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Clinical trial: Use of robotics for cholecystectomy
The Use of Robotics for Cholecystectomy study is a retrospective review currently recruiting patients who underwent robotic-assisted laparoscopic cholecystectomy from June 2004 through May 2015.
Several methods are considered standard of care for the surgical treatment of cholecystitis, including open surgery, laparoscopic, and robotic-assisted laparoscopic surgery. This study, a retrospective analysis of charts, operating room notes, and operating room documentation of procedures, will review intraoperative and postoperative clinical outcomes of robotic-assisted laparoscopic cholecystectomy.
The intent of the study is to establish the role of robotics in laparoscopic surgery and to assess the learning curve for surgeons. Primary outcomes will be to compare hernia rates between multiport and single-port approaches, and to compare multiport against single-port approaches through the standard of care model of normal postsurgery follow-ups, along with additional follow-ups if complications are seen.
Recruitment for the study ends in May 2019. About 500 people are expected to be included in the final analysis.
Find more information at the study page on Clinicaltrials.gov.
The Use of Robotics for Cholecystectomy study is a retrospective review currently recruiting patients who underwent robotic-assisted laparoscopic cholecystectomy from June 2004 through May 2015.
Several methods are considered standard of care for the surgical treatment of cholecystitis, including open surgery, laparoscopic, and robotic-assisted laparoscopic surgery. This study, a retrospective analysis of charts, operating room notes, and operating room documentation of procedures, will review intraoperative and postoperative clinical outcomes of robotic-assisted laparoscopic cholecystectomy.
The intent of the study is to establish the role of robotics in laparoscopic surgery and to assess the learning curve for surgeons. Primary outcomes will be to compare hernia rates between multiport and single-port approaches, and to compare multiport against single-port approaches through the standard of care model of normal postsurgery follow-ups, along with additional follow-ups if complications are seen.
Recruitment for the study ends in May 2019. About 500 people are expected to be included in the final analysis.
Find more information at the study page on Clinicaltrials.gov.
The Use of Robotics for Cholecystectomy study is a retrospective review currently recruiting patients who underwent robotic-assisted laparoscopic cholecystectomy from June 2004 through May 2015.
Several methods are considered standard of care for the surgical treatment of cholecystitis, including open surgery, laparoscopic, and robotic-assisted laparoscopic surgery. This study, a retrospective analysis of charts, operating room notes, and operating room documentation of procedures, will review intraoperative and postoperative clinical outcomes of robotic-assisted laparoscopic cholecystectomy.
The intent of the study is to establish the role of robotics in laparoscopic surgery and to assess the learning curve for surgeons. Primary outcomes will be to compare hernia rates between multiport and single-port approaches, and to compare multiport against single-port approaches through the standard of care model of normal postsurgery follow-ups, along with additional follow-ups if complications are seen.
Recruitment for the study ends in May 2019. About 500 people are expected to be included in the final analysis.
Find more information at the study page on Clinicaltrials.gov.
SUMMARY FROM CLINICALTRIALS.GOV
Paying it forward
I was 14 when my grandmother fell and broke her hip. She went to the emergency department by ambulance from the restaurant we were at, and Dad took me to the hospital with him. He was an only child, and not a medical person. He was very worried.
There, Grandma looked older and more frail than usual. She and my dad were both anxious when told she’d need surgery.
Then the orthopedic surgeon came in. Tall and confident, he was initially quite imposing. But he was polite and had a great bedside manner. He calmed my dad and grandmother down, explained what needed to be done, and was reassuring. After surgery, he came to the waiting room to let us know things had gone well. I remember how impressed Dad and I both were.
Now, here was that surgeon again, on the other side of my desk. Arthritis had taken away some of his height. But he still carried himself with a proud dignity.
His family had brought him to me for worsening memory problems. He thought he was still in practice, although he had retired years ago. He didn’t remember his address, what city we were in, or what a clock looked like.
You hear families talk about how much Alzheimer’s disease takes away from a loved one, but you rarely have the opportunity in a practice to see for yourself. But the impression he’d made on me over 35 years ago was still strong, and I remembered every detail in comparison to the person across from me today.
In his field, he fixed things. With screws, rods, and casts he could restore broken bones, returning them to strength and use – like he had with my grandmother.
Sadly, I can’t return the favor now. I can only offer his family comfort, and answer questions, the way he once did with mine.
I started donepezil and gave them the most optimistic talk I have for these cases. But I know we’re still far away from fixing broken brains.
After he left, I found myself looking in the mirror, thinking of how I saw him then, wondering if his family saw me the same way now, and realizing that someday my children and I may be in the same situation.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
I was 14 when my grandmother fell and broke her hip. She went to the emergency department by ambulance from the restaurant we were at, and Dad took me to the hospital with him. He was an only child, and not a medical person. He was very worried.
There, Grandma looked older and more frail than usual. She and my dad were both anxious when told she’d need surgery.
Then the orthopedic surgeon came in. Tall and confident, he was initially quite imposing. But he was polite and had a great bedside manner. He calmed my dad and grandmother down, explained what needed to be done, and was reassuring. After surgery, he came to the waiting room to let us know things had gone well. I remember how impressed Dad and I both were.
Now, here was that surgeon again, on the other side of my desk. Arthritis had taken away some of his height. But he still carried himself with a proud dignity.
His family had brought him to me for worsening memory problems. He thought he was still in practice, although he had retired years ago. He didn’t remember his address, what city we were in, or what a clock looked like.
You hear families talk about how much Alzheimer’s disease takes away from a loved one, but you rarely have the opportunity in a practice to see for yourself. But the impression he’d made on me over 35 years ago was still strong, and I remembered every detail in comparison to the person across from me today.
In his field, he fixed things. With screws, rods, and casts he could restore broken bones, returning them to strength and use – like he had with my grandmother.
Sadly, I can’t return the favor now. I can only offer his family comfort, and answer questions, the way he once did with mine.
I started donepezil and gave them the most optimistic talk I have for these cases. But I know we’re still far away from fixing broken brains.
After he left, I found myself looking in the mirror, thinking of how I saw him then, wondering if his family saw me the same way now, and realizing that someday my children and I may be in the same situation.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
I was 14 when my grandmother fell and broke her hip. She went to the emergency department by ambulance from the restaurant we were at, and Dad took me to the hospital with him. He was an only child, and not a medical person. He was very worried.
There, Grandma looked older and more frail than usual. She and my dad were both anxious when told she’d need surgery.
Then the orthopedic surgeon came in. Tall and confident, he was initially quite imposing. But he was polite and had a great bedside manner. He calmed my dad and grandmother down, explained what needed to be done, and was reassuring. After surgery, he came to the waiting room to let us know things had gone well. I remember how impressed Dad and I both were.
Now, here was that surgeon again, on the other side of my desk. Arthritis had taken away some of his height. But he still carried himself with a proud dignity.
His family had brought him to me for worsening memory problems. He thought he was still in practice, although he had retired years ago. He didn’t remember his address, what city we were in, or what a clock looked like.
You hear families talk about how much Alzheimer’s disease takes away from a loved one, but you rarely have the opportunity in a practice to see for yourself. But the impression he’d made on me over 35 years ago was still strong, and I remembered every detail in comparison to the person across from me today.
In his field, he fixed things. With screws, rods, and casts he could restore broken bones, returning them to strength and use – like he had with my grandmother.
Sadly, I can’t return the favor now. I can only offer his family comfort, and answer questions, the way he once did with mine.
I started donepezil and gave them the most optimistic talk I have for these cases. But I know we’re still far away from fixing broken brains.
After he left, I found myself looking in the mirror, thinking of how I saw him then, wondering if his family saw me the same way now, and realizing that someday my children and I may be in the same situation.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Researchers develop 30-min antibiotic susceptibility test for UTI
Researchers in Sweden have developed a 30-minute test capable of determining whether a bacterial urinary tract infection is susceptible or resistant to nine antibiotics. Their findings suggest that it is possible to develop a point-of-care test for patients with UTI.
Most phenotypic and genotypic antibiotic susceptibility tests are too slow to guide treatment, ranging from 2 days to 1 hour. The researchers at Uppsala (Sweden) University cut the testing time down to less than 30 minutes by using a microfluidic chip and direct single-cell imaging.
The chip traps the bacterial cells and allows growth media with different antibiotics (or none) to flow around them. “With this setup, we could detect the differential growth rate between treatment and reference populations in 3 min for ciprofloxacin, levofloxacin, mecillinam, nitrofurantoin, and trimethoprim-sulfamethoxazole; 7 min for amoxicillin-clavulanate and doripenem; 9 min for fosfomycin; and 11 min for ampicillin based on 99.9% confidence intervals,” wrote Özden Baltekin and his coauthors.
That test specifically used Escherichia coli cells; comparable speed and accuracy was replicated using Klebsiella pneumoniae and Staphylococcus saprophyticus. For the development of a point-of-care test for patients, the researchers said all that would be needed are about 100 bacteria cells.
“We have here focused on bacterial species and antibiotics related to UTIs, but it is likely that the same principles would work for sepsis, mastitis, or meningitis,” they suggested (Proc Natl Acad Sci. 2017 Aug 8. doi: 10.1073/pnas.1708558114).
