Hospitalist News (Archived)

SAN DIEGO – As the number of surgery patients over the age of 65 continues to burgeon, clinicians have a resource to help them provide optimal perioperative care to this patient population.

At the American College of Surgeons/National Surgical Quality Improvement Program National Conference, Ronnie A. Rosenthal, MD, discussed highlights from “Optimal Perioperative Management of the Geriatric Patient: A Best Practice Guideline from the ACS NSQIP/American Geriatrics Society,” which was published in January 2016.

Work on the guideline began in 2013, when a 28-member multidisciplinary panel began to conduct a structured search of Medline to identify systematic reviews, meta-analyses, practice guidelines, and clinical trials on the topic. The panel included experts from ACS, the ACS Geriatric Surgery Task Force, the American Society of Anesthesiologists, the American Geriatrics Society, and the AGS’ Geriatrics for Specialists Initiative. The 61-page document is divided into four categories: immediate preoperative period, intraoperative management, postoperative care, and care transitions.

Working with patients on goals

As noted in the guideline, a primary goal of the immediate preoperative period is to discuss with the patient his or her goals and expectations. Patient expectations are influenced by their treatment preferences. In fact, researchers have found that older patients are less likely to want a treatment – even if it results in cure – that may result in severe functional or cognitive impairment. For patients with existing advanced directives, organizations representing nurses, anesthesiologists, and surgeons all agree that there must be a “reconsideration” of these directives prior to surgery. A discussion that includes the new risks of the procedure must be conducted to ensure that the approach to potential life-threatening problems is consistent with the patient’s values.

Preoperative management of medications

Another recommendation for the preoperative period is to ensure that older patients have shorter fasts, have appropriate prophylactic antibiotics, continue medications with withdrawal potential, and discontinue medications that are not essential. The latter point is based on the Beers Criteria, a list of medications that are inappropriate or potentially inappropriate to use in older adults (J Am Geriatr Soc. 2015 Nov;63[11]:2227-46). “You want to discontinue as many inappropriate medications as possible, because one of the main side effects of their use is delirium, and you want to avoid that,” said Dr. Rosenthal, professor of surgery at the Yale University, New Haven, Conn., and one of the guideline authors.

©Thinkstockphotos.com

Anesthesia and pain management

Intraoperative management strategies contained in the guideline include establishing an anesthetic approach and a perioperative analgesia pain plan, preventing postoperative nausea and vomiting, assessing patient safety in the OR, preventing predictable complications, and optimizing fluid management. Physiologic effects of anesthesia medications include changes in systemic vascular resistance, cardiac preload, baroreceptor responses, lung mechanics, oxygen diffusion, neurotransmitter function, and end-organ blood flow, among others. “These physiologic changes of aging have significant clinical implications,” Dr. Rosenthal noted. “These are variable among individuals and variable among organ systems, and it’s important that we pay attention to that. Because of this variability, there is insufficient evidence to recommend a single ‘best’ anesthetic plan for all older adults.”

The guideline recommends that each patient have an individualized pain plan that consists of a directed pain history and physical exam and is appropriately titrated for increased sensitivity. “It should include a prophylactic bowel regimen for anybody who’s on an opioid in particular,” she said. “We should avoid inappropriate medications like benzodiazepines, and we should use a multimodal therapy with opioid-sparing and regional techniques.”

Pulmonary considerations for anesthesia include susceptibility to hypocarbia and hypoxemia, and susceptibility to residual anesthetic effects. “Because of physiologic changes, the anesthesia medications aren’t metabolized in the same way,” she said. “Older people may have lower drug requirements and may not recover as quickly from the effects of these drugs. This can lead to respiratory compromise and also can increase the risk of aspiration.” Strategies to prevent pulmonary complications include using regional anesthesia when possible and avoiding the use of intermediate- and long-acting neuromuscular blocking agents. Dr. Rosenthal said that there is insufficient evidence in the current medical literature to recommend a single “best” intraoperative fluid management plan for all older adults. “Part of the reason it’s so difficult is because of the cardiac physiologic changes [with aging],” she explained. “Older people are susceptible to volume overload. On the other hand, they also may have an exaggerated decline in cardiac function if you give them too little fluid and they have insufficient preload. It’s a very fine line and that’s why it’s hard to recommend a single best strategy.”

Be alert to postoperative delirium

Postoperatively, the guideline recommends that care plans include controlling perioperative acute pain; addressing delirium/cognitive issues; preventing functional decline, falls, pressure ulcers, and urinary track infections; maintaining adequate nutrition; and avoiding pulmonary complications. Dr. Rosenthal underscored the importance of using the four-question Short Confusion Assessment Method (Short CAM) to assess for delirium. “For it to be delirium, there has to be evidence of acute change in mental status from baseline; it has to be acute and fluctuating, and characterized by inattention,” she said. “The patient also has to have either disorganized thinking or an altered level of consciousness.”

Many of the precipitating factors of delirium can be prevented by treating pain, watching medications, preventing dehydration and undernutrition, removing catheters and other devices when possible, preventing constipation, and using minimally invasive techniques to reduce the physiologic stress of surgery. “Sometimes symptoms of delirium are a warning sign that something else is going on, such as an infection, hypoxemia, electrolyte imbalance, neurological events, and major organ dysfunction,” she said. The first-line therapy for treating delirium as recommended in the guideline is a multicomponent intervention that focuses on frequent reorientation with voice, calendars, and clocks; eliminating use of restraints; having familiar objects in the room; and ensuring the use of assistive devices. The second-line therapy is antipsychotic medications at the lowest effective dose. “The mantra is start low and go slow,” she said.

Preventing postoperative functional decline

Another postoperative strategy in the guideline involves targeted fall prevention, such as having an assistive device at the bedside if used as an outpatient and prescribing early physical therapy focused on maintaining mobility as the primary event. “Every day an older patient is immobilized it takes at least 3 days to regain the lost function,” Dr. Rosenthal said. “And for older surgical patients, one in four experiences a significant decline in function by hospital discharge and 60% experience some loss of independence.” (The latter statistic comes from a study published online July 13, 2016, in JAMA Surgery: doi:10.1001/jamasurg.2016.1689.) Interventions for preventing functional decline include promotion of family participation in care, early mobilization, early physical/occupational therapy referral, geriatric consultation, comprehensive discharge planning, and nutritional support. She pointed out that an estimated 40% of community-dwelling elders and two-thirds of nursing home residents are either malnourished or “at risk” of malnutrition.

Transition of care

The final category in the guideline, transition of care, recommends an assessment of social support/home health needs, complete medication review, predischarge geriatric assessment, formal written discharge instructions, and communication with the patient’s primary care physician. “Common models of transitional care involve good coordination with the primary care physician,” she said. “There’s good data to show that people who see their primary care physician within 2 weeks of discharge do better in terms of readmission.”

Dr. Rosenthal reported having no financial disclosures.

[email protected]

SAN DIEGO – As the number of surgery patients over the age of 65 continues to burgeon, clinicians have a resource to help them provide optimal perioperative care to this patient population.

At the American College of Surgeons/National Surgical Quality Improvement Program National Conference, Ronnie A. Rosenthal, MD, discussed highlights from “Optimal Perioperative Management of the Geriatric Patient: A Best Practice Guideline from the ACS NSQIP/American Geriatrics Society,” which was published in January 2016.

Work on the guideline began in 2013, when a 28-member multidisciplinary panel began to conduct a structured search of Medline to identify systematic reviews, meta-analyses, practice guidelines, and clinical trials on the topic. The panel included experts from ACS, the ACS Geriatric Surgery Task Force, the American Society of Anesthesiologists, the American Geriatrics Society, and the AGS’ Geriatrics for Specialists Initiative. The 61-page document is divided into four categories: immediate preoperative period, intraoperative management, postoperative care, and care transitions.

Working with patients on goals

As noted in the guideline, a primary goal of the immediate preoperative period is to discuss with the patient his or her goals and expectations. Patient expectations are influenced by their treatment preferences. In fact, researchers have found that older patients are less likely to want a treatment – even if it results in cure – that may result in severe functional or cognitive impairment. For patients with existing advanced directives, organizations representing nurses, anesthesiologists, and surgeons all agree that there must be a “reconsideration” of these directives prior to surgery. A discussion that includes the new risks of the procedure must be conducted to ensure that the approach to potential life-threatening problems is consistent with the patient’s values.

Preoperative management of medications

Another recommendation for the preoperative period is to ensure that older patients have shorter fasts, have appropriate prophylactic antibiotics, continue medications with withdrawal potential, and discontinue medications that are not essential. The latter point is based on the Beers Criteria, a list of medications that are inappropriate or potentially inappropriate to use in older adults (J Am Geriatr Soc. 2015 Nov;63[11]:2227-46). “You want to discontinue as many inappropriate medications as possible, because one of the main side effects of their use is delirium, and you want to avoid that,” said Dr. Rosenthal, professor of surgery at the Yale University, New Haven, Conn., and one of the guideline authors.

©Thinkstockphotos.com

Anesthesia and pain management

Intraoperative management strategies contained in the guideline include establishing an anesthetic approach and a perioperative analgesia pain plan, preventing postoperative nausea and vomiting, assessing patient safety in the OR, preventing predictable complications, and optimizing fluid management. Physiologic effects of anesthesia medications include changes in systemic vascular resistance, cardiac preload, baroreceptor responses, lung mechanics, oxygen diffusion, neurotransmitter function, and end-organ blood flow, among others. “These physiologic changes of aging have significant clinical implications,” Dr. Rosenthal noted. “These are variable among individuals and variable among organ systems, and it’s important that we pay attention to that. Because of this variability, there is insufficient evidence to recommend a single ‘best’ anesthetic plan for all older adults.”

The guideline recommends that each patient have an individualized pain plan that consists of a directed pain history and physical exam and is appropriately titrated for increased sensitivity. “It should include a prophylactic bowel regimen for anybody who’s on an opioid in particular,” she said. “We should avoid inappropriate medications like benzodiazepines, and we should use a multimodal therapy with opioid-sparing and regional techniques.”

Pulmonary considerations for anesthesia include susceptibility to hypocarbia and hypoxemia, and susceptibility to residual anesthetic effects. “Because of physiologic changes, the anesthesia medications aren’t metabolized in the same way,” she said. “Older people may have lower drug requirements and may not recover as quickly from the effects of these drugs. This can lead to respiratory compromise and also can increase the risk of aspiration.” Strategies to prevent pulmonary complications include using regional anesthesia when possible and avoiding the use of intermediate- and long-acting neuromuscular blocking agents. Dr. Rosenthal said that there is insufficient evidence in the current medical literature to recommend a single “best” intraoperative fluid management plan for all older adults. “Part of the reason it’s so difficult is because of the cardiac physiologic changes [with aging],” she explained. “Older people are susceptible to volume overload. On the other hand, they also may have an exaggerated decline in cardiac function if you give them too little fluid and they have insufficient preload. It’s a very fine line and that’s why it’s hard to recommend a single best strategy.”

Be alert to postoperative delirium

Postoperatively, the guideline recommends that care plans include controlling perioperative acute pain; addressing delirium/cognitive issues; preventing functional decline, falls, pressure ulcers, and urinary track infections; maintaining adequate nutrition; and avoiding pulmonary complications. Dr. Rosenthal underscored the importance of using the four-question Short Confusion Assessment Method (Short CAM) to assess for delirium. “For it to be delirium, there has to be evidence of acute change in mental status from baseline; it has to be acute and fluctuating, and characterized by inattention,” she said. “The patient also has to have either disorganized thinking or an altered level of consciousness.”

Many of the precipitating factors of delirium can be prevented by treating pain, watching medications, preventing dehydration and undernutrition, removing catheters and other devices when possible, preventing constipation, and using minimally invasive techniques to reduce the physiologic stress of surgery. “Sometimes symptoms of delirium are a warning sign that something else is going on, such as an infection, hypoxemia, electrolyte imbalance, neurological events, and major organ dysfunction,” she said. The first-line therapy for treating delirium as recommended in the guideline is a multicomponent intervention that focuses on frequent reorientation with voice, calendars, and clocks; eliminating use of restraints; having familiar objects in the room; and ensuring the use of assistive devices. The second-line therapy is antipsychotic medications at the lowest effective dose. “The mantra is start low and go slow,” she said.

Preventing postoperative functional decline

Another postoperative strategy in the guideline involves targeted fall prevention, such as having an assistive device at the bedside if used as an outpatient and prescribing early physical therapy focused on maintaining mobility as the primary event. “Every day an older patient is immobilized it takes at least 3 days to regain the lost function,” Dr. Rosenthal said. “And for older surgical patients, one in four experiences a significant decline in function by hospital discharge and 60% experience some loss of independence.” (The latter statistic comes from a study published online July 13, 2016, in JAMA Surgery: doi:10.1001/jamasurg.2016.1689.) Interventions for preventing functional decline include promotion of family participation in care, early mobilization, early physical/occupational therapy referral, geriatric consultation, comprehensive discharge planning, and nutritional support. She pointed out that an estimated 40% of community-dwelling elders and two-thirds of nursing home residents are either malnourished or “at risk” of malnutrition.

Transition of care

The final category in the guideline, transition of care, recommends an assessment of social support/home health needs, complete medication review, predischarge geriatric assessment, formal written discharge instructions, and communication with the patient’s primary care physician. “Common models of transitional care involve good coordination with the primary care physician,” she said. “There’s good data to show that people who see their primary care physician within 2 weeks of discharge do better in terms of readmission.”

Dr. Rosenthal reported having no financial disclosures.

[email protected]

SAN DIEGO – As the number of surgery patients over the age of 65 continues to burgeon, clinicians have a resource to help them provide optimal perioperative care to this patient population.

At the American College of Surgeons/National Surgical Quality Improvement Program National Conference, Ronnie A. Rosenthal, MD, discussed highlights from “Optimal Perioperative Management of the Geriatric Patient: A Best Practice Guideline from the ACS NSQIP/American Geriatrics Society,” which was published in January 2016.

Work on the guideline began in 2013, when a 28-member multidisciplinary panel began to conduct a structured search of Medline to identify systematic reviews, meta-analyses, practice guidelines, and clinical trials on the topic. The panel included experts from ACS, the ACS Geriatric Surgery Task Force, the American Society of Anesthesiologists, the American Geriatrics Society, and the AGS’ Geriatrics for Specialists Initiative. The 61-page document is divided into four categories: immediate preoperative period, intraoperative management, postoperative care, and care transitions.

