exercise program and at least 12 weeks of treatment with immediate-release metformin.

In addition to the improvements in HbA_1c, patients who took 25 mg empagliflozin lost an average of 2.46 kg, compared with 2.08 kg for patients who took 10 mg empagliflozin and 0.45 kg for the placebo group, the investigators reported. Likewise, mean daily glucose levels dropped 0.80 mmol/L from baseline in the 25 mg empagliflozin group, versus 0.54 mmol/L for the 10 mg group and 0.11 mmol/L for the placebo group. All these differences were statistically significant.

Rates of adverse events were 49.5%-58.7% with empagliflozin, and it was associated with a low risk of hypoglycemia (1.8%-1.4% vs. 0.5% for placebo), the investigators reported. The treatment groups had higher rates of mild to moderate genital infections than did the placebo group, but only two patients dropped out as a result, said the investigators.

"This trial demonstrates the potential of empagliflozin to be used as add-on therapy in patients with type 2 diabetes who fail to achieve glycemic control while receiving metformin monotherapy," the researchers wrote.

The Food and Drug Administration denied Boehringer Ingelheim (BI) approval in March, citing concerns about the facility where empagliflozin is to be manufactured. Two other SGLT2 inhibitors – canagliflozin (Invokana) and dapagliflozin (Farxiga) – have already been approved.

Eli Lilly and BI funded the study. Dr. Häring is an advisory board member with BI, and five coauthors were employed by the company.

Empagliflozin was associated with dose-dependent improvements in glycemic control and weight when added to metformin in adults with type 2 diabetes, according to researchers. The study was published online April 10 in Diabetes Care.

At week 24, patients who received 25 mg daily of the investigational selective sodium glucose cotransporter 2 (SGLT2) inhibitor had an adjusted mean change in hemoglobin A_1c of –0.77%, compared with –0.70% for the 10-mg empagliflozin group and –0.13% for patients who received placebo, both highly significant differences, reported Dr. Hans-Ulrich Häring of the University of Tübingen, Germany.

Empagliflozin also significantly reduced patients’ weight and mean daily glucose level compared with placebo, and was associated with similar rates of adverse effects, noted Dr. Häring and his associates (Diabetes Care 2014 April 10 [doi: 10.2337/dc13-2105]).

The double-blind, randomized trial comprised 637 adults whose HbA_1c levels remained suboptimal (defined as 7%-10%) despite a diet and exercise program and at least 12 weeks of treatment with immediate-release metformin.

In addition to the improvements in HbA_1c, patients who took 25 mg empagliflozin lost an average of 2.46 kg, compared with 2.08 kg for patients who took 10 mg empagliflozin and 0.45 kg for the placebo group, the investigators reported. Likewise, mean daily glucose levels dropped 0.80 mmol/L from baseline in the 25 mg empagliflozin group, versus 0.54 mmol/L for the 10 mg group and 0.11 mmol/L for the placebo group. All these differences were statistically significant.

Rates of adverse events were 49.5%-58.7% with empagliflozin, and it was associated with a low risk of hypoglycemia (1.8%-1.4% vs. 0.5% for placebo), the investigators reported. The treatment groups had higher rates of mild to moderate genital infections than did the placebo group, but only two patients dropped out as a result, said the investigators.

"This trial demonstrates the potential of empagliflozin to be used as add-on therapy in patients with type 2 diabetes who fail to achieve glycemic control while receiving metformin monotherapy," the researchers wrote.

The Food and Drug Administration denied Boehringer Ingelheim (BI) approval in March, citing concerns about the facility where empagliflozin is to be manufactured. Two other SGLT2 inhibitors – canagliflozin (Invokana) and dapagliflozin (Farxiga) – have already been approved.

Eli Lilly and BI funded the study. Dr. Häring is an advisory board member with BI, and five coauthors were employed by the company.