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Prognostic scores helpful in subset of COPD patients
LOS ANGELES – The Sequential Organ Failure Assessment (SOFA) score and the Glasgow Coma Scale (GCS) are simple, accurate tools for risk stratification of hospitalized patients with acute exacerbation of COPD, results from a single-center study showed.
“Acute exacerbations of chronic obstructive pulmonary disease often require hospitalization, may necessitate mechanical ventilation, and can be fatal,” Mohamed Metwally, MD, FCCP, said in an interview in advance of the annual meeting of the American College of Chest Physicians. “There are currently no validated disease-specific scores that measure the severity of acute exacerbation. Prognostic tools are needed to assess acute exacerbations of chronic obstructive pulmonary disease.”
For the 2-year study, Dr. Metwally and his associates prospectively evaluated 250 critically ill ICU AECOPD patients, mean age 65 years, at Assiut University Hospital between December 2012 and December 2014. The primary outcome was in-hospital mortality while the secondary endpoint was need for intubation and mechanical ventilation. The researchers excluded patients who died less than 24 hours after admission, those with underlying COPD who were admitted with another primary diagnosis such as an accident or a stroke, or for elective hospitalizations such as elective surgery or diagnostic procedures.
Dr. Metwally and his associates collected sociodemographic data, vital signs, and other clinical variables, and collected scores from five tools used to measure mortality prediction: the Acute Physiology and Chronic Health Evaluation (APACHE II), the SOFA score, the Early Warning Score (EWS), the GCS, and the Charlson Comorbidity Index (CCI). To assess performance of the scores, they used area under the receiver operating characteristic curve (AUC) analysis and the Hosmer-Lemeshow goodness-of-fit test for logistic regression.
Of the 250 patients, 43 (17%) died during their hospital stay and 54% required mechanical ventilation. All recorded scores were significantly higher in nonsurvivors, compared with survivors, and the risk of clinical deterioration increased with increasing scores. The discriminatory power of each score varied as measured by AUC analysis. The AUC of APACHE II, SOFA, EWS, GCS, and CCI were 0.79, 0.81, 0.76, 0.69, and 0.68, respectively “and all these models had good calibration in mortality prediction,” Dr. Metwally said. The SOFA score was the best in predicting mortality (its predicted mortality was 16%, compared with the actual mortality of 17%), while the APACHE II score overestimated mortality by at least twofold (46% vs. 17%). In addition, the EWS outperformed the GCS in predicting mortality. “This may be due to EWS containing all vital signs plus level of consciousness,” he said in an interview.
The GCS was found to be the most useful in predicting need for mechanical ventilation, with an AUC of 0.81. The AUCs of APACHE II, SOFA, EWS, and CCI were 0.79, 0.80, 0.73, and 0.61, respectively. All of the scores had good calibration in mortality prediction, Dr. Metwally said, with the exception of SOFA.
As for the APACHE II, Dr. Metwally said that instrument “can be used as a tool to predict both mortality and intubation in a specific group of patients, but with low discriminatory power.” He acknowledged certain limitations of the study, including the fact that it was limited to patients with AECOPD. “Future studies should include any critically ill respiratory patients,” he said.
He reported having no financial disclosures.
LOS ANGELES – The Sequential Organ Failure Assessment (SOFA) score and the Glasgow Coma Scale (GCS) are simple, accurate tools for risk stratification of hospitalized patients with acute exacerbation of COPD, results from a single-center study showed.
“Acute exacerbations of chronic obstructive pulmonary disease often require hospitalization, may necessitate mechanical ventilation, and can be fatal,” Mohamed Metwally, MD, FCCP, said in an interview in advance of the annual meeting of the American College of Chest Physicians. “There are currently no validated disease-specific scores that measure the severity of acute exacerbation. Prognostic tools are needed to assess acute exacerbations of chronic obstructive pulmonary disease.”
For the 2-year study, Dr. Metwally and his associates prospectively evaluated 250 critically ill ICU AECOPD patients, mean age 65 years, at Assiut University Hospital between December 2012 and December 2014. The primary outcome was in-hospital mortality while the secondary endpoint was need for intubation and mechanical ventilation. The researchers excluded patients who died less than 24 hours after admission, those with underlying COPD who were admitted with another primary diagnosis such as an accident or a stroke, or for elective hospitalizations such as elective surgery or diagnostic procedures.
Dr. Metwally and his associates collected sociodemographic data, vital signs, and other clinical variables, and collected scores from five tools used to measure mortality prediction: the Acute Physiology and Chronic Health Evaluation (APACHE II), the SOFA score, the Early Warning Score (EWS), the GCS, and the Charlson Comorbidity Index (CCI). To assess performance of the scores, they used area under the receiver operating characteristic curve (AUC) analysis and the Hosmer-Lemeshow goodness-of-fit test for logistic regression.
Of the 250 patients, 43 (17%) died during their hospital stay and 54% required mechanical ventilation. All recorded scores were significantly higher in nonsurvivors, compared with survivors, and the risk of clinical deterioration increased with increasing scores. The discriminatory power of each score varied as measured by AUC analysis. The AUC of APACHE II, SOFA, EWS, GCS, and CCI were 0.79, 0.81, 0.76, 0.69, and 0.68, respectively “and all these models had good calibration in mortality prediction,” Dr. Metwally said. The SOFA score was the best in predicting mortality (its predicted mortality was 16%, compared with the actual mortality of 17%), while the APACHE II score overestimated mortality by at least twofold (46% vs. 17%). In addition, the EWS outperformed the GCS in predicting mortality. “This may be due to EWS containing all vital signs plus level of consciousness,” he said in an interview.
The GCS was found to be the most useful in predicting need for mechanical ventilation, with an AUC of 0.81. The AUCs of APACHE II, SOFA, EWS, and CCI were 0.79, 0.80, 0.73, and 0.61, respectively. All of the scores had good calibration in mortality prediction, Dr. Metwally said, with the exception of SOFA.
As for the APACHE II, Dr. Metwally said that instrument “can be used as a tool to predict both mortality and intubation in a specific group of patients, but with low discriminatory power.” He acknowledged certain limitations of the study, including the fact that it was limited to patients with AECOPD. “Future studies should include any critically ill respiratory patients,” he said.
He reported having no financial disclosures.
LOS ANGELES – The Sequential Organ Failure Assessment (SOFA) score and the Glasgow Coma Scale (GCS) are simple, accurate tools for risk stratification of hospitalized patients with acute exacerbation of COPD, results from a single-center study showed.
“Acute exacerbations of chronic obstructive pulmonary disease often require hospitalization, may necessitate mechanical ventilation, and can be fatal,” Mohamed Metwally, MD, FCCP, said in an interview in advance of the annual meeting of the American College of Chest Physicians. “There are currently no validated disease-specific scores that measure the severity of acute exacerbation. Prognostic tools are needed to assess acute exacerbations of chronic obstructive pulmonary disease.”
For the 2-year study, Dr. Metwally and his associates prospectively evaluated 250 critically ill ICU AECOPD patients, mean age 65 years, at Assiut University Hospital between December 2012 and December 2014. The primary outcome was in-hospital mortality while the secondary endpoint was need for intubation and mechanical ventilation. The researchers excluded patients who died less than 24 hours after admission, those with underlying COPD who were admitted with another primary diagnosis such as an accident or a stroke, or for elective hospitalizations such as elective surgery or diagnostic procedures.
Dr. Metwally and his associates collected sociodemographic data, vital signs, and other clinical variables, and collected scores from five tools used to measure mortality prediction: the Acute Physiology and Chronic Health Evaluation (APACHE II), the SOFA score, the Early Warning Score (EWS), the GCS, and the Charlson Comorbidity Index (CCI). To assess performance of the scores, they used area under the receiver operating characteristic curve (AUC) analysis and the Hosmer-Lemeshow goodness-of-fit test for logistic regression.
Of the 250 patients, 43 (17%) died during their hospital stay and 54% required mechanical ventilation. All recorded scores were significantly higher in nonsurvivors, compared with survivors, and the risk of clinical deterioration increased with increasing scores. The discriminatory power of each score varied as measured by AUC analysis. The AUC of APACHE II, SOFA, EWS, GCS, and CCI were 0.79, 0.81, 0.76, 0.69, and 0.68, respectively “and all these models had good calibration in mortality prediction,” Dr. Metwally said. The SOFA score was the best in predicting mortality (its predicted mortality was 16%, compared with the actual mortality of 17%), while the APACHE II score overestimated mortality by at least twofold (46% vs. 17%). In addition, the EWS outperformed the GCS in predicting mortality. “This may be due to EWS containing all vital signs plus level of consciousness,” he said in an interview.
The GCS was found to be the most useful in predicting need for mechanical ventilation, with an AUC of 0.81. The AUCs of APACHE II, SOFA, EWS, and CCI were 0.79, 0.80, 0.73, and 0.61, respectively. All of the scores had good calibration in mortality prediction, Dr. Metwally said, with the exception of SOFA.
As for the APACHE II, Dr. Metwally said that instrument “can be used as a tool to predict both mortality and intubation in a specific group of patients, but with low discriminatory power.” He acknowledged certain limitations of the study, including the fact that it was limited to patients with AECOPD. “Future studies should include any critically ill respiratory patients,” he said.
He reported having no financial disclosures.
AT CHEST 2016
Key clinical point:
Major finding: The Sequential Organ Failure Assessment score was the best in predicting mortality of patients with acute exacerbation of COPD (its predicted mortality was 16%, compared with the actual mortality of 17%).
Data source: A prospective evaluation of 250 critically ill ICU patients hospitalized with acute exacerbation of COPD.
Disclosures: Dr. Metwally reported having no financial disclosures.
Comorbidities common in COPD patients
LOS ANGELES – Comorbidities are common in patients with chronic obstructive pulmonary disease, especially cardiovascular disease, diabetes, anemia, and osteoporosis, results from a single-center analysis showed.
“These affect the course and outcome of COPD, so identification and treatment of these comorbidities is very important,” Hamdy Mohammadien, MD, said in an interview in advance of the annual meeting of the American College of Chest Physicians.
In an effort to estimate the presence of comorbidities in patients with COPD and to assess the relationship of comorbid diseases with age, sex, C-reactive protein, and COPD severity, Dr. Mohammadien and his associates at Sohag (Egypt) University, retrospectively evaluated 400 COPD patients who were at least 40 years of age. Those who presented with bronchial asthma or other lung diseases were excluded from the analysis. The mean age of patients was 62 years, 69% were male, and 36% were current smokers. Their mean FEV1/FVC ratio (forced expiratory volume in 1 second/forced vital capacity) was 48%, and 57% had two or more exacerbations in the previous year.
Dr. Mohammadien reported that all patients had at least one comorbidity. The most common comorbidities were cardiovascular diseases (85%), diabetes (35%), dyslipidemia (23%), osteopenia (11%), anemia (10%), muscle wasting (9%), pneumonia (7%), osteoporosis (6%), GERD (2%), and lung cancer (2%). He also noted that the association between cardiovascular events, dyslipidemia, diabetes, osteoporosis, muscle wasting, and anemia was highly significant in COPD patients aged 60 years and older, in men, and in patients with stage III and IV COPD. In addition, a significant relationship was observed between a positive CRP level and each comorbidity, with the exception of gastroesophageal reflux disease and lung cancer. The three comorbidities with the greatest significance were ischemic heart disease (P = .0001), dyslipidemia (P = .0001), and pneumonia (P = .0003). Finally, frequent exacerbators were significantly more likely to have two or more comorbidities (odds ratio 2; P = .04) and to have more hospitalizations in the past year (P less than .01).
