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EMA gives green light to new CAR T-cell therapy
At its late January meeting, the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended for approval lisocabtagene maraleucel (Breyanzi, Bristol-Myers Squibb). This chimeric antigen receptor T-cell therapy is indicated for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), and follicular lymphoma grade 3B (FL3B). The indication is for use in patients who have received at least two lines of treatment.
The benefits of lisocabtagene maraleucel, noted the CHMP, are its ability to provide high and durable responses in patients with relapsed or refractory DLBCL, PMBCL, and FL3B. The most common side effects reported are neutropenia, anemia, cytokine release syndrome, fatigue, and thrombocytopenia.
The product is already approved in the United States for the same indication. The Food and Drug Administration’s approval came with a Risk Evaluation and Mitigation Strategy because of the risk for serious adverse events, including cytokine release syndrome.
During development, it was designated as an orphan medicine. The EMA will now review the information available to date to determine if the orphan designation can be maintained.
Biosimilar pegfilgrastim
At the same meeting, the committee recommended approval of a biosimilar product for pegfilgrastim (Stimufend, Fresenius Kabi Deutschland), which is used to reduce the duration of neutropenia and the incidence of febrile neutropenia after cytotoxic chemotherapy.
The committee noted that this product has been shown to be highly similar to the reference product Neulasta (pegfilgrastim), which has been available in the EU for 2 decades (authorized in 2002). Data have demonstrated that Stimufend has comparable quality, safety, and efficacy to Neulasta.
Its full indication is to reduce the duration of neutropenia and incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancies, with the exception of chronic myeloid leukemia (CML) and myelodysplastic syndromes.
Generic versions of dasatinib
Also recommended for approval were for two generic formulations of dasatinib (Dasatinib Accord and Dasatinib Accordpharma, both from Accord Healthcare) for the treatment of various leukemias.
These are generic versions of dasatinib (Sprycel), which has been available in the European Union since 2006.
The CHMP noted that studies have demonstrated the satisfactory quality of Dasatinib Accord, as well as its bioequivalence to the reference product. This generic is indicated for the treatment of adult patients with Philadelphia chromosome–positive acute lymphoblastic leukemia with resistance or intolerance to prior therapy and pediatric patients with newly diagnosed Ph+ ALL in combination with chemotherapy.
Dasatinib Accordpharma has a wider set of indications, which include the treatment of adult patients with newly diagnosed Ph+ CML in the chronic phase; chronic, accelerated, or blast phase CML with resistance or intolerance to prior therapy including imatinib; and Ph+ ALL and lymphoid blast CML with resistance or intolerance to prior therapy. In addition, this generic is indicated for the treatment of pediatric patients with newly diagnosed Ph+ CML in the chronic phase or Ph+ CML-CP resistant or intolerant to prior therapy including imatinib and newly diagnosed Ph+ ALL in combination with chemotherapy.
A version of this article first appeared on Medscape.com.
At its late January meeting, the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended for approval lisocabtagene maraleucel (Breyanzi, Bristol-Myers Squibb). This chimeric antigen receptor T-cell therapy is indicated for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), and follicular lymphoma grade 3B (FL3B). The indication is for use in patients who have received at least two lines of treatment.
The benefits of lisocabtagene maraleucel, noted the CHMP, are its ability to provide high and durable responses in patients with relapsed or refractory DLBCL, PMBCL, and FL3B. The most common side effects reported are neutropenia, anemia, cytokine release syndrome, fatigue, and thrombocytopenia.
The product is already approved in the United States for the same indication. The Food and Drug Administration’s approval came with a Risk Evaluation and Mitigation Strategy because of the risk for serious adverse events, including cytokine release syndrome.
During development, it was designated as an orphan medicine. The EMA will now review the information available to date to determine if the orphan designation can be maintained.
Biosimilar pegfilgrastim
At the same meeting, the committee recommended approval of a biosimilar product for pegfilgrastim (Stimufend, Fresenius Kabi Deutschland), which is used to reduce the duration of neutropenia and the incidence of febrile neutropenia after cytotoxic chemotherapy.
The committee noted that this product has been shown to be highly similar to the reference product Neulasta (pegfilgrastim), which has been available in the EU for 2 decades (authorized in 2002). Data have demonstrated that Stimufend has comparable quality, safety, and efficacy to Neulasta.
Its full indication is to reduce the duration of neutropenia and incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancies, with the exception of chronic myeloid leukemia (CML) and myelodysplastic syndromes.
Generic versions of dasatinib
Also recommended for approval were for two generic formulations of dasatinib (Dasatinib Accord and Dasatinib Accordpharma, both from Accord Healthcare) for the treatment of various leukemias.
These are generic versions of dasatinib (Sprycel), which has been available in the European Union since 2006.
The CHMP noted that studies have demonstrated the satisfactory quality of Dasatinib Accord, as well as its bioequivalence to the reference product. This generic is indicated for the treatment of adult patients with Philadelphia chromosome–positive acute lymphoblastic leukemia with resistance or intolerance to prior therapy and pediatric patients with newly diagnosed Ph+ ALL in combination with chemotherapy.
Dasatinib Accordpharma has a wider set of indications, which include the treatment of adult patients with newly diagnosed Ph+ CML in the chronic phase; chronic, accelerated, or blast phase CML with resistance or intolerance to prior therapy including imatinib; and Ph+ ALL and lymphoid blast CML with resistance or intolerance to prior therapy. In addition, this generic is indicated for the treatment of pediatric patients with newly diagnosed Ph+ CML in the chronic phase or Ph+ CML-CP resistant or intolerant to prior therapy including imatinib and newly diagnosed Ph+ ALL in combination with chemotherapy.
A version of this article first appeared on Medscape.com.
At its late January meeting, the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended for approval lisocabtagene maraleucel (Breyanzi, Bristol-Myers Squibb). This chimeric antigen receptor T-cell therapy is indicated for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), and follicular lymphoma grade 3B (FL3B). The indication is for use in patients who have received at least two lines of treatment.
The benefits of lisocabtagene maraleucel, noted the CHMP, are its ability to provide high and durable responses in patients with relapsed or refractory DLBCL, PMBCL, and FL3B. The most common side effects reported are neutropenia, anemia, cytokine release syndrome, fatigue, and thrombocytopenia.
The product is already approved in the United States for the same indication. The Food and Drug Administration’s approval came with a Risk Evaluation and Mitigation Strategy because of the risk for serious adverse events, including cytokine release syndrome.
During development, it was designated as an orphan medicine. The EMA will now review the information available to date to determine if the orphan designation can be maintained.
Biosimilar pegfilgrastim
At the same meeting, the committee recommended approval of a biosimilar product for pegfilgrastim (Stimufend, Fresenius Kabi Deutschland), which is used to reduce the duration of neutropenia and the incidence of febrile neutropenia after cytotoxic chemotherapy.
The committee noted that this product has been shown to be highly similar to the reference product Neulasta (pegfilgrastim), which has been available in the EU for 2 decades (authorized in 2002). Data have demonstrated that Stimufend has comparable quality, safety, and efficacy to Neulasta.
Its full indication is to reduce the duration of neutropenia and incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancies, with the exception of chronic myeloid leukemia (CML) and myelodysplastic syndromes.
Generic versions of dasatinib
Also recommended for approval were for two generic formulations of dasatinib (Dasatinib Accord and Dasatinib Accordpharma, both from Accord Healthcare) for the treatment of various leukemias.
These are generic versions of dasatinib (Sprycel), which has been available in the European Union since 2006.
The CHMP noted that studies have demonstrated the satisfactory quality of Dasatinib Accord, as well as its bioequivalence to the reference product. This generic is indicated for the treatment of adult patients with Philadelphia chromosome–positive acute lymphoblastic leukemia with resistance or intolerance to prior therapy and pediatric patients with newly diagnosed Ph+ ALL in combination with chemotherapy.
Dasatinib Accordpharma has a wider set of indications, which include the treatment of adult patients with newly diagnosed Ph+ CML in the chronic phase; chronic, accelerated, or blast phase CML with resistance or intolerance to prior therapy including imatinib; and Ph+ ALL and lymphoid blast CML with resistance or intolerance to prior therapy. In addition, this generic is indicated for the treatment of pediatric patients with newly diagnosed Ph+ CML in the chronic phase or Ph+ CML-CP resistant or intolerant to prior therapy including imatinib and newly diagnosed Ph+ ALL in combination with chemotherapy.
A version of this article first appeared on Medscape.com.
Global pediatric oncology workforce hit hard, but resilient amid pandemic
according to a study that surveyed workers from more than 200 institutions in 79 countries.
A snapshot of the extensive findings reveals that half of participating institutions experienced staffing shortages that had a “major impact” on pediatric cancer care. On the financial front, many respondents pointed to instances of unpaid leave and diminished salary, and others highlighted the psychological toll of providing care, including high rates of burnout and stress. The challenges were evident across high- and low-income countries.
Despite these barriers, pediatric oncology clinicians demonstrated incredible perseverance.
Health care professionals “caring for children with cancer across the world were shown to be incredibly resilient, coming together to continue to provide care even in the direst circumstances,” Elizabeth R. Sniderman, MSN, APRN, of St. Jude Children’s Research Hospital, Memphis, and colleagues concluded.
