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No easy answers for parastomal hernia repair
SEATTLE – At present, laparoscopic Sugarbaker repair is probably the best surgical option for parastomal hernias when stomas can’t be reversed, according to Mark Gudgeon, MS, FRCS, a consultant general surgeon at the Frimley Park Hospital in England.
Parastomal hernias are common in colorectal surgery; more than a quarter of ileostomy stomas and well over half of colostomy stomas herniate within 10 years of placement, leading to pain, leakage, appliance problems, and embarrassment for patients. There’s also the risk of bowel obstruction and strangulation. “It’s something that’s a challenge to all of us. It’s a very difficult problem,” Dr. Gudgeon said at the American Society of Colon and Rectal Surgeons annual meeting.
It can be difficult to decide whether or not to even offer patients a surgical fix because they often fail, and sometimes lead to fistulas and well-known mesh complications. Obese patients are “a no-go because they do not do well, and neither do smokers. Both are things patients have an opportunity to correct before we go ahead with surgery,” Dr. Gudgeon said.
On top of that, about 6% of repair patients die from complications. Patients “don’t believe that at first, but when you rub it in, a lot of them will change their minds” about surgery. “These patients don’t do well,” so avoid surgery when possible, he said. “Pain can be dealt with; leakage can be dealt with; cosmesis can be accepted,” especially with the help of stoma specialists who are experts in the art of appliance fit and support garments, Dr. Gudgeon said.
If the decision to operate is made, forget about suture repair, Dr. Gudgeon recommended. It should be “abandoned. I know it still goes on, but the evidence speaks for itself: [hernias] just come back again.”
Dr. Gudgeon suggested that it may be best to reverse the stoma, if possible, and repair the defect. Relocating the stoma “is always an attractive alternative,” and laparoscopic mesh keyhole repairs are straightforward. But the risk of recurrence is high, he said.
The Food and Drug Administration recently found that there’s not much difference between synthetic and biologic mesh, so Dr. Gudgeon said he usually opts for synthetics because they are less expensive.
He reported speakers’ fees from Intuitive, Medtronic, and Cook Medical.
SEATTLE – At present, laparoscopic Sugarbaker repair is probably the best surgical option for parastomal hernias when stomas can’t be reversed, according to Mark Gudgeon, MS, FRCS, a consultant general surgeon at the Frimley Park Hospital in England.
Parastomal hernias are common in colorectal surgery; more than a quarter of ileostomy stomas and well over half of colostomy stomas herniate within 10 years of placement, leading to pain, leakage, appliance problems, and embarrassment for patients. There’s also the risk of bowel obstruction and strangulation. “It’s something that’s a challenge to all of us. It’s a very difficult problem,” Dr. Gudgeon said at the American Society of Colon and Rectal Surgeons annual meeting.
It can be difficult to decide whether or not to even offer patients a surgical fix because they often fail, and sometimes lead to fistulas and well-known mesh complications. Obese patients are “a no-go because they do not do well, and neither do smokers. Both are things patients have an opportunity to correct before we go ahead with surgery,” Dr. Gudgeon said.
On top of that, about 6% of repair patients die from complications. Patients “don’t believe that at first, but when you rub it in, a lot of them will change their minds” about surgery. “These patients don’t do well,” so avoid surgery when possible, he said. “Pain can be dealt with; leakage can be dealt with; cosmesis can be accepted,” especially with the help of stoma specialists who are experts in the art of appliance fit and support garments, Dr. Gudgeon said.
If the decision to operate is made, forget about suture repair, Dr. Gudgeon recommended. It should be “abandoned. I know it still goes on, but the evidence speaks for itself: [hernias] just come back again.”
Dr. Gudgeon suggested that it may be best to reverse the stoma, if possible, and repair the defect. Relocating the stoma “is always an attractive alternative,” and laparoscopic mesh keyhole repairs are straightforward. But the risk of recurrence is high, he said.
The Food and Drug Administration recently found that there’s not much difference between synthetic and biologic mesh, so Dr. Gudgeon said he usually opts for synthetics because they are less expensive.
He reported speakers’ fees from Intuitive, Medtronic, and Cook Medical.
SEATTLE – At present, laparoscopic Sugarbaker repair is probably the best surgical option for parastomal hernias when stomas can’t be reversed, according to Mark Gudgeon, MS, FRCS, a consultant general surgeon at the Frimley Park Hospital in England.
Parastomal hernias are common in colorectal surgery; more than a quarter of ileostomy stomas and well over half of colostomy stomas herniate within 10 years of placement, leading to pain, leakage, appliance problems, and embarrassment for patients. There’s also the risk of bowel obstruction and strangulation. “It’s something that’s a challenge to all of us. It’s a very difficult problem,” Dr. Gudgeon said at the American Society of Colon and Rectal Surgeons annual meeting.
It can be difficult to decide whether or not to even offer patients a surgical fix because they often fail, and sometimes lead to fistulas and well-known mesh complications. Obese patients are “a no-go because they do not do well, and neither do smokers. Both are things patients have an opportunity to correct before we go ahead with surgery,” Dr. Gudgeon said.
On top of that, about 6% of repair patients die from complications. Patients “don’t believe that at first, but when you rub it in, a lot of them will change their minds” about surgery. “These patients don’t do well,” so avoid surgery when possible, he said. “Pain can be dealt with; leakage can be dealt with; cosmesis can be accepted,” especially with the help of stoma specialists who are experts in the art of appliance fit and support garments, Dr. Gudgeon said.
If the decision to operate is made, forget about suture repair, Dr. Gudgeon recommended. It should be “abandoned. I know it still goes on, but the evidence speaks for itself: [hernias] just come back again.”
Dr. Gudgeon suggested that it may be best to reverse the stoma, if possible, and repair the defect. Relocating the stoma “is always an attractive alternative,” and laparoscopic mesh keyhole repairs are straightforward. But the risk of recurrence is high, he said.
The Food and Drug Administration recently found that there’s not much difference between synthetic and biologic mesh, so Dr. Gudgeon said he usually opts for synthetics because they are less expensive.
He reported speakers’ fees from Intuitive, Medtronic, and Cook Medical.
EXPERT ANALYSIS AT THE ASCRS ANNUAL MEETING
Increased risk of death even in lower-risk PPI users
Proton pump inhibitors (PPIs) are associated with a significantly higher risk of death than are H2 receptor antagonists, according to a 5-year longitudinal cohort study.
The study, published online in BMJ Open, found that increased risk of death was evident even in people without gastrointestinal conditions, and it increased with longer duration of use.
Yan Xie, PhD, of the VA Saint Louis Health Care System and coauthors, wrote that PPIs are linked to a range of serious adverse outcomes – such as acute interstitial nephritis, chronic kidney disease, incident dementia, and Clostridium difficile infection – each of which is associated with higher risk of mortality.
“Whether PPI use is associated with excess risk of death is not known and has not been examined in large epidemiological studies spanning a sufficiently long duration of follow-up.”
In this study, a cohort of 349,312 veterans initiated on acid-suppression therapy was followed for a mean duration of 5.71 years (BMJ Open 2017. July 4;7:e015735. doi: 10.1136/bmjopen-2016-015735).
Researchers saw a 25% higher risk of death in the 275,977 participants treated with PPIs, compared with that in those who were treated with H2 receptor antagonists (95% confidence interval, 1.23-1.28), after adjusting for factors such as estimated glomerular filtration rate, age, hospitalizations, and a range of comorbidities, including gastrointestinal disorders.
When PPI use was compared with no PPI use, there was a 15% increase in the risk of death (95% CI, 1.14-1.15). When compared with no known exposure to any acid suppression therapy, the increased risk of death was 23% (95% CI, 1.22-1.24).
In an attempt to look at the risk of death in a lower-risk cohort, the researchers analyzed a subgroup of participants who did not have the conditions for which PPIs are normally prescribed, such as gastroesophageal reflux disease, upper gastrointestinal tract bleeding, ulcer disease, Helicobacter pylori infection, and Barrett’s esophagus.
However, even in this lower-risk cohort, the study still showed a 24% increase in the risk of death with PPIs, compared with that in H2 receptor antagonists (95% CI, 1.21-1.27); a 19% increase with PPIs, compared with no PPIs; and a 22% increase with PPIs, compared with no acid suppression.
Duration of exposure to PPIs was also associated with increasing risk of death. Participants who had taken PPIs for fewer than 90 days in total only had a 5% increase in risk, while those taking them for 361-720 days had a 51% increased risk of death.
“Although our results should not deter prescription and use of PPIs where medically indicated, they may be used to encourage and promote pharmacovigilance and emphasize the need to exercise judicious use of PPIs and limit use and duration of therapy to instances where there is a clear medical indication and where benefit outweighs potential risk,” the authors wrote.
“Standardized guidelines for initiating PPI prescription may lead to reduced overuse [and] regular review of prescription and over-the-counter medications, and deprescription, where a medical indication for PPI treatment ceases to exist, may be a meritorious approach.”
Examining possible physiologic mechanisms to explain the increased risk of death, the authors noted that animal studies suggested PPIs may limit the liver’s capacity to regenerate.
PPIs are also associated with increased activity of the heme oxygenase-1 enzyme in gastric and endothelial cells and impairment of lysosomal acidification and proteostasis and may alter gene expression in the cellular retinol metabolism pathway and the complement and coagulation cascades pathway.
However, the clinical mediator of the heightened risk of death was likely one of the adverse events linked to PPI use, they said.
No conflicts of interest were declared.
Proton pump inhibitors (PPIs) are associated with a significantly higher risk of death than are H2 receptor antagonists, according to a 5-year longitudinal cohort study.
The study, published online in BMJ Open, found that increased risk of death was evident even in people without gastrointestinal conditions, and it increased with longer duration of use.
Yan Xie, PhD, of the VA Saint Louis Health Care System and coauthors, wrote that PPIs are linked to a range of serious adverse outcomes – such as acute interstitial nephritis, chronic kidney disease, incident dementia, and Clostridium difficile infection – each of which is associated with higher risk of mortality.
“Whether PPI use is associated with excess risk of death is not known and has not been examined in large epidemiological studies spanning a sufficiently long duration of follow-up.”
In this study, a cohort of 349,312 veterans initiated on acid-suppression therapy was followed for a mean duration of 5.71 years (BMJ Open 2017. July 4;7:e015735. doi: 10.1136/bmjopen-2016-015735).
Researchers saw a 25% higher risk of death in the 275,977 participants treated with PPIs, compared with that in those who were treated with H2 receptor antagonists (95% confidence interval, 1.23-1.28), after adjusting for factors such as estimated glomerular filtration rate, age, hospitalizations, and a range of comorbidities, including gastrointestinal disorders.
When PPI use was compared with no PPI use, there was a 15% increase in the risk of death (95% CI, 1.14-1.15). When compared with no known exposure to any acid suppression therapy, the increased risk of death was 23% (95% CI, 1.22-1.24).
In an attempt to look at the risk of death in a lower-risk cohort, the researchers analyzed a subgroup of participants who did not have the conditions for which PPIs are normally prescribed, such as gastroesophageal reflux disease, upper gastrointestinal tract bleeding, ulcer disease, Helicobacter pylori infection, and Barrett’s esophagus.
However, even in this lower-risk cohort, the study still showed a 24% increase in the risk of death with PPIs, compared with that in H2 receptor antagonists (95% CI, 1.21-1.27); a 19% increase with PPIs, compared with no PPIs; and a 22% increase with PPIs, compared with no acid suppression.
Duration of exposure to PPIs was also associated with increasing risk of death. Participants who had taken PPIs for fewer than 90 days in total only had a 5% increase in risk, while those taking them for 361-720 days had a 51% increased risk of death.
“Although our results should not deter prescription and use of PPIs where medically indicated, they may be used to encourage and promote pharmacovigilance and emphasize the need to exercise judicious use of PPIs and limit use and duration of therapy to instances where there is a clear medical indication and where benefit outweighs potential risk,” the authors wrote.