“Comorbidities are common in patients with COPD, and have a significant impact on health status and prognosis, thus justifying the need for a comprehensive and integrating therapeutic approach,” Dr. Mohammadien said at the meeting. “In the management of COPD all these conditions need to be carefully evaluated and treated.”
He acknowledged certain limitations of the study, including its relatively small sample size and the fact that bone density was measured by sonar and not by dual-energy x-ray absorptiometry. Dr. Mohammadien reported having no financial disclosures.
LOS ANGELES – Comorbidities are common in patients with chronic obstructive pulmonary disease, especially cardiovascular disease, diabetes, anemia, and osteoporosis, results from a single-center analysis showed.
“These affect the course and outcome of COPD, so identification and treatment of these comorbidities is very important,” Hamdy Mohammadien, MD, said in an interview in advance of the annual meeting of the American College of Chest Physicians.
In an effort to estimate the presence of comorbidities in patients with COPD and to assess the relationship of comorbid diseases with age, sex, C-reactive protein, and COPD severity, Dr. Mohammadien and his associates at Sohag (Egypt) University, retrospectively evaluated 400 COPD patients who were at least 40 years of age. Those who presented with bronchial asthma or other lung diseases were excluded from the analysis. The mean age of patients was 62 years, 69% were male, and 36% were current smokers. Their mean FEV1/FVC ratio (forced expiratory volume in 1 second/forced vital capacity) was 48%, and 57% had two or more exacerbations in the previous year.
Dr. Mohammadien reported that all patients had at least one comorbidity. The most common comorbidities were cardiovascular diseases (85%), diabetes (35%), dyslipidemia (23%), osteopenia (11%), anemia (10%), muscle wasting (9%), pneumonia (7%), osteoporosis (6%), GERD (2%), and lung cancer (2%). He also noted that the association between cardiovascular events, dyslipidemia, diabetes, osteoporosis, muscle wasting, and anemia was highly significant in COPD patients aged 60 years and older, in men, and in patients with stage III and IV COPD. In addition, a significant relationship was observed between a positive CRP level and each comorbidity, with the exception of gastroesophageal reflux disease and lung cancer. The three comorbidities with the greatest significance were ischemic heart disease (P = .0001), dyslipidemia (P = .0001), and pneumonia (P = .0003). Finally, frequent exacerbators were significantly more likely to have two or more comorbidities (odds ratio 2; P = .04) and to have more hospitalizations in the past year (P less than .01).
“Comorbidities are common in patients with COPD, and have a significant impact on health status and prognosis, thus justifying the need for a comprehensive and integrating therapeutic approach,” Dr. Mohammadien said at the meeting. “In the management of COPD all these conditions need to be carefully evaluated and treated.”
He acknowledged certain limitations of the study, including its relatively small sample size and the fact that bone density was measured by sonar and not by dual-energy x-ray absorptiometry. Dr. Mohammadien reported having no financial disclosures.
LOS ANGELES – Comorbidities are common in patients with chronic obstructive pulmonary disease, especially cardiovascular disease, diabetes, anemia, and osteoporosis, results from a single-center analysis showed.
“These affect the course and outcome of COPD, so identification and treatment of these comorbidities is very important,” Hamdy Mohammadien, MD, said in an interview in advance of the annual meeting of the American College of Chest Physicians.
In an effort to estimate the presence of comorbidities in patients with COPD and to assess the relationship of comorbid diseases with age, sex, C-reactive protein, and COPD severity, Dr. Mohammadien and his associates at Sohag (Egypt) University, retrospectively evaluated 400 COPD patients who were at least 40 years of age. Those who presented with bronchial asthma or other lung diseases were excluded from the analysis. The mean age of patients was 62 years, 69% were male, and 36% were current smokers. Their mean FEV1/FVC ratio (forced expiratory volume in 1 second/forced vital capacity) was 48%, and 57% had two or more exacerbations in the previous year.
Dr. Mohammadien reported that all patients had at least one comorbidity. The most common comorbidities were cardiovascular diseases (85%), diabetes (35%), dyslipidemia (23%), osteopenia (11%), anemia (10%), muscle wasting (9%), pneumonia (7%), osteoporosis (6%), GERD (2%), and lung cancer (2%). He also noted that the association between cardiovascular events, dyslipidemia, diabetes, osteoporosis, muscle wasting, and anemia was highly significant in COPD patients aged 60 years and older, in men, and in patients with stage III and IV COPD. In addition, a significant relationship was observed between a positive CRP level and each comorbidity, with the exception of gastroesophageal reflux disease and lung cancer. The three comorbidities with the greatest significance were ischemic heart disease (P = .0001), dyslipidemia (P = .0001), and pneumonia (P = .0003). Finally, frequent exacerbators were significantly more likely to have two or more comorbidities (odds ratio 2; P = .04) and to have more hospitalizations in the past year (P less than .01).
“Comorbidities are common in patients with COPD, and have a significant impact on health status and prognosis, thus justifying the need for a comprehensive and integrating therapeutic approach,” Dr. Mohammadien said at the meeting. “In the management of COPD all these conditions need to be carefully evaluated and treated.”
He acknowledged certain limitations of the study, including its relatively small sample size and the fact that bone density was measured by sonar and not by dual-energy x-ray absorptiometry. Dr. Mohammadien reported having no financial disclosures.
AT CHEST 2016
Key clinical point:
Major finding: The three most common comorbidities in COPD patients were cardiovascular diseases (85%), diabetes (35%), and dyslipidemia (23%).
Data source: A retrospective study of 400 patients with COPD.
Disclosures: Dr. Mohammadien reported having no financial disclosures.
Optimal management of GERD in IPF unknown
EXPERT ANALYSIS FROM CHEST 2016
LOS ANGELES – The optimal management of gastroesophageal reflux disease in patients with idiopathic pulmonary fibrosis has yet to be determined, according to Joyce S. Lee, MD.
“We need strong randomized clinical trial data to tell us whether or not medical or surgical treatment of GERD in IPF is indicated,” she said at the annual meeting of the American College of Chest Physicians.
Two proposed hypotheses explain the relationship between reflux and IPF. The first holds that reflux and microaspiration are involved in the pathogenesis of IPF. The second, favored by Dr. Lee, proposes that reflux and microaspiration impact the natural history, either through acute exacerbation, disease progression, or survival. Patients with IPF “have weakening of the lower esophageal sphincter, whether that’s due to the presence of a hiatal hernia, medications, or just aging of the tissue there,” she said. “We know how to diagnose reflux disease, but we don’t know how to diagnose microaspiration, which is defined as subclinical aspiration of small droplets of gastric contents. Reflux is a risk factor for the condition of microaspiration, but it is not a perfect surrogate. Not everybody with reflux will aspirate. There is a potential role for bronchoalveolar lavage pepsin and/or bile salt as a biomarker of microaspiration, but it is not validated or standardized in IPF yet.”
Reflux becomes pathologic when reflux of stomach contents causes troublesome symptoms and/or complications. “Troublesome” is defined as mild symptoms 2 or more days a week or moderate to severe symptoms more than 1 day a week. Dr. Lee said that chest physicians can diagnose GERD in their IPF patients the same way that gastroenterologists and primary care doctors do: with symptoms, barium swallow, 24-hour pH monitoring, impedance testing, and sometimes endoscopy. The 2015 IPF guidelines recommend that clinicians “use regular antacid treatment for patients with IPF (conditional recommendation, very low confidence in estimates of effect).” It does not extend to surgical treatment with fundoplication. (Am J Resp Crit Care Med. 2015 Jul 15;192[2]: e3-19).
In an effort to measure the relationship between antacid therapy and change in forced vital capacity, Dr. Lee and her associates evaluated IPF patients from placebo arms of the three Idiopathic Pulmonary Fibrosis Clinical Research Network randomized controlled trials. They found that, compared with patients who did not take antacid therapy at baseline, those who did experienced a slower decline in their forced vital capacity over time (Lancet Resp Med. 2013 Jul;1[5]:369-76). However, a more-recent analysis conducted by different investigators examined the placebo arms of three pirfenidone studies and found no significant effect of antacid therapy in IPF patients (Lancet Resp Med. 2016 May;4[5]:381-9). Dr. Lee said that both evaluations differed because they were secondary analyses of previously captured data. “There were also differences in the ways the trials obtained GERD history, medication indication, and dosing of the antacid therapy,” she said. “There were also differences in outcomes and different populations studied.”
Dr. Lee’s current approach to counseling IPF patients with GERD includes discussing lifestyle modifications and PPI therapy – either daily or twice a day dosing, depending on their symptoms. “Lifestyle modifications include weight loss, smoking cessation, raising the head of the bed 6-8 inches, and avoiding foods that cause acid reflux, including chocolate, alcohol, peppermint, and fatty or spicy foods, and avoiding large and late meals,” she said. “In terms of acid suppression therapy with H2 blockers and PPIs [proton pump inhibitors], symptom relief and healing of the esophagus occurs in 85%-90% of patients taking them correctly. This does not alter their risk of having microaspiration.” Laparoscopic antireflux therapy (fundoplication) is indicated only after the failure of medical therapy. “The goal is to correct any hernia and tighten the lower esophageal sphincter,” she said. “Efficacy and symptom relief is reported to be around 95%.”
An NIH-funded trial called Weighing Risks and Benefits of Laparoscopic Anti-Reflux Surgery in Patients with Idiopathic Fibrosis, is ongoing at six centers. Dr. Lee said that some results are expected within the next year. She reported having no financial disclosures.
EXPERT ANALYSIS FROM CHEST 2016
LOS ANGELES – The optimal management of gastroesophageal reflux disease in patients with idiopathic pulmonary fibrosis has yet to be determined, according to Joyce S. Lee, MD.
“We need strong randomized clinical trial data to tell us whether or not medical or surgical treatment of GERD in IPF is indicated,” she said at the annual meeting of the American College of Chest Physicians.
Two proposed hypotheses explain the relationship between reflux and IPF. The first holds that reflux and microaspiration are involved in the pathogenesis of IPF. The second, favored by Dr. Lee, proposes that reflux and microaspiration impact the natural history, either through acute exacerbation, disease progression, or survival. Patients with IPF “have weakening of the lower esophageal sphincter, whether that’s due to the presence of a hiatal hernia, medications, or just aging of the tissue there,” she said. “We know how to diagnose reflux disease, but we don’t know how to diagnose microaspiration, which is defined as subclinical aspiration of small droplets of gastric contents. Reflux is a risk factor for the condition of microaspiration, but it is not a perfect surrogate. Not everybody with reflux will aspirate. There is a potential role for bronchoalveolar lavage pepsin and/or bile salt as a biomarker of microaspiration, but it is not validated or standardized in IPF yet.”
Reflux becomes pathologic when reflux of stomach contents causes troublesome symptoms and/or complications. “Troublesome” is defined as mild symptoms 2 or more days a week or moderate to severe symptoms more than 1 day a week. Dr. Lee said that chest physicians can diagnose GERD in their IPF patients the same way that gastroenterologists and primary care doctors do: with symptoms, barium swallow, 24-hour pH monitoring, impedance testing, and sometimes endoscopy. The 2015 IPF guidelines recommend that clinicians “use regular antacid treatment for patients with IPF (conditional recommendation, very low confidence in estimates of effect).” It does not extend to surgical treatment with fundoplication. (Am J Resp Crit Care Med. 2015 Jul 15;192[2]: e3-19).