The findings, published online Jan. 24, 2022, in Cancer, highlight the global impact of COVID-19 on pediatric oncology clinicians early in the pandemic.
The survey, conducted in summer 2020, included responses from 311 pediatric oncology clinicians who completed a 60-item questionnaire about their experiences of clinical care, resources, and support. The investigators also convened 19 multidisciplinary focus groups who answered questions related to teamwork, communication, and changes to care. Respondents practiced in low- to high-income countries, and included pediatric hematologists and oncologists, nurses, and infectious disease physicians.
Overall, the investigators found that just over half of institutions experienced “major” shortages of clinical staff (108 of 213), and two-thirds experienced reductions in staffing availability (141 of 213). Notably, national income was not associated with this reduction; rather, staffing shortages were more likely to occur in countries with greater COVID-19 incidence and mortality rates.
Respondents reported experiencing threats to their physical health, with half pointing to a lack of necessary personal protective equipment. The financial and psychological toll of the pandemic represented another major stressor, with the effects described across all income levels.
One respondent from Belarus commented on financial concerns, noting that “people don’t really want to admit that they don’t feel well ... they know, that if infected, unpaid self-isolation is waiting for them. Either you don’t go to work for 2 weeks, unpaid, or you go to work for 2 weeks, paid, and endanger all of your colleagues with your infection.”
A respondent from Mexico described the psychological stress: “Honestly, I think that sometimes we put aside the mental health of all of us involved, myself included. I think we were all on the verge of collapse ... practically all the residents who were rotating here told us that they had anxiety attacks, panic attacks, they could not sleep, [and] many of them needed psychiatric medicine.”
Others highlighted feelings of guilt about their ability to provide the highest level of care. An oncologist in the United States noted: “This was a major stress for many providers because [we are] feeling unable to provide the same level of care which we used to provide. And this is what eventually takes a toll.”
And despite these pandemic-related challenges, the study authors found that only 46% of institutions (99 of 213) made psychological support available to staff.
Rays of hope
But it was not all bad news.
Participants also described a greater sense of teamwork, communication, and collegiality throughout the pandemic – “stabilizing elements,” which helped mitigate the many physical, psychological, and financial stressors.
An infection-control physician in Belarus highlighted the importance of receiving “support and encouragement” from colleagues: “When a person gets tired and they have no more enthusiasm, it’s easy to give up and say: ‘I can’t do this anymore.’ But when you see a colleague who tries ... to share the work, and help each other, then you get extra strength.”
An oncologist in South Africa agreed, noting that “everyone has got their sleeves rolled up and are doing the work ... and that’s a testament to everyone that we work with. There was no one that shied away from work or used this as an excuse to do less work.”
An oncologist in Spain described practicing during the pandemic being “one of the best experiences I have had,” explaining that “I have been working in this hospital for ... 25 years, [and] I have never had the feeling of being so informed at all levels.”
Overall, the findings paint a picture of a resilient workforce, and offer lessons about preparedness for future crises, the investigators concluded.
“To protect pediatric oncology providers and their patients, organizations must pay attention to interventions that increase physical, psychological, and financial safety,” the authors stressed. For instance, providing adequate personal protective equipment and vaccines, allowing for time off and rest, and setting up professional psychology services as well as access to peer-support programs can help protect staff.
Although this survey took place relatively early in the pandemic, organizations should take heed of the findings, Lorena V. Baroni, MD, of Hospital J P Garrahan, Buenos Aires, and Eric Bouffet, MD, of The Hospital for Sick Children, Toronto, wrote in an accompanying editorial.
“The results presented in this study should not be taken lightly,” Dr. Baroni and Dr. Bouffet wrote. “The most concerning findings are the physical and psychological impact experienced by pediatric oncology providers.” And perhaps most surprisingly, “the survey did not identify any difference based on country income groups. Participants in both low- and high-income countries described similar oncologic care limitations.”
Overall, these findings “reflect a serious risk that can ultimately affect the care of children and compromise the success of their treatment,” Dr. Baroni and Dr. Bouffet wrote.
This study was supported by the American Lebanese Syrian Associated Charities. The study authors and editorialists have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a study that surveyed workers from more than 200 institutions in 79 countries.
A snapshot of the extensive findings reveals that half of participating institutions experienced staffing shortages that had a “major impact” on pediatric cancer care. On the financial front, many respondents pointed to instances of unpaid leave and diminished salary, and others highlighted the psychological toll of providing care, including high rates of burnout and stress. The challenges were evident across high- and low-income countries.
Despite these barriers, pediatric oncology clinicians demonstrated incredible perseverance.
Health care professionals “caring for children with cancer across the world were shown to be incredibly resilient, coming together to continue to provide care even in the direst circumstances,” Elizabeth R. Sniderman, MSN, APRN, of St. Jude Children’s Research Hospital, Memphis, and colleagues concluded.
The findings, published online Jan. 24, 2022, in Cancer, highlight the global impact of COVID-19 on pediatric oncology clinicians early in the pandemic.
The survey, conducted in summer 2020, included responses from 311 pediatric oncology clinicians who completed a 60-item questionnaire about their experiences of clinical care, resources, and support. The investigators also convened 19 multidisciplinary focus groups who answered questions related to teamwork, communication, and changes to care. Respondents practiced in low- to high-income countries, and included pediatric hematologists and oncologists, nurses, and infectious disease physicians.
Overall, the investigators found that just over half of institutions experienced “major” shortages of clinical staff (108 of 213), and two-thirds experienced reductions in staffing availability (141 of 213). Notably, national income was not associated with this reduction; rather, staffing shortages were more likely to occur in countries with greater COVID-19 incidence and mortality rates.
Respondents reported experiencing threats to their physical health, with half pointing to a lack of necessary personal protective equipment. The financial and psychological toll of the pandemic represented another major stressor, with the effects described across all income levels.
One respondent from Belarus commented on financial concerns, noting that “people don’t really want to admit that they don’t feel well ... they know, that if infected, unpaid self-isolation is waiting for them. Either you don’t go to work for 2 weeks, unpaid, or you go to work for 2 weeks, paid, and endanger all of your colleagues with your infection.”
A respondent from Mexico described the psychological stress: “Honestly, I think that sometimes we put aside the mental health of all of us involved, myself included. I think we were all on the verge of collapse ... practically all the residents who were rotating here told us that they had anxiety attacks, panic attacks, they could not sleep, [and] many of them needed psychiatric medicine.”
Others highlighted feelings of guilt about their ability to provide the highest level of care. An oncologist in the United States noted: “This was a major stress for many providers because [we are] feeling unable to provide the same level of care which we used to provide. And this is what eventually takes a toll.”
And despite these pandemic-related challenges, the study authors found that only 46% of institutions (99 of 213) made psychological support available to staff.
Rays of hope
But it was not all bad news.
Participants also described a greater sense of teamwork, communication, and collegiality throughout the pandemic – “stabilizing elements,” which helped mitigate the many physical, psychological, and financial stressors.
An infection-control physician in Belarus highlighted the importance of receiving “support and encouragement” from colleagues: “When a person gets tired and they have no more enthusiasm, it’s easy to give up and say: ‘I can’t do this anymore.’ But when you see a colleague who tries ... to share the work, and help each other, then you get extra strength.”
An oncologist in South Africa agreed, noting that “everyone has got their sleeves rolled up and are doing the work ... and that’s a testament to everyone that we work with. There was no one that shied away from work or used this as an excuse to do less work.”
An oncologist in Spain described practicing during the pandemic being “one of the best experiences I have had,” explaining that “I have been working in this hospital for ... 25 years, [and] I have never had the feeling of being so informed at all levels.”
Overall, the findings paint a picture of a resilient workforce, and offer lessons about preparedness for future crises, the investigators concluded.
“To protect pediatric oncology providers and their patients, organizations must pay attention to interventions that increase physical, psychological, and financial safety,” the authors stressed. For instance, providing adequate personal protective equipment and vaccines, allowing for time off and rest, and setting up professional psychology services as well as access to peer-support programs can help protect staff.
Although this survey took place relatively early in the pandemic, organizations should take heed of the findings, Lorena V. Baroni, MD, of Hospital J P Garrahan, Buenos Aires, and Eric Bouffet, MD, of The Hospital for Sick Children, Toronto, wrote in an accompanying editorial.
“The results presented in this study should not be taken lightly,” Dr. Baroni and Dr. Bouffet wrote. “The most concerning findings are the physical and psychological impact experienced by pediatric oncology providers.” And perhaps most surprisingly, “the survey did not identify any difference based on country income groups. Participants in both low- and high-income countries described similar oncologic care limitations.”
Overall, these findings “reflect a serious risk that can ultimately affect the care of children and compromise the success of their treatment,” Dr. Baroni and Dr. Bouffet wrote.
This study was supported by the American Lebanese Syrian Associated Charities. The study authors and editorialists have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a study that surveyed workers from more than 200 institutions in 79 countries.
A snapshot of the extensive findings reveals that half of participating institutions experienced staffing shortages that had a “major impact” on pediatric cancer care. On the financial front, many respondents pointed to instances of unpaid leave and diminished salary, and others highlighted the psychological toll of providing care, including high rates of burnout and stress. The challenges were evident across high- and low-income countries.
Despite these barriers, pediatric oncology clinicians demonstrated incredible perseverance.
