Will Boggs Md

NEW YORK (Reuters Health) - Sustained viral response (SVR) to hepatitis C virus (HCV) treatment is associated with a reduction in liver and non-liver complications in patients with compensated cirrhosis, researchers from France report.

"The achievement of HCV eradication strikingly decreases the risks of liver-related complications, a benefit that was up to now only suggested by retrospective studies," Dr. Pierre Nahon from Hôpital Jean Verdier in Bondy, France, told Reuters Health by email.

"These benefits extend beyond liver-related complications, in particular for cardiovascular disease and MACE (major adverse cardiovascular events) as well as bacterial infection," he said. "These positive effects are translated into survival benefits, whether considering liver-related or extra-hepatic mortality."

Dr. Nahon and colleagues from 35 clinical centers in France evaluated the impact of SVR in 1,671 patients, 1,323 of whom had HCV-related compensated cirrhosis.

After a median follow-up of 58.2 months, 59.5% of patients had a negative viral load, including 668 patients (51.7%) with SVR and 119 HCV-negative patients who were still undergoing antiviral treatment.

Male gender, absence of esophageal varices, and absence of diabetes were independent predictive factors for SVR, the researchers report in Gastroenterology, online the September 15.

SVR was associated with a significantly decreased risk of hepatocellular carcinoma (HCC; hazard ratio, 0.29) and mortality among patients who had HCC at baseline.

Patients who achieved SVR were also 74% less likely to develop liver decompensation during follow-up.

Extrahepatic events - including bacterial infections and cardiovascular events - were less than half as common among patients who achieved SVR than among others, but SVR had no apparent effect on the occurrence of extrahepatic malignancies.

SVR independently predicted a lower risk of hepatic and extrahepatic complications, a finding that was confirmed by a supporting propensity-matching analysis.

SVR was a protective factor for all-cause mortality (HR, 0.27; p<0.001), as well as a predictive factor for survival without liver-related or extrahepatic deaths.

"The present report, with the advantage of a longer follow-up and by studying virological clearance at endpoint as a time-dependent covariate after interferon- or direct-acting antivirals (DAA)-based regimen, now clearly shows that achieving SVR in HCV-infected cirrhotic patients leads to an improved prognosis," the researchers conclude.

"Overall, the present data are able to specifically highlight the independent influence of SVR on the incidence of liver complications, including HCC and mortality and interestingly a positive impact on the occurrence of extrahepatic manifestations," they add.

"However," the team notes, "the achievement of SVR in DAA-treated patients is too recent to draw any definite conclusion on this point, which will require a longer follow-up of the CirVir cohort to be adequately addressed."

"Although HCV eradication is achievable in almost all patients, physicians must be aware of the persisting risk of HCC occurrence in cirrhotic patients despite viral clearance, in particular in case of associated metabolic syndrome," Dr. Nahon cautioned. "These patients must be maintained in liver cancer surveillance programs."

The study did not have commercial funding. Several authors, including Dr. Nahon, reported financial ties to Gilead Sciences and other companies selling drugs for hepatitis C.

NEW YORK (Reuters Health) - Sustained viral response (SVR) to hepatitis C virus (HCV) treatment is associated with a reduction in liver and non-liver complications in patients with compensated cirrhosis, researchers from France report.

"The achievement of HCV eradication strikingly decreases the risks of liver-related complications, a benefit that was up to now only suggested by retrospective studies," Dr. Pierre Nahon from Hôpital Jean Verdier in Bondy, France, told Reuters Health by email.

"These benefits extend beyond liver-related complications, in particular for cardiovascular disease and MACE (major adverse cardiovascular events) as well as bacterial infection," he said. "These positive effects are translated into survival benefits, whether considering liver-related or extra-hepatic mortality."

Dr. Nahon and colleagues from 35 clinical centers in France evaluated the impact of SVR in 1,671 patients, 1,323 of whom had HCV-related compensated cirrhosis.

After a median follow-up of 58.2 months, 59.5% of patients had a negative viral load, including 668 patients (51.7%) with SVR and 119 HCV-negative patients who were still undergoing antiviral treatment.

Male gender, absence of esophageal varices, and absence of diabetes were independent predictive factors for SVR, the researchers report in Gastroenterology, online the September 15.

SVR was associated with a significantly decreased risk of hepatocellular carcinoma (HCC; hazard ratio, 0.29) and mortality among patients who had HCC at baseline.

Patients who achieved SVR were also 74% less likely to develop liver decompensation during follow-up.

Extrahepatic events - including bacterial infections and cardiovascular events - were less than half as common among patients who achieved SVR than among others, but SVR had no apparent effect on the occurrence of extrahepatic malignancies.

SVR independently predicted a lower risk of hepatic and extrahepatic complications, a finding that was confirmed by a supporting propensity-matching analysis.

SVR was a protective factor for all-cause mortality (HR, 0.27; p<0.001), as well as a predictive factor for survival without liver-related or extrahepatic deaths.

"The present report, with the advantage of a longer follow-up and by studying virological clearance at endpoint as a time-dependent covariate after interferon- or direct-acting antivirals (DAA)-based regimen, now clearly shows that achieving SVR in HCV-infected cirrhotic patients leads to an improved prognosis," the researchers conclude.

"Overall, the present data are able to specifically highlight the independent influence of SVR on the incidence of liver complications, including HCC and mortality and interestingly a positive impact on the occurrence of extrahepatic manifestations," they add.

"However," the team notes, "the achievement of SVR in DAA-treated patients is too recent to draw any definite conclusion on this point, which will require a longer follow-up of the CirVir cohort to be adequately addressed."

"Although HCV eradication is achievable in almost all patients, physicians must be aware of the persisting risk of HCC occurrence in cirrhotic patients despite viral clearance, in particular in case of associated metabolic syndrome," Dr. Nahon cautioned. "These patients must be maintained in liver cancer surveillance programs."

The study did not have commercial funding. Several authors, including Dr. Nahon, reported financial ties to Gilead Sciences and other companies selling drugs for hepatitis C.

NEW YORK (Reuters Health) - Sustained viral response (SVR) to hepatitis C virus (HCV) treatment is associated with a reduction in liver and non-liver complications in patients with compensated cirrhosis, researchers from France report.

"The achievement of HCV eradication strikingly decreases the risks of liver-related complications, a benefit that was up to now only suggested by retrospective studies," Dr. Pierre Nahon from Hôpital Jean Verdier in Bondy, France, told Reuters Health by email.

"These benefits extend beyond liver-related complications, in particular for cardiovascular disease and MACE (major adverse cardiovascular events) as well as bacterial infection," he said. "These positive effects are translated into survival benefits, whether considering liver-related or extra-hepatic mortality."

Dr. Nahon and colleagues from 35 clinical centers in France evaluated the impact of SVR in 1,671 patients, 1,323 of whom had HCV-related compensated cirrhosis.

After a median follow-up of 58.2 months, 59.5% of patients had a negative viral load, including 668 patients (51.7%) with SVR and 119 HCV-negative patients who were still undergoing antiviral treatment.

Male gender, absence of esophageal varices, and absence of diabetes were independent predictive factors for SVR, the researchers report in Gastroenterology, online the September 15.

SVR was associated with a significantly decreased risk of hepatocellular carcinoma (HCC; hazard ratio, 0.29) and mortality among patients who had HCC at baseline.

Patients who achieved SVR were also 74% less likely to develop liver decompensation during follow-up.

Extrahepatic events - including bacterial infections and cardiovascular events - were less than half as common among patients who achieved SVR than among others, but SVR had no apparent effect on the occurrence of extrahepatic malignancies.

SVR independently predicted a lower risk of hepatic and extrahepatic complications, a finding that was confirmed by a supporting propensity-matching analysis.

SVR was a protective factor for all-cause mortality (HR, 0.27; p<0.001), as well as a predictive factor for survival without liver-related or extrahepatic deaths.

"The present report, with the advantage of a longer follow-up and by studying virological clearance at endpoint as a time-dependent covariate after interferon- or direct-acting antivirals (DAA)-based regimen, now clearly shows that achieving SVR in HCV-infected cirrhotic patients leads to an improved prognosis," the researchers conclude.

"Overall, the present data are able to specifically highlight the independent influence of SVR on the incidence of liver complications, including HCC and mortality and interestingly a positive impact on the occurrence of extrahepatic manifestations," they add.

"However," the team notes, "the achievement of SVR in DAA-treated patients is too recent to draw any definite conclusion on this point, which will require a longer follow-up of the CirVir cohort to be adequately addressed."

"Although HCV eradication is achievable in almost all patients, physicians must be aware of the persisting risk of HCC occurrence in cirrhotic patients despite viral clearance, in particular in case of associated metabolic syndrome," Dr. Nahon cautioned. "These patients must be maintained in liver cancer surveillance programs."

The study did not have commercial funding. Several authors, including Dr. Nahon, reported financial ties to Gilead Sciences and other companies selling drugs for hepatitis C.

NEW YORK (Reuters Health) - The prevalence of antibiotic resistance in pediatric urinary tract infection (UTI) has reached such high levels in many countries that existing empiric therapies may no longer be effective, researchers from UK report."

Prevalence of resistance to commonly prescribed antibiotics in primary care in children with urinary tract infections caused by E. coli is high, and there was remarkable variability in E. coli resistance among countries in the study, particularly in countries outside the OECD (Organization for Economic Cooperation and Development), where one possible explanation is the availability of antibiotics over the counter," Ashley Bryce from the University of Bristol in the U.K. and Dr. Céire E. Costelloe from Imperial College London told Reuters Health in a joint email.

"This could render some antibiotics ineffective as first-line treatments for urinary tract infection," they said.

E. coli is responsible for more than 80% of all UTIs and is also the most common cause of bacteremia and foodborne infections and one cause of meningitis in neonates.

Bryce, Dr. Costelloe, and colleagues investigated the prevalence of resistance in community-acquired E. coli UTI to the most commonly prescribed antibiotics given to children in primary care in their systematic review of 58 published reports.

For all antibiotics tested, the prevalence of antibiotic resistance was higher in non-OECD countries than in OECD countries, the team reports in an article online March 15 in The BMJ.

The prevalence of resistance was highest for ampicillin, ranging from 41% in Switzerland to 100% in Ghana and Nigeria.

Resistance to co-trimoxazole and trimethoprim was 30% in OECD countries and 67% in Saudi Arabia, the only non-OECD country for which rates were available.

Pooled prevalences of resistance to ciprofloxacin and ceftazidime were around 2% in OECD countries but over 26% in non-OECD countries.

For all time periods analyzed, the odds of resistance were greater in children exposed to antibiotics than in those who were unexposed.

"The Infectious Diseases Society of America (IDSA) in collaboration with the European Society for Microbiology and Infectious Diseases (ESCMID) recommend that an antibiotic should be selected for first line empirical treatment of urinary tract infection only if the local prevalence of resistance is less than 20%," the researchers note.

"According to these guidelines, our review suggests ampicillin, co-trimoxazole, and trimethoprim are no longer suitable first line treatment options for urinary tract infection in many OECD countries and that as a result many guidelines, such as those published by the National Institute for Health and Care Excellence (NICE), might need updating," they write. "In non-OECD countries, resistance to all first line antibiotics specified for urinary tract infections was in excess of 20%, suggesting that choices of first line treatment might need to be re-evaluated in less well developed countries."

"We are not able to advise clinicians on which antibiotic is best to prescribe as this often depends on the individual case," Bryce and Dr. Costelloe said. "Clinicians should, however, adhere to local or national guidelines wherever possible, which is why it is of great importance that such guidelines are kept up to date and reflect current resistance rates."

"Clinicians may also wish to consider the antibiotic history of the child when they present to primary care with symptoms of an infection, especially in light of the suggestion of our results that previous treatment with an antibiotic is associated with resistance to that same antibiotic, and that this association may be present up to 6 months post treatment," they added.

Dr. Grant Russell from Monash University in Melbourne, Australia, wrote an editorial accompanying the report. He told Reuters Health by email, "I found the extent of the resistance (and the fact that it covered all of the regularly used empiric antibiotics) both concerning and surprising. The fact that choices are diminishing is disturbing, and the fact that the situation is dire in the developing world is deeply troubling."

"We need to do what we can do to prevent bacterial infections, and when treating them to consider that effective antibiotics are a finite resource," he said. "We all have a responsibility in attempting to conserve that resource."

"No new classes of antibiotics have been developed in the last 30 years - this and the dire situation in both the developed and the developing world suggests that the 'global problem' of antibiotic resistance is going to become more and more of an issue in years and decades to come," Dr. Russell concluded.

NEW YORK (Reuters Health) - The prevalence of antibiotic resistance in pediatric urinary tract infection (UTI) has reached such high levels in many countries that existing empiric therapies may no longer be effective, researchers from UK report."

Prevalence of resistance to commonly prescribed antibiotics in primary care in children with urinary tract infections caused by E. coli is high, and there was remarkable variability in E. coli resistance among countries in the study, particularly in countries outside the OECD (Organization for Economic Cooperation and Development), where one possible explanation is the availability of antibiotics over the counter," Ashley Bryce from the University of Bristol in the U.K. and Dr. Céire E. Costelloe from Imperial College London told Reuters Health in a joint email.

"This could render some antibiotics ineffective as first-line treatments for urinary tract infection," they said.

E. coli is responsible for more than 80% of all UTIs and is also the most common cause of bacteremia and foodborne infections and one cause of meningitis in neonates.

Bryce, Dr. Costelloe, and colleagues investigated the prevalence of resistance in community-acquired E. coli UTI to the most commonly prescribed antibiotics given to children in primary care in their systematic review of 58 published reports.

For all antibiotics tested, the prevalence of antibiotic resistance was higher in non-OECD countries than in OECD countries, the team reports in an article online March 15 in The BMJ.

The prevalence of resistance was highest for ampicillin, ranging from 41% in Switzerland to 100% in Ghana and Nigeria.

Resistance to co-trimoxazole and trimethoprim was 30% in OECD countries and 67% in Saudi Arabia, the only non-OECD country for which rates were available.

Pooled prevalences of resistance to ciprofloxacin and ceftazidime were around 2% in OECD countries but over 26% in non-OECD countries.

For all time periods analyzed, the odds of resistance were greater in children exposed to antibiotics than in those who were unexposed.

"The Infectious Diseases Society of America (IDSA) in collaboration with the European Society for Microbiology and Infectious Diseases (ESCMID) recommend that an antibiotic should be selected for first line empirical treatment of urinary tract infection only if the local prevalence of resistance is less than 20%," the researchers note.

"According to these guidelines, our review suggests ampicillin, co-trimoxazole, and trimethoprim are no longer suitable first line treatment options for urinary tract infection in many OECD countries and that as a result many guidelines, such as those published by the National Institute for Health and Care Excellence (NICE), might need updating," they write. "In non-OECD countries, resistance to all first line antibiotics specified for urinary tract infections was in excess of 20%, suggesting that choices of first line treatment might need to be re-evaluated in less well developed countries."

"We are not able to advise clinicians on which antibiotic is best to prescribe as this often depends on the individual case," Bryce and Dr. Costelloe said. "Clinicians should, however, adhere to local or national guidelines wherever possible, which is why it is of great importance that such guidelines are kept up to date and reflect current resistance rates."

"Clinicians may also wish to consider the antibiotic history of the child when they present to primary care with symptoms of an infection, especially in light of the suggestion of our results that previous treatment with an antibiotic is associated with resistance to that same antibiotic, and that this association may be present up to 6 months post treatment," they added.

Dr. Grant Russell from Monash University in Melbourne, Australia, wrote an editorial accompanying the report. He told Reuters Health by email, "I found the extent of the resistance (and the fact that it covered all of the regularly used empiric antibiotics) both concerning and surprising. The fact that choices are diminishing is disturbing, and the fact that the situation is dire in the developing world is deeply troubling."

"We need to do what we can do to prevent bacterial infections, and when treating them to consider that effective antibiotics are a finite resource," he said. "We all have a responsibility in attempting to conserve that resource."

"No new classes of antibiotics have been developed in the last 30 years - this and the dire situation in both the developed and the developing world suggests that the 'global problem' of antibiotic resistance is going to become more and more of an issue in years and decades to come," Dr. Russell concluded.

NEW YORK (Reuters Health) - The prevalence of antibiotic resistance in pediatric urinary tract infection (UTI) has reached such high levels in many countries that existing empiric therapies may no longer be effective, researchers from UK report."

Prevalence of resistance to commonly prescribed antibiotics in primary care in children with urinary tract infections caused by E. coli is high, and there was remarkable variability in E. coli resistance among countries in the study, particularly in countries outside the OECD (Organization for Economic Cooperation and Development), where one possible explanation is the availability of antibiotics over the counter," Ashley Bryce from the University of Bristol in the U.K. and Dr. Céire E. Costelloe from Imperial College London told Reuters Health in a joint email.

"This could render some antibiotics ineffective as first-line treatments for urinary tract infection," they said.

E. coli is responsible for more than 80% of all UTIs and is also the most common cause of bacteremia and foodborne infections and one cause of meningitis in neonates.

Bryce, Dr. Costelloe, and colleagues investigated the prevalence of resistance in community-acquired E. coli UTI to the most commonly prescribed antibiotics given to children in primary care in their systematic review of 58 published reports.

For all antibiotics tested, the prevalence of antibiotic resistance was higher in non-OECD countries than in OECD countries, the team reports in an article online March 15 in The BMJ.

The prevalence of resistance was highest for ampicillin, ranging from 41% in Switzerland to 100% in Ghana and Nigeria.

Resistance to co-trimoxazole and trimethoprim was 30% in OECD countries and 67% in Saudi Arabia, the only non-OECD country for which rates were available.

Pooled prevalences of resistance to ciprofloxacin and ceftazidime were around 2% in OECD countries but over 26% in non-OECD countries.

For all time periods analyzed, the odds of resistance were greater in children exposed to antibiotics than in those who were unexposed.

"The Infectious Diseases Society of America (IDSA) in collaboration with the European Society for Microbiology and Infectious Diseases (ESCMID) recommend that an antibiotic should be selected for first line empirical treatment of urinary tract infection only if the local prevalence of resistance is less than 20%," the researchers note.

"According to these guidelines, our review suggests ampicillin, co-trimoxazole, and trimethoprim are no longer suitable first line treatment options for urinary tract infection in many OECD countries and that as a result many guidelines, such as those published by the National Institute for Health and Care Excellence (NICE), might need updating," they write. "In non-OECD countries, resistance to all first line antibiotics specified for urinary tract infections was in excess of 20%, suggesting that choices of first line treatment might need to be re-evaluated in less well developed countries."

"We are not able to advise clinicians on which antibiotic is best to prescribe as this often depends on the individual case," Bryce and Dr. Costelloe said. "Clinicians should, however, adhere to local or national guidelines wherever possible, which is why it is of great importance that such guidelines are kept up to date and reflect current resistance rates."

"Clinicians may also wish to consider the antibiotic history of the child when they present to primary care with symptoms of an infection, especially in light of the suggestion of our results that previous treatment with an antibiotic is associated with resistance to that same antibiotic, and that this association may be present up to 6 months post treatment," they added.

Dr. Grant Russell from Monash University in Melbourne, Australia, wrote an editorial accompanying the report. He told Reuters Health by email, "I found the extent of the resistance (and the fact that it covered all of the regularly used empiric antibiotics) both concerning and surprising. The fact that choices are diminishing is disturbing, and the fact that the situation is dire in the developing world is deeply troubling."

"We need to do what we can do to prevent bacterial infections, and when treating them to consider that effective antibiotics are a finite resource," he said. "We all have a responsibility in attempting to conserve that resource."

"No new classes of antibiotics have been developed in the last 30 years - this and the dire situation in both the developed and the developing world suggests that the 'global problem' of antibiotic resistance is going to become more and more of an issue in years and decades to come," Dr. Russell concluded.

NEW YORK (Reuters Health) - In the absence of a congenital anomaly, the main cause of inferior vena cava (IVC) thrombosis is the presence of an unretrieved IVC filter, researchers report.

"Since IVC filter thrombosis is the main etiology for IVC thrombosis, physicians may want to ensure the absolute need for the filter before its placement," Dr. Mohamad Alkhouli from University of Rochester Medical Center, New York told Reuters Health by email. "A tracking system should be instituted to follow up with these patients, and the implanted IVC filter should be pulled out as soon as is safe and reasonable."

IVC thrombosis accompanies lower extremity deep vein thrombosis (DVT) in 4% or more of patients, leading to post-thrombotic syndrome (PTS) in up to 90% of patients, disabling venous claudication in 45%, pulmonary embolism in 30%, and venous ulceration in 15%, according to Dr. Alkhouli and colleagues, who reviewed the diagnosis and management of IVC thrombosis in a report online March 9th in JACC: Cardiovascular Interventions.

IVC filter placement rates are 25 times higher in the U.S. than in Europe, and late filter thrombosis has been reported in up to a third of patients, yet retrieval rates are consistently low.

Presenting symptoms of IVC thrombosis include leg heaviness, pain, swelling, and cramping, often preceded by nonspecific back and abdominal/pelvic pain. Because of the ambiguous symptoms and insidious onset, IVC thrombosis often goes undiagnosed until clot migration or embolization into the lungs and renal veins results in dyspnea and oliguria.

Lower extremity duplex ultrasound can be used to screen for IVC thrombosis, but appropriately timed CT and MRI are essential for diagnosis and assessment of the extent of thrombosis.

Once IVC thrombosis is diagnosed, the mainstay of treatment is anticoagulation, although specific guidelines are lacking.

In observational studies, thrombus removal with pharmacomechanical catheter directed thrombolysis (PMCT) has reduced the incidence of PTS and improved quality of life, but whether this is as safe as standard anticoagulation remains unclear.

While acute thrombosis may be amenable to PMCT and catheter-directed thrombolysis (CDT), the presence of a fibrotic component in patients who present late may require balloon venoplasty with or without stenting.

The available treatments work best when IVC thrombosis is recognized early, Dr. Alkhouli said.

Dr. Michael Jaff from Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, who wrote an editorial related to this report, told Reuters Health by email, "Limit placement of IVC filters to only absolute indications, and retrieve them as soon as possible."

Dr. Jaff explained, "There are three basic questions I ask myself when considering catheter-based intervention for IVC thrombosis: (1) How long has the patient had symptoms/signs suggestive of this, and how severe are they? (2) What is my estimation of bleeding risk? (3) Do I have an interventionist with skill and experience available to perform the intervention?"

He continued, "Regarding question 1, shorter duration of symptoms and more severe symptoms and signs prompt me to aggressively consider catheter-based intervention. Regarding question 2, if there is significant bleeding risk (for example, inflammatory bowel disease as the underlying culprit for the IVC thrombosis), I am reluctant to consider catheter-based intervention.Regarding question 3, don't consider this if your colleague has little experience performing this procedure or managing the complications of the procedure."

Dr. Xiao-Qiang Li from Second Affiliated Hospital of Soochow University in Suzhou, China, who recently described the experience with CDT combined with manual aspiration thrombectomy for acute inferior vena cava filter thrombosis, told Reuters Health by email, "As you see, no consensuses have been reached."

"For a new patient with acute DVT, if he or she has no contraindications for thrombolysis, especially with a life expectancy more than one year, we prefer to perform catheter-based interventions, including catheter-directed thrombolysis, pharmacomechanical thrombolysis, ultrasound-assisted catheter-directed thrombolysis and subsequent percutaneous transluminal angioplasty and stenting,"Dr. Li said."But, of note, anticoagulation is the basic treatment whatever catheter-based interventions are adopted."

NEW YORK (Reuters Health) - In the absence of a congenital anomaly, the main cause of inferior vena cava (IVC) thrombosis is the presence of an unretrieved IVC filter, researchers report.

"Since IVC filter thrombosis is the main etiology for IVC thrombosis, physicians may want to ensure the absolute need for the filter before its placement," Dr. Mohamad Alkhouli from University of Rochester Medical Center, New York told Reuters Health by email. "A tracking system should be instituted to follow up with these patients, and the implanted IVC filter should be pulled out as soon as is safe and reasonable."

IVC thrombosis accompanies lower extremity deep vein thrombosis (DVT) in 4% or more of patients, leading to post-thrombotic syndrome (PTS) in up to 90% of patients, disabling venous claudication in 45%, pulmonary embolism in 30%, and venous ulceration in 15%, according to Dr. Alkhouli and colleagues, who reviewed the diagnosis and management of IVC thrombosis in a report online March 9th in JACC: Cardiovascular Interventions.

IVC filter placement rates are 25 times higher in the U.S. than in Europe, and late filter thrombosis has been reported in up to a third of patients, yet retrieval rates are consistently low.

Presenting symptoms of IVC thrombosis include leg heaviness, pain, swelling, and cramping, often preceded by nonspecific back and abdominal/pelvic pain. Because of the ambiguous symptoms and insidious onset, IVC thrombosis often goes undiagnosed until clot migration or embolization into the lungs and renal veins results in dyspnea and oliguria.

Lower extremity duplex ultrasound can be used to screen for IVC thrombosis, but appropriately timed CT and MRI are essential for diagnosis and assessment of the extent of thrombosis.

Once IVC thrombosis is diagnosed, the mainstay of treatment is anticoagulation, although specific guidelines are lacking.

In observational studies, thrombus removal with pharmacomechanical catheter directed thrombolysis (PMCT) has reduced the incidence of PTS and improved quality of life, but whether this is as safe as standard anticoagulation remains unclear.

While acute thrombosis may be amenable to PMCT and catheter-directed thrombolysis (CDT), the presence of a fibrotic component in patients who present late may require balloon venoplasty with or without stenting.

The available treatments work best when IVC thrombosis is recognized early, Dr. Alkhouli said.

Dr. Michael Jaff from Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, who wrote an editorial related to this report, told Reuters Health by email, "Limit placement of IVC filters to only absolute indications, and retrieve them as soon as possible."

Dr. Jaff explained, "There are three basic questions I ask myself when considering catheter-based intervention for IVC thrombosis: (1) How long has the patient had symptoms/signs suggestive of this, and how severe are they? (2) What is my estimation of bleeding risk? (3) Do I have an interventionist with skill and experience available to perform the intervention?"

He continued, "Regarding question 1, shorter duration of symptoms and more severe symptoms and signs prompt me to aggressively consider catheter-based intervention. Regarding question 2, if there is significant bleeding risk (for example, inflammatory bowel disease as the underlying culprit for the IVC thrombosis), I am reluctant to consider catheter-based intervention.Regarding question 3, don't consider this if your colleague has little experience performing this procedure or managing the complications of the procedure."

Dr. Xiao-Qiang Li from Second Affiliated Hospital of Soochow University in Suzhou, China, who recently described the experience with CDT combined with manual aspiration thrombectomy for acute inferior vena cava filter thrombosis, told Reuters Health by email, "As you see, no consensuses have been reached."

"For a new patient with acute DVT, if he or she has no contraindications for thrombolysis, especially with a life expectancy more than one year, we prefer to perform catheter-based interventions, including catheter-directed thrombolysis, pharmacomechanical thrombolysis, ultrasound-assisted catheter-directed thrombolysis and subsequent percutaneous transluminal angioplasty and stenting,"Dr. Li said."But, of note, anticoagulation is the basic treatment whatever catheter-based interventions are adopted."

NEW YORK (Reuters Health) - In the absence of a congenital anomaly, the main cause of inferior vena cava (IVC) thrombosis is the presence of an unretrieved IVC filter, researchers report.

"Since IVC filter thrombosis is the main etiology for IVC thrombosis, physicians may want to ensure the absolute need for the filter before its placement," Dr. Mohamad Alkhouli from University of Rochester Medical Center, New York told Reuters Health by email. "A tracking system should be instituted to follow up with these patients, and the implanted IVC filter should be pulled out as soon as is safe and reasonable."

IVC thrombosis accompanies lower extremity deep vein thrombosis (DVT) in 4% or more of patients, leading to post-thrombotic syndrome (PTS) in up to 90% of patients, disabling venous claudication in 45%, pulmonary embolism in 30%, and venous ulceration in 15%, according to Dr. Alkhouli and colleagues, who reviewed the diagnosis and management of IVC thrombosis in a report online March 9th in JACC: Cardiovascular Interventions.

IVC filter placement rates are 25 times higher in the U.S. than in Europe, and late filter thrombosis has been reported in up to a third of patients, yet retrieval rates are consistently low.

Presenting symptoms of IVC thrombosis include leg heaviness, pain, swelling, and cramping, often preceded by nonspecific back and abdominal/pelvic pain. Because of the ambiguous symptoms and insidious onset, IVC thrombosis often goes undiagnosed until clot migration or embolization into the lungs and renal veins results in dyspnea and oliguria.

Lower extremity duplex ultrasound can be used to screen for IVC thrombosis, but appropriately timed CT and MRI are essential for diagnosis and assessment of the extent of thrombosis.

Once IVC thrombosis is diagnosed, the mainstay of treatment is anticoagulation, although specific guidelines are lacking.

In observational studies, thrombus removal with pharmacomechanical catheter directed thrombolysis (PMCT) has reduced the incidence of PTS and improved quality of life, but whether this is as safe as standard anticoagulation remains unclear.

While acute thrombosis may be amenable to PMCT and catheter-directed thrombolysis (CDT), the presence of a fibrotic component in patients who present late may require balloon venoplasty with or without stenting.

The available treatments work best when IVC thrombosis is recognized early, Dr. Alkhouli said.

Dr. Michael Jaff from Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, who wrote an editorial related to this report, told Reuters Health by email, "Limit placement of IVC filters to only absolute indications, and retrieve them as soon as possible."

Dr. Jaff explained, "There are three basic questions I ask myself when considering catheter-based intervention for IVC thrombosis: (1) How long has the patient had symptoms/signs suggestive of this, and how severe are they? (2) What is my estimation of bleeding risk? (3) Do I have an interventionist with skill and experience available to perform the intervention?"

He continued, "Regarding question 1, shorter duration of symptoms and more severe symptoms and signs prompt me to aggressively consider catheter-based intervention. Regarding question 2, if there is significant bleeding risk (for example, inflammatory bowel disease as the underlying culprit for the IVC thrombosis), I am reluctant to consider catheter-based intervention.Regarding question 3, don't consider this if your colleague has little experience performing this procedure or managing the complications of the procedure."

Dr. Xiao-Qiang Li from Second Affiliated Hospital of Soochow University in Suzhou, China, who recently described the experience with CDT combined with manual aspiration thrombectomy for acute inferior vena cava filter thrombosis, told Reuters Health by email, "As you see, no consensuses have been reached."

"For a new patient with acute DVT, if he or she has no contraindications for thrombolysis, especially with a life expectancy more than one year, we prefer to perform catheter-based interventions, including catheter-directed thrombolysis, pharmacomechanical thrombolysis, ultrasound-assisted catheter-directed thrombolysis and subsequent percutaneous transluminal angioplasty and stenting,"Dr. Li said."But, of note, anticoagulation is the basic treatment whatever catheter-based interventions are adopted."

NEW YORK (Reuters Health) - The Sepsis Definitions Task Force, using expanded quantitative information, has updated its definitions for sepsis and septic shock and the clinical criteria underlying them.

Two reports and one summary communication published in JAMA February 23 detail the processes used to reach the consensus

definitions that have remained largely unchanged for more than two decades.

"The new definitions and clinical criteria of sepsis and septic shock are aimed to help clinicians at the bedside recognize these deadly syndromes and start therapy promptly," Dr. Christopher W. Seymour, from the University of Pittsburgh School of Medicine in Pennsylvania, told Reuters Health by email.

"After two years of deliberations and research, we were surprised to uncover the broad differences in how clinicians approach sepsis, and variety of criteria used in septic shock trials in the past decade. This mandated a re-examination of the criteria, strong efforts to speak a common language, and generate simple, easy to use criteria," Dr. Seymour said.

Dr. Seymour and colleagues recommended elimination of the terms sepsis syndrome, septicemia, and severe sepsis and settled on the definition of sepsis as "life-threatening organ dysfunction due to a dysregulated host response to infection."

They explored several sets of clinical criteria and their predictive validity for hospital mortality, including the Sequential Organ Function Assessment (SOFA), Logistic Organ Dysfunction System (LODS), systemic inflammatory response syndrome (SIRS), and a simplified qSOFA model that included Glasgow Coma Scale (GCS) score of 13 or less, systolic blood pressure of 100 mm Hg or less, and respiratory rate of 22/min or more (1 point each; score range, 0-3).

For intensive care unit encounters with suspected infection, SOFA came out on top, whereas for encounters with suspected infection outside of the ICU, qSOFA offered the best predictive validity for in-hospital mortality.

"Sepsis has no gold standard for diagnosis," Dr. Seymour said. "Given its complex pathophysiology and our evolving knowledge base, the current definition and criteria for sepsis represent a first step. Our field will need to continue to embark on improvements in the practicality, validity, and scientific rationale for sepsis definitions/criteria in future iterations."

He added,"We also hope that physicians recognize that, for the first time, these criteria derive from new data analyses in real patients. More than 700,000 encounters in 170 hospitals were studied to evaluate existing and new sepsis criteria."

Dr. Manu Shankar-Hari, from Guy's and St. Thomas' NHS Foundation Trust, London, UK, and colleagues reviewed 44 studies of septic shock involving 166,479 patients and used a Delphi process to arrive at the new consensus definition: "septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone."

Dr. Shankar-Hari told Reuters Health by email, "The proposed definition for septic shock is a paradigm shift in illness concept. We wanted to provide consistency in diagnosing septic shock. The epidemiology of this illness as we measure currently is messy."

After examining six possible sets of clinical criteria, the group identified two criteria that proved most consistent with the proposed septic shock definition: hypotension requiring use of vasopressors to maintain mean blood pressure of 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L persisting after adequate fluid resuscitation.

In their summary report, Dr. Clifford S. Deutschman, from Hofstra-Northwell School of Medicine, Feinstein Institute for Medical Research, New Hyde Park, New York, and colleagues on the Task Force write, "The proposed criteria should aid diagnostic categorization once initial assessment and immediate management are completed. qSOFA or SOFA may at some point be used as entry criteria for clinical trials."

"Greater clarity and consistency will also facilitate research and more accurate coding," they add.

Dr. Edward Abraham, from Wake Forest School of Medicine, Winston Salem, North Carolina, who wrote an editorial related to these reports, told Reuters Health by email, "While the new definitions advance the field, particularly from an epidemiologic viewpoint and potentially in helping to identify the economic impact associated with sepsis and septic shock, they are only of limited help in defining care for an individual patient or in designing clinical trials to examine new therapies for sepsis."

"As noted in the editorial, more discriminatory definitions, based on specific cellular and genomic alterations, are necessary to truly affect care for individual patients and to assist in the development of novel therapeutic approaches to sepsis and septic shock," he said.

A number of organizations supported this research and a number of coauthors reported disclosures.

NEW YORK (Reuters Health) - The Sepsis Definitions Task Force, using expanded quantitative information, has updated its definitions for sepsis and septic shock and the clinical criteria underlying them.

Two reports and one summary communication published in JAMA February 23 detail the processes used to reach the consensus

definitions that have remained largely unchanged for more than two decades.

"The new definitions and clinical criteria of sepsis and septic shock are aimed to help clinicians at the bedside recognize these deadly syndromes and start therapy promptly," Dr. Christopher W. Seymour, from the University of Pittsburgh School of Medicine in Pennsylvania, told Reuters Health by email.

"After two years of deliberations and research, we were surprised to uncover the broad differences in how clinicians approach sepsis, and variety of criteria used in septic shock trials in the past decade. This mandated a re-examination of the criteria, strong efforts to speak a common language, and generate simple, easy to use criteria," Dr. Seymour said.

Dr. Seymour and colleagues recommended elimination of the terms sepsis syndrome, septicemia, and severe sepsis and settled on the definition of sepsis as "life-threatening organ dysfunction due to a dysregulated host response to infection."

They explored several sets of clinical criteria and their predictive validity for hospital mortality, including the Sequential Organ Function Assessment (SOFA), Logistic Organ Dysfunction System (LODS), systemic inflammatory response syndrome (SIRS), and a simplified qSOFA model that included Glasgow Coma Scale (GCS) score of 13 or less, systolic blood pressure of 100 mm Hg or less, and respiratory rate of 22/min or more (1 point each; score range, 0-3).

For intensive care unit encounters with suspected infection, SOFA came out on top, whereas for encounters with suspected infection outside of the ICU, qSOFA offered the best predictive validity for in-hospital mortality.

"Sepsis has no gold standard for diagnosis," Dr. Seymour said. "Given its complex pathophysiology and our evolving knowledge base, the current definition and criteria for sepsis represent a first step. Our field will need to continue to embark on improvements in the practicality, validity, and scientific rationale for sepsis definitions/criteria in future iterations."

He added,"We also hope that physicians recognize that, for the first time, these criteria derive from new data analyses in real patients. More than 700,000 encounters in 170 hospitals were studied to evaluate existing and new sepsis criteria."

Dr. Manu Shankar-Hari, from Guy's and St. Thomas' NHS Foundation Trust, London, UK, and colleagues reviewed 44 studies of septic shock involving 166,479 patients and used a Delphi process to arrive at the new consensus definition: "septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone."

Dr. Shankar-Hari told Reuters Health by email, "The proposed definition for septic shock is a paradigm shift in illness concept. We wanted to provide consistency in diagnosing septic shock. The epidemiology of this illness as we measure currently is messy."

After examining six possible sets of clinical criteria, the group identified two criteria that proved most consistent with the proposed septic shock definition: hypotension requiring use of vasopressors to maintain mean blood pressure of 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L persisting after adequate fluid resuscitation.

In their summary report, Dr. Clifford S. Deutschman, from Hofstra-Northwell School of Medicine, Feinstein Institute for Medical Research, New Hyde Park, New York, and colleagues on the Task Force write, "The proposed criteria should aid diagnostic categorization once initial assessment and immediate management are completed. qSOFA or SOFA may at some point be used as entry criteria for clinical trials."

"Greater clarity and consistency will also facilitate research and more accurate coding," they add.

Dr. Edward Abraham, from Wake Forest School of Medicine, Winston Salem, North Carolina, who wrote an editorial related to these reports, told Reuters Health by email, "While the new definitions advance the field, particularly from an epidemiologic viewpoint and potentially in helping to identify the economic impact associated with sepsis and septic shock, they are only of limited help in defining care for an individual patient or in designing clinical trials to examine new therapies for sepsis."

"As noted in the editorial, more discriminatory definitions, based on specific cellular and genomic alterations, are necessary to truly affect care for individual patients and to assist in the development of novel therapeutic approaches to sepsis and septic shock," he said.

A number of organizations supported this research and a number of coauthors reported disclosures.

NEW YORK (Reuters Health) - The Sepsis Definitions Task Force, using expanded quantitative information, has updated its definitions for sepsis and septic shock and the clinical criteria underlying them.

Two reports and one summary communication published in JAMA February 23 detail the processes used to reach the consensus

definitions that have remained largely unchanged for more than two decades.

"The new definitions and clinical criteria of sepsis and septic shock are aimed to help clinicians at the bedside recognize these deadly syndromes and start therapy promptly," Dr. Christopher W. Seymour, from the University of Pittsburgh School of Medicine in Pennsylvania, told Reuters Health by email.

"After two years of deliberations and research, we were surprised to uncover the broad differences in how clinicians approach sepsis, and variety of criteria used in septic shock trials in the past decade. This mandated a re-examination of the criteria, strong efforts to speak a common language, and generate simple, easy to use criteria," Dr. Seymour said.

Dr. Seymour and colleagues recommended elimination of the terms sepsis syndrome, septicemia, and severe sepsis and settled on the definition of sepsis as "life-threatening organ dysfunction due to a dysregulated host response to infection."

They explored several sets of clinical criteria and their predictive validity for hospital mortality, including the Sequential Organ Function Assessment (SOFA), Logistic Organ Dysfunction System (LODS), systemic inflammatory response syndrome (SIRS), and a simplified qSOFA model that included Glasgow Coma Scale (GCS) score of 13 or less, systolic blood pressure of 100 mm Hg or less, and respiratory rate of 22/min or more (1 point each; score range, 0-3).

For intensive care unit encounters with suspected infection, SOFA came out on top, whereas for encounters with suspected infection outside of the ICU, qSOFA offered the best predictive validity for in-hospital mortality.

"Sepsis has no gold standard for diagnosis," Dr. Seymour said. "Given its complex pathophysiology and our evolving knowledge base, the current definition and criteria for sepsis represent a first step. Our field will need to continue to embark on improvements in the practicality, validity, and scientific rationale for sepsis definitions/criteria in future iterations."

He added,"We also hope that physicians recognize that, for the first time, these criteria derive from new data analyses in real patients. More than 700,000 encounters in 170 hospitals were studied to evaluate existing and new sepsis criteria."

Dr. Manu Shankar-Hari, from Guy's and St. Thomas' NHS Foundation Trust, London, UK, and colleagues reviewed 44 studies of septic shock involving 166,479 patients and used a Delphi process to arrive at the new consensus definition: "septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone."

Dr. Shankar-Hari told Reuters Health by email, "The proposed definition for septic shock is a paradigm shift in illness concept. We wanted to provide consistency in diagnosing septic shock. The epidemiology of this illness as we measure currently is messy."

After examining six possible sets of clinical criteria, the group identified two criteria that proved most consistent with the proposed septic shock definition: hypotension requiring use of vasopressors to maintain mean blood pressure of 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L persisting after adequate fluid resuscitation.

In their summary report, Dr. Clifford S. Deutschman, from Hofstra-Northwell School of Medicine, Feinstein Institute for Medical Research, New Hyde Park, New York, and colleagues on the Task Force write, "The proposed criteria should aid diagnostic categorization once initial assessment and immediate management are completed. qSOFA or SOFA may at some point be used as entry criteria for clinical trials."

"Greater clarity and consistency will also facilitate research and more accurate coding," they add.

Dr. Edward Abraham, from Wake Forest School of Medicine, Winston Salem, North Carolina, who wrote an editorial related to these reports, told Reuters Health by email, "While the new definitions advance the field, particularly from an epidemiologic viewpoint and potentially in helping to identify the economic impact associated with sepsis and septic shock, they are only of limited help in defining care for an individual patient or in designing clinical trials to examine new therapies for sepsis."

"As noted in the editorial, more discriminatory definitions, based on specific cellular and genomic alterations, are necessary to truly affect care for individual patients and to assist in the development of novel therapeutic approaches to sepsis and septic shock," he said.

A number of organizations supported this research and a number of coauthors reported disclosures.

NEW YORK (Reuters Health) - Opioid modulation with the combination of buprenorphine and samidorphan (ALKS 5461) improves symptoms in patients whose depression has not responded adequately to antidepressant treatment, researchers report.

"If the findings are confirmed in phase 3 studies, ALKS 5461 could be used as an augmenting agent in patients not responding to standard antidepressant therapies as an alternative to the atypical antipsychotic agents currently approved for the treatment of this population," Dr. Maurizio Fava, from Massachusetts General Hospital and Harvard Medical School, Boston, told Reuters Health by email.

Buprenorphine is a mu- and kappa-opioid partial agonist, and samidorphan blocks the mu agonist effects of buprenorphine associated with its abuse and addictive potential. A growing body of evidence implicates dysregulation of the endogenous mu- and kappa-opioid system in mood disorders.

Dr. Fava and colleagues at 31 sites in the U.S. used a sequential parallel comparison design to investigate the efficacy of buprenorphine/samidorphan (2 mg/2 mg or 8 mg/8 mg) in 142 patients with major depression inadequately responsive to antidepressant therapy.

At the end of four weeks of treatment, patients in the ALKS 5461 2 mg/2 mg group showed significantly greater improvements in Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression severity scores, compared with patients in the placebo group. The ALKS 5461 8 mg/8 mg group showed smaller, nonsignificant improvements.

"The overall effect sizes for the 2/2 dosage were 0.50 for HAM-D and 0.54 for MADRS," the researchers noted. "The result compares favorably with results from a meta-analysis of 14 studies with atypical antipsychotics as adjunctive therapy for major depression, with reported effect sizes of 0.35 to 0.48 for individual drugs."

Treatment response rates according to HAM-D and MADRS (at least 50% reduction in scores) were highest with ALKS 5461 2 mg/2 mg treatment group, according to the February 12 onlinereport in the American Journal of Psychiatry.

Two patients (1.6%) in the placebo group and 17 patients (19.3%) in the ALKS 5461 groups discontinued because of treatment-emergent adverse events, but there was no evidence of opioid withdrawal in any patient.

"When depressed patients do not respond to standard monoamine-based therapies for depression, consider the use of an augmenting agent that modulates other systems, such as the opioid one," Dr. Fava concluded.

Dr. Jeffrey F. Scherrer, from Saint Louis University School of Medicine, St. Louis, Missouri, recently examined the association between opioid use and increased depression rates. He told Reuters Health by email, "Our analysis of opioid use and depression did not include buprenorphine among the opioid exposure variable. Therefore, it is difficult to extrapolate our results to a trial of buprenorphine/samidorphan and major depression."

"As the authors noted, the clinical trial was of short duration and the risks of depression that we have observed appears to be greatest among those patients remaining on opioids for more than 90 days," he explained. "Additional work is currently being done to determine if some opioid medications have a greater depressogenic effect than others, which further limits direct comparison of our findings to the current study."

"I will say that it is unlikely for oxycodone, codeine, and hydrocodone (which together account for more than 90% of prescribed opioids) would help depressed patients and be more likely to worsen their depression with chronic treatment," Dr. Scherrer concluded.

Alkermes sponsored the trial, employed seven coauthors, and had various relationships with the other four coauthors.

NEW YORK (Reuters Health) - Opioid modulation with the combination of buprenorphine and samidorphan (ALKS 5461) improves symptoms in patients whose depression has not responded adequately to antidepressant treatment, researchers report.

"If the findings are confirmed in phase 3 studies, ALKS 5461 could be used as an augmenting agent in patients not responding to standard antidepressant therapies as an alternative to the atypical antipsychotic agents currently approved for the treatment of this population," Dr. Maurizio Fava, from Massachusetts General Hospital and Harvard Medical School, Boston, told Reuters Health by email.

Buprenorphine is a mu- and kappa-opioid partial agonist, and samidorphan blocks the mu agonist effects of buprenorphine associated with its abuse and addictive potential. A growing body of evidence implicates dysregulation of the endogenous mu- and kappa-opioid system in mood disorders.

Dr. Fava and colleagues at 31 sites in the U.S. used a sequential parallel comparison design to investigate the efficacy of buprenorphine/samidorphan (2 mg/2 mg or 8 mg/8 mg) in 142 patients with major depression inadequately responsive to antidepressant therapy.

At the end of four weeks of treatment, patients in the ALKS 5461 2 mg/2 mg group showed significantly greater improvements in Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression severity scores, compared with patients in the placebo group. The ALKS 5461 8 mg/8 mg group showed smaller, nonsignificant improvements.

"The overall effect sizes for the 2/2 dosage were 0.50 for HAM-D and 0.54 for MADRS," the researchers noted. "The result compares favorably with results from a meta-analysis of 14 studies with atypical antipsychotics as adjunctive therapy for major depression, with reported effect sizes of 0.35 to 0.48 for individual drugs."

Treatment response rates according to HAM-D and MADRS (at least 50% reduction in scores) were highest with ALKS 5461 2 mg/2 mg treatment group, according to the February 12 onlinereport in the American Journal of Psychiatry.

Two patients (1.6%) in the placebo group and 17 patients (19.3%) in the ALKS 5461 groups discontinued because of treatment-emergent adverse events, but there was no evidence of opioid withdrawal in any patient.

"When depressed patients do not respond to standard monoamine-based therapies for depression, consider the use of an augmenting agent that modulates other systems, such as the opioid one," Dr. Fava concluded.

Dr. Jeffrey F. Scherrer, from Saint Louis University School of Medicine, St. Louis, Missouri, recently examined the association between opioid use and increased depression rates. He told Reuters Health by email, "Our analysis of opioid use and depression did not include buprenorphine among the opioid exposure variable. Therefore, it is difficult to extrapolate our results to a trial of buprenorphine/samidorphan and major depression."

"As the authors noted, the clinical trial was of short duration and the risks of depression that we have observed appears to be greatest among those patients remaining on opioids for more than 90 days," he explained. "Additional work is currently being done to determine if some opioid medications have a greater depressogenic effect than others, which further limits direct comparison of our findings to the current study."

"I will say that it is unlikely for oxycodone, codeine, and hydrocodone (which together account for more than 90% of prescribed opioids) would help depressed patients and be more likely to worsen their depression with chronic treatment," Dr. Scherrer concluded.

Alkermes sponsored the trial, employed seven coauthors, and had various relationships with the other four coauthors.

NEW YORK (Reuters Health) - Opioid modulation with the combination of buprenorphine and samidorphan (ALKS 5461) improves symptoms in patients whose depression has not responded adequately to antidepressant treatment, researchers report.

"If the findings are confirmed in phase 3 studies, ALKS 5461 could be used as an augmenting agent in patients not responding to standard antidepressant therapies as an alternative to the atypical antipsychotic agents currently approved for the treatment of this population," Dr. Maurizio Fava, from Massachusetts General Hospital and Harvard Medical School, Boston, told Reuters Health by email.

Buprenorphine is a mu- and kappa-opioid partial agonist, and samidorphan blocks the mu agonist effects of buprenorphine associated with its abuse and addictive potential. A growing body of evidence implicates dysregulation of the endogenous mu- and kappa-opioid system in mood disorders.

Dr. Fava and colleagues at 31 sites in the U.S. used a sequential parallel comparison design to investigate the efficacy of buprenorphine/samidorphan (2 mg/2 mg or 8 mg/8 mg) in 142 patients with major depression inadequately responsive to antidepressant therapy.

At the end of four weeks of treatment, patients in the ALKS 5461 2 mg/2 mg group showed significantly greater improvements in Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression severity scores, compared with patients in the placebo group. The ALKS 5461 8 mg/8 mg group showed smaller, nonsignificant improvements.

"The overall effect sizes for the 2/2 dosage were 0.50 for HAM-D and 0.54 for MADRS," the researchers noted. "The result compares favorably with results from a meta-analysis of 14 studies with atypical antipsychotics as adjunctive therapy for major depression, with reported effect sizes of 0.35 to 0.48 for individual drugs."

Treatment response rates according to HAM-D and MADRS (at least 50% reduction in scores) were highest with ALKS 5461 2 mg/2 mg treatment group, according to the February 12 onlinereport in the American Journal of Psychiatry.

Two patients (1.6%) in the placebo group and 17 patients (19.3%) in the ALKS 5461 groups discontinued because of treatment-emergent adverse events, but there was no evidence of opioid withdrawal in any patient.

"When depressed patients do not respond to standard monoamine-based therapies for depression, consider the use of an augmenting agent that modulates other systems, such as the opioid one," Dr. Fava concluded.

Dr. Jeffrey F. Scherrer, from Saint Louis University School of Medicine, St. Louis, Missouri, recently examined the association between opioid use and increased depression rates. He told Reuters Health by email, "Our analysis of opioid use and depression did not include buprenorphine among the opioid exposure variable. Therefore, it is difficult to extrapolate our results to a trial of buprenorphine/samidorphan and major depression."

"As the authors noted, the clinical trial was of short duration and the risks of depression that we have observed appears to be greatest among those patients remaining on opioids for more than 90 days," he explained. "Additional work is currently being done to determine if some opioid medications have a greater depressogenic effect than others, which further limits direct comparison of our findings to the current study."

"I will say that it is unlikely for oxycodone, codeine, and hydrocodone (which together account for more than 90% of prescribed opioids) would help depressed patients and be more likely to worsen their depression with chronic treatment," Dr. Scherrer concluded.

Alkermes sponsored the trial, employed seven coauthors, and had various relationships with the other four coauthors.

NEW YORK (Reuters Health) - Only two strategies offer some effectiveness in preventing contrast-induced nephropathy (CIN), according to a systematic review and meta-analysis of 86 randomized, controlled trials.

Those are use of N-acetylcysteine (NAc) in patients receiving low-osmolar contrast media (LOCM), and statins plus NAc.

The reported incidence of CIN, defined as an increase in serum creatinine levels >25% or 44.2 mmol/L (0.5 mg/dL) within three days of IV administration of contrast media, ranges from 7% to 11% and adds an average $10,345 to a CIN-related hospital stay. There is no clear consensus about the most effective intervention to prevent or reduce CIN.

Dr. Rathan M. Subramaniam and colleagues from Johns Hopkins University in Baltimore compared five strategies for preventing CIN in their systematic review and meta-analysis: IV NAc plus saline versus IV saline alone; IV sodium bicarbonate versus IV saline; NAc plus IV saline versus IV sodium bicarbonate; statins with or without NAc versus IV saline; and ascorbic acid versus NAc or IV saline.

In the NAc studies, all of which had low strength of evidence, NAc had a clinically important benefit in reducing CIN risk only when LOCM were used.

Low-dose NAc had a borderline clinically important effect on preventing CIN, whereas high-dose NAc had a statistically significant (but clinically unimportant) effect on reducing CIN risk (with low strength of evidence).

Similarly, statins when added to NAc showed a clinically important reduction in CIN risk, although with low strength of evidence.

IV sodium bicarbonate (versus IV saline), NAc (versus IV sodium bicarbonate), and ascorbic acid (versus other strategies) showed no statistically significant, clinically important benefit in reducing CIN risk, according to the report onine February 1 in Annals of Internal Medicine online.

"The studies span over two decades, and there may have been changes in the practice of CIN prevention, such as increased screening, variation in definition of acute kidney injury, and variation in hydration, over time," the researchers noted. "Such changes could contribute to differences in outcomes."

"This comprehensive review highlights the generally low strength of evidence on interventions for preventing CIN while indicating that the greatest reduction in CIN risk has been achieved with low-dose N-acetylcysteine in patients receiving LOCM or with statins plus N-acetylcysteine," they concluded.

In a related article, the group from Johns Hopkins University found no differences in CIN risk among the different types of LOCM. Iodixanol had a slightly lower risk of CIN than LOCM did, but the difference was not clinically important.

Dr. Guillaume Mahe from CHU de Rennes, Rennes, France recently reviewed remote ischemic preconditioning, another proposed method for preventing CIN (http://bit.ly/23EU40a). He told Reuters Health by email, "It seems of interest to use N-acetylcysteine, which is a low cost drug. Statins might be also a good option. This is another interesting effect of the statins, which is unknown by most physicians."

Even more important, Dr. Mahe said, is to "be sure that the patients need a computed tomography angiography with contrast media."

He expressed surprise that the authors did not assess the role of remote ischemic preconditioning in their review.

Dr. Subramaniam did not respond to a request for comments. The Agency for Healthcare Research and Quality funded both studies.

NEW YORK (Reuters Health) - Only two strategies offer some effectiveness in preventing contrast-induced nephropathy (CIN), according to a systematic review and meta-analysis of 86 randomized, controlled trials.

Those are use of N-acetylcysteine (NAc) in patients receiving low-osmolar contrast media (LOCM), and statins plus NAc.

The reported incidence of CIN, defined as an increase in serum creatinine levels >25% or 44.2 mmol/L (0.5 mg/dL) within three days of IV administration of contrast media, ranges from 7% to 11% and adds an average $10,345 to a CIN-related hospital stay. There is no clear consensus about the most effective intervention to prevent or reduce CIN.

Dr. Rathan M. Subramaniam and colleagues from Johns Hopkins University in Baltimore compared five strategies for preventing CIN in their systematic review and meta-analysis: IV NAc plus saline versus IV saline alone; IV sodium bicarbonate versus IV saline; NAc plus IV saline versus IV sodium bicarbonate; statins with or without NAc versus IV saline; and ascorbic acid versus NAc or IV saline.

In the NAc studies, all of which had low strength of evidence, NAc had a clinically important benefit in reducing CIN risk only when LOCM were used.

Low-dose NAc had a borderline clinically important effect on preventing CIN, whereas high-dose NAc had a statistically significant (but clinically unimportant) effect on reducing CIN risk (with low strength of evidence).

Similarly, statins when added to NAc showed a clinically important reduction in CIN risk, although with low strength of evidence.

IV sodium bicarbonate (versus IV saline), NAc (versus IV sodium bicarbonate), and ascorbic acid (versus other strategies) showed no statistically significant, clinically important benefit in reducing CIN risk, according to the report onine February 1 in Annals of Internal Medicine online.

"The studies span over two decades, and there may have been changes in the practice of CIN prevention, such as increased screening, variation in definition of acute kidney injury, and variation in hydration, over time," the researchers noted. "Such changes could contribute to differences in outcomes."

"This comprehensive review highlights the generally low strength of evidence on interventions for preventing CIN while indicating that the greatest reduction in CIN risk has been achieved with low-dose N-acetylcysteine in patients receiving LOCM or with statins plus N-acetylcysteine," they concluded.

In a related article, the group from Johns Hopkins University found no differences in CIN risk among the different types of LOCM. Iodixanol had a slightly lower risk of CIN than LOCM did, but the difference was not clinically important.

Dr. Guillaume Mahe from CHU de Rennes, Rennes, France recently reviewed remote ischemic preconditioning, another proposed method for preventing CIN (http://bit.ly/23EU40a). He told Reuters Health by email, "It seems of interest to use N-acetylcysteine, which is a low cost drug. Statins might be also a good option. This is another interesting effect of the statins, which is unknown by most physicians."

Even more important, Dr. Mahe said, is to "be sure that the patients need a computed tomography angiography with contrast media."

He expressed surprise that the authors did not assess the role of remote ischemic preconditioning in their review.

Dr. Subramaniam did not respond to a request for comments. The Agency for Healthcare Research and Quality funded both studies.

NEW YORK (Reuters Health) - Only two strategies offer some effectiveness in preventing contrast-induced nephropathy (CIN), according to a systematic review and meta-analysis of 86 randomized, controlled trials.

Those are use of N-acetylcysteine (NAc) in patients receiving low-osmolar contrast media (LOCM), and statins plus NAc.

The reported incidence of CIN, defined as an increase in serum creatinine levels >25% or 44.2 mmol/L (0.5 mg/dL) within three days of IV administration of contrast media, ranges from 7% to 11% and adds an average $10,345 to a CIN-related hospital stay. There is no clear consensus about the most effective intervention to prevent or reduce CIN.

Dr. Rathan M. Subramaniam and colleagues from Johns Hopkins University in Baltimore compared five strategies for preventing CIN in their systematic review and meta-analysis: IV NAc plus saline versus IV saline alone; IV sodium bicarbonate versus IV saline; NAc plus IV saline versus IV sodium bicarbonate; statins with or without NAc versus IV saline; and ascorbic acid versus NAc or IV saline.

In the NAc studies, all of which had low strength of evidence, NAc had a clinically important benefit in reducing CIN risk only when LOCM were used.

Low-dose NAc had a borderline clinically important effect on preventing CIN, whereas high-dose NAc had a statistically significant (but clinically unimportant) effect on reducing CIN risk (with low strength of evidence).

Similarly, statins when added to NAc showed a clinically important reduction in CIN risk, although with low strength of evidence.

IV sodium bicarbonate (versus IV saline), NAc (versus IV sodium bicarbonate), and ascorbic acid (versus other strategies) showed no statistically significant, clinically important benefit in reducing CIN risk, according to the report onine February 1 in Annals of Internal Medicine online.

"The studies span over two decades, and there may have been changes in the practice of CIN prevention, such as increased screening, variation in definition of acute kidney injury, and variation in hydration, over time," the researchers noted. "Such changes could contribute to differences in outcomes."

"This comprehensive review highlights the generally low strength of evidence on interventions for preventing CIN while indicating that the greatest reduction in CIN risk has been achieved with low-dose N-acetylcysteine in patients receiving LOCM or with statins plus N-acetylcysteine," they concluded.

In a related article, the group from Johns Hopkins University found no differences in CIN risk among the different types of LOCM. Iodixanol had a slightly lower risk of CIN than LOCM did, but the difference was not clinically important.

Dr. Guillaume Mahe from CHU de Rennes, Rennes, France recently reviewed remote ischemic preconditioning, another proposed method for preventing CIN (http://bit.ly/23EU40a). He told Reuters Health by email, "It seems of interest to use N-acetylcysteine, which is a low cost drug. Statins might be also a good option. This is another interesting effect of the statins, which is unknown by most physicians."

Even more important, Dr. Mahe said, is to "be sure that the patients need a computed tomography angiography with contrast media."

He expressed surprise that the authors did not assess the role of remote ischemic preconditioning in their review.

Dr. Subramaniam did not respond to a request for comments. The Agency for Healthcare Research and Quality funded both studies.

NEW YORK (Reuters Health) - Dabigatran and warfarin offer similar stroke-prevention efficacy in patients with atrial fibrillation (AF), but their side effect profiles differ, according to a systematic review and meta-analysis of real-world clinical practice.

"There could be many reasons for the differences in our findings, such as differences in the quality of evidence of observational studies and randomized controlled trials (RCTs) or differences in the included study populations between the observational studies in our review and the RE-LY trial," Dr. Robert J. Romanelli from Palo Alto Medical Foundation Research Institute, California, told Reuters Health by email.

The RE-LY trial is the only RCT to have evaluated dabigatran in stroke prevention, and RCTs are prone to selection biases less likely to be present in well designed observational studies, Dr. Romanelli and colleagues note in Circulation:Cardiovascular and Quality Outcomes, online January 26.

The team used data from seven retrospective cohort studies to compare the effectiveness and safety of dabigatran and warfarin among more than 348,750 patients with nonvalvular AF.

During an overall mean follow-up of 794 days, dabigatran 150mg or 110 mg was similar to warfarin in ischemic stroke prevention.

Both the higher and lower dabigatran doses had significantly lower hazards of intracranial bleeding compared with warfarin (pooled hazard ratio, 0.44 and 0.49, respectively). But the hazard of gastrointestinal bleeding was significantly greater for dabigatran 150 mg (but not for 110 mg) than for warfarin (pHR, 1.23). The 110 mg dose of dabigatran was only available during the trial; it's now sold in 150 mg or 75 mg capsules.

The increased risk of gastrointestinal bleeding with the higher dose of dabigatran was significant only in older populations (75 years or older).

"Data presented in this review reflect relative risk, which is not always clinically meaningful," the researchers caution. "It is important to bear in mind that event rates for the outcome of interest are low under standard treatment."

"I don't think the findings from this one reviewshould change clinical practice," Dr. Romanelli said. "If anything, this study revealed areas for future research.

NEW YORK (Reuters Health) - Dabigatran and warfarin offer similar stroke-prevention efficacy in patients with atrial fibrillation (AF), but their side effect profiles differ, according to a systematic review and meta-analysis of real-world clinical practice.

"There could be many reasons for the differences in our findings, such as differences in the quality of evidence of observational studies and randomized controlled trials (RCTs) or differences in the included study populations between the observational studies in our review and the RE-LY trial," Dr. Robert J. Romanelli from Palo Alto Medical Foundation Research Institute, California, told Reuters Health by email.

The RE-LY trial is the only RCT to have evaluated dabigatran in stroke prevention, and RCTs are prone to selection biases less likely to be present in well designed observational studies, Dr. Romanelli and colleagues note in Circulation:Cardiovascular and Quality Outcomes, online January 26.

The team used data from seven retrospective cohort studies to compare the effectiveness and safety of dabigatran and warfarin among more than 348,750 patients with nonvalvular AF.

During an overall mean follow-up of 794 days, dabigatran 150mg or 110 mg was similar to warfarin in ischemic stroke prevention.

Both the higher and lower dabigatran doses had significantly lower hazards of intracranial bleeding compared with warfarin (pooled hazard ratio, 0.44 and 0.49, respectively). But the hazard of gastrointestinal bleeding was significantly greater for dabigatran 150 mg (but not for 110 mg) than for warfarin (pHR, 1.23). The 110 mg dose of dabigatran was only available during the trial; it's now sold in 150 mg or 75 mg capsules.

The increased risk of gastrointestinal bleeding with the higher dose of dabigatran was significant only in older populations (75 years or older).

"Data presented in this review reflect relative risk, which is not always clinically meaningful," the researchers caution. "It is important to bear in mind that event rates for the outcome of interest are low under standard treatment."

"I don't think the findings from this one reviewshould change clinical practice," Dr. Romanelli said. "If anything, this study revealed areas for future research.

NEW YORK (Reuters Health) - Dabigatran and warfarin offer similar stroke-prevention efficacy in patients with atrial fibrillation (AF), but their side effect profiles differ, according to a systematic review and meta-analysis of real-world clinical practice.

"There could be many reasons for the differences in our findings, such as differences in the quality of evidence of observational studies and randomized controlled trials (RCTs) or differences in the included study populations between the observational studies in our review and the RE-LY trial," Dr. Robert J. Romanelli from Palo Alto Medical Foundation Research Institute, California, told Reuters Health by email.

The RE-LY trial is the only RCT to have evaluated dabigatran in stroke prevention, and RCTs are prone to selection biases less likely to be present in well designed observational studies, Dr. Romanelli and colleagues note in Circulation:Cardiovascular and Quality Outcomes, online January 26.

The team used data from seven retrospective cohort studies to compare the effectiveness and safety of dabigatran and warfarin among more than 348,750 patients with nonvalvular AF.

During an overall mean follow-up of 794 days, dabigatran 150mg or 110 mg was similar to warfarin in ischemic stroke prevention.

Both the higher and lower dabigatran doses had significantly lower hazards of intracranial bleeding compared with warfarin (pooled hazard ratio, 0.44 and 0.49, respectively). But the hazard of gastrointestinal bleeding was significantly greater for dabigatran 150 mg (but not for 110 mg) than for warfarin (pHR, 1.23). The 110 mg dose of dabigatran was only available during the trial; it's now sold in 150 mg or 75 mg capsules.

The increased risk of gastrointestinal bleeding with the higher dose of dabigatran was significant only in older populations (75 years or older).

"Data presented in this review reflect relative risk, which is not always clinically meaningful," the researchers caution. "It is important to bear in mind that event rates for the outcome of interest are low under standard treatment."

"I don't think the findings from this one reviewshould change clinical practice," Dr. Romanelli said. "If anything, this study revealed areas for future research.

NEW YORK (Reuters Health) - Hospital differences in pain management are tied to different patient-reported pain scores after colorectal resection, according to a study from the Michigan Surgical Quality Collaborative (MSQC).

"The best-performing hospitals achieved superior pain control through the use of analgesia regimens that more often used local anesthesia blocks in the operating room,non-steroidal anti-inflammatory drugs, and patient-controlled analgesia rather than intermittent narcotics," said Dr. Scott E. Regenbogen from the University of Michigan, Ann Arbor.

"This suggests that efforts to implement multimodal analgesia regimens may improve pain control in the immediate postoperative period," he told Reuters Health by email.

Despite increasing attention to postoperative pain management, most patients continue to experience severe pain after major surgery, Dr. Regenbogen and colleagues note in Annals of Surgery, online January 7.

The researchers used MSQC data from 52 hospitals to evaluate the extent to which multimodal pain management practices are used after major surgery and how hospitals' perioperative practices might affect patient-reported pain levels in real-world surgical practice. Their study included 7,221 patients who underwent colorectal resection between 2012 and 2014.

Nine hospitals had average adjusted pain scores significantly worse and eight hospitals had average adjusted pain scores significantly better than the overall average. The "best" hospitals were somewhat larger and had higher annual volumes of colorectal resection than the "worst" hospitals.

Patients in hospitals with best pain scores were significantly more likely to receive local anesthesia and epidural anesthesia during the operation and to have patient-controlled analgesia (PCA), nonsteroidal anti-inflammatory drugs (NSAIDs), or a combination of PCA and NSAIDs and significantly less likely to receive intermittent postoperative narcotics, compared with patients in hospitals with worst pain scores.

Hospitals with the lowest pain scores had a significantly higher proportion of operations with a minimally invasive approach than did hospitals with the highest pain scores.

Patients whose operations took place in hospitals in the lowest quartile of pain scores had significantly shorter mean postoperative length of stay and were significantly less likely to have a postoperative complication, emergency department visit, or readmission.

Patient factors contributing to worse pain scores included being younger than 50 (versus age over 75), a woman, black (versus white), a smoker, and uninsured or insured by Medicaid (versus Medicare or privately insured).

"Most likely," the researchers note, "both pain scores and clinical outcomes reflect more global features of the quality of care in hospitals' surgical performance. Thus, hospitals with the most streamlined, high-quality perioperative care pathways experience the best pain scores, as well as improved clinical outcomes."

"Early postoperative analgesia regimens are an essential component of efforts to improve the efficiency and quality of postoperative recovery," Dr. Regenbogen said."Effective pain control, even in the first postoperative day, is associated with reduced postoperative length of stay and fewer major complications and readmissions. Thus, effective multimodal analgesia is an essential component of high-value perioperative care around colorectal surgery."

"This study is hopefully just one example of a growing emphasis on patient-reported outcomes in surgery," Dr.Regenbogen said. "Within a statewide quality collaborative, we have begun to prioritize engagement of patients, in addition to our partnering surgeons, hospitals, and mayors, in efforts to improve surgical care in Michigan. In this study, we used patient-reported pain measures to evaluate quality of care. In the near future, we will elicit patient-reported measures of functional recovery, psychosocial support, and other outcomes to validate the perioperative outcomes we have relied on traditionally. We hope this study will serve as a model for those novel areas of investigation."

Dr. Antoni Sabate from Hospital Universitari de Bellvitge in Barcelona, Spain, who has researched postoperative analgesia told Reuters Health by email, "Pain is largely influenced by magnitude of the surgical procedure, surgical technique (minimally invasive), analgesia protocol (the use of local anesthetic infiltration in open and laparoscopic, the use of epidural in open procedures, implementation of PCA and NSAID in both laparoscopic and open procedures."

NEW YORK (Reuters Health) - Hospital differences in pain management are tied to different patient-reported pain scores after colorectal resection, according to a study from the Michigan Surgical Quality Collaborative (MSQC).

"The best-performing hospitals achieved superior pain control through the use of analgesia regimens that more often used local anesthesia blocks in the operating room,non-steroidal anti-inflammatory drugs, and patient-controlled analgesia rather than intermittent narcotics," said Dr. Scott E. Regenbogen from the University of Michigan, Ann Arbor.

"This suggests that efforts to implement multimodal analgesia regimens may improve pain control in the immediate postoperative period," he told Reuters Health by email.

Despite increasing attention to postoperative pain management, most patients continue to experience severe pain after major surgery, Dr. Regenbogen and colleagues note in Annals of Surgery, online January 7.

The researchers used MSQC data from 52 hospitals to evaluate the extent to which multimodal pain management practices are used after major surgery and how hospitals' perioperative practices might affect patient-reported pain levels in real-world surgical practice. Their study included 7,221 patients who underwent colorectal resection between 2012 and 2014.

Nine hospitals had average adjusted pain scores significantly worse and eight hospitals had average adjusted pain scores significantly better than the overall average. The "best" hospitals were somewhat larger and had higher annual volumes of colorectal resection than the "worst" hospitals.

Patients in hospitals with best pain scores were significantly more likely to receive local anesthesia and epidural anesthesia during the operation and to have patient-controlled analgesia (PCA), nonsteroidal anti-inflammatory drugs (NSAIDs), or a combination of PCA and NSAIDs and significantly less likely to receive intermittent postoperative narcotics, compared with patients in hospitals with worst pain scores.

Hospitals with the lowest pain scores had a significantly higher proportion of operations with a minimally invasive approach than did hospitals with the highest pain scores.

Patients whose operations took place in hospitals in the lowest quartile of pain scores had significantly shorter mean postoperative length of stay and were significantly less likely to have a postoperative complication, emergency department visit, or readmission.

Patient factors contributing to worse pain scores included being younger than 50 (versus age over 75), a woman, black (versus white), a smoker, and uninsured or insured by Medicaid (versus Medicare or privately insured).

"Most likely," the researchers note, "both pain scores and clinical outcomes reflect more global features of the quality of care in hospitals' surgical performance. Thus, hospitals with the most streamlined, high-quality perioperative care pathways experience the best pain scores, as well as improved clinical outcomes."

"Early postoperative analgesia regimens are an essential component of efforts to improve the efficiency and quality of postoperative recovery," Dr. Regenbogen said."Effective pain control, even in the first postoperative day, is associated with reduced postoperative length of stay and fewer major complications and readmissions. Thus, effective multimodal analgesia is an essential component of high-value perioperative care around colorectal surgery."

"This study is hopefully just one example of a growing emphasis on patient-reported outcomes in surgery," Dr.Regenbogen said. "Within a statewide quality collaborative, we have begun to prioritize engagement of patients, in addition to our partnering surgeons, hospitals, and mayors, in efforts to improve surgical care in Michigan. In this study, we used patient-reported pain measures to evaluate quality of care. In the near future, we will elicit patient-reported measures of functional recovery, psychosocial support, and other outcomes to validate the perioperative outcomes we have relied on traditionally. We hope this study will serve as a model for those novel areas of investigation."

Dr. Antoni Sabate from Hospital Universitari de Bellvitge in Barcelona, Spain, who has researched postoperative analgesia told Reuters Health by email, "Pain is largely influenced by magnitude of the surgical procedure, surgical technique (minimally invasive), analgesia protocol (the use of local anesthetic infiltration in open and laparoscopic, the use of epidural in open procedures, implementation of PCA and NSAID in both laparoscopic and open procedures."

NEW YORK (Reuters Health) - Hospital differences in pain management are tied to different patient-reported pain scores after colorectal resection, according to a study from the Michigan Surgical Quality Collaborative (MSQC).

"The best-performing hospitals achieved superior pain control through the use of analgesia regimens that more often used local anesthesia blocks in the operating room,non-steroidal anti-inflammatory drugs, and patient-controlled analgesia rather than intermittent narcotics," said Dr. Scott E. Regenbogen from the University of Michigan, Ann Arbor.

"This suggests that efforts to implement multimodal analgesia regimens may improve pain control in the immediate postoperative period," he told Reuters Health by email.

Despite increasing attention to postoperative pain management, most patients continue to experience severe pain after major surgery, Dr. Regenbogen and colleagues note in Annals of Surgery, online January 7.

The researchers used MSQC data from 52 hospitals to evaluate the extent to which multimodal pain management practices are used after major surgery and how hospitals' perioperative practices might affect patient-reported pain levels in real-world surgical practice. Their study included 7,221 patients who underwent colorectal resection between 2012 and 2014.

Nine hospitals had average adjusted pain scores significantly worse and eight hospitals had average adjusted pain scores significantly better than the overall average. The "best" hospitals were somewhat larger and had higher annual volumes of colorectal resection than the "worst" hospitals.

Patients in hospitals with best pain scores were significantly more likely to receive local anesthesia and epidural anesthesia during the operation and to have patient-controlled analgesia (PCA), nonsteroidal anti-inflammatory drugs (NSAIDs), or a combination of PCA and NSAIDs and significantly less likely to receive intermittent postoperative narcotics, compared with patients in hospitals with worst pain scores.

Hospitals with the lowest pain scores had a significantly higher proportion of operations with a minimally invasive approach than did hospitals with the highest pain scores.

Patients whose operations took place in hospitals in the lowest quartile of pain scores had significantly shorter mean postoperative length of stay and were significantly less likely to have a postoperative complication, emergency department visit, or readmission.

Patient factors contributing to worse pain scores included being younger than 50 (versus age over 75), a woman, black (versus white), a smoker, and uninsured or insured by Medicaid (versus Medicare or privately insured).

"Most likely," the researchers note, "both pain scores and clinical outcomes reflect more global features of the quality of care in hospitals' surgical performance. Thus, hospitals with the most streamlined, high-quality perioperative care pathways experience the best pain scores, as well as improved clinical outcomes."

"Early postoperative analgesia regimens are an essential component of efforts to improve the efficiency and quality of postoperative recovery," Dr. Regenbogen said."Effective pain control, even in the first postoperative day, is associated with reduced postoperative length of stay and fewer major complications and readmissions. Thus, effective multimodal analgesia is an essential component of high-value perioperative care around colorectal surgery."

"This study is hopefully just one example of a growing emphasis on patient-reported outcomes in surgery," Dr.Regenbogen said. "Within a statewide quality collaborative, we have begun to prioritize engagement of patients, in addition to our partnering surgeons, hospitals, and mayors, in efforts to improve surgical care in Michigan. In this study, we used patient-reported pain measures to evaluate quality of care. In the near future, we will elicit patient-reported measures of functional recovery, psychosocial support, and other outcomes to validate the perioperative outcomes we have relied on traditionally. We hope this study will serve as a model for those novel areas of investigation."

Dr. Antoni Sabate from Hospital Universitari de Bellvitge in Barcelona, Spain, who has researched postoperative analgesia told Reuters Health by email, "Pain is largely influenced by magnitude of the surgical procedure, surgical technique (minimally invasive), analgesia protocol (the use of local anesthetic infiltration in open and laparoscopic, the use of epidural in open procedures, implementation of PCA and NSAID in both laparoscopic and open procedures."

NEW YORK (Reuters Health) - Stent-retriever therapy for the treatment of acute ischemic stroke improves the rate of functional independence at 90 days, according to a systematic

review and meta-analysis.

Stent retrievers are deployed in an occluded vessel, temporarily expanded into the body of a thrombus, and then retracted along with the thrombus.

Dr. Mark J. Eisenberg, from Jewish General Hospital/McGill University, Montreal, Quebec, Canada, and colleagues compared stent retrievers with intravenous recombinant tissue plasminogen activator (rtPA) versus rtPA alone for the treatment of acute ischemic stroke in their systematic review and meta-analysis of five randomized controlled trials (RCTs) with a total of 1,287 patients.

In all five trials, patients randomized to stent-retriever therapy had significantly better functional independence (a modified Rankin Scale (mRS) score of 0-2) at 90 days than did patients randomized to rtPA alone.

Stent-retriever therapy also doubled the likelihood of a one-unit improvement in mRS score at 90 days, according to the January 25 JAMA Neurology online report.

In pooled analyses, there were no significant differences between treatment groups in all-cause mortality, intracranial hemorrhage, or parenchymal hematoma rates at 90 days.

The number needed to treat to achieve an mRS score of 0 to 2 at 90 days was six.

"Given the totality of the evidence regarding the benefits and risks of stent retrievers, our results suggest that the use of these devices in patients with acute ischemic stroke is warranted," the researchers conclude.

Dr. Raphael A. Carandang, from the University of Massachusetts Medical School, Worcester, who wrote an editorial related to this report, told Reuters Health by email, "The data from these five RCTs (as the meta-analysis confirms) provides level 1 class A evidence that in the properly selected patients, stent retriever treatment is superior to the current standard of care with intravenous rtPA and would endorse that it should be considered in all acute ischemic stroke patients that are eligible for it. As with any therapy, proper patient selection is needed, but I do think it changes the landscape of acute stroke treatment going forward. I think that systems of care should be organized in stroke centers around this new therapy."

"The current technology for acute stroke care has reached the point where effective interventional therapies are clearly and unequivocally beneficial in the properly selected patients, but the key takeaway is still that the patients need to be selected properly, and the biggest factor continues to be time to recanalization, which means that all practitioners and systems of care need to focus on getting patients to treatment sooner than ever before," Dr. Carandang concluded.

Dr. Woong Yoon, from Chonnam National University Hospital, Gwangju, Korea, recently found no improvement in outcomes with stent-retriever therapy for patients with acute anterior circulation stroke (http://bit.ly/1OT7M5I). He told Reuters Health by email, "Not all patients with acute ischemic stroke can benefit from this new treatment. Patients with acute stroke due to occlusions of intracranial large vessels such as internal carotid artery, middle cerebral artery, or basilar artery and who presented within six-eight hours of stroke onset can benefit from thrombectomy with stent retrievers."

"We should realize that we are facing the moment of change in the paradigm for acute stroke treatment," Dr. Yoon concluded."Further refinement in the patient selection for stent retrieverthrombectomy is needed in the near future."

Dr. Mayank Goyal, from the University of Calgary, Alberta, Canada, coauthored two of the studies included in the current review. He told Reuters Health by email," There are several additional data coming out on this issue in the near future, which will in fact be more powerful than what is mentioned in this study."

Dr. Goyal said, "However, the key issues going into the future are: how should those patients who were not included in the current trials be treated; how should we as a collective evaluate new devices/technologies; and how do societies/countries who cannot afford stent retrievers implement endovascular stroke treatment."

Dr. Eisenberg was unavailable for comment.

The authors reported no funding. Three coauthors reported disclosures.

NEW YORK (Reuters Health) - Stent-retriever therapy for the treatment of acute ischemic stroke improves the rate of functional independence at 90 days, according to a systematic

review and meta-analysis.

Stent retrievers are deployed in an occluded vessel, temporarily expanded into the body of a thrombus, and then retracted along with the thrombus.

Dr. Mark J. Eisenberg, from Jewish General Hospital/McGill University, Montreal, Quebec, Canada, and colleagues compared stent retrievers with intravenous recombinant tissue plasminogen activator (rtPA) versus rtPA alone for the treatment of acute ischemic stroke in their systematic review and meta-analysis of five randomized controlled trials (RCTs) with a total of 1,287 patients.

In all five trials, patients randomized to stent-retriever therapy had significantly better functional independence (a modified Rankin Scale (mRS) score of 0-2) at 90 days than did patients randomized to rtPA alone.

Stent-retriever therapy also doubled the likelihood of a one-unit improvement in mRS score at 90 days, according to the January 25 JAMA Neurology online report.

In pooled analyses, there were no significant differences between treatment groups in all-cause mortality, intracranial hemorrhage, or parenchymal hematoma rates at 90 days.

The number needed to treat to achieve an mRS score of 0 to 2 at 90 days was six.

"Given the totality of the evidence regarding the benefits and risks of stent retrievers, our results suggest that the use of these devices in patients with acute ischemic stroke is warranted," the researchers conclude.

Dr. Raphael A. Carandang, from the University of Massachusetts Medical School, Worcester, who wrote an editorial related to this report, told Reuters Health by email, "The data from these five RCTs (as the meta-analysis confirms) provides level 1 class A evidence that in the properly selected patients, stent retriever treatment is superior to the current standard of care with intravenous rtPA and would endorse that it should be considered in all acute ischemic stroke patients that are eligible for it. As with any therapy, proper patient selection is needed, but I do think it changes the landscape of acute stroke treatment going forward. I think that systems of care should be organized in stroke centers around this new therapy."

"The current technology for acute stroke care has reached the point where effective interventional therapies are clearly and unequivocally beneficial in the properly selected patients, but the key takeaway is still that the patients need to be selected properly, and the biggest factor continues to be time to recanalization, which means that all practitioners and systems of care need to focus on getting patients to treatment sooner than ever before," Dr. Carandang concluded.

Dr. Woong Yoon, from Chonnam National University Hospital, Gwangju, Korea, recently found no improvement in outcomes with stent-retriever therapy for patients with acute anterior circulation stroke (http://bit.ly/1OT7M5I). He told Reuters Health by email, "Not all patients with acute ischemic stroke can benefit from this new treatment. Patients with acute stroke due to occlusions of intracranial large vessels such as internal carotid artery, middle cerebral artery, or basilar artery and who presented within six-eight hours of stroke onset can benefit from thrombectomy with stent retrievers."

"We should realize that we are facing the moment of change in the paradigm for acute stroke treatment," Dr. Yoon concluded."Further refinement in the patient selection for stent retrieverthrombectomy is needed in the near future."

Dr. Mayank Goyal, from the University of Calgary, Alberta, Canada, coauthored two of the studies included in the current review. He told Reuters Health by email," There are several additional data coming out on this issue in the near future, which will in fact be more powerful than what is mentioned in this study."

Dr. Goyal said, "However, the key issues going into the future are: how should those patients who were not included in the current trials be treated; how should we as a collective evaluate new devices/technologies; and how do societies/countries who cannot afford stent retrievers implement endovascular stroke treatment."

Dr. Eisenberg was unavailable for comment.

The authors reported no funding. Three coauthors reported disclosures.

NEW YORK (Reuters Health) - Stent-retriever therapy for the treatment of acute ischemic stroke improves the rate of functional independence at 90 days, according to a systematic

review and meta-analysis.

Stent retrievers are deployed in an occluded vessel, temporarily expanded into the body of a thrombus, and then retracted along with the thrombus.

Dr. Mark J. Eisenberg, from Jewish General Hospital/McGill University, Montreal, Quebec, Canada, and colleagues compared stent retrievers with intravenous recombinant tissue plasminogen activator (rtPA) versus rtPA alone for the treatment of acute ischemic stroke in their systematic review and meta-analysis of five randomized controlled trials (RCTs) with a total of 1,287 patients.

In all five trials, patients randomized to stent-retriever therapy had significantly better functional independence (a modified Rankin Scale (mRS) score of 0-2) at 90 days than did patients randomized to rtPA alone.

Stent-retriever therapy also doubled the likelihood of a one-unit improvement in mRS score at 90 days, according to the January 25 JAMA Neurology online report.

In pooled analyses, there were no significant differences between treatment groups in all-cause mortality, intracranial hemorrhage, or parenchymal hematoma rates at 90 days.

The number needed to treat to achieve an mRS score of 0 to 2 at 90 days was six.

"Given the totality of the evidence regarding the benefits and risks of stent retrievers, our results suggest that the use of these devices in patients with acute ischemic stroke is warranted," the researchers conclude.

Dr. Raphael A. Carandang, from the University of Massachusetts Medical School, Worcester, who wrote an editorial related to this report, told Reuters Health by email, "The data from these five RCTs (as the meta-analysis confirms) provides level 1 class A evidence that in the properly selected patients, stent retriever treatment is superior to the current standard of care with intravenous rtPA and would endorse that it should be considered in all acute ischemic stroke patients that are eligible for it. As with any therapy, proper patient selection is needed, but I do think it changes the landscape of acute stroke treatment going forward. I think that systems of care should be organized in stroke centers around this new therapy."

"The current technology for acute stroke care has reached the point where effective interventional therapies are clearly and unequivocally beneficial in the properly selected patients, but the key takeaway is still that the patients need to be selected properly, and the biggest factor continues to be time to recanalization, which means that all practitioners and systems of care need to focus on getting patients to treatment sooner than ever before," Dr. Carandang concluded.

Dr. Woong Yoon, from Chonnam National University Hospital, Gwangju, Korea, recently found no improvement in outcomes with stent-retriever therapy for patients with acute anterior circulation stroke (http://bit.ly/1OT7M5I). He told Reuters Health by email, "Not all patients with acute ischemic stroke can benefit from this new treatment. Patients with acute stroke due to occlusions of intracranial large vessels such as internal carotid artery, middle cerebral artery, or basilar artery and who presented within six-eight hours of stroke onset can benefit from thrombectomy with stent retrievers."

"We should realize that we are facing the moment of change in the paradigm for acute stroke treatment," Dr. Yoon concluded."Further refinement in the patient selection for stent retrieverthrombectomy is needed in the near future."

Dr. Mayank Goyal, from the University of Calgary, Alberta, Canada, coauthored two of the studies included in the current review. He told Reuters Health by email," There are several additional data coming out on this issue in the near future, which will in fact be more powerful than what is mentioned in this study."

Dr. Goyal said, "However, the key issues going into the future are: how should those patients who were not included in the current trials be treated; how should we as a collective evaluate new devices/technologies; and how do societies/countries who cannot afford stent retrievers implement endovascular stroke treatment."

Dr. Eisenberg was unavailable for comment.

The authors reported no funding. Three coauthors reported disclosures.

NEW YORK (Reuters Health) - An early invasive strategy provides better outcomes than a conservative strategy in octogenarians with non-ST-elevation myocardial infarction

(NSTEMI) or unstable angina, according to the After Eighty clinical trial.

"Management of the very elderly with myocardial infarction (NSTE-ACS) is challenging, because they often present later, have atypical symptoms, and are a more heterogeneous group dueto comorbidities," Dr. Bjorn Bendz and Dr. Nicolai Tegn from Oslo University Hospital in Norway told Reuters Health in a joint email. "These factors may reduce the benefits and increase the risk of complications from invasive treatment."

Large randomized trials have demonstrated the superiority of an invasive strategy in this setting, but patients aged 80 years and over are underrepresented in these studies.

Dr. Bendz and Dr. Tegn and colleagues from 16 hospitals in Norway investigated whether patients aged 80 years or older would benefit from an early invasive strategy versus a

conservative strategy in terms of a composite primary endpoint of MI, need for urgent revascularization, and death.