Working with patients on goals

As noted in the guideline, a primary goal of the immediate preoperative period is to discuss with the patient his or her goals and expectations. Patient expectations are influenced by their treatment preferences. In fact, researchers have found that older patients are less likely to want a treatment – even if it results in cure – that may result in severe functional or cognitive impairment. For patients with existing advanced directives, organizations representing nurses, anesthesiologists, and surgeons all agree that there must be a “reconsideration” of these directives prior to surgery. A discussion that includes the new risks of the procedure must be conducted to ensure that the approach to potential life-threatening problems is consistent with the patient’s values.

Preoperative management of medications

Another recommendation for the preoperative period is to ensure that older patients have shorter fasts, have appropriate prophylactic antibiotics, continue medications with withdrawal potential, and discontinue medications that are not essential. The latter point is based on the Beers Criteria, a list of medications that are inappropriate or potentially inappropriate to use in older adults (J Am Geriatr Soc. 2015 Nov;63[11]:2227-46). “You want to discontinue as many inappropriate medications as possible, because one of the main side effects of their use is delirium, and you want to avoid that,” said Dr. Rosenthal, professor of surgery at the Yale University, New Haven, Conn., and one of the guideline authors.

©Thinkstockphotos.com

Anesthesia and pain management

Intraoperative management strategies contained in the guideline include establishing an anesthetic approach and a perioperative analgesia pain plan, preventing postoperative nausea and vomiting, assessing patient safety in the OR, preventing predictable complications, and optimizing fluid management. Physiologic effects of anesthesia medications include changes in systemic vascular resistance, cardiac preload, baroreceptor responses, lung mechanics, oxygen diffusion, neurotransmitter function, and end-organ blood flow, among others. “These physiologic changes of aging have significant clinical implications,” Dr. Rosenthal noted. “These are variable among individuals and variable among organ systems, and it’s important that we pay attention to that. Because of this variability, there is insufficient evidence to recommend a single ‘best’ anesthetic plan for all older adults.”

The guideline recommends that each patient have an individualized pain plan that consists of a directed pain history and physical exam and is appropriately titrated for increased sensitivity. “It should include a prophylactic bowel regimen for anybody who’s on an opioid in particular,” she said. “We should avoid inappropriate medications like benzodiazepines, and we should use a multimodal therapy with opioid-sparing and regional techniques.”

Pulmonary considerations for anesthesia include susceptibility to hypocarbia and hypoxemia, and susceptibility to residual anesthetic effects. “Because of physiologic changes, the anesthesia medications aren’t metabolized in the same way,” she said. “Older people may have lower drug requirements and may not recover as quickly from the effects of these drugs. This can lead to respiratory compromise and also can increase the risk of aspiration.” Strategies to prevent pulmonary complications include using regional anesthesia when possible and avoiding the use of intermediate- and long-acting neuromuscular blocking agents. Dr. Rosenthal said that there is insufficient evidence in the current medical literature to recommend a single “best” intraoperative fluid management plan for all older adults. “Part of the reason it’s so difficult is because of the cardiac physiologic changes [with aging],” she explained. “Older people are susceptible to volume overload. On the other hand, they also may have an exaggerated decline in cardiac function if you give them too little fluid and they have insufficient preload. It’s a very fine line and that’s why it’s hard to recommend a single best strategy.”

Be alert to postoperative delirium

Postoperatively, the guideline recommends that care plans include controlling perioperative acute pain; addressing delirium/cognitive issues; preventing functional decline, falls, pressure ulcers, and urinary track infections; maintaining adequate nutrition; and avoiding pulmonary complications. Dr. Rosenthal underscored the importance of using the four-question Short Confusion Assessment Method (Short CAM) to assess for delirium. “For it to be delirium, there has to be evidence of acute change in mental status from baseline; it has to be acute and fluctuating, and characterized by inattention,” she said. “The patient also has to have either disorganized thinking or an altered level of consciousness.”

Many of the precipitating factors of delirium can be prevented by treating pain, watching medications, preventing dehydration and undernutrition, removing catheters and other devices when possible, preventing constipation, and using minimally invasive techniques to reduce the physiologic stress of surgery. “Sometimes symptoms of delirium are a warning sign that something else is going on, such as an infection, hypoxemia, electrolyte imbalance, neurological events, and major organ dysfunction,” she said. The first-line therapy for treating delirium as recommended in the guideline is a multicomponent intervention that focuses on frequent reorientation with voice, calendars, and clocks; eliminating use of restraints; having familiar objects in the room; and ensuring the use of assistive devices. The second-line therapy is antipsychotic medications at the lowest effective dose. “The mantra is start low and go slow,” she said.

Preventing postoperative functional decline

Another postoperative strategy in the guideline involves targeted fall prevention, such as having an assistive device at the bedside if used as an outpatient and prescribing early physical therapy focused on maintaining mobility as the primary event. “Every day an older patient is immobilized it takes at least 3 days to regain the lost function,” Dr. Rosenthal said. “And for older surgical patients, one in four experiences a significant decline in function by hospital discharge and 60% experience some loss of independence.” (The latter statistic comes from a study published online July 13, 2016, in JAMA Surgery: doi:10.1001/jamasurg.2016.1689.) Interventions for preventing functional decline include promotion of family participation in care, early mobilization, early physical/occupational therapy referral, geriatric consultation, comprehensive discharge planning, and nutritional support. She pointed out that an estimated 40% of community-dwelling elders and two-thirds of nursing home residents are either malnourished or “at risk” of malnutrition.

Transition of care

The final category in the guideline, transition of care, recommends an assessment of social support/home health needs, complete medication review, predischarge geriatric assessment, formal written discharge instructions, and communication with the patient’s primary care physician. “Common models of transitional care involve good coordination with the primary care physician,” she said. “There’s good data to show that people who see their primary care physician within 2 weeks of discharge do better in terms of readmission.”

Dr. Rosenthal reported having no financial disclosures.

[email protected]

ROME – LDL cholesterol treatment targets remain alive and well in non-U.S. lipid management guidelines.

New dyslipidemia management guidelines from the European Society of Cardiology, issued in late August, retain the same LDL cholesterol targets as the prior, 2011 guidelines, a sharp and purposeful departure from the “risk-based” U.S. guidelines introduced in 2013 that eliminated treating patients to specific LDL cholesterol targets.

Mitchel L. Zoler/Frontline Medical News

The new ESC guidelines also incorporated the new class of lipid-lowering drugs, PCSK9 inhibitors (evolocumab [Repatha] and alirocumab [Praluent]), into the treatment algorithm, and carved out a role for ezetimibe (Zetia) following its proven success as an add-on agent to statins (Eur Heart J. 2016. doi: 10.1093/eurheartj/ehw272).

But it’s retention of LDL cholesterol targets as a cornerstone of dyslipidemia management in the new ESC report, written jointly with the European Atherosclerosis Society, that especially distinguishes the new guidelines.

“It seemed to us logical that if you have drugs [statins] that lower LDL cholesterol, then you target LDL cholesterol,” explained Ian M. Graham, MD, professor of cardiovascular medicine at Trinity College in Dublin and cochair of the guidelines panel. “If a patient’s risk is high, they still need to lower LDL cholesterol. It’s not really contradictory to the U.S. approach,” Dr. Graham said in an interview.

Mitchel L. Zoler/Frontline Medical News

The ESC panel’s discussions about the LDL cholesterol targets were “difficult and long,” said Guy De Backer, MD, a member of the guidelines committee and professor of cardiology at the University of Ghent, Belgium, in a session devoted to the new guidelines during the annual congress of the ESC.

The ESC’s decision to retain the 2011 LDL cholesterol targets won praise from U.S. cardiologist Eugene Braunwald, MD. “I think that not measuring and following LDL cholesterol is silly. I don’t agree” with current U.S. guidelines, he said in a talk during the congress. “If you don’t follow LDL cholesterol then you don’t know a patient’s compliance.

Regularly measuring LDL cholesterol is important,” said Dr. Braunwald, professor of medicine at Harvard Medical School in Boston. But he questioned the LDL cholesterol targets set by the ESC panel, specifically the LDL cholesterol goal of less than 70 mg/dL for very-high-risk patients.

Mitchel L. Zoler/Frontline Medical News

“I don’t think the ESC went low enough; the goal should be less than 50 mg/dL,” declared Dr. Braunwald, who added “anything above 50 mg/dL is toxic.”

The new guidelines also made the definition of “very-high-risk” patients “stricter and more precise,” said Alberico L. Catapano, MD, cochair of the panel and professor of pharmacology at the University of Milan.

The guideline’s detailed list defining very-high-risk patients includes those with either clinical or “unequivocal” imaging evidence for cardiovascular disease, as well as patients with diabetes and target-organ damage, severe chronic kidney disease, or a 10% or greater 10-year risk for fatal cardiovascular disease calculated by the European Score risk formula.

The potent lipid-lowering PCSK9 inhibitors came onto the U.S. and European markets in 2015, labeled in the United States specifically for patients with familial hypercholesterolemia.

Mitchel L. Zoler/Frontline Medical News

In July 2016, an American College of Cardiology Task Force issued a model clinical-decision pathway for lowering LDL cholesterol levels that for the first time included the PCSK9 inhibitors, specified as a “may be considered” option for selected patients (J Am Coll Cardiol. 2016 Jul;68[1]:92-125). This consensus decision pathway was not a set of actual guidelines, which means the ESC revision is the first guideline to include the PCSK9 inhibitors. The panel took the same stance as the U.S. decision pathway and designated the PCSK9 inhibitors as a “may be considered” option.

Dr. Graham explained that this designation was driven by the current absence of evidence for clinical benefit from the large lipid-lowering effect of the PCSK9 antibodies, although trial results that address this are expected to appear very soon. Experts not on the guidelines panel agreed with this decision.

“We know that it’s crucial to await results from the clinical endpoint studies” before the guidelines committee makes a more forceful recommendation, commented Erik S.G. Stroes, MD, professor of vascular medicine at the Academic Medical Center in Amsterdam. He added, however, that many clinicians, himself included, have been pleased to offer PCSK9-inhibitor treatment to very-high-risk patients with no good alternatives for effectively lowering their LDL cholesterol to target levels, such as statin-intolerant patients or those with LDL cholesterol levels that remain high despite maximal therapy.

The current ESC guideline’s statement on when to use a PCSK9 inhibitor “is vague” said Dr. Braunwald. “Within the next year, we’ll have results from two huge trials that will show clinical outcomes. We know that PCSK9 inhibitors are extremely powerful at lowering LDL cholesterol, but I would like to see the loop closed” with proven effects on clinical outcomes. “I would bet 100 to 1 that they will be effective, but LDL cholesterol is just a surrogate marker, and you need to look in large populations before you make a guideline recommendation to use these drugs, so we’ll wait.”

Once the clinical value of treatment with PCSK9 inhibitors is settled, the next issue will be the cost of these drugs, something that will become a big consideration once they become more widely used, Dr. Braunwald added.

Dr. De Backer and Dr. Graham had no disclosures. Dr. Catapano has been a consultant to Aegerion, Amgen, AstraZeneca, Merck, Pfizer, and Sigma-Tau. Dr. Braunwald has been a consultant to Bayer, Daiichi Sankyo, the Medicines Company, Merck, Novartis, and Sanofi. Dr. Stroes has been a consultant to Amgen, Bristol-Myers Squibb, Merck, and Sanofi.

[email protected]

On Twitter @mitchelzoler

ROME – LDL cholesterol treatment targets remain alive and well in non-U.S. lipid management guidelines.

New dyslipidemia management guidelines from the European Society of Cardiology, issued in late August, retain the same LDL cholesterol targets as the prior, 2011 guidelines, a sharp and purposeful departure from the “risk-based” U.S. guidelines introduced in 2013 that eliminated treating patients to specific LDL cholesterol targets.

Mitchel L. Zoler/Frontline Medical News

The new ESC guidelines also incorporated the new class of lipid-lowering drugs, PCSK9 inhibitors (evolocumab [Repatha] and alirocumab [Praluent]), into the treatment algorithm, and carved out a role for ezetimibe (Zetia) following its proven success as an add-on agent to statins (Eur Heart J. 2016. doi: 10.1093/eurheartj/ehw272).

But it’s retention of LDL cholesterol targets as a cornerstone of dyslipidemia management in the new ESC report, written jointly with the European Atherosclerosis Society, that especially distinguishes the new guidelines.

“It seemed to us logical that if you have drugs [statins] that lower LDL cholesterol, then you target LDL cholesterol,” explained Ian M. Graham, MD, professor of cardiovascular medicine at Trinity College in Dublin and cochair of the guidelines panel. “If a patient’s risk is high, they still need to lower LDL cholesterol. It’s not really contradictory to the U.S. approach,” Dr. Graham said in an interview.

Mitchel L. Zoler/Frontline Medical News

The ESC panel’s discussions about the LDL cholesterol targets were “difficult and long,” said Guy De Backer, MD, a member of the guidelines committee and professor of cardiology at the University of Ghent, Belgium, in a session devoted to the new guidelines during the annual congress of the ESC.

The ESC’s decision to retain the 2011 LDL cholesterol targets won praise from U.S. cardiologist Eugene Braunwald, MD. “I think that not measuring and following LDL cholesterol is silly. I don’t agree” with current U.S. guidelines, he said in a talk during the congress. “If you don’t follow LDL cholesterol then you don’t know a patient’s compliance.

Regularly measuring LDL cholesterol is important,” said Dr. Braunwald, professor of medicine at Harvard Medical School in Boston. But he questioned the LDL cholesterol targets set by the ESC panel, specifically the LDL cholesterol goal of less than 70 mg/dL for very-high-risk patients.

Mitchel L. Zoler/Frontline Medical News

“I don’t think the ESC went low enough; the goal should be less than 50 mg/dL,” declared Dr. Braunwald, who added “anything above 50 mg/dL is toxic.”

The new guidelines also made the definition of “very-high-risk” patients “stricter and more precise,” said Alberico L. Catapano, MD, cochair of the panel and professor of pharmacology at the University of Milan.

The guideline’s detailed list defining very-high-risk patients includes those with either clinical or “unequivocal” imaging evidence for cardiovascular disease, as well as patients with diabetes and target-organ damage, severe chronic kidney disease, or a 10% or greater 10-year risk for fatal cardiovascular disease calculated by the European Score risk formula.

The potent lipid-lowering PCSK9 inhibitors came onto the U.S. and European markets in 2015, labeled in the United States specifically for patients with familial hypercholesterolemia.

Mitchel L. Zoler/Frontline Medical News

In July 2016, an American College of Cardiology Task Force issued a model clinical-decision pathway for lowering LDL cholesterol levels that for the first time included the PCSK9 inhibitors, specified as a “may be considered” option for selected patients (J Am Coll Cardiol. 2016 Jul;68[1]:92-125). This consensus decision pathway was not a set of actual guidelines, which means the ESC revision is the first guideline to include the PCSK9 inhibitors. The panel took the same stance as the U.S. decision pathway and designated the PCSK9 inhibitors as a “may be considered” option.

Dr. Graham explained that this designation was driven by the current absence of evidence for clinical benefit from the large lipid-lowering effect of the PCSK9 antibodies, although trial results that address this are expected to appear very soon. Experts not on the guidelines panel agreed with this decision.

“We know that it’s crucial to await results from the clinical endpoint studies” before the guidelines committee makes a more forceful recommendation, commented Erik S.G. Stroes, MD, professor of vascular medicine at the Academic Medical Center in Amsterdam. He added, however, that many clinicians, himself included, have been pleased to offer PCSK9-inhibitor treatment to very-high-risk patients with no good alternatives for effectively lowering their LDL cholesterol to target levels, such as statin-intolerant patients or those with LDL cholesterol levels that remain high despite maximal therapy.

The current ESC guideline’s statement on when to use a PCSK9 inhibitor “is vague” said Dr. Braunwald. “Within the next year, we’ll have results from two huge trials that will show clinical outcomes. We know that PCSK9 inhibitors are extremely powerful at lowering LDL cholesterol, but I would like to see the loop closed” with proven effects on clinical outcomes. “I would bet 100 to 1 that they will be effective, but LDL cholesterol is just a surrogate marker, and you need to look in large populations before you make a guideline recommendation to use these drugs, so we’ll wait.”

Once the clinical value of treatment with PCSK9 inhibitors is settled, the next issue will be the cost of these drugs, something that will become a big consideration once they become more widely used, Dr. Braunwald added.

Dr. De Backer and Dr. Graham had no disclosures. Dr. Catapano has been a consultant to Aegerion, Amgen, AstraZeneca, Merck, Pfizer, and Sigma-Tau. Dr. Braunwald has been a consultant to Bayer, Daiichi Sankyo, the Medicines Company, Merck, Novartis, and Sanofi. Dr. Stroes has been a consultant to Amgen, Bristol-Myers Squibb, Merck, and Sanofi.

[email protected]

On Twitter @mitchelzoler

ROME – LDL cholesterol treatment targets remain alive and well in non-U.S. lipid management guidelines.

New dyslipidemia management guidelines from the European Society of Cardiology, issued in late August, retain the same LDL cholesterol targets as the prior, 2011 guidelines, a sharp and purposeful departure from the “risk-based” U.S. guidelines introduced in 2013 that eliminated treating patients to specific LDL cholesterol targets.

Mitchel L. Zoler/Frontline Medical News

The new ESC guidelines also incorporated the new class of lipid-lowering drugs, PCSK9 inhibitors (evolocumab [Repatha] and alirocumab [Praluent]), into the treatment algorithm, and carved out a role for ezetimibe (Zetia) following its proven success as an add-on agent to statins (Eur Heart J. 2016. doi: 10.1093/eurheartj/ehw272).

But it’s retention of LDL cholesterol targets as a cornerstone of dyslipidemia management in the new ESC report, written jointly with the European Atherosclerosis Society, that especially distinguishes the new guidelines.

“It seemed to us logical that if you have drugs [statins] that lower LDL cholesterol, then you target LDL cholesterol,” explained Ian M. Graham, MD, professor of cardiovascular medicine at Trinity College in Dublin and cochair of the guidelines panel. “If a patient’s risk is high, they still need to lower LDL cholesterol. It’s not really contradictory to the U.S. approach,” Dr. Graham said in an interview.

Mitchel L. Zoler/Frontline Medical News

The ESC panel’s discussions about the LDL cholesterol targets were “difficult and long,” said Guy De Backer, MD, a member of the guidelines committee and professor of cardiology at the University of Ghent, Belgium, in a session devoted to the new guidelines during the annual congress of the ESC.

The ESC’s decision to retain the 2011 LDL cholesterol targets won praise from U.S. cardiologist Eugene Braunwald, MD. “I think that not measuring and following LDL cholesterol is silly. I don’t agree” with current U.S. guidelines, he said in a talk during the congress. “If you don’t follow LDL cholesterol then you don’t know a patient’s compliance.

Regularly measuring LDL cholesterol is important,” said Dr. Braunwald, professor of medicine at Harvard Medical School in Boston. But he questioned the LDL cholesterol targets set by the ESC panel, specifically the LDL cholesterol goal of less than 70 mg/dL for very-high-risk patients.

Mitchel L. Zoler/Frontline Medical News

“I don’t think the ESC went low enough; the goal should be less than 50 mg/dL,” declared Dr. Braunwald, who added “anything above 50 mg/dL is toxic.”

The new guidelines also made the definition of “very-high-risk” patients “stricter and more precise,” said Alberico L. Catapano, MD, cochair of the panel and professor of pharmacology at the University of Milan.

The guideline’s detailed list defining very-high-risk patients includes those with either clinical or “unequivocal” imaging evidence for cardiovascular disease, as well as patients with diabetes and target-organ damage, severe chronic kidney disease, or a 10% or greater 10-year risk for fatal cardiovascular disease calculated by the European Score risk formula.

The potent lipid-lowering PCSK9 inhibitors came onto the U.S. and European markets in 2015, labeled in the United States specifically for patients with familial hypercholesterolemia.

Mitchel L. Zoler/Frontline Medical News

In July 2016, an American College of Cardiology Task Force issued a model clinical-decision pathway for lowering LDL cholesterol levels that for the first time included the PCSK9 inhibitors, specified as a “may be considered” option for selected patients (J Am Coll Cardiol. 2016 Jul;68[1]:92-125). This consensus decision pathway was not a set of actual guidelines, which means the ESC revision is the first guideline to include the PCSK9 inhibitors. The panel took the same stance as the U.S. decision pathway and designated the PCSK9 inhibitors as a “may be considered” option.

Dr. Graham explained that this designation was driven by the current absence of evidence for clinical benefit from the large lipid-lowering effect of the PCSK9 antibodies, although trial results that address this are expected to appear very soon. Experts not on the guidelines panel agreed with this decision.

“We know that it’s crucial to await results from the clinical endpoint studies” before the guidelines committee makes a more forceful recommendation, commented Erik S.G. Stroes, MD, professor of vascular medicine at the Academic Medical Center in Amsterdam. He added, however, that many clinicians, himself included, have been pleased to offer PCSK9-inhibitor treatment to very-high-risk patients with no good alternatives for effectively lowering their LDL cholesterol to target levels, such as statin-intolerant patients or those with LDL cholesterol levels that remain high despite maximal therapy.

The current ESC guideline’s statement on when to use a PCSK9 inhibitor “is vague” said Dr. Braunwald. “Within the next year, we’ll have results from two huge trials that will show clinical outcomes. We know that PCSK9 inhibitors are extremely powerful at lowering LDL cholesterol, but I would like to see the loop closed” with proven effects on clinical outcomes. “I would bet 100 to 1 that they will be effective, but LDL cholesterol is just a surrogate marker, and you need to look in large populations before you make a guideline recommendation to use these drugs, so we’ll wait.”

Once the clinical value of treatment with PCSK9 inhibitors is settled, the next issue will be the cost of these drugs, something that will become a big consideration once they become more widely used, Dr. Braunwald added.

Dr. De Backer and Dr. Graham had no disclosures. Dr. Catapano has been a consultant to Aegerion, Amgen, AstraZeneca, Merck, Pfizer, and Sigma-Tau. Dr. Braunwald has been a consultant to Bayer, Daiichi Sankyo, the Medicines Company, Merck, Novartis, and Sanofi. Dr. Stroes has been a consultant to Amgen, Bristol-Myers Squibb, Merck, and Sanofi.

[email protected]

On Twitter @mitchelzoler

WAIKOLOA, HAWAII – The risk of anastomotic failure among emergency general surgery patients requiring bowel resection and anastomosis stands at 12.5% and is similar between stapled and hand-sewn techniques, results from a multicenter analysis demonstrated.

Surgeons participating in the study, known as Stapled vs. Handsewn: A Prospective Emergency Surgery Study (SHAPES), “appear to be performing hand-sewn techniques in patients who have a higher burden of disease,” Brandon R. Bruns, MD, said at the annual meeting of the American Association for the Surgery of Trauma. “Without adjustment and despite being performed in a more ill population, there was no difference in failure rate between hand-sewn and stapled techniques. After modeling, only being managed with an open abdomen and contamination at initial operation were associated with anastomotic failure.”

For SHAPES, which is the largest study of its kind and was sponsored by the AAST Multi-Institutional Studies Committee, Dr. Bruns and his associates set out to prospectively evaluate anastomotic failure rates for hand-sewn and stapled anastomoses in patients undergoing urgent/emergent operations. A 1999 study by Seattle researchers found that stapled techniques seemed to be associated with anastomotic failure (J Trauma. 1999;47[3]:500-08). Two years later, the same researchers pooled 4-year retrospective data from four trauma centers and concluded that again, hand-sewn techniques appeared to be superior to stapled techniques after traumatic bowel resection and anastomosis (J Trauma. 2001;51[6]:1054-61). Also in 2001, AAST sponsored a multi-institutional study that examined the same question, this time in penetrative colonic injury. Investigators found no difference in complications between the two groups (J Trauma. 2002;52[1]:117-21). They did, however, find a 22.7% overall incidence of colon-related complications.

“With this background we hypothesized that anastomotic failure rate would be high for emergency general surgery patients undergoing bowel resection and anastomosis,” said Dr. Bruns, an acute care surgeon at the R. Adams Cowley Shock Trauma Center at the University of Maryland Medical Center, Baltimore. “We also hypothesized that failure rates would be higher for stapled techniques, compared with hand-sewn.”

The SHAPES researchers prospectively enrolled 595 patients at 15 medical centers in the United States who underwent urgent/emergent bowel resection for emergency general surgery pathology between July 22, 2013, and Dec. 31, 2015. The patients were grouped by hand-sewn vs. stapled anastomoses and demographic and clinical variables were collected. The primary outcome was anastomotic failure. As in other studies, anastomotic failure was evaluated at the anastomosis level. Multivariable logistic regression was done, controlling for age and risk factors for anastomotic failure.

Dr. Bruns reported that the 595 patients had 649 anastomoses. Of these, 61% were stapled and 39% were hand-sewn. The mean age of patients was 62 years, 51% were male, and the overall mortality rate was 7.7%. More than two-thirds of the patients (35%) had more than one indication for operative intervention. The most common single indication for operation was small bowel obstruction, at 23%. The majority of the anastomoses were small bowel to small bowel (72%), while 21% were small bowel to large bowel, and 7% were large bowel to large bowel. There were a total of 81 anastomotic failures, for a rate of 12.5%.

When the researchers compared the hand-sewn and stapled groups, they were similar with respect to sex and age, with higher Charlson comorbidity indices in stapled and a higher body mass index in the hand-sewn group. They also observed a lower hemoglobin, higher INR, higher lactate, lower albumin, and worse renal function in the hand-sewn group, compared with the stapled group. Moreover, hand-sewn anastomotic techniques were performed more frequently in patients that were on vasopressor support. “Despite patients receiving hand-sewn techniques, having worse laboratory values, and more intraoperative vasopressors, the two techniques had equivalent failure rates, at 15.4% for hand-sewn and 10.6% for stapled,” Dr. Bruns said. “Patients with hand-sewn techniques had longer hospital length of stay, longer ICU length of stay, and a significantly higher mortality, compared with those who underwent stapled techniques. Interestingly and different from most other studies on the topic, operating time between the two groups was equivalent.”

On multivariate regression, the presence of contamination at initial bowel resection (OR 1.96) and the patient being managed with an open abdomen (OR 2.53) were independently associated with anastomotic failure, while the type of anastomosis (hand-sewn vs. stapled) was not.

The researchers also conducted a subanalysis of 165 patients managed with an open abdomen who had bowel resection and anastomosis. These patients had higher BMIs, higher lactates, higher INRs, and more negative base deficits, compared with those who were not managed with an open abdomen. “Perhaps not unexpectedly, open abdomen patients were more likely to be on vasopressor agents,” Dr. Bruns said. “They had longer hospital lengths of stay, more ICU days, and an 18.2% overall mortality. Overall there was an almost 22% anastomotic failure rate in patients managed with an open abdomen, compared with an 8.5% rate in patients managed with non-open techniques.” Comparing hand-sewn and stapled techniques, there was no difference in failure rate in patients managed with an open abdomen (25.2% vs. 17.5%, respectively; P = .20).

“An overall mortality rate of 8% and an anastomotic complication rate of 12.5% should emphasize the dire needs for these operations and the need for meticulous operative as well as surgically directed perioperative care in these patients,” the invited discussant, Gregory Jurkovich, MD, professor of surgery at the Davis Medical Center, University of California, said at the meeting. “We as surgeons must pay attention to all aspects of care in these patients.”

Dr. Bruns acknowledged certain limitations of the study, including the fact that it was not a randomized, controlled trial. Also, “surgeon preference did dictate the type of anastomosis that was created, and the patient and surgeon populations were heterogeneous,” he said. “The multivariable model was limited by missing laboratory data, likely given the urgent nature of some of the operative procedures.”

He reported having no financial disclosures.

[email protected]

WAIKOLOA, HAWAII – The risk of anastomotic failure among emergency general surgery patients requiring bowel resection and anastomosis stands at 12.5% and is similar between stapled and hand-sewn techniques, results from a multicenter analysis demonstrated.

Surgeons participating in the study, known as Stapled vs. Handsewn: A Prospective Emergency Surgery Study (SHAPES), “appear to be performing hand-sewn techniques in patients who have a higher burden of disease,” Brandon R. Bruns, MD, said at the annual meeting of the American Association for the Surgery of Trauma. “Without adjustment and despite being performed in a more ill population, there was no difference in failure rate between hand-sewn and stapled techniques. After modeling, only being managed with an open abdomen and contamination at initial operation were associated with anastomotic failure.”

For SHAPES, which is the largest study of its kind and was sponsored by the AAST Multi-Institutional Studies Committee, Dr. Bruns and his associates set out to prospectively evaluate anastomotic failure rates for hand-sewn and stapled anastomoses in patients undergoing urgent/emergent operations. A 1999 study by Seattle researchers found that stapled techniques seemed to be associated with anastomotic failure (J Trauma. 1999;47[3]:500-08). Two years later, the same researchers pooled 4-year retrospective data from four trauma centers and concluded that again, hand-sewn techniques appeared to be superior to stapled techniques after traumatic bowel resection and anastomosis (J Trauma. 2001;51[6]:1054-61). Also in 2001, AAST sponsored a multi-institutional study that examined the same question, this time in penetrative colonic injury. Investigators found no difference in complications between the two groups (J Trauma. 2002;52[1]:117-21). They did, however, find a 22.7% overall incidence of colon-related complications.

“With this background we hypothesized that anastomotic failure rate would be high for emergency general surgery patients undergoing bowel resection and anastomosis,” said Dr. Bruns, an acute care surgeon at the R. Adams Cowley Shock Trauma Center at the University of Maryland Medical Center, Baltimore. “We also hypothesized that failure rates would be higher for stapled techniques, compared with hand-sewn.”

The SHAPES researchers prospectively enrolled 595 patients at 15 medical centers in the United States who underwent urgent/emergent bowel resection for emergency general surgery pathology between July 22, 2013, and Dec. 31, 2015. The patients were grouped by hand-sewn vs. stapled anastomoses and demographic and clinical variables were collected. The primary outcome was anastomotic failure. As in other studies, anastomotic failure was evaluated at the anastomosis level. Multivariable logistic regression was done, controlling for age and risk factors for anastomotic failure.

Dr. Bruns reported that the 595 patients had 649 anastomoses. Of these, 61% were stapled and 39% were hand-sewn. The mean age of patients was 62 years, 51% were male, and the overall mortality rate was 7.7%. More than two-thirds of the patients (35%) had more than one indication for operative intervention. The most common single indication for operation was small bowel obstruction, at 23%. The majority of the anastomoses were small bowel to small bowel (72%), while 21% were small bowel to large bowel, and 7% were large bowel to large bowel. There were a total of 81 anastomotic failures, for a rate of 12.5%.

When the researchers compared the hand-sewn and stapled groups, they were similar with respect to sex and age, with higher Charlson comorbidity indices in stapled and a higher body mass index in the hand-sewn group. They also observed a lower hemoglobin, higher INR, higher lactate, lower albumin, and worse renal function in the hand-sewn group, compared with the stapled group. Moreover, hand-sewn anastomotic techniques were performed more frequently in patients that were on vasopressor support. “Despite patients receiving hand-sewn techniques, having worse laboratory values, and more intraoperative vasopressors, the two techniques had equivalent failure rates, at 15.4% for hand-sewn and 10.6% for stapled,” Dr. Bruns said. “Patients with hand-sewn techniques had longer hospital length of stay, longer ICU length of stay, and a significantly higher mortality, compared with those who underwent stapled techniques. Interestingly and different from most other studies on the topic, operating time between the two groups was equivalent.”

On multivariate regression, the presence of contamination at initial bowel resection (OR 1.96) and the patient being managed with an open abdomen (OR 2.53) were independently associated with anastomotic failure, while the type of anastomosis (hand-sewn vs. stapled) was not.

The researchers also conducted a subanalysis of 165 patients managed with an open abdomen who had bowel resection and anastomosis. These patients had higher BMIs, higher lactates, higher INRs, and more negative base deficits, compared with those who were not managed with an open abdomen. “Perhaps not unexpectedly, open abdomen patients were more likely to be on vasopressor agents,” Dr. Bruns said. “They had longer hospital lengths of stay, more ICU days, and an 18.2% overall mortality. Overall there was an almost 22% anastomotic failure rate in patients managed with an open abdomen, compared with an 8.5% rate in patients managed with non-open techniques.” Comparing hand-sewn and stapled techniques, there was no difference in failure rate in patients managed with an open abdomen (25.2% vs. 17.5%, respectively; P = .20).

“An overall mortality rate of 8% and an anastomotic complication rate of 12.5% should emphasize the dire needs for these operations and the need for meticulous operative as well as surgically directed perioperative care in these patients,” the invited discussant, Gregory Jurkovich, MD, professor of surgery at the Davis Medical Center, University of California, said at the meeting. “We as surgeons must pay attention to all aspects of care in these patients.”

Dr. Bruns acknowledged certain limitations of the study, including the fact that it was not a randomized, controlled trial. Also, “surgeon preference did dictate the type of anastomosis that was created, and the patient and surgeon populations were heterogeneous,” he said. “The multivariable model was limited by missing laboratory data, likely given the urgent nature of some of the operative procedures.”

He reported having no financial disclosures.

[email protected]

WAIKOLOA, HAWAII – The risk of anastomotic failure among emergency general surgery patients requiring bowel resection and anastomosis stands at 12.5% and is similar between stapled and hand-sewn techniques, results from a multicenter analysis demonstrated.

Surgeons participating in the study, known as Stapled vs. Handsewn: A Prospective Emergency Surgery Study (SHAPES), “appear to be performing hand-sewn techniques in patients who have a higher burden of disease,” Brandon R. Bruns, MD, said at the annual meeting of the American Association for the Surgery of Trauma. “Without adjustment and despite being performed in a more ill population, there was no difference in failure rate between hand-sewn and stapled techniques. After modeling, only being managed with an open abdomen and contamination at initial operation were associated with anastomotic failure.”

For SHAPES, which is the largest study of its kind and was sponsored by the AAST Multi-Institutional Studies Committee, Dr. Bruns and his associates set out to prospectively evaluate anastomotic failure rates for hand-sewn and stapled anastomoses in patients undergoing urgent/emergent operations. A 1999 study by Seattle researchers found that stapled techniques seemed to be associated with anastomotic failure (J Trauma. 1999;47[3]:500-08). Two years later, the same researchers pooled 4-year retrospective data from four trauma centers and concluded that again, hand-sewn techniques appeared to be superior to stapled techniques after traumatic bowel resection and anastomosis (J Trauma. 2001;51[6]:1054-61). Also in 2001, AAST sponsored a multi-institutional study that examined the same question, this time in penetrative colonic injury. Investigators found no difference in complications between the two groups (J Trauma. 2002;52[1]:117-21). They did, however, find a 22.7% overall incidence of colon-related complications.

“With this background we hypothesized that anastomotic failure rate would be high for emergency general surgery patients undergoing bowel resection and anastomosis,” said Dr. Bruns, an acute care surgeon at the R. Adams Cowley Shock Trauma Center at the University of Maryland Medical Center, Baltimore. “We also hypothesized that failure rates would be higher for stapled techniques, compared with hand-sewn.”

The SHAPES researchers prospectively enrolled 595 patients at 15 medical centers in the United States who underwent urgent/emergent bowel resection for emergency general surgery pathology between July 22, 2013, and Dec. 31, 2015. The patients were grouped by hand-sewn vs. stapled anastomoses and demographic and clinical variables were collected. The primary outcome was anastomotic failure. As in other studies, anastomotic failure was evaluated at the anastomosis level. Multivariable logistic regression was done, controlling for age and risk factors for anastomotic failure.

Dr. Bruns reported that the 595 patients had 649 anastomoses. Of these, 61% were stapled and 39% were hand-sewn. The mean age of patients was 62 years, 51% were male, and the overall mortality rate was 7.7%. More than two-thirds of the patients (35%) had more than one indication for operative intervention. The most common single indication for operation was small bowel obstruction, at 23%. The majority of the anastomoses were small bowel to small bowel (72%), while 21% were small bowel to large bowel, and 7% were large bowel to large bowel. There were a total of 81 anastomotic failures, for a rate of 12.5%.

When the researchers compared the hand-sewn and stapled groups, they were similar with respect to sex and age, with higher Charlson comorbidity indices in stapled and a higher body mass index in the hand-sewn group. They also observed a lower hemoglobin, higher INR, higher lactate, lower albumin, and worse renal function in the hand-sewn group, compared with the stapled group. Moreover, hand-sewn anastomotic techniques were performed more frequently in patients that were on vasopressor support. “Despite patients receiving hand-sewn techniques, having worse laboratory values, and more intraoperative vasopressors, the two techniques had equivalent failure rates, at 15.4% for hand-sewn and 10.6% for stapled,” Dr. Bruns said. “Patients with hand-sewn techniques had longer hospital length of stay, longer ICU length of stay, and a significantly higher mortality, compared with those who underwent stapled techniques. Interestingly and different from most other studies on the topic, operating time between the two groups was equivalent.”

On multivariate regression, the presence of contamination at initial bowel resection (OR 1.96) and the patient being managed with an open abdomen (OR 2.53) were independently associated with anastomotic failure, while the type of anastomosis (hand-sewn vs. stapled) was not.

The researchers also conducted a subanalysis of 165 patients managed with an open abdomen who had bowel resection and anastomosis. These patients had higher BMIs, higher lactates, higher INRs, and more negative base deficits, compared with those who were not managed with an open abdomen. “Perhaps not unexpectedly, open abdomen patients were more likely to be on vasopressor agents,” Dr. Bruns said. “They had longer hospital lengths of stay, more ICU days, and an 18.2% overall mortality. Overall there was an almost 22% anastomotic failure rate in patients managed with an open abdomen, compared with an 8.5% rate in patients managed with non-open techniques.” Comparing hand-sewn and stapled techniques, there was no difference in failure rate in patients managed with an open abdomen (25.2% vs. 17.5%, respectively; P = .20).

“An overall mortality rate of 8% and an anastomotic complication rate of 12.5% should emphasize the dire needs for these operations and the need for meticulous operative as well as surgically directed perioperative care in these patients,” the invited discussant, Gregory Jurkovich, MD, professor of surgery at the Davis Medical Center, University of California, said at the meeting. “We as surgeons must pay attention to all aspects of care in these patients.”

Dr. Bruns acknowledged certain limitations of the study, including the fact that it was not a randomized, controlled trial. Also, “surgeon preference did dictate the type of anastomosis that was created, and the patient and surgeon populations were heterogeneous,” he said. “The multivariable model was limited by missing laboratory data, likely given the urgent nature of some of the operative procedures.”

He reported having no financial disclosures.

[email protected]

Sepsis is the primary cause of death from infection. Early identification and treatment of sepsis is important in improving patient outcomes. The consensus conference sought to differentiate sepsis, which is defined as “life-threatening organ dysfunction caused by a dysregulated host response to infection” from uncomplicated infection.

Sepsis was last classified in a 2001 guideline that based its definition on the presence of two or more systemic inflammatory response syndrome (SIRS) criteria, which included an elevated temperature, heart rate higher than 90 bpm, respiratory rate higher than 20 breaths per minute, and a white blood cell count greater than greater than 12,000 mcL or less than 4,000 mcL or greater than 10% immature bands.

The problem with the SIRS definition of sepsis is that while it reflects a response to infection, it does not sufficiently distinguish between individuals with infections and those with a dysregulated response that leads to a poor prognosis, which is the definition of sepsis. The current consensus conference redefines sepsis with a more direct emphasis on organ dysfunction, as this is the aspect of sepsis that is most clearly linked to patient outcomes.

In the consensus conference document, sepsis is defined as a “life-threatening organ dysfunction caused by a dysregulated host response to infection.” The guidelines recommend using the quick version of the sequential (sepsis-related) organ failure assessment score (qSOFA) to identify patients with sepsis. In its long form, the SOFA used seven clinical and laboratory data points for completion, and is best suited to use in an intensive care setting where detailed data are available. The qSOFA score has only three criteria and by being easier to use can aid in rapid identification of sepsis and the patients most likely to deteriorate from sepsis.

The qSOFA criteria predict poor outcome in patients with infection who have two or more of the following: respiratory rate greater than or equal to 22 breaths/min, new or worsened altered mentation, or systolic blood pressure less than or equal to 100 mm Hg. Unlike the full SOFA score, the qSOFA does not require any laboratory testing and so can be performed in the office or bedside on a hospital floor. The qSOFA does not necessarily define sepsis, rather it identifies patients at a higher risk of hospital death or prolonged ICU stay. The consensus conference suggests that “qSOFA criteria be used to prompt clinicians to further investigate for organ dysfunction, initiate or escalate therapy as appropriate, and consider referral to critical care or increase the frequency of monitoring, if such actions have not already been undertaken.” The task force suggested that the qSOFA score may be a helpful adjunct to best clinical judgment for identifying patients who might benefit from a higher level of care.

Septic shock is defined as a subset of sepsis in which profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk for death than sepsis alone. Septic shock can be identified when, after adequate fluid resuscitation, the patient requires vasopressor therapy to maintain mean arterial pressure of at least 65 mm Hg and has a serum lactate level greater than 2 mmol/L.

Once sepsis is suspected, prompt therapy needs to be started as per the Surviving Sepsis Campaign Guidelines. The qSOFA criteria can be used to identify patients at high risk for morbidity and mortality. Within 3 hours, a lactate level should be obtained as well as blood cultures from two separate sites drawn prior to administration of antibiotics (but do not delay antibiotic administration). Empiric broad-spectrum antibiotics should be given within 45 minutes of the identification of sepsis. Antibiotic choice will vary per clinician/institution preference, but should likely include coverage for Pseudomonas and MRSA (piperacillin/tazobactam and vancomycin, for example). Antibiotics should be reassessed daily for de-escalation. Administer 30 mL/kg crystalloid for hypotension or lactate greater than or equal to 4 mmol/L. Within 6 hours, vasopressors should be given for hypotension that does not respond to initial fluid resuscitation to maintain a mean arterial pressure (MAP) of at least 65mm Hg. In the event of persistent hypotension after initial fluid administration (MAP under 65 mm Hg) or if initial lactate was greater than or equal to 4 mmol/L, volume status and tissue perfusion should be reassessed and lactate should be rechecked if it was initially elevated.

The bottom line

A 2016 international task force recommended that the definition of sepsis should be changed to emphasize organ dysfunction rather than a systemic inflammatory response. Use of the qSOFA score, which relies only on clinically observable data rather than laboratory evaluation, is recommended to identify patients at high risk for morbidity and mortality. Early recognition of sepsis and evaluation with qSOFT should facilitate early treatment and improve survival.

References

Singer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) FRCP; JAMA. 2016;315[8]:801-10. doi: 10.1001/jama.2016.0287.

Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003 Apr;31(4):1250-6.

Singer M, Deutschman CS, Seymour C, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016 Feb 23;315(8):801-10.

Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004 Mar;32(3):858-73.

Dr. Mills is assistant residency program director and assistant professor in the department of family and community medicine and department of physiology at Sidney Kimmel Medical College at Thomas Jefferson University. Dr. Botti is a second-year resident in the family medicine residency program department of family and community medicine at Sidney Kimmel Medical College at Thomas Jefferson University. Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia.

Sepsis is the primary cause of death from infection. Early identification and treatment of sepsis is important in improving patient outcomes. The consensus conference sought to differentiate sepsis, which is defined as “life-threatening organ dysfunction caused by a dysregulated host response to infection” from uncomplicated infection.

Sepsis was last classified in a 2001 guideline that based its definition on the presence of two or more systemic inflammatory response syndrome (SIRS) criteria, which included an elevated temperature, heart rate higher than 90 bpm, respiratory rate higher than 20 breaths per minute, and a white blood cell count greater than greater than 12,000 mcL or less than 4,000 mcL or greater than 10% immature bands.

The problem with the SIRS definition of sepsis is that while it reflects a response to infection, it does not sufficiently distinguish between individuals with infections and those with a dysregulated response that leads to a poor prognosis, which is the definition of sepsis. The current consensus conference redefines sepsis with a more direct emphasis on organ dysfunction, as this is the aspect of sepsis that is most clearly linked to patient outcomes.

In the consensus conference document, sepsis is defined as a “life-threatening organ dysfunction caused by a dysregulated host response to infection.” The guidelines recommend using the quick version of the sequential (sepsis-related) organ failure assessment score (qSOFA) to identify patients with sepsis. In its long form, the SOFA used seven clinical and laboratory data points for completion, and is best suited to use in an intensive care setting where detailed data are available. The qSOFA score has only three criteria and by being easier to use can aid in rapid identification of sepsis and the patients most likely to deteriorate from sepsis.

The qSOFA criteria predict poor outcome in patients with infection who have two or more of the following: respiratory rate greater than or equal to 22 breaths/min, new or worsened altered mentation, or systolic blood pressure less than or equal to 100 mm Hg. Unlike the full SOFA score, the qSOFA does not require any laboratory testing and so can be performed in the office or bedside on a hospital floor. The qSOFA does not necessarily define sepsis, rather it identifies patients at a higher risk of hospital death or prolonged ICU stay. The consensus conference suggests that “qSOFA criteria be used to prompt clinicians to further investigate for organ dysfunction, initiate or escalate therapy as appropriate, and consider referral to critical care or increase the frequency of monitoring, if such actions have not already been undertaken.” The task force suggested that the qSOFA score may be a helpful adjunct to best clinical judgment for identifying patients who might benefit from a higher level of care.

Septic shock is defined as a subset of sepsis in which profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk for death than sepsis alone. Septic shock can be identified when, after adequate fluid resuscitation, the patient requires vasopressor therapy to maintain mean arterial pressure of at least 65 mm Hg and has a serum lactate level greater than 2 mmol/L.

Once sepsis is suspected, prompt therapy needs to be started as per the Surviving Sepsis Campaign Guidelines. The qSOFA criteria can be used to identify patients at high risk for morbidity and mortality. Within 3 hours, a lactate level should be obtained as well as blood cultures from two separate sites drawn prior to administration of antibiotics (but do not delay antibiotic administration). Empiric broad-spectrum antibiotics should be given within 45 minutes of the identification of sepsis. Antibiotic choice will vary per clinician/institution preference, but should likely include coverage for Pseudomonas and MRSA (piperacillin/tazobactam and vancomycin, for example). Antibiotics should be reassessed daily for de-escalation. Administer 30 mL/kg crystalloid for hypotension or lactate greater than or equal to 4 mmol/L. Within 6 hours, vasopressors should be given for hypotension that does not respond to initial fluid resuscitation to maintain a mean arterial pressure (MAP) of at least 65mm Hg. In the event of persistent hypotension after initial fluid administration (MAP under 65 mm Hg) or if initial lactate was greater than or equal to 4 mmol/L, volume status and tissue perfusion should be reassessed and lactate should be rechecked if it was initially elevated.

The bottom line

A 2016 international task force recommended that the definition of sepsis should be changed to emphasize organ dysfunction rather than a systemic inflammatory response. Use of the qSOFA score, which relies only on clinically observable data rather than laboratory evaluation, is recommended to identify patients at high risk for morbidity and mortality. Early recognition of sepsis and evaluation with qSOFT should facilitate early treatment and improve survival.

References

Singer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) FRCP; JAMA. 2016;315[8]:801-10. doi: 10.1001/jama.2016.0287.

Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003 Apr;31(4):1250-6.

Singer M, Deutschman CS, Seymour C, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016 Feb 23;315(8):801-10.

Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004 Mar;32(3):858-73.

Dr. Mills is assistant residency program director and assistant professor in the department of family and community medicine and department of physiology at Sidney Kimmel Medical College at Thomas Jefferson University. Dr. Botti is a second-year resident in the family medicine residency program department of family and community medicine at Sidney Kimmel Medical College at Thomas Jefferson University. Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia.

Sepsis is the primary cause of death from infection. Early identification and treatment of sepsis is important in improving patient outcomes. The consensus conference sought to differentiate sepsis, which is defined as “life-threatening organ dysfunction caused by a dysregulated host response to infection” from uncomplicated infection.

Sepsis was last classified in a 2001 guideline that based its definition on the presence of two or more systemic inflammatory response syndrome (SIRS) criteria, which included an elevated temperature, heart rate higher than 90 bpm, respiratory rate higher than 20 breaths per minute, and a white blood cell count greater than greater than 12,000 mcL or less than 4,000 mcL or greater than 10% immature bands.

The problem with the SIRS definition of sepsis is that while it reflects a response to infection, it does not sufficiently distinguish between individuals with infections and those with a dysregulated response that leads to a poor prognosis, which is the definition of sepsis. The current consensus conference redefines sepsis with a more direct emphasis on organ dysfunction, as this is the aspect of sepsis that is most clearly linked to patient outcomes.

In the consensus conference document, sepsis is defined as a “life-threatening organ dysfunction caused by a dysregulated host response to infection.” The guidelines recommend using the quick version of the sequential (sepsis-related) organ failure assessment score (qSOFA) to identify patients with sepsis. In its long form, the SOFA used seven clinical and laboratory data points for completion, and is best suited to use in an intensive care setting where detailed data are available. The qSOFA score has only three criteria and by being easier to use can aid in rapid identification of sepsis and the patients most likely to deteriorate from sepsis.

The qSOFA criteria predict poor outcome in patients with infection who have two or more of the following: respiratory rate greater than or equal to 22 breaths/min, new or worsened altered mentation, or systolic blood pressure less than or equal to 100 mm Hg. Unlike the full SOFA score, the qSOFA does not require any laboratory testing and so can be performed in the office or bedside on a hospital floor. The qSOFA does not necessarily define sepsis, rather it identifies patients at a higher risk of hospital death or prolonged ICU stay. The consensus conference suggests that “qSOFA criteria be used to prompt clinicians to further investigate for organ dysfunction, initiate or escalate therapy as appropriate, and consider referral to critical care or increase the frequency of monitoring, if such actions have not already been undertaken.” The task force suggested that the qSOFA score may be a helpful adjunct to best clinical judgment for identifying patients who might benefit from a higher level of care.

Septic shock is defined as a subset of sepsis in which profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk for death than sepsis alone. Septic shock can be identified when, after adequate fluid resuscitation, the patient requires vasopressor therapy to maintain mean arterial pressure of at least 65 mm Hg and has a serum lactate level greater than 2 mmol/L.

Once sepsis is suspected, prompt therapy needs to be started as per the Surviving Sepsis Campaign Guidelines. The qSOFA criteria can be used to identify patients at high risk for morbidity and mortality. Within 3 hours, a lactate level should be obtained as well as blood cultures from two separate sites drawn prior to administration of antibiotics (but do not delay antibiotic administration). Empiric broad-spectrum antibiotics should be given within 45 minutes of the identification of sepsis. Antibiotic choice will vary per clinician/institution preference, but should likely include coverage for Pseudomonas and MRSA (piperacillin/tazobactam and vancomycin, for example). Antibiotics should be reassessed daily for de-escalation. Administer 30 mL/kg crystalloid for hypotension or lactate greater than or equal to 4 mmol/L. Within 6 hours, vasopressors should be given for hypotension that does not respond to initial fluid resuscitation to maintain a mean arterial pressure (MAP) of at least 65mm Hg. In the event of persistent hypotension after initial fluid administration (MAP under 65 mm Hg) or if initial lactate was greater than or equal to 4 mmol/L, volume status and tissue perfusion should be reassessed and lactate should be rechecked if it was initially elevated.

The bottom line

A 2016 international task force recommended that the definition of sepsis should be changed to emphasize organ dysfunction rather than a systemic inflammatory response. Use of the qSOFA score, which relies only on clinically observable data rather than laboratory evaluation, is recommended to identify patients at high risk for morbidity and mortality. Early recognition of sepsis and evaluation with qSOFT should facilitate early treatment and improve survival.

References

Singer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) FRCP; JAMA. 2016;315[8]:801-10. doi: 10.1001/jama.2016.0287.

Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003 Apr;31(4):1250-6.

Singer M, Deutschman CS, Seymour C, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016 Feb 23;315(8):801-10.

Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004 Mar;32(3):858-73.

Dr. Mills is assistant residency program director and assistant professor in the department of family and community medicine and department of physiology at Sidney Kimmel Medical College at Thomas Jefferson University. Dr. Botti is a second-year resident in the family medicine residency program department of family and community medicine at Sidney Kimmel Medical College at Thomas Jefferson University. Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia.

LONDON – Based on readily available clinical data, patients with chronic obstructive pulmonary disease (COPD) can be placed into five phenotypes with different characteristics and risk profiles, according to data generated by a cluster analysis and presented at the European Respiratory Society International Congress 2016.

The algorithm that places patients into these phenotypes was developed from a cluster analysis, reported Pierre-Regis Burgel, MD, PhD, professor of respiratory medicine, Université Réné Descartes, Paris. Mortality rates at 3 years for these phenotypes ranged from 2.6% to 49.5%

“We think that this could be the basis for recognizing clinically distinct COPD phenotypes and designing better tailored management,” Dr. Burgel explained. “We also think it has potential use in routine clinical assessment.”

To create these phenotypes, data from 2,049 COPD patients enrolled in a French-Belgian collaborative cohort were evaluated with Classification And Regression Tree (CART) analyses. The five phenotypes were derived from symptom burden, respiratory function, relative age, and presence of comorbidities.

Based on these characteristics, “a set of clinical rules” to phenotype patients was developed, according to Dr. Burgel. This algorithm was then further validated with the 3,651 COPD patients enrolled in the prospective COPD Cohorts Collaborative International Assessment (3CIA) initiative.

The two initial branches in the algorithm are created by dividing patients into those with and without cardiovascular comorbidities or diabetes. In those without cardiovascular disease, the phenotypes are defined by relative symptom severity, using cut-off scores from the modified Medical Research Council (mMRC) dyspnea assessment tool and relative degrees of lung function impairment as measured with forced expiratory volume in 1 second (FEV₁).

In those with cardiovascular disease or diabetes, mMRC-defined symptoms and FEV₁-defined lung function impairment also create decision points in the algorithm, but age and body mass index (BMI) are additional variables that direct patients to a specific phenotype. Class 4 and 5 are reached in the absence of cardiovascular disease or diabetes only, while cardiovascular disease is a prerequisite to reach Classes 4 and 5. Class 2 is the only phenotype that can be reached through the algorithm irrespective of the presence or absence of cardiovascular disease.

Using this algorithm, each of the phenotypes was associated with similar relative hierarchy in mortality in the two cohorts, even though mortality rates for each phenotype were consistently lower in the 3CIA group.

For class 1, which was reached by patients with cardiovascular disease or diabetes, the greatest symptom burden, and the lowest lung function, the mortality rates at 3 years were 49.5% and 23.2% for the French-Belgian and 3CIA cohorts, respectively.

For class 4, which was also defined by the greatest symptom burden and the lowest lung function without cardiovascular disease or diabetes the mortality rates were 45.3% and 27.3%, respectively. The lowest mortality rates, which were 2.6% and 4.0%, respectively, were found in the class 5 phenotype, which contained patients with a low symptom burden (mMRC less than or equal to 1), relatively good lung function (FEV₁ greater than or equal to 60%), and no history of cardiovascular disease or diabetes.

In classes 2 and 3, the mortality rates fell in between those of the lowest- and highest-risk phenotypes. Specifically, these 3-year mortality rates were 22.9% and 24%, respectively, in the French-Belgian cohort, and 11.1% and 14.1%, respectively, in the 3CIA cohort.

The consistency of the hierarchy of outcomes in the two cohorts provides the basis for suggesting that these phenotypes are effective for categorizing relative risk, according to Dr. Burgel. He believes that the phenotypes are clinically important, and he emphasized that the algorithm relies on clinical information that is already routinely collected and readily accessible.

“There is growing awareness that COPD phenotypes are important and are likely to be valuable in managing patients,” Dr. Burgel explained. “We feel that we have created simple rules for allocating patients that we think will be useful for research and for clinical application.”

Dr. Burgel reported financial relationships with AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Pfizer, and Vertex.

LONDON – Based on readily available clinical data, patients with chronic obstructive pulmonary disease (COPD) can be placed into five phenotypes with different characteristics and risk profiles, according to data generated by a cluster analysis and presented at the European Respiratory Society International Congress 2016.

The algorithm that places patients into these phenotypes was developed from a cluster analysis, reported Pierre-Regis Burgel, MD, PhD, professor of respiratory medicine, Université Réné Descartes, Paris. Mortality rates at 3 years for these phenotypes ranged from 2.6% to 49.5%

“We think that this could be the basis for recognizing clinically distinct COPD phenotypes and designing better tailored management,” Dr. Burgel explained. “We also think it has potential use in routine clinical assessment.”

To create these phenotypes, data from 2,049 COPD patients enrolled in a French-Belgian collaborative cohort were evaluated with Classification And Regression Tree (CART) analyses. The five phenotypes were derived from symptom burden, respiratory function, relative age, and presence of comorbidities.

Based on these characteristics, “a set of clinical rules” to phenotype patients was developed, according to Dr. Burgel. This algorithm was then further validated with the 3,651 COPD patients enrolled in the prospective COPD Cohorts Collaborative International Assessment (3CIA) initiative.

The two initial branches in the algorithm are created by dividing patients into those with and without cardiovascular comorbidities or diabetes. In those without cardiovascular disease, the phenotypes are defined by relative symptom severity, using cut-off scores from the modified Medical Research Council (mMRC) dyspnea assessment tool and relative degrees of lung function impairment as measured with forced expiratory volume in 1 second (FEV₁).

In those with cardiovascular disease or diabetes, mMRC-defined symptoms and FEV₁-defined lung function impairment also create decision points in the algorithm, but age and body mass index (BMI) are additional variables that direct patients to a specific phenotype. Class 4 and 5 are reached in the absence of cardiovascular disease or diabetes only, while cardiovascular disease is a prerequisite to reach Classes 4 and 5. Class 2 is the only phenotype that can be reached through the algorithm irrespective of the presence or absence of cardiovascular disease.

Using this algorithm, each of the phenotypes was associated with similar relative hierarchy in mortality in the two cohorts, even though mortality rates for each phenotype were consistently lower in the 3CIA group.