Health care professionals “caring for children with cancer across the world were shown to be incredibly resilient, coming together to continue to provide care even in the direst circumstances,” Elizabeth R. Sniderman, MSN, APRN, of St. Jude Children’s Research Hospital, Memphis, and colleagues concluded.
The findings, published online Jan. 24, 2022, in Cancer, highlight the global impact of COVID-19 on pediatric oncology clinicians early in the pandemic.
The survey, conducted in summer 2020, included responses from 311 pediatric oncology clinicians who completed a 60-item questionnaire about their experiences of clinical care, resources, and support. The investigators also convened 19 multidisciplinary focus groups who answered questions related to teamwork, communication, and changes to care. Respondents practiced in low- to high-income countries, and included pediatric hematologists and oncologists, nurses, and infectious disease physicians.
Overall, the investigators found that just over half of institutions experienced “major” shortages of clinical staff (108 of 213), and two-thirds experienced reductions in staffing availability (141 of 213). Notably, national income was not associated with this reduction; rather, staffing shortages were more likely to occur in countries with greater COVID-19 incidence and mortality rates.
Respondents reported experiencing threats to their physical health, with half pointing to a lack of necessary personal protective equipment. The financial and psychological toll of the pandemic represented another major stressor, with the effects described across all income levels.
One respondent from Belarus commented on financial concerns, noting that “people don’t really want to admit that they don’t feel well ... they know, that if infected, unpaid self-isolation is waiting for them. Either you don’t go to work for 2 weeks, unpaid, or you go to work for 2 weeks, paid, and endanger all of your colleagues with your infection.”
A respondent from Mexico described the psychological stress: “Honestly, I think that sometimes we put aside the mental health of all of us involved, myself included. I think we were all on the verge of collapse ... practically all the residents who were rotating here told us that they had anxiety attacks, panic attacks, they could not sleep, [and] many of them needed psychiatric medicine.”
Others highlighted feelings of guilt about their ability to provide the highest level of care. An oncologist in the United States noted: “This was a major stress for many providers because [we are] feeling unable to provide the same level of care which we used to provide. And this is what eventually takes a toll.”
And despite these pandemic-related challenges, the study authors found that only 46% of institutions (99 of 213) made psychological support available to staff.
Rays of hope
But it was not all bad news.
Participants also described a greater sense of teamwork, communication, and collegiality throughout the pandemic – “stabilizing elements,” which helped mitigate the many physical, psychological, and financial stressors.
An infection-control physician in Belarus highlighted the importance of receiving “support and encouragement” from colleagues: “When a person gets tired and they have no more enthusiasm, it’s easy to give up and say: ‘I can’t do this anymore.’ But when you see a colleague who tries ... to share the work, and help each other, then you get extra strength.”
An oncologist in South Africa agreed, noting that “everyone has got their sleeves rolled up and are doing the work ... and that’s a testament to everyone that we work with. There was no one that shied away from work or used this as an excuse to do less work.”
An oncologist in Spain described practicing during the pandemic being “one of the best experiences I have had,” explaining that “I have been working in this hospital for ... 25 years, [and] I have never had the feeling of being so informed at all levels.”
Overall, the findings paint a picture of a resilient workforce, and offer lessons about preparedness for future crises, the investigators concluded.
“To protect pediatric oncology providers and their patients, organizations must pay attention to interventions that increase physical, psychological, and financial safety,” the authors stressed. For instance, providing adequate personal protective equipment and vaccines, allowing for time off and rest, and setting up professional psychology services as well as access to peer-support programs can help protect staff.
Although this survey took place relatively early in the pandemic, organizations should take heed of the findings, Lorena V. Baroni, MD, of Hospital J P Garrahan, Buenos Aires, and Eric Bouffet, MD, of The Hospital for Sick Children, Toronto, wrote in an accompanying editorial.
“The results presented in this study should not be taken lightly,” Dr. Baroni and Dr. Bouffet wrote. “The most concerning findings are the physical and psychological impact experienced by pediatric oncology providers.” And perhaps most surprisingly, “the survey did not identify any difference based on country income groups. Participants in both low- and high-income countries described similar oncologic care limitations.”
Overall, these findings “reflect a serious risk that can ultimately affect the care of children and compromise the success of their treatment,” Dr. Baroni and Dr. Bouffet wrote.
This study was supported by the American Lebanese Syrian Associated Charities. The study authors and editorialists have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CANCER
CLL patients ‘cured’: 10 years post infusion, CAR T cells persist
“We can now conclude that CAR T cells can actually cure patients with leukemia based on these results,” said senior author Carl H. June, MD, in a press briefing on the study published in Nature.
“The major finding from this paper is that, 10 years down the road, you can find these [CAR T] cells,” Dr. June, director of the Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, added. “The cells have evolved, and that was a big surprise ... but they are still able to kill leukemia cells 10 years after infusion.”
CAR T-cell therapy, in which patients’ own T cells are removed, reprogrammed in a lab to recognize and attack cancer cells, and then infused back into the patients, has transformed treatment of various blood cancers and shows often-remarkable results in achieving remissions.
While the treatment has become a routine therapy for certain leukemias, long-term results on the fate and function of the cells over time has been highly anticipated.
In the first published observations of a 10-year follow-up of patients treated with CAR T cells, Dr. June and colleagues described the findings for two patients, both with CLL, who back in 2010 were among the first to be treated with this groundbreaking therapy at the University of Pennsylvania.
A decade later, the CAR T cells are found to have remained detectable in both patients, who achieved complete remission in their first year of treatment, and both have sustained that remission.
Notably, the cells have evolved over the years – from initially being dominated by killer T cells to being dominated primarily by proliferative CD4-positive CAR T cells – with one of the patients exclusively having CD4-positive cells at year 9.3.
“The killer T cells did the initial heavy lifting of eliminating the tumor, “ first author J. Joseph Melenhorst, PhD, said in an interview.
“Once their job was done, those cells went down to very low levels, but the CD4-positive population persisted,” said Dr. Melenhorst, who established the lab at the University of Pennsylvania to follow patients treated with CAR T-cell therapy. “[This] delayed phase of immune response against cancer is a novel insight, and we were surprised to see it.”
Dr. Melenhorst noted that the clonal makeup of the CD4-positive cells importantly stabilized and became dominated by a small number of clones, suggesting further sustainability.
When one of the two patients, Doug Olson, who participated in the press conference, donated his cells back to the center after 9.3 years, the researchers found that his cells were still capable of destroying leukemia cells in the lab.
“Ten years [post infusion], we can’t find any of the leukemia cells and we still have the CAR T cells that are on patrol and on surveillance for residual leukemia,” Dr. June said.
One challenge of the otherwise desirable elimination of leukemia cells is that some aspects of sustaining CAR T-cell activity become problematic.
“The aspect of how the remission is maintained [is] very hard to study in a patient when there is no leukemia at all,” Dr. June explained. “It could be the last cell was gone within 3 weeks [of treatment], or it could be that the [cancer cells] are coming up like whack-a-moles, and they are killed because these CAR T cells are on patrol.”
Sadly, the other CLL patient, Bill Ludwig, who was first to receive the CAR T-cell treatment, died in 2021 from COVID-19.
Effects in other blood diseases similar?
CAR T-cell therapy is currently approved in the United States for several blood cancers, and whether similar long-term patterns of the cells may be observed in other patient and cancer types remains to be seen, Dr. Melenhorst said.
“I think in CLL we will see something similar, but in other diseases, we have yet to learn,” he said. “It may depend on issues including which domain has been engineered into the CAR.”
While the prospect of some patients being “cured” is exciting, responses to the therapy have generally been mixed. In CLL, for instance, full remissions have been observed to be maintained in about a quarter of patients, with higher rates observed in some lymphomas and pediatric ALL patients, Dr. Melenhorst explained.
The effects of CAR T-cell therapy in solid cancers have so far been more disappointing, with no research centers reproducing the kinds of results that have been seen with blood cancers.
“There appear to be a number of reasons, including that the [solid] tumor is more complex, and these solid cancers have ways to evade the immune system that need to be overcome,” Dr. June explained.
And despite the more encouraging findings in blood cancers, even with those, “the biggest disappointment is that CAR T-cell therapy doesn’t work all the time. It doesn’t work in every patient,” coauthor David Porter, MD, the University of Pennsylvania oncologist who treated the two patients, said in the press briefing.
“I think the importance of the Nature study is that we are starting to learn the mechanisms of why and how this works, so that we can start to get at how to make it work for more people,” Dr. Porter added. “But what we do see is that, when it works, it really is beyond what we expected 10 or 11 years ago.”
Speaking in the press briefing, Mr. Olson described how several weeks after his treatment in 2010, he became very ill with what has become known as the common, short-term side effect of cytokine release syndrome.
However, after Mr. Olson recovered a few days later, Dr. Porter gave him the remarkable news that “we cannot find a single cancer cell. You appear completely free of CLL.”
Mr. Olson reported that he has since lived a “full life,” kept working, and has even run some half-marathons.
Dr. June confided that the current 10-year results far exceed the team’s early expectations for CAR T-cell therapy. “After Doug [initially] signed his informed consent document for this, we thought that the cells would all be gone within a month or 2. The fact that they have survived for 10 years was a major surprise – and a happy one at that.”
