Adolescents who use e-cigarettes are more likely to progress to smoking cigarettes, and are likely to continue using both products at once instead of substituting one for the other, according to research published in Nicotine & Tobacco Research.

mauro grigollo/Thinkstock

“Our work provides more evidence that young people who use e-cigarettes progress to smoking cigarettes in the future,” Michael S. Dunbar, PhD, a behavioral scientist at the RAND Corp. stated in a press release. “This study also suggests that teens don’t substitute vaping products for cigarettes. Instead, they go on to use both products more frequently as they get older.”

Dr. Dunbar and his colleagues followed 2,039 adolescents aged 16-20 years who were originally enrolled in a Los Angeles–based substance use prevention program in sixth and seventh grade (2008) and completed annual Web-based surveys during 2015-2017 on their use of e-cigarettes (EC), cigarettes, alcohol, and marijuana. They also answered questions about their mental health with questions about anxiety and depression. The researchers used two models to measures associations between different factors.

The first model showed an association between EC and cigarette use. Then other factors, such as alcohol use, were introduced. Alcohol use was associated with increased cigarette use, and cigarette use was associated with increased use of alcohol. When introducing marijuana as a factor, associations remained between cigarette use and EC use, with higher EC use associated with greater marijuana use and vice versa. Greater cigarette use, however, was not predictive of later marijuana use. There was no association between EC use and mental health, but more cigarette use was associated with poorer mental health.

Under the second model, there was a moderate to strong association between EC use and cigarette use, and participants with greater EC use and greater cigarette use also reported higher alcohol use. There also was a significant between-person association with higher EC use, cigarette use, and marijuana use. There was a small negative association between mental health and cigarette use, but not with mental health and EC use,the researchers said.

“For young people, using these products may actually lead to more harm in the long run,” Dr. Dunbar said in the press release. “This highlights the importance of taking steps to prevent youth from vaping in the first place. One way to do this could be to limit e-cigarette and other tobacco advertising in kid-accessible spaces.”

This study was funded by grants from the National Institute of Alcohol Abuse and Alcoholism. The authors reported no relevant conflicts of interest.
 

SOURCE: Dunbar MS et al. Nicotine Tob Res. 2018 Oct 3. doi: 10.1093/ntr/nty179.

Adolescents who use e-cigarettes are more likely to progress to smoking cigarettes, and are likely to continue using both products at once instead of substituting one for the other, according to research published in Nicotine & Tobacco Research.

mauro grigollo/Thinkstock

“Our work provides more evidence that young people who use e-cigarettes progress to smoking cigarettes in the future,” Michael S. Dunbar, PhD, a behavioral scientist at the RAND Corp. stated in a press release. “This study also suggests that teens don’t substitute vaping products for cigarettes. Instead, they go on to use both products more frequently as they get older.”

Dr. Dunbar and his colleagues followed 2,039 adolescents aged 16-20 years who were originally enrolled in a Los Angeles–based substance use prevention program in sixth and seventh grade (2008) and completed annual Web-based surveys during 2015-2017 on their use of e-cigarettes (EC), cigarettes, alcohol, and marijuana. They also answered questions about their mental health with questions about anxiety and depression. The researchers used two models to measures associations between different factors.

The first model showed an association between EC and cigarette use. Then other factors, such as alcohol use, were introduced. Alcohol use was associated with increased cigarette use, and cigarette use was associated with increased use of alcohol. When introducing marijuana as a factor, associations remained between cigarette use and EC use, with higher EC use associated with greater marijuana use and vice versa. Greater cigarette use, however, was not predictive of later marijuana use. There was no association between EC use and mental health, but more cigarette use was associated with poorer mental health.

Under the second model, there was a moderate to strong association between EC use and cigarette use, and participants with greater EC use and greater cigarette use also reported higher alcohol use. There also was a significant between-person association with higher EC use, cigarette use, and marijuana use. There was a small negative association between mental health and cigarette use, but not with mental health and EC use,the researchers said.

“For young people, using these products may actually lead to more harm in the long run,” Dr. Dunbar said in the press release. “This highlights the importance of taking steps to prevent youth from vaping in the first place. One way to do this could be to limit e-cigarette and other tobacco advertising in kid-accessible spaces.”

This study was funded by grants from the National Institute of Alcohol Abuse and Alcoholism. The authors reported no relevant conflicts of interest.
 

SOURCE: Dunbar MS et al. Nicotine Tob Res. 2018 Oct 3. doi: 10.1093/ntr/nty179.

Adolescents who use e-cigarettes are more likely to progress to smoking cigarettes, and are likely to continue using both products at once instead of substituting one for the other, according to research published in Nicotine & Tobacco Research.

mauro grigollo/Thinkstock

“Our work provides more evidence that young people who use e-cigarettes progress to smoking cigarettes in the future,” Michael S. Dunbar, PhD, a behavioral scientist at the RAND Corp. stated in a press release. “This study also suggests that teens don’t substitute vaping products for cigarettes. Instead, they go on to use both products more frequently as they get older.”

Dr. Dunbar and his colleagues followed 2,039 adolescents aged 16-20 years who were originally enrolled in a Los Angeles–based substance use prevention program in sixth and seventh grade (2008) and completed annual Web-based surveys during 2015-2017 on their use of e-cigarettes (EC), cigarettes, alcohol, and marijuana. They also answered questions about their mental health with questions about anxiety and depression. The researchers used two models to measures associations between different factors.

The first model showed an association between EC and cigarette use. Then other factors, such as alcohol use, were introduced. Alcohol use was associated with increased cigarette use, and cigarette use was associated with increased use of alcohol. When introducing marijuana as a factor, associations remained between cigarette use and EC use, with higher EC use associated with greater marijuana use and vice versa. Greater cigarette use, however, was not predictive of later marijuana use. There was no association between EC use and mental health, but more cigarette use was associated with poorer mental health.

Under the second model, there was a moderate to strong association between EC use and cigarette use, and participants with greater EC use and greater cigarette use also reported higher alcohol use. There also was a significant between-person association with higher EC use, cigarette use, and marijuana use. There was a small negative association between mental health and cigarette use, but not with mental health and EC use,the researchers said.

“For young people, using these products may actually lead to more harm in the long run,” Dr. Dunbar said in the press release. “This highlights the importance of taking steps to prevent youth from vaping in the first place. One way to do this could be to limit e-cigarette and other tobacco advertising in kid-accessible spaces.”

This study was funded by grants from the National Institute of Alcohol Abuse and Alcoholism. The authors reported no relevant conflicts of interest.
 

SOURCE: Dunbar MS et al. Nicotine Tob Res. 2018 Oct 3. doi: 10.1093/ntr/nty179.

SAN DIEGO – The rule-in cutoff level for high-sensitivity cardiac troponin measures in the diagnosis of acute MI have been established by the European Society of Cardiology, but the value might not be applicable to a U.S. population.

In a video interview at the annual scientific assembly of the American College of Emergency Physicians, Richard M. Nowak, MD, of the department of emergency medicine at Henry Ford Hospital, Detroit, explains why the rule-in cutoff is not likely to apply to American patients and may be associated with a higher risk of false positives.

Since high-sensitivity troponin measures will soon be coming to every ED, each institution may have to arrive at their own rule-in cutoff value in order to diagnose acute MI with an acceptable number of false positives, he said. Dr. Nowak explains how to begin addressing that process.

SAN DIEGO – The rule-in cutoff level for high-sensitivity cardiac troponin measures in the diagnosis of acute MI have been established by the European Society of Cardiology, but the value might not be applicable to a U.S. population.

In a video interview at the annual scientific assembly of the American College of Emergency Physicians, Richard M. Nowak, MD, of the department of emergency medicine at Henry Ford Hospital, Detroit, explains why the rule-in cutoff is not likely to apply to American patients and may be associated with a higher risk of false positives.

Since high-sensitivity troponin measures will soon be coming to every ED, each institution may have to arrive at their own rule-in cutoff value in order to diagnose acute MI with an acceptable number of false positives, he said. Dr. Nowak explains how to begin addressing that process.

SAN DIEGO – The rule-in cutoff level for high-sensitivity cardiac troponin measures in the diagnosis of acute MI have been established by the European Society of Cardiology, but the value might not be applicable to a U.S. population.

In a video interview at the annual scientific assembly of the American College of Emergency Physicians, Richard M. Nowak, MD, of the department of emergency medicine at Henry Ford Hospital, Detroit, explains why the rule-in cutoff is not likely to apply to American patients and may be associated with a higher risk of false positives.

Since high-sensitivity troponin measures will soon be coming to every ED, each institution may have to arrive at their own rule-in cutoff value in order to diagnose acute MI with an acceptable number of false positives, he said. Dr. Nowak explains how to begin addressing that process.

Proximal adenoma location did not predict high-grade dysplasia in a large registry study.

In fact, the odds of high-grade dysplasia were about 25% lower for proximal versus distal adenomas (odds ratio, 0.75), reported Thomas Rösch, MD, of University Hospital Hamburg-Eppendorf, Hamburg, Germany, and his associates. A third of adenomas in the study lacked location data, but in sensitivity analyses, the odds of high-grade dysplasia fell to 0.72 when these lesions were assumed to be proximal and rose to 0.96 when they were assumed to be distal.

Interval colorectal cancers probably are more likely to be proximal than distal because of a “combination of endoscopy-related factors and biology,” not because of histologic differences alone, the researchers wrote. The report was published in Clinical Gastroenterology and Hepatology.

Interval cancers are more common in the right colon, as several studies have noted. However, it was unclear whether this phenomenon represented a higher miss rate, a lower rate of successful polypectomy, or an increased risk of malignant histology in the proximal colon, the researchers wrote. Accordingly, they analyzed data on 594,614 index adenomas detected during more than 2.5 million screening colonoscopies performed between 2007 and 2012 and entered into the German National Screening Colonoscopy Registry.

A total of 3.5% of index adenomas showed high-grade dysplasia, which correlated most strongly with larger size, said the researchers. In fact, the odds of high-grade dysplasia were 10-fold higher when index adenomas measured at least 1 cm than when they were smaller. High-grade dysplasia also was significantly more frequent when patients were older than 64 years, were male, and when they had pedunculated versus flat lesions. Given the large size of the dataset, all these associations were statistically significant.

Sessile lesions were slightly more likely to be high-grade compared with flat lesions, the investigators noted. Many proximal interval cancers arise from sessile serrated polyps, which may be subtle and difficult to detect or to resect completely, they continued. At the same time, colonoscopy also might be more likely to miss flat, serrated lesions when they are located proximally, and these lesions can become more aggressive over time. Thus, “[e]ndoscopist factors, such as missed lesions or incompletely removed lesions, may account for the predominance of proximal interval colorectal cancers.”

Like other registry studies, this study lacked uniform histopathologic definitions or central histopathology review. The dataset also covered only the largest or most histologically remarkable adenoma for each patient. However, the study findings did not change substantially after the researchers controlled for patients with missing location data, which presumably included patients with multiple polyps in both proximal and distal locations.

The researchers did not disclose external funding sources. They reported having no conflicts of interest.

SOURCE: Rösch T et al. Clin Gastroenterol Hepatol. 2018 Jun 11. doi: 10.1016/j.cgh.2018.05.043.

Proximal adenoma location did not predict high-grade dysplasia in a large registry study.

In fact, the odds of high-grade dysplasia were about 25% lower for proximal versus distal adenomas (odds ratio, 0.75), reported Thomas Rösch, MD, of University Hospital Hamburg-Eppendorf, Hamburg, Germany, and his associates. A third of adenomas in the study lacked location data, but in sensitivity analyses, the odds of high-grade dysplasia fell to 0.72 when these lesions were assumed to be proximal and rose to 0.96 when they were assumed to be distal.

Interval colorectal cancers probably are more likely to be proximal than distal because of a “combination of endoscopy-related factors and biology,” not because of histologic differences alone, the researchers wrote. The report was published in Clinical Gastroenterology and Hepatology.

Interval cancers are more common in the right colon, as several studies have noted. However, it was unclear whether this phenomenon represented a higher miss rate, a lower rate of successful polypectomy, or an increased risk of malignant histology in the proximal colon, the researchers wrote. Accordingly, they analyzed data on 594,614 index adenomas detected during more than 2.5 million screening colonoscopies performed between 2007 and 2012 and entered into the German National Screening Colonoscopy Registry.

A total of 3.5% of index adenomas showed high-grade dysplasia, which correlated most strongly with larger size, said the researchers. In fact, the odds of high-grade dysplasia were 10-fold higher when index adenomas measured at least 1 cm than when they were smaller. High-grade dysplasia also was significantly more frequent when patients were older than 64 years, were male, and when they had pedunculated versus flat lesions. Given the large size of the dataset, all these associations were statistically significant.

Sessile lesions were slightly more likely to be high-grade compared with flat lesions, the investigators noted. Many proximal interval cancers arise from sessile serrated polyps, which may be subtle and difficult to detect or to resect completely, they continued. At the same time, colonoscopy also might be more likely to miss flat, serrated lesions when they are located proximally, and these lesions can become more aggressive over time. Thus, “[e]ndoscopist factors, such as missed lesions or incompletely removed lesions, may account for the predominance of proximal interval colorectal cancers.”

Like other registry studies, this study lacked uniform histopathologic definitions or central histopathology review. The dataset also covered only the largest or most histologically remarkable adenoma for each patient. However, the study findings did not change substantially after the researchers controlled for patients with missing location data, which presumably included patients with multiple polyps in both proximal and distal locations.

The researchers did not disclose external funding sources. They reported having no conflicts of interest.

SOURCE: Rösch T et al. Clin Gastroenterol Hepatol. 2018 Jun 11. doi: 10.1016/j.cgh.2018.05.043.

Proximal adenoma location did not predict high-grade dysplasia in a large registry study.

In fact, the odds of high-grade dysplasia were about 25% lower for proximal versus distal adenomas (odds ratio, 0.75), reported Thomas Rösch, MD, of University Hospital Hamburg-Eppendorf, Hamburg, Germany, and his associates. A third of adenomas in the study lacked location data, but in sensitivity analyses, the odds of high-grade dysplasia fell to 0.72 when these lesions were assumed to be proximal and rose to 0.96 when they were assumed to be distal.

Interval colorectal cancers probably are more likely to be proximal than distal because of a “combination of endoscopy-related factors and biology,” not because of histologic differences alone, the researchers wrote. The report was published in Clinical Gastroenterology and Hepatology.

Interval cancers are more common in the right colon, as several studies have noted. However, it was unclear whether this phenomenon represented a higher miss rate, a lower rate of successful polypectomy, or an increased risk of malignant histology in the proximal colon, the researchers wrote. Accordingly, they analyzed data on 594,614 index adenomas detected during more than 2.5 million screening colonoscopies performed between 2007 and 2012 and entered into the German National Screening Colonoscopy Registry.

A total of 3.5% of index adenomas showed high-grade dysplasia, which correlated most strongly with larger size, said the researchers. In fact, the odds of high-grade dysplasia were 10-fold higher when index adenomas measured at least 1 cm than when they were smaller. High-grade dysplasia also was significantly more frequent when patients were older than 64 years, were male, and when they had pedunculated versus flat lesions. Given the large size of the dataset, all these associations were statistically significant.

Sessile lesions were slightly more likely to be high-grade compared with flat lesions, the investigators noted. Many proximal interval cancers arise from sessile serrated polyps, which may be subtle and difficult to detect or to resect completely, they continued. At the same time, colonoscopy also might be more likely to miss flat, serrated lesions when they are located proximally, and these lesions can become more aggressive over time. Thus, “[e]ndoscopist factors, such as missed lesions or incompletely removed lesions, may account for the predominance of proximal interval colorectal cancers.”

Like other registry studies, this study lacked uniform histopathologic definitions or central histopathology review. The dataset also covered only the largest or most histologically remarkable adenoma for each patient. However, the study findings did not change substantially after the researchers controlled for patients with missing location data, which presumably included patients with multiple polyps in both proximal and distal locations.

The researchers did not disclose external funding sources. They reported having no conflicts of interest.

SOURCE: Rösch T et al. Clin Gastroenterol Hepatol. 2018 Jun 11. doi: 10.1016/j.cgh.2018.05.043.

PARIS – In a sham-controlled randomized trial that enrolled patients with moderate to severe chronic obstructive pulmonary disease (COPD), targeted lung denervation (TLD) was not only found safe, which was the primary goal of the study, but effective, according to data presented at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

Within the first year of follow-up, “the positive benefit in those randomized to TLD persisted with a more than 50% reduction in the number of patients hospitalized for respiratory complications,” reported Dirk-Jan Slebos, MD, department of lung diseases and tuberculosis, University of Gröningen, the Netherlands.

In this phase 2 trial, called AIRFLOW-2, 82 patients were randomized to receive TLD, which ablates nerves with radiofrequency energy, or a sham procedure. The study enrolled patients with moderate to severe COPD and forced expiratory volume in 1 second of 30%-60% predicted. All patients were treated with the long-acting muscarinic antagonist (LAMA) tiotropium.

The primary endpoint was a composite of respiratory-related adverse events, such as respiratory failure, worsening bronchitis, or worsening dyspnea. Secondary endpoints included serious adverse events of any kind as well as a variety of measures of efficacy, including changes in quality of life as measured with standardized tools such as the St. George’s Respiratory Questionnaire (SGRQ).

Within 6 months of the procedure, 71% of those randomized to the sham procedure and 32% of those treated with TLD experienced one of the predefined respiratory adverse events (P = .0008). At 1 year, 25% of patients in the sham group versus 12% in the TLD group were hospitalized for an exacerbation (P = .039). In addition to achieving greater improvement in several of the individual symptoms, such as dyspnea, those randomized to TLD also achieved numerical improvements in SGRQ scores (–8.3 vs. –3.8) at 12 months.

Gastrointestinal adverse events were more common in the TLD group (15% vs. 5%). Although the higher rate of GI events, which included nausea, bloating, and abdominal discomfort, did not reach statistical significance, it was attributed to off-target exposure of nerves in the GI system to the radiofrequency energy.

“We are improving our imaging process in order to implement additional measures to avoid these nerves,” said Dr. Slebos, who added that this potential risk can be modified. In this study, all of the GI symptoms resolved.

Dr. Slebos emphasized that the 12-month follow-up permitted the study to “confirm that TLD is safe and technically feasible with no late-onset safety signals.” It has set the stage for AIRFLOW-3, a phase 3 trial that is expected to lead to regulatory approval of the catheter if it shows similar safety and efficacy.

The principle of TLD is to deliver energy to ablate parasympathetic pulmonary nerves. The exact mechanism of benefit has not been proved, but it is believed that inhibiting release of acetylcholine that induces smooth muscle constriction has several beneficial downstream effects, including prevention of hyperinflation and reduced mucus production. AIRFLOW-3, like AIRFLOW-2, will evaluate a proprietary catheter developed for this purpose.

“TLD will not replace pharmaceutical therapy. Rather, it appears to have a synergistic effect,” explained Dr. Slebos, who said the procedure is performed on an outpatient basis. The average procedure time for TLD in AIRFLOW-2 was 42 minutes.

The first human study of TLD, also led by Dr. Slebos, was published in 2015. While several subsequent patient series support efficacy and benefit, Daiana Stolz, MD, Clinic for Respiratory Medicine and Pulmonary Cell Research, University of Basel (Switzerland), called the data from this sham-controlled trial “really exciting and important.” However, she said, the larger AIRFLOW-3 trial is needed “to confirm this is an effective and safe treatment.”
 

Dr. Slebos receives consultancy fees from Aeris Therapeutics, Boston Scientific, Broncus Technologies, CSA Medical. Olympus, Portaero, PulmonX, PneumRx/BTG, and Nuvaira, which provided the funding for this study.

PARIS – In a sham-controlled randomized trial that enrolled patients with moderate to severe chronic obstructive pulmonary disease (COPD), targeted lung denervation (TLD) was not only found safe, which was the primary goal of the study, but effective, according to data presented at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

Within the first year of follow-up, “the positive benefit in those randomized to TLD persisted with a more than 50% reduction in the number of patients hospitalized for respiratory complications,” reported Dirk-Jan Slebos, MD, department of lung diseases and tuberculosis, University of Gröningen, the Netherlands.

In this phase 2 trial, called AIRFLOW-2, 82 patients were randomized to receive TLD, which ablates nerves with radiofrequency energy, or a sham procedure. The study enrolled patients with moderate to severe COPD and forced expiratory volume in 1 second of 30%-60% predicted. All patients were treated with the long-acting muscarinic antagonist (LAMA) tiotropium.

The primary endpoint was a composite of respiratory-related adverse events, such as respiratory failure, worsening bronchitis, or worsening dyspnea. Secondary endpoints included serious adverse events of any kind as well as a variety of measures of efficacy, including changes in quality of life as measured with standardized tools such as the St. George’s Respiratory Questionnaire (SGRQ).

Within 6 months of the procedure, 71% of those randomized to the sham procedure and 32% of those treated with TLD experienced one of the predefined respiratory adverse events (P = .0008). At 1 year, 25% of patients in the sham group versus 12% in the TLD group were hospitalized for an exacerbation (P = .039). In addition to achieving greater improvement in several of the individual symptoms, such as dyspnea, those randomized to TLD also achieved numerical improvements in SGRQ scores (–8.3 vs. –3.8) at 12 months.

Gastrointestinal adverse events were more common in the TLD group (15% vs. 5%). Although the higher rate of GI events, which included nausea, bloating, and abdominal discomfort, did not reach statistical significance, it was attributed to off-target exposure of nerves in the GI system to the radiofrequency energy.

“We are improving our imaging process in order to implement additional measures to avoid these nerves,” said Dr. Slebos, who added that this potential risk can be modified. In this study, all of the GI symptoms resolved.

Dr. Slebos emphasized that the 12-month follow-up permitted the study to “confirm that TLD is safe and technically feasible with no late-onset safety signals.” It has set the stage for AIRFLOW-3, a phase 3 trial that is expected to lead to regulatory approval of the catheter if it shows similar safety and efficacy.

The principle of TLD is to deliver energy to ablate parasympathetic pulmonary nerves. The exact mechanism of benefit has not been proved, but it is believed that inhibiting release of acetylcholine that induces smooth muscle constriction has several beneficial downstream effects, including prevention of hyperinflation and reduced mucus production. AIRFLOW-3, like AIRFLOW-2, will evaluate a proprietary catheter developed for this purpose.

“TLD will not replace pharmaceutical therapy. Rather, it appears to have a synergistic effect,” explained Dr. Slebos, who said the procedure is performed on an outpatient basis. The average procedure time for TLD in AIRFLOW-2 was 42 minutes.

The first human study of TLD, also led by Dr. Slebos, was published in 2015. While several subsequent patient series support efficacy and benefit, Daiana Stolz, MD, Clinic for Respiratory Medicine and Pulmonary Cell Research, University of Basel (Switzerland), called the data from this sham-controlled trial “really exciting and important.” However, she said, the larger AIRFLOW-3 trial is needed “to confirm this is an effective and safe treatment.”
 

Dr. Slebos receives consultancy fees from Aeris Therapeutics, Boston Scientific, Broncus Technologies, CSA Medical. Olympus, Portaero, PulmonX, PneumRx/BTG, and Nuvaira, which provided the funding for this study.

PARIS – In a sham-controlled randomized trial that enrolled patients with moderate to severe chronic obstructive pulmonary disease (COPD), targeted lung denervation (TLD) was not only found safe, which was the primary goal of the study, but effective, according to data presented at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

Within the first year of follow-up, “the positive benefit in those randomized to TLD persisted with a more than 50% reduction in the number of patients hospitalized for respiratory complications,” reported Dirk-Jan Slebos, MD, department of lung diseases and tuberculosis, University of Gröningen, the Netherlands.

In this phase 2 trial, called AIRFLOW-2, 82 patients were randomized to receive TLD, which ablates nerves with radiofrequency energy, or a sham procedure. The study enrolled patients with moderate to severe COPD and forced expiratory volume in 1 second of 30%-60% predicted. All patients were treated with the long-acting muscarinic antagonist (LAMA) tiotropium.

The primary endpoint was a composite of respiratory-related adverse events, such as respiratory failure, worsening bronchitis, or worsening dyspnea. Secondary endpoints included serious adverse events of any kind as well as a variety of measures of efficacy, including changes in quality of life as measured with standardized tools such as the St. George’s Respiratory Questionnaire (SGRQ).

Within 6 months of the procedure, 71% of those randomized to the sham procedure and 32% of those treated with TLD experienced one of the predefined respiratory adverse events (P = .0008). At 1 year, 25% of patients in the sham group versus 12% in the TLD group were hospitalized for an exacerbation (P = .039). In addition to achieving greater improvement in several of the individual symptoms, such as dyspnea, those randomized to TLD also achieved numerical improvements in SGRQ scores (–8.3 vs. –3.8) at 12 months.

Gastrointestinal adverse events were more common in the TLD group (15% vs. 5%). Although the higher rate of GI events, which included nausea, bloating, and abdominal discomfort, did not reach statistical significance, it was attributed to off-target exposure of nerves in the GI system to the radiofrequency energy.

“We are improving our imaging process in order to implement additional measures to avoid these nerves,” said Dr. Slebos, who added that this potential risk can be modified. In this study, all of the GI symptoms resolved.

Dr. Slebos emphasized that the 12-month follow-up permitted the study to “confirm that TLD is safe and technically feasible with no late-onset safety signals.” It has set the stage for AIRFLOW-3, a phase 3 trial that is expected to lead to regulatory approval of the catheter if it shows similar safety and efficacy.

The principle of TLD is to deliver energy to ablate parasympathetic pulmonary nerves. The exact mechanism of benefit has not been proved, but it is believed that inhibiting release of acetylcholine that induces smooth muscle constriction has several beneficial downstream effects, including prevention of hyperinflation and reduced mucus production. AIRFLOW-3, like AIRFLOW-2, will evaluate a proprietary catheter developed for this purpose.

“TLD will not replace pharmaceutical therapy. Rather, it appears to have a synergistic effect,” explained Dr. Slebos, who said the procedure is performed on an outpatient basis. The average procedure time for TLD in AIRFLOW-2 was 42 minutes.

The first human study of TLD, also led by Dr. Slebos, was published in 2015. While several subsequent patient series support efficacy and benefit, Daiana Stolz, MD, Clinic for Respiratory Medicine and Pulmonary Cell Research, University of Basel (Switzerland), called the data from this sham-controlled trial “really exciting and important.” However, she said, the larger AIRFLOW-3 trial is needed “to confirm this is an effective and safe treatment.”
 

Dr. Slebos receives consultancy fees from Aeris Therapeutics, Boston Scientific, Broncus Technologies, CSA Medical. Olympus, Portaero, PulmonX, PneumRx/BTG, and Nuvaira, which provided the funding for this study.

SAN DIEGO – Simply offering an ice pop to children who are receiving care in an ED boosts satisfaction scores and physician ratings by their children’s parents, according to data presented at the annual meeting of the American College of Emergency Physicians.

Patient experience and subsequently patient satisfaction scores “have become an increasingly important component of health care delivery. ... Does [the act of] administering Popsicles actually make us better clinicians?” asked Ryan Finn, MD, of the Mayo Clinic, Rochester, Minn., who presented these data.

Exploring low-cost ways to improve patient experience and, by extension, patient satisfaction led to this study of an ice pop intervention, Dr. Finn explained. The study design was simple. During a 3-month period, all children under the age of 14 years (mean age, 6 years) who visited the ED on an even numbered date were offered an ice pop. On odd numbered dates, no ice pop was given. There were no other differences in care.

Parent perceptions of care were assessed with the proprietary Press Ganey patient satisfaction survey. Although a completed survey was submitted for less than 5% of the more than 4,500 patients treated during the study period, differences between the groups still reached statistical significance.

When parents were asked to rate physicians on concern for their child’s comfort, 74% of the group given ice pops and 58% of the group given no ice pops gave favorable responses (P less than.05). The parents of children in the ice pop group also were significantly more likely to rate physicians favorably for their courtesy (77% vs. 62%; P less than .04) and for their willingness to take the time to listen (84% vs. 57%; P less than .03).

Overall rating of care (64% vs. 61%) and likelihood of recommending the ED to others (66% vs. 59%) did not approach statistical significance, according to Dr. Finn.

There are numerous potential advantages to improving the patient experience and boosting patient satisfaction in the ED, as is the case in other areas of the hospital. Even if medical care is of high quality, patient satisfaction does not necessarily follow. Although this single-center study had limitations, such as the low survey completion rate, the measurable effects of the ice pop intervention encourages this direction of research.

“Further studies should increase sample size, assess age group subsets, and assess return on investment for this and other low-cost interventions with the potential to alter patient perceptions,” Dr. Finn said. Because patient satisfaction can be reasonably expected to favorably affect quality of care assessments, he indicated that this is a reasonable target for quality improvement strategies.

SAN DIEGO – Simply offering an ice pop to children who are receiving care in an ED boosts satisfaction scores and physician ratings by their children’s parents, according to data presented at the annual meeting of the American College of Emergency Physicians.

Patient experience and subsequently patient satisfaction scores “have become an increasingly important component of health care delivery. ... Does [the act of] administering Popsicles actually make us better clinicians?” asked Ryan Finn, MD, of the Mayo Clinic, Rochester, Minn., who presented these data.

Exploring low-cost ways to improve patient experience and, by extension, patient satisfaction led to this study of an ice pop intervention, Dr. Finn explained. The study design was simple. During a 3-month period, all children under the age of 14 years (mean age, 6 years) who visited the ED on an even numbered date were offered an ice pop. On odd numbered dates, no ice pop was given. There were no other differences in care.

Parent perceptions of care were assessed with the proprietary Press Ganey patient satisfaction survey. Although a completed survey was submitted for less than 5% of the more than 4,500 patients treated during the study period, differences between the groups still reached statistical significance.

When parents were asked to rate physicians on concern for their child’s comfort, 74% of the group given ice pops and 58% of the group given no ice pops gave favorable responses (P less than.05). The parents of children in the ice pop group also were significantly more likely to rate physicians favorably for their courtesy (77% vs. 62%; P less than .04) and for their willingness to take the time to listen (84% vs. 57%; P less than .03).

Overall rating of care (64% vs. 61%) and likelihood of recommending the ED to others (66% vs. 59%) did not approach statistical significance, according to Dr. Finn.

There are numerous potential advantages to improving the patient experience and boosting patient satisfaction in the ED, as is the case in other areas of the hospital. Even if medical care is of high quality, patient satisfaction does not necessarily follow. Although this single-center study had limitations, such as the low survey completion rate, the measurable effects of the ice pop intervention encourages this direction of research.

“Further studies should increase sample size, assess age group subsets, and assess return on investment for this and other low-cost interventions with the potential to alter patient perceptions,” Dr. Finn said. Because patient satisfaction can be reasonably expected to favorably affect quality of care assessments, he indicated that this is a reasonable target for quality improvement strategies.

SAN DIEGO – Simply offering an ice pop to children who are receiving care in an ED boosts satisfaction scores and physician ratings by their children’s parents, according to data presented at the annual meeting of the American College of Emergency Physicians.

Patient experience and subsequently patient satisfaction scores “have become an increasingly important component of health care delivery. ... Does [the act of] administering Popsicles actually make us better clinicians?” asked Ryan Finn, MD, of the Mayo Clinic, Rochester, Minn., who presented these data.

Exploring low-cost ways to improve patient experience and, by extension, patient satisfaction led to this study of an ice pop intervention, Dr. Finn explained. The study design was simple. During a 3-month period, all children under the age of 14 years (mean age, 6 years) who visited the ED on an even numbered date were offered an ice pop. On odd numbered dates, no ice pop was given. There were no other differences in care.

Parent perceptions of care were assessed with the proprietary Press Ganey patient satisfaction survey. Although a completed survey was submitted for less than 5% of the more than 4,500 patients treated during the study period, differences between the groups still reached statistical significance.

When parents were asked to rate physicians on concern for their child’s comfort, 74% of the group given ice pops and 58% of the group given no ice pops gave favorable responses (P less than.05). The parents of children in the ice pop group also were significantly more likely to rate physicians favorably for their courtesy (77% vs. 62%; P less than .04) and for their willingness to take the time to listen (84% vs. 57%; P less than .03).

Overall rating of care (64% vs. 61%) and likelihood of recommending the ED to others (66% vs. 59%) did not approach statistical significance, according to Dr. Finn.

There are numerous potential advantages to improving the patient experience and boosting patient satisfaction in the ED, as is the case in other areas of the hospital. Even if medical care is of high quality, patient satisfaction does not necessarily follow. Although this single-center study had limitations, such as the low survey completion rate, the measurable effects of the ice pop intervention encourages this direction of research.

“Further studies should increase sample size, assess age group subsets, and assess return on investment for this and other low-cost interventions with the potential to alter patient perceptions,” Dr. Finn said. Because patient satisfaction can be reasonably expected to favorably affect quality of care assessments, he indicated that this is a reasonable target for quality improvement strategies.

The FDA’s MedWatch program safety labeling changes for boxed warnings are compiled quarterly for drugs and therapeutic biologics where important changes have been made to the safety information. These and other label changes are searchable in the Drug Safety Labeling Changes (SLC) database, where data are available to the public in downloadable and searchable formats. Boxed warnings are ordinarily used to highlight either adverse reactions so serious in proportion to the potential benefi t from the drug that it is essential that it be considered in assessing the risks and benefi ts of using the drug; or serious adverse reactions that can be prevented/reduced in frequency or severity by appropriate use of the drug; or FDA approved the drug with restrictions to ensure safe use because FDA concluded that the drug can be safely used only if distribution or use is restricted. For complete FDA Drug Safety Labeling changes, please visit http://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges.

DESOGEN (DESOGESTREL AND ETHINYL ESTRADIOL TABLETS

• Edited boxed warning, June 2018

WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS

Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs are contraindicated in women who are over 35 years of age, and smoke.

TRIZIVIR (ABACAVIR, LAMIVUDINE, AND ZIDOVUDINE TABLETS)

• Edited boxed warning, April 2018

Lactic Acidosis and Severe Hepatomegaly with Steatosis: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues, including abacavir, lamivudine, and zidovudine (components of TRIZIVIR). Discontinue TRIZIVIR if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur [see Warnings and Precautions (5.4)].

ERBITUX (CETUXIMAB)

• Edited boxed warning, June 2018

WARNING: INFUSION REACTIONS and CARDIOPULMONARY ARREST

Infusion Reactions: ERBITUX can cause serious and fatal infusion reactions [see Warnings and Precautions (5.1), Adverse Reactions (6)]. Immediately interrupt and permanently discontinue ERBITUX for serious infusion reactions [see Dosage and Administration (2.4)].

Cardiopulmonary Arrest: Cardiopulmonary arrest or sudden death occurred in patients with squamous cell carcinoma of the head and neck receiving ERBITUX with radiation therapy or a cetuximab product with platinum-based therapy and fluorouracil. Monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after ERBITUX administration [see Warnings and Precautions (5.2, 5.6)].

AUSTEDO (DEUTETRABENAZINE)

• Edited boxed warning, June 2018

WARNING: DEPRESSION AND SUICIDALITY IN PATIENTS WITH HUNTINGTON’S DISEASE

AUSTEDO can increase the risk of depression …

EXJADE (DEFERASIROX)

• Edited boxed warning, May 2018

Renal Failure: EXJADE can cause acute renal failure and death, particularly in patients with comorbidities and those who are in the advanced stages of their hematologic disorders. Evaluate baseline renal function prior to starting or increasing Exjade dosing in all patients. Exjade is contraindicated in adult and pediatric patients with eGFR less than 40 mL/min/1.73 m2. Measure serum creatinine in duplicate prior to initiation of therapy. Monitor renal function at least monthly. For patients with baseline renal impairment or increased risk of acute renal failure, monitor renal function weekly for the first month, then at least monthly. Reduce the starting dose in patients with pre-existing renal disease. During therapy, increase the frequency of monitoring and modify the dose for patients with an increased risk of renal impairment, including use of concomitant nephrotoxic drugs, and pediatric patients with volume depletion or overchelation.

TUXARIN ER (CODEINE PHOSPHATE AND CHLORPHENIRAMINE MALEATE)

• Edited boxed warning, June 2018

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; ULTRA-RAPID METABOLISM OF CODEINE AND OTHER RISK FACTORS FOR LIFE-THREATENING RESPIRATORY DEPRESSION IN CHILDREN; MEDICATION ERRORS; INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES; CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; NEONATAL OPIOID WITHDRAWAL SYNDROME.

Addiction, Abuse, and Misuse: TUXARIN ER exposes patients and other users to the risks of opioid addiction, abuse, and misuse,
which can lead to overdose and death. Reserve TUXARIN ER for use in adult patients for whom the benefits of cough suppression
are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made. Assess each
patient’s risk prior to prescribing TUXARIN ER, prescribe TUXARIN ER for the shortest duration that is consistent with individual patient
treatment goals, monitor all patients regularly for the development of addition or abuse, and refill only after reevaluation of the need for continued treatment. [see Warnings and Precautions (5.1)]

Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression may occur with use of TUXARIN ER.
Monitor for respiratory depression, especially during initiation of TUXARIN ER therapy or when used in patients at higher risk [see Warnings and Precautions (5.2)].

Accidental Ingestion: Accidental ingestion of even one dose of TUXARIN ER, especially by children, can result in a fatal overdose of codeine [see Warnings and Precautions (5.2)].

Ultra-Rapid Metabolism of Codeine and Other Risk Factors for Life-Threatening Respiratory Depression in Children: Life threatening
respiratory depression and death have occurred in children who received codeine. Most of the reported cases occurred following tonsillectomy and/or adenoidectomy, and many of the children had evidence of being an ultra-rapid metabolizer of codeine due to a
CYP2D6 polymorphism. [see Warnings and Precautions (5.3)]. TUXARIN ER is contraindicated in children younger than 12 years of age and
in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Contraindications (4)]. Avoid the use of TUXARIN ER in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine. [see Warnings and Precautions (5.1)].

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes: The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex, requiring careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine. Avoid the use of TUXARIN ER in patients who are taking a CYP3A4 inhibitor, CYP3A4 inducer, or 2D6 inhibitor [see Warnings and Precautions (5.8), Drug Interactions (7.1,7.2, 7.4)]

Risks from Concomitant Use with Benzodiazepines, CNS Depressants: Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Avoid use of TUXARIN ER in patients taking benzodiazepines, other CNS depressants, or alcohol. [see Warning and Precautions (5.9) Drug Interactions (7.5)].

Neonatal Opioid Withdrawal Syndrome: TUXARIN ER is not recommended for use in pregnant women [see Use in Specific Populations
(8.1)]. Prolonged use of TUXARIN ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If TUXARIN ER is used for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Warnings and Precautions (5.15)].

PROGRAF (TACROLIMUS)

• Edited boxed warning, May 2018

Increased risk for developing serious infections and malignancies with PROGRAF or other immunosuppressants that may lead to hospitalization or death [(see Warnings and Precautions 5.1,5.2)].

SAMSCA (TOLVAPTAN)

• Edited boxed warning, April 2018

Addition of the following:

WARNING: NOT FOR USE FOR AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD)

Because of the risk of hepatoxicity, tolvaptan should not be used for ADPKD outside of the FDA-approved REMS

GLUCOPHAGE/GLUCOPHAGE XR (METFORMIN HYDROCHLORIDE)

• Edited boxed warning, May 2018

PLR conversion; Lactic Acidosis warning is highlighted as boxed warning.

The FDA’s MedWatch program safety labeling changes for boxed warnings are compiled quarterly for drugs and therapeutic biologics where important changes have been made to the safety information. These and other label changes are searchable in the Drug Safety Labeling Changes (SLC) database, where data are available to the public in downloadable and searchable formats. Boxed warnings are ordinarily used to highlight either adverse reactions so serious in proportion to the potential benefi t from the drug that it is essential that it be considered in assessing the risks and benefi ts of using the drug; or serious adverse reactions that can be prevented/reduced in frequency or severity by appropriate use of the drug; or FDA approved the drug with restrictions to ensure safe use because FDA concluded that the drug can be safely used only if distribution or use is restricted. For complete FDA Drug Safety Labeling changes, please visit http://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges.

DESOGEN (DESOGESTREL AND ETHINYL ESTRADIOL TABLETS

• Edited boxed warning, June 2018

WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS

Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs are contraindicated in women who are over 35 years of age, and smoke.

TRIZIVIR (ABACAVIR, LAMIVUDINE, AND ZIDOVUDINE TABLETS)

• Edited boxed warning, April 2018

Lactic Acidosis and Severe Hepatomegaly with Steatosis: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues, including abacavir, lamivudine, and zidovudine (components of TRIZIVIR). Discontinue TRIZIVIR if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur [see Warnings and Precautions (5.4)].

ERBITUX (CETUXIMAB)

• Edited boxed warning, June 2018

WARNING: INFUSION REACTIONS and CARDIOPULMONARY ARREST

Infusion Reactions: ERBITUX can cause serious and fatal infusion reactions [see Warnings and Precautions (5.1), Adverse Reactions (6)]. Immediately interrupt and permanently discontinue ERBITUX for serious infusion reactions [see Dosage and Administration (2.4)].

Cardiopulmonary Arrest: Cardiopulmonary arrest or sudden death occurred in patients with squamous cell carcinoma of the head and neck receiving ERBITUX with radiation therapy or a cetuximab product with platinum-based therapy and fluorouracil. Monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after ERBITUX administration [see Warnings and Precautions (5.2, 5.6)].

AUSTEDO (DEUTETRABENAZINE)

• Edited boxed warning, June 2018

WARNING: DEPRESSION AND SUICIDALITY IN PATIENTS WITH HUNTINGTON’S DISEASE

AUSTEDO can increase the risk of depression …

EXJADE (DEFERASIROX)

• Edited boxed warning, May 2018

Renal Failure: EXJADE can cause acute renal failure and death, particularly in patients with comorbidities and those who are in the advanced stages of their hematologic disorders. Evaluate baseline renal function prior to starting or increasing Exjade dosing in all patients. Exjade is contraindicated in adult and pediatric patients with eGFR less than 40 mL/min/1.73 m2. Measure serum creatinine in duplicate prior to initiation of therapy. Monitor renal function at least monthly. For patients with baseline renal impairment or increased risk of acute renal failure, monitor renal function weekly for the first month, then at least monthly. Reduce the starting dose in patients with pre-existing renal disease. During therapy, increase the frequency of monitoring and modify the dose for patients with an increased risk of renal impairment, including use of concomitant nephrotoxic drugs, and pediatric patients with volume depletion or overchelation.

TUXARIN ER (CODEINE PHOSPHATE AND CHLORPHENIRAMINE MALEATE)

• Edited boxed warning, June 2018

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; ULTRA-RAPID METABOLISM OF CODEINE AND OTHER RISK FACTORS FOR LIFE-THREATENING RESPIRATORY DEPRESSION IN CHILDREN; MEDICATION ERRORS; INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES; CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; NEONATAL OPIOID WITHDRAWAL SYNDROME.

Addiction, Abuse, and Misuse: TUXARIN ER exposes patients and other users to the risks of opioid addiction, abuse, and misuse,
which can lead to overdose and death. Reserve TUXARIN ER for use in adult patients for whom the benefits of cough suppression
are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made. Assess each
patient’s risk prior to prescribing TUXARIN ER, prescribe TUXARIN ER for the shortest duration that is consistent with individual patient
treatment goals, monitor all patients regularly for the development of addition or abuse, and refill only after reevaluation of the need for continued treatment. [see Warnings and Precautions (5.1)]

Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression may occur with use of TUXARIN ER.
Monitor for respiratory depression, especially during initiation of TUXARIN ER therapy or when used in patients at higher risk [see Warnings and Precautions (5.2)].

Accidental Ingestion: Accidental ingestion of even one dose of TUXARIN ER, especially by children, can result in a fatal overdose of codeine [see Warnings and Precautions (5.2)].

Ultra-Rapid Metabolism of Codeine and Other Risk Factors for Life-Threatening Respiratory Depression in Children: Life threatening
respiratory depression and death have occurred in children who received codeine. Most of the reported cases occurred following tonsillectomy and/or adenoidectomy, and many of the children had evidence of being an ultra-rapid metabolizer of codeine due to a
CYP2D6 polymorphism. [see Warnings and Precautions (5.3)]. TUXARIN ER is contraindicated in children younger than 12 years of age and
in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Contraindications (4)]. Avoid the use of TUXARIN ER in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine. [see Warnings and Precautions (5.1)].

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes: The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex, requiring careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine. Avoid the use of TUXARIN ER in patients who are taking a CYP3A4 inhibitor, CYP3A4 inducer, or 2D6 inhibitor [see Warnings and Precautions (5.8), Drug Interactions (7.1,7.2, 7.4)]

Risks from Concomitant Use with Benzodiazepines, CNS Depressants: Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Avoid use of TUXARIN ER in patients taking benzodiazepines, other CNS depressants, or alcohol. [see Warning and Precautions (5.9) Drug Interactions (7.5)].

Neonatal Opioid Withdrawal Syndrome: TUXARIN ER is not recommended for use in pregnant women [see Use in Specific Populations
(8.1)]. Prolonged use of TUXARIN ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If TUXARIN ER is used for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Warnings and Precautions (5.15)].

PROGRAF (TACROLIMUS)

• Edited boxed warning, May 2018

Increased risk for developing serious infections and malignancies with PROGRAF or other immunosuppressants that may lead to hospitalization or death [(see Warnings and Precautions 5.1,5.2)].

SAMSCA (TOLVAPTAN)

• Edited boxed warning, April 2018

Addition of the following:

WARNING: NOT FOR USE FOR AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD)

Because of the risk of hepatoxicity, tolvaptan should not be used for ADPKD outside of the FDA-approved REMS

GLUCOPHAGE/GLUCOPHAGE XR (METFORMIN HYDROCHLORIDE)

• Edited boxed warning, May 2018

PLR conversion; Lactic Acidosis warning is highlighted as boxed warning.

The FDA’s MedWatch program safety labeling changes for boxed warnings are compiled quarterly for drugs and therapeutic biologics where important changes have been made to the safety information. These and other label changes are searchable in the Drug Safety Labeling Changes (SLC) database, where data are available to the public in downloadable and searchable formats. Boxed warnings are ordinarily used to highlight either adverse reactions so serious in proportion to the potential benefi t from the drug that it is essential that it be considered in assessing the risks and benefi ts of using the drug; or serious adverse reactions that can be prevented/reduced in frequency or severity by appropriate use of the drug; or FDA approved the drug with restrictions to ensure safe use because FDA concluded that the drug can be safely used only if distribution or use is restricted. For complete FDA Drug Safety Labeling changes, please visit http://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges.

DESOGEN (DESOGESTREL AND ETHINYL ESTRADIOL TABLETS

• Edited boxed warning, June 2018

WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS

Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs are contraindicated in women who are over 35 years of age, and smoke.

TRIZIVIR (ABACAVIR, LAMIVUDINE, AND ZIDOVUDINE TABLETS)

• Edited boxed warning, April 2018

Lactic Acidosis and Severe Hepatomegaly with Steatosis: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues, including abacavir, lamivudine, and zidovudine (components of TRIZIVIR). Discontinue TRIZIVIR if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur [see Warnings and Precautions (5.4)].

ERBITUX (CETUXIMAB)

• Edited boxed warning, June 2018

WARNING: INFUSION REACTIONS and CARDIOPULMONARY ARREST

Infusion Reactions: ERBITUX can cause serious and fatal infusion reactions [see Warnings and Precautions (5.1), Adverse Reactions (6)]. Immediately interrupt and permanently discontinue ERBITUX for serious infusion reactions [see Dosage and Administration (2.4)].

Cardiopulmonary Arrest: Cardiopulmonary arrest or sudden death occurred in patients with squamous cell carcinoma of the head and neck receiving ERBITUX with radiation therapy or a cetuximab product with platinum-based therapy and fluorouracil. Monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after ERBITUX administration [see Warnings and Precautions (5.2, 5.6)].

AUSTEDO (DEUTETRABENAZINE)

• Edited boxed warning, June 2018

WARNING: DEPRESSION AND SUICIDALITY IN PATIENTS WITH HUNTINGTON’S DISEASE

AUSTEDO can increase the risk of depression …

EXJADE (DEFERASIROX)

• Edited boxed warning, May 2018

Renal Failure: EXJADE can cause acute renal failure and death, particularly in patients with comorbidities and those who are in the advanced stages of their hematologic disorders. Evaluate baseline renal function prior to starting or increasing Exjade dosing in all patients. Exjade is contraindicated in adult and pediatric patients with eGFR less than 40 mL/min/1.73 m2. Measure serum creatinine in duplicate prior to initiation of therapy. Monitor renal function at least monthly. For patients with baseline renal impairment or increased risk of acute renal failure, monitor renal function weekly for the first month, then at least monthly. Reduce the starting dose in patients with pre-existing renal disease. During therapy, increase the frequency of monitoring and modify the dose for patients with an increased risk of renal impairment, including use of concomitant nephrotoxic drugs, and pediatric patients with volume depletion or overchelation.

TUXARIN ER (CODEINE PHOSPHATE AND CHLORPHENIRAMINE MALEATE)

• Edited boxed warning, June 2018

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; ULTRA-RAPID METABOLISM OF CODEINE AND OTHER RISK FACTORS FOR LIFE-THREATENING RESPIRATORY DEPRESSION IN CHILDREN; MEDICATION ERRORS; INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES; CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; NEONATAL OPIOID WITHDRAWAL SYNDROME.

Addiction, Abuse, and Misuse: TUXARIN ER exposes patients and other users to the risks of opioid addiction, abuse, and misuse,
which can lead to overdose and death. Reserve TUXARIN ER for use in adult patients for whom the benefits of cough suppression
are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made. Assess each
patient’s risk prior to prescribing TUXARIN ER, prescribe TUXARIN ER for the shortest duration that is consistent with individual patient
treatment goals, monitor all patients regularly for the development of addition or abuse, and refill only after reevaluation of the need for continued treatment. [see Warnings and Precautions (5.1)]

Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression may occur with use of TUXARIN ER.
Monitor for respiratory depression, especially during initiation of TUXARIN ER therapy or when used in patients at higher risk [see Warnings and Precautions (5.2)].

Accidental Ingestion: Accidental ingestion of even one dose of TUXARIN ER, especially by children, can result in a fatal overdose of codeine [see Warnings and Precautions (5.2)].

Ultra-Rapid Metabolism of Codeine and Other Risk Factors for Life-Threatening Respiratory Depression in Children: Life threatening
respiratory depression and death have occurred in children who received codeine. Most of the reported cases occurred following tonsillectomy and/or adenoidectomy, and many of the children had evidence of being an ultra-rapid metabolizer of codeine due to a
CYP2D6 polymorphism. [see Warnings and Precautions (5.3)]. TUXARIN ER is contraindicated in children younger than 12 years of age and
in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Contraindications (4)]. Avoid the use of TUXARIN ER in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine. [see Warnings and Precautions (5.1)].

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes: The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex, requiring careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine. Avoid the use of TUXARIN ER in patients who are taking a CYP3A4 inhibitor, CYP3A4 inducer, or 2D6 inhibitor [see Warnings and Precautions (5.8), Drug Interactions (7.1,7.2, 7.4)]

Risks from Concomitant Use with Benzodiazepines, CNS Depressants: Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Avoid use of TUXARIN ER in patients taking benzodiazepines, other CNS depressants, or alcohol. [see Warning and Precautions (5.9) Drug Interactions (7.5)].

Neonatal Opioid Withdrawal Syndrome: TUXARIN ER is not recommended for use in pregnant women [see Use in Specific Populations
(8.1)]. Prolonged use of TUXARIN ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If TUXARIN ER is used for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Warnings and Precautions (5.15)].

PROGRAF (TACROLIMUS)

• Edited boxed warning, May 2018

Increased risk for developing serious infections and malignancies with PROGRAF or other immunosuppressants that may lead to hospitalization or death [(see Warnings and Precautions 5.1,5.2)].

SAMSCA (TOLVAPTAN)

• Edited boxed warning, April 2018

Addition of the following:

WARNING: NOT FOR USE FOR AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD)

Because of the risk of hepatoxicity, tolvaptan should not be used for ADPKD outside of the FDA-approved REMS

GLUCOPHAGE/GLUCOPHAGE XR (METFORMIN HYDROCHLORIDE)

• Edited boxed warning, May 2018

PLR conversion; Lactic Acidosis warning is highlighted as boxed warning.

Patients with pulmonary arterial hypertension as a consequence of systemic lupus erythematosus can be classified into two different subtypes, one of which shows significantly greater mortality, new research suggests.

Systemic lupus erythematosus–associated pulmonary arterial hypertension (SLE-PAH) has a poor prognosis with 3-year mortality ranging from 45% to 88%, leading the first author of the study Fangfang Sun of the School of Medicine at Shanghai (China) Jiaotong University and coauthors to seek “to further differentiate among SLE-PAH patterns to better understand the disease and optimize its management,

In a letter published online in Annals of the Rheumatic Diseases, the researchers presented data from a retrospective study of a derivation cohort of 108 Chinese patients with SLE-PAH and a validation cohort of 87 patients. Using clinical and laboratory characteristics, the researchers classified the derivation cohort into two clusters, which they labeled as the vasculitic and vasculopathic subtypes.

Patients with the vasculitic subtype of SLE-PAH had higher levels of SLE disease activity and manifestations, such as pericarditis, rash, arthritis, nephritis, and neuropsychiatric lupus, while those with the vasculopathic subtype showed “purer” PAH and lower lupus disease activity.

The researchers found that the vasculitic subtype had around a threefold higher 3-year mortality than did the vasculopathic subtype (34.5%-40.2% vs. 13.0%-18.6%; hazard ratio, 2.84-3.15; P less than .05), even after adjusting for differences in treatments.

Patients who developed PAH less than 2 years after being diagnosed with SLE were significantly more likely to have the vasculitic subtype of SLE-PAH (P less than .0001). A SLE disease activity index score greater than nine was also significantly associated with the vasculitic subtype (P = .001).

The prediction model developed based on these two factors had a sensitivity of 98.5% and a specificity of 74.4% (area under the curve = 0.94; P less than .0001), for a weighted score of two or more, in identifying patients with the vasculitic subtype of SLE-PAH.

Dr. Sun and colleagues suggested that the existence of two distinct clinical subtypes of SLE-PAH points to different underlying pathophysiologic mechanisms; one that is autoimmune mediated and one that involves noninflammatory vascular remodeling. However, the authors stressed that their findings needed confirmation in prospective studies.

“The next key question that remains unanswered is how to balance the utility of immunosuppressants and PAH-targeted drugs in patients with different phenotypes,” they wrote.

Two authors declared research funding from academic and government agencies. No conflicts of interest were declared.

SOURCE: Sun F et al. Ann Rheum Dis. 2018 Sep 19. doi: 10.1136/annrheumdis-2018-214197.

Patients with pulmonary arterial hypertension as a consequence of systemic lupus erythematosus can be classified into two different subtypes, one of which shows significantly greater mortality, new research suggests.

Systemic lupus erythematosus–associated pulmonary arterial hypertension (SLE-PAH) has a poor prognosis with 3-year mortality ranging from 45% to 88%, leading the first author of the study Fangfang Sun of the School of Medicine at Shanghai (China) Jiaotong University and coauthors to seek “to further differentiate among SLE-PAH patterns to better understand the disease and optimize its management,

In a letter published online in Annals of the Rheumatic Diseases, the researchers presented data from a retrospective study of a derivation cohort of 108 Chinese patients with SLE-PAH and a validation cohort of 87 patients. Using clinical and laboratory characteristics, the researchers classified the derivation cohort into two clusters, which they labeled as the vasculitic and vasculopathic subtypes.

Patients with the vasculitic subtype of SLE-PAH had higher levels of SLE disease activity and manifestations, such as pericarditis, rash, arthritis, nephritis, and neuropsychiatric lupus, while those with the vasculopathic subtype showed “purer” PAH and lower lupus disease activity.

The researchers found that the vasculitic subtype had around a threefold higher 3-year mortality than did the vasculopathic subtype (34.5%-40.2% vs. 13.0%-18.6%; hazard ratio, 2.84-3.15; P less than .05), even after adjusting for differences in treatments.

Patients who developed PAH less than 2 years after being diagnosed with SLE were significantly more likely to have the vasculitic subtype of SLE-PAH (P less than .0001). A SLE disease activity index score greater than nine was also significantly associated with the vasculitic subtype (P = .001).

The prediction model developed based on these two factors had a sensitivity of 98.5% and a specificity of 74.4% (area under the curve = 0.94; P less than .0001), for a weighted score of two or more, in identifying patients with the vasculitic subtype of SLE-PAH.

Dr. Sun and colleagues suggested that the existence of two distinct clinical subtypes of SLE-PAH points to different underlying pathophysiologic mechanisms; one that is autoimmune mediated and one that involves noninflammatory vascular remodeling. However, the authors stressed that their findings needed confirmation in prospective studies.

“The next key question that remains unanswered is how to balance the utility of immunosuppressants and PAH-targeted drugs in patients with different phenotypes,” they wrote.

Two authors declared research funding from academic and government agencies. No conflicts of interest were declared.

SOURCE: Sun F et al. Ann Rheum Dis. 2018 Sep 19. doi: 10.1136/annrheumdis-2018-214197.

Patients with pulmonary arterial hypertension as a consequence of systemic lupus erythematosus can be classified into two different subtypes, one of which shows significantly greater mortality, new research suggests.

Systemic lupus erythematosus–associated pulmonary arterial hypertension (SLE-PAH) has a poor prognosis with 3-year mortality ranging from 45% to 88%, leading the first author of the study Fangfang Sun of the School of Medicine at Shanghai (China) Jiaotong University and coauthors to seek “to further differentiate among SLE-PAH patterns to better understand the disease and optimize its management,

In a letter published online in Annals of the Rheumatic Diseases, the researchers presented data from a retrospective study of a derivation cohort of 108 Chinese patients with SLE-PAH and a validation cohort of 87 patients. Using clinical and laboratory characteristics, the researchers classified the derivation cohort into two clusters, which they labeled as the vasculitic and vasculopathic subtypes.

Patients with the vasculitic subtype of SLE-PAH had higher levels of SLE disease activity and manifestations, such as pericarditis, rash, arthritis, nephritis, and neuropsychiatric lupus, while those with the vasculopathic subtype showed “purer” PAH and lower lupus disease activity.

The researchers found that the vasculitic subtype had around a threefold higher 3-year mortality than did the vasculopathic subtype (34.5%-40.2% vs. 13.0%-18.6%; hazard ratio, 2.84-3.15; P less than .05), even after adjusting for differences in treatments.

Patients who developed PAH less than 2 years after being diagnosed with SLE were significantly more likely to have the vasculitic subtype of SLE-PAH (P less than .0001). A SLE disease activity index score greater than nine was also significantly associated with the vasculitic subtype (P = .001).

The prediction model developed based on these two factors had a sensitivity of 98.5% and a specificity of 74.4% (area under the curve = 0.94; P less than .0001), for a weighted score of two or more, in identifying patients with the vasculitic subtype of SLE-PAH.

Dr. Sun and colleagues suggested that the existence of two distinct clinical subtypes of SLE-PAH points to different underlying pathophysiologic mechanisms; one that is autoimmune mediated and one that involves noninflammatory vascular remodeling. However, the authors stressed that their findings needed confirmation in prospective studies.

“The next key question that remains unanswered is how to balance the utility of immunosuppressants and PAH-targeted drugs in patients with different phenotypes,” they wrote.

Two authors declared research funding from academic and government agencies. No conflicts of interest were declared.

SOURCE: Sun F et al. Ann Rheum Dis. 2018 Sep 19. doi: 10.1136/annrheumdis-2018-214197.

SAN DIEGO – Being prepared to manage difficult dislocations is key to maintaining the flow of patient care in any emergency department.

In a video interview at the annual meeting of the American College of Emergency Physicians, Danielle D. Campagne, MD, FACEP, shared her clinical pearls for managing dislocations of the jaw, hip, ankle, and shoulder.

Dr. Campagne is an emergency medicine physician who practices at Community Regional Medical Center in Fresno, Calif. She is also vice chief of emergency medicine at University of California, San Francisco, Fresno. She reported having no financial disclosures.

dbrunk@mdedge.com

SAN DIEGO – Being prepared to manage difficult dislocations is key to maintaining the flow of patient care in any emergency department.

In a video interview at the annual meeting of the American College of Emergency Physicians, Danielle D. Campagne, MD, FACEP, shared her clinical pearls for managing dislocations of the jaw, hip, ankle, and shoulder.

Dr. Campagne is an emergency medicine physician who practices at Community Regional Medical Center in Fresno, Calif. She is also vice chief of emergency medicine at University of California, San Francisco, Fresno. She reported having no financial disclosures.

dbrunk@mdedge.com

SAN DIEGO – Being prepared to manage difficult dislocations is key to maintaining the flow of patient care in any emergency department.

In a video interview at the annual meeting of the American College of Emergency Physicians, Danielle D. Campagne, MD, FACEP, shared her clinical pearls for managing dislocations of the jaw, hip, ankle, and shoulder.

Dr. Campagne is an emergency medicine physician who practices at Community Regional Medical Center in Fresno, Calif. She is also vice chief of emergency medicine at University of California, San Francisco, Fresno. She reported having no financial disclosures.

dbrunk@mdedge.com

Cancer geneticists have identified 21 clusters of complex chromosomal rearrangements in breast cancers that contain both known oncogenes and potential new driver loci.

A systematic analysis of chromosomal rearrangements in tissues from 560 patients with breast cancer identified 21 “hotspots,” some of which contain known oncogene chromosomal loci, and others of which contain genes not typically associated with breast cancer, reported Serena Nik-Zainal, PhD, of the University of Cambridge, England, and her colleagues.

“Detailed analysis of rearrangements at these hotspots highlights chromosomal aberrations likely driven by selection, and reveal underlying mutational processes,” they wrote in a study published online in Annals of Oncology.

The investigators sought insight into mutational mechanisms of gene amplifications by examining clustered rearrangements – somatic breakpoints occurring in high densities – in individual patients.

To see whether these rearrangements were associated with breast cancer, they identified the aforementioned chromosomal hotspots where clustered rearrangements were seen in samples from different patients.

They identified 624 cluster rearrangements in the 560 breast cancer genomes, including 17,247 within-chromosome rearrangements, and 6,509 between-chromosome translocations.

Of the 560 samples, 372 had at least one rearrangement cluster, with the frequency of clusters similar between some breast cancer types. For example, there were 0.96 rearrangements clusters per sample from patients with triple negative breast cancers, and 1.00 per sample from women with estrogen receptor–positive tumors.

“To identify loci where clusters of rearrangements recur across multiple independent tumor samples, we pooled all breakpoints in the ‘clustered’ category and sorted them according to position in the reference genome,” the investigators explained.

They used a Piecewise-Constant-Fitting algorithm to identify genome sequences where there were short inter-mutation distances between rearrangement clusters, suggesting the presence of hotspots.

In the 21 hotspots they identified, they found, as expected, common driver amplification regions (e.g., CCND1, ERBB2, ZNF217, chr8:ZNF703/FGFR1, IGF1R, and MYC), but also several hotspots near oncogenes that are not typically associated with breast cancer.

Notably, they saw simultaneous amplification of regions on chromosomes 8 and 11 (chr8:ZNF703/FGFR1 and chr11:CCND1). Amplification of these regions are frequent in estrogen receptor–positive breast cancers. The investigators propose a pathogenic model in which a chromosome 8 to chromosome 11 translocation is an early, critical event leading to breast tumor development.

“Clustered rearrangements are common in breast cancer genomes, and often associated with gene amplifications that drive oncogenesis. Understanding the process of amplicon formation, an example of which we present here for the chr8:ZNF703/FGFR1 and chr11:CCND1 co-amplifications, will be important for our understanding of the origins of a subset of breast cancers,” they concluded.

The study was supported by an award from the Wellcome Trust. Dr. Nik-Zainal and coauthor Dominik Glodzik are inventors on several patent applications. All remaining authors declared no conflicts of interest.
 

SOURCE: Glodzik D et al. Ann Oncol. 2018 Sept 25. doi: 10.1093/annonc/mdy404.

Cancer geneticists have identified 21 clusters of complex chromosomal rearrangements in breast cancers that contain both known oncogenes and potential new driver loci.

A systematic analysis of chromosomal rearrangements in tissues from 560 patients with breast cancer identified 21 “hotspots,” some of which contain known oncogene chromosomal loci, and others of which contain genes not typically associated with breast cancer, reported Serena Nik-Zainal, PhD, of the University of Cambridge, England, and her colleagues.

“Detailed analysis of rearrangements at these hotspots highlights chromosomal aberrations likely driven by selection, and reveal underlying mutational processes,” they wrote in a study published online in Annals of Oncology.

The investigators sought insight into mutational mechanisms of gene amplifications by examining clustered rearrangements – somatic breakpoints occurring in high densities – in individual patients.

To see whether these rearrangements were associated with breast cancer, they identified the aforementioned chromosomal hotspots where clustered rearrangements were seen in samples from different patients.

They identified 624 cluster rearrangements in the 560 breast cancer genomes, including 17,247 within-chromosome rearrangements, and 6,509 between-chromosome translocations.

Of the 560 samples, 372 had at least one rearrangement cluster, with the frequency of clusters similar between some breast cancer types. For example, there were 0.96 rearrangements clusters per sample from patients with triple negative breast cancers, and 1.00 per sample from women with estrogen receptor–positive tumors.

“To identify loci where clusters of rearrangements recur across multiple independent tumor samples, we pooled all breakpoints in the ‘clustered’ category and sorted them according to position in the reference genome,” the investigators explained.

They used a Piecewise-Constant-Fitting algorithm to identify genome sequences where there were short inter-mutation distances between rearrangement clusters, suggesting the presence of hotspots.

In the 21 hotspots they identified, they found, as expected, common driver amplification regions (e.g., CCND1, ERBB2, ZNF217, chr8:ZNF703/FGFR1, IGF1R, and MYC), but also several hotspots near oncogenes that are not typically associated with breast cancer.

Notably, they saw simultaneous amplification of regions on chromosomes 8 and 11 (chr8:ZNF703/FGFR1 and chr11:CCND1). Amplification of these regions are frequent in estrogen receptor–positive breast cancers. The investigators propose a pathogenic model in which a chromosome 8 to chromosome 11 translocation is an early, critical event leading to breast tumor development.

“Clustered rearrangements are common in breast cancer genomes, and often associated with gene amplifications that drive oncogenesis. Understanding the process of amplicon formation, an example of which we present here for the chr8:ZNF703/FGFR1 and chr11:CCND1 co-amplifications, will be important for our understanding of the origins of a subset of breast cancers,” they concluded.

The study was supported by an award from the Wellcome Trust. Dr. Nik-Zainal and coauthor Dominik Glodzik are inventors on several patent applications. All remaining authors declared no conflicts of interest.
 

SOURCE: Glodzik D et al. Ann Oncol. 2018 Sept 25. doi: 10.1093/annonc/mdy404.

Cancer geneticists have identified 21 clusters of complex chromosomal rearrangements in breast cancers that contain both known oncogenes and potential new driver loci.

A systematic analysis of chromosomal rearrangements in tissues from 560 patients with breast cancer identified 21 “hotspots,” some of which contain known oncogene chromosomal loci, and others of which contain genes not typically associated with breast cancer, reported Serena Nik-Zainal, PhD, of the University of Cambridge, England, and her colleagues.

“Detailed analysis of rearrangements at these hotspots highlights chromosomal aberrations likely driven by selection, and reveal underlying mutational processes,” they wrote in a study published online in Annals of Oncology.

The investigators sought insight into mutational mechanisms of gene amplifications by examining clustered rearrangements – somatic breakpoints occurring in high densities – in individual patients.

To see whether these rearrangements were associated with breast cancer, they identified the aforementioned chromosomal hotspots where clustered rearrangements were seen in samples from different patients.

They identified 624 cluster rearrangements in the 560 breast cancer genomes, including 17,247 within-chromosome rearrangements, and 6,509 between-chromosome translocations.

Of the 560 samples, 372 had at least one rearrangement cluster, with the frequency of clusters similar between some breast cancer types. For example, there were 0.96 rearrangements clusters per sample from patients with triple negative breast cancers, and 1.00 per sample from women with estrogen receptor–positive tumors.

“To identify loci where clusters of rearrangements recur across multiple independent tumor samples, we pooled all breakpoints in the ‘clustered’ category and sorted them according to position in the reference genome,” the investigators explained.

They used a Piecewise-Constant-Fitting algorithm to identify genome sequences where there were short inter-mutation distances between rearrangement clusters, suggesting the presence of hotspots.

In the 21 hotspots they identified, they found, as expected, common driver amplification regions (e.g., CCND1, ERBB2, ZNF217, chr8:ZNF703/FGFR1, IGF1R, and MYC), but also several hotspots near oncogenes that are not typically associated with breast cancer.

Notably, they saw simultaneous amplification of regions on chromosomes 8 and 11 (chr8:ZNF703/FGFR1 and chr11:CCND1). Amplification of these regions are frequent in estrogen receptor–positive breast cancers. The investigators propose a pathogenic model in which a chromosome 8 to chromosome 11 translocation is an early, critical event leading to breast tumor development.

“Clustered rearrangements are common in breast cancer genomes, and often associated with gene amplifications that drive oncogenesis. Understanding the process of amplicon formation, an example of which we present here for the chr8:ZNF703/FGFR1 and chr11:CCND1 co-amplifications, will be important for our understanding of the origins of a subset of breast cancers,” they concluded.

The study was supported by an award from the Wellcome Trust. Dr. Nik-Zainal and coauthor Dominik Glodzik are inventors on several patent applications. All remaining authors declared no conflicts of interest.
 

SOURCE: Glodzik D et al. Ann Oncol. 2018 Sept 25. doi: 10.1093/annonc/mdy404.

Sexual harassment and assault may have significant health impacts on women in midlife, including greater risk of hypertension, poor sleep, depression, and anxiety, research suggests.

thodonal/Thinkstock

In the Oct. 3 online edition of JAMA Internal Medicine, a study of 304 women aged 40-60 years showed that 19% reported a history of workplace sexual harassment, 22% reported a history of sexual assault, and 10% reported both. The report was presented simultaneously at the North American Menopause Society annual meeting in San Diego.

The researchers found that those with a history of sexual assault had an almost threefold higher odds of clinically elevated depressive symptoms (OR, 2.86, P = .003), and more than twofold greater odds of anxiety and poor sleep (OR, 2.26, P = .006 and OR, 2.15, P = .007 respectively).

Women who reported experiencing sexual harassment in the workplace – and who were not taking antihypertensive medication – were more than twice as likely to have stage 1 or 2 hypertension, compared with women who had not experienced sexual harassment (OR, 2.36, P = .03). They also had 89% higher odds of poor sleep consistent with clinical insomnia (P = .03).

These associations all persisted even after adjustment for demographic and biomedical factors such as age, ethnicity, body mass index, snoring, and the use of antihypertensive, antidepressant, and anti-anxiety medications.

“Given the high prevalence of sexual harassment and assault, addressing these prevalent and potent social exposures may be critical to promoting health and preventing disease in women,” wrote Rebecca C. Thurston, PhD, of the department of psychiatry at the University of Pittsburgh, and her coauthors.

The study was supported by the National Institutes of Health, National Heart Lung and Blood Institute, and the University of Pittsburgh Clinical and Translational Science Institute. Dr. Thurston declared consultancies for MAS Innovations, Procter & Gamble, and Pfizer, but no other conflicts of interest were declared.

SOURCE: Thurston R et al. JAMA Intern Med. 2018, Oct 3. doi: 10.1001/jamainternmed.2018.4886.

Sexual harassment and assault may have significant health impacts on women in midlife, including greater risk of hypertension, poor sleep, depression, and anxiety, research suggests.

thodonal/Thinkstock

In the Oct. 3 online edition of JAMA Internal Medicine, a study of 304 women aged 40-60 years showed that 19% reported a history of workplace sexual harassment, 22% reported a history of sexual assault, and 10% reported both. The report was presented simultaneously at the North American Menopause Society annual meeting in San Diego.

The researchers found that those with a history of sexual assault had an almost threefold higher odds of clinically elevated depressive symptoms (OR, 2.86, P = .003), and more than twofold greater odds of anxiety and poor sleep (OR, 2.26, P = .006 and OR, 2.15, P = .007 respectively).

Women who reported experiencing sexual harassment in the workplace – and who were not taking antihypertensive medication – were more than twice as likely to have stage 1 or 2 hypertension, compared with women who had not experienced sexual harassment (OR, 2.36, P = .03). They also had 89% higher odds of poor sleep consistent with clinical insomnia (P = .03).

These associations all persisted even after adjustment for demographic and biomedical factors such as age, ethnicity, body mass index, snoring, and the use of antihypertensive, antidepressant, and anti-anxiety medications.

“Given the high prevalence of sexual harassment and assault, addressing these prevalent and potent social exposures may be critical to promoting health and preventing disease in women,” wrote Rebecca C. Thurston, PhD, of the department of psychiatry at the University of Pittsburgh, and her coauthors.

The study was supported by the National Institutes of Health, National Heart Lung and Blood Institute, and the University of Pittsburgh Clinical and Translational Science Institute. Dr. Thurston declared consultancies for MAS Innovations, Procter & Gamble, and Pfizer, but no other conflicts of interest were declared.

SOURCE: Thurston R et al. JAMA Intern Med. 2018, Oct 3. doi: 10.1001/jamainternmed.2018.4886.

Sexual harassment and assault may have significant health impacts on women in midlife, including greater risk of hypertension, poor sleep, depression, and anxiety, research suggests.

thodonal/Thinkstock

In the Oct. 3 online edition of JAMA Internal Medicine, a study of 304 women aged 40-60 years showed that 19% reported a history of workplace sexual harassment, 22% reported a history of sexual assault, and 10% reported both. The report was presented simultaneously at the North American Menopause Society annual meeting in San Diego.

The researchers found that those with a history of sexual assault had an almost threefold higher odds of clinically elevated depressive symptoms (OR, 2.86, P = .003), and more than twofold greater odds of anxiety and poor sleep (OR, 2.26, P = .006 and OR, 2.15, P = .007 respectively).

Women who reported experiencing sexual harassment in the workplace – and who were not taking antihypertensive medication – were more than twice as likely to have stage 1 or 2 hypertension, compared with women who had not experienced sexual harassment (OR, 2.36, P = .03). They also had 89% higher odds of poor sleep consistent with clinical insomnia (P = .03).

These associations all persisted even after adjustment for demographic and biomedical factors such as age, ethnicity, body mass index, snoring, and the use of antihypertensive, antidepressant, and anti-anxiety medications.

“Given the high prevalence of sexual harassment and assault, addressing these prevalent and potent social exposures may be critical to promoting health and preventing disease in women,” wrote Rebecca C. Thurston, PhD, of the department of psychiatry at the University of Pittsburgh, and her coauthors.

The study was supported by the National Institutes of Health, National Heart Lung and Blood Institute, and the University of Pittsburgh Clinical and Translational Science Institute. Dr. Thurston declared consultancies for MAS Innovations, Procter & Gamble, and Pfizer, but no other conflicts of interest were declared.

SOURCE: Thurston R et al. JAMA Intern Med. 2018, Oct 3. doi: 10.1001/jamainternmed.2018.4886.