In an effort to measure the relationship between antacid therapy and change in forced vital capacity, Dr. Lee and her associates evaluated IPF patients from placebo arms of the three Idiopathic Pulmonary Fibrosis Clinical Research Network randomized controlled trials. They found that, compared with patients who did not take antacid therapy at baseline, those who did experienced a slower decline in their forced vital capacity over time (Lancet Resp Med. 2013 Jul;1[5]:369-76). However, a more-recent analysis conducted by different investigators examined the placebo arms of three pirfenidone studies and found no significant effect of antacid therapy in IPF patients (Lancet Resp Med. 2016 May;4[5]:381-9). Dr. Lee said that both evaluations differed because they were secondary analyses of previously captured data. “There were also differences in the ways the trials obtained GERD history, medication indication, and dosing of the antacid therapy,” she said. “There were also differences in outcomes and different populations studied.”
Dr. Lee’s current approach to counseling IPF patients with GERD includes discussing lifestyle modifications and PPI therapy – either daily or twice a day dosing, depending on their symptoms. “Lifestyle modifications include weight loss, smoking cessation, raising the head of the bed 6-8 inches, and avoiding foods that cause acid reflux, including chocolate, alcohol, peppermint, and fatty or spicy foods, and avoiding large and late meals,” she said. “In terms of acid suppression therapy with H2 blockers and PPIs [proton pump inhibitors], symptom relief and healing of the esophagus occurs in 85%-90% of patients taking them correctly. This does not alter their risk of having microaspiration.” Laparoscopic antireflux therapy (fundoplication) is indicated only after the failure of medical therapy. “The goal is to correct any hernia and tighten the lower esophageal sphincter,” she said. “Efficacy and symptom relief is reported to be around 95%.”
An NIH-funded trial called Weighing Risks and Benefits of Laparoscopic Anti-Reflux Surgery in Patients with Idiopathic Fibrosis, is ongoing at six centers. Dr. Lee said that some results are expected within the next year. She reported having no financial disclosures.
EXPERT ANALYSIS FROM CHEST 2016
LOS ANGELES – The optimal management of gastroesophageal reflux disease in patients with idiopathic pulmonary fibrosis has yet to be determined, according to Joyce S. Lee, MD.
“We need strong randomized clinical trial data to tell us whether or not medical or surgical treatment of GERD in IPF is indicated,” she said at the annual meeting of the American College of Chest Physicians.
Two proposed hypotheses explain the relationship between reflux and IPF. The first holds that reflux and microaspiration are involved in the pathogenesis of IPF. The second, favored by Dr. Lee, proposes that reflux and microaspiration impact the natural history, either through acute exacerbation, disease progression, or survival. Patients with IPF “have weakening of the lower esophageal sphincter, whether that’s due to the presence of a hiatal hernia, medications, or just aging of the tissue there,” she said. “We know how to diagnose reflux disease, but we don’t know how to diagnose microaspiration, which is defined as subclinical aspiration of small droplets of gastric contents. Reflux is a risk factor for the condition of microaspiration, but it is not a perfect surrogate. Not everybody with reflux will aspirate. There is a potential role for bronchoalveolar lavage pepsin and/or bile salt as a biomarker of microaspiration, but it is not validated or standardized in IPF yet.”
Reflux becomes pathologic when reflux of stomach contents causes troublesome symptoms and/or complications. “Troublesome” is defined as mild symptoms 2 or more days a week or moderate to severe symptoms more than 1 day a week. Dr. Lee said that chest physicians can diagnose GERD in their IPF patients the same way that gastroenterologists and primary care doctors do: with symptoms, barium swallow, 24-hour pH monitoring, impedance testing, and sometimes endoscopy. The 2015 IPF guidelines recommend that clinicians “use regular antacid treatment for patients with IPF (conditional recommendation, very low confidence in estimates of effect).” It does not extend to surgical treatment with fundoplication. (Am J Resp Crit Care Med. 2015 Jul 15;192[2]: e3-19).
In an effort to measure the relationship between antacid therapy and change in forced vital capacity, Dr. Lee and her associates evaluated IPF patients from placebo arms of the three Idiopathic Pulmonary Fibrosis Clinical Research Network randomized controlled trials. They found that, compared with patients who did not take antacid therapy at baseline, those who did experienced a slower decline in their forced vital capacity over time (Lancet Resp Med. 2013 Jul;1[5]:369-76). However, a more-recent analysis conducted by different investigators examined the placebo arms of three pirfenidone studies and found no significant effect of antacid therapy in IPF patients (Lancet Resp Med. 2016 May;4[5]:381-9). Dr. Lee said that both evaluations differed because they were secondary analyses of previously captured data. “There were also differences in the ways the trials obtained GERD history, medication indication, and dosing of the antacid therapy,” she said. “There were also differences in outcomes and different populations studied.”
Dr. Lee’s current approach to counseling IPF patients with GERD includes discussing lifestyle modifications and PPI therapy – either daily or twice a day dosing, depending on their symptoms. “Lifestyle modifications include weight loss, smoking cessation, raising the head of the bed 6-8 inches, and avoiding foods that cause acid reflux, including chocolate, alcohol, peppermint, and fatty or spicy foods, and avoiding large and late meals,” she said. “In terms of acid suppression therapy with H2 blockers and PPIs [proton pump inhibitors], symptom relief and healing of the esophagus occurs in 85%-90% of patients taking them correctly. This does not alter their risk of having microaspiration.” Laparoscopic antireflux therapy (fundoplication) is indicated only after the failure of medical therapy. “The goal is to correct any hernia and tighten the lower esophageal sphincter,” she said. “Efficacy and symptom relief is reported to be around 95%.”
An NIH-funded trial called Weighing Risks and Benefits of Laparoscopic Anti-Reflux Surgery in Patients with Idiopathic Fibrosis, is ongoing at six centers. Dr. Lee said that some results are expected within the next year. She reported having no financial disclosures.
‘Stepping’ up to a better way to teach robotic lobectomy
Teaching minimally invasive robotic surgery to residents can be difficult in a health care environment obsessed with quality outcome measures and under scrutiny by hospital administrators and payers, but researchers at the University of Alabama at Birmingham may have devised a method to instruct residents in robotic lobectomy without compromising patient outcomes, according to a study published in the October issue of the Journal of Thoracic and Cardiovascular Surgery (2016;152:991-7).
Robert J. Cerfolio, MD, MBA, and his coauthors divided the procedure into 19 sequential, teachable steps and allowed residents to perform selected steps during operations that Dr. Cerfolio directed. “We then applied simulation training, coaching techniques, and video review of each step to help improve the steps that residents could not complete,” Dr. Cerfolio and his coauthors said. 
Surgeons in academic centers face the challenge of teaching “the art and science of surgery,” Dr. Cerfolio and his colleagues said, while maintaining quality outcomes. “Teaching minimally invasive surgery, especially robotic surgery, is challenging given the risks and the limited availability of the robot.”
The researchers acknowledged that other groups have taken a similar approach to training, but this is the first study that included video review, coaching, and instruction tied to time constraints, they said. “A major concern is that while teaching robotic surgery, patients can be injured, care is worse, and metrics that are increasingly used as surrogates for quality outcomes suffer,” they noted.
They allotted each step in the procedure a set amount of time in which the resident had to complete it, totaling 80 minutes for all 19 steps and ranging from 1 minute to inspect the pleura after placing ports (9 minutes) to 20 minutes to close the five incisions. If the resident completed the task in the allotted time, it was recorded as “performed.”
Between February 2010 and December 2010 Dr. Cerfolio performed 520 robotic lobectomies, and over time the percentage of successful steps per resident improved. For example, in the first year, 50% of thoracic surgery residents completed the first five steps (mark and place ports, inspect pleura, resect the inferior pulmonary ligament, and remove three lymph nodes), but by the last year of the study 90% of them successfully completed the five steps.
Dr. Cerfolio and coauthors acknowledged “many flaws” in their study, but the study also had strengths: It involved only one operation and corroborated the database with each resident’s own surgical logs.
“Operations such as robotic lobectomy can be successfully taught by dividing them into a series of surgical maneuvers or steps,” the researchers noted. Recording what residents can and can’t do, reviewing video, and coaching contribute to the process to improve their skills. “Further studies that scientifically measure ‘ways to teach’ and ways to coach and mentor are needed,” they said.
Dr. Cerfolio disclosed relationships with Intuitive Surgical, Ethicon, Community Health Services, KCL, Bovie and C-SATS. Coauthor Douglas Minnich, MD, is a consultant to Medtronic. The other co-authors had no financial relationships to disclose.
Inderpal S. Sarkaria, MD, of the University of Pittsburgh acknowledged in his invited commentary how “metric-driven patient outcomes” have changed cardiothoracic surgical training (J Thorac Cardiovasc Surg. 2016;152:998).
But Dr. Sarkaria questioned the validity of using time performed as a metric in this study to evaluate a trainee’s competency. “Although ‘time’ is an important component, should not the primary focus be on ‘quality’ of the trainee’s work?” Dr. Sarkaria asked. 
Despite these questions and the limitations of the study, he found the approach to surgical training “laudable.” Said Dr. Sarkaria: “It is arguable that the limitations of the study speak more to a common wisdom that certain aspects of surgical education remain an art to a greater or lesser extent, not easily amenable to our efforts to discretely compartmentalize and quantify the process.”
While the premise demands further study, Dr. Cerfolio and his coauthors “have laid a solid foundation on which further to build, explore, and potentially improve the science and art of teaching complex operations to our surgical residents,” Dr. Sarkaria said.
Dr. Sarkaria had no relationships to disclose.
Inderpal S. Sarkaria, MD, of the University of Pittsburgh acknowledged in his invited commentary how “metric-driven patient outcomes” have changed cardiothoracic surgical training (J Thorac Cardiovasc Surg. 2016;152:998).
But Dr. Sarkaria questioned the validity of using time performed as a metric in this study to evaluate a trainee’s competency. “Although ‘time’ is an important component, should not the primary focus be on ‘quality’ of the trainee’s work?” Dr. Sarkaria asked.
Despite these questions and the limitations of the study, he found the approach to surgical training “laudable.” Said Dr. Sarkaria: “It is arguable that the limitations of the study speak more to a common wisdom that certain aspects of surgical education remain an art to a greater or lesser extent, not easily amenable to our efforts to discretely compartmentalize and quantify the process.”
While the premise demands further study, Dr. Cerfolio and his coauthors “have laid a solid foundation on which further to build, explore, and potentially improve the science and art of teaching complex operations to our surgical residents,” Dr. Sarkaria said.
Dr. Sarkaria had no relationships to disclose.
Inderpal S. Sarkaria, MD, of the University of Pittsburgh acknowledged in his invited commentary how “metric-driven patient outcomes” have changed cardiothoracic surgical training (J Thorac Cardiovasc Surg. 2016;152:998).
But Dr. Sarkaria questioned the validity of using time performed as a metric in this study to evaluate a trainee’s competency. “Although ‘time’ is an important component, should not the primary focus be on ‘quality’ of the trainee’s work?” Dr. Sarkaria asked.
Despite these questions and the limitations of the study, he found the approach to surgical training “laudable.” Said Dr. Sarkaria: “It is arguable that the limitations of the study speak more to a common wisdom that certain aspects of surgical education remain an art to a greater or lesser extent, not easily amenable to our efforts to discretely compartmentalize and quantify the process.”