“Standardized guidelines for initiating PPI prescription may lead to reduced overuse [and] regular review of prescription and over-the-counter medications, and deprescription, where a medical indication for PPI treatment ceases to exist, may be a meritorious approach.”
Examining possible physiologic mechanisms to explain the increased risk of death, the authors noted that animal studies suggested PPIs may limit the liver’s capacity to regenerate.
PPIs are also associated with increased activity of the heme oxygenase-1 enzyme in gastric and endothelial cells and impairment of lysosomal acidification and proteostasis and may alter gene expression in the cellular retinol metabolism pathway and the complement and coagulation cascades pathway.
However, the clinical mediator of the heightened risk of death was likely one of the adverse events linked to PPI use, they said.
No conflicts of interest were declared.
Proton pump inhibitors (PPIs) are associated with a significantly higher risk of death than are H2 receptor antagonists, according to a 5-year longitudinal cohort study.
The study, published online in BMJ Open, found that increased risk of death was evident even in people without gastrointestinal conditions, and it increased with longer duration of use.
Yan Xie, PhD, of the VA Saint Louis Health Care System and coauthors, wrote that PPIs are linked to a range of serious adverse outcomes – such as acute interstitial nephritis, chronic kidney disease, incident dementia, and Clostridium difficile infection – each of which is associated with higher risk of mortality.
“Whether PPI use is associated with excess risk of death is not known and has not been examined in large epidemiological studies spanning a sufficiently long duration of follow-up.”
In this study, a cohort of 349,312 veterans initiated on acid-suppression therapy was followed for a mean duration of 5.71 years (BMJ Open 2017. July 4;7:e015735. doi: 10.1136/bmjopen-2016-015735).
Researchers saw a 25% higher risk of death in the 275,977 participants treated with PPIs, compared with that in those who were treated with H2 receptor antagonists (95% confidence interval, 1.23-1.28), after adjusting for factors such as estimated glomerular filtration rate, age, hospitalizations, and a range of comorbidities, including gastrointestinal disorders.
When PPI use was compared with no PPI use, there was a 15% increase in the risk of death (95% CI, 1.14-1.15). When compared with no known exposure to any acid suppression therapy, the increased risk of death was 23% (95% CI, 1.22-1.24).
In an attempt to look at the risk of death in a lower-risk cohort, the researchers analyzed a subgroup of participants who did not have the conditions for which PPIs are normally prescribed, such as gastroesophageal reflux disease, upper gastrointestinal tract bleeding, ulcer disease, Helicobacter pylori infection, and Barrett’s esophagus.
However, even in this lower-risk cohort, the study still showed a 24% increase in the risk of death with PPIs, compared with that in H2 receptor antagonists (95% CI, 1.21-1.27); a 19% increase with PPIs, compared with no PPIs; and a 22% increase with PPIs, compared with no acid suppression.
Duration of exposure to PPIs was also associated with increasing risk of death. Participants who had taken PPIs for fewer than 90 days in total only had a 5% increase in risk, while those taking them for 361-720 days had a 51% increased risk of death.
“Although our results should not deter prescription and use of PPIs where medically indicated, they may be used to encourage and promote pharmacovigilance and emphasize the need to exercise judicious use of PPIs and limit use and duration of therapy to instances where there is a clear medical indication and where benefit outweighs potential risk,” the authors wrote.
“Standardized guidelines for initiating PPI prescription may lead to reduced overuse [and] regular review of prescription and over-the-counter medications, and deprescription, where a medical indication for PPI treatment ceases to exist, may be a meritorious approach.”
Examining possible physiologic mechanisms to explain the increased risk of death, the authors noted that animal studies suggested PPIs may limit the liver’s capacity to regenerate.
PPIs are also associated with increased activity of the heme oxygenase-1 enzyme in gastric and endothelial cells and impairment of lysosomal acidification and proteostasis and may alter gene expression in the cellular retinol metabolism pathway and the complement and coagulation cascades pathway.
However, the clinical mediator of the heightened risk of death was likely one of the adverse events linked to PPI use, they said.
No conflicts of interest were declared.
FROM BMJ OPEN
Key clinical point: Proton pump inhibitors are associated with a significantly higher risk of death, even among people without the gastrointestinal conditions for which the drugs are normally prescribed.
Major finding: People taking PPIs have a 25% higher risk of death, compared with those taking H2 receptor antagonists.
Data source: A longitudinal cohort study in 349,312 veterans.
Disclosures: No conflicts of interest were declared.
Hospital isolates C. difficile carriers and rates drop
NEW ORLEANS – A Montreal hospital grappling with high Clostridium difficile infections rates launched an intervention in October 2013 to screen patients at admission and detect asymptomatic carriers, and investigators found 4.8% of 7,599 people admitted through the ED over 15 months were carriers of C. difficile.
To protect Jewish General Hospital physicians, staff and other patients from potential transmission, these patients were placed in isolation. However, because they were fairly numerous – 1 in 20 admissions – and because infectious disease (ID) experts feared a substantial backlash, these patients were put in less restrictive isolation. They were permitted to share rooms as long as the dividing curtains remained drawn, for example. In addition, clinicians could skip wearing traditional isolation hats and gowns.
The ID team at the hospital considered the intervention a success. “It is estimated we prevented 64 cases over 15 months,” Dr. Longtin said during a packed session at the annual meeting of the American Society for Microbiology.
The hospital’s C. difficile rate dropped from 6.9 per 10,000 patient-days before the screening and isolation protocol to 3.0 per 10,000 during the intervention. The difference was statically significant (P less than .001).
“Compared to other hospitals in the province, we used to be in the middle of the pack [for C. difficile infection rates], and now we are the lowest,” Dr. Longtin said.
Asymptomatic carriers were detected using rectal sampling with sterile swab and polymerase chain reaction analysis. Testing was performed 7 days a week and analyzed once daily, with results generated within 24 hours and documented in the patient chart. Only patients admitted through the ED were screened, which prompted some questions from colleagues, Dr. Longtin said. However, he defends this approach because the 30% or so of patients admitted from the ED tend to spend more days on the ward. The risk of becoming colonized increases steadily with duration of hospitalization. This occurs despite isolating patients with C. difficile infection. Initial results of the study were published in JAMA Internal Medicine (2016 Jun 1;176[6]:796-804).
Risk to health care workers
C. difficile carriers are contagious, but not as much as people with C. difficile infection, Dr. Longtin said. In one study, the microorganism was present on the skin of 61% of symptomatic carriers versus 78% of those infected (Clin Infect Dis. 2007 Oct 15;45[8]:992-8). In addition, C. difficile present on patient skin can be transferred to health care worker hands, even up to 6 weeks after resolution of associated diarrhea (Infect Control Hosp Epidemiol. 2016 Apr;37[4]:475-7).
Prior to the intervention, C. difficile prevention at Jewish General involved guidelines that “have not really changed in the last 20 years,” Dr. Longtin said. Contact precautions around infected patients, hand hygiene, environmental cleaning, and antibiotic stewardship were the main strategies.
“Despite all these measures, we were not completely blocking dissemination of C difficile in our hospital,” Dr. Longtin said. He added that soap and water are better than alcohol for C. difficile, “but honestly not very good. Even the best hand hygiene technique is poorly effective to remove C. difficile. On the other hand – get it? – gloves are very effective. We felt we had to combine hand washing with gloves.”
Hand hygiene compliance increased from 37% to 50% during the intervention, and Dr. Longtin expected further improvements over time.
Risk to other patients
“Transmission of C. difficile cannot only be explained by infected patients in a hospital, so likely carriers also play a role,” Dr. Longtin said.
Another set of investigators found that hospital patients exposed to a carrier of C. difficile had nearly twice the risk of acquiring the infection (odds ratio, 1.79) (Gastroenterology. 2017 Apr;152[5]:1031-41.e2).
“For every patient with C. difficile infection, it’s estimated there are 5-7 C. difficile carriers, so they are numerous as well,” he said.
The bigger picture
During the study period, the C. difficile infection trends did not significantly change on the city level, further supporting the effectiveness of the carrier screen-and-isolate strategy.
There was slight increase in antibiotic use during the intervention period, Dr. Longtin said. “The only type of antibiotics that really decreased were vancomycin and metronidazole... which suggests in turn there were fewer cases of C. difficile infection.”
Long-term follow-up is ongoing, Dr. Longtin said. “We have more than 3 years of intervention. In the past year, our rate was 2.2 per 10,000 patient-days.”
Unanswered questions include the generalizability of the results “because we’re a very pro–infection control hospital,” he said. In addition, a formal cost-benefit analysis of this strategy would be worthwhile in the future.
Dr. Longtin is a consultant for AMG Medical and receives research support from Merck and BD Medical.
NEW ORLEANS – A Montreal hospital grappling with high Clostridium difficile infections rates launched an intervention in October 2013 to screen patients at admission and detect asymptomatic carriers, and investigators found 4.8% of 7,599 people admitted through the ED over 15 months were carriers of C. difficile.
To protect Jewish General Hospital physicians, staff and other patients from potential transmission, these patients were placed in isolation. However, because they were fairly numerous – 1 in 20 admissions – and because infectious disease (ID) experts feared a substantial backlash, these patients were put in less restrictive isolation. They were permitted to share rooms as long as the dividing curtains remained drawn, for example. In addition, clinicians could skip wearing traditional isolation hats and gowns.
The ID team at the hospital considered the intervention a success. “It is estimated we prevented 64 cases over 15 months,” Dr. Longtin said during a packed session at the annual meeting of the American Society for Microbiology.
The hospital’s C. difficile rate dropped from 6.9 per 10,000 patient-days before the screening and isolation protocol to 3.0 per 10,000 during the intervention. The difference was statically significant (P less than .001).
“Compared to other hospitals in the province, we used to be in the middle of the pack [for C. difficile infection rates], and now we are the lowest,” Dr. Longtin said.
Asymptomatic carriers were detected using rectal sampling with sterile swab and polymerase chain reaction analysis. Testing was performed 7 days a week and analyzed once daily, with results generated within 24 hours and documented in the patient chart. Only patients admitted through the ED were screened, which prompted some questions from colleagues, Dr. Longtin said. However, he defends this approach because the 30% or so of patients admitted from the ED tend to spend more days on the ward. The risk of becoming colonized increases steadily with duration of hospitalization. This occurs despite isolating patients with C. difficile infection. Initial results of the study were published in JAMA Internal Medicine (2016 Jun 1;176[6]:796-804).
Risk to health care workers
C. difficile carriers are contagious, but not as much as people with C. difficile infection, Dr. Longtin said. In one study, the microorganism was present on the skin of 61% of symptomatic carriers versus 78% of those infected (Clin Infect Dis. 2007 Oct 15;45[8]:992-8). In addition, C. difficile present on patient skin can be transferred to health care worker hands, even up to 6 weeks after resolution of associated diarrhea (Infect Control Hosp Epidemiol. 2016 Apr;37[4]:475-7).
Prior to the intervention, C. difficile prevention at Jewish General involved guidelines that “have not really changed in the last 20 years,” Dr. Longtin said. Contact precautions around infected patients, hand hygiene, environmental cleaning, and antibiotic stewardship were the main strategies.
“Despite all these measures, we were not completely blocking dissemination of C difficile in our hospital,” Dr. Longtin said. He added that soap and water are better than alcohol for C. difficile, “but honestly not very good. Even the best hand hygiene technique is poorly effective to remove C. difficile. On the other hand – get it? – gloves are very effective. We felt we had to combine hand washing with gloves.”
Hand hygiene compliance increased from 37% to 50% during the intervention, and Dr. Longtin expected further improvements over time.
Risk to other patients
“Transmission of C. difficile cannot only be explained by infected patients in a hospital, so likely carriers also play a role,” Dr. Longtin said.
Another set of investigators found that hospital patients exposed to a carrier of C. difficile had nearly twice the risk of acquiring the infection (odds ratio, 1.79) (Gastroenterology. 2017 Apr;152[5]:1031-41.e2).
“For every patient with C. difficile infection, it’s estimated there are 5-7 C. difficile carriers, so they are numerous as well,” he said.
The bigger picture
During the study period, the C. difficile infection trends did not significantly change on the city level, further supporting the effectiveness of the carrier screen-and-isolate strategy.
There was slight increase in antibiotic use during the intervention period, Dr. Longtin said. “The only type of antibiotics that really decreased were vancomycin and metronidazole... which suggests in turn there were fewer cases of C. difficile infection.”
Long-term follow-up is ongoing, Dr. Longtin said. “We have more than 3 years of intervention. In the past year, our rate was 2.2 per 10,000 patient-days.”
Unanswered questions include the generalizability of the results “because we’re a very pro–infection control hospital,” he said. In addition, a formal cost-benefit analysis of this strategy would be worthwhile in the future.
Dr. Longtin is a consultant for AMG Medical and receives research support from Merck and BD Medical.
NEW ORLEANS – A Montreal hospital grappling with high Clostridium difficile infections rates launched an intervention in October 2013 to screen patients at admission and detect asymptomatic carriers, and investigators found 4.8% of 7,599 people admitted through the ED over 15 months were carriers of C. difficile.
To protect Jewish General Hospital physicians, staff and other patients from potential transmission, these patients were placed in isolation. However, because they were fairly numerous – 1 in 20 admissions – and because infectious disease (ID) experts feared a substantial backlash, these patients were put in less restrictive isolation. They were permitted to share rooms as long as the dividing curtains remained drawn, for example. In addition, clinicians could skip wearing traditional isolation hats and gowns.
The ID team at the hospital considered the intervention a success. “It is estimated we prevented 64 cases over 15 months,” Dr. Longtin said during a packed session at the annual meeting of the American Society for Microbiology.
The hospital’s C. difficile rate dropped from 6.9 per 10,000 patient-days before the screening and isolation protocol to 3.0 per 10,000 during the intervention. The difference was statically significant (P less than .001).
“Compared to other hospitals in the province, we used to be in the middle of the pack [for C. difficile infection rates], and now we are the lowest,” Dr. Longtin said.
Asymptomatic carriers were detected using rectal sampling with sterile swab and polymerase chain reaction analysis. Testing was performed 7 days a week and analyzed once daily, with results generated within 24 hours and documented in the patient chart. Only patients admitted through the ED were screened, which prompted some questions from colleagues, Dr. Longtin said. However, he defends this approach because the 30% or so of patients admitted from the ED tend to spend more days on the ward. The risk of becoming colonized increases steadily with duration of hospitalization. This occurs despite isolating patients with C. difficile infection. Initial results of the study were published in JAMA Internal Medicine (2016 Jun 1;176[6]:796-804).
Risk to health care workers
C. difficile carriers are contagious, but not as much as people with C. difficile infection, Dr. Longtin said. In one study, the microorganism was present on the skin of 61% of symptomatic carriers versus 78% of those infected (Clin Infect Dis. 2007 Oct 15;45[8]:992-8). In addition, C. difficile present on patient skin can be transferred to health care worker hands, even up to 6 weeks after resolution of associated diarrhea (Infect Control Hosp Epidemiol. 2016 Apr;37[4]:475-7).
Prior to the intervention, C. difficile prevention at Jewish General involved guidelines that “have not really changed in the last 20 years,” Dr. Longtin said. Contact precautions around infected patients, hand hygiene, environmental cleaning, and antibiotic stewardship were the main strategies.
“Despite all these measures, we were not completely blocking dissemination of C difficile in our hospital,” Dr. Longtin said. He added that soap and water are better than alcohol for C. difficile, “but honestly not very good. Even the best hand hygiene technique is poorly effective to remove C. difficile. On the other hand – get it? – gloves are very effective. We felt we had to combine hand washing with gloves.”
Hand hygiene compliance increased from 37% to 50% during the intervention, and Dr. Longtin expected further improvements over time.
Risk to other patients
“Transmission of C. difficile cannot only be explained by infected patients in a hospital, so likely carriers also play a role,” Dr. Longtin said.
Another set of investigators found that hospital patients exposed to a carrier of C. difficile had nearly twice the risk of acquiring the infection (odds ratio, 1.79) (Gastroenterology. 2017 Apr;152[5]:1031-41.e2).
“For every patient with C. difficile infection, it’s estimated there are 5-7 C. difficile carriers, so they are numerous as well,” he said.
The bigger picture
During the study period, the C. difficile infection trends did not significantly change on the city level, further supporting the effectiveness of the carrier screen-and-isolate strategy.
There was slight increase in antibiotic use during the intervention period, Dr. Longtin said. “The only type of antibiotics that really decreased were vancomycin and metronidazole... which suggests in turn there were fewer cases of C. difficile infection.”
Long-term follow-up is ongoing, Dr. Longtin said. “We have more than 3 years of intervention. In the past year, our rate was 2.2 per 10,000 patient-days.”
Unanswered questions include the generalizability of the results “because we’re a very pro–infection control hospital,” he said. In addition, a formal cost-benefit analysis of this strategy would be worthwhile in the future.
Dr. Longtin is a consultant for AMG Medical and receives research support from Merck and BD Medical.
AT ASM MICROBE 2017
Key clinical point: Identification and isolation of asymptomatic carriers of Clostridium difficile decreased a hospital’s infection rates over time.
Major finding: (P less than .001).
Data source: A study of 7,599 people screened at admission through the ED at an acute care hospital.
Disclosures: Dr. Longtin is a consultant for AMG Medical and receives research support from Merck and BD Medical.
Add-on aripiprazole shows modest improvement over bupropion in depression
In men with major depressive disorder (MMD) who were not responding well to an antidepressant treatment, adding aripiprazole resulted in a modest increase in the likelihood of remission, compared with switching to bupropion monotherapy, according to results from a new randomized study.
The findings, published online July 11 in JAMA, come from a randomized, single-blinded trial enrolling more than 1,500 Veterans Health Administration patients (85% men; mean age, 54) with persistent MDD symptoms despite a trial of at least 1 antidepressant drug (JAMA. 2017;318[2]:132-45.).
The VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study, led by Somaia Mohamed, MD, PhD, of the VA Connecticut Healthcare System in West Haven, Conn., and carried out at 35 Veterans Health Administration treatment centers, was designed to help answer some of the lingering questions about augmentation strategies that the landmark, federally funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, from 2006, could not answer.
While the STAR*D investigators found bupropion to be an effective switching and augmentation agent in people who had failed citalopram monotherapy, the study was not powered to compare results for switching and augmentation. Nor did STAR*D include augmentation with atypical antipsychotics such as aripiprazole, a treatment strategy that was not yet in wide use.
The VAST-D study also differed from most depression trials in that most of the patients were men. The main outcome was clinical remission within 12 weeks of initiating one of the three treatment strategies. Subjects were randomized to augmentation of current treatment with aripiprazole 2-15 mg (n = 505) or bupropion 150-400 mg (n = 506) or were switched from current treatment to bupropion monotherapy (n = 511).
Remission rates during the first 12 weeks were 22% for patients switched from their current drug to bupropion, 27% for those who augmented treatment with bupropion, and 29% for those who augmented treatment with aripiprazole, though the difference in remission reached statistical significance only for the adjunctive aripiprazole group vs. the bupropion monotherapy group (relative risk, 1.30; 95% confidence interval, 1.05-1.60; P = .02).
Clinical response, as measured using two validated scoring systems, was higher (74%) in the aripiprazole group at 12 weeks, compared with the bupropion only (62%) or bupropion augmentation (66%) groups, a difference that reached statistical significance. Anxiety was more commonly reported among patients in the bupropion groups, while somnolence, akathisia, and weight gain were more frequently reported among patients treated with aripiprazole.
Though aripiprazole augmentation was seen associated with a higher rate of remission and greater response, Dr. Mohamed and her colleagues cautioned that, “given the small effect size and adverse effects” associated with the atypical antipsychotic drug, “further analysis, including cost-effectiveness, is needed to understand the net utility of this approach.”
The Department of Veterans Affairs sponsored the study. Bristol-Myers Squibb provided aripiprazole to investigators. Of the study’s 16 listed coauthors, 5 reported financial relationships with Bristol-Myers Squibb or other manufacturers.
“The modest advantage of aripiprazole augmentation over the two other treatment options in the VAST-D study suggests that this approach should be considered earlier by clinicians for patients with MDD who have an inadequate response to antidepressant therapies,” Maurizio Fava, MD, wrote in an editorial accompanying the study published by JAMA.
He also pointed out that the demographic makeup of the patients study was largely male, which is significantly different “from the usual study population in large trials of MDD, in which women typically far exceed the proportion of male study participants, as was the case with STAR*D.”
Dr. Fava cited the differences in the proportion of patients with posttraumatic stress disorder in the VAST-D and STAR*D study. In VAST-D, 44%-48% had PTSD, compared with a rate of 17% in the STAR*D cohort. “Did such enrichment potentially favor one of the treatment options of VAST-D? Although a placebo-controlled study of bupropion in chronic PTSD showed no benefit of this therapy, a meta-analysis of eight randomized, double-blind, placebo-controlled clinical trials of atypical antipsychotics for the treatment of PTSD found that these agents may be superior to placebo,” Dr. Fava wrote.
Finally, he cited the differences in mean age of onset of MDD in the two studies. In the VAST-D study, the mean age of onset ranged from 36 to 38 years and compared with a mean age of onset of 25 in STAR*D. “The older age of onset of MDD in the VAST-D study suggests that, in many cases, the MDD may have been secondary to other psychiatric conditions, such as PTSD. Therefore, there might be some significant neurobiological differences between the two populations,” Dr. Fava wrote (JAMA. 2017;318[2]:126-8).
Dr. Fava is affiliated with the division of clinical research at Massachusetts General Hospital, Boston. He reported financial relationships with numerous pharmaceutical companies.
“The modest advantage of aripiprazole augmentation over the two other treatment options in the VAST-D study suggests that this approach should be considered earlier by clinicians for patients with MDD who have an inadequate response to antidepressant therapies,” Maurizio Fava, MD, wrote in an editorial accompanying the study published by JAMA.
He also pointed out that the demographic makeup of the patients study was largely male, which is significantly different “from the usual study population in large trials of MDD, in which women typically far exceed the proportion of male study participants, as was the case with STAR*D.”
Dr. Fava cited the differences in the proportion of patients with posttraumatic stress disorder in the VAST-D and STAR*D study. In VAST-D, 44%-48% had PTSD, compared with a rate of 17% in the STAR*D cohort. “Did such enrichment potentially favor one of the treatment options of VAST-D? Although a placebo-controlled study of bupropion in chronic PTSD showed no benefit of this therapy, a meta-analysis of eight randomized, double-blind, placebo-controlled clinical trials of atypical antipsychotics for the treatment of PTSD found that these agents may be superior to placebo,” Dr. Fava wrote.
Finally, he cited the differences in mean age of onset of MDD in the two studies. In the VAST-D study, the mean age of onset ranged from 36 to 38 years and compared with a mean age of onset of 25 in STAR*D. “The older age of onset of MDD in the VAST-D study suggests that, in many cases, the MDD may have been secondary to other psychiatric conditions, such as PTSD. Therefore, there might be some significant neurobiological differences between the two populations,” Dr. Fava wrote (JAMA. 2017;318[2]:126-8).
Dr. Fava is affiliated with the division of clinical research at Massachusetts General Hospital, Boston. He reported financial relationships with numerous pharmaceutical companies.
“The modest advantage of aripiprazole augmentation over the two other treatment options in the VAST-D study suggests that this approach should be considered earlier by clinicians for patients with MDD who have an inadequate response to antidepressant therapies,” Maurizio Fava, MD, wrote in an editorial accompanying the study published by JAMA.
He also pointed out that the demographic makeup of the patients study was largely male, which is significantly different “from the usual study population in large trials of MDD, in which women typically far exceed the proportion of male study participants, as was the case with STAR*D.”
Dr. Fava cited the differences in the proportion of patients with posttraumatic stress disorder in the VAST-D and STAR*D study. In VAST-D, 44%-48% had PTSD, compared with a rate of 17% in the STAR*D cohort. “Did such enrichment potentially favor one of the treatment options of VAST-D? Although a placebo-controlled study of bupropion in chronic PTSD showed no benefit of this therapy, a meta-analysis of eight randomized, double-blind, placebo-controlled clinical trials of atypical antipsychotics for the treatment of PTSD found that these agents may be superior to placebo,” Dr. Fava wrote.
Finally, he cited the differences in mean age of onset of MDD in the two studies. In the VAST-D study, the mean age of onset ranged from 36 to 38 years and compared with a mean age of onset of 25 in STAR*D. “The older age of onset of MDD in the VAST-D study suggests that, in many cases, the MDD may have been secondary to other psychiatric conditions, such as PTSD. Therefore, there might be some significant neurobiological differences between the two populations,” Dr. Fava wrote (JAMA. 2017;318[2]:126-8).
Dr. Fava is affiliated with the division of clinical research at Massachusetts General Hospital, Boston. He reported financial relationships with numerous pharmaceutical companies.
In men with major depressive disorder (MMD) who were not responding well to an antidepressant treatment, adding aripiprazole resulted in a modest increase in the likelihood of remission, compared with switching to bupropion monotherapy, according to results from a new randomized study.
The findings, published online July 11 in JAMA, come from a randomized, single-blinded trial enrolling more than 1,500 Veterans Health Administration patients (85% men; mean age, 54) with persistent MDD symptoms despite a trial of at least 1 antidepressant drug (JAMA. 2017;318[2]:132-45.).
The VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study, led by Somaia Mohamed, MD, PhD, of the VA Connecticut Healthcare System in West Haven, Conn., and carried out at 35 Veterans Health Administration treatment centers, was designed to help answer some of the lingering questions about augmentation strategies that the landmark, federally funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, from 2006, could not answer.
While the STAR*D investigators found bupropion to be an effective switching and augmentation agent in people who had failed citalopram monotherapy, the study was not powered to compare results for switching and augmentation. Nor did STAR*D include augmentation with atypical antipsychotics such as aripiprazole, a treatment strategy that was not yet in wide use.
The VAST-D study also differed from most depression trials in that most of the patients were men. The main outcome was clinical remission within 12 weeks of initiating one of the three treatment strategies. Subjects were randomized to augmentation of current treatment with aripiprazole 2-15 mg (n = 505) or bupropion 150-400 mg (n = 506) or were switched from current treatment to bupropion monotherapy (n = 511).
Remission rates during the first 12 weeks were 22% for patients switched from their current drug to bupropion, 27% for those who augmented treatment with bupropion, and 29% for those who augmented treatment with aripiprazole, though the difference in remission reached statistical significance only for the adjunctive aripiprazole group vs. the bupropion monotherapy group (relative risk, 1.30; 95% confidence interval, 1.05-1.60; P = .02).
Clinical response, as measured using two validated scoring systems, was higher (74%) in the aripiprazole group at 12 weeks, compared with the bupropion only (62%) or bupropion augmentation (66%) groups, a difference that reached statistical significance. Anxiety was more commonly reported among patients in the bupropion groups, while somnolence, akathisia, and weight gain were more frequently reported among patients treated with aripiprazole.
Though aripiprazole augmentation was seen associated with a higher rate of remission and greater response, Dr. Mohamed and her colleagues cautioned that, “given the small effect size and adverse effects” associated with the atypical antipsychotic drug, “further analysis, including cost-effectiveness, is needed to understand the net utility of this approach.”
The Department of Veterans Affairs sponsored the study. Bristol-Myers Squibb provided aripiprazole to investigators. Of the study’s 16 listed coauthors, 5 reported financial relationships with Bristol-Myers Squibb or other manufacturers.
In men with major depressive disorder (MMD) who were not responding well to an antidepressant treatment, adding aripiprazole resulted in a modest increase in the likelihood of remission, compared with switching to bupropion monotherapy, according to results from a new randomized study.
The findings, published online July 11 in JAMA, come from a randomized, single-blinded trial enrolling more than 1,500 Veterans Health Administration patients (85% men; mean age, 54) with persistent MDD symptoms despite a trial of at least 1 antidepressant drug (JAMA. 2017;318[2]:132-45.).
The VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study, led by Somaia Mohamed, MD, PhD, of the VA Connecticut Healthcare System in West Haven, Conn., and carried out at 35 Veterans Health Administration treatment centers, was designed to help answer some of the lingering questions about augmentation strategies that the landmark, federally funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, from 2006, could not answer.
While the STAR*D investigators found bupropion to be an effective switching and augmentation agent in people who had failed citalopram monotherapy, the study was not powered to compare results for switching and augmentation. Nor did STAR*D include augmentation with atypical antipsychotics such as aripiprazole, a treatment strategy that was not yet in wide use.
The VAST-D study also differed from most depression trials in that most of the patients were men. The main outcome was clinical remission within 12 weeks of initiating one of the three treatment strategies. Subjects were randomized to augmentation of current treatment with aripiprazole 2-15 mg (n = 505) or bupropion 150-400 mg (n = 506) or were switched from current treatment to bupropion monotherapy (n = 511).
Remission rates during the first 12 weeks were 22% for patients switched from their current drug to bupropion, 27% for those who augmented treatment with bupropion, and 29% for those who augmented treatment with aripiprazole, though the difference in remission reached statistical significance only for the adjunctive aripiprazole group vs. the bupropion monotherapy group (relative risk, 1.30; 95% confidence interval, 1.05-1.60; P = .02).
Clinical response, as measured using two validated scoring systems, was higher (74%) in the aripiprazole group at 12 weeks, compared with the bupropion only (62%) or bupropion augmentation (66%) groups, a difference that reached statistical significance. Anxiety was more commonly reported among patients in the bupropion groups, while somnolence, akathisia, and weight gain were more frequently reported among patients treated with aripiprazole.
Though aripiprazole augmentation was seen associated with a higher rate of remission and greater response, Dr. Mohamed and her colleagues cautioned that, “given the small effect size and adverse effects” associated with the atypical antipsychotic drug, “further analysis, including cost-effectiveness, is needed to understand the net utility of this approach.”
The Department of Veterans Affairs sponsored the study. Bristol-Myers Squibb provided aripiprazole to investigators. Of the study’s 16 listed coauthors, 5 reported financial relationships with Bristol-Myers Squibb or other manufacturers.
FROM JAMA
Key clinical point: Aripiprazole added to a current antidepressant was associated with a modestly higher remission rate among men with MDD than was switching to bupropion monotherapy.
Major finding: Remission by 12 weeks was 28.9% among patients receiving add-on aripiprazole, vs. 22.3% for bupropion alone (RR, 1.30; 95% CI, 1.05-1.60; P = 0.02).
Data source: A randomized, single-blinded multicenter trial enrolling more than 1,500 patients (85% men) with persistent MDD despite treatment.
Disclosures: The Veterans Health Administration sponsored the study. One of the study drugs was donated by a manufacturer, and 5 of 16 coauthors disclosed financial conflicts of interest.
Counsel low-risk patients case by case on diet, exercise
Clinical judgment should drive referrals for diet and exercise behavioral counseling for adults with a low risk for cardiovascular disease (CVD), according to a new recommendation statement from the U.S. Preventive Services Task Force published online July 11 in JAMA.
“Persons who are interested and ready to make behavioral changes may be most likely to benefit from behavioral counseling,” according to the statement (JAMA 2017 Jul 11;318:167-74. doi: 10.1001/jama.2017.7171).
The recommendation is a C, which means that clinicians should consider patient preferences and clinical judgment, wrote David C. Grossman, MD, of Kaiser Permanente Washington Health Research Institute, Seattle, and his colleagues.
To assess the value of behavioral counseling in adults at low risk for cardiovascular disease, the USPSTF reviewed 88 trials including more than 120 interventions related to a healthful diet, physical activity, or both. None of the trials included in the review noted specific adverse events related to counseling.
Although the evidence was insufficient to support benefits from behavioral counseling for reducing death or CVD rates, the data showed that behavioral counseling was associated with improved systolic and diastolic blood pressure levels, cholesterol, body mass index, and waist circumference over 6-12 months.
In data from 34 trials, behavior counseling resulted in significant changes to several CVD risk factors, with average improvements of –1.26 mm Hg for systolic blood pressure, –0.49 mm Hg for diastolic blood pressure, –2.85 mg/dL for total cholesterol, –0.41 kg/m2 for body mass index, –1.04 kg for weight, and –0.19 cm for waist circumference.
The current recommendation updates the 2012 recommendations that primary care clinicians “selectively provide or refer patients who do not have hypertension, dyslipidemia, diabetes, or CVD to behavioral counseling to promote a healthful diet and physical activity rather than incorporating counseling into the routine care of adults.”
Separate USPSTF recommendations focus on behavioral counseling in adults with risk factors including obesity, abnormal blood glucose levels, diabetes, or CVD, therefore, the current recommendation “focuses on persons without these risk factors,” the researchers noted.
In the evidence report accompanying the recommendations, Carrie D. Patnode, PhD, of Kaiser Permanente in Portland, Ore., and her colleagues concluded that higher-intensity interventions may promote greater improvements in health outcomes, but that “there is very limited evidence on longer-term intermediate and health outcomes or on harmful effects of these interventions” (JAMA 2017;318:175-93. doi: 10.1001/jama.2017.3303).
The researchers had no financial conflicts to disclose.
“The evidence is strong, consistent, and persuasive that CVD risk factor prevention and treatment are associated with lower rates of CVD,” wrote Philip Greenland, MD, and Valentin Fuster, MD, PhD, in an accompanying editorial (JAMA 2017 Jul 11;318:130-1). “There are no universally effective solutions to accomplish this, but certain principles apply. Recommended dietary patterns focus on meals high in vegetables, fruit, whole grains, seafood, legumes, and nuts; moderate in low-fat and nonfat dairy products; lower in red and processed meat, foods and beverages containing added sugar, and refined grains,” they said. In addition, “physical activity must be encouraged in children and adults and emphasize a regular and consistent commitment to daily exercise habits. Research findings support the need to begin interventions in preschool children, [and should] involve the family, and continue lifelong,” they noted.
Although the guidelines address the challenges faced by clinicians in controlling CVD risk factors, “risk factor control in the clinical setting begins with risk assessment, aims at targeting all risk factors above ideal levels, and moves patients in measured steps toward more ideal cardiovascular health,” the editorialists said.
Dr. Greenland is affiliated with the department of preventive medicine at Northwestern University, Chicago. Dr. Fuster is director of the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, N.Y. They had no financial conflicts to disclose.
“The evidence is strong, consistent, and persuasive that CVD risk factor prevention and treatment are associated with lower rates of CVD,” wrote Philip Greenland, MD, and Valentin Fuster, MD, PhD, in an accompanying editorial (JAMA 2017 Jul 11;318:130-1). “There are no universally effective solutions to accomplish this, but certain principles apply. Recommended dietary patterns focus on meals high in vegetables, fruit, whole grains, seafood, legumes, and nuts; moderate in low-fat and nonfat dairy products; lower in red and processed meat, foods and beverages containing added sugar, and refined grains,” they said. In addition, “physical activity must be encouraged in children and adults and emphasize a regular and consistent commitment to daily exercise habits. Research findings support the need to begin interventions in preschool children, [and should] involve the family, and continue lifelong,” they noted.
Although the guidelines address the challenges faced by clinicians in controlling CVD risk factors, “risk factor control in the clinical setting begins with risk assessment, aims at targeting all risk factors above ideal levels, and moves patients in measured steps toward more ideal cardiovascular health,” the editorialists said.
Dr. Greenland is affiliated with the department of preventive medicine at Northwestern University, Chicago. Dr. Fuster is director of the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, N.Y. They had no financial conflicts to disclose.