For class 1, which was reached by patients with cardiovascular disease or diabetes, the greatest symptom burden, and the lowest lung function, the mortality rates at 3 years were 49.5% and 23.2% for the French-Belgian and 3CIA cohorts, respectively.

For class 4, which was also defined by the greatest symptom burden and the lowest lung function without cardiovascular disease or diabetes the mortality rates were 45.3% and 27.3%, respectively. The lowest mortality rates, which were 2.6% and 4.0%, respectively, were found in the class 5 phenotype, which contained patients with a low symptom burden (mMRC less than or equal to 1), relatively good lung function (FEV₁ greater than or equal to 60%), and no history of cardiovascular disease or diabetes.

In classes 2 and 3, the mortality rates fell in between those of the lowest- and highest-risk phenotypes. Specifically, these 3-year mortality rates were 22.9% and 24%, respectively, in the French-Belgian cohort, and 11.1% and 14.1%, respectively, in the 3CIA cohort.

The consistency of the hierarchy of outcomes in the two cohorts provides the basis for suggesting that these phenotypes are effective for categorizing relative risk, according to Dr. Burgel. He believes that the phenotypes are clinically important, and he emphasized that the algorithm relies on clinical information that is already routinely collected and readily accessible.

“There is growing awareness that COPD phenotypes are important and are likely to be valuable in managing patients,” Dr. Burgel explained. “We feel that we have created simple rules for allocating patients that we think will be useful for research and for clinical application.”

Dr. Burgel reported financial relationships with AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Pfizer, and Vertex.

LONDON – Based on readily available clinical data, patients with chronic obstructive pulmonary disease (COPD) can be placed into five phenotypes with different characteristics and risk profiles, according to data generated by a cluster analysis and presented at the European Respiratory Society International Congress 2016.

The algorithm that places patients into these phenotypes was developed from a cluster analysis, reported Pierre-Regis Burgel, MD, PhD, professor of respiratory medicine, Université Réné Descartes, Paris. Mortality rates at 3 years for these phenotypes ranged from 2.6% to 49.5%

“We think that this could be the basis for recognizing clinically distinct COPD phenotypes and designing better tailored management,” Dr. Burgel explained. “We also think it has potential use in routine clinical assessment.”

To create these phenotypes, data from 2,049 COPD patients enrolled in a French-Belgian collaborative cohort were evaluated with Classification And Regression Tree (CART) analyses. The five phenotypes were derived from symptom burden, respiratory function, relative age, and presence of comorbidities.

Based on these characteristics, “a set of clinical rules” to phenotype patients was developed, according to Dr. Burgel. This algorithm was then further validated with the 3,651 COPD patients enrolled in the prospective COPD Cohorts Collaborative International Assessment (3CIA) initiative.

The two initial branches in the algorithm are created by dividing patients into those with and without cardiovascular comorbidities or diabetes. In those without cardiovascular disease, the phenotypes are defined by relative symptom severity, using cut-off scores from the modified Medical Research Council (mMRC) dyspnea assessment tool and relative degrees of lung function impairment as measured with forced expiratory volume in 1 second (FEV₁).

In those with cardiovascular disease or diabetes, mMRC-defined symptoms and FEV₁-defined lung function impairment also create decision points in the algorithm, but age and body mass index (BMI) are additional variables that direct patients to a specific phenotype. Class 4 and 5 are reached in the absence of cardiovascular disease or diabetes only, while cardiovascular disease is a prerequisite to reach Classes 4 and 5. Class 2 is the only phenotype that can be reached through the algorithm irrespective of the presence or absence of cardiovascular disease.

Using this algorithm, each of the phenotypes was associated with similar relative hierarchy in mortality in the two cohorts, even though mortality rates for each phenotype were consistently lower in the 3CIA group.

For class 1, which was reached by patients with cardiovascular disease or diabetes, the greatest symptom burden, and the lowest lung function, the mortality rates at 3 years were 49.5% and 23.2% for the French-Belgian and 3CIA cohorts, respectively.

For class 4, which was also defined by the greatest symptom burden and the lowest lung function without cardiovascular disease or diabetes the mortality rates were 45.3% and 27.3%, respectively. The lowest mortality rates, which were 2.6% and 4.0%, respectively, were found in the class 5 phenotype, which contained patients with a low symptom burden (mMRC less than or equal to 1), relatively good lung function (FEV₁ greater than or equal to 60%), and no history of cardiovascular disease or diabetes.

In classes 2 and 3, the mortality rates fell in between those of the lowest- and highest-risk phenotypes. Specifically, these 3-year mortality rates were 22.9% and 24%, respectively, in the French-Belgian cohort, and 11.1% and 14.1%, respectively, in the 3CIA cohort.

The consistency of the hierarchy of outcomes in the two cohorts provides the basis for suggesting that these phenotypes are effective for categorizing relative risk, according to Dr. Burgel. He believes that the phenotypes are clinically important, and he emphasized that the algorithm relies on clinical information that is already routinely collected and readily accessible.

“There is growing awareness that COPD phenotypes are important and are likely to be valuable in managing patients,” Dr. Burgel explained. “We feel that we have created simple rules for allocating patients that we think will be useful for research and for clinical application.”

Dr. Burgel reported financial relationships with AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Pfizer, and Vertex.

The Food and Drug Administration has given an orphan drug designation to the compound BIV201 for the treatment of ascites, according to a press release from the drug’s manufacturer, BioVie.

The FDA designation for BIV201 is for the treatment of ascites due to all etiologies except cancer. Clinical trials could commence by 2017, if accepted by the FDA. If trials are successful, other applications for BIV201 could be tested. BIV201 is a vasoconstricter, and could also be used to treat diseases like type 1 hepatorenal syndrome, esophageal variceal bleeds, and sepsis.

Ascites, a common complication of liver cirrhosis, has no specific approved treatment, and 40% of patients diagnosed with ascites die within 2 years. Other treatments may work initially, but become ineffective as the patient worsens. Treatment costs in the United States for liver cirrhosis and related complications, including ascites, totals over $4 billion.

“Orphan drug designation represents a major milestone supporting the clinical development and eventual commercialization of BIV201 therapy. It recognizes the importance of pioneering a new therapeutic approach for this relatively small group of desperately ill patients,” Jonathan Adams, BioVie CEO, said in the press release.

Find the full press release on the BioVie website.

[email protected]

The Food and Drug Administration has given an orphan drug designation to the compound BIV201 for the treatment of ascites, according to a press release from the drug’s manufacturer, BioVie.

The FDA designation for BIV201 is for the treatment of ascites due to all etiologies except cancer. Clinical trials could commence by 2017, if accepted by the FDA. If trials are successful, other applications for BIV201 could be tested. BIV201 is a vasoconstricter, and could also be used to treat diseases like type 1 hepatorenal syndrome, esophageal variceal bleeds, and sepsis.

Ascites, a common complication of liver cirrhosis, has no specific approved treatment, and 40% of patients diagnosed with ascites die within 2 years. Other treatments may work initially, but become ineffective as the patient worsens. Treatment costs in the United States for liver cirrhosis and related complications, including ascites, totals over $4 billion.

“Orphan drug designation represents a major milestone supporting the clinical development and eventual commercialization of BIV201 therapy. It recognizes the importance of pioneering a new therapeutic approach for this relatively small group of desperately ill patients,” Jonathan Adams, BioVie CEO, said in the press release.

Find the full press release on the BioVie website.

[email protected]

The Food and Drug Administration has given an orphan drug designation to the compound BIV201 for the treatment of ascites, according to a press release from the drug’s manufacturer, BioVie.

The FDA designation for BIV201 is for the treatment of ascites due to all etiologies except cancer. Clinical trials could commence by 2017, if accepted by the FDA. If trials are successful, other applications for BIV201 could be tested. BIV201 is a vasoconstricter, and could also be used to treat diseases like type 1 hepatorenal syndrome, esophageal variceal bleeds, and sepsis.

Ascites, a common complication of liver cirrhosis, has no specific approved treatment, and 40% of patients diagnosed with ascites die within 2 years. Other treatments may work initially, but become ineffective as the patient worsens. Treatment costs in the United States for liver cirrhosis and related complications, including ascites, totals over $4 billion.

“Orphan drug designation represents a major milestone supporting the clinical development and eventual commercialization of BIV201 therapy. It recognizes the importance of pioneering a new therapeutic approach for this relatively small group of desperately ill patients,” Jonathan Adams, BioVie CEO, said in the press release.

Find the full press release on the BioVie website.

[email protected]

LONDON – A cytokine known as tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is showing potential as a biomarker for evaluating the severity of sepsis and septic shock, according to results of a prospective study presented at the annual congress of the European Respiratory Society.

In a prospective study undertaken in patients administered to an intensive care unit, “lower levels of plasma TRAIL correlated with both organ system dysfunction and mortality,” reported Thomas Nicholson, MD, of Cornell University, New York.

A series of studies associating low levels of TRAIL with increased sepsis severity have attracted attention to this potential biomarker, according to Dr. Nicholson. In a mouse model of sepsis, for example, exogenous administration of TRAIL was associated with improved survival. In a clinical study conducted in CHINA that was cited by Dr. Nicholson, low levels of TRAIL correlated with lower rates of survival.

In the data presented at the ERS Congress, plasma TRAIL was collected from 108 patients on the first day of ICU admission. Of these patients 59 (54%) had sepsis and 23 (21%) had septic shock. Those with a noninfectious critical illness served as controls.

All patients with sepsis or septic shock were required to meet diagnostic criteria from the recently published Third International Consensus Definitions for Sepsis and Septic Shock (JAMA. 2016;315[8]:801-10). This is important because the newer criteria, relative to previous criteria, have “moved conceptually away from a condition defined by inflammatory biomarkers toward one that emphasizes signs of organ dysfunction,” Dr. Nicholson reported.

Although a dysregulated host response to infection is still a fundamental concept to the newer definition of sepsis, the importance of biomarkers of inflammation has been deemphasized, a change that would not be expected to favor an inflammatory cytokine as a biomarker.

Despite this, plasma TRAIL levels, which were measured with commercially available ELISA kits, were significantly lower for those with sepsis (P = .038) and for those with septic shock (P less than .001) relative to those with a noninfectious critical illness. There was a trend (P = .077) for lower plasma levels of TRAIL in patients with septic shock relative to sepsis.

In addition, there was a positive and significant correlation (r = –0.1983; P = .0397) between plasma TRAIL and degree of organ dysfunction as measured with the Sequential Organ Failure Assessment (SOFA) score. Higher plasma TRAIL levels also predicted survival at 28 days (P = .016). Although the overall mortality for patients with sepsis or septic shock in this series was 23%, there were no deaths among sepsis or septic shock patients with a TRAIL above the mean, which was 26.8 pg/mL.

“For every 10 mg/mL increase in TRAIL the odds ratio for survival increased by 1.9-fold,” Dr. Nicholson reported.

TRAIL is implicated in several processes that may explain these observations, according to Dr. Nicholson. For example, he reported that there is evidence that TRAIL induces apoptosis in neutrophils, a suspected mediator of sepsis-related injury.

“The observations in our study are consistent with a growing literature suggesting that TRAIL is an important mediator of inflammatory cells, such as neutrophils, tempering the degree of inflammation,” Dr. Nicholson explained.

More data are needed to verify that TRAIL is a clinically useful biomarker, but Dr. Nicholson emphasized that this is a promising area of research. He said the biomarker is being developed as a potential tool for evaluating sepsis severity.

Dr. Nicholson reported no relevant financial relationships.

LONDON – A cytokine known as tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is showing potential as a biomarker for evaluating the severity of sepsis and septic shock, according to results of a prospective study presented at the annual congress of the European Respiratory Society.

In a prospective study undertaken in patients administered to an intensive care unit, “lower levels of plasma TRAIL correlated with both organ system dysfunction and mortality,” reported Thomas Nicholson, MD, of Cornell University, New York.

A series of studies associating low levels of TRAIL with increased sepsis severity have attracted attention to this potential biomarker, according to Dr. Nicholson. In a mouse model of sepsis, for example, exogenous administration of TRAIL was associated with improved survival. In a clinical study conducted in CHINA that was cited by Dr. Nicholson, low levels of TRAIL correlated with lower rates of survival.

In the data presented at the ERS Congress, plasma TRAIL was collected from 108 patients on the first day of ICU admission. Of these patients 59 (54%) had sepsis and 23 (21%) had septic shock. Those with a noninfectious critical illness served as controls.

All patients with sepsis or septic shock were required to meet diagnostic criteria from the recently published Third International Consensus Definitions for Sepsis and Septic Shock (JAMA. 2016;315[8]:801-10). This is important because the newer criteria, relative to previous criteria, have “moved conceptually away from a condition defined by inflammatory biomarkers toward one that emphasizes signs of organ dysfunction,” Dr. Nicholson reported.

Although a dysregulated host response to infection is still a fundamental concept to the newer definition of sepsis, the importance of biomarkers of inflammation has been deemphasized, a change that would not be expected to favor an inflammatory cytokine as a biomarker.

Despite this, plasma TRAIL levels, which were measured with commercially available ELISA kits, were significantly lower for those with sepsis (P = .038) and for those with septic shock (P less than .001) relative to those with a noninfectious critical illness. There was a trend (P = .077) for lower plasma levels of TRAIL in patients with septic shock relative to sepsis.

In addition, there was a positive and significant correlation (r = –0.1983; P = .0397) between plasma TRAIL and degree of organ dysfunction as measured with the Sequential Organ Failure Assessment (SOFA) score. Higher plasma TRAIL levels also predicted survival at 28 days (P = .016). Although the overall mortality for patients with sepsis or septic shock in this series was 23%, there were no deaths among sepsis or septic shock patients with a TRAIL above the mean, which was 26.8 pg/mL.

“For every 10 mg/mL increase in TRAIL the odds ratio for survival increased by 1.9-fold,” Dr. Nicholson reported.

TRAIL is implicated in several processes that may explain these observations, according to Dr. Nicholson. For example, he reported that there is evidence that TRAIL induces apoptosis in neutrophils, a suspected mediator of sepsis-related injury.

“The observations in our study are consistent with a growing literature suggesting that TRAIL is an important mediator of inflammatory cells, such as neutrophils, tempering the degree of inflammation,” Dr. Nicholson explained.

More data are needed to verify that TRAIL is a clinically useful biomarker, but Dr. Nicholson emphasized that this is a promising area of research. He said the biomarker is being developed as a potential tool for evaluating sepsis severity.

Dr. Nicholson reported no relevant financial relationships.

LONDON – A cytokine known as tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is showing potential as a biomarker for evaluating the severity of sepsis and septic shock, according to results of a prospective study presented at the annual congress of the European Respiratory Society.

In a prospective study undertaken in patients administered to an intensive care unit, “lower levels of plasma TRAIL correlated with both organ system dysfunction and mortality,” reported Thomas Nicholson, MD, of Cornell University, New York.

A series of studies associating low levels of TRAIL with increased sepsis severity have attracted attention to this potential biomarker, according to Dr. Nicholson. In a mouse model of sepsis, for example, exogenous administration of TRAIL was associated with improved survival. In a clinical study conducted in CHINA that was cited by Dr. Nicholson, low levels of TRAIL correlated with lower rates of survival.

In the data presented at the ERS Congress, plasma TRAIL was collected from 108 patients on the first day of ICU admission. Of these patients 59 (54%) had sepsis and 23 (21%) had septic shock. Those with a noninfectious critical illness served as controls.

All patients with sepsis or septic shock were required to meet diagnostic criteria from the recently published Third International Consensus Definitions for Sepsis and Septic Shock (JAMA. 2016;315[8]:801-10). This is important because the newer criteria, relative to previous criteria, have “moved conceptually away from a condition defined by inflammatory biomarkers toward one that emphasizes signs of organ dysfunction,” Dr. Nicholson reported.

Although a dysregulated host response to infection is still a fundamental concept to the newer definition of sepsis, the importance of biomarkers of inflammation has been deemphasized, a change that would not be expected to favor an inflammatory cytokine as a biomarker.

Despite this, plasma TRAIL levels, which were measured with commercially available ELISA kits, were significantly lower for those with sepsis (P = .038) and for those with septic shock (P less than .001) relative to those with a noninfectious critical illness. There was a trend (P = .077) for lower plasma levels of TRAIL in patients with septic shock relative to sepsis.

In addition, there was a positive and significant correlation (r = –0.1983; P = .0397) between plasma TRAIL and degree of organ dysfunction as measured with the Sequential Organ Failure Assessment (SOFA) score. Higher plasma TRAIL levels also predicted survival at 28 days (P = .016). Although the overall mortality for patients with sepsis or septic shock in this series was 23%, there were no deaths among sepsis or septic shock patients with a TRAIL above the mean, which was 26.8 pg/mL.

“For every 10 mg/mL increase in TRAIL the odds ratio for survival increased by 1.9-fold,” Dr. Nicholson reported.

TRAIL is implicated in several processes that may explain these observations, according to Dr. Nicholson. For example, he reported that there is evidence that TRAIL induces apoptosis in neutrophils, a suspected mediator of sepsis-related injury.

“The observations in our study are consistent with a growing literature suggesting that TRAIL is an important mediator of inflammatory cells, such as neutrophils, tempering the degree of inflammation,” Dr. Nicholson explained.

More data are needed to verify that TRAIL is a clinically useful biomarker, but Dr. Nicholson emphasized that this is a promising area of research. He said the biomarker is being developed as a potential tool for evaluating sepsis severity.

Dr. Nicholson reported no relevant financial relationships.

The concentration of lactate in the cerebrospinal fluid accurately identifies bacterial meningitis that develops after neurosurgery, distinguishing it from other conditions, according to a report published in BMC Infectious Diseases.

In patients who have undergone neurosurgery, failure to promptly identify and treat bacterial meningitis is associated with patient mortality as high as 50%, reported Xiong Xiao of the department of neurosurgery and the China National Clinical Research Center for Neurological Diseases at Beijing Tiantan Hospital and Capital Medical University, Beijing, and associates.

Courtesy CDC

A recent small study suggested that cerebrospinal fluid (CSF) lactate was accurate at differentiating postoperative bacterial meningitis from aseptic meningitis. To examine this possibility in a larger patient population, Dr. Xiao and associates reviewed 1,672 articles in the medical literature. They found few high-quality studies of this topic, but were able to perform a meta-analysis and pool the data from five studies involving 404 postneurosurgical patients treated during a 15-year period.

CSF lactate concentration identified bacterial meningitis with a pooled sensitivity of 92% and a pooled specificity of 88%. “Moreover, this test is fast, simple, objective, and affordable, and can be widely applied in hospitals,” the investigators wrote (BMC Infect Dis. 2016;16:483. doi: 10.1186/s12879-016-1818-2).Larger prospective studies are needed to confirm this finding and to provide a more thorough understanding of the indicators of postneurosurgical meningitis, Dr. Xiao and associates added.

This study was supported by Beijing Tiantan Hospital Funds for Young Scholars, the Ministry of Science and Technology of China, and the Beijing Talents Fund. Dr. Xiao and associates reported having no relevant financial disclosures.

The concentration of lactate in the cerebrospinal fluid accurately identifies bacterial meningitis that develops after neurosurgery, distinguishing it from other conditions, according to a report published in BMC Infectious Diseases.

In patients who have undergone neurosurgery, failure to promptly identify and treat bacterial meningitis is associated with patient mortality as high as 50%, reported Xiong Xiao of the department of neurosurgery and the China National Clinical Research Center for Neurological Diseases at Beijing Tiantan Hospital and Capital Medical University, Beijing, and associates.

Courtesy CDC

A recent small study suggested that cerebrospinal fluid (CSF) lactate was accurate at differentiating postoperative bacterial meningitis from aseptic meningitis. To examine this possibility in a larger patient population, Dr. Xiao and associates reviewed 1,672 articles in the medical literature. They found few high-quality studies of this topic, but were able to perform a meta-analysis and pool the data from five studies involving 404 postneurosurgical patients treated during a 15-year period.

CSF lactate concentration identified bacterial meningitis with a pooled sensitivity of 92% and a pooled specificity of 88%. “Moreover, this test is fast, simple, objective, and affordable, and can be widely applied in hospitals,” the investigators wrote (BMC Infect Dis. 2016;16:483. doi: 10.1186/s12879-016-1818-2).Larger prospective studies are needed to confirm this finding and to provide a more thorough understanding of the indicators of postneurosurgical meningitis, Dr. Xiao and associates added.

This study was supported by Beijing Tiantan Hospital Funds for Young Scholars, the Ministry of Science and Technology of China, and the Beijing Talents Fund. Dr. Xiao and associates reported having no relevant financial disclosures.

The concentration of lactate in the cerebrospinal fluid accurately identifies bacterial meningitis that develops after neurosurgery, distinguishing it from other conditions, according to a report published in BMC Infectious Diseases.

In patients who have undergone neurosurgery, failure to promptly identify and treat bacterial meningitis is associated with patient mortality as high as 50%, reported Xiong Xiao of the department of neurosurgery and the China National Clinical Research Center for Neurological Diseases at Beijing Tiantan Hospital and Capital Medical University, Beijing, and associates.

Courtesy CDC

A recent small study suggested that cerebrospinal fluid (CSF) lactate was accurate at differentiating postoperative bacterial meningitis from aseptic meningitis. To examine this possibility in a larger patient population, Dr. Xiao and associates reviewed 1,672 articles in the medical literature. They found few high-quality studies of this topic, but were able to perform a meta-analysis and pool the data from five studies involving 404 postneurosurgical patients treated during a 15-year period.

CSF lactate concentration identified bacterial meningitis with a pooled sensitivity of 92% and a pooled specificity of 88%. “Moreover, this test is fast, simple, objective, and affordable, and can be widely applied in hospitals,” the investigators wrote (BMC Infect Dis. 2016;16:483. doi: 10.1186/s12879-016-1818-2).Larger prospective studies are needed to confirm this finding and to provide a more thorough understanding of the indicators of postneurosurgical meningitis, Dr. Xiao and associates added.

This study was supported by Beijing Tiantan Hospital Funds for Young Scholars, the Ministry of Science and Technology of China, and the Beijing Talents Fund. Dr. Xiao and associates reported having no relevant financial disclosures.

LONDON – In chronic obstructive pulmonary disease (COPD), the advantage of a long-acting beta agonist (LABA) plus a long-acting muscarinic antagonist (LAMA) over a LABA plus an inhaled corticosteroid (ICS) was observed in every subgroup in the FLAME trial evaluated, according to post hoc analyses presented at the annual congress of the European Respiratory Society.

“We thought that we might not see the difference in the COPD patients with more severe disease, but the advantage was consistent even among those who entered the trial on triple therapy,” reported Jadwiga A. Wedzicha, MD, professor of respiratory medicine at the National Heart and Lung Institute, Imperial College, London.

FLAME, the recently published study that compared LABA/LAMA to LABA/ICS, was planned as a noninferiority study with the underlying hypothesis that LABA/LAMA would perform as well as LABA/ICS for the primary outcome of annual rate of COPD exacerbations (N Engl J Med. 2016;374:2222-34). Instead, the 11% lower rate of exacerbations for LABA/LAMA proved statistically significant (P = .003).

Six post hoc FLAME analyses were presented at the 2016 ERS Congress to further explore this result. All supported the main result. In addition to evaluating those who entered the trial on a LABA/LAMA/ICS triple-therapy combination, the analyses covered a broad array of subgroups defined by age, smoking history, and COPD severity as defined by Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifications.

In FLAME, 3,362 COPD patients who had at least one exacerbation in the preceding year were randomized to the LABA indacaterol (110 mcg) plus the LAMA glycopyrronium (50 mcg) once daily or the combination of the LABA salmeterol (50 mcg) and the ICS fluticasone (500 mcg) twice daily. In addition to the relative advantage on the primary outcome of any exacerbation, the LABA/LAMA combination also significantly reduced the rate of moderate to severe exacerbations (P less than .001), and it extended the times to the first moderate to severe exacerbation (P less than .001) and the first severe exacerbation (P = .046), according to the published data.

In the post hoc analyses, the advantage of LABA/LAMA relative to LAMA/ICS was remarkably consistent. For example, in stratifications made for age (less than 55 years, 55 to less than 65 years, 65-75 years, and greater than or equal to 75 years) at least a numerical advantage of LABA/LAMA was seen in all age groups for prevention of any exacerbation, and the difference reached statistical significance for those in the age group 55 to greater than 65 years. For prevention of moderate to severe exacerbations, the treatments were found to be equivalent for individuals younger than 55 years, but LABA/LAMA was statistically superior for the other three age categories.

For ex-smokers, unlike current smokers, the numerical advantage of LABA/LAMA over LABA/ICS for reduction in the rate ratio of all exacerbations did not reach statistical significance, but the LABA/LAMA combination did provide a statistically significant advantage for both ex-smokers and current smokers for moderate to severe exacerbations.

For patients with two or more exacerbations in the year prior to enrollment in FLAME, the relative degree of protection was of magnitude similar to that of patients with only one exacerbation even though the relative advantage in those with multiple prior exacerbations did not reach statistical significance. However, the lack of significance was likely due to the relatively small number of patients in this subpopulation, according to Dr. Wedzicha.

Similarly, the LABA/LAMA combination was at least numerically superior to LABA/ICS for all exacerbations and for moderate to severe exacerbations across GOLD classifications with one exception. When compared for relative protection against moderate to severe exacerbations, there was a slight and nonsignificant disadvantage for LABA/LAMA, but, again, Dr. Wedzicha reported, “the number of patients in this subgroup was quite small.”

In another FLAME post hoc analysis, the odds ratio (OR) for exacerbations among the 1,893 patients (56.3%) who were on ICS at study entry was found to be almost identical to the OR among those who were not. Specifically, the ORs for all exacerbations and moderate to severe exacerbations were 0.88 (P = .008) and 0.86 (P = .018), respectively, for those previously treated with ICS and 0.88 (P = .021) and 0.78 (P = .002), respectively, for those who had not been treated with ICS.

The LABA/LAMA combination was also superior to LABA/ICS for improvements in quality of life, which was measured via the St. George’s Respiratory Questionnaire. With an improvement of at least four units on the St. George’s Respiratory Questionnaire defined as clinically meaningful, 49.5% of LABA/LAMA patients versus 43.8% of LABA/ICS patients (P less than .024) benefited on this measure.

Overall, the results from the FLAME post hoc analyses have demonstrated “remarkable consistency,” Dr. Wedzicha reported. Taken together, she said the data “imply that LABA/LAMA is the first choice of treatment for COPD patients at risk of exacerbation.”

LONDON – In chronic obstructive pulmonary disease (COPD), the advantage of a long-acting beta agonist (LABA) plus a long-acting muscarinic antagonist (LAMA) over a LABA plus an inhaled corticosteroid (ICS) was observed in every subgroup in the FLAME trial evaluated, according to post hoc analyses presented at the annual congress of the European Respiratory Society.

“We thought that we might not see the difference in the COPD patients with more severe disease, but the advantage was consistent even among those who entered the trial on triple therapy,” reported Jadwiga A. Wedzicha, MD, professor of respiratory medicine at the National Heart and Lung Institute, Imperial College, London.

FLAME, the recently published study that compared LABA/LAMA to LABA/ICS, was planned as a noninferiority study with the underlying hypothesis that LABA/LAMA would perform as well as LABA/ICS for the primary outcome of annual rate of COPD exacerbations (N Engl J Med. 2016;374:2222-34). Instead, the 11% lower rate of exacerbations for LABA/LAMA proved statistically significant (P = .003).

Six post hoc FLAME analyses were presented at the 2016 ERS Congress to further explore this result. All supported the main result. In addition to evaluating those who entered the trial on a LABA/LAMA/ICS triple-therapy combination, the analyses covered a broad array of subgroups defined by age, smoking history, and COPD severity as defined by Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifications.

In FLAME, 3,362 COPD patients who had at least one exacerbation in the preceding year were randomized to the LABA indacaterol (110 mcg) plus the LAMA glycopyrronium (50 mcg) once daily or the combination of the LABA salmeterol (50 mcg) and the ICS fluticasone (500 mcg) twice daily. In addition to the relative advantage on the primary outcome of any exacerbation, the LABA/LAMA combination also significantly reduced the rate of moderate to severe exacerbations (P less than .001), and it extended the times to the first moderate to severe exacerbation (P less than .001) and the first severe exacerbation (P = .046), according to the published data.

In the post hoc analyses, the advantage of LABA/LAMA relative to LAMA/ICS was remarkably consistent. For example, in stratifications made for age (less than 55 years, 55 to less than 65 years, 65-75 years, and greater than or equal to 75 years) at least a numerical advantage of LABA/LAMA was seen in all age groups for prevention of any exacerbation, and the difference reached statistical significance for those in the age group 55 to greater than 65 years. For prevention of moderate to severe exacerbations, the treatments were found to be equivalent for individuals younger than 55 years, but LABA/LAMA was statistically superior for the other three age categories.

For ex-smokers, unlike current smokers, the numerical advantage of LABA/LAMA over LABA/ICS for reduction in the rate ratio of all exacerbations did not reach statistical significance, but the LABA/LAMA combination did provide a statistically significant advantage for both ex-smokers and current smokers for moderate to severe exacerbations.

For patients with two or more exacerbations in the year prior to enrollment in FLAME, the relative degree of protection was of magnitude similar to that of patients with only one exacerbation even though the relative advantage in those with multiple prior exacerbations did not reach statistical significance. However, the lack of significance was likely due to the relatively small number of patients in this subpopulation, according to Dr. Wedzicha.

Similarly, the LABA/LAMA combination was at least numerically superior to LABA/ICS for all exacerbations and for moderate to severe exacerbations across GOLD classifications with one exception. When compared for relative protection against moderate to severe exacerbations, there was a slight and nonsignificant disadvantage for LABA/LAMA, but, again, Dr. Wedzicha reported, “the number of patients in this subgroup was quite small.”

In another FLAME post hoc analysis, the odds ratio (OR) for exacerbations among the 1,893 patients (56.3%) who were on ICS at study entry was found to be almost identical to the OR among those who were not. Specifically, the ORs for all exacerbations and moderate to severe exacerbations were 0.88 (P = .008) and 0.86 (P = .018), respectively, for those previously treated with ICS and 0.88 (P = .021) and 0.78 (P = .002), respectively, for those who had not been treated with ICS.

The LABA/LAMA combination was also superior to LABA/ICS for improvements in quality of life, which was measured via the St. George’s Respiratory Questionnaire. With an improvement of at least four units on the St. George’s Respiratory Questionnaire defined as clinically meaningful, 49.5% of LABA/LAMA patients versus 43.8% of LABA/ICS patients (P less than .024) benefited on this measure.

Overall, the results from the FLAME post hoc analyses have demonstrated “remarkable consistency,” Dr. Wedzicha reported. Taken together, she said the data “imply that LABA/LAMA is the first choice of treatment for COPD patients at risk of exacerbation.”

LONDON – In chronic obstructive pulmonary disease (COPD), the advantage of a long-acting beta agonist (LABA) plus a long-acting muscarinic antagonist (LAMA) over a LABA plus an inhaled corticosteroid (ICS) was observed in every subgroup in the FLAME trial evaluated, according to post hoc analyses presented at the annual congress of the European Respiratory Society.

“We thought that we might not see the difference in the COPD patients with more severe disease, but the advantage was consistent even among those who entered the trial on triple therapy,” reported Jadwiga A. Wedzicha, MD, professor of respiratory medicine at the National Heart and Lung Institute, Imperial College, London.

FLAME, the recently published study that compared LABA/LAMA to LABA/ICS, was planned as a noninferiority study with the underlying hypothesis that LABA/LAMA would perform as well as LABA/ICS for the primary outcome of annual rate of COPD exacerbations (N Engl J Med. 2016;374:2222-34). Instead, the 11% lower rate of exacerbations for LABA/LAMA proved statistically significant (P = .003).

Six post hoc FLAME analyses were presented at the 2016 ERS Congress to further explore this result. All supported the main result. In addition to evaluating those who entered the trial on a LABA/LAMA/ICS triple-therapy combination, the analyses covered a broad array of subgroups defined by age, smoking history, and COPD severity as defined by Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifications.

In FLAME, 3,362 COPD patients who had at least one exacerbation in the preceding year were randomized to the LABA indacaterol (110 mcg) plus the LAMA glycopyrronium (50 mcg) once daily or the combination of the LABA salmeterol (50 mcg) and the ICS fluticasone (500 mcg) twice daily. In addition to the relative advantage on the primary outcome of any exacerbation, the LABA/LAMA combination also significantly reduced the rate of moderate to severe exacerbations (P less than .001), and it extended the times to the first moderate to severe exacerbation (P less than .001) and the first severe exacerbation (P = .046), according to the published data.

In the post hoc analyses, the advantage of LABA/LAMA relative to LAMA/ICS was remarkably consistent. For example, in stratifications made for age (less than 55 years, 55 to less than 65 years, 65-75 years, and greater than or equal to 75 years) at least a numerical advantage of LABA/LAMA was seen in all age groups for prevention of any exacerbation, and the difference reached statistical significance for those in the age group 55 to greater than 65 years. For prevention of moderate to severe exacerbations, the treatments were found to be equivalent for individuals younger than 55 years, but LABA/LAMA was statistically superior for the other three age categories.

For ex-smokers, unlike current smokers, the numerical advantage of LABA/LAMA over LABA/ICS for reduction in the rate ratio of all exacerbations did not reach statistical significance, but the LABA/LAMA combination did provide a statistically significant advantage for both ex-smokers and current smokers for moderate to severe exacerbations.

For patients with two or more exacerbations in the year prior to enrollment in FLAME, the relative degree of protection was of magnitude similar to that of patients with only one exacerbation even though the relative advantage in those with multiple prior exacerbations did not reach statistical significance. However, the lack of significance was likely due to the relatively small number of patients in this subpopulation, according to Dr. Wedzicha.

Similarly, the LABA/LAMA combination was at least numerically superior to LABA/ICS for all exacerbations and for moderate to severe exacerbations across GOLD classifications with one exception. When compared for relative protection against moderate to severe exacerbations, there was a slight and nonsignificant disadvantage for LABA/LAMA, but, again, Dr. Wedzicha reported, “the number of patients in this subgroup was quite small.”

In another FLAME post hoc analysis, the odds ratio (OR) for exacerbations among the 1,893 patients (56.3%) who were on ICS at study entry was found to be almost identical to the OR among those who were not. Specifically, the ORs for all exacerbations and moderate to severe exacerbations were 0.88 (P = .008) and 0.86 (P = .018), respectively, for those previously treated with ICS and 0.88 (P = .021) and 0.78 (P = .002), respectively, for those who had not been treated with ICS.

The LABA/LAMA combination was also superior to LABA/ICS for improvements in quality of life, which was measured via the St. George’s Respiratory Questionnaire. With an improvement of at least four units on the St. George’s Respiratory Questionnaire defined as clinically meaningful, 49.5% of LABA/LAMA patients versus 43.8% of LABA/ICS patients (P less than .024) benefited on this measure.

Overall, the results from the FLAME post hoc analyses have demonstrated “remarkable consistency,” Dr. Wedzicha reported. Taken together, she said the data “imply that LABA/LAMA is the first choice of treatment for COPD patients at risk of exacerbation.”

Routine thromboembolism risk assessment and use of both pharmacologic and mechanical thromboprophylaxis is an important part of obstetrics care, according to new recommendations from the National Partnership for Maternal Safety.

Although obstetric venous thromboembolism (VTE) remains a common cause of maternal morbidity and mortality, prophylaxis recommendations are varied and nonspecific across obstetric organizations. The new maternity safety bundle from the National Partnership for Maternal Safety (NPMS) aims to eliminate some of the confusion.

©monkeybusinessimages/Thinkstock

“Based on increasing maternal risk of obstetric venous thromboembolism in the United States, the failure of current strategies to decrease venous thromboembolism as a proportionate cause of maternal death, and observational evidence from the United Kingdom that risk factor–based prophylaxis may reduce risk, the NPMS working group has interpreted current epidemiology and clinical research evidence to support routine thromboembolism risk assessment and consideration of more extensive risk factor–based prophylaxis,” the authors wrote (Obstet Gynecol. 2016;128:688-98).

In the recommendations, prophylactic management of obstetric thromboembolism is organized into four categories: readiness, recognition, response, and reporting and systems learning.

The readiness component includes a recommendation to use a standard thromboembolism risk assessment tool at the first prenatal visit, all antepartum admissions, immediately post partum during childbirth hospitalization, and on discharge from the hospital after a birth. The Caprini and Padua scoring systems, which are tools designed for nonobstetric hospitalized patients, can be modified for obstetric patients, according to the recommendations.

The recognition component of the bundle emphasizes the use of education and guidelines to help physicians identify obstetric patients at risk for thromboembolism. The response component proposes a thromboembolism risk assessment at the first prenatal visit, followed by the use of standardized recommendations for mechanical thromboprophylaxis, dosing of prophylactic and therapeutic pharmacologic anticoagulation, and appropriate timing of pharmacologic prophylaxis with neuraxial anesthesia.

The reporting and systems learning component calls for reviews of a sample of a facility’s obstetric population to determine comorbid risk factors for VTE, followed by routine auditing of records to monitor risk assessment programs and patient care.

The NPMS suggests applying the American College of Chest Physicians recommendations for hospitalized, nonsurgical patients to pregnant women and postpartum women who have had a vaginal birth. However, they recommend using the American College of Obstetricians and Gynecologists’ guidelines for pregnant and postpartum women with thrombophilia.

The NPMS also recommends that women receiving pharmacologic VTE prophylaxis plus low-dose aspirin for the prevention of preeclampsia, should discontinue aspirin at 35-36 weeks of gestation.

“Given the wide diversity of birthing facilities, a single national protocol is not recommended; instead, each facility should adapt a single protocol to improve maternal safety based on its patient population and resources,” the NPMS members wrote.

The NPMS is a joint effort including leaders from a range of women’s health care organizations, hospitals, professional societies, and regulators.

The authors reported having no financial disclosures.

Routine thromboembolism risk assessment and use of both pharmacologic and mechanical thromboprophylaxis is an important part of obstetrics care, according to new recommendations from the National Partnership for Maternal Safety.

Although obstetric venous thromboembolism (VTE) remains a common cause of maternal morbidity and mortality, prophylaxis recommendations are varied and nonspecific across obstetric organizations. The new maternity safety bundle from the National Partnership for Maternal Safety (NPMS) aims to eliminate some of the confusion.

©monkeybusinessimages/Thinkstock

“Based on increasing maternal risk of obstetric venous thromboembolism in the United States, the failure of current strategies to decrease venous thromboembolism as a proportionate cause of maternal death, and observational evidence from the United Kingdom that risk factor–based prophylaxis may reduce risk, the NPMS working group has interpreted current epidemiology and clinical research evidence to support routine thromboembolism risk assessment and consideration of more extensive risk factor–based prophylaxis,” the authors wrote (Obstet Gynecol. 2016;128:688-98).

In the recommendations, prophylactic management of obstetric thromboembolism is organized into four categories: readiness, recognition, response, and reporting and systems learning.

The readiness component includes a recommendation to use a standard thromboembolism risk assessment tool at the first prenatal visit, all antepartum admissions, immediately post partum during childbirth hospitalization, and on discharge from the hospital after a birth. The Caprini and Padua scoring systems, which are tools designed for nonobstetric hospitalized patients, can be modified for obstetric patients, according to the recommendations.

The recognition component of the bundle emphasizes the use of education and guidelines to help physicians identify obstetric patients at risk for thromboembolism. The response component proposes a thromboembolism risk assessment at the first prenatal visit, followed by the use of standardized recommendations for mechanical thromboprophylaxis, dosing of prophylactic and therapeutic pharmacologic anticoagulation, and appropriate timing of pharmacologic prophylaxis with neuraxial anesthesia.

The reporting and systems learning component calls for reviews of a sample of a facility’s obstetric population to determine comorbid risk factors for VTE, followed by routine auditing of records to monitor risk assessment programs and patient care.

The NPMS suggests applying the American College of Chest Physicians recommendations for hospitalized, nonsurgical patients to pregnant women and postpartum women who have had a vaginal birth. However, they recommend using the American College of Obstetricians and Gynecologists’ guidelines for pregnant and postpartum women with thrombophilia.

The NPMS also recommends that women receiving pharmacologic VTE prophylaxis plus low-dose aspirin for the prevention of preeclampsia, should discontinue aspirin at 35-36 weeks of gestation.

“Given the wide diversity of birthing facilities, a single national protocol is not recommended; instead, each facility should adapt a single protocol to improve maternal safety based on its patient population and resources,” the NPMS members wrote.

The NPMS is a joint effort including leaders from a range of women’s health care organizations, hospitals, professional societies, and regulators.

The authors reported having no financial disclosures.

Routine thromboembolism risk assessment and use of both pharmacologic and mechanical thromboprophylaxis is an important part of obstetrics care, according to new recommendations from the National Partnership for Maternal Safety.

Although obstetric venous thromboembolism (VTE) remains a common cause of maternal morbidity and mortality, prophylaxis recommendations are varied and nonspecific across obstetric organizations. The new maternity safety bundle from the National Partnership for Maternal Safety (NPMS) aims to eliminate some of the confusion.

©monkeybusinessimages/Thinkstock

“Based on increasing maternal risk of obstetric venous thromboembolism in the United States, the failure of current strategies to decrease venous thromboembolism as a proportionate cause of maternal death, and observational evidence from the United Kingdom that risk factor–based prophylaxis may reduce risk, the NPMS working group has interpreted current epidemiology and clinical research evidence to support routine thromboembolism risk assessment and consideration of more extensive risk factor–based prophylaxis,” the authors wrote (Obstet Gynecol. 2016;128:688-98).

In the recommendations, prophylactic management of obstetric thromboembolism is organized into four categories: readiness, recognition, response, and reporting and systems learning.

The readiness component includes a recommendation to use a standard thromboembolism risk assessment tool at the first prenatal visit, all antepartum admissions, immediately post partum during childbirth hospitalization, and on discharge from the hospital after a birth. The Caprini and Padua scoring systems, which are tools designed for nonobstetric hospitalized patients, can be modified for obstetric patients, according to the recommendations.

The recognition component of the bundle emphasizes the use of education and guidelines to help physicians identify obstetric patients at risk for thromboembolism. The response component proposes a thromboembolism risk assessment at the first prenatal visit, followed by the use of standardized recommendations for mechanical thromboprophylaxis, dosing of prophylactic and therapeutic pharmacologic anticoagulation, and appropriate timing of pharmacologic prophylaxis with neuraxial anesthesia.

The reporting and systems learning component calls for reviews of a sample of a facility’s obstetric population to determine comorbid risk factors for VTE, followed by routine auditing of records to monitor risk assessment programs and patient care.

The NPMS suggests applying the American College of Chest Physicians recommendations for hospitalized, nonsurgical patients to pregnant women and postpartum women who have had a vaginal birth. However, they recommend using the American College of Obstetricians and Gynecologists’ guidelines for pregnant and postpartum women with thrombophilia.

The NPMS also recommends that women receiving pharmacologic VTE prophylaxis plus low-dose aspirin for the prevention of preeclampsia, should discontinue aspirin at 35-36 weeks of gestation.

“Given the wide diversity of birthing facilities, a single national protocol is not recommended; instead, each facility should adapt a single protocol to improve maternal safety based on its patient population and resources,” the NPMS members wrote.

The NPMS is a joint effort including leaders from a range of women’s health care organizations, hospitals, professional societies, and regulators.

The authors reported having no financial disclosures.