While the premise demands further study, Dr. Cerfolio and his coauthors “have laid a solid foundation on which further to build, explore, and potentially improve the science and art of teaching complex operations to our surgical residents,” Dr. Sarkaria said.
Dr. Sarkaria had no relationships to disclose.
Teaching minimally invasive robotic surgery to residents can be difficult in a health care environment obsessed with quality outcome measures and under scrutiny by hospital administrators and payers, but researchers at the University of Alabama at Birmingham may have devised a method to instruct residents in robotic lobectomy without compromising patient outcomes, according to a study published in the October issue of the Journal of Thoracic and Cardiovascular Surgery (2016;152:991-7).
Robert J. Cerfolio, MD, MBA, and his coauthors divided the procedure into 19 sequential, teachable steps and allowed residents to perform selected steps during operations that Dr. Cerfolio directed. “We then applied simulation training, coaching techniques, and video review of each step to help improve the steps that residents could not complete,” Dr. Cerfolio and his coauthors said.
Surgeons in academic centers face the challenge of teaching “the art and science of surgery,” Dr. Cerfolio and his colleagues said, while maintaining quality outcomes. “Teaching minimally invasive surgery, especially robotic surgery, is challenging given the risks and the limited availability of the robot.”
The researchers acknowledged that other groups have taken a similar approach to training, but this is the first study that included video review, coaching, and instruction tied to time constraints, they said. “A major concern is that while teaching robotic surgery, patients can be injured, care is worse, and metrics that are increasingly used as surrogates for quality outcomes suffer,” they noted.
They allotted each step in the procedure a set amount of time in which the resident had to complete it, totaling 80 minutes for all 19 steps and ranging from 1 minute to inspect the pleura after placing ports (9 minutes) to 20 minutes to close the five incisions. If the resident completed the task in the allotted time, it was recorded as “performed.”
Between February 2010 and December 2010 Dr. Cerfolio performed 520 robotic lobectomies, and over time the percentage of successful steps per resident improved. For example, in the first year, 50% of thoracic surgery residents completed the first five steps (mark and place ports, inspect pleura, resect the inferior pulmonary ligament, and remove three lymph nodes), but by the last year of the study 90% of them successfully completed the five steps.
Dr. Cerfolio and coauthors acknowledged “many flaws” in their study, but the study also had strengths: It involved only one operation and corroborated the database with each resident’s own surgical logs.
“Operations such as robotic lobectomy can be successfully taught by dividing them into a series of surgical maneuvers or steps,” the researchers noted. Recording what residents can and can’t do, reviewing video, and coaching contribute to the process to improve their skills. “Further studies that scientifically measure ‘ways to teach’ and ways to coach and mentor are needed,” they said.
Dr. Cerfolio disclosed relationships with Intuitive Surgical, Ethicon, Community Health Services, KCL, Bovie and C-SATS. Coauthor Douglas Minnich, MD, is a consultant to Medtronic. The other co-authors had no financial relationships to disclose.
Teaching minimally invasive robotic surgery to residents can be difficult in a health care environment obsessed with quality outcome measures and under scrutiny by hospital administrators and payers, but researchers at the University of Alabama at Birmingham may have devised a method to instruct residents in robotic lobectomy without compromising patient outcomes, according to a study published in the October issue of the Journal of Thoracic and Cardiovascular Surgery (2016;152:991-7).
Robert J. Cerfolio, MD, MBA, and his coauthors divided the procedure into 19 sequential, teachable steps and allowed residents to perform selected steps during operations that Dr. Cerfolio directed. “We then applied simulation training, coaching techniques, and video review of each step to help improve the steps that residents could not complete,” Dr. Cerfolio and his coauthors said.
Surgeons in academic centers face the challenge of teaching “the art and science of surgery,” Dr. Cerfolio and his colleagues said, while maintaining quality outcomes. “Teaching minimally invasive surgery, especially robotic surgery, is challenging given the risks and the limited availability of the robot.”
The researchers acknowledged that other groups have taken a similar approach to training, but this is the first study that included video review, coaching, and instruction tied to time constraints, they said. “A major concern is that while teaching robotic surgery, patients can be injured, care is worse, and metrics that are increasingly used as surrogates for quality outcomes suffer,” they noted.
They allotted each step in the procedure a set amount of time in which the resident had to complete it, totaling 80 minutes for all 19 steps and ranging from 1 minute to inspect the pleura after placing ports (9 minutes) to 20 minutes to close the five incisions. If the resident completed the task in the allotted time, it was recorded as “performed.”
Between February 2010 and December 2010 Dr. Cerfolio performed 520 robotic lobectomies, and over time the percentage of successful steps per resident improved. For example, in the first year, 50% of thoracic surgery residents completed the first five steps (mark and place ports, inspect pleura, resect the inferior pulmonary ligament, and remove three lymph nodes), but by the last year of the study 90% of them successfully completed the five steps.
Dr. Cerfolio and coauthors acknowledged “many flaws” in their study, but the study also had strengths: It involved only one operation and corroborated the database with each resident’s own surgical logs.
“Operations such as robotic lobectomy can be successfully taught by dividing them into a series of surgical maneuvers or steps,” the researchers noted. Recording what residents can and can’t do, reviewing video, and coaching contribute to the process to improve their skills. “Further studies that scientifically measure ‘ways to teach’ and ways to coach and mentor are needed,” they said.
Dr. Cerfolio disclosed relationships with Intuitive Surgical, Ethicon, Community Health Services, KCL, Bovie and C-SATS. Coauthor Douglas Minnich, MD, is a consultant to Medtronic. The other co-authors had no financial relationships to disclose.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: Surgical residents learn and safely perform robotic lobectomy by dividing the procedure into a series of surgical maneuvers.
Major finding: The percentage of thoracic surgery residents who completed the first 5 of 19 procedural steps of the operation improved from 50% in the first year to 90% in the fifth year.
Data source: Single-center study of 520 consecutive lobectomies over 5 years by 35 general surgery residents and 7 cardiothoracic residents from February 2010 to December 2015.
Disclosures: Dr. Cerfolio disclosed relationships with Intuitive Surgical, Ethicon, Community Health Services, KCL, Bovie and C-SATS. Coauthor Douglas Minnich, MD, is a consultant to Medtronic. The other coauthors had no financial relationships to disclose.
Adaptive servo ventilation cuts atrial fib burden
ORLANDO – Adaptive servo ventilation produced a significant and clinically meaningful reduction in atrial fibrillation burden in patients with heart failure and sleep apnea in results from an exploratory, prospective, randomized study with 35 patients.
Adaptive servo ventilation (ASV) “may be an effective antiarrhythmic treatment producing a significant reduction in atrial fibrillation without clear evidence of being proarrhythmogenic,” Jonathan P. Piccini, MD, said at the annual scientific meeting of the Heart Failure Society of America. “Given the potential importance of this finding further studies should validate and quantify the efficacy of ASV for reducing atrial fibrillation in patients with or without heart failure.”
“A mound of data has shown that treating sleep apnea reduced arrhythmias, but until now it’s all been observational and retrospective,” Dr. Piccini, an electrophysiologist at Duke University in Durham, N.C., said in an interview. The study he reported is “the first time” the arrhythmia effects of a sleep apnea intervention, in this case ASV, was studied in a prospective, randomized way while using implanted devices to measure the antiarrhythmic effect of the treatment.
The new finding means that additional, larger studies are now needed, he said. “If patients have sleep apnea, treating the apnea may be an incredibly important way to prevent AF or reduce its burden”
The CAT-HF (Cardiovascular Improvements With Minute Ventilation-Targeted ASV Therapy in Heart Failure) trial was originally designed to randomize 215 heart failure patients with sleep disordered breathing – and who were hospitalized for heart failure – to optimal medical therapy with or without ASV at any of 15 centers in the United States and Germany. But in August 2015, results from the SERVE-HF (Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients with Heart Failure) trial, which generally had a similar design to CAT-HF, showed an unexpected danger from ASV in patients with central sleep apnea and heart failure with reduced ejection fraction (N Engl J Med. 2015 Sept 17;373[12]:1095-105). In SERVE-HF, ASV was associated with significant increases in all-cause and cardiovascular mortality. As a result, enrollment into CAT-HF stopped prematurely with just 126 patients entered, and ASV treatment of patients already enrolled came to a halt.
The primary endpoint in the underpowered and shortened CAT-HF study, survival without cardiovascular hospitalization and with improved functional capacity measured on a 6-minute walk test, showed similar outcomes in both the ASV and control arms. But in a prespecified subgroup analysis by baseline ejection fraction, the 24 patients with heart failure with preserved ejection fraction (19% of the CAT-HF enrollment) showed a statistically significant, 62% relative improvement in the primary endpoint linked with ASV treatment compared with similar patients who did not receive ASV, Christopher M. O’Connor, MD, professor of medicine at Duke University, reported in May 2016 at the European Heart Failure meeting in Florence.
Dr. Piccini’s report focused on a prespecified subgroup analysis of CAT-HF designed to examine the impact of ASV on arrhythmias. Assessment of the impact of ASV on atrial fibrillation was possible in 35 of the 126 patients in CAT-HF who had an implanted cardiac device (pacemaker, defibrillator, or cardiac resynchronization device) with an atrial lead, and assessment of ventricular arrhythmias occurred in 46 of the CAT-HF patients with an implanted high-voltage device (a defibrillator or resynchronization device) that allowed monitoring of ventricular arrhythmias.
For the atrial fibrillation analysis, the 35 patients averaged 60 years of age, and about 90% had a reduced ejection fraction. About two-thirds had an apnea-hypopnea index greater than 30.
The results showed that the 19 patients randomized to receive ASV had an average atrial fibrillation burden of 30% at baseline that dropped to 14% after 6 months of treatment. In contrast, the 16 patients in the control arm had a AF burden of 6% at baseline and 8% after 6 months. The between-group difference for change in AF burden was statistically significant, Dr. Piccini reported, with a burden that decreased by a relative 21% with ASV treatment and increased by a relative 31% in the control arm.
Analysis of the ventricular arrhythmia subgroup showed that ASV had no statistically significant impact for either lowering or raising ventricular tachyarrhythmias or fibrillations.
Trying to reconcile this AF benefit and lack of ventricular arrhythmia harm from ASV in CAT-HF with the excess in cardiovascular deaths seen with ASV in SERVE-HF, Dr. Piccini speculated that some of the SERVE-HF deaths may not have been related to arrhythmia.
“Sudden cardiac death adjudication is profoundly difficult, and does not always equal ventricular arrhythmia,” he said. “We need to consider that some of the adverse events in patients with severe central sleep apnea and low left ventricular ejection fraction [enrolled in SERVE-HF] may have been due to causes other than arrhythmias. The CAT-HF results should motivate investigations of alternative mechanisms of death in SERVE-HF.”
The CAT-HF trial was funded by ResMed, a company that markets adaptive servo ventilation equipment. Dr. Piccini has received research support from ResMed and from Janssen, Gilead, St. Jude, Spectranetics, and he has been a consultant to Janssen, Spectranetics, Medtronic, GSK and BMS-Pfizer. Dr. O’Connor has been a consultant to ResMed and to several other drug and device companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
A small prespecified sub-group of patients in the CAT-HF (Cardiovascuar improvements with minute ventilation-targeted ASV therapy in heart failure) trial randomized to adaptive servo ventilation (ASV) showed a 21% relative reduction in atrial fibrillation burden as compared to the control arm which had only 31% relative reduction. While the CAT-HF study was discontinued following results of SERVE-HF trial, this subgroup analysis included 35 patients (19 ASV arm; 16 control arm), the majority of whom had a reduced ejection fraction. This report poses interesting questions about effects of ASV on atrial fibrillation burden in those with reduced EF given the finding that central sleep apnea and Cheyne-Stokes respiration are shown to be associated with incident atrial fibrillation in older men (May et al. Am J Respir Crit Care Med 2016).
A small prespecified sub-group of patients in the CAT-HF (Cardiovascuar improvements with minute ventilation-targeted ASV therapy in heart failure) trial randomized to adaptive servo ventilation (ASV) showed a 21% relative reduction in atrial fibrillation burden as compared to the control arm which had only 31% relative reduction. While the CAT-HF study was discontinued following results of SERVE-HF trial, this subgroup analysis included 35 patients (19 ASV arm; 16 control arm), the majority of whom had a reduced ejection fraction. This report poses interesting questions about effects of ASV on atrial fibrillation burden in those with reduced EF given the finding that central sleep apnea and Cheyne-Stokes respiration are shown to be associated with incident atrial fibrillation in older men (May et al. Am J Respir Crit Care Med 2016).
A small prespecified sub-group of patients in the CAT-HF (Cardiovascuar improvements with minute ventilation-targeted ASV therapy in heart failure) trial randomized to adaptive servo ventilation (ASV) showed a 21% relative reduction in atrial fibrillation burden as compared to the control arm which had only 31% relative reduction. While the CAT-HF study was discontinued following results of SERVE-HF trial, this subgroup analysis included 35 patients (19 ASV arm; 16 control arm), the majority of whom had a reduced ejection fraction. This report poses interesting questions about effects of ASV on atrial fibrillation burden in those with reduced EF given the finding that central sleep apnea and Cheyne-Stokes respiration are shown to be associated with incident atrial fibrillation in older men (May et al. Am J Respir Crit Care Med 2016).
ORLANDO – Adaptive servo ventilation produced a significant and clinically meaningful reduction in atrial fibrillation burden in patients with heart failure and sleep apnea in results from an exploratory, prospective, randomized study with 35 patients.
Adaptive servo ventilation (ASV) “may be an effective antiarrhythmic treatment producing a significant reduction in atrial fibrillation without clear evidence of being proarrhythmogenic,” Jonathan P. Piccini, MD, said at the annual scientific meeting of the Heart Failure Society of America. “Given the potential importance of this finding further studies should validate and quantify the efficacy of ASV for reducing atrial fibrillation in patients with or without heart failure.”
“A mound of data has shown that treating sleep apnea reduced arrhythmias, but until now it’s all been observational and retrospective,” Dr. Piccini, an electrophysiologist at Duke University in Durham, N.C., said in an interview. The study he reported is “the first time” the arrhythmia effects of a sleep apnea intervention, in this case ASV, was studied in a prospective, randomized way while using implanted devices to measure the antiarrhythmic effect of the treatment.
The new finding means that additional, larger studies are now needed, he said. “If patients have sleep apnea, treating the apnea may be an incredibly important way to prevent AF or reduce its burden”
The CAT-HF (Cardiovascular Improvements With Minute Ventilation-Targeted ASV Therapy in Heart Failure) trial was originally designed to randomize 215 heart failure patients with sleep disordered breathing – and who were hospitalized for heart failure – to optimal medical therapy with or without ASV at any of 15 centers in the United States and Germany. But in August 2015, results from the SERVE-HF (Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients with Heart Failure) trial, which generally had a similar design to CAT-HF, showed an unexpected danger from ASV in patients with central sleep apnea and heart failure with reduced ejection fraction (N Engl J Med. 2015 Sept 17;373[12]:1095-105). In SERVE-HF, ASV was associated with significant increases in all-cause and cardiovascular mortality. As a result, enrollment into CAT-HF stopped prematurely with just 126 patients entered, and ASV treatment of patients already enrolled came to a halt.
The primary endpoint in the underpowered and shortened CAT-HF study, survival without cardiovascular hospitalization and with improved functional capacity measured on a 6-minute walk test, showed similar outcomes in both the ASV and control arms. But in a prespecified subgroup analysis by baseline ejection fraction, the 24 patients with heart failure with preserved ejection fraction (19% of the CAT-HF enrollment) showed a statistically significant, 62% relative improvement in the primary endpoint linked with ASV treatment compared with similar patients who did not receive ASV, Christopher M. O’Connor, MD, professor of medicine at Duke University, reported in May 2016 at the European Heart Failure meeting in Florence.
Dr. Piccini’s report focused on a prespecified subgroup analysis of CAT-HF designed to examine the impact of ASV on arrhythmias. Assessment of the impact of ASV on atrial fibrillation was possible in 35 of the 126 patients in CAT-HF who had an implanted cardiac device (pacemaker, defibrillator, or cardiac resynchronization device) with an atrial lead, and assessment of ventricular arrhythmias occurred in 46 of the CAT-HF patients with an implanted high-voltage device (a defibrillator or resynchronization device) that allowed monitoring of ventricular arrhythmias.
For the atrial fibrillation analysis, the 35 patients averaged 60 years of age, and about 90% had a reduced ejection fraction. About two-thirds had an apnea-hypopnea index greater than 30.
The results showed that the 19 patients randomized to receive ASV had an average atrial fibrillation burden of 30% at baseline that dropped to 14% after 6 months of treatment. In contrast, the 16 patients in the control arm had a AF burden of 6% at baseline and 8% after 6 months. The between-group difference for change in AF burden was statistically significant, Dr. Piccini reported, with a burden that decreased by a relative 21% with ASV treatment and increased by a relative 31% in the control arm.
Analysis of the ventricular arrhythmia subgroup showed that ASV had no statistically significant impact for either lowering or raising ventricular tachyarrhythmias or fibrillations.
Trying to reconcile this AF benefit and lack of ventricular arrhythmia harm from ASV in CAT-HF with the excess in cardiovascular deaths seen with ASV in SERVE-HF, Dr. Piccini speculated that some of the SERVE-HF deaths may not have been related to arrhythmia.
“Sudden cardiac death adjudication is profoundly difficult, and does not always equal ventricular arrhythmia,” he said. “We need to consider that some of the adverse events in patients with severe central sleep apnea and low left ventricular ejection fraction [enrolled in SERVE-HF] may have been due to causes other than arrhythmias. The CAT-HF results should motivate investigations of alternative mechanisms of death in SERVE-HF.”
The CAT-HF trial was funded by ResMed, a company that markets adaptive servo ventilation equipment. Dr. Piccini has received research support from ResMed and from Janssen, Gilead, St. Jude, Spectranetics, and he has been a consultant to Janssen, Spectranetics, Medtronic, GSK and BMS-Pfizer. Dr. O’Connor has been a consultant to ResMed and to several other drug and device companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
ORLANDO – Adaptive servo ventilation produced a significant and clinically meaningful reduction in atrial fibrillation burden in patients with heart failure and sleep apnea in results from an exploratory, prospective, randomized study with 35 patients.
Adaptive servo ventilation (ASV) “may be an effective antiarrhythmic treatment producing a significant reduction in atrial fibrillation without clear evidence of being proarrhythmogenic,” Jonathan P. Piccini, MD, said at the annual scientific meeting of the Heart Failure Society of America. “Given the potential importance of this finding further studies should validate and quantify the efficacy of ASV for reducing atrial fibrillation in patients with or without heart failure.”
“A mound of data has shown that treating sleep apnea reduced arrhythmias, but until now it’s all been observational and retrospective,” Dr. Piccini, an electrophysiologist at Duke University in Durham, N.C., said in an interview. The study he reported is “the first time” the arrhythmia effects of a sleep apnea intervention, in this case ASV, was studied in a prospective, randomized way while using implanted devices to measure the antiarrhythmic effect of the treatment.
The new finding means that additional, larger studies are now needed, he said. “If patients have sleep apnea, treating the apnea may be an incredibly important way to prevent AF or reduce its burden”
The CAT-HF (Cardiovascular Improvements With Minute Ventilation-Targeted ASV Therapy in Heart Failure) trial was originally designed to randomize 215 heart failure patients with sleep disordered breathing – and who were hospitalized for heart failure – to optimal medical therapy with or without ASV at any of 15 centers in the United States and Germany. But in August 2015, results from the SERVE-HF (Treatment of Sleep-Disordered Breathing with Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients with Heart Failure) trial, which generally had a similar design to CAT-HF, showed an unexpected danger from ASV in patients with central sleep apnea and heart failure with reduced ejection fraction (N Engl J Med. 2015 Sept 17;373[12]:1095-105). In SERVE-HF, ASV was associated with significant increases in all-cause and cardiovascular mortality. As a result, enrollment into CAT-HF stopped prematurely with just 126 patients entered, and ASV treatment of patients already enrolled came to a halt.
The primary endpoint in the underpowered and shortened CAT-HF study, survival without cardiovascular hospitalization and with improved functional capacity measured on a 6-minute walk test, showed similar outcomes in both the ASV and control arms. But in a prespecified subgroup analysis by baseline ejection fraction, the 24 patients with heart failure with preserved ejection fraction (19% of the CAT-HF enrollment) showed a statistically significant, 62% relative improvement in the primary endpoint linked with ASV treatment compared with similar patients who did not receive ASV, Christopher M. O’Connor, MD, professor of medicine at Duke University, reported in May 2016 at the European Heart Failure meeting in Florence.
Dr. Piccini’s report focused on a prespecified subgroup analysis of CAT-HF designed to examine the impact of ASV on arrhythmias. Assessment of the impact of ASV on atrial fibrillation was possible in 35 of the 126 patients in CAT-HF who had an implanted cardiac device (pacemaker, defibrillator, or cardiac resynchronization device) with an atrial lead, and assessment of ventricular arrhythmias occurred in 46 of the CAT-HF patients with an implanted high-voltage device (a defibrillator or resynchronization device) that allowed monitoring of ventricular arrhythmias.
For the atrial fibrillation analysis, the 35 patients averaged 60 years of age, and about 90% had a reduced ejection fraction. About two-thirds had an apnea-hypopnea index greater than 30.
The results showed that the 19 patients randomized to receive ASV had an average atrial fibrillation burden of 30% at baseline that dropped to 14% after 6 months of treatment. In contrast, the 16 patients in the control arm had a AF burden of 6% at baseline and 8% after 6 months. The between-group difference for change in AF burden was statistically significant, Dr. Piccini reported, with a burden that decreased by a relative 21% with ASV treatment and increased by a relative 31% in the control arm.
Analysis of the ventricular arrhythmia subgroup showed that ASV had no statistically significant impact for either lowering or raising ventricular tachyarrhythmias or fibrillations.
Trying to reconcile this AF benefit and lack of ventricular arrhythmia harm from ASV in CAT-HF with the excess in cardiovascular deaths seen with ASV in SERVE-HF, Dr. Piccini speculated that some of the SERVE-HF deaths may not have been related to arrhythmia.
“Sudden cardiac death adjudication is profoundly difficult, and does not always equal ventricular arrhythmia,” he said. “We need to consider that some of the adverse events in patients with severe central sleep apnea and low left ventricular ejection fraction [enrolled in SERVE-HF] may have been due to causes other than arrhythmias. The CAT-HF results should motivate investigations of alternative mechanisms of death in SERVE-HF.”
The CAT-HF trial was funded by ResMed, a company that markets adaptive servo ventilation equipment. Dr. Piccini has received research support from ResMed and from Janssen, Gilead, St. Jude, Spectranetics, and he has been a consultant to Janssen, Spectranetics, Medtronic, GSK and BMS-Pfizer. Dr. O’Connor has been a consultant to ResMed and to several other drug and device companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
Key clinical point:
Major finding: After 6 months, ASV produced a relative 21% drop in atrial fibrillation burden, compared with increased burden in control patients.
Data source: CAT-HF, a multicenter randomized trial that enrolled 126 heart failure patients with sleep apnea.
Disclosures: The CAT-HF trial was funded by ResMed, a company that markets adaptive servo ventilation equipment. Dr. Piccini has received research support and/or consultant fees from ResMed, Janssen, Gilead, St. Jude, Spectranetics, Medtronic, GSK and BMS-Pfizer.
FDA expands indication for pembrolizumab in NSCLC
The Food and Drug Administration has approved pembrolizumab for the treatment of patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test. This is the first approval of a checkpoint inhibitor for first-line treatment of the disease.
Pembrolizumab (Keytruda) is now approved to treat patients with metastatic NSCLC whose tumors have high PD-L1 expression (Tumor Proportion Score [TPS] greater than or equal to 50%), with no EGFR or ALK genomic tumor aberrations, and no prior systemic chemotherapy treatment for metastatic NSCLC, the FDA said in a written statement.
The FDA based its approval on improvement in overall survival in two trials comparing treatment with pembrolizumab to treatment from chemotherapy. In one trial of 305 patients who had no prior treatment for metastatic NSCLC and TPS greater than or equal to 50%, those who received pembrolizumab (200 mg every 3 weeks) had a statistically significant improvement in overall survival, compared with patients randomized to receive chemotherapy (hazard ratio, 0.60; 95% confidence interval, 0.41-0.89; P less than .005). There was also significant improvement in progression-free survival for those receiving the checkpoint inhibitor (HR, 0.50; 95% CI, 0.37-0.68; P less than .001).
In the second trial, a three-arm trial of 1,033 patients who were previously treated for metastatic NSCLC with a TPS greater than or equal to 1%, those randomized to pembrolizumab 2 mg/kg every 3 weeks (HR, 0.71; 95% CI, 0.58-0.88; P less than .001) or pembrolizumab 10 mg/kg every 3 weeks (HR, 0.61; 95% CI, 0.49-0.75; P less than .001) had an improved overall survival, compared with patients receiving docetaxel. The median survival was 10.4 months in the pembrolizumab 2 mg/kg arm, 12.7 months in the pembrolizumab 10 mg/kg arm, and 8.5 months in the docetaxel arm.
The most common side effects of treatment with pembrolizumab included decreased appetite, fatigue, nausea, dyspnea, cough, and constipation. Rare but serious adverse events included immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis, the FDA said.
The recommended dose and schedule of pembrolizumab for NSCLC is 200 mg intravenously every 3 weeks. Full prescribing information is available here.
The Food and Drug Administration has approved pembrolizumab for the treatment of patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test. This is the first approval of a checkpoint inhibitor for first-line treatment of the disease.
Pembrolizumab (Keytruda) is now approved to treat patients with metastatic NSCLC whose tumors have high PD-L1 expression (Tumor Proportion Score [TPS] greater than or equal to 50%), with no EGFR or ALK genomic tumor aberrations, and no prior systemic chemotherapy treatment for metastatic NSCLC, the FDA said in a written statement.
The FDA based its approval on improvement in overall survival in two trials comparing treatment with pembrolizumab to treatment from chemotherapy. In one trial of 305 patients who had no prior treatment for metastatic NSCLC and TPS greater than or equal to 50%, those who received pembrolizumab (200 mg every 3 weeks) had a statistically significant improvement in overall survival, compared with patients randomized to receive chemotherapy (hazard ratio, 0.60; 95% confidence interval, 0.41-0.89; P less than .005). There was also significant improvement in progression-free survival for those receiving the checkpoint inhibitor (HR, 0.50; 95% CI, 0.37-0.68; P less than .001).
In the second trial, a three-arm trial of 1,033 patients who were previously treated for metastatic NSCLC with a TPS greater than or equal to 1%, those randomized to pembrolizumab 2 mg/kg every 3 weeks (HR, 0.71; 95% CI, 0.58-0.88; P less than .001) or pembrolizumab 10 mg/kg every 3 weeks (HR, 0.61; 95% CI, 0.49-0.75; P less than .001) had an improved overall survival, compared with patients receiving docetaxel. The median survival was 10.4 months in the pembrolizumab 2 mg/kg arm, 12.7 months in the pembrolizumab 10 mg/kg arm, and 8.5 months in the docetaxel arm.
The most common side effects of treatment with pembrolizumab included decreased appetite, fatigue, nausea, dyspnea, cough, and constipation. Rare but serious adverse events included immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis, the FDA said.
The recommended dose and schedule of pembrolizumab for NSCLC is 200 mg intravenously every 3 weeks. Full prescribing information is available here.
The Food and Drug Administration has approved pembrolizumab for the treatment of patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test. This is the first approval of a checkpoint inhibitor for first-line treatment of the disease.
Pembrolizumab (Keytruda) is now approved to treat patients with metastatic NSCLC whose tumors have high PD-L1 expression (Tumor Proportion Score [TPS] greater than or equal to 50%), with no EGFR or ALK genomic tumor aberrations, and no prior systemic chemotherapy treatment for metastatic NSCLC, the FDA said in a written statement.
The FDA based its approval on improvement in overall survival in two trials comparing treatment with pembrolizumab to treatment from chemotherapy. In one trial of 305 patients who had no prior treatment for metastatic NSCLC and TPS greater than or equal to 50%, those who received pembrolizumab (200 mg every 3 weeks) had a statistically significant improvement in overall survival, compared with patients randomized to receive chemotherapy (hazard ratio, 0.60; 95% confidence interval, 0.41-0.89; P less than .005). There was also significant improvement in progression-free survival for those receiving the checkpoint inhibitor (HR, 0.50; 95% CI, 0.37-0.68; P less than .001).
In the second trial, a three-arm trial of 1,033 patients who were previously treated for metastatic NSCLC with a TPS greater than or equal to 1%, those randomized to pembrolizumab 2 mg/kg every 3 weeks (HR, 0.71; 95% CI, 0.58-0.88; P less than .001) or pembrolizumab 10 mg/kg every 3 weeks (HR, 0.61; 95% CI, 0.49-0.75; P less than .001) had an improved overall survival, compared with patients receiving docetaxel. The median survival was 10.4 months in the pembrolizumab 2 mg/kg arm, 12.7 months in the pembrolizumab 10 mg/kg arm, and 8.5 months in the docetaxel arm.
The most common side effects of treatment with pembrolizumab included decreased appetite, fatigue, nausea, dyspnea, cough, and constipation. Rare but serious adverse events included immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis, the FDA said.
The recommended dose and schedule of pembrolizumab for NSCLC is 200 mg intravenously every 3 weeks. Full prescribing information is available here.
Inhaled antibiotic for bronchiectasis shows promise
AT CHEST 2016
LOS ANGELES – Long-term inhaled ciprofloxacin therapy appears to be a safe and effective treatment option in patients with bronchiectasis, results from an international phase III trial showed.
“This is really exciting; it’s the first large study of an inhaled antibiotic to show a benefit in this population,” study investigator Kevin Winthrop, MD, said in an interview prior to the annual meeting of the American College of Chest Physicians. “There’s a tremendous unmet need and a lot of these patients have daily struggles and their quality of life is low. To have something that would improve that would be a benefit for patients and physicians alike.”
Compared with patients in the placebo arm, those in the ciprofloxacin dry powder for inhalation (DPI) 14-day on/off arm experienced a significantly prolonged time to first exacerbation (a mean of 336 days versus 186 days, respectively; adjusted hazard ratio, 0.53; P = .0005) and a significantly reduced exacerbation frequency over 48 weeks (a mean of 0.78 vs. 1.42; adjusted incident rate of 0.61; P = .0061). A nonsignificant trend in favor of ciprofloxacin DPI was observed for both primary endpoints among patients in the 28-day on/off arm (time to first exacerbation: HR, 0.73; P = .065; frequency of exacerbations: adjusted incidence rate ratio, 0.98; P = .89).
Treatment-emergent adverse events and adverse events leading to discontinuation were similar across treatment groups (82% in the ciprofloxacin DPI 14-day on/off arm, 83% in the ciprofloxacin DPI 28-day on/off arm, and 83% in the pooled placebo arm. The rates of serious adverse events were also similar in the three treatment groups (17%, 20%, and 23%, respectively). “Tolerability markers like hoarseness, bronchospasm, shortness of breath, or increased cough were similar between the treatment arms,” said Dr. Winthrop, who is an infectious diseases specialist at Oregon Health and Science University, Portland.“The safety profile looks really good. There were no typical fluoroquinolone types of problems such as tendinopathy reported.”
A follow-up trial known as RESPIRE 2 is ongoing. RESPIRE 1 was funded by Bayer. Dr. Winthrop disclosed that he is a consultant for the company.
This article was updated on 10/25/2016 at 9:51 AM Est
AT CHEST 2016
LOS ANGELES – Long-term inhaled ciprofloxacin therapy appears to be a safe and effective treatment option in patients with bronchiectasis, results from an international phase III trial showed.
“This is really exciting; it’s the first large study of an inhaled antibiotic to show a benefit in this population,” study investigator Kevin Winthrop, MD, said in an interview prior to the annual meeting of the American College of Chest Physicians. “There’s a tremendous unmet need and a lot of these patients have daily struggles and their quality of life is low. To have something that would improve that would be a benefit for patients and physicians alike.”
Compared with patients in the placebo arm, those in the ciprofloxacin dry powder for inhalation (DPI) 14-day on/off arm experienced a significantly prolonged time to first exacerbation (a mean of 336 days versus 186 days, respectively; adjusted hazard ratio, 0.53; P = .0005) and a significantly reduced exacerbation frequency over 48 weeks (a mean of 0.78 vs. 1.42; adjusted incident rate of 0.61; P = .0061). A nonsignificant trend in favor of ciprofloxacin DPI was observed for both primary endpoints among patients in the 28-day on/off arm (time to first exacerbation: HR, 0.73; P = .065; frequency of exacerbations: adjusted incidence rate ratio, 0.98; P = .89).
Treatment-emergent adverse events and adverse events leading to discontinuation were similar across treatment groups (82% in the ciprofloxacin DPI 14-day on/off arm, 83% in the ciprofloxacin DPI 28-day on/off arm, and 83% in the pooled placebo arm. The rates of serious adverse events were also similar in the three treatment groups (17%, 20%, and 23%, respectively). “Tolerability markers like hoarseness, bronchospasm, shortness of breath, or increased cough were similar between the treatment arms,” said Dr. Winthrop, who is an infectious diseases specialist at Oregon Health and Science University, Portland.“The safety profile looks really good. There were no typical fluoroquinolone types of problems such as tendinopathy reported.”
A follow-up trial known as RESPIRE 2 is ongoing. RESPIRE 1 was funded by Bayer. Dr. Winthrop disclosed that he is a consultant for the company.
This article was updated on 10/25/2016 at 9:51 AM Est
AT CHEST 2016
LOS ANGELES – Long-term inhaled ciprofloxacin therapy appears to be a safe and effective treatment option in patients with bronchiectasis, results from an international phase III trial showed.
“This is really exciting; it’s the first large study of an inhaled antibiotic to show a benefit in this population,” study investigator Kevin Winthrop, MD, said in an interview prior to the annual meeting of the American College of Chest Physicians. “There’s a tremendous unmet need and a lot of these patients have daily struggles and their quality of life is low. To have something that would improve that would be a benefit for patients and physicians alike.”
Compared with patients in the placebo arm, those in the ciprofloxacin dry powder for inhalation (DPI) 14-day on/off arm experienced a significantly prolonged time to first exacerbation (a mean of 336 days versus 186 days, respectively; adjusted hazard ratio, 0.53; P = .0005) and a significantly reduced exacerbation frequency over 48 weeks (a mean of 0.78 vs. 1.42; adjusted incident rate of 0.61; P = .0061). A nonsignificant trend in favor of ciprofloxacin DPI was observed for both primary endpoints among patients in the 28-day on/off arm (time to first exacerbation: HR, 0.73; P = .065; frequency of exacerbations: adjusted incidence rate ratio, 0.98; P = .89).
Treatment-emergent adverse events and adverse events leading to discontinuation were similar across treatment groups (82% in the ciprofloxacin DPI 14-day on/off arm, 83% in the ciprofloxacin DPI 28-day on/off arm, and 83% in the pooled placebo arm. The rates of serious adverse events were also similar in the three treatment groups (17%, 20%, and 23%, respectively). “Tolerability markers like hoarseness, bronchospasm, shortness of breath, or increased cough were similar between the treatment arms,” said Dr. Winthrop, who is an infectious diseases specialist at Oregon Health and Science University, Portland.“The safety profile looks really good. There were no typical fluoroquinolone types of problems such as tendinopathy reported.”
A follow-up trial known as RESPIRE 2 is ongoing. RESPIRE 1 was funded by Bayer. Dr. Winthrop disclosed that he is a consultant for the company.
This article was updated on 10/25/2016 at 9:51 AM Est
Key clinical point:
Major finding: Compared with patients in the placebo arm, those in the ciprofloxacin 14-day on/off arm experienced a significantly prolonged time to first exacerbation (a mean of 336 days vs. 186 days, respectively; adjusted hazard ratio, 0.53; P = .0005).
Data source: A multicenter study of 416 patients who were randomized 2:1 to ciprofloxacin 32.5 mg or placebo administered twice per day using a pocket-sized inhaler as a cyclical regimen of either 14 days on/off drug or 28 days on/off drug, for 48 weeks.
Disclosures: RESPIRE 1 was funded by Bayer. Dr. Winthrop disclosed that he is a consultant for the company.
Lung cancer screening found effective in a community hospital
LOS ANGELES – Lung cancer screening with low-dose CT scans in a community hospital setting replicates results from international and multicenter trials when it comes to diagnosing early-stage lung cancer, findings from a single-center study showed.
“It’s too early in our experience to say that we’re saving lives, but the fact that we’re detecting early lung cancers in the predicted percentages is good for community hospitals that are wondering, ‘Is it worth it to screen for lung cancer? Can we do it?’ ” Richard P. Salzano Jr., MD, said in an interview in advance of the annual meeting of the American College of Chest Physicians.
In July 2013, the 130-bed Griffin Hospital launched a lung cancer screening program codirected by a pulmonologist and a cardiothoracic surgeon. All low-dose CT scans were read by two designated radiologists. Dr. Salzano reported results from 514 patients enrolled in the program between July 2013 and December 2015. A total of nine lung cancers were detected. Seven (78%) were stage I or II lung cancers, and the remaining two (22%) were stage II or IV, results that are in line with data from the I-ELCAP and NLST trials.
In another component of the study, the researchers randomly selected 101 patients from the lung cancer screening program to answer questions by telephone intended to quantify their anxiety about lung cancer before and after participating in the program, attitudes about smoking behaviors, and general impressions of the screening process. On a scale of 0-10, with 10 being “very anxious,” Dr. Salzano reported that the mean anxiety level about lung cancer fell from a level of 4.69 before screening to 3.87 afterward, a difference that reached statistical significance, with a P value of .014. “None of the patients reported negative impacts of the program,” he added. “They reported a general improvement in their well-being as a result of participating in the program.” In addition, of the 53 respondents who were current smokers upon enrolling in the screening program, five quit after intake, and the remaining 48 indicated that they were “more likely to quit” as a result of being enrolled.
“Community hospitals need to embrace lung screening,” Dr. Salzano concluded. “The findings from the large studies are transferable. It’s helping your patients in terms of their attitudes about lung cancer, about smoking cessation, and about improving their wellness.”
He reported having no relevant financial disclosures.
LOS ANGELES – Lung cancer screening with low-dose CT scans in a community hospital setting replicates results from international and multicenter trials when it comes to diagnosing early-stage lung cancer, findings from a single-center study showed.
“It’s too early in our experience to say that we’re saving lives, but the fact that we’re detecting early lung cancers in the predicted percentages is good for community hospitals that are wondering, ‘Is it worth it to screen for lung cancer? Can we do it?’ ” Richard P. Salzano Jr., MD, said in an interview in advance of the annual meeting of the American College of Chest Physicians.
In July 2013, the 130-bed Griffin Hospital launched a lung cancer screening program codirected by a pulmonologist and a cardiothoracic surgeon. All low-dose CT scans were read by two designated radiologists. Dr. Salzano reported results from 514 patients enrolled in the program between July 2013 and December 2015. A total of nine lung cancers were detected. Seven (78%) were stage I or II lung cancers, and the remaining two (22%) were stage II or IV, results that are in line with data from the I-ELCAP and NLST trials.
In another component of the study, the researchers randomly selected 101 patients from the lung cancer screening program to answer questions by telephone intended to quantify their anxiety about lung cancer before and after participating in the program, attitudes about smoking behaviors, and general impressions of the screening process. On a scale of 0-10, with 10 being “very anxious,” Dr. Salzano reported that the mean anxiety level about lung cancer fell from a level of 4.69 before screening to 3.87 afterward, a difference that reached statistical significance, with a P value of .014. “None of the patients reported negative impacts of the program,” he added. “They reported a general improvement in their well-being as a result of participating in the program.” In addition, of the 53 respondents who were current smokers upon enrolling in the screening program, five quit after intake, and the remaining 48 indicated that they were “more likely to quit” as a result of being enrolled.
“Community hospitals need to embrace lung screening,” Dr. Salzano concluded. “The findings from the large studies are transferable. It’s helping your patients in terms of their attitudes about lung cancer, about smoking cessation, and about improving their wellness.”
He reported having no relevant financial disclosures.
LOS ANGELES – Lung cancer screening with low-dose CT scans in a community hospital setting replicates results from international and multicenter trials when it comes to diagnosing early-stage lung cancer, findings from a single-center study showed.
“It’s too early in our experience to say that we’re saving lives, but the fact that we’re detecting early lung cancers in the predicted percentages is good for community hospitals that are wondering, ‘Is it worth it to screen for lung cancer? Can we do it?’ ” Richard P. Salzano Jr., MD, said in an interview in advance of the annual meeting of the American College of Chest Physicians.
In July 2013, the 130-bed Griffin Hospital launched a lung cancer screening program codirected by a pulmonologist and a cardiothoracic surgeon. All low-dose CT scans were read by two designated radiologists. Dr. Salzano reported results from 514 patients enrolled in the program between July 2013 and December 2015. A total of nine lung cancers were detected. Seven (78%) were stage I or II lung cancers, and the remaining two (22%) were stage II or IV, results that are in line with data from the I-ELCAP and NLST trials.
In another component of the study, the researchers randomly selected 101 patients from the lung cancer screening program to answer questions by telephone intended to quantify their anxiety about lung cancer before and after participating in the program, attitudes about smoking behaviors, and general impressions of the screening process. On a scale of 0-10, with 10 being “very anxious,” Dr. Salzano reported that the mean anxiety level about lung cancer fell from a level of 4.69 before screening to 3.87 afterward, a difference that reached statistical significance, with a P value of .014. “None of the patients reported negative impacts of the program,” he added. “They reported a general improvement in their well-being as a result of participating in the program.” In addition, of the 53 respondents who were current smokers upon enrolling in the screening program, five quit after intake, and the remaining 48 indicated that they were “more likely to quit” as a result of being enrolled.
“Community hospitals need to embrace lung screening,” Dr. Salzano concluded. “The findings from the large studies are transferable. It’s helping your patients in terms of their attitudes about lung cancer, about smoking cessation, and about improving their wellness.”
He reported having no relevant financial disclosures.
AT CHEST 2016
Key clinical point:
Major finding: Of nine lung cancers detected, seven (78%) were stage I or II lung cancers and the remaining two (22%) were stage II or IV.
Data source: Results from 514 patients enrolled in a community hospital–based lung cancer screening program between July 2013 and December 2015.
Disclosures: Dr. Salzano reported having no relevant financial disclosures.
Age of blood did not affect mortality in transfused patients
In-hospital mortality did not vary for patients who received transfusions of blood that had been stored for 2 weeks and for patients who got blood that had been stored for 4 weeks, based on results from 20,858 hospitalized patients in the randomized, controlled INFORM (Informing Fresh versus Old Red Cell Management) trial conducted at six hospitals in four countries.
While previous trials have concluded that the storage time of blood did not affect patient mortality, those studies largely included high-risk patients and were not statistically powered to detect small mortality differences, Nancy M. Heddle, professor of medicine and director of the McMaster (University) transfusion research program, Hamilton, Ont., and colleagues reported in an article published online in the New England Journal of Medicine (doi: 10.1056/NEJMoa1609014). Standard practice is to transfuse with the oldest available blood, which can be stored up to 42 days.
Their study included general hospitalized patients who required a red cell transfusion. From April 2012 through October 2015, patients were randomly assigned in a 1:2 ratio patients to receive blood that had been stored for the shortest duration (mean duration 13 days, 6,936 patients) or the longest duration (mean duration 23.6 days, 13,922 patients).
Only patients with type A or O blood were included in the study’s primary analysis, because of the difficulty of achieving a difference of at least 10 days in the mean duration of blood storage with other blood types.
There were 634 deaths (9.1% mortality) among patients in the short-term blood storage group and 1,213 deaths (8.7% mortality) in the long-term blood storage group. The difference was not statistically significant. Similar results were seen when the analysis was expanded to include all 24,736 patients with any blood type; the mortality rates were 9.1% and 8.8%, respectively.
An additional analysis found similar results in three prespecified high-risk subgroups – patients undergoing cardiovascular surgery, those admitted to intensive care, and those with cancer.
INFORM, Current Controlled Trials number ISRCTN08118744, was funded by the Canadian Institutes of Health Research, Canadian Blood Services, and Health Canada. Ms. Heddle had no relevant financial disclosures.
mdales@frontlinemedcom.com
On Twitter @maryjodales
The results of the INFORM trial should end the debate regarding whether short-term or long-term storage of blood is advantageous. However, questions remain about whether red cells transfused during the last allowed week of storage (35-42 days) pose more risk. Observational studies continue to raise concerns about the use of the oldest blood.
The INFORM trial, with its large numbers of patients, should permit researchers to analyze enough data to address this remaining issue. The transfusion medicine community needs to know whether the storage period should be reduced to less than 35 and whether new preservative solutions should be sought.
Aaron A.R. Tobian, MD, PhD, and Paul M. Ness, MD, are with the division of transfusion medicine, department of pathology, Johns Hopkins University, Baltimore. They had no relevant financial conflicts of interest and made their remarks in an editorial (10.1056/NEJMe1612444) that accompanied the published study.
The results of the INFORM trial should end the debate regarding whether short-term or long-term storage of blood is advantageous. However, questions remain about whether red cells transfused during the last allowed week of storage (35-42 days) pose more risk. Observational studies continue to raise concerns about the use of the oldest blood.
The INFORM trial, with its large numbers of patients, should permit researchers to analyze enough data to address this remaining issue. The transfusion medicine community needs to know whether the storage period should be reduced to less than 35 and whether new preservative solutions should be sought.
Aaron A.R. Tobian, MD, PhD, and Paul M. Ness, MD, are with the division of transfusion medicine, department of pathology, Johns Hopkins University, Baltimore. They had no relevant financial conflicts of interest and made their remarks in an editorial (10.1056/NEJMe1612444) that accompanied the published study.
The results of the INFORM trial should end the debate regarding whether short-term or long-term storage of blood is advantageous. However, questions remain about whether red cells transfused during the last allowed week of storage (35-42 days) pose more risk. Observational studies continue to raise concerns about the use of the oldest blood.
The INFORM trial, with its large numbers of patients, should permit researchers to analyze enough data to address this remaining issue. The transfusion medicine community needs to know whether the storage period should be reduced to less than 35 and whether new preservative solutions should be sought.
Aaron A.R. Tobian, MD, PhD, and Paul M. Ness, MD, are with the division of transfusion medicine, department of pathology, Johns Hopkins University, Baltimore. They had no relevant financial conflicts of interest and made their remarks in an editorial (10.1056/NEJMe1612444) that accompanied the published study.
In-hospital mortality did not vary for patients who received transfusions of blood that had been stored for 2 weeks and for patients who got blood that had been stored for 4 weeks, based on results from 20,858 hospitalized patients in the randomized, controlled INFORM (Informing Fresh versus Old Red Cell Management) trial conducted at six hospitals in four countries.
While previous trials have concluded that the storage time of blood did not affect patient mortality, those studies largely included high-risk patients and were not statistically powered to detect small mortality differences, Nancy M. Heddle, professor of medicine and director of the McMaster (University) transfusion research program, Hamilton, Ont., and colleagues reported in an article published online in the New England Journal of Medicine (doi: 10.1056/NEJMoa1609014). Standard practice is to transfuse with the oldest available blood, which can be stored up to 42 days.
Their study included general hospitalized patients who required a red cell transfusion. From April 2012 through October 2015, patients were randomly assigned in a 1:2 ratio patients to receive blood that had been stored for the shortest duration (mean duration 13 days, 6,936 patients) or the longest duration (mean duration 23.6 days, 13,922 patients).
Only patients with type A or O blood were included in the study’s primary analysis, because of the difficulty of achieving a difference of at least 10 days in the mean duration of blood storage with other blood types.
There were 634 deaths (9.1% mortality) among patients in the short-term blood storage group and 1,213 deaths (8.7% mortality) in the long-term blood storage group. The difference was not statistically significant. Similar results were seen when the analysis was expanded to include all 24,736 patients with any blood type; the mortality rates were 9.1% and 8.8%, respectively.
An additional analysis found similar results in three prespecified high-risk subgroups – patients undergoing cardiovascular surgery, those admitted to intensive care, and those with cancer.
INFORM, Current Controlled Trials number ISRCTN08118744, was funded by the Canadian Institutes of Health Research, Canadian Blood Services, and Health Canada. Ms. Heddle had no relevant financial disclosures.
mdales@frontlinemedcom.com
On Twitter @maryjodales
In-hospital mortality did not vary for patients who received transfusions of blood that had been stored for 2 weeks and for patients who got blood that had been stored for 4 weeks, based on results from 20,858 hospitalized patients in the randomized, controlled INFORM (Informing Fresh versus Old Red Cell Management) trial conducted at six hospitals in four countries.
While previous trials have concluded that the storage time of blood did not affect patient mortality, those studies largely included high-risk patients and were not statistically powered to detect small mortality differences, Nancy M. Heddle, professor of medicine and director of the McMaster (University) transfusion research program, Hamilton, Ont., and colleagues reported in an article published online in the New England Journal of Medicine (doi: 10.1056/NEJMoa1609014). Standard practice is to transfuse with the oldest available blood, which can be stored up to 42 days.
Their study included general hospitalized patients who required a red cell transfusion. From April 2012 through October 2015, patients were randomly assigned in a 1:2 ratio patients to receive blood that had been stored for the shortest duration (mean duration 13 days, 6,936 patients) or the longest duration (mean duration 23.6 days, 13,922 patients).
Only patients with type A or O blood were included in the study’s primary analysis, because of the difficulty of achieving a difference of at least 10 days in the mean duration of blood storage with other blood types.
There were 634 deaths (9.1% mortality) among patients in the short-term blood storage group and 1,213 deaths (8.7% mortality) in the long-term blood storage group. The difference was not statistically significant. Similar results were seen when the analysis was expanded to include all 24,736 patients with any blood type; the mortality rates were 9.1% and 8.8%, respectively.
An additional analysis found similar results in three prespecified high-risk subgroups – patients undergoing cardiovascular surgery, those admitted to intensive care, and those with cancer.
INFORM, Current Controlled Trials number ISRCTN08118744, was funded by the Canadian Institutes of Health Research, Canadian Blood Services, and Health Canada. Ms. Heddle had no relevant financial disclosures.
mdales@frontlinemedcom.com
On Twitter @maryjodales
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: There were 634 deaths (9.1% mortality) among patients in the short-term blood storage group and 1,213 deaths (8.7% mortality) in the long-term blood storage group.
Data source: The randomized, controlled INFORM (Informing Fresh versus Old Red Cell Management) trial.
Disclosures: INFORM, Current Controlled Trials number ISRCTN08118744, was funded by the Canadian Institutes of Health Research, Canadian Blood Services, and Health Canada. Ms. Heddle had no relevant financial disclosures.
FDA approves atezolizumab for advanced NSCLC
The Food and Drug Administration has approved the programmed death-ligand 1 (PD-L1) blocking antibody atezolizumab for the treatment of patients with metastatic non–small cell lung cancer (NSCLC) whose disease has progressed during or following platinum-containing chemotherapy.
The FDA previously approved atezolizumab (Tecentriq) for the treatment of locally advanced or metastatic urothelial carcinoma that has progressed after platinum-containing chemotherapy.
Approval for treatment of NSCLC was based on results from the phase III OAK and phase II POPLAR trials that enrolled a total of 1,137 patients with NSCLC whose disease had progressed on platinum-containing chemotherapy. In OAK, median overall survival for patients assigned to atezolizumab was 13.8 months, compared with 9.6 months for patients assigned to docetaxel, as recently reported at the European Society for Medical Oncology Congress.
In POPLAR, overall survival was 12.6 months for patients receiving atezolizumab versus 9.7 months for those assigned to docetaxel, as reported at the European Cancer Congress in 2015.
The most common (greater than or equal to 20%) adverse reactions in patients treated with atezolizumab were fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation, according to the FDA website. The most common (greater than or equal to 2%) grade 3-4 adverse events in patients treated with atezolizumab were dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, AST increase, ALT increase, dysphagia, and arthralgia. Clinically significant immune-related adverse events for patients receiving atezolizumab have included pneumonitis, hepatitis, colitis, and thyroid disease.
The recommended dose is 1,200 mg administered as an intravenous infusion over 60 minutes every 3 weeks until disease progression or unacceptable toxicity.
Patients with EGFR or ALK genomic tumor aberrations should not receive atezolizumab before having disease progression on FDA-approved therapy for these aberrations, the FDA said.
Full prescribing information is available on the FDA website.
The Food and Drug Administration has approved the programmed death-ligand 1 (PD-L1) blocking antibody atezolizumab for the treatment of patients with metastatic non–small cell lung cancer (NSCLC) whose disease has progressed during or following platinum-containing chemotherapy.
The FDA previously approved atezolizumab (Tecentriq) for the treatment of locally advanced or metastatic urothelial carcinoma that has progressed after platinum-containing chemotherapy.
Approval for treatment of NSCLC was based on results from the phase III OAK and phase II POPLAR trials that enrolled a total of 1,137 patients with NSCLC whose disease had progressed on platinum-containing chemotherapy. In OAK, median overall survival for patients assigned to atezolizumab was 13.8 months, compared with 9.6 months for patients assigned to docetaxel, as recently reported at the European Society for Medical Oncology Congress.
In POPLAR, overall survival was 12.6 months for patients receiving atezolizumab versus 9.7 months for those assigned to docetaxel, as reported at the European Cancer Congress in 2015.
The most common (greater than or equal to 20%) adverse reactions in patients treated with atezolizumab were fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation, according to the FDA website. The most common (greater than or equal to 2%) grade 3-4 adverse events in patients treated with atezolizumab were dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, AST increase, ALT increase, dysphagia, and arthralgia. Clinically significant immune-related adverse events for patients receiving atezolizumab have included pneumonitis, hepatitis, colitis, and thyroid disease.
The recommended dose is 1,200 mg administered as an intravenous infusion over 60 minutes every 3 weeks until disease progression or unacceptable toxicity.
Patients with EGFR or ALK genomic tumor aberrations should not receive atezolizumab before having disease progression on FDA-approved therapy for these aberrations, the FDA said.
Full prescribing information is available on the FDA website.
The Food and Drug Administration has approved the programmed death-ligand 1 (PD-L1) blocking antibody atezolizumab for the treatment of patients with metastatic non–small cell lung cancer (NSCLC) whose disease has progressed during or following platinum-containing chemotherapy.
The FDA previously approved atezolizumab (Tecentriq) for the treatment of locally advanced or metastatic urothelial carcinoma that has progressed after platinum-containing chemotherapy.
Approval for treatment of NSCLC was based on results from the phase III OAK and phase II POPLAR trials that enrolled a total of 1,137 patients with NSCLC whose disease had progressed on platinum-containing chemotherapy. In OAK, median overall survival for patients assigned to atezolizumab was 13.8 months, compared with 9.6 months for patients assigned to docetaxel, as recently reported at the European Society for Medical Oncology Congress.
In POPLAR, overall survival was 12.6 months for patients receiving atezolizumab versus 9.7 months for those assigned to docetaxel, as reported at the European Cancer Congress in 2015.
The most common (greater than or equal to 20%) adverse reactions in patients treated with atezolizumab were fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation, according to the FDA website. The most common (greater than or equal to 2%) grade 3-4 adverse events in patients treated with atezolizumab were dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, AST increase, ALT increase, dysphagia, and arthralgia. Clinically significant immune-related adverse events for patients receiving atezolizumab have included pneumonitis, hepatitis, colitis, and thyroid disease.
The recommended dose is 1,200 mg administered as an intravenous infusion over 60 minutes every 3 weeks until disease progression or unacceptable toxicity.
Patients with EGFR or ALK genomic tumor aberrations should not receive atezolizumab before having disease progression on FDA-approved therapy for these aberrations, the FDA said.
Full prescribing information is available on the FDA website.