Dr. June, Dr. Melenhorst, and Dr. Porter reported holding patents related to CAR T-cell manufacturing and biomarker discovery.
“We can now conclude that CAR T cells can actually cure patients with leukemia based on these results,” said senior author Carl H. June, MD, in a press briefing on the study published in Nature.
“The major finding from this paper is that, 10 years down the road, you can find these [CAR T] cells,” Dr. June, director of the Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, added. “The cells have evolved, and that was a big surprise ... but they are still able to kill leukemia cells 10 years after infusion.”
CAR T-cell therapy, in which patients’ own T cells are removed, reprogrammed in a lab to recognize and attack cancer cells, and then infused back into the patients, has transformed treatment of various blood cancers and shows often-remarkable results in achieving remissions.
While the treatment has become a routine therapy for certain leukemias, long-term results on the fate and function of the cells over time has been highly anticipated.
In the first published observations of a 10-year follow-up of patients treated with CAR T cells, Dr. June and colleagues described the findings for two patients, both with CLL, who back in 2010 were among the first to be treated with this groundbreaking therapy at the University of Pennsylvania.
A decade later, the CAR T cells are found to have remained detectable in both patients, who achieved complete remission in their first year of treatment, and both have sustained that remission.
Notably, the cells have evolved over the years – from initially being dominated by killer T cells to being dominated primarily by proliferative CD4-positive CAR T cells – with one of the patients exclusively having CD4-positive cells at year 9.3.
“The killer T cells did the initial heavy lifting of eliminating the tumor, “ first author J. Joseph Melenhorst, PhD, said in an interview.
“Once their job was done, those cells went down to very low levels, but the CD4-positive population persisted,” said Dr. Melenhorst, who established the lab at the University of Pennsylvania to follow patients treated with CAR T-cell therapy. “[This] delayed phase of immune response against cancer is a novel insight, and we were surprised to see it.”
Dr. Melenhorst noted that the clonal makeup of the CD4-positive cells importantly stabilized and became dominated by a small number of clones, suggesting further sustainability.
When one of the two patients, Doug Olson, who participated in the press conference, donated his cells back to the center after 9.3 years, the researchers found that his cells were still capable of destroying leukemia cells in the lab.
“Ten years [post infusion], we can’t find any of the leukemia cells and we still have the CAR T cells that are on patrol and on surveillance for residual leukemia,” Dr. June said.
One challenge of the otherwise desirable elimination of leukemia cells is that some aspects of sustaining CAR T-cell activity become problematic.
“The aspect of how the remission is maintained [is] very hard to study in a patient when there is no leukemia at all,” Dr. June explained. “It could be the last cell was gone within 3 weeks [of treatment], or it could be that the [cancer cells] are coming up like whack-a-moles, and they are killed because these CAR T cells are on patrol.”
Sadly, the other CLL patient, Bill Ludwig, who was first to receive the CAR T-cell treatment, died in 2021 from COVID-19.
Effects in other blood diseases similar?
CAR T-cell therapy is currently approved in the United States for several blood cancers, and whether similar long-term patterns of the cells may be observed in other patient and cancer types remains to be seen, Dr. Melenhorst said.
“I think in CLL we will see something similar, but in other diseases, we have yet to learn,” he said. “It may depend on issues including which domain has been engineered into the CAR.”
While the prospect of some patients being “cured” is exciting, responses to the therapy have generally been mixed. In CLL, for instance, full remissions have been observed to be maintained in about a quarter of patients, with higher rates observed in some lymphomas and pediatric ALL patients, Dr. Melenhorst explained.
The effects of CAR T-cell therapy in solid cancers have so far been more disappointing, with no research centers reproducing the kinds of results that have been seen with blood cancers.
“There appear to be a number of reasons, including that the [solid] tumor is more complex, and these solid cancers have ways to evade the immune system that need to be overcome,” Dr. June explained.
And despite the more encouraging findings in blood cancers, even with those, “the biggest disappointment is that CAR T-cell therapy doesn’t work all the time. It doesn’t work in every patient,” coauthor David Porter, MD, the University of Pennsylvania oncologist who treated the two patients, said in the press briefing.
“I think the importance of the Nature study is that we are starting to learn the mechanisms of why and how this works, so that we can start to get at how to make it work for more people,” Dr. Porter added. “But what we do see is that, when it works, it really is beyond what we expected 10 or 11 years ago.”
Speaking in the press briefing, Mr. Olson described how several weeks after his treatment in 2010, he became very ill with what has become known as the common, short-term side effect of cytokine release syndrome.
However, after Mr. Olson recovered a few days later, Dr. Porter gave him the remarkable news that “we cannot find a single cancer cell. You appear completely free of CLL.”
Mr. Olson reported that he has since lived a “full life,” kept working, and has even run some half-marathons.
Dr. June confided that the current 10-year results far exceed the team’s early expectations for CAR T-cell therapy. “After Doug [initially] signed his informed consent document for this, we thought that the cells would all be gone within a month or 2. The fact that they have survived for 10 years was a major surprise – and a happy one at that.”
Dr. June, Dr. Melenhorst, and Dr. Porter reported holding patents related to CAR T-cell manufacturing and biomarker discovery.
“We can now conclude that CAR T cells can actually cure patients with leukemia based on these results,” said senior author Carl H. June, MD, in a press briefing on the study published in Nature.
“The major finding from this paper is that, 10 years down the road, you can find these [CAR T] cells,” Dr. June, director of the Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, added. “The cells have evolved, and that was a big surprise ... but they are still able to kill leukemia cells 10 years after infusion.”
CAR T-cell therapy, in which patients’ own T cells are removed, reprogrammed in a lab to recognize and attack cancer cells, and then infused back into the patients, has transformed treatment of various blood cancers and shows often-remarkable results in achieving remissions.
While the treatment has become a routine therapy for certain leukemias, long-term results on the fate and function of the cells over time has been highly anticipated.
In the first published observations of a 10-year follow-up of patients treated with CAR T cells, Dr. June and colleagues described the findings for two patients, both with CLL, who back in 2010 were among the first to be treated with this groundbreaking therapy at the University of Pennsylvania.
A decade later, the CAR T cells are found to have remained detectable in both patients, who achieved complete remission in their first year of treatment, and both have sustained that remission.
Notably, the cells have evolved over the years – from initially being dominated by killer T cells to being dominated primarily by proliferative CD4-positive CAR T cells – with one of the patients exclusively having CD4-positive cells at year 9.3.
“The killer T cells did the initial heavy lifting of eliminating the tumor, “ first author J. Joseph Melenhorst, PhD, said in an interview.
“Once their job was done, those cells went down to very low levels, but the CD4-positive population persisted,” said Dr. Melenhorst, who established the lab at the University of Pennsylvania to follow patients treated with CAR T-cell therapy. “[This] delayed phase of immune response against cancer is a novel insight, and we were surprised to see it.”
Dr. Melenhorst noted that the clonal makeup of the CD4-positive cells importantly stabilized and became dominated by a small number of clones, suggesting further sustainability.
When one of the two patients, Doug Olson, who participated in the press conference, donated his cells back to the center after 9.3 years, the researchers found that his cells were still capable of destroying leukemia cells in the lab.
“Ten years [post infusion], we can’t find any of the leukemia cells and we still have the CAR T cells that are on patrol and on surveillance for residual leukemia,” Dr. June said.
One challenge of the otherwise desirable elimination of leukemia cells is that some aspects of sustaining CAR T-cell activity become problematic.
“The aspect of how the remission is maintained [is] very hard to study in a patient when there is no leukemia at all,” Dr. June explained. “It could be the last cell was gone within 3 weeks [of treatment], or it could be that the [cancer cells] are coming up like whack-a-moles, and they are killed because these CAR T cells are on patrol.”
Sadly, the other CLL patient, Bill Ludwig, who was first to receive the CAR T-cell treatment, died in 2021 from COVID-19.
Effects in other blood diseases similar?
CAR T-cell therapy is currently approved in the United States for several blood cancers, and whether similar long-term patterns of the cells may be observed in other patient and cancer types remains to be seen, Dr. Melenhorst said.
“I think in CLL we will see something similar, but in other diseases, we have yet to learn,” he said. “It may depend on issues including which domain has been engineered into the CAR.”
While the prospect of some patients being “cured” is exciting, responses to the therapy have generally been mixed. In CLL, for instance, full remissions have been observed to be maintained in about a quarter of patients, with higher rates observed in some lymphomas and pediatric ALL patients, Dr. Melenhorst explained.
The effects of CAR T-cell therapy in solid cancers have so far been more disappointing, with no research centers reproducing the kinds of results that have been seen with blood cancers.
“There appear to be a number of reasons, including that the [solid] tumor is more complex, and these solid cancers have ways to evade the immune system that need to be overcome,” Dr. June explained.
And despite the more encouraging findings in blood cancers, even with those, “the biggest disappointment is that CAR T-cell therapy doesn’t work all the time. It doesn’t work in every patient,” coauthor David Porter, MD, the University of Pennsylvania oncologist who treated the two patients, said in the press briefing.
“I think the importance of the Nature study is that we are starting to learn the mechanisms of why and how this works, so that we can start to get at how to make it work for more people,” Dr. Porter added. “But what we do see is that, when it works, it really is beyond what we expected 10 or 11 years ago.”
Speaking in the press briefing, Mr. Olson described how several weeks after his treatment in 2010, he became very ill with what has become known as the common, short-term side effect of cytokine release syndrome.
However, after Mr. Olson recovered a few days later, Dr. Porter gave him the remarkable news that “we cannot find a single cancer cell. You appear completely free of CLL.”
Mr. Olson reported that he has since lived a “full life,” kept working, and has even run some half-marathons.
Dr. June confided that the current 10-year results far exceed the team’s early expectations for CAR T-cell therapy. “After Doug [initially] signed his informed consent document for this, we thought that the cells would all be gone within a month or 2. The fact that they have survived for 10 years was a major surprise – and a happy one at that.”
Dr. June, Dr. Melenhorst, and Dr. Porter reported holding patents related to CAR T-cell manufacturing and biomarker discovery.
FROM NATURE
Yescarta label updated: Prophylactic steroids to prevent CRS
This is a chimeric antigen receptor T-cell product indicated for use in adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy.
The product label carries a black box warning that CRS is a potentially fatal complication. With the update, the new labeling advises clinicians to “consider the use of prophylactic corticosteroid in patients after weighing the potential benefits and risks ... to delay the onset and decrease the duration of CRS.”
However, labeling also notes that “prophylactic corticosteroids ... may result in [a] higher grade of neurologic toxicities or prolongation of neurologic toxicities,” another potentially fatal complication noted in the black box warning.
The addition of prophylactic corticosteroids to labeling was based on data from 39 patients with relapsed or refractory LBCL who received dexamethasone 10 mg orally once daily for 3 days starting prior to Yescarta infusion. In this cohort, 31 of the 39 patients (79%) developed CRS, at which point they were managed with tocilizumab and/or corticosteroids. No one developed grade 3 or higher CRS. The median time to CRS onset was 5 days and the median duration was 4 days, according to labeling.
In contrast, in another cohort of 41 patients who were started on tocilizumab and/or corticosteroids only after becoming symptomatic, the overall incidence of CRS was 93% (38/41), with a median onset at 2 days, median duration of 7 days, and two patients who developed grade 3 CRS.
Prophylactic steroids do not compromise the activity of the cell therapy, Kite said in a press release.
“These new data will enable doctors to more easily and confidently manage treatment for patients,” said Frank Neumann, MD, PhD, the company’s global head of clinical development.
Yescarta is currently under review in the United States and Europe for second-line use in relapsed or refractory LBCL, Kite noted.
A version of this article first appeared on Medscape.com.
This is a chimeric antigen receptor T-cell product indicated for use in adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy.
The product label carries a black box warning that CRS is a potentially fatal complication. With the update, the new labeling advises clinicians to “consider the use of prophylactic corticosteroid in patients after weighing the potential benefits and risks ... to delay the onset and decrease the duration of CRS.”
However, labeling also notes that “prophylactic corticosteroids ... may result in [a] higher grade of neurologic toxicities or prolongation of neurologic toxicities,” another potentially fatal complication noted in the black box warning.
The addition of prophylactic corticosteroids to labeling was based on data from 39 patients with relapsed or refractory LBCL who received dexamethasone 10 mg orally once daily for 3 days starting prior to Yescarta infusion. In this cohort, 31 of the 39 patients (79%) developed CRS, at which point they were managed with tocilizumab and/or corticosteroids. No one developed grade 3 or higher CRS. The median time to CRS onset was 5 days and the median duration was 4 days, according to labeling.
In contrast, in another cohort of 41 patients who were started on tocilizumab and/or corticosteroids only after becoming symptomatic, the overall incidence of CRS was 93% (38/41), with a median onset at 2 days, median duration of 7 days, and two patients who developed grade 3 CRS.
Prophylactic steroids do not compromise the activity of the cell therapy, Kite said in a press release.
“These new data will enable doctors to more easily and confidently manage treatment for patients,” said Frank Neumann, MD, PhD, the company’s global head of clinical development.
Yescarta is currently under review in the United States and Europe for second-line use in relapsed or refractory LBCL, Kite noted.
A version of this article first appeared on Medscape.com.
This is a chimeric antigen receptor T-cell product indicated for use in adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy.
The product label carries a black box warning that CRS is a potentially fatal complication. With the update, the new labeling advises clinicians to “consider the use of prophylactic corticosteroid in patients after weighing the potential benefits and risks ... to delay the onset and decrease the duration of CRS.”
However, labeling also notes that “prophylactic corticosteroids ... may result in [a] higher grade of neurologic toxicities or prolongation of neurologic toxicities,” another potentially fatal complication noted in the black box warning.
The addition of prophylactic corticosteroids to labeling was based on data from 39 patients with relapsed or refractory LBCL who received dexamethasone 10 mg orally once daily for 3 days starting prior to Yescarta infusion. In this cohort, 31 of the 39 patients (79%) developed CRS, at which point they were managed with tocilizumab and/or corticosteroids. No one developed grade 3 or higher CRS. The median time to CRS onset was 5 days and the median duration was 4 days, according to labeling.
In contrast, in another cohort of 41 patients who were started on tocilizumab and/or corticosteroids only after becoming symptomatic, the overall incidence of CRS was 93% (38/41), with a median onset at 2 days, median duration of 7 days, and two patients who developed grade 3 CRS.
Prophylactic steroids do not compromise the activity of the cell therapy, Kite said in a press release.
“These new data will enable doctors to more easily and confidently manage treatment for patients,” said Frank Neumann, MD, PhD, the company’s global head of clinical development.
Yescarta is currently under review in the United States and Europe for second-line use in relapsed or refractory LBCL, Kite noted.
A version of this article first appeared on Medscape.com.
“I didn’t want to meet you.” Dispelling myths about palliative care
The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.
but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.
A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.1 Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.1
It’s not giving up
This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.
I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.
“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.
“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.
I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.
“I looked up palliative care on Google and saw the word hospice.”
“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”
She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”
That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.
Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.2 As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
More than pain management
Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.3
“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”
“Tell me about the patient,” I ask, taking a few steps in their direction.
“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”
“I might be able to help her with the appetite and the mood changes.
I can at least talk with her and see where she’s at,” I offer.
“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her?
She doesn’t have any pain.” He sounds skeptical.
“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”
I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.4
In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
Palliative care is more than medical or nursing care
A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.
We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.
I ask her what else is bothering her.
She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.
We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.
I ask her what conversations with her priest have been like.
At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.4 That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”
A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.
I say my own small prayer for Ms. Lopez and head home, the day’s work completed.
Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles.
References
1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.
2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.
3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.
4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.
The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.
but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.
A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.1 Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.1
It’s not giving up
This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.
I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.
“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.
“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.
I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.
“I looked up palliative care on Google and saw the word hospice.”
“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”
She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”
That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.
Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.2 As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
More than pain management
Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.3
“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”
“Tell me about the patient,” I ask, taking a few steps in their direction.
“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”
“I might be able to help her with the appetite and the mood changes.
I can at least talk with her and see where she’s at,” I offer.
“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her?
She doesn’t have any pain.” He sounds skeptical.
“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”
I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.4
In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
Palliative care is more than medical or nursing care
A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.
We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.
I ask her what else is bothering her.
She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.
We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.
I ask her what conversations with her priest have been like.
At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.4 That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”
A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.
I say my own small prayer for Ms. Lopez and head home, the day’s work completed.
Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles.
References
1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.
2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.
3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.
4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.
The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.
but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.
A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.1 Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.1
It’s not giving up
This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.
I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.
“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.
“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.
I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.
“I looked up palliative care on Google and saw the word hospice.”
“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”
She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”
That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.
Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.2 As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
More than pain management
Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.3
“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”
“Tell me about the patient,” I ask, taking a few steps in their direction.
“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”
“I might be able to help her with the appetite and the mood changes.
I can at least talk with her and see where she’s at,” I offer.
“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her?
She doesn’t have any pain.” He sounds skeptical.
“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”
I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.4
In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
Palliative care is more than medical or nursing care
A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.
We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.
I ask her what else is bothering her.
She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.
We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.
I ask her what conversations with her priest have been like.
At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.4 That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”
A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.
I say my own small prayer for Ms. Lopez and head home, the day’s work completed.
Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles.
References
1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.
2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.
3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.
4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.
Newly approved drug improves sleep onset in insomnia
In the first of two studies, a 50-mg dose of daridorexant was associated with a reduction in latency to persistent sleep (LPS) of 11.7 minutes at month 3 versus placebo. The drug also was associated with improved daytime function.
Based on these results, the Food and Drug Administration approved daridorexant for the treatment of insomnia in adults earlier in January.
“The study shows that it is a really good drug that works differently from most other drugs,” said Emmanuel Mignot, MD, PhD, professor of sleep medicine at Stanford (Calif.) University. “It’s more specific to sleep,” Dr. Mignot added.
The findings were published in the February issue of The Lancet Neurology.
Two trials, three doses
Daridorexant is a dual orexin receptor antagonist intended to reduce excessive wakefulness. The investigators hypothesized that, because of its therapeutic target, the drug would not cause sleepiness on the morning after administration.
To examine daridorexant’s safety and efficacy, the researchers conducted two double-blind, parallel-group, phase 3 trials. Eligible participants were aged 18 years or older, had moderate to severe insomnia disorder, and had a self-reported history of disturbed sleep at least 3 nights per week for at least 3 months before screening.
In study 1, investigators randomly assigned participants in groups of equal size to daridorexant 25 mg, 50 mg, or placebo. In study 2, participants were randomly assigned to daridorexant 10 mg, 25 mg, or placebo.
During a placebo run-in period, participants underwent polysomnography on two consecutive nights to define baseline values. At the end of months 1 and 3 of the treatment period, participants again underwent 2 nights of polysomnography. A final night of polysomnography occurred during the placebo run-out period.
Self-assessments included the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ). This questionnaire, to which participants responded daily, is designed to measure the daytime impairments related to insomnia. The IDSIQ questions focus on sleepiness, mood, alertness, and cognition.
The study’s primary endpoints were change from baseline in wake after sleep onset (WASO) and LPS at months 1 and 3. Secondary endpoints were change from baseline in self-reported total sleep time and change in the IDSIQ sleepiness domain score at months 1 and 3.
The investigators enrolled 930 participants in study 1 and 924 in study 2. In each study, more than two-thirds of participants were women, 39% were aged 65 or older, and demographic and baseline characteristics were similar between treatment groups.
Dose-dependent effects
At month 1 in study 1, WASO was reduced by 22.8 minutes (P < .0001) in patients who received the 50-mg dose and by 12.2 minutes (P < .0001) in the 25-mg dose. At month 3, WASO was reduced by 18.3 minutes (P < .0001) in those assigned to 50 mg and by 11.9 minutes (P < .0001) in those assigned to 25 mg.
LPS was reduced by 11.4 minutes (P < .0001) at month 1 and by 11.7 minutes (P < .0001) at month 3 with the 50-mg dose versus placebo. LPS was reduced by 8.3 minutes (P = .0005) at month 1 and by 7.6 minutes (P = .0015) at month 3 with the 25-mg dose versus placebo.
At both time points, self-reported total sleep time was significantly increased and the IDSIQ sleepiness score significantly improved with the 50-mg dose. The 25-mg dose was associated with significant improvements in self-reported total sleep time at both time points, but not with significant improvements in IDSIQ sleepiness score.
In study 2, the 25-mg dose was associated with significant reductions in WASO at month 1 (11.6 minutes, P = .0001) and month 3 (10.3 minutes, P = .0028) compared with placebo. The 25-mg dose was not associated with significant differences in LPS at either time point, however.
Similarly, the 25-mg dose was associated with improvements in self-reported total sleep time, but not with the IDSIQ sleepiness score. The 10-mg dose was not associated with improvements on any endpoint compared with placebo.
Longer studies needed
In an accompanying editorial, Kai Spiegelhalder, PhD, University of Freiburg, Germany, and colleagues pointed out that although insomnia disorder is defined by self-reported difficulty initiating or maintaining sleep, none of the primary or secondary endpoints in these trials addressed these symptoms.
However, Dr. Mignot noted the use of the IDSIQ scale is the most interesting aspect of the study. Although difficulty with concentration and mood impairment are major symptoms of insomnia, they are often neglected. “This drug was reversing the daytime impairment that insomniacs have,” said Dr. Mignot. “We now need to systematically study people not only for the effect on sleep, but also that it makes them feel better the day after.”
He added that most of the current hypnotics were not developed to treat insomnia. Daridorexant, in contrast, targets the wake-promoting orexin system. “It works more selectively on sleep and not on other things. Most of the other sleeping pills have more complex effects on the brain,” Dr. Mignot said.
Commenting on the study, John Winkelman, MD, PhD, professor of psychiatry at Harvard Medical School, Boston, said the low prevalence of side effects associated with daridorexant was remarkable. “This is not what most of the benzodiazepine receptor agonists looked like,” said Dr. Winkelman, who was not involved with the research.
Many insomnia drugs affect transmitter systems that are widespread in the brain, thus provoking side effects. But orexin-receptor antagonists “don’t seem to produce a lot of side effects,” he noted.
Although the study duration was reasonable, longer studies will be necessary, he added. “And it would be nice to see comparative data. Prescribers want to see some context.” said Dr. Winkelman.
The study was funded by Idorsia Pharmaceuticals. Dr. Mignot reported receiving research or clinical trial funding from Axsome, Jazz Pharmaceuticals, Avadel, Apple, Huami, Sunovion, and Takeda. He has also received consulting fees or speakers’ conference reimbursement from Idorsia, Centessa Pharmaceuticals, Jazz Pharmaceuticals, Avadel, Dreem, and Takeda. Dr. Winkelman has consulted for Idorsia and has participated in investigator-initiated studies supported by Merck.
A version of this article first appeared on Medscape.com.
In the first of two studies, a 50-mg dose of daridorexant was associated with a reduction in latency to persistent sleep (LPS) of 11.7 minutes at month 3 versus placebo. The drug also was associated with improved daytime function.
Based on these results, the Food and Drug Administration approved daridorexant for the treatment of insomnia in adults earlier in January.
“The study shows that it is a really good drug that works differently from most other drugs,” said Emmanuel Mignot, MD, PhD, professor of sleep medicine at Stanford (Calif.) University. “It’s more specific to sleep,” Dr. Mignot added.
The findings were published in the February issue of The Lancet Neurology.
Two trials, three doses
Daridorexant is a dual orexin receptor antagonist intended to reduce excessive wakefulness. The investigators hypothesized that, because of its therapeutic target, the drug would not cause sleepiness on the morning after administration.
To examine daridorexant’s safety and efficacy, the researchers conducted two double-blind, parallel-group, phase 3 trials. Eligible participants were aged 18 years or older, had moderate to severe insomnia disorder, and had a self-reported history of disturbed sleep at least 3 nights per week for at least 3 months before screening.
In study 1, investigators randomly assigned participants in groups of equal size to daridorexant 25 mg, 50 mg, or placebo. In study 2, participants were randomly assigned to daridorexant 10 mg, 25 mg, or placebo.
During a placebo run-in period, participants underwent polysomnography on two consecutive nights to define baseline values. At the end of months 1 and 3 of the treatment period, participants again underwent 2 nights of polysomnography. A final night of polysomnography occurred during the placebo run-out period.
Self-assessments included the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ). This questionnaire, to which participants responded daily, is designed to measure the daytime impairments related to insomnia. The IDSIQ questions focus on sleepiness, mood, alertness, and cognition.
The study’s primary endpoints were change from baseline in wake after sleep onset (WASO) and LPS at months 1 and 3. Secondary endpoints were change from baseline in self-reported total sleep time and change in the IDSIQ sleepiness domain score at months 1 and 3.
The investigators enrolled 930 participants in study 1 and 924 in study 2. In each study, more than two-thirds of participants were women, 39% were aged 65 or older, and demographic and baseline characteristics were similar between treatment groups.
Dose-dependent effects
At month 1 in study 1, WASO was reduced by 22.8 minutes (P < .0001) in patients who received the 50-mg dose and by 12.2 minutes (P < .0001) in the 25-mg dose. At month 3, WASO was reduced by 18.3 minutes (P < .0001) in those assigned to 50 mg and by 11.9 minutes (P < .0001) in those assigned to 25 mg.
LPS was reduced by 11.4 minutes (P < .0001) at month 1 and by 11.7 minutes (P < .0001) at month 3 with the 50-mg dose versus placebo. LPS was reduced by 8.3 minutes (P = .0005) at month 1 and by 7.6 minutes (P = .0015) at month 3 with the 25-mg dose versus placebo.
At both time points, self-reported total sleep time was significantly increased and the IDSIQ sleepiness score significantly improved with the 50-mg dose. The 25-mg dose was associated with significant improvements in self-reported total sleep time at both time points, but not with significant improvements in IDSIQ sleepiness score.
In study 2, the 25-mg dose was associated with significant reductions in WASO at month 1 (11.6 minutes, P = .0001) and month 3 (10.3 minutes, P = .0028) compared with placebo. The 25-mg dose was not associated with significant differences in LPS at either time point, however.
Similarly, the 25-mg dose was associated with improvements in self-reported total sleep time, but not with the IDSIQ sleepiness score. The 10-mg dose was not associated with improvements on any endpoint compared with placebo.
Longer studies needed
In an accompanying editorial, Kai Spiegelhalder, PhD, University of Freiburg, Germany, and colleagues pointed out that although insomnia disorder is defined by self-reported difficulty initiating or maintaining sleep, none of the primary or secondary endpoints in these trials addressed these symptoms.
However, Dr. Mignot noted the use of the IDSIQ scale is the most interesting aspect of the study. Although difficulty with concentration and mood impairment are major symptoms of insomnia, they are often neglected. “This drug was reversing the daytime impairment that insomniacs have,” said Dr. Mignot. “We now need to systematically study people not only for the effect on sleep, but also that it makes them feel better the day after.”
He added that most of the current hypnotics were not developed to treat insomnia. Daridorexant, in contrast, targets the wake-promoting orexin system. “It works more selectively on sleep and not on other things. Most of the other sleeping pills have more complex effects on the brain,” Dr. Mignot said.
Commenting on the study, John Winkelman, MD, PhD, professor of psychiatry at Harvard Medical School, Boston, said the low prevalence of side effects associated with daridorexant was remarkable. “This is not what most of the benzodiazepine receptor agonists looked like,” said Dr. Winkelman, who was not involved with the research.
Many insomnia drugs affect transmitter systems that are widespread in the brain, thus provoking side effects. But orexin-receptor antagonists “don’t seem to produce a lot of side effects,” he noted.
Although the study duration was reasonable, longer studies will be necessary, he added. “And it would be nice to see comparative data. Prescribers want to see some context.” said Dr. Winkelman.
The study was funded by Idorsia Pharmaceuticals. Dr. Mignot reported receiving research or clinical trial funding from Axsome, Jazz Pharmaceuticals, Avadel, Apple, Huami, Sunovion, and Takeda. He has also received consulting fees or speakers’ conference reimbursement from Idorsia, Centessa Pharmaceuticals, Jazz Pharmaceuticals, Avadel, Dreem, and Takeda. Dr. Winkelman has consulted for Idorsia and has participated in investigator-initiated studies supported by Merck.
A version of this article first appeared on Medscape.com.
In the first of two studies, a 50-mg dose of daridorexant was associated with a reduction in latency to persistent sleep (LPS) of 11.7 minutes at month 3 versus placebo. The drug also was associated with improved daytime function.
Based on these results, the Food and Drug Administration approved daridorexant for the treatment of insomnia in adults earlier in January.
“The study shows that it is a really good drug that works differently from most other drugs,” said Emmanuel Mignot, MD, PhD, professor of sleep medicine at Stanford (Calif.) University. “It’s more specific to sleep,” Dr. Mignot added.
The findings were published in the February issue of The Lancet Neurology.
Two trials, three doses
Daridorexant is a dual orexin receptor antagonist intended to reduce excessive wakefulness. The investigators hypothesized that, because of its therapeutic target, the drug would not cause sleepiness on the morning after administration.
To examine daridorexant’s safety and efficacy, the researchers conducted two double-blind, parallel-group, phase 3 trials. Eligible participants were aged 18 years or older, had moderate to severe insomnia disorder, and had a self-reported history of disturbed sleep at least 3 nights per week for at least 3 months before screening.
In study 1, investigators randomly assigned participants in groups of equal size to daridorexant 25 mg, 50 mg, or placebo. In study 2, participants were randomly assigned to daridorexant 10 mg, 25 mg, or placebo.
During a placebo run-in period, participants underwent polysomnography on two consecutive nights to define baseline values. At the end of months 1 and 3 of the treatment period, participants again underwent 2 nights of polysomnography. A final night of polysomnography occurred during the placebo run-out period.
Self-assessments included the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ). This questionnaire, to which participants responded daily, is designed to measure the daytime impairments related to insomnia. The IDSIQ questions focus on sleepiness, mood, alertness, and cognition.
The study’s primary endpoints were change from baseline in wake after sleep onset (WASO) and LPS at months 1 and 3. Secondary endpoints were change from baseline in self-reported total sleep time and change in the IDSIQ sleepiness domain score at months 1 and 3.
The investigators enrolled 930 participants in study 1 and 924 in study 2. In each study, more than two-thirds of participants were women, 39% were aged 65 or older, and demographic and baseline characteristics were similar between treatment groups.
Dose-dependent effects
At month 1 in study 1, WASO was reduced by 22.8 minutes (P < .0001) in patients who received the 50-mg dose and by 12.2 minutes (P < .0001) in the 25-mg dose. At month 3, WASO was reduced by 18.3 minutes (P < .0001) in those assigned to 50 mg and by 11.9 minutes (P < .0001) in those assigned to 25 mg.
LPS was reduced by 11.4 minutes (P < .0001) at month 1 and by 11.7 minutes (P < .0001) at month 3 with the 50-mg dose versus placebo. LPS was reduced by 8.3 minutes (P = .0005) at month 1 and by 7.6 minutes (P = .0015) at month 3 with the 25-mg dose versus placebo.
At both time points, self-reported total sleep time was significantly increased and the IDSIQ sleepiness score significantly improved with the 50-mg dose. The 25-mg dose was associated with significant improvements in self-reported total sleep time at both time points, but not with significant improvements in IDSIQ sleepiness score.
In study 2, the 25-mg dose was associated with significant reductions in WASO at month 1 (11.6 minutes, P = .0001) and month 3 (10.3 minutes, P = .0028) compared with placebo. The 25-mg dose was not associated with significant differences in LPS at either time point, however.
Similarly, the 25-mg dose was associated with improvements in self-reported total sleep time, but not with the IDSIQ sleepiness score. The 10-mg dose was not associated with improvements on any endpoint compared with placebo.
Longer studies needed
In an accompanying editorial, Kai Spiegelhalder, PhD, University of Freiburg, Germany, and colleagues pointed out that although insomnia disorder is defined by self-reported difficulty initiating or maintaining sleep, none of the primary or secondary endpoints in these trials addressed these symptoms.
However, Dr. Mignot noted the use of the IDSIQ scale is the most interesting aspect of the study. Although difficulty with concentration and mood impairment are major symptoms of insomnia, they are often neglected. “This drug was reversing the daytime impairment that insomniacs have,” said Dr. Mignot. “We now need to systematically study people not only for the effect on sleep, but also that it makes them feel better the day after.”
He added that most of the current hypnotics were not developed to treat insomnia. Daridorexant, in contrast, targets the wake-promoting orexin system. “It works more selectively on sleep and not on other things. Most of the other sleeping pills have more complex effects on the brain,” Dr. Mignot said.
Commenting on the study, John Winkelman, MD, PhD, professor of psychiatry at Harvard Medical School, Boston, said the low prevalence of side effects associated with daridorexant was remarkable. “This is not what most of the benzodiazepine receptor agonists looked like,” said Dr. Winkelman, who was not involved with the research.
Many insomnia drugs affect transmitter systems that are widespread in the brain, thus provoking side effects. But orexin-receptor antagonists “don’t seem to produce a lot of side effects,” he noted.
Although the study duration was reasonable, longer studies will be necessary, he added. “And it would be nice to see comparative data. Prescribers want to see some context.” said Dr. Winkelman.
The study was funded by Idorsia Pharmaceuticals. Dr. Mignot reported receiving research or clinical trial funding from Axsome, Jazz Pharmaceuticals, Avadel, Apple, Huami, Sunovion, and Takeda. He has also received consulting fees or speakers’ conference reimbursement from Idorsia, Centessa Pharmaceuticals, Jazz Pharmaceuticals, Avadel, Dreem, and Takeda. Dr. Winkelman has consulted for Idorsia and has participated in investigator-initiated studies supported by Merck.
A version of this article first appeared on Medscape.com.
FROM THE LANCET NEUROLOGY
Kids’ mask use linked with fewer childcare closings
Mask-wearing in childcare programs is linked with fewer COVID-19–related program closures, new data released suggest.
Researchers included 6,654 childcare professionals in a prospective, 1-year, longitudinal electronic survey study of home- and center-based childcare programs in all 50 states.
Findings by Thomas S. Murray, MD, PhD, with the department of pediatrics, Yale University, New Haven, Conn., and coauthors, were published in JAMA Network Open on Jan. 28, 2022.
They found that mask-wearing from the May 22, 2020, baseline to June 8, 2020, was associated with a 13% reduction in program closures within the following year (adjusted relative risk, 0.87; 95% confidence interval, 0.77-0.99). Continued mask-wearing throughout the 1-year follow-up was associated with a 14% reduction in program closures (aRR, 0.86; 95% CI, 0.74-1.00).
The authors said the evidence supports current masking recommendation in younger children provided by the Centers for Disease Control and Prevention.
They wrote: “This finding has important public health policy implications for families that rely on childcare to sustain employment.”
The benefits of masking in preventing COVID-19 transmission within kindergarten through 12th-grade classes are well documented. Masks are particularly important in areas where vaccinations are not widespread.
Masks can be worn safely by young children without harming respiratory function, studies have shown.
William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., pointed out that the American Academy of Pediatrics has said there are no noteworthy effects on breathing function for most children.
“There’s been so much discussion about the contribution of masks to reducing the risk of COVID that it’s nice to have the data,” he said, adding that this is a relationship that has been difficult to study, but this analysis was able to make the connection with hard numbers.
“It’s an important outcome,” he said in an interview.
The authors pointed out there is evidence that school-age children can identify most emotions in masked faces.
They added that “2-year-old children recognize spoken words better through an opaque mask, compared with a clear face shield, suggesting verbal communication to infants is not harmed by face masks.”
Studies have shown that childhood infection with other respiratory viruses also decreased and asthma symptoms were not reported when preschool children wore masks and used other preventative steps.
The authors wrote that a potential reason for that may be that those who wear masks have less face touching, known to increase the spread of COVID-19.
Paloma Beamer, PhD, an engineer and exposure scientist at University of Arizona, Tucson, who also has a 3-year-old son who wears masks at his daycare center, said in an interview that she works closely with his school on training kids how to wear their masks because getting young children to keep them on and finding ones that fit is challenging.
“We need layered controls and protections in place at schools as much as possible,” she said, adding that the authors didn’t mention ventilation, but that’s another important component as well.
“We’re fortunate in Arizona that we are in an old school and the windows are open as much as possible,” she said.
She said this study shows that “masks are a great form of additional control.” Her son is on his third quarantine this month after three kids tested positive, she added.
She said: “I think these newer variants perhaps make the findings of this study more compelling and it will be interesting to see if the researchers do a follow-up study.”
Strengths of the study include that it utilized prospective data from a large national cohort of childcare professionals. Additionally, the retention rate was high at 1 year. And the self-reported information likely gives better information than looking at policies that may or may not be well followed.
Limitations include potential reporting bias because the self-reports were not independently confirmed. Also, family behavior outside childcare, such as social gatherings where masking is not enforced, also influence COVID-19 cases when children gather and may affect the numbers of closures.
Having the option of childcare centers benefits kids with in-person early education and social interactions with staff, the authors noted. The centers also help parents return to work without interruptions at home.
“Our findings support current national recommendations endorsed by many local and state governments for masking children 2 years and older in childcare programs when community COVID-19 transmission levels are elevated,” the authors wrote.
Dr. Schaffner said the results have implications outside of childcare centers and should be included in discussions of masking in schools and in the general public.
All phases of this study were supported by and coauthors report grants from the Andrew & Julie Klingenstein Family Fund, Esther A. & Joseph Klingenstein Fund, Heising-Simons Foundation, W.K. Kellogg Foundation, Foundation for Child Development, Early Educator Investment Collaborative, and Scholastic. The study was partially funded by the Yale Institute for Global Health. Dr. Schaffner and Dr. Beamer reported no relevant financial relationships.
Mask-wearing in childcare programs is linked with fewer COVID-19–related program closures, new data released suggest.
Researchers included 6,654 childcare professionals in a prospective, 1-year, longitudinal electronic survey study of home- and center-based childcare programs in all 50 states.
Findings by Thomas S. Murray, MD, PhD, with the department of pediatrics, Yale University, New Haven, Conn., and coauthors, were published in JAMA Network Open on Jan. 28, 2022.
They found that mask-wearing from the May 22, 2020, baseline to June 8, 2020, was associated with a 13% reduction in program closures within the following year (adjusted relative risk, 0.87; 95% confidence interval, 0.77-0.99). Continued mask-wearing throughout the 1-year follow-up was associated with a 14% reduction in program closures (aRR, 0.86; 95% CI, 0.74-1.00).
The authors said the evidence supports current masking recommendation in younger children provided by the Centers for Disease Control and Prevention.
They wrote: “This finding has important public health policy implications for families that rely on childcare to sustain employment.”
The benefits of masking in preventing COVID-19 transmission within kindergarten through 12th-grade classes are well documented. Masks are particularly important in areas where vaccinations are not widespread.
Masks can be worn safely by young children without harming respiratory function, studies have shown.
William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., pointed out that the American Academy of Pediatrics has said there are no noteworthy effects on breathing function for most children.
“There’s been so much discussion about the contribution of masks to reducing the risk of COVID that it’s nice to have the data,” he said, adding that this is a relationship that has been difficult to study, but this analysis was able to make the connection with hard numbers.
“It’s an important outcome,” he said in an interview.
The authors pointed out there is evidence that school-age children can identify most emotions in masked faces.
They added that “2-year-old children recognize spoken words better through an opaque mask, compared with a clear face shield, suggesting verbal communication to infants is not harmed by face masks.”
Studies have shown that childhood infection with other respiratory viruses also decreased and asthma symptoms were not reported when preschool children wore masks and used other preventative steps.
The authors wrote that a potential reason for that may be that those who wear masks have less face touching, known to increase the spread of COVID-19.
Paloma Beamer, PhD, an engineer and exposure scientist at University of Arizona, Tucson, who also has a 3-year-old son who wears masks at his daycare center, said in an interview that she works closely with his school on training kids how to wear their masks because getting young children to keep them on and finding ones that fit is challenging.
“We need layered controls and protections in place at schools as much as possible,” she said, adding that the authors didn’t mention ventilation, but that’s another important component as well.
“We’re fortunate in Arizona that we are in an old school and the windows are open as much as possible,” she said.
She said this study shows that “masks are a great form of additional control.” Her son is on his third quarantine this month after three kids tested positive, she added.
She said: “I think these newer variants perhaps make the findings of this study more compelling and it will be interesting to see if the researchers do a follow-up study.”
Strengths of the study include that it utilized prospective data from a large national cohort of childcare professionals. Additionally, the retention rate was high at 1 year. And the self-reported information likely gives better information than looking at policies that may or may not be well followed.
Limitations include potential reporting bias because the self-reports were not independently confirmed. Also, family behavior outside childcare, such as social gatherings where masking is not enforced, also influence COVID-19 cases when children gather and may affect the numbers of closures.
Having the option of childcare centers benefits kids with in-person early education and social interactions with staff, the authors noted. The centers also help parents return to work without interruptions at home.
“Our findings support current national recommendations endorsed by many local and state governments for masking children 2 years and older in childcare programs when community COVID-19 transmission levels are elevated,” the authors wrote.
Dr. Schaffner said the results have implications outside of childcare centers and should be included in discussions of masking in schools and in the general public.
All phases of this study were supported by and coauthors report grants from the Andrew & Julie Klingenstein Family Fund, Esther A. & Joseph Klingenstein Fund, Heising-Simons Foundation, W.K. Kellogg Foundation, Foundation for Child Development, Early Educator Investment Collaborative, and Scholastic. The study was partially funded by the Yale Institute for Global Health. Dr. Schaffner and Dr. Beamer reported no relevant financial relationships.
Mask-wearing in childcare programs is linked with fewer COVID-19–related program closures, new data released suggest.
Researchers included 6,654 childcare professionals in a prospective, 1-year, longitudinal electronic survey study of home- and center-based childcare programs in all 50 states.
Findings by Thomas S. Murray, MD, PhD, with the department of pediatrics, Yale University, New Haven, Conn., and coauthors, were published in JAMA Network Open on Jan. 28, 2022.
They found that mask-wearing from the May 22, 2020, baseline to June 8, 2020, was associated with a 13% reduction in program closures within the following year (adjusted relative risk, 0.87; 95% confidence interval, 0.77-0.99). Continued mask-wearing throughout the 1-year follow-up was associated with a 14% reduction in program closures (aRR, 0.86; 95% CI, 0.74-1.00).
The authors said the evidence supports current masking recommendation in younger children provided by the Centers for Disease Control and Prevention.
They wrote: “This finding has important public health policy implications for families that rely on childcare to sustain employment.”
The benefits of masking in preventing COVID-19 transmission within kindergarten through 12th-grade classes are well documented. Masks are particularly important in areas where vaccinations are not widespread.
Masks can be worn safely by young children without harming respiratory function, studies have shown.
William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., pointed out that the American Academy of Pediatrics has said there are no noteworthy effects on breathing function for most children.
“There’s been so much discussion about the contribution of masks to reducing the risk of COVID that it’s nice to have the data,” he said, adding that this is a relationship that has been difficult to study, but this analysis was able to make the connection with hard numbers.
“It’s an important outcome,” he said in an interview.
The authors pointed out there is evidence that school-age children can identify most emotions in masked faces.
They added that “2-year-old children recognize spoken words better through an opaque mask, compared with a clear face shield, suggesting verbal communication to infants is not harmed by face masks.”
Studies have shown that childhood infection with other respiratory viruses also decreased and asthma symptoms were not reported when preschool children wore masks and used other preventative steps.
The authors wrote that a potential reason for that may be that those who wear masks have less face touching, known to increase the spread of COVID-19.
Paloma Beamer, PhD, an engineer and exposure scientist at University of Arizona, Tucson, who also has a 3-year-old son who wears masks at his daycare center, said in an interview that she works closely with his school on training kids how to wear their masks because getting young children to keep them on and finding ones that fit is challenging.
“We need layered controls and protections in place at schools as much as possible,” she said, adding that the authors didn’t mention ventilation, but that’s another important component as well.
“We’re fortunate in Arizona that we are in an old school and the windows are open as much as possible,” she said.
She said this study shows that “masks are a great form of additional control.” Her son is on his third quarantine this month after three kids tested positive, she added.
She said: “I think these newer variants perhaps make the findings of this study more compelling and it will be interesting to see if the researchers do a follow-up study.”
Strengths of the study include that it utilized prospective data from a large national cohort of childcare professionals. Additionally, the retention rate was high at 1 year. And the self-reported information likely gives better information than looking at policies that may or may not be well followed.
Limitations include potential reporting bias because the self-reports were not independently confirmed. Also, family behavior outside childcare, such as social gatherings where masking is not enforced, also influence COVID-19 cases when children gather and may affect the numbers of closures.
Having the option of childcare centers benefits kids with in-person early education and social interactions with staff, the authors noted. The centers also help parents return to work without interruptions at home.
“Our findings support current national recommendations endorsed by many local and state governments for masking children 2 years and older in childcare programs when community COVID-19 transmission levels are elevated,” the authors wrote.
Dr. Schaffner said the results have implications outside of childcare centers and should be included in discussions of masking in schools and in the general public.
All phases of this study were supported by and coauthors report grants from the Andrew & Julie Klingenstein Family Fund, Esther A. & Joseph Klingenstein Fund, Heising-Simons Foundation, W.K. Kellogg Foundation, Foundation for Child Development, Early Educator Investment Collaborative, and Scholastic. The study was partially funded by the Yale Institute for Global Health. Dr. Schaffner and Dr. