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Serious mental illness gets serious attention in 21st Century Cures Act
WASHINGTON – Bipartisan legislation to improve care of patients with serious mental illness is just a pen stroke from passage, now that the 21st Century Cures Act is headed for the President’s desk.
While the mental health care reform provisions in the legislation (H.R. 34) will impact mental health services broadly, the bulk of the reform language comes from H.R. 2646, a bill sponsored by Rep. Tim Murphy (R-Penn.), which was intended to reverse decades of fragmented – and at times nonexistent – care for persons with serious mental illness.
The legislation calls for the expanded use of assisted outpatient treatment, federal guidance on how states can be reimbursed for offering inpatient psychiatric services, better data collection on mental health services paid for with state and federal dollars, new oversight of the federal agency in charge of mental health, and clarification of HIPAA laws, among other provisions.
“This is big,” Rep. Murphy said at a press conference Dec. 5. “After all the tears and suffering … know that those times when you felt no one was willing to listen, and you were ready to give up, now there is hope.”
Treatment vs. incarceration
Currently, states and communities can draw from $80 million dollars in federal grants for assisted outpatient treatment for patients with serious mental illness. The new legislation adds another $20 million and extends availability of the funding until 2022. It also allows state criminal justice systems to use assisted outpatient treatment grants to treat convicted criminals with serious mental illness instead of incarcerating them.
“[In prison], their illness gets worse, not better, creating a turnstile through which they will return time and again through our criminal justice system,” Senate Majority Whip John Cornyn (R.-Tex.) said during the press conference.
Paying for inpatient psychiatric care
The Cures Act also strengthens momentum for overhauling the Medicaid Institutions of Mental Diseases (IMD) exclusion, long a focus of mental health care advocates who view it as a governor on the number of psychiatric beds available nationally.
The exclusion prohibits any medical facility with more than 16 beds from using federal funds to pay for inpatient mental health care for adults under age 65 years. The Cures Act requires the Centers for Medicare & Medicaid Services to offer guidance on how states can use Medicaid demonstration projects to provide innovative inpatient psychiatric services using these waivers.
This follows an April 2016 CMS final rule that matches state funding dollar-per-dollar for up to 15 days of inpatient psychiatric treatment given to Medicaid managed care patients.
Although Rep. Murphy’s original bill called for abolishing the exclusion, he and other advocates are not disappointed in the progress made so far. “We didn’t get everything we wanted, but we needed everything we got,” he said.
“That 15 days was a massive win,” Frankie Berger, advocacy director of the Treatment Advocacy Center in Arlington, Va., said in an interview. “Now we have this legislation that requires CMS to tell state Medicaid directors what their wiggle room is when solving the problem on how to get care to these patients. If you read between the lines, this is care that is going to be provided by an IMD.”
The legislation also calls for more data collection and evaluation of IMDs, something that until now has been missing, Ms. Berger said. “A lot of us who work on this issue have found there is absolutely no data on where IMDs are, or who the folks are that are getting treatment in them. We need that information to make good choices,” she said.
“I think we will find savings as we expand the number of psychiatric beds … [and persons with serious mental illness] do not end up in jail cells, homeless, or in the morgue,” Sen. Bill Cassidy (R-La.) said at the press conference. He predicted that for each additional psychiatric bed introduced, savings would amount to between $30,000 and $50,000.
Restructuring, clarifying
The Cures Act reforms also restructure the Substance Abuse and Mental Health Services Administration, putting it under the authority of a new assistant secretary of Health and Human Services and giving it a chief medical officer. The law calls for the new CMO to have “real-world” experience treating patients with serious mental illness. The reformed SAMHSA will have responsibility for centralizing data collection to be used in creating best practices in mental health care. These reforms are particular victories for Rep. Murphy who has railed against the agency for years, citing its lack of medically trained leadership and lack of evidence-based approaches to care.
HIPAA requirements in serious mental illness are also clarified.
“Existing HIPAA laws are badly misunderstood,” said Sen. Chris Murphy (D-Conn.) at the briefing. “Many physicians think there is an outright ban on sharing [patient health] information.”
The legislation calls for the U.S. Department of Health and Human Services secretary to clarify when providers can disclose protected health information related to the treatment of an adult with a mental illness or substance use disorder.
“I would argue that [HIPAA] may be an area we will have to work on down the line, if the education campaign doesn’t work, but we will give this a try,” said Sen. Murphy, who has cosponsored legislation to do so.
As passed, the mental health provisions of the 21st Century Cures Act are an amalgamation of several bills introduced during the 114th Congress and are unique in that they largely were written by health care professionals with direct, relevant experience. Rep. Murphy is a clinical psychologist, while Rep. Cassidy is a physician with experience treating uninsured and incarcerated patients. Rep. Eddie Bernice Johnson (D-Tex.), who cosponsored Rep. Murphy’s bill, previously served as chief psychiatric nurse at the Dallas Veterans Affairs Medical Center.
WASHINGTON – Bipartisan legislation to improve care of patients with serious mental illness is just a pen stroke from passage, now that the 21st Century Cures Act is headed for the President’s desk.
While the mental health care reform provisions in the legislation (H.R. 34) will impact mental health services broadly, the bulk of the reform language comes from H.R. 2646, a bill sponsored by Rep. Tim Murphy (R-Penn.), which was intended to reverse decades of fragmented – and at times nonexistent – care for persons with serious mental illness.
The legislation calls for the expanded use of assisted outpatient treatment, federal guidance on how states can be reimbursed for offering inpatient psychiatric services, better data collection on mental health services paid for with state and federal dollars, new oversight of the federal agency in charge of mental health, and clarification of HIPAA laws, among other provisions.
“This is big,” Rep. Murphy said at a press conference Dec. 5. “After all the tears and suffering … know that those times when you felt no one was willing to listen, and you were ready to give up, now there is hope.”
Treatment vs. incarceration
Currently, states and communities can draw from $80 million dollars in federal grants for assisted outpatient treatment for patients with serious mental illness. The new legislation adds another $20 million and extends availability of the funding until 2022. It also allows state criminal justice systems to use assisted outpatient treatment grants to treat convicted criminals with serious mental illness instead of incarcerating them.
“[In prison], their illness gets worse, not better, creating a turnstile through which they will return time and again through our criminal justice system,” Senate Majority Whip John Cornyn (R.-Tex.) said during the press conference.
Paying for inpatient psychiatric care
The Cures Act also strengthens momentum for overhauling the Medicaid Institutions of Mental Diseases (IMD) exclusion, long a focus of mental health care advocates who view it as a governor on the number of psychiatric beds available nationally.
The exclusion prohibits any medical facility with more than 16 beds from using federal funds to pay for inpatient mental health care for adults under age 65 years. The Cures Act requires the Centers for Medicare & Medicaid Services to offer guidance on how states can use Medicaid demonstration projects to provide innovative inpatient psychiatric services using these waivers.
This follows an April 2016 CMS final rule that matches state funding dollar-per-dollar for up to 15 days of inpatient psychiatric treatment given to Medicaid managed care patients.
Although Rep. Murphy’s original bill called for abolishing the exclusion, he and other advocates are not disappointed in the progress made so far. “We didn’t get everything we wanted, but we needed everything we got,” he said.
“That 15 days was a massive win,” Frankie Berger, advocacy director of the Treatment Advocacy Center in Arlington, Va., said in an interview. “Now we have this legislation that requires CMS to tell state Medicaid directors what their wiggle room is when solving the problem on how to get care to these patients. If you read between the lines, this is care that is going to be provided by an IMD.”
The legislation also calls for more data collection and evaluation of IMDs, something that until now has been missing, Ms. Berger said. “A lot of us who work on this issue have found there is absolutely no data on where IMDs are, or who the folks are that are getting treatment in them. We need that information to make good choices,” she said.
“I think we will find savings as we expand the number of psychiatric beds … [and persons with serious mental illness] do not end up in jail cells, homeless, or in the morgue,” Sen. Bill Cassidy (R-La.) said at the press conference. He predicted that for each additional psychiatric bed introduced, savings would amount to between $30,000 and $50,000.
Restructuring, clarifying
The Cures Act reforms also restructure the Substance Abuse and Mental Health Services Administration, putting it under the authority of a new assistant secretary of Health and Human Services and giving it a chief medical officer. The law calls for the new CMO to have “real-world” experience treating patients with serious mental illness. The reformed SAMHSA will have responsibility for centralizing data collection to be used in creating best practices in mental health care. These reforms are particular victories for Rep. Murphy who has railed against the agency for years, citing its lack of medically trained leadership and lack of evidence-based approaches to care.
HIPAA requirements in serious mental illness are also clarified.
“Existing HIPAA laws are badly misunderstood,” said Sen. Chris Murphy (D-Conn.) at the briefing. “Many physicians think there is an outright ban on sharing [patient health] information.”
The legislation calls for the U.S. Department of Health and Human Services secretary to clarify when providers can disclose protected health information related to the treatment of an adult with a mental illness or substance use disorder.
“I would argue that [HIPAA] may be an area we will have to work on down the line, if the education campaign doesn’t work, but we will give this a try,” said Sen. Murphy, who has cosponsored legislation to do so.
As passed, the mental health provisions of the 21st Century Cures Act are an amalgamation of several bills introduced during the 114th Congress and are unique in that they largely were written by health care professionals with direct, relevant experience. Rep. Murphy is a clinical psychologist, while Rep. Cassidy is a physician with experience treating uninsured and incarcerated patients. Rep. Eddie Bernice Johnson (D-Tex.), who cosponsored Rep. Murphy’s bill, previously served as chief psychiatric nurse at the Dallas Veterans Affairs Medical Center.
WASHINGTON – Bipartisan legislation to improve care of patients with serious mental illness is just a pen stroke from passage, now that the 21st Century Cures Act is headed for the President’s desk.
While the mental health care reform provisions in the legislation (H.R. 34) will impact mental health services broadly, the bulk of the reform language comes from H.R. 2646, a bill sponsored by Rep. Tim Murphy (R-Penn.), which was intended to reverse decades of fragmented – and at times nonexistent – care for persons with serious mental illness.
The legislation calls for the expanded use of assisted outpatient treatment, federal guidance on how states can be reimbursed for offering inpatient psychiatric services, better data collection on mental health services paid for with state and federal dollars, new oversight of the federal agency in charge of mental health, and clarification of HIPAA laws, among other provisions.
“This is big,” Rep. Murphy said at a press conference Dec. 5. “After all the tears and suffering … know that those times when you felt no one was willing to listen, and you were ready to give up, now there is hope.”
Treatment vs. incarceration
Currently, states and communities can draw from $80 million dollars in federal grants for assisted outpatient treatment for patients with serious mental illness. The new legislation adds another $20 million and extends availability of the funding until 2022. It also allows state criminal justice systems to use assisted outpatient treatment grants to treat convicted criminals with serious mental illness instead of incarcerating them.
“[In prison], their illness gets worse, not better, creating a turnstile through which they will return time and again through our criminal justice system,” Senate Majority Whip John Cornyn (R.-Tex.) said during the press conference.
Paying for inpatient psychiatric care
The Cures Act also strengthens momentum for overhauling the Medicaid Institutions of Mental Diseases (IMD) exclusion, long a focus of mental health care advocates who view it as a governor on the number of psychiatric beds available nationally.
The exclusion prohibits any medical facility with more than 16 beds from using federal funds to pay for inpatient mental health care for adults under age 65 years. The Cures Act requires the Centers for Medicare & Medicaid Services to offer guidance on how states can use Medicaid demonstration projects to provide innovative inpatient psychiatric services using these waivers.
This follows an April 2016 CMS final rule that matches state funding dollar-per-dollar for up to 15 days of inpatient psychiatric treatment given to Medicaid managed care patients.
Although Rep. Murphy’s original bill called for abolishing the exclusion, he and other advocates are not disappointed in the progress made so far. “We didn’t get everything we wanted, but we needed everything we got,” he said.
“That 15 days was a massive win,” Frankie Berger, advocacy director of the Treatment Advocacy Center in Arlington, Va., said in an interview. “Now we have this legislation that requires CMS to tell state Medicaid directors what their wiggle room is when solving the problem on how to get care to these patients. If you read between the lines, this is care that is going to be provided by an IMD.”
The legislation also calls for more data collection and evaluation of IMDs, something that until now has been missing, Ms. Berger said. “A lot of us who work on this issue have found there is absolutely no data on where IMDs are, or who the folks are that are getting treatment in them. We need that information to make good choices,” she said.
“I think we will find savings as we expand the number of psychiatric beds … [and persons with serious mental illness] do not end up in jail cells, homeless, or in the morgue,” Sen. Bill Cassidy (R-La.) said at the press conference. He predicted that for each additional psychiatric bed introduced, savings would amount to between $30,000 and $50,000.
Restructuring, clarifying
The Cures Act reforms also restructure the Substance Abuse and Mental Health Services Administration, putting it under the authority of a new assistant secretary of Health and Human Services and giving it a chief medical officer. The law calls for the new CMO to have “real-world” experience treating patients with serious mental illness. The reformed SAMHSA will have responsibility for centralizing data collection to be used in creating best practices in mental health care. These reforms are particular victories for Rep. Murphy who has railed against the agency for years, citing its lack of medically trained leadership and lack of evidence-based approaches to care.
HIPAA requirements in serious mental illness are also clarified.
“Existing HIPAA laws are badly misunderstood,” said Sen. Chris Murphy (D-Conn.) at the briefing. “Many physicians think there is an outright ban on sharing [patient health] information.”
The legislation calls for the U.S. Department of Health and Human Services secretary to clarify when providers can disclose protected health information related to the treatment of an adult with a mental illness or substance use disorder.
“I would argue that [HIPAA] may be an area we will have to work on down the line, if the education campaign doesn’t work, but we will give this a try,” said Sen. Murphy, who has cosponsored legislation to do so.
As passed, the mental health provisions of the 21st Century Cures Act are an amalgamation of several bills introduced during the 114th Congress and are unique in that they largely were written by health care professionals with direct, relevant experience. Rep. Murphy is a clinical psychologist, while Rep. Cassidy is a physician with experience treating uninsured and incarcerated patients. Rep. Eddie Bernice Johnson (D-Tex.), who cosponsored Rep. Murphy’s bill, previously served as chief psychiatric nurse at the Dallas Veterans Affairs Medical Center.
KRAS-targeted T-cell therapy derails metastatic cancer
Adoptive transfer of cytotoxic T cells targeting a specific KRAS mutation (KRAS G12D) expressed by a metastatic colorectal cancer induced the regression of all seven lung metastases in a single patient, investigators report in the New England Journal of Medicine.
Mutations of the KRAS oncogene are frequent and drive the formation and progression of many human cancers. “The high incidence of KRAS G12D expression in [colorectal, pancreatic, and multiple other] cancers means that in the United States alone, thousands of patients per year would be potentially eligible for T-cell–based immunotherapy targeting KRAS G12D,” said Eric Tran, PhD, and his associates in the surgery branch, National Cancer Institute, Bethesda, Md.
They described the case of a 50-year-old woman participating in an ongoing phase II clinical trial assessing adoptive transfer of tumor-infiltrating lymphocytes targeting personalized cancer neoepitopes (individualized T-cell therapy). This patient was the only participant to date in whom the treatment induced tumor regression.
A total of 3 of her 10 lung metastases were resected to identify mutations expressed by the tumors, and these were found to express mutant KRAS G12D and HLA-C*08:02. The lymphocyte cultures that reacted most strongly against these antigens were expanded and made into a single infusion, which was administered after the patient had undergone nonmyeloablative conditioning using cyclophosphamide and fludarabine. The patient then received five doses of interleukin-2, which produced the only adverse effect of the entire regimen, fatigue.
At 40-day follow-up, all seven remaining lung metastases showed marked regression. One lesion showed progression at 9-month follow-up and was resected, and the patient has remained cancer free for the subsequent 4 months (N Engl J Med. 2016 Dec 8. doi:10.1056/NEJMoa1609279).
Laboratory analysis of the one metastasis that progressed showed that it had mutated further, losing heterozygosity of the copy of chromosome 6 that encoded HLA-C*08:02. “The presence of this molecule is required for direct tumor recognition by the transferred KRAS G12D-specific T cells. ... [Such a loss] has been observed in human cancers and may represent a hurdle that needs to be overcome to enhance immunotherapeutic efficacy in some patients,” Dr. Tran and his associates wrote.
“In such cases, targeting antigens that are presented by the remaining HLA class I alleles or exploiting the CD4+ T-cell response or the innate immune system against cancer may be necessary to induce a durable clinical response,” they added.
Adoptive transfer of cytotoxic T cells targeting a specific KRAS mutation (KRAS G12D) expressed by a metastatic colorectal cancer induced the regression of all seven lung metastases in a single patient, investigators report in the New England Journal of Medicine.
Mutations of the KRAS oncogene are frequent and drive the formation and progression of many human cancers. “The high incidence of KRAS G12D expression in [colorectal, pancreatic, and multiple other] cancers means that in the United States alone, thousands of patients per year would be potentially eligible for T-cell–based immunotherapy targeting KRAS G12D,” said Eric Tran, PhD, and his associates in the surgery branch, National Cancer Institute, Bethesda, Md.
They described the case of a 50-year-old woman participating in an ongoing phase II clinical trial assessing adoptive transfer of tumor-infiltrating lymphocytes targeting personalized cancer neoepitopes (individualized T-cell therapy). This patient was the only participant to date in whom the treatment induced tumor regression.
A total of 3 of her 10 lung metastases were resected to identify mutations expressed by the tumors, and these were found to express mutant KRAS G12D and HLA-C*08:02. The lymphocyte cultures that reacted most strongly against these antigens were expanded and made into a single infusion, which was administered after the patient had undergone nonmyeloablative conditioning using cyclophosphamide and fludarabine. The patient then received five doses of interleukin-2, which produced the only adverse effect of the entire regimen, fatigue.
At 40-day follow-up, all seven remaining lung metastases showed marked regression. One lesion showed progression at 9-month follow-up and was resected, and the patient has remained cancer free for the subsequent 4 months (N Engl J Med. 2016 Dec 8. doi:10.1056/NEJMoa1609279).
Laboratory analysis of the one metastasis that progressed showed that it had mutated further, losing heterozygosity of the copy of chromosome 6 that encoded HLA-C*08:02. “The presence of this molecule is required for direct tumor recognition by the transferred KRAS G12D-specific T cells. ... [Such a loss] has been observed in human cancers and may represent a hurdle that needs to be overcome to enhance immunotherapeutic efficacy in some patients,” Dr. Tran and his associates wrote.
“In such cases, targeting antigens that are presented by the remaining HLA class I alleles or exploiting the CD4+ T-cell response or the innate immune system against cancer may be necessary to induce a durable clinical response,” they added.
Adoptive transfer of cytotoxic T cells targeting a specific KRAS mutation (KRAS G12D) expressed by a metastatic colorectal cancer induced the regression of all seven lung metastases in a single patient, investigators report in the New England Journal of Medicine.
Mutations of the KRAS oncogene are frequent and drive the formation and progression of many human cancers. “The high incidence of KRAS G12D expression in [colorectal, pancreatic, and multiple other] cancers means that in the United States alone, thousands of patients per year would be potentially eligible for T-cell–based immunotherapy targeting KRAS G12D,” said Eric Tran, PhD, and his associates in the surgery branch, National Cancer Institute, Bethesda, Md.
They described the case of a 50-year-old woman participating in an ongoing phase II clinical trial assessing adoptive transfer of tumor-infiltrating lymphocytes targeting personalized cancer neoepitopes (individualized T-cell therapy). This patient was the only participant to date in whom the treatment induced tumor regression.
A total of 3 of her 10 lung metastases were resected to identify mutations expressed by the tumors, and these were found to express mutant KRAS G12D and HLA-C*08:02. The lymphocyte cultures that reacted most strongly against these antigens were expanded and made into a single infusion, which was administered after the patient had undergone nonmyeloablative conditioning using cyclophosphamide and fludarabine. The patient then received five doses of interleukin-2, which produced the only adverse effect of the entire regimen, fatigue.
At 40-day follow-up, all seven remaining lung metastases showed marked regression. One lesion showed progression at 9-month follow-up and was resected, and the patient has remained cancer free for the subsequent 4 months (N Engl J Med. 2016 Dec 8. doi:10.1056/NEJMoa1609279).
Laboratory analysis of the one metastasis that progressed showed that it had mutated further, losing heterozygosity of the copy of chromosome 6 that encoded HLA-C*08:02. “The presence of this molecule is required for direct tumor recognition by the transferred KRAS G12D-specific T cells. ... [Such a loss] has been observed in human cancers and may represent a hurdle that needs to be overcome to enhance immunotherapeutic efficacy in some patients,” Dr. Tran and his associates wrote.
“In such cases, targeting antigens that are presented by the remaining HLA class I alleles or exploiting the CD4+ T-cell response or the innate immune system against cancer may be necessary to induce a durable clinical response,” they added.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Adoptive transfer of cytotoxic T cells targeting a specific KRAS mutation expressed by a metastatic colorectal cancer induced the regression of all seven lung metastases in a single patient.
Major finding: At 40-day follow-up, all seven lung metastases showed marked regression; the single metastasis that showed progression at 9-month follow-up was resected, and the patient has remained cancer free for the subsequent 4 months.
Data source: A single case study involving a woman with metastatic colorectal cancer treated with a experimental immunotherapy and followed for 13 months.
Disclosures: This work was supported by the National Cancer Institute. Dr. Tran and some of his associates reported holding a pending patent related to anti-KRAS G12D T-cell receptors.
Senate sends 21st Century Cures bill to president
With little debate and less dissent, the Senate passed the 21st Century Cures bill and sent it to President Obama for his promised signature.
The legislation passed the House by an overwhelming 392-26 vote on Nov. 30. Key provisions of the bill (H.R. 34) include:
• Food and Drug Administration reforms, including expedited review for certain medical devices, streamlined review for drug/device combinations, and increased patient involvement in the drug approval process, with $500 million to implement the reforms.
• $4.8 billion over 10 years for key biomedical research efforts including the BRAIN Initiative, the Cancer Moonshot, and the Precision Medicine Initiative.
• $1 billion in grants to states over a 2-year period to help supplement opioid abuse prevention and treatment activities.
• Provisions to improve the interoperability of EHRs.
• Provisions to improve treatment of serious mental illness.
“This bipartisan legislation – which [Senate] Majority Leader Mitch McConnell [R-Ky.] has called ‘the most important legislation Congress will pass this year’ – will help us take advantage of the breathtaking advances in biomedical research and bring those innovations to doctors’ offices and patients’ medicine cabinets around the county,” Sen. Lamar Alexander (R-Tenn.), chair of the Senate Health, Education, Labor, and Pensions Committee, said in a statement.
“The most important prescription drug-related crisis facing our country right now is the skyrocketing price of prescription drugs. This bill does not even deal with that issue,” Sen. Sanders said on the Senate floor. “How can we talk about a bill dealing with the pharmaceutical industry without addressing the elephant in the room, which is the fact that we pay the highest prices in the world for medicine?”
In his weekly address on Dec. 3, President Obama promised to “sign [the bill] as soon as it reaches my desk.”
Gregory Twachtman contributed to this report.
dfulton@frontlinemedcom.com
On Twitter @denisefulton
With little debate and less dissent, the Senate passed the 21st Century Cures bill and sent it to President Obama for his promised signature.
The legislation passed the House by an overwhelming 392-26 vote on Nov. 30. Key provisions of the bill (H.R. 34) include:
• Food and Drug Administration reforms, including expedited review for certain medical devices, streamlined review for drug/device combinations, and increased patient involvement in the drug approval process, with $500 million to implement the reforms.
• $4.8 billion over 10 years for key biomedical research efforts including the BRAIN Initiative, the Cancer Moonshot, and the Precision Medicine Initiative.
• $1 billion in grants to states over a 2-year period to help supplement opioid abuse prevention and treatment activities.
• Provisions to improve the interoperability of EHRs.
• Provisions to improve treatment of serious mental illness.
“This bipartisan legislation – which [Senate] Majority Leader Mitch McConnell [R-Ky.] has called ‘the most important legislation Congress will pass this year’ – will help us take advantage of the breathtaking advances in biomedical research and bring those innovations to doctors’ offices and patients’ medicine cabinets around the county,” Sen. Lamar Alexander (R-Tenn.), chair of the Senate Health, Education, Labor, and Pensions Committee, said in a statement.
“The most important prescription drug-related crisis facing our country right now is the skyrocketing price of prescription drugs. This bill does not even deal with that issue,” Sen. Sanders said on the Senate floor. “How can we talk about a bill dealing with the pharmaceutical industry without addressing the elephant in the room, which is the fact that we pay the highest prices in the world for medicine?”
In his weekly address on Dec. 3, President Obama promised to “sign [the bill] as soon as it reaches my desk.”
Gregory Twachtman contributed to this report.
dfulton@frontlinemedcom.com
On Twitter @denisefulton
With little debate and less dissent, the Senate passed the 21st Century Cures bill and sent it to President Obama for his promised signature.
The legislation passed the House by an overwhelming 392-26 vote on Nov. 30. Key provisions of the bill (H.R. 34) include:
• Food and Drug Administration reforms, including expedited review for certain medical devices, streamlined review for drug/device combinations, and increased patient involvement in the drug approval process, with $500 million to implement the reforms.
• $4.8 billion over 10 years for key biomedical research efforts including the BRAIN Initiative, the Cancer Moonshot, and the Precision Medicine Initiative.
• $1 billion in grants to states over a 2-year period to help supplement opioid abuse prevention and treatment activities.
• Provisions to improve the interoperability of EHRs.
• Provisions to improve treatment of serious mental illness.
“This bipartisan legislation – which [Senate] Majority Leader Mitch McConnell [R-Ky.] has called ‘the most important legislation Congress will pass this year’ – will help us take advantage of the breathtaking advances in biomedical research and bring those innovations to doctors’ offices and patients’ medicine cabinets around the county,” Sen. Lamar Alexander (R-Tenn.), chair of the Senate Health, Education, Labor, and Pensions Committee, said in a statement.
“The most important prescription drug-related crisis facing our country right now is the skyrocketing price of prescription drugs. This bill does not even deal with that issue,” Sen. Sanders said on the Senate floor. “How can we talk about a bill dealing with the pharmaceutical industry without addressing the elephant in the room, which is the fact that we pay the highest prices in the world for medicine?”
In his weekly address on Dec. 3, President Obama promised to “sign [the bill] as soon as it reaches my desk.”
Gregory Twachtman contributed to this report.
dfulton@frontlinemedcom.com
On Twitter @denisefulton
VIDEO: Angiogenesis has a role to play in NASH and NAFLD
BOSTON – A multimodal research process has provided clues to the role of angiogenesis in nonalcoholic fatty liver disease (NAFLD) and its more serious cousin, nonalcoholic steatohepatitis (NASH).
In constructing a protocol that began with patients, moved on to bioinformatics and then performed final validation in the petri dish, Savneet Kaur, PhD, and her colleagues were able to identify several angiogenesis genes likely to contribute to the development of NAFLD and NASH.
“We have seen angiogenic mechanisms and angiogenic genes in the pathophysiology of nonalcoholic fatty liver disease,” said Dr. Kaur, professor of biotechnology at Gautam Buddha Medical School, Greater Noida, India, in a video interview at the annual meeting of the American Association for the Study of Liver Diseases.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Kaur said that she and her coinvestigators began with a small group of eight patients with NASH, and seven patients with NAFLD, and also with seven healthy control participants. Genetic analysis and comparison of these patients yielded differential expression of certain genes already known to be associated with angiogenesis in the NASH and NAFLD, but not the healthy control participants.
“We did a microarray analysis, a high throughput gene expression study, and then we selected around 25 to 26 genes which were associated with oxidative stress and angiogenesis,” said Dr. Kaur.
For validation of these genes, Dr. Kaur and her associates used a larger study group of about 150 participants, again approximately evenly divided between those with mild NAFLD, those with more severe steatohepatitis, and healthy controls. “We validated the angiogenic genes in the subject group, and found that around 13 genes are preferentially expressed.”
“About 13 genes including VEGFR1, PIK3CA, CXCL8, NOS3, EREG, CCL2, PRKCE, PPar-gamma, PROK2, RUNX1, SIRT1, HMOX1 and CXCR4 showed significantly different gene expression in the [reverse transcription–polymerase chain reaction] analysis in Gr3 as compared to Gr1 (P less than .05 for each), whereas genes such as PIK3CA, CXCL8, NOS3, CCL2, PROK2, RUNX1, and HMOX1 were differentially expressed in Gr3 in comparison to Gr2 (P less than .05 each). A few genes, PPar-gamma, SIRT1, VEGFR1, HMOX1, PIK3CA, CXCR4, PROK2, and CCL2, showed correlations with fibrosis scores, angiogenesis scores, and NAFLD activity scores of the patients,” wrote Dr. Kaur and her colleagues in the abstract accompanying the poster presentation.
Taking these candidate genes, Dr. Kaur and her colleagues conducted a bioinformatics analysis to determine which transcription factors were controlling the genes. “We wanted to study the pathway – the mechanisms – to determine the upregulation and downregulation of these genes,” said Dr. Kaur.
Finally, Dr. Kaur and her associates took an in vitro approach, using human steatotic hepatocytes and endothelial cells, since “angiogenesis is a property of endothelial cells.” The two types of cells were cultured together, and angiogenic function and gene expression were examined, and checked against the genes and pathways identified in the first two steps. They again saw expression of the angiogenic pathways in the cell culture model. This was consistent with what is seen in patients with NAFLD and NASH: “Definitely, there’s an increase in angiogenesis. There’s an increase in the endothelial cell proliferation, with more fat, more steatosis in the patients,” said Dr. Kaur. Some genes, said Dr. Kaur, are “really important” to this process. Her group is now investigating how the genes are regulated, in order to understand better the precise role of angiogenesis in steatohepatitis.
The study was part of a joint Indo-German project, and sponsored by the Indian Council for Medical Research and the German Federal Ministry of Education and Research. Dr. Kaur reported no relevant conflicts of interest.
koakes@frontlinemedcom.com
On Twitter @karioakes
BOSTON – A multimodal research process has provided clues to the role of angiogenesis in nonalcoholic fatty liver disease (NAFLD) and its more serious cousin, nonalcoholic steatohepatitis (NASH).
In constructing a protocol that began with patients, moved on to bioinformatics and then performed final validation in the petri dish, Savneet Kaur, PhD, and her colleagues were able to identify several angiogenesis genes likely to contribute to the development of NAFLD and NASH.
“We have seen angiogenic mechanisms and angiogenic genes in the pathophysiology of nonalcoholic fatty liver disease,” said Dr. Kaur, professor of biotechnology at Gautam Buddha Medical School, Greater Noida, India, in a video interview at the annual meeting of the American Association for the Study of Liver Diseases.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Kaur said that she and her coinvestigators began with a small group of eight patients with NASH, and seven patients with NAFLD, and also with seven healthy control participants. Genetic analysis and comparison of these patients yielded differential expression of certain genes already known to be associated with angiogenesis in the NASH and NAFLD, but not the healthy control participants.
“We did a microarray analysis, a high throughput gene expression study, and then we selected around 25 to 26 genes which were associated with oxidative stress and angiogenesis,” said Dr. Kaur.
For validation of these genes, Dr. Kaur and her associates used a larger study group of about 150 participants, again approximately evenly divided between those with mild NAFLD, those with more severe steatohepatitis, and healthy controls. “We validated the angiogenic genes in the subject group, and found that around 13 genes are preferentially expressed.”
“About 13 genes including VEGFR1, PIK3CA, CXCL8, NOS3, EREG, CCL2, PRKCE, PPar-gamma, PROK2, RUNX1, SIRT1, HMOX1 and CXCR4 showed significantly different gene expression in the [reverse transcription–polymerase chain reaction] analysis in Gr3 as compared to Gr1 (P less than .05 for each), whereas genes such as PIK3CA, CXCL8, NOS3, CCL2, PROK2, RUNX1, and HMOX1 were differentially expressed in Gr3 in comparison to Gr2 (P less than .05 each). A few genes, PPar-gamma, SIRT1, VEGFR1, HMOX1, PIK3CA, CXCR4, PROK2, and CCL2, showed correlations with fibrosis scores, angiogenesis scores, and NAFLD activity scores of the patients,” wrote Dr. Kaur and her colleagues in the abstract accompanying the poster presentation.
Taking these candidate genes, Dr. Kaur and her colleagues conducted a bioinformatics analysis to determine which transcription factors were controlling the genes. “We wanted to study the pathway – the mechanisms – to determine the upregulation and downregulation of these genes,” said Dr. Kaur.
Finally, Dr. Kaur and her associates took an in vitro approach, using human steatotic hepatocytes and endothelial cells, since “angiogenesis is a property of endothelial cells.” The two types of cells were cultured together, and angiogenic function and gene expression were examined, and checked against the genes and pathways identified in the first two steps. They again saw expression of the angiogenic pathways in the cell culture model. This was consistent with what is seen in patients with NAFLD and NASH: “Definitely, there’s an increase in angiogenesis. There’s an increase in the endothelial cell proliferation, with more fat, more steatosis in the patients,” said Dr. Kaur. Some genes, said Dr. Kaur, are “really important” to this process. Her group is now investigating how the genes are regulated, in order to understand better the precise role of angiogenesis in steatohepatitis.
The study was part of a joint Indo-German project, and sponsored by the Indian Council for Medical Research and the German Federal Ministry of Education and Research. Dr. Kaur reported no relevant conflicts of interest.
koakes@frontlinemedcom.com
On Twitter @karioakes
BOSTON – A multimodal research process has provided clues to the role of angiogenesis in nonalcoholic fatty liver disease (NAFLD) and its more serious cousin, nonalcoholic steatohepatitis (NASH).
In constructing a protocol that began with patients, moved on to bioinformatics and then performed final validation in the petri dish, Savneet Kaur, PhD, and her colleagues were able to identify several angiogenesis genes likely to contribute to the development of NAFLD and NASH.
“We have seen angiogenic mechanisms and angiogenic genes in the pathophysiology of nonalcoholic fatty liver disease,” said Dr. Kaur, professor of biotechnology at Gautam Buddha Medical School, Greater Noida, India, in a video interview at the annual meeting of the American Association for the Study of Liver Diseases.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Kaur said that she and her coinvestigators began with a small group of eight patients with NASH, and seven patients with NAFLD, and also with seven healthy control participants. Genetic analysis and comparison of these patients yielded differential expression of certain genes already known to be associated with angiogenesis in the NASH and NAFLD, but not the healthy control participants.
“We did a microarray analysis, a high throughput gene expression study, and then we selected around 25 to 26 genes which were associated with oxidative stress and angiogenesis,” said Dr. Kaur.
For validation of these genes, Dr. Kaur and her associates used a larger study group of about 150 participants, again approximately evenly divided between those with mild NAFLD, those with more severe steatohepatitis, and healthy controls. “We validated the angiogenic genes in the subject group, and found that around 13 genes are preferentially expressed.”
“About 13 genes including VEGFR1, PIK3CA, CXCL8, NOS3, EREG, CCL2, PRKCE, PPar-gamma, PROK2, RUNX1, SIRT1, HMOX1 and CXCR4 showed significantly different gene expression in the [reverse transcription–polymerase chain reaction] analysis in Gr3 as compared to Gr1 (P less than .05 for each), whereas genes such as PIK3CA, CXCL8, NOS3, CCL2, PROK2, RUNX1, and HMOX1 were differentially expressed in Gr3 in comparison to Gr2 (P less than .05 each). A few genes, PPar-gamma, SIRT1, VEGFR1, HMOX1, PIK3CA, CXCR4, PROK2, and CCL2, showed correlations with fibrosis scores, angiogenesis scores, and NAFLD activity scores of the patients,” wrote Dr. Kaur and her colleagues in the abstract accompanying the poster presentation.
Taking these candidate genes, Dr. Kaur and her colleagues conducted a bioinformatics analysis to determine which transcription factors were controlling the genes. “We wanted to study the pathway – the mechanisms – to determine the upregulation and downregulation of these genes,” said Dr. Kaur.
Finally, Dr. Kaur and her associates took an in vitro approach, using human steatotic hepatocytes and endothelial cells, since “angiogenesis is a property of endothelial cells.” The two types of cells were cultured together, and angiogenic function and gene expression were examined, and checked against the genes and pathways identified in the first two steps. They again saw expression of the angiogenic pathways in the cell culture model. This was consistent with what is seen in patients with NAFLD and NASH: “Definitely, there’s an increase in angiogenesis. There’s an increase in the endothelial cell proliferation, with more fat, more steatosis in the patients,” said Dr. Kaur. Some genes, said Dr. Kaur, are “really important” to this process. Her group is now investigating how the genes are regulated, in order to understand better the precise role of angiogenesis in steatohepatitis.
The study was part of a joint Indo-German project, and sponsored by the Indian Council for Medical Research and the German Federal Ministry of Education and Research. Dr. Kaur reported no relevant conflicts of interest.
koakes@frontlinemedcom.com
On Twitter @karioakes
AT THE LIVER MEETING 2016
Key clinical point:
Major finding: PPar-gamma, SIRT1, VEGFR1, and other genes are associated with fibrosis, angiogenesis, and steatosis.
Data source: Human bioinformatics–in vitro exploration of genetic pathways associated with angiogenesis in NASH and nonalcoholic fatty liver disease (NAFLD).
Disclosures: The study was part of a joint Indo-German project, and funded by the Indian Council for Medical Research and the German Federal Ministry of Education and Research. Dr. Kaur reported no relevant financial disclosures.
Rising injectable drug use among whites may reverse declining HIV infection rates
Shifts in injectable drug use behaviors among white Americans could threaten years of declining U.S. HIV rates in persons who inject drugs, according to a federal report.
Between 2008 and 2014, the number of new HIV diagnoses in injectable drug users across all demographic groups declined nationally by nearly half, according to an analysis of national HIV surveillance survey data by the Centers for Disease Control and Prevention.
African Americans who inject drugs had a 60% drop nationally in the number of HIV diagnoses between 2008 and 2014. Latinos/Hispanics who inject drugs had a 50% decline nationally in the number of HIV diagnoses between 2008 and 2014. Whites who inject drugs had a 27% decline in HIV rates between 2008 and 2014, but stable rates between 2012 and 2014.
The report was published online in Morbidity and Mortality Weekly Report. Of note is that 2014 marked the first time that rates of HIV diagnoses were higher in whites who inject drugs than in any other U.S. demographic, according to lead author Cyprian Wejnert, PhD, of the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention at the CDC.
The overall drop in new HIV cases largely is due to safer drug use behaviors among blacks and Hispanics. Between 2005 and 2015, syringe sharing among blacks decreased by 34% – African Americans who inject drugs had a 48% increase between 2005 and 2015 in use of sterile drug equipment – and syringe sharing by Hispanics decreased by 12%. Among whites, however, needle sharing rates remained essentially unchanged at 43%, and the rate of receiving all syringes from sterile sources was also unchanged, at 22% across 22 cities. This steady rate, combined with the fact that more whites than ever are using heroin and other drugs intravenously, worries federal health officials (MMWR. 2016 Dec 2;65[47]:1336-42).
From 2005 to 2015, the total percentage of injectable drug users in 22 urban centers who were white rose from 38% to 54%, while the number of urban blacks using injectable drugs decreased from 38% to 19%. Among new injectable drug users, 40% were white, while the percentage of new users who were black decreased by more than half, according to the report. Rates of novel injectable drug use among urban Hispanics remained unchanged at 21%.
Although more than half of those who reported injecting drugs in 2015 said they had obtained sterile equipment from a syringe sharing program, one in three also reported that during that time they also continued to share needles and syringes, meaning that needle sharing rates are virtually unchanged from 2005.
Because sharing needles and syringes is a direct route of transmission for HIV, as well as the hepatitis B and C viruses, federal health officials are stressing the importance of syringe sharing programs. Injectable drug use is associated with about 1 in 10 new cases of HIV, and has also contributed to a 150% increase in acute cases of hepatitis C infections in the past decade, according to the CDC.
“Until now, the nation has made substantial progress in preventing HIV among people who inject drugs, but this success is threatened,” Jonathan Mermin, MD, MPH, director of the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, said in a statement. He called for an expansion of current syringe sharing programs, especially in rural areas where access to sterile injection equipment is limited.
The authors reported no relevant disclosures.
Shifts in injectable drug use behaviors among white Americans could threaten years of declining U.S. HIV rates in persons who inject drugs, according to a federal report.
Between 2008 and 2014, the number of new HIV diagnoses in injectable drug users across all demographic groups declined nationally by nearly half, according to an analysis of national HIV surveillance survey data by the Centers for Disease Control and Prevention.
African Americans who inject drugs had a 60% drop nationally in the number of HIV diagnoses between 2008 and 2014. Latinos/Hispanics who inject drugs had a 50% decline nationally in the number of HIV diagnoses between 2008 and 2014. Whites who inject drugs had a 27% decline in HIV rates between 2008 and 2014, but stable rates between 2012 and 2014.
The report was published online in Morbidity and Mortality Weekly Report. Of note is that 2014 marked the first time that rates of HIV diagnoses were higher in whites who inject drugs than in any other U.S. demographic, according to lead author Cyprian Wejnert, PhD, of the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention at the CDC.
The overall drop in new HIV cases largely is due to safer drug use behaviors among blacks and Hispanics. Between 2005 and 2015, syringe sharing among blacks decreased by 34% – African Americans who inject drugs had a 48% increase between 2005 and 2015 in use of sterile drug equipment – and syringe sharing by Hispanics decreased by 12%. Among whites, however, needle sharing rates remained essentially unchanged at 43%, and the rate of receiving all syringes from sterile sources was also unchanged, at 22% across 22 cities. This steady rate, combined with the fact that more whites than ever are using heroin and other drugs intravenously, worries federal health officials (MMWR. 2016 Dec 2;65[47]:1336-42).
From 2005 to 2015, the total percentage of injectable drug users in 22 urban centers who were white rose from 38% to 54%, while the number of urban blacks using injectable drugs decreased from 38% to 19%. Among new injectable drug users, 40% were white, while the percentage of new users who were black decreased by more than half, according to the report. Rates of novel injectable drug use among urban Hispanics remained unchanged at 21%.
Although more than half of those who reported injecting drugs in 2015 said they had obtained sterile equipment from a syringe sharing program, one in three also reported that during that time they also continued to share needles and syringes, meaning that needle sharing rates are virtually unchanged from 2005.
Because sharing needles and syringes is a direct route of transmission for HIV, as well as the hepatitis B and C viruses, federal health officials are stressing the importance of syringe sharing programs. Injectable drug use is associated with about 1 in 10 new cases of HIV, and has also contributed to a 150% increase in acute cases of hepatitis C infections in the past decade, according to the CDC.
“Until now, the nation has made substantial progress in preventing HIV among people who inject drugs, but this success is threatened,” Jonathan Mermin, MD, MPH, director of the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, said in a statement. He called for an expansion of current syringe sharing programs, especially in rural areas where access to sterile injection equipment is limited.
The authors reported no relevant disclosures.
Shifts in injectable drug use behaviors among white Americans could threaten years of declining U.S. HIV rates in persons who inject drugs, according to a federal report.
Between 2008 and 2014, the number of new HIV diagnoses in injectable drug users across all demographic groups declined nationally by nearly half, according to an analysis of national HIV surveillance survey data by the Centers for Disease Control and Prevention.
African Americans who inject drugs had a 60% drop nationally in the number of HIV diagnoses between 2008 and 2014. Latinos/Hispanics who inject drugs had a 50% decline nationally in the number of HIV diagnoses between 2008 and 2014. Whites who inject drugs had a 27% decline in HIV rates between 2008 and 2014, but stable rates between 2012 and 2014.
The report was published online in Morbidity and Mortality Weekly Report. Of note is that 2014 marked the first time that rates of HIV diagnoses were higher in whites who inject drugs than in any other U.S. demographic, according to lead author Cyprian Wejnert, PhD, of the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention at the CDC.
The overall drop in new HIV cases largely is due to safer drug use behaviors among blacks and Hispanics. Between 2005 and 2015, syringe sharing among blacks decreased by 34% – African Americans who inject drugs had a 48% increase between 2005 and 2015 in use of sterile drug equipment – and syringe sharing by Hispanics decreased by 12%. Among whites, however, needle sharing rates remained essentially unchanged at 43%, and the rate of receiving all syringes from sterile sources was also unchanged, at 22% across 22 cities. This steady rate, combined with the fact that more whites than ever are using heroin and other drugs intravenously, worries federal health officials (MMWR. 2016 Dec 2;65[47]:1336-42).
From 2005 to 2015, the total percentage of injectable drug users in 22 urban centers who were white rose from 38% to 54%, while the number of urban blacks using injectable drugs decreased from 38% to 19%. Among new injectable drug users, 40% were white, while the percentage of new users who were black decreased by more than half, according to the report. Rates of novel injectable drug use among urban Hispanics remained unchanged at 21%.
Although more than half of those who reported injecting drugs in 2015 said they had obtained sterile equipment from a syringe sharing program, one in three also reported that during that time they also continued to share needles and syringes, meaning that needle sharing rates are virtually unchanged from 2005.
Because sharing needles and syringes is a direct route of transmission for HIV, as well as the hepatitis B and C viruses, federal health officials are stressing the importance of syringe sharing programs. Injectable drug use is associated with about 1 in 10 new cases of HIV, and has also contributed to a 150% increase in acute cases of hepatitis C infections in the past decade, according to the CDC.
“Until now, the nation has made substantial progress in preventing HIV among people who inject drugs, but this success is threatened,” Jonathan Mermin, MD, MPH, director of the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, said in a statement. He called for an expansion of current syringe sharing programs, especially in rural areas where access to sterile injection equipment is limited.
The authors reported no relevant disclosures.
FROM MMWR
Key clinical point:
Major finding: Diagnoses among urban white PWID decreased 28%, but the decline stopped in 2012. Whites have the highest rate of syringe sharing and now make up more than 50% of new PWID.
Data source: National HIV Surveillance System data from 2008-2014.
Disclosures: The authors reported no relevant disclosures.
FDA approves treatment for platinum-sensitive ovarian cancer
The Food and Drug Administration approved bevacizumab (Avastin), used in combination with certain types of chemotherapy, for the treatment of patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary perioneal cancer.
The FDA approved its use in combination with either carboplatin and paclitaxel or carboplatin and gemcitabine chemotherapy, followed by bevacizumab alone. In November 2014, the FDA approved bevacizumab for use in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan chemotherapy for women with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.
The GOG-0213 study showed an overall survival improvement of 5 months with bevacizumab plus chemotherapy, compared with chemotherapy alone (hazard ratio, 0.84). The study also showed improved progression-free survival of 3.4 months (HR, 0.61). In the OCEANS study, progression-free survival was 12.4 months for bevacizumab plus chemotherapy, compared with 8.4 months for placebo plus chemotherapy (HR, 0.46). Overall survival was not significantly improved by the addition of bevacizumab in the OCEANS study.
Some adverse events observed in the trials included fatigue, hypertension, febrile neutropenia, proteinuria, abdominal pain, hyponatremia, headache, nausea, and pain in the extremity.
Bevacizumab is manufactured by Genentech, and full prescribing information and a boxed warning are available on the drug’s website, www.avastin.com.
mschneider@frontlinemedcom.com
On Twitter @maryellenny
The Food and Drug Administration approved bevacizumab (Avastin), used in combination with certain types of chemotherapy, for the treatment of patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary perioneal cancer.
The FDA approved its use in combination with either carboplatin and paclitaxel or carboplatin and gemcitabine chemotherapy, followed by bevacizumab alone. In November 2014, the FDA approved bevacizumab for use in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan chemotherapy for women with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.
The GOG-0213 study showed an overall survival improvement of 5 months with bevacizumab plus chemotherapy, compared with chemotherapy alone (hazard ratio, 0.84). The study also showed improved progression-free survival of 3.4 months (HR, 0.61). In the OCEANS study, progression-free survival was 12.4 months for bevacizumab plus chemotherapy, compared with 8.4 months for placebo plus chemotherapy (HR, 0.46). Overall survival was not significantly improved by the addition of bevacizumab in the OCEANS study.
Some adverse events observed in the trials included fatigue, hypertension, febrile neutropenia, proteinuria, abdominal pain, hyponatremia, headache, nausea, and pain in the extremity.
Bevacizumab is manufactured by Genentech, and full prescribing information and a boxed warning are available on the drug’s website, www.avastin.com.
mschneider@frontlinemedcom.com
On Twitter @maryellenny
The Food and Drug Administration approved bevacizumab (Avastin), used in combination with certain types of chemotherapy, for the treatment of patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary perioneal cancer.
The FDA approved its use in combination with either carboplatin and paclitaxel or carboplatin and gemcitabine chemotherapy, followed by bevacizumab alone. In November 2014, the FDA approved bevacizumab for use in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan chemotherapy for women with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.
The GOG-0213 study showed an overall survival improvement of 5 months with bevacizumab plus chemotherapy, compared with chemotherapy alone (hazard ratio, 0.84). The study also showed improved progression-free survival of 3.4 months (HR, 0.61). In the OCEANS study, progression-free survival was 12.4 months for bevacizumab plus chemotherapy, compared with 8.4 months for placebo plus chemotherapy (HR, 0.46). Overall survival was not significantly improved by the addition of bevacizumab in the OCEANS study.
Some adverse events observed in the trials included fatigue, hypertension, febrile neutropenia, proteinuria, abdominal pain, hyponatremia, headache, nausea, and pain in the extremity.
Bevacizumab is manufactured by Genentech, and full prescribing information and a boxed warning are available on the drug’s website, www.avastin.com.
mschneider@frontlinemedcom.com
On Twitter @maryellenny
Pembrolizumab proves promising for treating advanced SCLC
VIENNA – One third of patients with extensive-stage small-cell lung cancer (SCLC) treated with the checkpoint inhibitor pembrolizumab achieved an objective response, according to updated data from the KEYNOTE-28 trial.
Of the 24 patients with advanced SCLC who received pembrolizumab in the multicohort phase Ib study, one had a complete response, seven had a partial response, and one further patient had stable disease for 6 or more months, giving a clinical benefit rate of 33.3% (95% CI, 15.6-53.3%).
“Pembrolizumab demonstrated meaningful antitumor activity in previously treated patients with PD-L1-positive small-cell lung cancer,” said presenting study author Patrick A. Ott, MD, PhD, of the Dana-Faber Cancer Institute in Boston.
“Responses were durable, with a median duration of response of 19.4 months,” Dr. Ott said at the World Conference on Cancer, which is sponsored by the International Association for the Study of Lung Cancer. About 40% of patients exhibited a decrease in tumor size, he added.
Treatment with pembrolizumab was associated with a progression-free survival (PFS) of 1.2 months, with a range of 1.7-5.9 months. The 6- and 12-month PFS rates were 28.6% and 23.8%, respectively.
The median overall survival (OS) was 9.7 months, ranging from 4.1 months to an upper limit that has not yet been reached. The respective 6- and 12-month OS rates were 66.0% and 37.7%.
“The safety experience was consistent with previous experience for pembrolizumab in other tumor types, and was identical with longer follow-up” Dr. Ott said.
Over a median follow-up duration of 9.8 months, treatment-related adverse events occurred in two-thirds of patients, with arthralgia, asthenia, and rash reported by four (16.7%) patients each, and diarrhea and fatigue by three (12.5%) patients each. There were no cases of pneumonitis.
The mean age of patients recruited into the KEYNOTE-28 trial was 60.5 years; more than half of the patients (58%) were male. Five (20.8%) had stable brain metastases, and 95.8% had small cell histology.
All recruited patients had received prior standard-of-care chemotherapy with cisplatin or carboplatin plus etoposide, 45.8% had received irinotecan or topotecan, and 29.2% had been treated with a taxane. In addition, one patient had received prior radiotherapy, one had been given an investigational tyrosine kinase inhibitor therapy, and another had received another, unspecified, investigational treatment.
After enrollment, all patients were treated with pembrolizumab at an intravenous dose of 10 mg/kg every 2 weeks. Response was assessed every 8 weeks for the first 6 months and then annually, with patients continuing to respond continuing to be treated for up to 2 years or until progression or unacceptable toxicity.
There are two ongoing, phase II trials with pembrolizumab in patients with advanced SCLC. One is looking at maintenance therapy with pembrolizumab after combination chemotherapy and is sponsored by the Barbara Ann Karmanos Cancer Institute in collaboration with the National Cancer Institute (NCT02359019). The other, the REACTION trial sponsored by the European Organisation for Research and Treatment of Cancer, is looking at the use of pembrolizumab together with etoposide and platinum chemotherapy in previously untreated patients (NCT02580994).
Merck funded the KEYNOTE-28 study. Dr. Ott disclosed ties with Bristol-Myers Squibb, Merck, ArmoBiosciences, AstraZeneca/MedImmune, Celldex, Genentech, Alexion, and CytomX.
VIENNA – One third of patients with extensive-stage small-cell lung cancer (SCLC) treated with the checkpoint inhibitor pembrolizumab achieved an objective response, according to updated data from the KEYNOTE-28 trial.
Of the 24 patients with advanced SCLC who received pembrolizumab in the multicohort phase Ib study, one had a complete response, seven had a partial response, and one further patient had stable disease for 6 or more months, giving a clinical benefit rate of 33.3% (95% CI, 15.6-53.3%).
“Pembrolizumab demonstrated meaningful antitumor activity in previously treated patients with PD-L1-positive small-cell lung cancer,” said presenting study author Patrick A. Ott, MD, PhD, of the Dana-Faber Cancer Institute in Boston.
“Responses were durable, with a median duration of response of 19.4 months,” Dr. Ott said at the World Conference on Cancer, which is sponsored by the International Association for the Study of Lung Cancer. About 40% of patients exhibited a decrease in tumor size, he added.
Treatment with pembrolizumab was associated with a progression-free survival (PFS) of 1.2 months, with a range of 1.7-5.9 months. The 6- and 12-month PFS rates were 28.6% and 23.8%, respectively.
The median overall survival (OS) was 9.7 months, ranging from 4.1 months to an upper limit that has not yet been reached. The respective 6- and 12-month OS rates were 66.0% and 37.7%.
“The safety experience was consistent with previous experience for pembrolizumab in other tumor types, and was identical with longer follow-up” Dr. Ott said.
Over a median follow-up duration of 9.8 months, treatment-related adverse events occurred in two-thirds of patients, with arthralgia, asthenia, and rash reported by four (16.7%) patients each, and diarrhea and fatigue by three (12.5%) patients each. There were no cases of pneumonitis.
The mean age of patients recruited into the KEYNOTE-28 trial was 60.5 years; more than half of the patients (58%) were male. Five (20.8%) had stable brain metastases, and 95.8% had small cell histology.
All recruited patients had received prior standard-of-care chemotherapy with cisplatin or carboplatin plus etoposide, 45.8% had received irinotecan or topotecan, and 29.2% had been treated with a taxane. In addition, one patient had received prior radiotherapy, one had been given an investigational tyrosine kinase inhibitor therapy, and another had received another, unspecified, investigational treatment.
After enrollment, all patients were treated with pembrolizumab at an intravenous dose of 10 mg/kg every 2 weeks. Response was assessed every 8 weeks for the first 6 months and then annually, with patients continuing to respond continuing to be treated for up to 2 years or until progression or unacceptable toxicity.
There are two ongoing, phase II trials with pembrolizumab in patients with advanced SCLC. One is looking at maintenance therapy with pembrolizumab after combination chemotherapy and is sponsored by the Barbara Ann Karmanos Cancer Institute in collaboration with the National Cancer Institute (NCT02359019). The other, the REACTION trial sponsored by the European Organisation for Research and Treatment of Cancer, is looking at the use of pembrolizumab together with etoposide and platinum chemotherapy in previously untreated patients (NCT02580994).
Merck funded the KEYNOTE-28 study. Dr. Ott disclosed ties with Bristol-Myers Squibb, Merck, ArmoBiosciences, AstraZeneca/MedImmune, Celldex, Genentech, Alexion, and CytomX.
VIENNA – One third of patients with extensive-stage small-cell lung cancer (SCLC) treated with the checkpoint inhibitor pembrolizumab achieved an objective response, according to updated data from the KEYNOTE-28 trial.
Of the 24 patients with advanced SCLC who received pembrolizumab in the multicohort phase Ib study, one had a complete response, seven had a partial response, and one further patient had stable disease for 6 or more months, giving a clinical benefit rate of 33.3% (95% CI, 15.6-53.3%).
“Pembrolizumab demonstrated meaningful antitumor activity in previously treated patients with PD-L1-positive small-cell lung cancer,” said presenting study author Patrick A. Ott, MD, PhD, of the Dana-Faber Cancer Institute in Boston.
“Responses were durable, with a median duration of response of 19.4 months,” Dr. Ott said at the World Conference on Cancer, which is sponsored by the International Association for the Study of Lung Cancer. About 40% of patients exhibited a decrease in tumor size, he added.
Treatment with pembrolizumab was associated with a progression-free survival (PFS) of 1.2 months, with a range of 1.7-5.9 months. The 6- and 12-month PFS rates were 28.6% and 23.8%, respectively.
The median overall survival (OS) was 9.7 months, ranging from 4.1 months to an upper limit that has not yet been reached. The respective 6- and 12-month OS rates were 66.0% and 37.7%.
“The safety experience was consistent with previous experience for pembrolizumab in other tumor types, and was identical with longer follow-up” Dr. Ott said.
Over a median follow-up duration of 9.8 months, treatment-related adverse events occurred in two-thirds of patients, with arthralgia, asthenia, and rash reported by four (16.7%) patients each, and diarrhea and fatigue by three (12.5%) patients each. There were no cases of pneumonitis.
The mean age of patients recruited into the KEYNOTE-28 trial was 60.5 years; more than half of the patients (58%) were male. Five (20.8%) had stable brain metastases, and 95.8% had small cell histology.
All recruited patients had received prior standard-of-care chemotherapy with cisplatin or carboplatin plus etoposide, 45.8% had received irinotecan or topotecan, and 29.2% had been treated with a taxane. In addition, one patient had received prior radiotherapy, one had been given an investigational tyrosine kinase inhibitor therapy, and another had received another, unspecified, investigational treatment.
After enrollment, all patients were treated with pembrolizumab at an intravenous dose of 10 mg/kg every 2 weeks. Response was assessed every 8 weeks for the first 6 months and then annually, with patients continuing to respond continuing to be treated for up to 2 years or until progression or unacceptable toxicity.
There are two ongoing, phase II trials with pembrolizumab in patients with advanced SCLC. One is looking at maintenance therapy with pembrolizumab after combination chemotherapy and is sponsored by the Barbara Ann Karmanos Cancer Institute in collaboration with the National Cancer Institute (NCT02359019). The other, the REACTION trial sponsored by the European Organisation for Research and Treatment of Cancer, is looking at the use of pembrolizumab together with etoposide and platinum chemotherapy in previously untreated patients (NCT02580994).
Merck funded the KEYNOTE-28 study. Dr. Ott disclosed ties with Bristol-Myers Squibb, Merck, ArmoBiosciences, AstraZeneca/MedImmune, Celldex, Genentech, Alexion, and CytomX.
AT WCLC 2016
Key clinical point: Pembrolizumab has antitumor activity in patients with advanced small-cell lung cancer.
Major finding: The objective response rate was 33.3% (95% CI 15.6-55.3%), including one complete and seven partial responses.
Data source: Phase Ib, nonrandomized, multicohort trial of 24 heavily pretreated patients with extensive-disease small-cell lung cancer.
Disclosures: Merck funded the study. Dr. Ott disclosed ties with Bristol-Myers Squibb, Merck, ArmoBiosciences, AstraZeneca/MedImmune, Celldex, Genentech, Alexion, and CytomX.
Skin cancer a concern in pediatric solid organ transplant recipients
As survival rates among pediatric organ transplant recipients increase, so do the rates of cutaneous malignancies later in life for this population, who are at a greater risk for skin cancers that include nonmelanoma skin cancers (NMSCs), melanoma, Kaposi sarcoma, and anogenital carcinoma, according to the authors of a literature review.
In studies, skin cancers account for 13%-55% of all cancers in pediatric organ transplant recipients (POTRs), according to Alexander L. Fogel of Stanford (Calif.) University and his coauthors. The review article provides an update on this topic, as well as information on the prevention and management of skin cancers in this population, and the differences between this group and adult organ transplant recipients (AOTRs).
NMSC is the most common type of skin cancer in the pediatric group – and the second most common type of malignancy (NMSCs are the most common type of cancer affecting adult organ transplant recipients). NMSCs typically appear an average of 12-18 years post transplantation in this population (at an average age of 26-34 years). Length of posttransplantation follow-up, sunlight exposure, fair skin, and Northern European ancestry are among the factors associated with increased risk. This type of cancer involves the lip nearly twice as often as in adult recipients: 23% vs. 12%. The pediatric cohort also experiences more nonmelanoma cancer spreading to the lymph nodes than do adults: 9% vs. 6%.
Among pediatric transplant recipients, squamous cell carcinomas appear 2.8 times more often than basal cell carcinomas, “a trend that is opposite that observed in the nontransplant population,” the authors wrote.
In one study, anogenital carcinomas accounted for 4% of posttransplant cancers in this cohort, at an average of 12 years after the transplant, at a mean age of 27 years.
Some data indicate that in adult transplant recipients, there is an association between the human papillomavirus, and anal and genital warts and posttransplant anogenital cancer, but there are little data looking at this association in the pediatric group, the authors noted.
Although melanoma and Kaposi sarcoma are also found in this cohort at rates greater than in the general population, and are associated with high mortality rates, the data are too few to draw conclusions, the authors wrote.
In 2014, 1,795 pediatric solid organ transplants were performed, accounting for 6% of all such transplants. The absolute number of pediatric transplants has remained fairly stable over 5 years, yet very little pediatric-specific literature exists for prevention and management of skin cancers post transplantation, the authors pointed out.
Changing immunosuppressive medications used in transplantation may be effective in reducing skin cancer risk, they said, noting that including rapamycin inhibitors in combination therapy has been shown to reduce the risk of developing skin cancers in some transplant patients by more than half.
The authors emphasized that regular sunscreen use and dermatologic checkups are also essential in this population, and that “the importance of regular dermatologic evaluation should be stressed to patients and their families.”
Mr. Fogel’s coauthors were Mari Miyar, MD, of the department of dermatology, Kaiser Permanente, San Jose, Calif., and Joyce Teng, MD, of the departments of dermatology and pediatrics, Stanford. The authors had no disclosures listed, and no funding source for the review was listed.
This article was updated 12/8/16.
As survival rates among pediatric organ transplant recipients increase, so do the rates of cutaneous malignancies later in life for this population, who are at a greater risk for skin cancers that include nonmelanoma skin cancers (NMSCs), melanoma, Kaposi sarcoma, and anogenital carcinoma, according to the authors of a literature review.
In studies, skin cancers account for 13%-55% of all cancers in pediatric organ transplant recipients (POTRs), according to Alexander L. Fogel of Stanford (Calif.) University and his coauthors. The review article provides an update on this topic, as well as information on the prevention and management of skin cancers in this population, and the differences between this group and adult organ transplant recipients (AOTRs).
NMSC is the most common type of skin cancer in the pediatric group – and the second most common type of malignancy (NMSCs are the most common type of cancer affecting adult organ transplant recipients). NMSCs typically appear an average of 12-18 years post transplantation in this population (at an average age of 26-34 years). Length of posttransplantation follow-up, sunlight exposure, fair skin, and Northern European ancestry are among the factors associated with increased risk. This type of cancer involves the lip nearly twice as often as in adult recipients: 23% vs. 12%. The pediatric cohort also experiences more nonmelanoma cancer spreading to the lymph nodes than do adults: 9% vs. 6%.
Among pediatric transplant recipients, squamous cell carcinomas appear 2.8 times more often than basal cell carcinomas, “a trend that is opposite that observed in the nontransplant population,” the authors wrote.
In one study, anogenital carcinomas accounted for 4% of posttransplant cancers in this cohort, at an average of 12 years after the transplant, at a mean age of 27 years.
Some data indicate that in adult transplant recipients, there is an association between the human papillomavirus, and anal and genital warts and posttransplant anogenital cancer, but there are little data looking at this association in the pediatric group, the authors noted.
Although melanoma and Kaposi sarcoma are also found in this cohort at rates greater than in the general population, and are associated with high mortality rates, the data are too few to draw conclusions, the authors wrote.
In 2014, 1,795 pediatric solid organ transplants were performed, accounting for 6% of all such transplants. The absolute number of pediatric transplants has remained fairly stable over 5 years, yet very little pediatric-specific literature exists for prevention and management of skin cancers post transplantation, the authors pointed out.
Changing immunosuppressive medications used in transplantation may be effective in reducing skin cancer risk, they said, noting that including rapamycin inhibitors in combination therapy has been shown to reduce the risk of developing skin cancers in some transplant patients by more than half.
The authors emphasized that regular sunscreen use and dermatologic checkups are also essential in this population, and that “the importance of regular dermatologic evaluation should be stressed to patients and their families.”
Mr. Fogel’s coauthors were Mari Miyar, MD, of the department of dermatology, Kaiser Permanente, San Jose, Calif., and Joyce Teng, MD, of the departments of dermatology and pediatrics, Stanford. The authors had no disclosures listed, and no funding source for the review was listed.
This article was updated 12/8/16.
As survival rates among pediatric organ transplant recipients increase, so do the rates of cutaneous malignancies later in life for this population, who are at a greater risk for skin cancers that include nonmelanoma skin cancers (NMSCs), melanoma, Kaposi sarcoma, and anogenital carcinoma, according to the authors of a literature review.
In studies, skin cancers account for 13%-55% of all cancers in pediatric organ transplant recipients (POTRs), according to Alexander L. Fogel of Stanford (Calif.) University and his coauthors. The review article provides an update on this topic, as well as information on the prevention and management of skin cancers in this population, and the differences between this group and adult organ transplant recipients (AOTRs).
NMSC is the most common type of skin cancer in the pediatric group – and the second most common type of malignancy (NMSCs are the most common type of cancer affecting adult organ transplant recipients). NMSCs typically appear an average of 12-18 years post transplantation in this population (at an average age of 26-34 years). Length of posttransplantation follow-up, sunlight exposure, fair skin, and Northern European ancestry are among the factors associated with increased risk. This type of cancer involves the lip nearly twice as often as in adult recipients: 23% vs. 12%. The pediatric cohort also experiences more nonmelanoma cancer spreading to the lymph nodes than do adults: 9% vs. 6%.
Among pediatric transplant recipients, squamous cell carcinomas appear 2.8 times more often than basal cell carcinomas, “a trend that is opposite that observed in the nontransplant population,” the authors wrote.
In one study, anogenital carcinomas accounted for 4% of posttransplant cancers in this cohort, at an average of 12 years after the transplant, at a mean age of 27 years.
Some data indicate that in adult transplant recipients, there is an association between the human papillomavirus, and anal and genital warts and posttransplant anogenital cancer, but there are little data looking at this association in the pediatric group, the authors noted.
Although melanoma and Kaposi sarcoma are also found in this cohort at rates greater than in the general population, and are associated with high mortality rates, the data are too few to draw conclusions, the authors wrote.
In 2014, 1,795 pediatric solid organ transplants were performed, accounting for 6% of all such transplants. The absolute number of pediatric transplants has remained fairly stable over 5 years, yet very little pediatric-specific literature exists for prevention and management of skin cancers post transplantation, the authors pointed out.
Changing immunosuppressive medications used in transplantation may be effective in reducing skin cancer risk, they said, noting that including rapamycin inhibitors in combination therapy has been shown to reduce the risk of developing skin cancers in some transplant patients by more than half.
The authors emphasized that regular sunscreen use and dermatologic checkups are also essential in this population, and that “the importance of regular dermatologic evaluation should be stressed to patients and their families.”
Mr. Fogel’s coauthors were Mari Miyar, MD, of the department of dermatology, Kaiser Permanente, San Jose, Calif., and Joyce Teng, MD, of the departments of dermatology and pediatrics, Stanford. The authors had no disclosures listed, and no funding source for the review was listed.
This article was updated 12/8/16.
FROM PEDIATRIC DERMATOLOGY
Key clinical point:
Major finding: Pediatric solid organ transplant recipients experience skin cancer rates between 13% and 55%.
Data source: A literature review of malignancies among pediatric organ transplant recipients.
Disclosures: The authors listed no disclosures, and no funding source for the review was listed.
New-onset pain rare after Essure placement
ORLANDO – While some women report new-onset pelvic pain after placement of an Essure sterilization device, results of a retrospective study suggest this pain is actually associated with placement of the device in about 1% of cases.
Among 1,430 women who had an Essure micro-insert (Bayer) placed at a tertiary care hospital in Canada from June 2002 to June 2013, 62 secondary surgeries were performed, including some for removal of fallopian tubes and removal of the device.
In total, 27 patients reported new-onset pelvic pain after Essure placement and another 11 reported worsening of previous pain. Upon further workup, 15 of the 27 women in the new-onset pain group had another possible explanation for their pain, including surgical or pathology findings of endometriosis or adenomyosis. The investigators concluded there was a link between the pain and the device in just 12 (0.8%) of the women.
Among these dozen patients, the investigators linked the pain in eight women to perforation or migration of the Essure device. Investigators found no other obvious cause for the new-onset pain in the remaining four patients and attributed it to the Essure device.
Set realistic expectations, take a comprehensive pain history, and reassure women when they report post-Essure placement pain, James Robinson, MD, a minimally invasive gynecologic surgeon at Medstar Washington Hospital in Washington, D.C., advised at the meeting, which was sponsored by AAGL.
Dr. Robinson pointed out that there is no standardized approach to managing women with complaints of pain or guidelines on how best to remove the device. Imaging to confirm proper placement and to rule out other sources of pelvic pain, followed by medical or surgical management as warranted, can be effective strategies.
“There is less science here – it’s more the art of medicine, I think,” he said.
Dr. Robinson filled in as a presenter for one of the study coauthors, John A. Thiel, MD, of the University of Saskatchewan, Saskatoon, who was unable to attend the conference.
The study by Dr. Thiel and his colleagues suggests a thorough examination will typically reveal other reasons for pelvic pain and rules out the Essure device as the cause, Dr. Robinson said. The full findings of the study are published in the Journal of Minimally Invasive Gynecology (2016 Nov-Dec;23[7]:1158-1162).
Does removal help?
In a recently published case series of 29 women who had their Essure device removed laparoscopically because of pain, 23 reported relief following excision (Contraception. 2016 Aug;94[2]:190-2).
“Again, a subset had misplaced inserts or had another condition such as endometriosis,” Dr. Robinson said.
The majority of women whose pain resolved with removal of the devices reported their pain early on, so there is an important takeaway from this,” Dr. Robinson said. “We need to listen to our patients when they report pain shortly after device placement … and respond to that.”
Dr. Robinson advised physicians to be ready to surgically remove the device if that is warranted. “I think a lot of people doing these procedures are not comfortable taking their patient back to the operating room or don’t know who to send them to,” he said. “If you are going to place the device, you should be able to take it out or know someone who can.”
The bigger picture
Even though the Essure device is not frequently the cause of pelvic pain, physicians needs to be aware that some patients are likely to assume that it is.
Dr. Robinson pointed to a case in which a woman who had the Essure micro-insert placed 7 years earlier presented with a complaint of a bilateral tingling sensation over the course of 6 months. Online research led her to suspect Essure as the cause of her symptoms. However, on further investigation, it turned out she had relatively high levels of lead in her system from leaky pipes in her home. “It wasn’t an Essure issue,” he said. “But because it’s out there, people will jump to the conclusion that the foreign body is likely the cause of their problem.”
Ob.gyns. should become familiar with websites such as essureproblems.webs.com, which chronicle problems patients have reported with the device, he said.
When talking to patients, start with informed consent and listen to their concerns, Dr. Robinson advised. As part of the counseling about Essure permanent birth control, discuss the risks and benefits of alternatives, such as laparoscopic tubal ligation, long-acting reversible contraception, and vasectomy.
“I took the time to listen to the FDA hearing in Sept 2015 and … it moved me to listen to those patients, and I’ve been a huge advocate of Essure sterilization. I felt for a while I would never do another tubal ligation,” Dr. Robinson said. “But when you listen to patients who have real complaints, what sticks out in your mind is so many of these people are upset because no one took them seriously and listened to them.”
ORLANDO – While some women report new-onset pelvic pain after placement of an Essure sterilization device, results of a retrospective study suggest this pain is actually associated with placement of the device in about 1% of cases.
Among 1,430 women who had an Essure micro-insert (Bayer) placed at a tertiary care hospital in Canada from June 2002 to June 2013, 62 secondary surgeries were performed, including some for removal of fallopian tubes and removal of the device.
In total, 27 patients reported new-onset pelvic pain after Essure placement and another 11 reported worsening of previous pain. Upon further workup, 15 of the 27 women in the new-onset pain group had another possible explanation for their pain, including surgical or pathology findings of endometriosis or adenomyosis. The investigators concluded there was a link between the pain and the device in just 12 (0.8%) of the women.
Among these dozen patients, the investigators linked the pain in eight women to perforation or migration of the Essure device. Investigators found no other obvious cause for the new-onset pain in the remaining four patients and attributed it to the Essure device.
Set realistic expectations, take a comprehensive pain history, and reassure women when they report post-Essure placement pain, James Robinson, MD, a minimally invasive gynecologic surgeon at Medstar Washington Hospital in Washington, D.C., advised at the meeting, which was sponsored by AAGL.
Dr. Robinson pointed out that there is no standardized approach to managing women with complaints of pain or guidelines on how best to remove the device. Imaging to confirm proper placement and to rule out other sources of pelvic pain, followed by medical or surgical management as warranted, can be effective strategies.
“There is less science here – it’s more the art of medicine, I think,” he said.
Dr. Robinson filled in as a presenter for one of the study coauthors, John A. Thiel, MD, of the University of Saskatchewan, Saskatoon, who was unable to attend the conference.
The study by Dr. Thiel and his colleagues suggests a thorough examination will typically reveal other reasons for pelvic pain and rules out the Essure device as the cause, Dr. Robinson said. The full findings of the study are published in the Journal of Minimally Invasive Gynecology (2016 Nov-Dec;23[7]:1158-1162).
Does removal help?
In a recently published case series of 29 women who had their Essure device removed laparoscopically because of pain, 23 reported relief following excision (Contraception. 2016 Aug;94[2]:190-2).
“Again, a subset had misplaced inserts or had another condition such as endometriosis,” Dr. Robinson said.
The majority of women whose pain resolved with removal of the devices reported their pain early on, so there is an important takeaway from this,” Dr. Robinson said. “We need to listen to our patients when they report pain shortly after device placement … and respond to that.”
Dr. Robinson advised physicians to be ready to surgically remove the device if that is warranted. “I think a lot of people doing these procedures are not comfortable taking their patient back to the operating room or don’t know who to send them to,” he said. “If you are going to place the device, you should be able to take it out or know someone who can.”
The bigger picture
Even though the Essure device is not frequently the cause of pelvic pain, physicians needs to be aware that some patients are likely to assume that it is.
Dr. Robinson pointed to a case in which a woman who had the Essure micro-insert placed 7 years earlier presented with a complaint of a bilateral tingling sensation over the course of 6 months. Online research led her to suspect Essure as the cause of her symptoms. However, on further investigation, it turned out she had relatively high levels of lead in her system from leaky pipes in her home. “It wasn’t an Essure issue,” he said. “But because it’s out there, people will jump to the conclusion that the foreign body is likely the cause of their problem.”
Ob.gyns. should become familiar with websites such as essureproblems.webs.com, which chronicle problems patients have reported with the device, he said.
When talking to patients, start with informed consent and listen to their concerns, Dr. Robinson advised. As part of the counseling about Essure permanent birth control, discuss the risks and benefits of alternatives, such as laparoscopic tubal ligation, long-acting reversible contraception, and vasectomy.
“I took the time to listen to the FDA hearing in Sept 2015 and … it moved me to listen to those patients, and I’ve been a huge advocate of Essure sterilization. I felt for a while I would never do another tubal ligation,” Dr. Robinson said. “But when you listen to patients who have real complaints, what sticks out in your mind is so many of these people are upset because no one took them seriously and listened to them.”
ORLANDO – While some women report new-onset pelvic pain after placement of an Essure sterilization device, results of a retrospective study suggest this pain is actually associated with placement of the device in about 1% of cases.
Among 1,430 women who had an Essure micro-insert (Bayer) placed at a tertiary care hospital in Canada from June 2002 to June 2013, 62 secondary surgeries were performed, including some for removal of fallopian tubes and removal of the device.
In total, 27 patients reported new-onset pelvic pain after Essure placement and another 11 reported worsening of previous pain. Upon further workup, 15 of the 27 women in the new-onset pain group had another possible explanation for their pain, including surgical or pathology findings of endometriosis or adenomyosis. The investigators concluded there was a link between the pain and the device in just 12 (0.8%) of the women.
Among these dozen patients, the investigators linked the pain in eight women to perforation or migration of the Essure device. Investigators found no other obvious cause for the new-onset pain in the remaining four patients and attributed it to the Essure device.
Set realistic expectations, take a comprehensive pain history, and reassure women when they report post-Essure placement pain, James Robinson, MD, a minimally invasive gynecologic surgeon at Medstar Washington Hospital in Washington, D.C., advised at the meeting, which was sponsored by AAGL.
Dr. Robinson pointed out that there is no standardized approach to managing women with complaints of pain or guidelines on how best to remove the device. Imaging to confirm proper placement and to rule out other sources of pelvic pain, followed by medical or surgical management as warranted, can be effective strategies.
“There is less science here – it’s more the art of medicine, I think,” he said.
Dr. Robinson filled in as a presenter for one of the study coauthors, John A. Thiel, MD, of the University of Saskatchewan, Saskatoon, who was unable to attend the conference.
The study by Dr. Thiel and his colleagues suggests a thorough examination will typically reveal other reasons for pelvic pain and rules out the Essure device as the cause, Dr. Robinson said. The full findings of the study are published in the Journal of Minimally Invasive Gynecology (2016 Nov-Dec;23[7]:1158-1162).
Does removal help?
In a recently published case series of 29 women who had their Essure device removed laparoscopically because of pain, 23 reported relief following excision (Contraception. 2016 Aug;94[2]:190-2).
“Again, a subset had misplaced inserts or had another condition such as endometriosis,” Dr. Robinson said.
The majority of women whose pain resolved with removal of the devices reported their pain early on, so there is an important takeaway from this,” Dr. Robinson said. “We need to listen to our patients when they report pain shortly after device placement … and respond to that.”
Dr. Robinson advised physicians to be ready to surgically remove the device if that is warranted. “I think a lot of people doing these procedures are not comfortable taking their patient back to the operating room or don’t know who to send them to,” he said. “If you are going to place the device, you should be able to take it out or know someone who can.”
The bigger picture
Even though the Essure device is not frequently the cause of pelvic pain, physicians needs to be aware that some patients are likely to assume that it is.
Dr. Robinson pointed to a case in which a woman who had the Essure micro-insert placed 7 years earlier presented with a complaint of a bilateral tingling sensation over the course of 6 months. Online research led her to suspect Essure as the cause of her symptoms. However, on further investigation, it turned out she had relatively high levels of lead in her system from leaky pipes in her home. “It wasn’t an Essure issue,” he said. “But because it’s out there, people will jump to the conclusion that the foreign body is likely the cause of their problem.”
Ob.gyns. should become familiar with websites such as essureproblems.webs.com, which chronicle problems patients have reported with the device, he said.
When talking to patients, start with informed consent and listen to their concerns, Dr. Robinson advised. As part of the counseling about Essure permanent birth control, discuss the risks and benefits of alternatives, such as laparoscopic tubal ligation, long-acting reversible contraception, and vasectomy.
“I took the time to listen to the FDA hearing in Sept 2015 and … it moved me to listen to those patients, and I’ve been a huge advocate of Essure sterilization. I felt for a while I would never do another tubal ligation,” Dr. Robinson said. “But when you listen to patients who have real complaints, what sticks out in your mind is so many of these people are upset because no one took them seriously and listened to them.”
Key clinical point:
Major finding: Of 1,430 women who had the Essure inserts placed, just 12 had new-onset pain that was found to be related to the device.
Data source: Retrospective cohort study of 1,430 women treated at a tertiary care hospital in Canada.
Disclosures: Dr. Robinson reported having no financial disclosures.
Prescribing the landmark hemangioma drug: The challenges and the benefits
For Beth Drolet, MD, a pediatric dermatologist in Wisconsin, the tremendous impact oral propranolol has had on the treatment of severe infantile hemangioma is written on the faces of children diagnosed with the condition in recent years.
“You can tell which drugs the kids were on by their age,” said Dr. Drolet, professor of dermatology and pediatrics at the Medical College of Wisconsin, Milwaukee. “If they were born before 2008, before we used this medication, those kids have had multiple surgeries and are still not looking that good. But we rarely see that in the kids born after.”
Still, it is possible for dermatologists to successfully treat their smallest patients with oral propranolol, according to Dr. Drolet and Ilona J. Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco.
In interviews, the two pediatric dermatologists spoke about the challenges and benefits of treating hemangioma patients with oral propranolol solution, which was approved by the Food and Drug Administration in 2014 for “proliferating infantile hemangioma requiring systemic therapy.” It is the only FDA-approved systemic treatment for this indication.
The oral form of the drug was used off label to treat patients with hemangioma after a French dermatologist discovered in 2007 that it could effectively treat the condition. A topical form of propranolol is also used for hemangiomas that do not require systemic treatment.
Prior to about a decade ago, Dr. Drolet said, steroids were used to treat severe hemangiomas with limited success.
In general, infantile hemangiomas “have a natural course of gradually involuting even without treatment,” Dr. Frieden noted. But the most severe cases can produce functional impairment, scarring, and anatomic distortion.
Dr. Drolet said she considers treatment if hemangioma threatens a vital function (hearing, sight, breathing) or can lead to pain, infection, or scarring.
One challenge for dermatologists is that standard of care treatment with oral propranolol requires in-office cardiac monitoring, especially as the dose is increased over the first week or two of treatment.
“I don’t think most dermatologists are comfortable taking a heart rate and blood pressure in an infant,” said Dr. Drolet, who is director of the birthmarks and vascular anomalies section at Children’s Hospital of Wisconsin, Milwaukee. Instead, they tend to refer patients to a pediatrician or pediatric cardiologist.
Her clinic hired a cardiac nurse to train the staff in how to take heart rate and blood pressure in babies. “Partnering with cardiology was really important for us,” she commented. “We worked really closely with our pediatric cardiology team to gain that expertise for our staff to assess that. You have to be pretty comfortable with it. If you’re not, you’re going to have to find someone else.”
Another option for dermatologists, Dr. Frieden said, is to focus on heart rate alone since blood pressure in infants is difficult to measure. “It’s not FDA sanctioned, but many people seem to do that and it’s OK,” she said.
Dr. Frieden and Dr. Drolet provided the following recommendations about treating babies with oral propranolol:
• Caution parents about side effects. Cardiac side effects have been “extraordinarily rare,” Dr. Drolet said. “We have seen problems with wheezing and, very rarely, severe hypoglycemia,” which can be prevented by educating the family. While it’s uncommon for the medication alone to produce wheezing, this may occur when a respiratory infection and propranolol combine to stress the body, she noted.
In some cases, physicians prescribe albuterol for wheezing without realizing that it will interact with propranolol, she added. “One is a beta-blocker, and the other is a beta-antagonist. They completely cancel each other out.”
To prevent hypoglycemia, Dr. Frieden said she recommends that children be fed every 6 hours if they’re under 6 months old or every 8 hours if they’re over 6 months of age. And Dr. Drolet said she advises parents to stop propranolol when their infants are sick.
A major focus of an educational video provided by Dr. Drolet’s clinic is advising parents “to stop the medication if the infant is not eating regularly, vomiting, or has diarrhea. It interferes with how you respond to low blood sugar if you’re not eating,” she said. “That surprised us. Now that we’ve been teaching parents about when to call us, that’s been pretty preventable.”
Minor side effects include cold hands and feet and sleep disturbances such as sleepiness and apparent nightmares, Dr. Frieden pointed out.
• Monitor guidelines regarding safety and protocols. “Over time, we’re getting more and more expertise,” Dr. Drolet said. For example, her clinic no longer performs ECGs on babies who take the medication because research has suggested they are not needed.
• Spend time developing an education program for parents. Dr. Drolet’s clinic provides the educational video to teach parents about how oral propranolol is used. “We haven’t done that for any other drugs,” she said. “But we want to make sure we aren’t overdosing it. We’ve been very careful about our parent education to prevent that.”
Guidelines on the diagnosis and management of infantile hemangioma were published in 2015 in Pediatrics (2015 Oct;136[4]:e1060-104).
Dr. Frieden has consulted for Pierre Fabre Dermatologie, the manufacturer of the oral propranolol product, marketed as Hemangeol. Dr. Drolet has received an investigator-initiated grant from the company.
For Beth Drolet, MD, a pediatric dermatologist in Wisconsin, the tremendous impact oral propranolol has had on the treatment of severe infantile hemangioma is written on the faces of children diagnosed with the condition in recent years.
“You can tell which drugs the kids were on by their age,” said Dr. Drolet, professor of dermatology and pediatrics at the Medical College of Wisconsin, Milwaukee. “If they were born before 2008, before we used this medication, those kids have had multiple surgeries and are still not looking that good. But we rarely see that in the kids born after.”
Still, it is possible for dermatologists to successfully treat their smallest patients with oral propranolol, according to Dr. Drolet and Ilona J. Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco.
In interviews, the two pediatric dermatologists spoke about the challenges and benefits of treating hemangioma patients with oral propranolol solution, which was approved by the Food and Drug Administration in 2014 for “proliferating infantile hemangioma requiring systemic therapy.” It is the only FDA-approved systemic treatment for this indication.
The oral form of the drug was used off label to treat patients with hemangioma after a French dermatologist discovered in 2007 that it could effectively treat the condition. A topical form of propranolol is also used for hemangiomas that do not require systemic treatment.
Prior to about a decade ago, Dr. Drolet said, steroids were used to treat severe hemangiomas with limited success.
In general, infantile hemangiomas “have a natural course of gradually involuting even without treatment,” Dr. Frieden noted. But the most severe cases can produce functional impairment, scarring, and anatomic distortion.
Dr. Drolet said she considers treatment if hemangioma threatens a vital function (hearing, sight, breathing) or can lead to pain, infection, or scarring.
One challenge for dermatologists is that standard of care treatment with oral propranolol requires in-office cardiac monitoring, especially as the dose is increased over the first week or two of treatment.
“I don’t think most dermatologists are comfortable taking a heart rate and blood pressure in an infant,” said Dr. Drolet, who is director of the birthmarks and vascular anomalies section at Children’s Hospital of Wisconsin, Milwaukee. Instead, they tend to refer patients to a pediatrician or pediatric cardiologist.
Her clinic hired a cardiac nurse to train the staff in how to take heart rate and blood pressure in babies. “Partnering with cardiology was really important for us,” she commented. “We worked really closely with our pediatric cardiology team to gain that expertise for our staff to assess that. You have to be pretty comfortable with it. If you’re not, you’re going to have to find someone else.”
Another option for dermatologists, Dr. Frieden said, is to focus on heart rate alone since blood pressure in infants is difficult to measure. “It’s not FDA sanctioned, but many people seem to do that and it’s OK,” she said.
Dr. Frieden and Dr. Drolet provided the following recommendations about treating babies with oral propranolol:
• Caution parents about side effects. Cardiac side effects have been “extraordinarily rare,” Dr. Drolet said. “We have seen problems with wheezing and, very rarely, severe hypoglycemia,” which can be prevented by educating the family. While it’s uncommon for the medication alone to produce wheezing, this may occur when a respiratory infection and propranolol combine to stress the body, she noted.
In some cases, physicians prescribe albuterol for wheezing without realizing that it will interact with propranolol, she added. “One is a beta-blocker, and the other is a beta-antagonist. They completely cancel each other out.”
To prevent hypoglycemia, Dr. Frieden said she recommends that children be fed every 6 hours if they’re under 6 months old or every 8 hours if they’re over 6 months of age. And Dr. Drolet said she advises parents to stop propranolol when their infants are sick.
A major focus of an educational video provided by Dr. Drolet’s clinic is advising parents “to stop the medication if the infant is not eating regularly, vomiting, or has diarrhea. It interferes with how you respond to low blood sugar if you’re not eating,” she said. “That surprised us. Now that we’ve been teaching parents about when to call us, that’s been pretty preventable.”
Minor side effects include cold hands and feet and sleep disturbances such as sleepiness and apparent nightmares, Dr. Frieden pointed out.
• Monitor guidelines regarding safety and protocols. “Over time, we’re getting more and more expertise,” Dr. Drolet said. For example, her clinic no longer performs ECGs on babies who take the medication because research has suggested they are not needed.
• Spend time developing an education program for parents. Dr. Drolet’s clinic provides the educational video to teach parents about how oral propranolol is used. “We haven’t done that for any other drugs,” she said. “But we want to make sure we aren’t overdosing it. We’ve been very careful about our parent education to prevent that.”
Guidelines on the diagnosis and management of infantile hemangioma were published in 2015 in Pediatrics (2015 Oct;136[4]:e1060-104).
Dr. Frieden has consulted for Pierre Fabre Dermatologie, the manufacturer of the oral propranolol product, marketed as Hemangeol. Dr. Drolet has received an investigator-initiated grant from the company.
For Beth Drolet, MD, a pediatric dermatologist in Wisconsin, the tremendous impact oral propranolol has had on the treatment of severe infantile hemangioma is written on the faces of children diagnosed with the condition in recent years.
“You can tell which drugs the kids were on by their age,” said Dr. Drolet, professor of dermatology and pediatrics at the Medical College of Wisconsin, Milwaukee. “If they were born before 2008, before we used this medication, those kids have had multiple surgeries and are still not looking that good. But we rarely see that in the kids born after.”
Still, it is possible for dermatologists to successfully treat their smallest patients with oral propranolol, according to Dr. Drolet and Ilona J. Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco.
In interviews, the two pediatric dermatologists spoke about the challenges and benefits of treating hemangioma patients with oral propranolol solution, which was approved by the Food and Drug Administration in 2014 for “proliferating infantile hemangioma requiring systemic therapy.” It is the only FDA-approved systemic treatment for this indication.
The oral form of the drug was used off label to treat patients with hemangioma after a French dermatologist discovered in 2007 that it could effectively treat the condition. A topical form of propranolol is also used for hemangiomas that do not require systemic treatment.
Prior to about a decade ago, Dr. Drolet said, steroids were used to treat severe hemangiomas with limited success.
In general, infantile hemangiomas “have a natural course of gradually involuting even without treatment,” Dr. Frieden noted. But the most severe cases can produce functional impairment, scarring, and anatomic distortion.
Dr. Drolet said she considers treatment if hemangioma threatens a vital function (hearing, sight, breathing) or can lead to pain, infection, or scarring.
One challenge for dermatologists is that standard of care treatment with oral propranolol requires in-office cardiac monitoring, especially as the dose is increased over the first week or two of treatment.
“I don’t think most dermatologists are comfortable taking a heart rate and blood pressure in an infant,” said Dr. Drolet, who is director of the birthmarks and vascular anomalies section at Children’s Hospital of Wisconsin, Milwaukee. Instead, they tend to refer patients to a pediatrician or pediatric cardiologist.
Her clinic hired a cardiac nurse to train the staff in how to take heart rate and blood pressure in babies. “Partnering with cardiology was really important for us,” she commented. “We worked really closely with our pediatric cardiology team to gain that expertise for our staff to assess that. You have to be pretty comfortable with it. If you’re not, you’re going to have to find someone else.”
Another option for dermatologists, Dr. Frieden said, is to focus on heart rate alone since blood pressure in infants is difficult to measure. “It’s not FDA sanctioned, but many people seem to do that and it’s OK,” she said.
Dr. Frieden and Dr. Drolet provided the following recommendations about treating babies with oral propranolol:
• Caution parents about side effects. Cardiac side effects have been “extraordinarily rare,” Dr. Drolet said. “We have seen problems with wheezing and, very rarely, severe hypoglycemia,” which can be prevented by educating the family. While it’s uncommon for the medication alone to produce wheezing, this may occur when a respiratory infection and propranolol combine to stress the body, she noted.
In some cases, physicians prescribe albuterol for wheezing without realizing that it will interact with propranolol, she added. “One is a beta-blocker, and the other is a beta-antagonist. They completely cancel each other out.”
To prevent hypoglycemia, Dr. Frieden said she recommends that children be fed every 6 hours if they’re under 6 months old or every 8 hours if they’re over 6 months of age. And Dr. Drolet said she advises parents to stop propranolol when their infants are sick.
A major focus of an educational video provided by Dr. Drolet’s clinic is advising parents “to stop the medication if the infant is not eating regularly, vomiting, or has diarrhea. It interferes with how you respond to low blood sugar if you’re not eating,” she said. “That surprised us. Now that we’ve been teaching parents about when to call us, that’s been pretty preventable.”
Minor side effects include cold hands and feet and sleep disturbances such as sleepiness and apparent nightmares, Dr. Frieden pointed out.
• Monitor guidelines regarding safety and protocols. “Over time, we’re getting more and more expertise,” Dr. Drolet said. For example, her clinic no longer performs ECGs on babies who take the medication because research has suggested they are not needed.
• Spend time developing an education program for parents. Dr. Drolet’s clinic provides the educational video to teach parents about how oral propranolol is used. “We haven’t done that for any other drugs,” she said. “But we want to make sure we aren’t overdosing it. We’ve been very careful about our parent education to prevent that.”
Guidelines on the diagnosis and management of infantile hemangioma were published in 2015 in Pediatrics (2015 Oct;136[4]:e1060-104).
Dr. Frieden has consulted for Pierre Fabre Dermatologie, the manufacturer of the oral propranolol product, marketed as Hemangeol. Dr. Drolet has received an investigator-initiated grant from the company.