“The evidence is strong, consistent, and persuasive that CVD risk factor prevention and treatment are associated with lower rates of CVD,” wrote Philip Greenland, MD, and Valentin Fuster, MD, PhD, in an accompanying editorial (JAMA 2017 Jul 11;318:130-1). “There are no universally effective solutions to accomplish this, but certain principles apply. Recommended dietary patterns focus on meals high in vegetables, fruit, whole grains, seafood, legumes, and nuts; moderate in low-fat and nonfat dairy products; lower in red and processed meat, foods and beverages containing added sugar, and refined grains,” they said. In addition, “physical activity must be encouraged in children and adults and emphasize a regular and consistent commitment to daily exercise habits. Research findings support the need to begin interventions in preschool children, [and should] involve the family, and continue lifelong,” they noted.
Although the guidelines address the challenges faced by clinicians in controlling CVD risk factors, “risk factor control in the clinical setting begins with risk assessment, aims at targeting all risk factors above ideal levels, and moves patients in measured steps toward more ideal cardiovascular health,” the editorialists said.
Dr. Greenland is affiliated with the department of preventive medicine at Northwestern University, Chicago. Dr. Fuster is director of the Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, N.Y. They had no financial conflicts to disclose.
Clinical judgment should drive referrals for diet and exercise behavioral counseling for adults with a low risk for cardiovascular disease (CVD), according to a new recommendation statement from the U.S. Preventive Services Task Force published online July 11 in JAMA.
“Persons who are interested and ready to make behavioral changes may be most likely to benefit from behavioral counseling,” according to the statement (JAMA 2017 Jul 11;318:167-74. doi: 10.1001/jama.2017.7171).
The recommendation is a C, which means that clinicians should consider patient preferences and clinical judgment, wrote David C. Grossman, MD, of Kaiser Permanente Washington Health Research Institute, Seattle, and his colleagues.
To assess the value of behavioral counseling in adults at low risk for cardiovascular disease, the USPSTF reviewed 88 trials including more than 120 interventions related to a healthful diet, physical activity, or both. None of the trials included in the review noted specific adverse events related to counseling.
Although the evidence was insufficient to support benefits from behavioral counseling for reducing death or CVD rates, the data showed that behavioral counseling was associated with improved systolic and diastolic blood pressure levels, cholesterol, body mass index, and waist circumference over 6-12 months.
In data from 34 trials, behavior counseling resulted in significant changes to several CVD risk factors, with average improvements of –1.26 mm Hg for systolic blood pressure, –0.49 mm Hg for diastolic blood pressure, –2.85 mg/dL for total cholesterol, –0.41 kg/m2 for body mass index, –1.04 kg for weight, and –0.19 cm for waist circumference.
The current recommendation updates the 2012 recommendations that primary care clinicians “selectively provide or refer patients who do not have hypertension, dyslipidemia, diabetes, or CVD to behavioral counseling to promote a healthful diet and physical activity rather than incorporating counseling into the routine care of adults.”
Separate USPSTF recommendations focus on behavioral counseling in adults with risk factors including obesity, abnormal blood glucose levels, diabetes, or CVD, therefore, the current recommendation “focuses on persons without these risk factors,” the researchers noted.
In the evidence report accompanying the recommendations, Carrie D. Patnode, PhD, of Kaiser Permanente in Portland, Ore., and her colleagues concluded that higher-intensity interventions may promote greater improvements in health outcomes, but that “there is very limited evidence on longer-term intermediate and health outcomes or on harmful effects of these interventions” (JAMA 2017;318:175-93. doi: 10.1001/jama.2017.3303).
The researchers had no financial conflicts to disclose.
Clinical judgment should drive referrals for diet and exercise behavioral counseling for adults with a low risk for cardiovascular disease (CVD), according to a new recommendation statement from the U.S. Preventive Services Task Force published online July 11 in JAMA.
“Persons who are interested and ready to make behavioral changes may be most likely to benefit from behavioral counseling,” according to the statement (JAMA 2017 Jul 11;318:167-74. doi: 10.1001/jama.2017.7171).
The recommendation is a C, which means that clinicians should consider patient preferences and clinical judgment, wrote David C. Grossman, MD, of Kaiser Permanente Washington Health Research Institute, Seattle, and his colleagues.
To assess the value of behavioral counseling in adults at low risk for cardiovascular disease, the USPSTF reviewed 88 trials including more than 120 interventions related to a healthful diet, physical activity, or both. None of the trials included in the review noted specific adverse events related to counseling.
Although the evidence was insufficient to support benefits from behavioral counseling for reducing death or CVD rates, the data showed that behavioral counseling was associated with improved systolic and diastolic blood pressure levels, cholesterol, body mass index, and waist circumference over 6-12 months.
In data from 34 trials, behavior counseling resulted in significant changes to several CVD risk factors, with average improvements of –1.26 mm Hg for systolic blood pressure, –0.49 mm Hg for diastolic blood pressure, –2.85 mg/dL for total cholesterol, –0.41 kg/m2 for body mass index, –1.04 kg for weight, and –0.19 cm for waist circumference.
The current recommendation updates the 2012 recommendations that primary care clinicians “selectively provide or refer patients who do not have hypertension, dyslipidemia, diabetes, or CVD to behavioral counseling to promote a healthful diet and physical activity rather than incorporating counseling into the routine care of adults.”
Separate USPSTF recommendations focus on behavioral counseling in adults with risk factors including obesity, abnormal blood glucose levels, diabetes, or CVD, therefore, the current recommendation “focuses on persons without these risk factors,” the researchers noted.
In the evidence report accompanying the recommendations, Carrie D. Patnode, PhD, of Kaiser Permanente in Portland, Ore., and her colleagues concluded that higher-intensity interventions may promote greater improvements in health outcomes, but that “there is very limited evidence on longer-term intermediate and health outcomes or on harmful effects of these interventions” (JAMA 2017;318:175-93. doi: 10.1001/jama.2017.3303).
The researchers had no financial conflicts to disclose.
FROM JAMA
Key clinical point: Even adults with no CVD risk factors benefit from behavioral counseling about diet and exercise, according to the USPSTF.
Major finding: In 34 trials involving intermediate outcomes, behavior counseling was associated with significant improvements in systolic blood pressure, diastolic blood pressure, total cholesterol, BMI, weight, and waist circumference.
Data source: The data come from a USPSTF review of 88 trials and more 120 interventions.
Disclosures: The researchers had no relevant financial conflicts to disclose.
CPAP doesn’t cut rates of CV events, death
Positive airway pressure, whether delivered continuously (CPAP) or as adaptive servoventilation, doesn’t reduce the rate of cardiovascular (CV) events or death in patients who have sleep apnea, according to a report published online July 11 in JAMA.
Positive airway pressure (PAP) relieves the symptoms of sleep apnea and has been reported to improve cardiovascular risk factors such as hypertension, insulin resistance, and endothelial dysfunction. However, whether the treatment improves “hard” vascular outcomes such as stroke and MI has never been established, said Jie Yu, MD, of the department of cardiology, Peking University and the Ministries of Health and Education, Beijing, and his associates.
They performed a systematic review of the literature and a meta-analysis of 10 randomized clinical trials that compared PAP against standard care or a sham treatment and had at least 6 months of follow-up for CV events. The meta-analysis involved 7,266 participants who had either obstructive (5,683 patients) or central (1,583 patients) sleep apnea. There were 356 major adverse CV events and 613 deaths during a median follow-up of 6-68 months.
The use of PAP showed no significant association with a range of outcomes: major adverse CV events (relative risk, 0.77; P = .19), major adverse CV events plus hospitalization for unstable angina (RR, 0.92; P = .54), cardiovascular death (RR, 1.15; P = .30), all-cause mortality (RR, 1.13; P = .08), noncardiovascular death (RR, 0.85; P = .33), acute coronary syndromes (RR, 1.00; P = .99), stroke (RR, 0.90; P = .47), and heart failure (RR, 1.03; P = .60). This lack of treatment benefit persisted regardless of length of follow-up, adherence to treatment, or baseline score on the apnea-hypopnea index, the investigators said (JAMA. 2017 July 11. doi: 10.1001/jama.2017.7967).
PAP also failed to improve blood pressure, body mass index, any lipid parameter, glycemia, or quality-of-life scores on the EQ-5D. It did improve sleepiness and some measures of physical and mental well-being.
“The evidence from these [randomized clinical trials] suggests that the association [between] sleep apnea and vascular outcomes and death ... may represent disease processes that cannot be ameliorated by PAP delivered at the average intensity achieved in these clinical trials or by currently feasible methods in clinical practice,” Dr. Yu and his associates said.
Their findings also “emphasize the importance of proven therapies, such as blood-pressure lowering, lipid lowering, and antiplatelet therapy, in patients with sleep apnea, who should be treated according to established guidelines for patients at elevated cardiovascular risk,” they added.
This study was supported by the National Health and Medical Research Council of Australia. Dr. Yu reported having no relevant financial disclosures. His associates reported ties to numerous industry sources.
The estimated relative risk for the association between PAP and the composite outcome of acute coronary events, stroke, or vascular death was 0.77 in the study by Yu et al. It did not reach statistical significance but is similar to the estimated risk reduction associated with antiplatelet therapy, statins, and beta-blockers in preventing recurrent vascular events.
This magnitude of benefit could be of substantial clinical importance. Far from discouraging further research, this meta-analysis should be an impetus for more studies examining whether treatment of sleep apnea reduces vascular disease risk.
Daniel J. Gottlieb, M.D., is in the Medical Service at the V.A. Boston Healthcare System and in the division of sleep medicine at Harvard. He reported receiving personal fees from VIVUS. Dr. Gottlieb made these remarks in an editorial accompanying Dr. Yu’s report (JAMA. 2017;318:128-30).
The estimated relative risk for the association between PAP and the composite outcome of acute coronary events, stroke, or vascular death was 0.77 in the study by Yu et al. It did not reach statistical significance but is similar to the estimated risk reduction associated with antiplatelet therapy, statins, and beta-blockers in preventing recurrent vascular events.
This magnitude of benefit could be of substantial clinical importance. Far from discouraging further research, this meta-analysis should be an impetus for more studies examining whether treatment of sleep apnea reduces vascular disease risk.
Daniel J. Gottlieb, M.D., is in the Medical Service at the V.A. Boston Healthcare System and in the division of sleep medicine at Harvard. He reported receiving personal fees from VIVUS. Dr. Gottlieb made these remarks in an editorial accompanying Dr. Yu’s report (JAMA. 2017;318:128-30).
The estimated relative risk for the association between PAP and the composite outcome of acute coronary events, stroke, or vascular death was 0.77 in the study by Yu et al. It did not reach statistical significance but is similar to the estimated risk reduction associated with antiplatelet therapy, statins, and beta-blockers in preventing recurrent vascular events.
This magnitude of benefit could be of substantial clinical importance. Far from discouraging further research, this meta-analysis should be an impetus for more studies examining whether treatment of sleep apnea reduces vascular disease risk.
Daniel J. Gottlieb, M.D., is in the Medical Service at the V.A. Boston Healthcare System and in the division of sleep medicine at Harvard. He reported receiving personal fees from VIVUS. Dr. Gottlieb made these remarks in an editorial accompanying Dr. Yu’s report (JAMA. 2017;318:128-30).
Positive airway pressure, whether delivered continuously (CPAP) or as adaptive servoventilation, doesn’t reduce the rate of cardiovascular (CV) events or death in patients who have sleep apnea, according to a report published online July 11 in JAMA.
Positive airway pressure (PAP) relieves the symptoms of sleep apnea and has been reported to improve cardiovascular risk factors such as hypertension, insulin resistance, and endothelial dysfunction. However, whether the treatment improves “hard” vascular outcomes such as stroke and MI has never been established, said Jie Yu, MD, of the department of cardiology, Peking University and the Ministries of Health and Education, Beijing, and his associates.
They performed a systematic review of the literature and a meta-analysis of 10 randomized clinical trials that compared PAP against standard care or a sham treatment and had at least 6 months of follow-up for CV events. The meta-analysis involved 7,266 participants who had either obstructive (5,683 patients) or central (1,583 patients) sleep apnea. There were 356 major adverse CV events and 613 deaths during a median follow-up of 6-68 months.
The use of PAP showed no significant association with a range of outcomes: major adverse CV events (relative risk, 0.77; P = .19), major adverse CV events plus hospitalization for unstable angina (RR, 0.92; P = .54), cardiovascular death (RR, 1.15; P = .30), all-cause mortality (RR, 1.13; P = .08), noncardiovascular death (RR, 0.85; P = .33), acute coronary syndromes (RR, 1.00; P = .99), stroke (RR, 0.90; P = .47), and heart failure (RR, 1.03; P = .60). This lack of treatment benefit persisted regardless of length of follow-up, adherence to treatment, or baseline score on the apnea-hypopnea index, the investigators said (JAMA. 2017 July 11. doi: 10.1001/jama.2017.7967).
PAP also failed to improve blood pressure, body mass index, any lipid parameter, glycemia, or quality-of-life scores on the EQ-5D. It did improve sleepiness and some measures of physical and mental well-being.
“The evidence from these [randomized clinical trials] suggests that the association [between] sleep apnea and vascular outcomes and death ... may represent disease processes that cannot be ameliorated by PAP delivered at the average intensity achieved in these clinical trials or by currently feasible methods in clinical practice,” Dr. Yu and his associates said.
Their findings also “emphasize the importance of proven therapies, such as blood-pressure lowering, lipid lowering, and antiplatelet therapy, in patients with sleep apnea, who should be treated according to established guidelines for patients at elevated cardiovascular risk,” they added.
This study was supported by the National Health and Medical Research Council of Australia. Dr. Yu reported having no relevant financial disclosures. His associates reported ties to numerous industry sources.
Positive airway pressure, whether delivered continuously (CPAP) or as adaptive servoventilation, doesn’t reduce the rate of cardiovascular (CV) events or death in patients who have sleep apnea, according to a report published online July 11 in JAMA.
Positive airway pressure (PAP) relieves the symptoms of sleep apnea and has been reported to improve cardiovascular risk factors such as hypertension, insulin resistance, and endothelial dysfunction. However, whether the treatment improves “hard” vascular outcomes such as stroke and MI has never been established, said Jie Yu, MD, of the department of cardiology, Peking University and the Ministries of Health and Education, Beijing, and his associates.
They performed a systematic review of the literature and a meta-analysis of 10 randomized clinical trials that compared PAP against standard care or a sham treatment and had at least 6 months of follow-up for CV events. The meta-analysis involved 7,266 participants who had either obstructive (5,683 patients) or central (1,583 patients) sleep apnea. There were 356 major adverse CV events and 613 deaths during a median follow-up of 6-68 months.
The use of PAP showed no significant association with a range of outcomes: major adverse CV events (relative risk, 0.77; P = .19), major adverse CV events plus hospitalization for unstable angina (RR, 0.92; P = .54), cardiovascular death (RR, 1.15; P = .30), all-cause mortality (RR, 1.13; P = .08), noncardiovascular death (RR, 0.85; P = .33), acute coronary syndromes (RR, 1.00; P = .99), stroke (RR, 0.90; P = .47), and heart failure (RR, 1.03; P = .60). This lack of treatment benefit persisted regardless of length of follow-up, adherence to treatment, or baseline score on the apnea-hypopnea index, the investigators said (JAMA. 2017 July 11. doi: 10.1001/jama.2017.7967).
PAP also failed to improve blood pressure, body mass index, any lipid parameter, glycemia, or quality-of-life scores on the EQ-5D. It did improve sleepiness and some measures of physical and mental well-being.
“The evidence from these [randomized clinical trials] suggests that the association [between] sleep apnea and vascular outcomes and death ... may represent disease processes that cannot be ameliorated by PAP delivered at the average intensity achieved in these clinical trials or by currently feasible methods in clinical practice,” Dr. Yu and his associates said.
Their findings also “emphasize the importance of proven therapies, such as blood-pressure lowering, lipid lowering, and antiplatelet therapy, in patients with sleep apnea, who should be treated according to established guidelines for patients at elevated cardiovascular risk,” they added.
This study was supported by the National Health and Medical Research Council of Australia. Dr. Yu reported having no relevant financial disclosures. His associates reported ties to numerous industry sources.
FROM JAMA
Key clinical point: Positive airway pressure, whether delivered continuously (CPAP) or as adaptive servoventilation, doesn’t reduce the rate of cardiovascular events or death in patients with sleep apnea.
Major finding: The use of PAP showed no association with a range of outcomes: major adverse CV events (RR, 0.77), major adverse CV events plus hospitalization for unstable angina (RR, 0.92), cardiovascular death (RR, 1.15), all-cause mortality (RR, 1.13), noncardiovascular death (RR, 0.85), acute coronary syndromes (RR, 1.00), stroke (RR, 0.90), and heart failure (RR, 1.03).
Data source: A meta-analysis of 10 randomized clinical trials involving 7,266 adults who had either central or obstructive sleep apnea.
Disclosures: This study was supported by the National Health and Medical Research Council of Australia. Dr. Yu reported having no relevant financial disclosures. His associates reported ties to numerous industry sources.
Don’t be bullied by patients threatening bad reviews
“I’m giving you a bad review on Yelp over this.”
He said that, and I honestly didn’t care.
When he called for the appointment, he told my staff he was on a PPO plan that I’m contracted with. But when he came in 2 weeks later, he had a completely different card: an HMO that I’ve never been affiliated with.
I’m an adult neurologist, and don’t see anyone under 18. If you’re an adult, you need to start taking responsibility for your actions. One of them should be knowing what your medical insurance is. This is your job. Not ours. When you tell us what your insurance is, we take you at your word.
But I’m here to help people, and he said he really needed to see me. So I offered to see him at my cash discount rate.
He said no.
I then said I’d see him, and bill it to his insurance to see if they paid anything, and we could work out what he still might owe after that. I was genuinely trying to help him.
Not surprisingly, he again said no.
Then he made me this counteroffer: See me for free, and I won’t post a negative online review about you.
Predictably, he left. And wrote the review on a rate-a-doc site.
Does the bad review bother me? Not at all. The nature of medicine is such that you can’t please everyone. And those you do please likely won’t write a review.
I come here each day to do my best to help people. Threatening me to start a medical relationship will find you going nowhere.
And taking responsibility for your own actions, like I tell my kids, is a big part of being a grownup.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
“I’m giving you a bad review on Yelp over this.”
He said that, and I honestly didn’t care.
When he called for the appointment, he told my staff he was on a PPO plan that I’m contracted with. But when he came in 2 weeks later, he had a completely different card: an HMO that I’ve never been affiliated with.
I’m an adult neurologist, and don’t see anyone under 18. If you’re an adult, you need to start taking responsibility for your actions. One of them should be knowing what your medical insurance is. This is your job. Not ours. When you tell us what your insurance is, we take you at your word.
But I’m here to help people, and he said he really needed to see me. So I offered to see him at my cash discount rate.
He said no.
I then said I’d see him, and bill it to his insurance to see if they paid anything, and we could work out what he still might owe after that. I was genuinely trying to help him.
Not surprisingly, he again said no.
Then he made me this counteroffer: See me for free, and I won’t post a negative online review about you.
Predictably, he left. And wrote the review on a rate-a-doc site.
Does the bad review bother me? Not at all. The nature of medicine is such that you can’t please everyone. And those you do please likely won’t write a review.
I come here each day to do my best to help people. Threatening me to start a medical relationship will find you going nowhere.
And taking responsibility for your own actions, like I tell my kids, is a big part of being a grownup.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
“I’m giving you a bad review on Yelp over this.”
He said that, and I honestly didn’t care.
When he called for the appointment, he told my staff he was on a PPO plan that I’m contracted with. But when he came in 2 weeks later, he had a completely different card: an HMO that I’ve never been affiliated with.
I’m an adult neurologist, and don’t see anyone under 18. If you’re an adult, you need to start taking responsibility for your actions. One of them should be knowing what your medical insurance is. This is your job. Not ours. When you tell us what your insurance is, we take you at your word.
But I’m here to help people, and he said he really needed to see me. So I offered to see him at my cash discount rate.
He said no.
I then said I’d see him, and bill it to his insurance to see if they paid anything, and we could work out what he still might owe after that. I was genuinely trying to help him.
Not surprisingly, he again said no.
Then he made me this counteroffer: See me for free, and I won’t post a negative online review about you.
Predictably, he left. And wrote the review on a rate-a-doc site.
Does the bad review bother me? Not at all. The nature of medicine is such that you can’t please everyone. And those you do please likely won’t write a review.
I come here each day to do my best to help people. Threatening me to start a medical relationship will find you going nowhere.
And taking responsibility for your own actions, like I tell my kids, is a big part of being a grownup.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Copanlisib makes inroads against relapsed/refractory follicular lymphoma
LUGANO, SWITZERLAND – Copanlisib, an investigational intravenous inhibitor of phosphatidylinositol 3-kinase (PI3K), was associated with “promising” efficacy and a better safety profile than has been seen with oral PI3K inhibitors in patients with relapsed or refractory indolent lymphomas.
In a phase 2 trial of the drug as monotherapy in patients with indolent lymphomas, copanlisib was associated with an overall response rate of 58.6% among 104 patients with follicular lymphoma (FL), including 14.4% complete responses (CR) and 44.2% partial responses (PR), reported Martin Dreyling, MD, of the Universität München-Grosshadern in Munich, Germany.
“The favorable risk-benefit profile of this compound suggests further [need for] testing in follicular lymphoma. My personal interpretation is that the different safety profile is due to the intermittent dosing and the IV application, avoiding adverse cause-effect both in the gut and the liver,” he said at the 14th International Conference on Malignant Lymphoma.
Dr. Dreyling noted that the oral PI3K inhibitor idelalisib (Zydelig) is approved for the treatment of patients with relapsed chronic lymphocytic leukemia in combination with rituximab and in patients with relapsed FL or small lymphocytic lymphomas (SLL) who have received at least two prior lines of systemic therapy. This agent, however, carries a black box warning about fatal and serious toxicities, including hepatic events, severe diarrhea, colitis, pneumonitis, infections, and intestinal perforation.
Copanlisib inhibits all isoforms of P13K but is predominantly active against the alpha and delta isoforms of the kinase. The alpha form, expressed in many cell types, is involved in insulin signaling and angiogenesis and in resistance mechanisms to lymphoma. The delta form, expressed in leukocytes, is involved in B-cell signaling, development, and survival, making PIK3 an attractive target, Dr. Dreyling explained.
The study included patients with indolent B-cell lymphomas, including FL grades 1-3a, marginal zone lymphoma, SLL, or lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM) for whom at least two prior lines of therapy had failed.
The patients received copanlisib 60 mg IV on days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.
Of 142 assigned to and started on treatment, 46 patients (32.3%) remained on treatment at the time of data cutoff. Of the 96 patients (67.7%) who discontinued, 35 did so because of adverse events, 36 discontinued for radiologic or clinical evidence of progression, 16 withdrew, 5 were discontinued on the treating physician’s decision, and 4 stopped for other, unspecified reasons.
Among all 142 patients, the median duration of therapy was 22 weeks and the median number of cycles was 5.5. In all, 26.1% of patients required a dosage reduction to 45 mg, and 5.6% required reduction to 30 mg.
As noted, the objective tumor response rate (ORR) among patients was 58.6% for 104 patients with FL. For the 23 patients with marginal zone lymphoma, the ORR was 69.6%, consisting of two complete and 14 partial responses. Among eight patients with SLL, there were six partial responses and no complete responses. For the six patients with LPL/WM, there was one partial response.
The overall median duration of response was 22.6 months. Among patients with refractory disease and in all patients with FL the median duration of response was 12.2 months.
The median progression-free survival after 24 months of follow-up was 11.2 months for all patients. The median overall survival has not been reached.
The most frequent adverse events of grade 3 or 4 were hyperglycemia in 40.1% (33.1% grade 3 and 7.0% grade 4) and hypertension in 22.5% (all grade 3).
Grade 3 diarrhea, a significant problem with idelalisib, occurred in 4.2% of patients, and there were no grade 4 events.
Grade 3 pneumonitis was seen in two patients, and one had grade 4 colitis. There were three drug related deaths, including one patient each from lung infection, respiratory failure, or thromboembolic event..
The study was supported by Bayer. Dr. Dreyling disclosed receiving honoraria from the company and serving on a scientific/advisory board for the company.
LUGANO, SWITZERLAND – Copanlisib, an investigational intravenous inhibitor of phosphatidylinositol 3-kinase (PI3K), was associated with “promising” efficacy and a better safety profile than has been seen with oral PI3K inhibitors in patients with relapsed or refractory indolent lymphomas.
In a phase 2 trial of the drug as monotherapy in patients with indolent lymphomas, copanlisib was associated with an overall response rate of 58.6% among 104 patients with follicular lymphoma (FL), including 14.4% complete responses (CR) and 44.2% partial responses (PR), reported Martin Dreyling, MD, of the Universität München-Grosshadern in Munich, Germany.
“The favorable risk-benefit profile of this compound suggests further [need for] testing in follicular lymphoma. My personal interpretation is that the different safety profile is due to the intermittent dosing and the IV application, avoiding adverse cause-effect both in the gut and the liver,” he said at the 14th International Conference on Malignant Lymphoma.
Dr. Dreyling noted that the oral PI3K inhibitor idelalisib (Zydelig) is approved for the treatment of patients with relapsed chronic lymphocytic leukemia in combination with rituximab and in patients with relapsed FL or small lymphocytic lymphomas (SLL) who have received at least two prior lines of systemic therapy. This agent, however, carries a black box warning about fatal and serious toxicities, including hepatic events, severe diarrhea, colitis, pneumonitis, infections, and intestinal perforation.
Copanlisib inhibits all isoforms of P13K but is predominantly active against the alpha and delta isoforms of the kinase. The alpha form, expressed in many cell types, is involved in insulin signaling and angiogenesis and in resistance mechanisms to lymphoma. The delta form, expressed in leukocytes, is involved in B-cell signaling, development, and survival, making PIK3 an attractive target, Dr. Dreyling explained.
The study included patients with indolent B-cell lymphomas, including FL grades 1-3a, marginal zone lymphoma, SLL, or lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM) for whom at least two prior lines of therapy had failed.
The patients received copanlisib 60 mg IV on days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.
Of 142 assigned to and started on treatment, 46 patients (32.3%) remained on treatment at the time of data cutoff. Of the 96 patients (67.7%) who discontinued, 35 did so because of adverse events, 36 discontinued for radiologic or clinical evidence of progression, 16 withdrew, 5 were discontinued on the treating physician’s decision, and 4 stopped for other, unspecified reasons.
Among all 142 patients, the median duration of therapy was 22 weeks and the median number of cycles was 5.5. In all, 26.1% of patients required a dosage reduction to 45 mg, and 5.6% required reduction to 30 mg.
As noted, the objective tumor response rate (ORR) among patients was 58.6% for 104 patients with FL. For the 23 patients with marginal zone lymphoma, the ORR was 69.6%, consisting of two complete and 14 partial responses. Among eight patients with SLL, there were six partial responses and no complete responses. For the six patients with LPL/WM, there was one partial response.
The overall median duration of response was 22.6 months. Among patients with refractory disease and in all patients with FL the median duration of response was 12.2 months.
The median progression-free survival after 24 months of follow-up was 11.2 months for all patients. The median overall survival has not been reached.
The most frequent adverse events of grade 3 or 4 were hyperglycemia in 40.1% (33.1% grade 3 and 7.0% grade 4) and hypertension in 22.5% (all grade 3).
Grade 3 diarrhea, a significant problem with idelalisib, occurred in 4.2% of patients, and there were no grade 4 events.
Grade 3 pneumonitis was seen in two patients, and one had grade 4 colitis. There were three drug related deaths, including one patient each from lung infection, respiratory failure, or thromboembolic event..
The study was supported by Bayer. Dr. Dreyling disclosed receiving honoraria from the company and serving on a scientific/advisory board for the company.
LUGANO, SWITZERLAND – Copanlisib, an investigational intravenous inhibitor of phosphatidylinositol 3-kinase (PI3K), was associated with “promising” efficacy and a better safety profile than has been seen with oral PI3K inhibitors in patients with relapsed or refractory indolent lymphomas.
In a phase 2 trial of the drug as monotherapy in patients with indolent lymphomas, copanlisib was associated with an overall response rate of 58.6% among 104 patients with follicular lymphoma (FL), including 14.4% complete responses (CR) and 44.2% partial responses (PR), reported Martin Dreyling, MD, of the Universität München-Grosshadern in Munich, Germany.
“The favorable risk-benefit profile of this compound suggests further [need for] testing in follicular lymphoma. My personal interpretation is that the different safety profile is due to the intermittent dosing and the IV application, avoiding adverse cause-effect both in the gut and the liver,” he said at the 14th International Conference on Malignant Lymphoma.
Dr. Dreyling noted that the oral PI3K inhibitor idelalisib (Zydelig) is approved for the treatment of patients with relapsed chronic lymphocytic leukemia in combination with rituximab and in patients with relapsed FL or small lymphocytic lymphomas (SLL) who have received at least two prior lines of systemic therapy. This agent, however, carries a black box warning about fatal and serious toxicities, including hepatic events, severe diarrhea, colitis, pneumonitis, infections, and intestinal perforation.
Copanlisib inhibits all isoforms of P13K but is predominantly active against the alpha and delta isoforms of the kinase. The alpha form, expressed in many cell types, is involved in insulin signaling and angiogenesis and in resistance mechanisms to lymphoma. The delta form, expressed in leukocytes, is involved in B-cell signaling, development, and survival, making PIK3 an attractive target, Dr. Dreyling explained.
The study included patients with indolent B-cell lymphomas, including FL grades 1-3a, marginal zone lymphoma, SLL, or lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM) for whom at least two prior lines of therapy had failed.
The patients received copanlisib 60 mg IV on days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.
Of 142 assigned to and started on treatment, 46 patients (32.3%) remained on treatment at the time of data cutoff. Of the 96 patients (67.7%) who discontinued, 35 did so because of adverse events, 36 discontinued for radiologic or clinical evidence of progression, 16 withdrew, 5 were discontinued on the treating physician’s decision, and 4 stopped for other, unspecified reasons.
Among all 142 patients, the median duration of therapy was 22 weeks and the median number of cycles was 5.5. In all, 26.1% of patients required a dosage reduction to 45 mg, and 5.6% required reduction to 30 mg.
As noted, the objective tumor response rate (ORR) among patients was 58.6% for 104 patients with FL. For the 23 patients with marginal zone lymphoma, the ORR was 69.6%, consisting of two complete and 14 partial responses. Among eight patients with SLL, there were six partial responses and no complete responses. For the six patients with LPL/WM, there was one partial response.
The overall median duration of response was 22.6 months. Among patients with refractory disease and in all patients with FL the median duration of response was 12.2 months.
The median progression-free survival after 24 months of follow-up was 11.2 months for all patients. The median overall survival has not been reached.
The most frequent adverse events of grade 3 or 4 were hyperglycemia in 40.1% (33.1% grade 3 and 7.0% grade 4) and hypertension in 22.5% (all grade 3).
Grade 3 diarrhea, a significant problem with idelalisib, occurred in 4.2% of patients, and there were no grade 4 events.
Grade 3 pneumonitis was seen in two patients, and one had grade 4 colitis. There were three drug related deaths, including one patient each from lung infection, respiratory failure, or thromboembolic event..
The study was supported by Bayer. Dr. Dreyling disclosed receiving honoraria from the company and serving on a scientific/advisory board for the company.
AT 14-ICML
Key clinical point: Copanlisib, an intravenous PI3K inhibitor, was active against relapsed/refractory follicular lymphoma (FL).
Major finding: The overall response rate among 104 patients was 58.6%
Data source: A multicenter international phase 2 study in patients with relapsed/refractory indolent lymphomas
Disclosures: The study was supported by Bayer. Dr. Dreyling disclosed receiving honoraria from the company and serving on a scientific/advisory board for the company.
How to pump up the donor heart pool
COLORADO SPRINGS – Diminished left ventricular systolic function alone should not be used as a basis for declining a donor heart for transplantation, Agustin Sibona, MD, asserted at the annual meeting of the Western Thoracic Surgical Association.
“Expansion of the donor pool to include more of these organs is appropriate,” said Dr. Sibona of Loma Linda (Calif.) University.
He presented an analysis of the United Network for Organ Sharing database that encompassed all adult isolated first-time heart transplants in the United States from 2000 through March 2016.
“Carefully selected potential donor hearts with LVEF of 30% or higher should not be excluded from consideration of transplantation on the basis of depressed LVEF alone,” he concluded. “We’re not saying we should use every heart that has an EF of 35% or 45%. We say you should thoroughly evaluate those patients and those hearts and consider them.”
Roughly 500,000 people develop new end-stage heart failure each year. Heart transplantation has long been considered the definitive therapy for this condition. However, heart transplantation rates have remained static at 2,000-2,500 per year in the United States for the past 15 years because of the shortage of donor organs.
Previous work by Dr. Sibona’s senior coinvestigators has documented that 19% of potential donor hearts are not utilized for transplant solely based upon the presence of left ventricular dysfunction. That’s about 1,300 hearts per year.
“About 60% of those hearts had an LVEF greater than 40%. That’s 785 hearts. If only half of those are used, that still represents an increase in the domestic transplant rate of almost 20%,” he observed.
Twenty-one patients in the study received a heart with an LVEF of 20%-29.9%. They had an unacceptably high perioperative mortality.
There was no significant difference between the LVEF groups in terms of race, cause of death, or ischemic time.
Mean transplantation hospital length of stay varied inversely with donor heart LVEF, from 20.3 days in patients with a normal LVEF, to 23.9 days with an LVEF of 40%-49.9%, and 31.1 days with an LVEF of 30%-39.9%.
Dr. Sibona replied that unfortunately the UNOS database is not informative on that score.
Dr. Kwon offered a practical reservation about embracing the use of compromised donor hearts: “Ninety-one percent of programs in the U.S. do less than 30 heart transplants per year, and 76% do less than 20. Smaller programs won’t necessarily have the luxury of 6,000 days to see if their survival statistics bear out. If they have two or three deaths per year, that’s enough to get a notice from UNOS and CMS and private payers. So I would note some caution in that regard.”
He also posed a question: In this new era of highly effective left ventricular assist devices serving as a long-term bridge to transplant, does it make sense to turn to dysfunctional donor hearts?
“Ventricular assist devices are an evolving technology,” Dr. Sibona responded. “Short-term outcomes are equivalent to transplant, but the devices often have complications: GI bleed, stroke, thrombosis, and infections. So we still believe that heart transplantation is the gold standard for treatment. Remember, these patients have end-stage heart failure. Many can’t get out of bed without shortness of breath. So, yes, I would take those hearts.”
He reported having no financial conflicts regarding his study, which was supported by Loma Linda and Stanford universities.
COLORADO SPRINGS – Diminished left ventricular systolic function alone should not be used as a basis for declining a donor heart for transplantation, Agustin Sibona, MD, asserted at the annual meeting of the Western Thoracic Surgical Association.
“Expansion of the donor pool to include more of these organs is appropriate,” said Dr. Sibona of Loma Linda (Calif.) University.
He presented an analysis of the United Network for Organ Sharing database that encompassed all adult isolated first-time heart transplants in the United States from 2000 through March 2016.
“Carefully selected potential donor hearts with LVEF of 30% or higher should not be excluded from consideration of transplantation on the basis of depressed LVEF alone,” he concluded. “We’re not saying we should use every heart that has an EF of 35% or 45%. We say you should thoroughly evaluate those patients and those hearts and consider them.”
Roughly 500,000 people develop new end-stage heart failure each year. Heart transplantation has long been considered the definitive therapy for this condition. However, heart transplantation rates have remained static at 2,000-2,500 per year in the United States for the past 15 years because of the shortage of donor organs.
Previous work by Dr. Sibona’s senior coinvestigators has documented that 19% of potential donor hearts are not utilized for transplant solely based upon the presence of left ventricular dysfunction. That’s about 1,300 hearts per year.
“About 60% of those hearts had an LVEF greater than 40%. That’s 785 hearts. If only half of those are used, that still represents an increase in the domestic transplant rate of almost 20%,” he observed.
Twenty-one patients in the study received a heart with an LVEF of 20%-29.9%. They had an unacceptably high perioperative mortality.
There was no significant difference between the LVEF groups in terms of race, cause of death, or ischemic time.
Mean transplantation hospital length of stay varied inversely with donor heart LVEF, from 20.3 days in patients with a normal LVEF, to 23.9 days with an LVEF of 40%-49.9%, and 31.1 days with an LVEF of 30%-39.9%.
Dr. Sibona replied that unfortunately the UNOS database is not informative on that score.
Dr. Kwon offered a practical reservation about embracing the use of compromised donor hearts: “Ninety-one percent of programs in the U.S. do less than 30 heart transplants per year, and 76% do less than 20. Smaller programs won’t necessarily have the luxury of 6,000 days to see if their survival statistics bear out. If they have two or three deaths per year, that’s enough to get a notice from UNOS and CMS and private payers. So I would note some caution in that regard.”
He also posed a question: In this new era of highly effective left ventricular assist devices serving as a long-term bridge to transplant, does it make sense to turn to dysfunctional donor hearts?
“Ventricular assist devices are an evolving technology,” Dr. Sibona responded. “Short-term outcomes are equivalent to transplant, but the devices often have complications: GI bleed, stroke, thrombosis, and infections. So we still believe that heart transplantation is the gold standard for treatment. Remember, these patients have end-stage heart failure. Many can’t get out of bed without shortness of breath. So, yes, I would take those hearts.”
He reported having no financial conflicts regarding his study, which was supported by Loma Linda and Stanford universities.
COLORADO SPRINGS – Diminished left ventricular systolic function alone should not be used as a basis for declining a donor heart for transplantation, Agustin Sibona, MD, asserted at the annual meeting of the Western Thoracic Surgical Association.
“Expansion of the donor pool to include more of these organs is appropriate,” said Dr. Sibona of Loma Linda (Calif.) University.
He presented an analysis of the United Network for Organ Sharing database that encompassed all adult isolated first-time heart transplants in the United States from 2000 through March 2016.
“Carefully selected potential donor hearts with LVEF of 30% or higher should not be excluded from consideration of transplantation on the basis of depressed LVEF alone,” he concluded. “We’re not saying we should use every heart that has an EF of 35% or 45%. We say you should thoroughly evaluate those patients and those hearts and consider them.”
Roughly 500,000 people develop new end-stage heart failure each year. Heart transplantation has long been considered the definitive therapy for this condition. However, heart transplantation rates have remained static at 2,000-2,500 per year in the United States for the past 15 years because of the shortage of donor organs.
Previous work by Dr. Sibona’s senior coinvestigators has documented that 19% of potential donor hearts are not utilized for transplant solely based upon the presence of left ventricular dysfunction. That’s about 1,300 hearts per year.
“About 60% of those hearts had an LVEF greater than 40%. That’s 785 hearts. If only half of those are used, that still represents an increase in the domestic transplant rate of almost 20%,” he observed.
Twenty-one patients in the study received a heart with an LVEF of 20%-29.9%. They had an unacceptably high perioperative mortality.
There was no significant difference between the LVEF groups in terms of race, cause of death, or ischemic time.
Mean transplantation hospital length of stay varied inversely with donor heart LVEF, from 20.3 days in patients with a normal LVEF, to 23.9 days with an LVEF of 40%-49.9%, and 31.1 days with an LVEF of 30%-39.9%.
Dr. Sibona replied that unfortunately the UNOS database is not informative on that score.
Dr. Kwon offered a practical reservation about embracing the use of compromised donor hearts: “Ninety-one percent of programs in the U.S. do less than 30 heart transplants per year, and 76% do less than 20. Smaller programs won’t necessarily have the luxury of 6,000 days to see if their survival statistics bear out. If they have two or three deaths per year, that’s enough to get a notice from UNOS and CMS and private payers. So I would note some caution in that regard.”
He also posed a question: In this new era of highly effective left ventricular assist devices serving as a long-term bridge to transplant, does it make sense to turn to dysfunctional donor hearts?
“Ventricular assist devices are an evolving technology,” Dr. Sibona responded. “Short-term outcomes are equivalent to transplant, but the devices often have complications: GI bleed, stroke, thrombosis, and infections. So we still believe that heart transplantation is the gold standard for treatment. Remember, these patients have end-stage heart failure. Many can’t get out of bed without shortness of breath. So, yes, I would take those hearts.”
He reported having no financial conflicts regarding his study, which was supported by Loma Linda and Stanford universities.
AT THE WTSA ANNUAL MEETING
Key clinical point:
Major finding: Survival of heart transplant recipients whose donor organ had left ventricular systolic dysfunction with an LVEF as low as 30%-39% was not significantly less than for those with a normal donor heart.
Data source: A retrospective study of all of the nearly 31,000 isolated first-time adult heart transplants performed in the U.S. during 2000-March 2016.
Disclosures: Loma Linda and Stanford universities supported the study. The presenter reported having no financial conflicts.
C. difficile travels on the soles of our shoes
NEW ORLEANS – For an explanation to the spread of Clostridium difficile, one needs to look to our soles.
Based on ribosomal analysis, C. difficile often is transmitted from the hospital into the community and back into the hospital on the soles of shoes, researchers have concluded, based on findings from thousands of samples from patients, hospital environments, and shoes.
Dr. Alam of the University of Houston College of Pharmacy and his colleagues collected thousands of samples from the state of Texas to see how C. difficile strains in the community are related to clinical strains in the hospital.
The researchers collected 3,109 stool samples from people hospitalized with C. difficile, another 1,697 swabs taken from environmental surfaces in hospitals across the state, plus another 400 samples taken from the soles of shoes of clinicians and non–health care workers.
C. difficile was found in 44% of clinical stool samples, 13% of high-touch hospital environment surfaces, and 26% of community shoe sole samples. Among these positive C. difficile samples, toxigenic strains were detected in 93% of patient samples, 66% of hospital environment swabs and 64% of shoe samples. Importantly, the most predominant toxigenic strains appeared in all three sample types.
“When we collected some hospital environmental samples, we saw the isolate ribotypes perfectly matched the patient samples,” Dr. Alam said.
Further, “we saw the exact same ribotypes on our shoe bottoms, from these community, nonclinical sources,” Dr. Alam said. “Apparently, it seems, these dangerous pathogens are everywhere.”
In fact, “we may have brought many different strains from all over the world here to this meeting,” he added. “When we are taking antibiotics, we are susceptible to these different strains.”
Hospitals are cleaned daily, “but how many of us care about the shoes” on those who walk through the hospital, he asked. “We are loading the hospital with Clostridium difficile, and the hospital environment is also loaded with Clostridium difficile so we are bringing it into the community. We are spreading it everywhere.”
“Maybe we are blaming the doctors, nurses, and other staff, but [we are] not thinking about our shoes,” Dr. Alam added.
NEW ORLEANS – For an explanation to the spread of Clostridium difficile, one needs to look to our soles.
Based on ribosomal analysis, C. difficile often is transmitted from the hospital into the community and back into the hospital on the soles of shoes, researchers have concluded, based on findings from thousands of samples from patients, hospital environments, and shoes.
Dr. Alam of the University of Houston College of Pharmacy and his colleagues collected thousands of samples from the state of Texas to see how C. difficile strains in the community are related to clinical strains in the hospital.
The researchers collected 3,109 stool samples from people hospitalized with C. difficile, another 1,697 swabs taken from environmental surfaces in hospitals across the state, plus another 400 samples taken from the soles of shoes of clinicians and non–health care workers.
C. difficile was found in 44% of clinical stool samples, 13% of high-touch hospital environment surfaces, and 26% of community shoe sole samples. Among these positive C. difficile samples, toxigenic strains were detected in 93% of patient samples, 66% of hospital environment swabs and 64% of shoe samples. Importantly, the most predominant toxigenic strains appeared in all three sample types.
“When we collected some hospital environmental samples, we saw the isolate ribotypes perfectly matched the patient samples,” Dr. Alam said.
Further, “we saw the exact same ribotypes on our shoe bottoms, from these community, nonclinical sources,” Dr. Alam said. “Apparently, it seems, these dangerous pathogens are everywhere.”
In fact, “we may have brought many different strains from all over the world here to this meeting,” he added. “When we are taking antibiotics, we are susceptible to these different strains.”
Hospitals are cleaned daily, “but how many of us care about the shoes” on those who walk through the hospital, he asked. “We are loading the hospital with Clostridium difficile, and the hospital environment is also loaded with Clostridium difficile so we are bringing it into the community. We are spreading it everywhere.”
“Maybe we are blaming the doctors, nurses, and other staff, but [we are] not thinking about our shoes,” Dr. Alam added.
NEW ORLEANS – For an explanation to the spread of Clostridium difficile, one needs to look to our soles.
Based on ribosomal analysis, C. difficile often is transmitted from the hospital into the community and back into the hospital on the soles of shoes, researchers have concluded, based on findings from thousands of samples from patients, hospital environments, and shoes.
Dr. Alam of the University of Houston College of Pharmacy and his colleagues collected thousands of samples from the state of Texas to see how C. difficile strains in the community are related to clinical strains in the hospital.
The researchers collected 3,109 stool samples from people hospitalized with C. difficile, another 1,697 swabs taken from environmental surfaces in hospitals across the state, plus another 400 samples taken from the soles of shoes of clinicians and non–health care workers.
C. difficile was found in 44% of clinical stool samples, 13% of high-touch hospital environment surfaces, and 26% of community shoe sole samples. Among these positive C. difficile samples, toxigenic strains were detected in 93% of patient samples, 66% of hospital environment swabs and 64% of shoe samples. Importantly, the most predominant toxigenic strains appeared in all three sample types.
“When we collected some hospital environmental samples, we saw the isolate ribotypes perfectly matched the patient samples,” Dr. Alam said.
Further, “we saw the exact same ribotypes on our shoe bottoms, from these community, nonclinical sources,” Dr. Alam said. “Apparently, it seems, these dangerous pathogens are everywhere.”
In fact, “we may have brought many different strains from all over the world here to this meeting,” he added. “When we are taking antibiotics, we are susceptible to these different strains.”
Hospitals are cleaned daily, “but how many of us care about the shoes” on those who walk through the hospital, he asked. “We are loading the hospital with Clostridium difficile, and the hospital environment is also loaded with Clostridium difficile so we are bringing it into the community. We are spreading it everywhere.”
“Maybe we are blaming the doctors, nurses, and other staff, but [we are] not thinking about our shoes,” Dr. Alam added.
AT ASM MICROBE 2017
Key clinical point: Clostridium difficile transfer between the hospital and community and back could be driven in part by contaminated shoes.
Major finding: Toxigenic strains of C. difficile were found in 93% of patient samples, 66% of hospital environment swabs, and 64% of shoe samples.
Data source: Study of 3,109 stool samples from infected hospitalized patients, 1,697 hospital environmental surface swabs, and 400 samples from the soles of shoes.
Disclosures: Dr. Alam reported having no financial disclosures.