The invasive strategy (n=229) included early coronary angiography with immediate assessment for ad hoc percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), or optimal medical treatment, whereas the conservative strategy (n=228) included optimal medical treatment alone.

In the invasive group, 107 underwent PCI and six had CABG, the researchers report in The Lancet, online January 12.

During follow-up, patients in the invasive group were significantly less likely to experience the primary endpoint (41% vs. 61%, p=0.0001).

Compared with patients in the conservative-strategy group, those in the invasive-strategy group were 48% less likely to experience MI and 81% less likely to require urgent revascularization. They were also 40% less likely to have a stroke and 11% less likely to die, but these latter differences were not significant.

Minor bleeding complications (but not major bleeding complications) were somewhat more common in the invasive strategy group (10%) than in the conservative strategy group (7%).

"The present results support an invasive strategy in patients over 80 years with NSTEMI and unstable angina," Dr.Bendz and Dr. Tegn said. "However, the efficacy was less with increasing age, and for patients older than 90 years we cannot conclude if an invasive strategy is beneficial. Thus, management of acute coronary syndrome (ACS) patients over 90 must be individually tailored, considering life expectancy, comorbid illnesses, bleeding risk, cognitive and functional status, and patient preference."

Dr. Peter Psaltis from the University of Adelaide in South Australia, who co-wrote an accompanying editorial, told Reuters Health by email, "The After-80 study now provides the direct

evidence we needed to support this 'early invasive' approach. Given how difficult it is to recruit very elderly patients to clinical studies - and this was reflected by the fact that almost 80% of screened patients were not actually enrolled into After-80 - the investigators deserve credit for taking this study on. Their study is especially important because in developed countries, we see so many 'very old' patients admitted to our cardiology and general medicine wards with ACS."

"In extrapolating the results of After-80 to real-world clinical practice, we firstly have to remember that 70-80% of patients who were screened for this study were ultimately not

enrolled," he reiterated. "There would have been many reasons why so many patients were excluded, but it does emphasize that the study's findings won't apply to everyone over the age of 80 who presents with ACS."

"As always, the decision making process needs to be individually tailored," Dr. Psaltis said. "The patient's pre-existing comorbid status, quality of life, cognitive function and personal wishes are all important factors that need to be taken into account."

"Moreover, we should not just consider its potential benefits in terms of whether it will reduce mortality or risk of recurrent infarcts," Dr. Psaltis added. "In certain individuals >90, an invasive approach may be taken to improve quality of life and symptom burden, help to keep patients in independent living at home, or reduce readmission rates to hospital or even

the use of anti-anginal medications that can be associated with debilitating side-effects."

Dr. Paul Erne from the University of Zurich in Switzerland, who heads the steering committee of the Acute Myocardial Infarction in Sweden (AMIS), stressed, "Conservative treatment

does not result in a poor outcome in every patient and we need to know much more about differential approach."

"However, active treatment remains a great option for part of the elderly patients," regardless of age, he told Reuters Health by email. "Please note the increasing number of patients

treated at age above 100 years which proves to be a good option if the patients want to live actively."

Dr. Rahul Potluri, founder of the ACALM (Algorithm for Comorbidities, Associations, Length of Stay and Mortality) Study Unit, Birmingham, U.K., recently reviewed the role of

angioplasty in octogenarian ACS patients.

He told Reuters Health by email, "This study is the most conclusive evidence to date, showing the benefits of an invasive approach in patients above the age of 80 with the most common types of ACS (namely NSTEMI and unstable angina). The findings are most surprising given that both the groups were very similar in terms of patient characteristics and medications taken, thus delineating the true benefit of the invasive strategy in the most controlled fashion and in a short follow-up period."

The study did not have commercial funding and the researchers declared no competing interests.

NEW YORK (Reuters Health) - An early invasive strategy provides better outcomes than a conservative strategy in octogenarians with non-ST-elevation myocardial infarction

(NSTEMI) or unstable angina, according to the After Eighty clinical trial.

"Management of the very elderly with myocardial infarction (NSTE-ACS) is challenging, because they often present later, have atypical symptoms, and are a more heterogeneous group dueto comorbidities," Dr. Bjorn Bendz and Dr. Nicolai Tegn from Oslo University Hospital in Norway told Reuters Health in a joint email. "These factors may reduce the benefits and increase the risk of complications from invasive treatment."

Large randomized trials have demonstrated the superiority of an invasive strategy in this setting, but patients aged 80 years and over are underrepresented in these studies.

Dr. Bendz and Dr. Tegn and colleagues from 16 hospitals in Norway investigated whether patients aged 80 years or older would benefit from an early invasive strategy versus a

conservative strategy in terms of a composite primary endpoint of MI, need for urgent revascularization, and death.

The invasive strategy (n=229) included early coronary angiography with immediate assessment for ad hoc percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), or optimal medical treatment, whereas the conservative strategy (n=228) included optimal medical treatment alone.

In the invasive group, 107 underwent PCI and six had CABG, the researchers report in The Lancet, online January 12.

During follow-up, patients in the invasive group were significantly less likely to experience the primary endpoint (41% vs. 61%, p=0.0001).

Compared with patients in the conservative-strategy group, those in the invasive-strategy group were 48% less likely to experience MI and 81% less likely to require urgent revascularization. They were also 40% less likely to have a stroke and 11% less likely to die, but these latter differences were not significant.

Minor bleeding complications (but not major bleeding complications) were somewhat more common in the invasive strategy group (10%) than in the conservative strategy group (7%).

"The present results support an invasive strategy in patients over 80 years with NSTEMI and unstable angina," Dr.Bendz and Dr. Tegn said. "However, the efficacy was less with increasing age, and for patients older than 90 years we cannot conclude if an invasive strategy is beneficial. Thus, management of acute coronary syndrome (ACS) patients over 90 must be individually tailored, considering life expectancy, comorbid illnesses, bleeding risk, cognitive and functional status, and patient preference."

Dr. Peter Psaltis from the University of Adelaide in South Australia, who co-wrote an accompanying editorial, told Reuters Health by email, "The After-80 study now provides the direct

evidence we needed to support this 'early invasive' approach. Given how difficult it is to recruit very elderly patients to clinical studies - and this was reflected by the fact that almost 80% of screened patients were not actually enrolled into After-80 - the investigators deserve credit for taking this study on. Their study is especially important because in developed countries, we see so many 'very old' patients admitted to our cardiology and general medicine wards with ACS."

"In extrapolating the results of After-80 to real-world clinical practice, we firstly have to remember that 70-80% of patients who were screened for this study were ultimately not

enrolled," he reiterated. "There would have been many reasons why so many patients were excluded, but it does emphasize that the study's findings won't apply to everyone over the age of 80 who presents with ACS."

"As always, the decision making process needs to be individually tailored," Dr. Psaltis said. "The patient's pre-existing comorbid status, quality of life, cognitive function and personal wishes are all important factors that need to be taken into account."

"Moreover, we should not just consider its potential benefits in terms of whether it will reduce mortality or risk of recurrent infarcts," Dr. Psaltis added. "In certain individuals >90, an invasive approach may be taken to improve quality of life and symptom burden, help to keep patients in independent living at home, or reduce readmission rates to hospital or even

the use of anti-anginal medications that can be associated with debilitating side-effects."

Dr. Paul Erne from the University of Zurich in Switzerland, who heads the steering committee of the Acute Myocardial Infarction in Sweden (AMIS), stressed, "Conservative treatment

does not result in a poor outcome in every patient and we need to know much more about differential approach."

"However, active treatment remains a great option for part of the elderly patients," regardless of age, he told Reuters Health by email. "Please note the increasing number of patients

treated at age above 100 years which proves to be a good option if the patients want to live actively."

Dr. Rahul Potluri, founder of the ACALM (Algorithm for Comorbidities, Associations, Length of Stay and Mortality) Study Unit, Birmingham, U.K., recently reviewed the role of

angioplasty in octogenarian ACS patients.

He told Reuters Health by email, "This study is the most conclusive evidence to date, showing the benefits of an invasive approach in patients above the age of 80 with the most common types of ACS (namely NSTEMI and unstable angina). The findings are most surprising given that both the groups were very similar in terms of patient characteristics and medications taken, thus delineating the true benefit of the invasive strategy in the most controlled fashion and in a short follow-up period."

The study did not have commercial funding and the researchers declared no competing interests.

NEW YORK (Reuters Health) - An early invasive strategy provides better outcomes than a conservative strategy in octogenarians with non-ST-elevation myocardial infarction

(NSTEMI) or unstable angina, according to the After Eighty clinical trial.

"Management of the very elderly with myocardial infarction (NSTE-ACS) is challenging, because they often present later, have atypical symptoms, and are a more heterogeneous group dueto comorbidities," Dr. Bjorn Bendz and Dr. Nicolai Tegn from Oslo University Hospital in Norway told Reuters Health in a joint email. "These factors may reduce the benefits and increase the risk of complications from invasive treatment."

Large randomized trials have demonstrated the superiority of an invasive strategy in this setting, but patients aged 80 years and over are underrepresented in these studies.

Dr. Bendz and Dr. Tegn and colleagues from 16 hospitals in Norway investigated whether patients aged 80 years or older would benefit from an early invasive strategy versus a

conservative strategy in terms of a composite primary endpoint of MI, need for urgent revascularization, and death.

The invasive strategy (n=229) included early coronary angiography with immediate assessment for ad hoc percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), or optimal medical treatment, whereas the conservative strategy (n=228) included optimal medical treatment alone.

In the invasive group, 107 underwent PCI and six had CABG, the researchers report in The Lancet, online January 12.

During follow-up, patients in the invasive group were significantly less likely to experience the primary endpoint (41% vs. 61%, p=0.0001).

Compared with patients in the conservative-strategy group, those in the invasive-strategy group were 48% less likely to experience MI and 81% less likely to require urgent revascularization. They were also 40% less likely to have a stroke and 11% less likely to die, but these latter differences were not significant.

Minor bleeding complications (but not major bleeding complications) were somewhat more common in the invasive strategy group (10%) than in the conservative strategy group (7%).

"The present results support an invasive strategy in patients over 80 years with NSTEMI and unstable angina," Dr.Bendz and Dr. Tegn said. "However, the efficacy was less with increasing age, and for patients older than 90 years we cannot conclude if an invasive strategy is beneficial. Thus, management of acute coronary syndrome (ACS) patients over 90 must be individually tailored, considering life expectancy, comorbid illnesses, bleeding risk, cognitive and functional status, and patient preference."

Dr. Peter Psaltis from the University of Adelaide in South Australia, who co-wrote an accompanying editorial, told Reuters Health by email, "The After-80 study now provides the direct

evidence we needed to support this 'early invasive' approach. Given how difficult it is to recruit very elderly patients to clinical studies - and this was reflected by the fact that almost 80% of screened patients were not actually enrolled into After-80 - the investigators deserve credit for taking this study on. Their study is especially important because in developed countries, we see so many 'very old' patients admitted to our cardiology and general medicine wards with ACS."

"In extrapolating the results of After-80 to real-world clinical practice, we firstly have to remember that 70-80% of patients who were screened for this study were ultimately not

enrolled," he reiterated. "There would have been many reasons why so many patients were excluded, but it does emphasize that the study's findings won't apply to everyone over the age of 80 who presents with ACS."

"As always, the decision making process needs to be individually tailored," Dr. Psaltis said. "The patient's pre-existing comorbid status, quality of life, cognitive function and personal wishes are all important factors that need to be taken into account."

"Moreover, we should not just consider its potential benefits in terms of whether it will reduce mortality or risk of recurrent infarcts," Dr. Psaltis added. "In certain individuals >90, an invasive approach may be taken to improve quality of life and symptom burden, help to keep patients in independent living at home, or reduce readmission rates to hospital or even

the use of anti-anginal medications that can be associated with debilitating side-effects."

Dr. Paul Erne from the University of Zurich in Switzerland, who heads the steering committee of the Acute Myocardial Infarction in Sweden (AMIS), stressed, "Conservative treatment

does not result in a poor outcome in every patient and we need to know much more about differential approach."

"However, active treatment remains a great option for part of the elderly patients," regardless of age, he told Reuters Health by email. "Please note the increasing number of patients

treated at age above 100 years which proves to be a good option if the patients want to live actively."

Dr. Rahul Potluri, founder of the ACALM (Algorithm for Comorbidities, Associations, Length of Stay and Mortality) Study Unit, Birmingham, U.K., recently reviewed the role of

angioplasty in octogenarian ACS patients.

He told Reuters Health by email, "This study is the most conclusive evidence to date, showing the benefits of an invasive approach in patients above the age of 80 with the most common types of ACS (namely NSTEMI and unstable angina). The findings are most surprising given that both the groups were very similar in terms of patient characteristics and medications taken, thus delineating the true benefit of the invasive strategy in the most controlled fashion and in a short follow-up period."

The study did not have commercial funding and the researchers declared no competing interests.