Researchers in Sweden have developed a 30-minute test capable of determining whether a bacterial urinary tract infection is susceptible or resistant to nine antibiotics. Their findings suggest that it is possible to develop a point-of-care test for patients with UTI.
Most phenotypic and genotypic antibiotic susceptibility tests are too slow to guide treatment, ranging from 2 days to 1 hour. The researchers at Uppsala (Sweden) University cut the testing time down to less than 30 minutes by using a microfluidic chip and direct single-cell imaging.
The chip traps the bacterial cells and allows growth media with different antibiotics (or none) to flow around them. “With this setup, we could detect the differential growth rate between treatment and reference populations in 3 min for ciprofloxacin, levofloxacin, mecillinam, nitrofurantoin, and trimethoprim-sulfamethoxazole; 7 min for amoxicillin-clavulanate and doripenem; 9 min for fosfomycin; and 11 min for ampicillin based on 99.9% confidence intervals,” wrote Özden Baltekin and his coauthors.
That test specifically used Escherichia coli cells; comparable speed and accuracy was replicated using Klebsiella pneumoniae and Staphylococcus saprophyticus. For the development of a point-of-care test for patients, the researchers said all that would be needed are about 100 bacteria cells.
“We have here focused on bacterial species and antibiotics related to UTIs, but it is likely that the same principles would work for sepsis, mastitis, or meningitis,” they suggested (Proc Natl Acad Sci. 2017 Aug 8. doi: 10.1073/pnas.1708558114).
Researchers in Sweden have developed a 30-minute test capable of determining whether a bacterial urinary tract infection is susceptible or resistant to nine antibiotics. Their findings suggest that it is possible to develop a point-of-care test for patients with UTI.
Most phenotypic and genotypic antibiotic susceptibility tests are too slow to guide treatment, ranging from 2 days to 1 hour. The researchers at Uppsala (Sweden) University cut the testing time down to less than 30 minutes by using a microfluidic chip and direct single-cell imaging.
The chip traps the bacterial cells and allows growth media with different antibiotics (or none) to flow around them. “With this setup, we could detect the differential growth rate between treatment and reference populations in 3 min for ciprofloxacin, levofloxacin, mecillinam, nitrofurantoin, and trimethoprim-sulfamethoxazole; 7 min for amoxicillin-clavulanate and doripenem; 9 min for fosfomycin; and 11 min for ampicillin based on 99.9% confidence intervals,” wrote Özden Baltekin and his coauthors.
That test specifically used Escherichia coli cells; comparable speed and accuracy was replicated using Klebsiella pneumoniae and Staphylococcus saprophyticus. For the development of a point-of-care test for patients, the researchers said all that would be needed are about 100 bacteria cells.
“We have here focused on bacterial species and antibiotics related to UTIs, but it is likely that the same principles would work for sepsis, mastitis, or meningitis,” they suggested (Proc Natl Acad Sci. 2017 Aug 8. doi: 10.1073/pnas.1708558114).
FROM PNAS
Physicians express mixed views on new FDA tobacco plan
Physicians associations are expressing mixed opinions about the Food and Drug Administration’s new plan for regulating tobacco products, such as flavored cigars, hookah tobacco, and e-cigarettes.
As part of the new plan, announced July 28, the FDA will relax previous application deadlines set for makers of newer tobacco products. The agency will also seek more public input on the role of flavors in tobacco products before moving forward with specific regulations.
“The delay outlined in [FDA Commissioner Scott Gottlieb’s] vision will cost the American public continued death and disease as a result of tobacco use,” Enid Neptune, MD, vice chair of the ATS Tobacco Action Committee said in the statement. “In short, Dr. Gottlieb’s announcement of the FDA’s new vision for regulating tobacco products is long on delay and short on action. The health of the American public, and particularly today’s youth, will suffer as a result of the FDA’s failure to act.”
The American College of Chest Physicians, meanwhile, applauded the FDA’s plan and expressed its support of the actions outlined.
“We welcome opportunities and actions that reduce tobacco use, addiction, and tobacco-related disease and death,” said Gerard Silvestri, MD, president for the college, in a statement. “We support the actions proposed by the FDA, which are likely to improve public health and reduce the burden of disease on patients and our country.”
As part of the FDA’s revised plan, the agency intends to begin a public dialogue about lowering nicotine levels in combustible cigarettes to nonaddictive levels through “achievable product standards.” The agency also plans to issue an advance notice of proposed rule making to seek input on the potential public health benefits and possible adverse effects of lowering nicotine in cigarettes.
Under revised time lines, applications for newly regulated combustible products, such as cigars, pipe tobacco, and hookah tobacco, must be submitted by makers to the FDA by Aug. 8, 2021, and applications for noncombustible products, such as e-cigarettes, must be submitted by Aug. 8, 2022. Manufacturers can continue to market their products while the agency reviews their product applications. The time frames push back previous deadlines that were established in a May 2016 final rule by the FDA. In the prior rule, manufacturers of all new tobacco products had 12-24 months to prepare and send applications for marketing authorization to the FDA and a 12-month continued compliance period after those dates in which to obtain FDA authorization.
“This comprehensive plan and sweeping approach to tobacco and nicotine allows the FDA to apply the powerful tools given by Congress to achieve the most significant public health impact,” Mitch Zeller, director of the FDA’s Center for Tobacco Products said in a statement. “Public input on these complex issues will help ensure the agency has the proper science-based policies in place to meaningfully reduce the harms caused by tobacco use.”
However, the ATS said that many of the issues raised in the FDA’s revised plan have already been discussed at length in the scientific literature and with the public.
“Scientific literature documenting the role cigars play in tobacco-related disease is extensive,” said Harold J. Farber, MD, chair of the ATS Tobacco Action Committee. “The FDA sought and received extensive public and industry input regarding exempting cigars during the proposed deeming rule. The FDA provided an extensive rational for why premium cigars should be regulated in its final deeming rule.”
In addition, the role of flavoring agents in tobacco products has also been discussed by the FDA, Dr. Neptune added. The agency previously sought, and received, extensive scientific, industry, and public input on the role of flavoring agents in tobacco products, she said. In addition, multiple reports have been issued on the role of flavoring agents, showing that flavoring agents increase tobacco initiation and make tobacco cessation harder, she noted.
“While more scientific information is always welcomed, Commissioner Gottlieb’s call for a new public discussion seeks to hide or ignore the extensive public discussion that has already occurred,” Dr. Neptune said. “In short, Commissioner Gottlieb has more than enough information to take action on flavored nicotine products today.”
[email protected]
On Twitter @legal_med
Physicians associations are expressing mixed opinions about the Food and Drug Administration’s new plan for regulating tobacco products, such as flavored cigars, hookah tobacco, and e-cigarettes.
As part of the new plan, announced July 28, the FDA will relax previous application deadlines set for makers of newer tobacco products. The agency will also seek more public input on the role of flavors in tobacco products before moving forward with specific regulations.
“The delay outlined in [FDA Commissioner Scott Gottlieb’s] vision will cost the American public continued death and disease as a result of tobacco use,” Enid Neptune, MD, vice chair of the ATS Tobacco Action Committee said in the statement. “In short, Dr. Gottlieb’s announcement of the FDA’s new vision for regulating tobacco products is long on delay and short on action. The health of the American public, and particularly today’s youth, will suffer as a result of the FDA’s failure to act.”
The American College of Chest Physicians, meanwhile, applauded the FDA’s plan and expressed its support of the actions outlined.
“We welcome opportunities and actions that reduce tobacco use, addiction, and tobacco-related disease and death,” said Gerard Silvestri, MD, president for the college, in a statement. “We support the actions proposed by the FDA, which are likely to improve public health and reduce the burden of disease on patients and our country.”
As part of the FDA’s revised plan, the agency intends to begin a public dialogue about lowering nicotine levels in combustible cigarettes to nonaddictive levels through “achievable product standards.” The agency also plans to issue an advance notice of proposed rule making to seek input on the potential public health benefits and possible adverse effects of lowering nicotine in cigarettes.
Under revised time lines, applications for newly regulated combustible products, such as cigars, pipe tobacco, and hookah tobacco, must be submitted by makers to the FDA by Aug. 8, 2021, and applications for noncombustible products, such as e-cigarettes, must be submitted by Aug. 8, 2022. Manufacturers can continue to market their products while the agency reviews their product applications. The time frames push back previous deadlines that were established in a May 2016 final rule by the FDA. In the prior rule, manufacturers of all new tobacco products had 12-24 months to prepare and send applications for marketing authorization to the FDA and a 12-month continued compliance period after those dates in which to obtain FDA authorization.
“This comprehensive plan and sweeping approach to tobacco and nicotine allows the FDA to apply the powerful tools given by Congress to achieve the most significant public health impact,” Mitch Zeller, director of the FDA’s Center for Tobacco Products said in a statement. “Public input on these complex issues will help ensure the agency has the proper science-based policies in place to meaningfully reduce the harms caused by tobacco use.”
However, the ATS said that many of the issues raised in the FDA’s revised plan have already been discussed at length in the scientific literature and with the public.
“Scientific literature documenting the role cigars play in tobacco-related disease is extensive,” said Harold J. Farber, MD, chair of the ATS Tobacco Action Committee. “The FDA sought and received extensive public and industry input regarding exempting cigars during the proposed deeming rule. The FDA provided an extensive rational for why premium cigars should be regulated in its final deeming rule.”
In addition, the role of flavoring agents in tobacco products has also been discussed by the FDA, Dr. Neptune added. The agency previously sought, and received, extensive scientific, industry, and public input on the role of flavoring agents in tobacco products, she said. In addition, multiple reports have been issued on the role of flavoring agents, showing that flavoring agents increase tobacco initiation and make tobacco cessation harder, she noted.
“While more scientific information is always welcomed, Commissioner Gottlieb’s call for a new public discussion seeks to hide or ignore the extensive public discussion that has already occurred,” Dr. Neptune said. “In short, Commissioner Gottlieb has more than enough information to take action on flavored nicotine products today.”
[email protected]
On Twitter @legal_med
Physicians associations are expressing mixed opinions about the Food and Drug Administration’s new plan for regulating tobacco products, such as flavored cigars, hookah tobacco, and e-cigarettes.
As part of the new plan, announced July 28, the FDA will relax previous application deadlines set for makers of newer tobacco products. The agency will also seek more public input on the role of flavors in tobacco products before moving forward with specific regulations.
“The delay outlined in [FDA Commissioner Scott Gottlieb’s] vision will cost the American public continued death and disease as a result of tobacco use,” Enid Neptune, MD, vice chair of the ATS Tobacco Action Committee said in the statement. “In short, Dr. Gottlieb’s announcement of the FDA’s new vision for regulating tobacco products is long on delay and short on action. The health of the American public, and particularly today’s youth, will suffer as a result of the FDA’s failure to act.”
The American College of Chest Physicians, meanwhile, applauded the FDA’s plan and expressed its support of the actions outlined.
“We welcome opportunities and actions that reduce tobacco use, addiction, and tobacco-related disease and death,” said Gerard Silvestri, MD, president for the college, in a statement. “We support the actions proposed by the FDA, which are likely to improve public health and reduce the burden of disease on patients and our country.”
As part of the FDA’s revised plan, the agency intends to begin a public dialogue about lowering nicotine levels in combustible cigarettes to nonaddictive levels through “achievable product standards.” The agency also plans to issue an advance notice of proposed rule making to seek input on the potential public health benefits and possible adverse effects of lowering nicotine in cigarettes.
Under revised time lines, applications for newly regulated combustible products, such as cigars, pipe tobacco, and hookah tobacco, must be submitted by makers to the FDA by Aug. 8, 2021, and applications for noncombustible products, such as e-cigarettes, must be submitted by Aug. 8, 2022. Manufacturers can continue to market their products while the agency reviews their product applications. The time frames push back previous deadlines that were established in a May 2016 final rule by the FDA. In the prior rule, manufacturers of all new tobacco products had 12-24 months to prepare and send applications for marketing authorization to the FDA and a 12-month continued compliance period after those dates in which to obtain FDA authorization.
“This comprehensive plan and sweeping approach to tobacco and nicotine allows the FDA to apply the powerful tools given by Congress to achieve the most significant public health impact,” Mitch Zeller, director of the FDA’s Center for Tobacco Products said in a statement. “Public input on these complex issues will help ensure the agency has the proper science-based policies in place to meaningfully reduce the harms caused by tobacco use.”
However, the ATS said that many of the issues raised in the FDA’s revised plan have already been discussed at length in the scientific literature and with the public.
“Scientific literature documenting the role cigars play in tobacco-related disease is extensive,” said Harold J. Farber, MD, chair of the ATS Tobacco Action Committee. “The FDA sought and received extensive public and industry input regarding exempting cigars during the proposed deeming rule. The FDA provided an extensive rational for why premium cigars should be regulated in its final deeming rule.”
In addition, the role of flavoring agents in tobacco products has also been discussed by the FDA, Dr. Neptune added. The agency previously sought, and received, extensive scientific, industry, and public input on the role of flavoring agents in tobacco products, she said. In addition, multiple reports have been issued on the role of flavoring agents, showing that flavoring agents increase tobacco initiation and make tobacco cessation harder, she noted.
“While more scientific information is always welcomed, Commissioner Gottlieb’s call for a new public discussion seeks to hide or ignore the extensive public discussion that has already occurred,” Dr. Neptune said. “In short, Commissioner Gottlieb has more than enough information to take action on flavored nicotine products today.”
[email protected]
On Twitter @legal_med
VIDEO: How to catch postpartum necrotizing fasciitis in time
PARK CITY, UTAH – , and it’s easy to misdiagnose at first.
There’s no pus, and the skin can look mostly normal with just a little swelling. The tipoff is pain that seems out of proportion to the clinical signs.
David Eschenbach, MD, chair of the department of obstetrics and gynecology at the University of Washington, Seattle, knows the infection well. In an interview at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology, he shared his insights on how physicians can recognize and treat postpartum necrotizing fasciitis in time to limit the damage.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
PARK CITY, UTAH – , and it’s easy to misdiagnose at first.
There’s no pus, and the skin can look mostly normal with just a little swelling. The tipoff is pain that seems out of proportion to the clinical signs.
David Eschenbach, MD, chair of the department of obstetrics and gynecology at the University of Washington, Seattle, knows the infection well. In an interview at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology, he shared his insights on how physicians can recognize and treat postpartum necrotizing fasciitis in time to limit the damage.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
PARK CITY, UTAH – , and it’s easy to misdiagnose at first.
There’s no pus, and the skin can look mostly normal with just a little swelling. The tipoff is pain that seems out of proportion to the clinical signs.
David Eschenbach, MD, chair of the department of obstetrics and gynecology at the University of Washington, Seattle, knows the infection well. In an interview at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology, he shared his insights on how physicians can recognize and treat postpartum necrotizing fasciitis in time to limit the damage.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT IDSOG
VIDEO: When to turn to surgery in postpartum uterine infection
PARK CITY, UTAH – When postpartum infections don’t respond to antibiotics, doctors and surgeons need to move fast; surgery – often hysterectomy – is the only thing that will save the woman’s life.
The problem is that with today’s antibiotics, doctors may have never encountered the situation, and sometimes continue to treat with antibiotics until it’s too late.
In Seattle, physicians turn to David Eschenbach, MD, chair of the department of obstetrics and gynecology at the University of Washington, for advice on when it’s time to give up on antibiotics and go to the OR. It’s a difficult decision, especially when patients are young.
In an interview at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology, Dr. Eschenbach shared what he’s learned from decades of experience in dealing with one of the most devastating postpartum complications.
PARK CITY, UTAH – When postpartum infections don’t respond to antibiotics, doctors and surgeons need to move fast; surgery – often hysterectomy – is the only thing that will save the woman’s life.
The problem is that with today’s antibiotics, doctors may have never encountered the situation, and sometimes continue to treat with antibiotics until it’s too late.
In Seattle, physicians turn to David Eschenbach, MD, chair of the department of obstetrics and gynecology at the University of Washington, for advice on when it’s time to give up on antibiotics and go to the OR. It’s a difficult decision, especially when patients are young.
In an interview at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology, Dr. Eschenbach shared what he’s learned from decades of experience in dealing with one of the most devastating postpartum complications.
PARK CITY, UTAH – When postpartum infections don’t respond to antibiotics, doctors and surgeons need to move fast; surgery – often hysterectomy – is the only thing that will save the woman’s life.
The problem is that with today’s antibiotics, doctors may have never encountered the situation, and sometimes continue to treat with antibiotics until it’s too late.
In Seattle, physicians turn to David Eschenbach, MD, chair of the department of obstetrics and gynecology at the University of Washington, for advice on when it’s time to give up on antibiotics and go to the OR. It’s a difficult decision, especially when patients are young.
In an interview at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology, Dr. Eschenbach shared what he’s learned from decades of experience in dealing with one of the most devastating postpartum complications.
AT IDSOG
Fewer severe hypoglycemia episodes seen over time in patients on tight control
Episodes of severe hypoglycemia became less frequent over a period of 26 years in patients with type 1 diabetes whose glucose was initially intensively managed to a hemoglobin A1c target of 7%, but, conversely, these problems increased in patients who had been managed to a conventional target of 9%, .
At the end of the 20-year-long Epidemiology of Diabetes Interventions and Complications (EDIC) study, which used an 8% HbA1c target for everyone, rates of severe hypoglycemia were 37 cases per 100 patient-years in patients managed intensively in the preceding Diabetes Control and Complications Trial (DCCT) – a significant decrease from the 61 cases per 100 patient-years observed when the DCCT concluded. However, rates of severe hypoglycemia also increased in the conventionally managed group, from 19 to 41 cases per 100 patient-years, according to Rose A. Gubitosi-Klug, MD, PhD, and her coauthors (Diab Care. 2017;40[8]:1010-6).
“The equalization of rates between the two original treatment groups is largely attributable to their similar HbA1c levels during EDIC,” wrote Dr. Gubitosi-Klug, who is division chief of pediatric endocrinology at University Hospital, Cleveland Medical Center, and her coauthors. “[There was] a 13%-15% rise in severe hypoglycemia risk for every 10% decrement in HbA1c.”
The DCCT enrolled 1,441 patients with type 1 diabetes from 1983 to 1989. They were either managed intensively, with a target HbA1c of 7%, or, conventionally, with a 9% target. Specifically, during the DCCT, participants in the intensive group had lower current and mean HbA1c levels (~2% mean difference; P less than .001) as well as higher insulin doses than those in the conventional group (mean difference, 0.04 units/kg per day; P less than .001). During the DCCT, pump use across all quarterly visits averaged 35.7% in the intensive group versus 0.7% in the conventional group and rose to 41% and 1.6%, respectively, by the DCCT closeout (P less than .001).
Almost everyone in the DCCT then enrolled in the EDIC study, which ran from 1995 to 2013. EDIC used an 8% HbA1c target. During EDIC, diabetes management has evolved dramatically, with the introduction of rapid- and long-acting insulins and improved insulin pumps and blood glucose meters. Dr. Gubitosi-Klug and her colleagues examined how rates of severe hypoglycemia have changed with those advances.
During the DCCT, intensively managed patients were three times more likely than those conventionally managed to experience an episode of severe hypoglycemia, including seizure or coma. During EDIC, the frequency of severe hypoglycemia increased in patients who had been conventionally managed but decreased among those who had been intensively managed.
When the DCCT ended with an average 6.5 years follow-up, 65% of the intensive group and 35% of the conventional group had experienced at least one episode of severe hypoglycemia. But when the 20-year EDIC study ended, about half of everyone in the group had experienced at least one episode. Many experienced multiple events. In the DCCT, 54% of the intensive group and 30% of the conventional group had experienced at least four episodes. In EDIC, 37% of the intensive group and 33% of the conventional group had experienced at least four.
But the repeat events seemed to occur in a subset of patients, with 14% in the DCCT experiencing about half of the study’s severe hypoglycemic events, and 7% in EDIC experiencing about a third of them in that study.
The biggest risk factor for severe hypoglycemia was similar for both groups. A first incident doubled the risk for another in the conventional therapy group and tripled it in the intensive therapy group.
“The current data support the clinical perception that a small subset of individuals is more susceptible to severe hypoglycemia,” with 7% of patients with 11 or more episodes during EDIC representing 32% all the events in that study.
These events impart a risk of serious consequences, the authors said. There were 51 major accidents during the 6.5 years of the DCCT and 143 during the 20 years of EDIC, and these were similar between treatment groups. Most of these were motor vehicle accidents, and hypoglycemia was the possible, probable, or principal cause of 18 of the 28 in the DCCT and 23 of the 54 in EDIC.
Nevertheless, the finding that intensively managed patients did better over the years is encouraging, the authors noted. “Advancements in the tools for diabetes management and additional clinical trials have also demonstrated the importance of educational programs to support intensive diabetes therapy. Thus, with increasing years of experience, participants have likely benefitted from tailored educational efforts provided by treating physicians and certified diabetes educators to minimize hypoglycemia.”
None of the study authors reported any financial conflicts.
[email protected]
On Twitter @Alz_gal
Episodes of severe hypoglycemia became less frequent over a period of 26 years in patients with type 1 diabetes whose glucose was initially intensively managed to a hemoglobin A1c target of 7%, but, conversely, these problems increased in patients who had been managed to a conventional target of 9%, .
At the end of the 20-year-long Epidemiology of Diabetes Interventions and Complications (EDIC) study, which used an 8% HbA1c target for everyone, rates of severe hypoglycemia were 37 cases per 100 patient-years in patients managed intensively in the preceding Diabetes Control and Complications Trial (DCCT) – a significant decrease from the 61 cases per 100 patient-years observed when the DCCT concluded. However, rates of severe hypoglycemia also increased in the conventionally managed group, from 19 to 41 cases per 100 patient-years, according to Rose A. Gubitosi-Klug, MD, PhD, and her coauthors (Diab Care. 2017;40[8]:1010-6).
“The equalization of rates between the two original treatment groups is largely attributable to their similar HbA1c levels during EDIC,” wrote Dr. Gubitosi-Klug, who is division chief of pediatric endocrinology at University Hospital, Cleveland Medical Center, and her coauthors. “[There was] a 13%-15% rise in severe hypoglycemia risk for every 10% decrement in HbA1c.”
The DCCT enrolled 1,441 patients with type 1 diabetes from 1983 to 1989. They were either managed intensively, with a target HbA1c of 7%, or, conventionally, with a 9% target. Specifically, during the DCCT, participants in the intensive group had lower current and mean HbA1c levels (~2% mean difference; P less than .001) as well as higher insulin doses than those in the conventional group (mean difference, 0.04 units/kg per day; P less than .001). During the DCCT, pump use across all quarterly visits averaged 35.7% in the intensive group versus 0.7% in the conventional group and rose to 41% and 1.6%, respectively, by the DCCT closeout (P less than .001).
Almost everyone in the DCCT then enrolled in the EDIC study, which ran from 1995 to 2013. EDIC used an 8% HbA1c target. During EDIC, diabetes management has evolved dramatically, with the introduction of rapid- and long-acting insulins and improved insulin pumps and blood glucose meters. Dr. Gubitosi-Klug and her colleagues examined how rates of severe hypoglycemia have changed with those advances.
During the DCCT, intensively managed patients were three times more likely than those conventionally managed to experience an episode of severe hypoglycemia, including seizure or coma. During EDIC, the frequency of severe hypoglycemia increased in patients who had been conventionally managed but decreased among those who had been intensively managed.
When the DCCT ended with an average 6.5 years follow-up, 65% of the intensive group and 35% of the conventional group had experienced at least one episode of severe hypoglycemia. But when the 20-year EDIC study ended, about half of everyone in the group had experienced at least one episode. Many experienced multiple events. In the DCCT, 54% of the intensive group and 30% of the conventional group had experienced at least four episodes. In EDIC, 37% of the intensive group and 33% of the conventional group had experienced at least four.
But the repeat events seemed to occur in a subset of patients, with 14% in the DCCT experiencing about half of the study’s severe hypoglycemic events, and 7% in EDIC experiencing about a third of them in that study.
The biggest risk factor for severe hypoglycemia was similar for both groups. A first incident doubled the risk for another in the conventional therapy group and tripled it in the intensive therapy group.
“The current data support the clinical perception that a small subset of individuals is more susceptible to severe hypoglycemia,” with 7% of patients with 11 or more episodes during EDIC representing 32% all the events in that study.
These events impart a risk of serious consequences, the authors said. There were 51 major accidents during the 6.5 years of the DCCT and 143 during the 20 years of EDIC, and these were similar between treatment groups. Most of these were motor vehicle accidents, and hypoglycemia was the possible, probable, or principal cause of 18 of the 28 in the DCCT and 23 of the 54 in EDIC.
Nevertheless, the finding that intensively managed patients did better over the years is encouraging, the authors noted. “Advancements in the tools for diabetes management and additional clinical trials have also demonstrated the importance of educational programs to support intensive diabetes therapy. Thus, with increasing years of experience, participants have likely benefitted from tailored educational efforts provided by treating physicians and certified diabetes educators to minimize hypoglycemia.”
None of the study authors reported any financial conflicts.
[email protected]
On Twitter @Alz_gal
Episodes of severe hypoglycemia became less frequent over a period of 26 years in patients with type 1 diabetes whose glucose was initially intensively managed to a hemoglobin A1c target of 7%, but, conversely, these problems increased in patients who had been managed to a conventional target of 9%, .
At the end of the 20-year-long Epidemiology of Diabetes Interventions and Complications (EDIC) study, which used an 8% HbA1c target for everyone, rates of severe hypoglycemia were 37 cases per 100 patient-years in patients managed intensively in the preceding Diabetes Control and Complications Trial (DCCT) – a significant decrease from the 61 cases per 100 patient-years observed when the DCCT concluded. However, rates of severe hypoglycemia also increased in the conventionally managed group, from 19 to 41 cases per 100 patient-years, according to Rose A. Gubitosi-Klug, MD, PhD, and her coauthors (Diab Care. 2017;40[8]:1010-6).
“The equalization of rates between the two original treatment groups is largely attributable to their similar HbA1c levels during EDIC,” wrote Dr. Gubitosi-Klug, who is division chief of pediatric endocrinology at University Hospital, Cleveland Medical Center, and her coauthors. “[There was] a 13%-15% rise in severe hypoglycemia risk for every 10% decrement in HbA1c.”
The DCCT enrolled 1,441 patients with type 1 diabetes from 1983 to 1989. They were either managed intensively, with a target HbA1c of 7%, or, conventionally, with a 9% target. Specifically, during the DCCT, participants in the intensive group had lower current and mean HbA1c levels (~2% mean difference; P less than .001) as well as higher insulin doses than those in the conventional group (mean difference, 0.04 units/kg per day; P less than .001). During the DCCT, pump use across all quarterly visits averaged 35.7% in the intensive group versus 0.7% in the conventional group and rose to 41% and 1.6%, respectively, by the DCCT closeout (P less than .001).
Almost everyone in the DCCT then enrolled in the EDIC study, which ran from 1995 to 2013. EDIC used an 8% HbA1c target. During EDIC, diabetes management has evolved dramatically, with the introduction of rapid- and long-acting insulins and improved insulin pumps and blood glucose meters. Dr. Gubitosi-Klug and her colleagues examined how rates of severe hypoglycemia have changed with those advances.
During the DCCT, intensively managed patients were three times more likely than those conventionally managed to experience an episode of severe hypoglycemia, including seizure or coma. During EDIC, the frequency of severe hypoglycemia increased in patients who had been conventionally managed but decreased among those who had been intensively managed.
When the DCCT ended with an average 6.5 years follow-up, 65% of the intensive group and 35% of the conventional group had experienced at least one episode of severe hypoglycemia. But when the 20-year EDIC study ended, about half of everyone in the group had experienced at least one episode. Many experienced multiple events. In the DCCT, 54% of the intensive group and 30% of the conventional group had experienced at least four episodes. In EDIC, 37% of the intensive group and 33% of the conventional group had experienced at least four.
But the repeat events seemed to occur in a subset of patients, with 14% in the DCCT experiencing about half of the study’s severe hypoglycemic events, and 7% in EDIC experiencing about a third of them in that study.
The biggest risk factor for severe hypoglycemia was similar for both groups. A first incident doubled the risk for another in the conventional therapy group and tripled it in the intensive therapy group.
“The current data support the clinical perception that a small subset of individuals is more susceptible to severe hypoglycemia,” with 7% of patients with 11 or more episodes during EDIC representing 32% all the events in that study.
These events impart a risk of serious consequences, the authors said. There were 51 major accidents during the 6.5 years of the DCCT and 143 during the 20 years of EDIC, and these were similar between treatment groups. Most of these were motor vehicle accidents, and hypoglycemia was the possible, probable, or principal cause of 18 of the 28 in the DCCT and 23 of the 54 in EDIC.
Nevertheless, the finding that intensively managed patients did better over the years is encouraging, the authors noted. “Advancements in the tools for diabetes management and additional clinical trials have also demonstrated the importance of educational programs to support intensive diabetes therapy. Thus, with increasing years of experience, participants have likely benefitted from tailored educational efforts provided by treating physicians and certified diabetes educators to minimize hypoglycemia.”
None of the study authors reported any financial conflicts.
[email protected]
On Twitter @Alz_gal
FROM DIABETES CARE
Key clinical point:
Major finding: About half of the patients in the follow-up study, the Epidemiology of Diabetes Interventions and Complications trial, experienced at least one severe hypoglycemia event, regardless of their initial management.
Data source: The Diabetes Control and Complications Trial involving 1,441 patients, 97% of whom enrolled in the Epidemiology of Diabetes Interventions and Complications trial.
Disclosures: The authors had no financial disclosures.
Crizotinib shows responses in pediatric ALCL and IMT
Treatment with the ALK-inhibitor crizotinib produced high response rates in pediatric patients with ALK-positive anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumors (IMTs), according to phase 2 trial results.
“The robust and sustained clinical responses to crizotinib in patients with relapsed or refractory ALK-driven ALCL and IMT highlight the importance of this oncogene and the sensitivity to ALK inhibition in these diseases,” said Yaël P. Mossé, MD, of Children’s Hospital of Philadelphia, and her associates.
Twenty-six patients with recurrent ALCL and 14 with unresectable IMTs – not older than 22 years – were enrolled. Six of the ALCL patients were treated at 165 mg/m2 (ALCL165) and 20 at 280 mg/m2 (ALCL280), which was found to be the recommended phase 2 dose. Ten of the ALCL280 patients had been treated at an equivalent to this dose in phase 1 and they were included in the phase 2 analysis. Those in the ALCL280 group tended to be older, at a median age of 12.2 years, than the other patients in the study, the investigators reported (J Clin Oncol. 2017 Aug 8 doi: 10.1200/JCO.2017.73.4830).
Eight of the IMT patients were enrolled in a dose-escalation portion of the study, with one receiving a 100 mg/m2 dose, one receiving 165 mg/m2, and the other six receiving 280 mg/m2. The other six were treated at 280 mg/m2. All of the IMT patient results are presented as one pool because those at the lower doses had toxicity and responses similar to those in patients given the higher dose.
Sixteen of 20 patients in the ALCL280 group – 80% – had a complete response, two had a partial response, and two were found to have stable disease. The median duration of treatment in this group was 0.4 years, and the median time to the first partial or complete response was 27 days. In the ALCL165 group, five of six, or 83%, had a complete response, along with one found to have stable disease. This group had a median treatment duration of 2.79 years, and the median time to the first partial or complete response was 26.5 days.
In the IMT group, 5 of 14, or 36%, had a complete response; 7, or 50%, had a partial response, and 2 had stable disease. They received treatment for a median of 1.63 years, and the median time to the first partial or complete response was 28.5 days.
Investigators reported that at least one grade 3 or 4 adverse event occurred in 83% of patients in the ALCL165 group, in all of the patients in the ALCL280 group, and in 71% in the IMT group. Adverse events considered possibly, probably, or definitely related to the study treatment occurred in 33% of the ALCL165 group, in 85% of the ALCL280 group, and in 57% of the IMT group. The most common adverse event was a decreased neutrophil count.
“Notable objective and sustained responses were observed in patients with ALK fusion-positive ALCL and IMT,” the investigators wrote, “establishing a precedent in pediatric oncology for studying the early-phase activity of a targeted agent in a biomarker-selected and histology-independent cohort of patients.
“In the cohort of patients with ALK-positive unresectable IMTs,” they continued, “ALK inhibition was a highly effective therapy and supports consideration of frontline therapy with crizotinib, a strategy that could also be relevant to adults with this rare disease.”
Treatment with the ALK-inhibitor crizotinib produced high response rates in pediatric patients with ALK-positive anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumors (IMTs), according to phase 2 trial results.
“The robust and sustained clinical responses to crizotinib in patients with relapsed or refractory ALK-driven ALCL and IMT highlight the importance of this oncogene and the sensitivity to ALK inhibition in these diseases,” said Yaël P. Mossé, MD, of Children’s Hospital of Philadelphia, and her associates.
Twenty-six patients with recurrent ALCL and 14 with unresectable IMTs – not older than 22 years – were enrolled. Six of the ALCL patients were treated at 165 mg/m2 (ALCL165) and 20 at 280 mg/m2 (ALCL280), which was found to be the recommended phase 2 dose. Ten of the ALCL280 patients had been treated at an equivalent to this dose in phase 1 and they were included in the phase 2 analysis. Those in the ALCL280 group tended to be older, at a median age of 12.2 years, than the other patients in the study, the investigators reported (J Clin Oncol. 2017 Aug 8 doi: 10.1200/JCO.2017.73.4830).
Eight of the IMT patients were enrolled in a dose-escalation portion of the study, with one receiving a 100 mg/m2 dose, one receiving 165 mg/m2, and the other six receiving 280 mg/m2. The other six were treated at 280 mg/m2. All of the IMT patient results are presented as one pool because those at the lower doses had toxicity and responses similar to those in patients given the higher dose.
Sixteen of 20 patients in the ALCL280 group – 80% – had a complete response, two had a partial response, and two were found to have stable disease. The median duration of treatment in this group was 0.4 years, and the median time to the first partial or complete response was 27 days. In the ALCL165 group, five of six, or 83%, had a complete response, along with one found to have stable disease. This group had a median treatment duration of 2.79 years, and the median time to the first partial or complete response was 26.5 days.
In the IMT group, 5 of 14, or 36%, had a complete response; 7, or 50%, had a partial response, and 2 had stable disease. They received treatment for a median of 1.63 years, and the median time to the first partial or complete response was 28.5 days.
Investigators reported that at least one grade 3 or 4 adverse event occurred in 83% of patients in the ALCL165 group, in all of the patients in the ALCL280 group, and in 71% in the IMT group. Adverse events considered possibly, probably, or definitely related to the study treatment occurred in 33% of the ALCL165 group, in 85% of the ALCL280 group, and in 57% of the IMT group. The most common adverse event was a decreased neutrophil count.
“Notable objective and sustained responses were observed in patients with ALK fusion-positive ALCL and IMT,” the investigators wrote, “establishing a precedent in pediatric oncology for studying the early-phase activity of a targeted agent in a biomarker-selected and histology-independent cohort of patients.
“In the cohort of patients with ALK-positive unresectable IMTs,” they continued, “ALK inhibition was a highly effective therapy and supports consideration of frontline therapy with crizotinib, a strategy that could also be relevant to adults with this rare disease.”
Treatment with the ALK-inhibitor crizotinib produced high response rates in pediatric patients with ALK-positive anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumors (IMTs), according to phase 2 trial results.
“The robust and sustained clinical responses to crizotinib in patients with relapsed or refractory ALK-driven ALCL and IMT highlight the importance of this oncogene and the sensitivity to ALK inhibition in these diseases,” said Yaël P. Mossé, MD, of Children’s Hospital of Philadelphia, and her associates.
Twenty-six patients with recurrent ALCL and 14 with unresectable IMTs – not older than 22 years – were enrolled. Six of the ALCL patients were treated at 165 mg/m2 (ALCL165) and 20 at 280 mg/m2 (ALCL280), which was found to be the recommended phase 2 dose. Ten of the ALCL280 patients had been treated at an equivalent to this dose in phase 1 and they were included in the phase 2 analysis. Those in the ALCL280 group tended to be older, at a median age of 12.2 years, than the other patients in the study, the investigators reported (J Clin Oncol. 2017 Aug 8 doi: 10.1200/JCO.2017.73.4830).
Eight of the IMT patients were enrolled in a dose-escalation portion of the study, with one receiving a 100 mg/m2 dose, one receiving 165 mg/m2, and the other six receiving 280 mg/m2. The other six were treated at 280 mg/m2. All of the IMT patient results are presented as one pool because those at the lower doses had toxicity and responses similar to those in patients given the higher dose.
Sixteen of 20 patients in the ALCL280 group – 80% – had a complete response, two had a partial response, and two were found to have stable disease. The median duration of treatment in this group was 0.4 years, and the median time to the first partial or complete response was 27 days. In the ALCL165 group, five of six, or 83%, had a complete response, along with one found to have stable disease. This group had a median treatment duration of 2.79 years, and the median time to the first partial or complete response was 26.5 days.
In the IMT group, 5 of 14, or 36%, had a complete response; 7, or 50%, had a partial response, and 2 had stable disease. They received treatment for a median of 1.63 years, and the median time to the first partial or complete response was 28.5 days.
Investigators reported that at least one grade 3 or 4 adverse event occurred in 83% of patients in the ALCL165 group, in all of the patients in the ALCL280 group, and in 71% in the IMT group. Adverse events considered possibly, probably, or definitely related to the study treatment occurred in 33% of the ALCL165 group, in 85% of the ALCL280 group, and in 57% of the IMT group. The most common adverse event was a decreased neutrophil count.
“Notable objective and sustained responses were observed in patients with ALK fusion-positive ALCL and IMT,” the investigators wrote, “establishing a precedent in pediatric oncology for studying the early-phase activity of a targeted agent in a biomarker-selected and histology-independent cohort of patients.
“In the cohort of patients with ALK-positive unresectable IMTs,” they continued, “ALK inhibition was a highly effective therapy and supports consideration of frontline therapy with crizotinib, a strategy that could also be relevant to adults with this rare disease.”
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: The ALK-inhibitor crizotinib produced good responses in pediatric, relapsed/refractory ALK-positive anaplastic large cell lymphoma and unresectable inflammatory myofibroblastic tumors.
Major finding: Eighty percent of ALCL patients in the high-dose group had a complete response, along with 83% given the lower dose. In the IMT group, 36%, had a complete response.
Data source: A 26-patient trial with a two-stage design, including phase 2 results as well as some data from phase 1, conducted across four U.S. centers.
Disclosures: Several study authors reported financial conflicts, including stock or other ownership, speaking fees, or institutional research funding from Pfizer, Novartis, Johnson & Johnson and other companies.
Lenalidomide maintenance boosts survival in de novo myeloma after ASCT
Patients with newly diagnosed multiple myeloma who received lenalidomide as maintenance therapy following an autologous stem cell transplant (ASCT) had significantly better progression-free and overall survival, compared with patients who received placebo or observation after transplant, results of a meta-analysis showed.
Among 1,208 patients in an intention-to-treat analysis, the median progression-free survival (PFS) for patients who received lenalidomide maintenance was nearly double that of patients treated with placebo or observation alone after ASCT, and the median overall survival for patients on maintenance had not been reached after a median follow-up of 79.5 months, reported Phillip J McCarthy, MD, of Roswell Park Cancer Institute in Buffalo, N.Y., and his colleagues.
“This study demonstrates a statistically significant and clinically meaningful improvement in OS with lenalidomide maintenance. With new, highly active, triplet induction regimens enhancing depth and duration of response, as well as ongoing studies evaluating the optimal timing of ASCT, the use of lenalidomide maintenance for transplantation-eligible patients can be considered a standard of care,” they wrote in the Journal of Clinical Oncology.
The authors drew on data from three randomized controlled trials in which patients with newly diagnosed multiple myeloma underwent ASCT followed by lenalidomide maintenance, placebo, or observation. The trials were the Cancer and Leukemia Group B (CALGB) 100104, Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) RV-MM-PI-209, and Intergroupe Francophone du Myelome (IFM) 2005-02.
Because all three studies had PFS as the primary endpoint and were not powered to detect an overall survival (OS) benefit, the investigators conducted a meta-analysis to get a better sense of the effect of maintenance on both PFS and OS.
The meta-analysis included 605 patients randomized to lenalidomide maintenance and 603 to placebo or observation.
The median PFS was 52.8 months with lenalidomide, vs. 23.5 months for placebo or observation (hazard ratio [HR] 0.48; 95% confidence interval, 0.41-0.55).
After a median follow-up of 79.5 months for all survivors, the median OS for patients on lenalidomide was not reached, compared with 86.0 months for placebo/observation (HR, 0.75, P = .001).
An analysis of safety data from the CALGB and IFM studies (GIMEMA data were not available) showed that second primary malignancies occurring before disease progression were more frequent in the lenalidomide maintenance group, at 5.3%, compared with 0.8%. In contrast, the cumulative incidence rates of progression, death, or myeloma-specific death were all higher with placebo or observation versus lenalidomide maintenance, the investigators found.
Although lenalidomide maintenance adds to the cost of care, the “costs of maintenance therapy should be weighed against the costs of shorter survival, earlier progression, and earlier use of subsequent lines of therapies for patients without maintenance,” the researchers wrote.
The study was supported by Celgene. Dr. McCarthy and multiple coauthors reported consulting/advisory roles, honoraria, travel support, and/or research support from the company.
Patients with newly diagnosed multiple myeloma who received lenalidomide as maintenance therapy following an autologous stem cell transplant (ASCT) had significantly better progression-free and overall survival, compared with patients who received placebo or observation after transplant, results of a meta-analysis showed.
Among 1,208 patients in an intention-to-treat analysis, the median progression-free survival (PFS) for patients who received lenalidomide maintenance was nearly double that of patients treated with placebo or observation alone after ASCT, and the median overall survival for patients on maintenance had not been reached after a median follow-up of 79.5 months, reported Phillip J McCarthy, MD, of Roswell Park Cancer Institute in Buffalo, N.Y., and his colleagues.
“This study demonstrates a statistically significant and clinically meaningful improvement in OS with lenalidomide maintenance. With new, highly active, triplet induction regimens enhancing depth and duration of response, as well as ongoing studies evaluating the optimal timing of ASCT, the use of lenalidomide maintenance for transplantation-eligible patients can be considered a standard of care,” they wrote in the Journal of Clinical Oncology.
The authors drew on data from three randomized controlled trials in which patients with newly diagnosed multiple myeloma underwent ASCT followed by lenalidomide maintenance, placebo, or observation. The trials were the Cancer and Leukemia Group B (CALGB) 100104, Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) RV-MM-PI-209, and Intergroupe Francophone du Myelome (IFM) 2005-02.
Because all three studies had PFS as the primary endpoint and were not powered to detect an overall survival (OS) benefit, the investigators conducted a meta-analysis to get a better sense of the effect of maintenance on both PFS and OS.
The meta-analysis included 605 patients randomized to lenalidomide maintenance and 603 to placebo or observation.
The median PFS was 52.8 months with lenalidomide, vs. 23.5 months for placebo or observation (hazard ratio [HR] 0.48; 95% confidence interval, 0.41-0.55).
After a median follow-up of 79.5 months for all survivors, the median OS for patients on lenalidomide was not reached, compared with 86.0 months for placebo/observation (HR, 0.75, P = .001).
An analysis of safety data from the CALGB and IFM studies (GIMEMA data were not available) showed that second primary malignancies occurring before disease progression were more frequent in the lenalidomide maintenance group, at 5.3%, compared with 0.8%. In contrast, the cumulative incidence rates of progression, death, or myeloma-specific death were all higher with placebo or observation versus lenalidomide maintenance, the investigators found.
Although lenalidomide maintenance adds to the cost of care, the “costs of maintenance therapy should be weighed against the costs of shorter survival, earlier progression, and earlier use of subsequent lines of therapies for patients without maintenance,” the researchers wrote.
The study was supported by Celgene. Dr. McCarthy and multiple coauthors reported consulting/advisory roles, honoraria, travel support, and/or research support from the company.
Patients with newly diagnosed multiple myeloma who received lenalidomide as maintenance therapy following an autologous stem cell transplant (ASCT) had significantly better progression-free and overall survival, compared with patients who received placebo or observation after transplant, results of a meta-analysis showed.
Among 1,208 patients in an intention-to-treat analysis, the median progression-free survival (PFS) for patients who received lenalidomide maintenance was nearly double that of patients treated with placebo or observation alone after ASCT, and the median overall survival for patients on maintenance had not been reached after a median follow-up of 79.5 months, reported Phillip J McCarthy, MD, of Roswell Park Cancer Institute in Buffalo, N.Y., and his colleagues.
“This study demonstrates a statistically significant and clinically meaningful improvement in OS with lenalidomide maintenance. With new, highly active, triplet induction regimens enhancing depth and duration of response, as well as ongoing studies evaluating the optimal timing of ASCT, the use of lenalidomide maintenance for transplantation-eligible patients can be considered a standard of care,” they wrote in the Journal of Clinical Oncology.
The authors drew on data from three randomized controlled trials in which patients with newly diagnosed multiple myeloma underwent ASCT followed by lenalidomide maintenance, placebo, or observation. The trials were the Cancer and Leukemia Group B (CALGB) 100104, Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) RV-MM-PI-209, and Intergroupe Francophone du Myelome (IFM) 2005-02.
Because all three studies had PFS as the primary endpoint and were not powered to detect an overall survival (OS) benefit, the investigators conducted a meta-analysis to get a better sense of the effect of maintenance on both PFS and OS.
The meta-analysis included 605 patients randomized to lenalidomide maintenance and 603 to placebo or observation.
The median PFS was 52.8 months with lenalidomide, vs. 23.5 months for placebo or observation (hazard ratio [HR] 0.48; 95% confidence interval, 0.41-0.55).
After a median follow-up of 79.5 months for all survivors, the median OS for patients on lenalidomide was not reached, compared with 86.0 months for placebo/observation (HR, 0.75, P = .001).
An analysis of safety data from the CALGB and IFM studies (GIMEMA data were not available) showed that second primary malignancies occurring before disease progression were more frequent in the lenalidomide maintenance group, at 5.3%, compared with 0.8%. In contrast, the cumulative incidence rates of progression, death, or myeloma-specific death were all higher with placebo or observation versus lenalidomide maintenance, the investigators found.
Although lenalidomide maintenance adds to the cost of care, the “costs of maintenance therapy should be weighed against the costs of shorter survival, earlier progression, and earlier use of subsequent lines of therapies for patients without maintenance,” the researchers wrote.
The study was supported by Celgene. Dr. McCarthy and multiple coauthors reported consulting/advisory roles, honoraria, travel support, and/or research support from the company.
FROM JCO
Key clinical point: Lenalidomide maintenance after stem cell transplant in patients with newly diagnosed multiple myeloma is associated with better progression-free and overall survival.
Major finding: Median overall survival was not reached with lenalidomide after a median 79.5 months’ follow-up, vs. 86 months for placebo/observation.
Data source: A meta-analysis of data from three randomized controlled trials, with a total of 1,208 patients with newly diagnosed multiple myeloma.
Disclosures: The study was supported by Celgene. Dr. McCarthy and multiple coauthors reported consulting/advisory roles, honoraria, travel support, and/or research support from the company.
Pertussis resurgence is real, but possible solutions exist
MADRID – The explanation for the ongoing resurgence in pertussis in adolescents and adults in the United States and other developed countries lies largely in the waning effectiveness of current acellular pertussis vaccines as early as 2-3 years post boosters, according to Stanley A. Plotkin, MD, chair of the steering committee for the Global Pertussis Initiative.
“The problem seems to lie in the lack of persistence of immunity after vaccination using the acellular pertussis vaccines. To say that this is not controversial would clearly be wrong, but that is my view,” he declared at the annual meeting of the European Society for Paediatric Infectious Diseases.
It’s a view supported by persuasive evidence, added Dr. Plotkin, emeritus professor of pediatrics at the University of Pennsylvania, Philadelphia.
In the United States, investigators at Northern California Kaiser Permanente have shown that the effectiveness of acellular pertussis in the Tdap vaccine wanes rapidly in adolescents. Indeed, it plunged from 69% effectiveness in the first year after vaccination to less than 9% by year 4 (Pediatrics. 2016 Mar;137[3]:e20153326).
In contrast, whole-cell pertussis vaccines provide roughly 6-10 years of protection against infection, and native infection provides persistent protection against reinfection for 7-20 years, Dr. Plotkin noted.
He was senior coauthor of a recent study that addresses why acellular pertussis vaccine immunity wanes so quickly. He and his coinvestigators demonstrated that while whole-cell pertussis vaccines promote vigorous Th1 and Th17 responses, which discourage pharyngeal colonization, acellular pertussis vaccines orient the immune system toward a less salutary Th1/Th2 response (Cold Spring Harb Perspect Biol. 2017 Mar 13. doi: 10.1101/cshperspect.a029454).
In addition, other investigators have shown that repeated booster doses of acellular pertussis vaccine generate higher levels of antigen-specific IgG4, which doesn’t bind complement and results in impaired phagocytosis and a suboptimal inflammatory response. In contrast, priming of the immune system via administration of a whole-cell pertussis vaccine at birth followed by acellular pertussis boosters results in improved phagocytosis and complement-mediated microbial killing via preferential induction of IgG1(Cold Spring Harb Perspect Biol. 2017 Mar 13. doi: 10.1101/cshperspect.a029553).
Possible solutions to the pertussis problem
Infants don’t need a new vaccine; that’s not where the vaccine failures are occurring. “Again, I stress that the problem so far has not been in infants, it has been in adolescents and adults,” he said.
A new vaccine is a daunting prospect. Given the huge investment vaccine manufacturers made in the 1990s to bring the current acellular vaccines to the market, they are hardly eager to launch development programs for new pertussis vaccines. They have other vaccine development priorities.
Moreover, the regulatory challenges are huge unless the Food and Drug Administration and other licensing authorities are willing to forgo the large, long, and expensive clinical trials that have traditionally been required. In lieu of such efficacy studies, they would need to consider studies demonstrating better immunogenicity based upon antibody titers, or animal studies.
“The possibility of a human challenge study in adults is an idea I like; I’m not sure about the FDA,” the pediatrician said.
Until a new or improved vaccine becomes available, the most important strategy to control the resurgence of pertussis is acellular vaccination of pregnant women in their third trimester to provide passive protection to the newborn via transplacental antibody. That practice is already recommended in the United States and many other countries. And while it reduces the risk of pertussis in early infancy – the most serious form of the disease – that strategy won’t have any real impact on the adult burden of disease, which Dr. Plotkin estimated at more than 600,000 cases annually.
Cocooning – a strategy of vaccinating all of a newborn’s family contacts – has been promoted in guidelines but has proved difficult to implement. “I think cocooning strategies by and large have been a failure,” he declared.
More frequent boosters of current acellular pertussis vaccines would presumably increase effectiveness, but that would be costly and tough to put in place on a public health scale.
A return to using conventional whole-cell pertussis vaccines would be a tough sell to the public and is probably flat out unacceptable. Developing a less reactogenic whole-cell vaccine might be a work-around, but it hasn’t been done yet.
The easiest way to improve acellular pertussis vaccine for adolescents and adults is to improve the pertussis toxin antigen component. Increasing the dose of pertussis toxin could generate more and longer-lasting antibodies to it. An even more exciting possibility is based upon evidence more than a decade old that genetic inactivation of pertussis toxin results in antibody levels far higher and presumably more bactericidal than the formalin-inactivated pertussis toxin included in current vaccines, according to Dr. Plotkin.
Adding stronger adjuvants to a Tdap vaccine for adolescents is another appealing strategy. There are plenty to choose from, including some that would presumably have an easier pathway to regulatory approval because they are already contained in licensed vaccines. This beefed-up adjuvant strategy, like the notion of changing the antigens in acellular pertussis vaccines to those from currently circulating strains, is feasible albeit more difficult than simply improving the pertussis toxin component of existing vaccines, he said.
The Global Pertussis Initiative is sponsored by Sanofi Pasteur. Dr. Plotkin reported serving as a consultant to that vaccine manufacturer and numerous others but declared he had no financial conflicts regarding his presentation.
MADRID – The explanation for the ongoing resurgence in pertussis in adolescents and adults in the United States and other developed countries lies largely in the waning effectiveness of current acellular pertussis vaccines as early as 2-3 years post boosters, according to Stanley A. Plotkin, MD, chair of the steering committee for the Global Pertussis Initiative.
“The problem seems to lie in the lack of persistence of immunity after vaccination using the acellular pertussis vaccines. To say that this is not controversial would clearly be wrong, but that is my view,” he declared at the annual meeting of the European Society for Paediatric Infectious Diseases.
It’s a view supported by persuasive evidence, added Dr. Plotkin, emeritus professor of pediatrics at the University of Pennsylvania, Philadelphia.
In the United States, investigators at Northern California Kaiser Permanente have shown that the effectiveness of acellular pertussis in the Tdap vaccine wanes rapidly in adolescents. Indeed, it plunged from 69% effectiveness in the first year after vaccination to less than 9% by year 4 (Pediatrics. 2016 Mar;137[3]:e20153326).
In contrast, whole-cell pertussis vaccines provide roughly 6-10 years of protection against infection, and native infection provides persistent protection against reinfection for 7-20 years, Dr. Plotkin noted.
He was senior coauthor of a recent study that addresses why acellular pertussis vaccine immunity wanes so quickly. He and his coinvestigators demonstrated that while whole-cell pertussis vaccines promote vigorous Th1 and Th17 responses, which discourage pharyngeal colonization, acellular pertussis vaccines orient the immune system toward a less salutary Th1/Th2 response (Cold Spring Harb Perspect Biol. 2017 Mar 13. doi: 10.1101/cshperspect.a029454).
In addition, other investigators have shown that repeated booster doses of acellular pertussis vaccine generate higher levels of antigen-specific IgG4, which doesn’t bind complement and results in impaired phagocytosis and a suboptimal inflammatory response. In contrast, priming of the immune system via administration of a whole-cell pertussis vaccine at birth followed by acellular pertussis boosters results in improved phagocytosis and complement-mediated microbial killing via preferential induction of IgG1(Cold Spring Harb Perspect Biol. 2017 Mar 13. doi: 10.1101/cshperspect.a029553).
Possible solutions to the pertussis problem
Infants don’t need a new vaccine; that’s not where the vaccine failures are occurring. “Again, I stress that the problem so far has not been in infants, it has been in adolescents and adults,” he said.
A new vaccine is a daunting prospect. Given the huge investment vaccine manufacturers made in the 1990s to bring the current acellular vaccines to the market, they are hardly eager to launch development programs for new pertussis vaccines. They have other vaccine development priorities.
Moreover, the regulatory challenges are huge unless the Food and Drug Administration and other licensing authorities are willing to forgo the large, long, and expensive clinical trials that have traditionally been required. In lieu of such efficacy studies, they would need to consider studies demonstrating better immunogenicity based upon antibody titers, or animal studies.
“The possibility of a human challenge study in adults is an idea I like; I’m not sure about the FDA,” the pediatrician said.
Until a new or improved vaccine becomes available, the most important strategy to control the resurgence of pertussis is acellular vaccination of pregnant women in their third trimester to provide passive protection to the newborn via transplacental antibody. That practice is already recommended in the United States and many other countries. And while it reduces the risk of pertussis in early infancy – the most serious form of the disease – that strategy won’t have any real impact on the adult burden of disease, which Dr. Plotkin estimated at more than 600,000 cases annually.
Cocooning – a strategy of vaccinating all of a newborn’s family contacts – has been promoted in guidelines but has proved difficult to implement. “I think cocooning strategies by and large have been a failure,” he declared.
More frequent boosters of current acellular pertussis vaccines would presumably increase effectiveness, but that would be costly and tough to put in place on a public health scale.
A return to using conventional whole-cell pertussis vaccines would be a tough sell to the public and is probably flat out unacceptable. Developing a less reactogenic whole-cell vaccine might be a work-around, but it hasn’t been done yet.
The easiest way to improve acellular pertussis vaccine for adolescents and adults is to improve the pertussis toxin antigen component. Increasing the dose of pertussis toxin could generate more and longer-lasting antibodies to it. An even more exciting possibility is based upon evidence more than a decade old that genetic inactivation of pertussis toxin results in antibody levels far higher and presumably more bactericidal than the formalin-inactivated pertussis toxin included in current vaccines, according to Dr. Plotkin.
Adding stronger adjuvants to a Tdap vaccine for adolescents is another appealing strategy. There are plenty to choose from, including some that would presumably have an easier pathway to regulatory approval because they are already contained in licensed vaccines. This beefed-up adjuvant strategy, like the notion of changing the antigens in acellular pertussis vaccines to those from currently circulating strains, is feasible albeit more difficult than simply improving the pertussis toxin component of existing vaccines, he said.
The Global Pertussis Initiative is sponsored by Sanofi Pasteur. Dr. Plotkin reported serving as a consultant to that vaccine manufacturer and numerous others but declared he had no financial conflicts regarding his presentation.
MADRID – The explanation for the ongoing resurgence in pertussis in adolescents and adults in the United States and other developed countries lies largely in the waning effectiveness of current acellular pertussis vaccines as early as 2-3 years post boosters, according to Stanley A. Plotkin, MD, chair of the steering committee for the Global Pertussis Initiative.
“The problem seems to lie in the lack of persistence of immunity after vaccination using the acellular pertussis vaccines. To say that this is not controversial would clearly be wrong, but that is my view,” he declared at the annual meeting of the European Society for Paediatric Infectious Diseases.
It’s a view supported by persuasive evidence, added Dr. Plotkin, emeritus professor of pediatrics at the University of Pennsylvania, Philadelphia.
In the United States, investigators at Northern California Kaiser Permanente have shown that the effectiveness of acellular pertussis in the Tdap vaccine wanes rapidly in adolescents. Indeed, it plunged from 69% effectiveness in the first year after vaccination to less than 9% by year 4 (Pediatrics. 2016 Mar;137[3]:e20153326).
In contrast, whole-cell pertussis vaccines provide roughly 6-10 years of protection against infection, and native infection provides persistent protection against reinfection for 7-20 years, Dr. Plotkin noted.
He was senior coauthor of a recent study that addresses why acellular pertussis vaccine immunity wanes so quickly. He and his coinvestigators demonstrated that while whole-cell pertussis vaccines promote vigorous Th1 and Th17 responses, which discourage pharyngeal colonization, acellular pertussis vaccines orient the immune system toward a less salutary Th1/Th2 response (Cold Spring Harb Perspect Biol. 2017 Mar 13. doi: 10.1101/cshperspect.a029454).
In addition, other investigators have shown that repeated booster doses of acellular pertussis vaccine generate higher levels of antigen-specific IgG4, which doesn’t bind complement and results in impaired phagocytosis and a suboptimal inflammatory response. In contrast, priming of the immune system via administration of a whole-cell pertussis vaccine at birth followed by acellular pertussis boosters results in improved phagocytosis and complement-mediated microbial killing via preferential induction of IgG1(Cold Spring Harb Perspect Biol. 2017 Mar 13. doi: 10.1101/cshperspect.a029553).
Possible solutions to the pertussis problem
Infants don’t need a new vaccine; that’s not where the vaccine failures are occurring. “Again, I stress that the problem so far has not been in infants, it has been in adolescents and adults,” he said.
A new vaccine is a daunting prospect. Given the huge investment vaccine manufacturers made in the 1990s to bring the current acellular vaccines to the market, they are hardly eager to launch development programs for new pertussis vaccines. They have other vaccine development priorities.
Moreover, the regulatory challenges are huge unless the Food and Drug Administration and other licensing authorities are willing to forgo the large, long, and expensive clinical trials that have traditionally been required. In lieu of such efficacy studies, they would need to consider studies demonstrating better immunogenicity based upon antibody titers, or animal studies.
“The possibility of a human challenge study in adults is an idea I like; I’m not sure about the FDA,” the pediatrician said.
Until a new or improved vaccine becomes available, the most important strategy to control the resurgence of pertussis is acellular vaccination of pregnant women in their third trimester to provide passive protection to the newborn via transplacental antibody. That practice is already recommended in the United States and many other countries. And while it reduces the risk of pertussis in early infancy – the most serious form of the disease – that strategy won’t have any real impact on the adult burden of disease, which Dr. Plotkin estimated at more than 600,000 cases annually.
Cocooning – a strategy of vaccinating all of a newborn’s family contacts – has been promoted in guidelines but has proved difficult to implement. “I think cocooning strategies by and large have been a failure,” he declared.
More frequent boosters of current acellular pertussis vaccines would presumably increase effectiveness, but that would be costly and tough to put in place on a public health scale.
A return to using conventional whole-cell pertussis vaccines would be a tough sell to the public and is probably flat out unacceptable. Developing a less reactogenic whole-cell vaccine might be a work-around, but it hasn’t been done yet.
The easiest way to improve acellular pertussis vaccine for adolescents and adults is to improve the pertussis toxin antigen component. Increasing the dose of pertussis toxin could generate more and longer-lasting antibodies to it. An even more exciting possibility is based upon evidence more than a decade old that genetic inactivation of pertussis toxin results in antibody levels far higher and presumably more bactericidal than the formalin-inactivated pertussis toxin included in current vaccines, according to Dr. Plotkin.
Adding stronger adjuvants to a Tdap vaccine for adolescents is another appealing strategy. There are plenty to choose from, including some that would presumably have an easier pathway to regulatory approval because they are already contained in licensed vaccines. This beefed-up adjuvant strategy, like the notion of changing the antigens in acellular pertussis vaccines to those from currently circulating strains, is feasible albeit more difficult than simply improving the pertussis toxin component of existing vaccines, he said.
The Global Pertussis Initiative is sponsored by Sanofi Pasteur. Dr. Plotkin reported serving as a consultant to that vaccine manufacturer and numerous others but declared he had no financial conflicts regarding his presentation.
EXPERT ANALYSIS FROM ESPID 2017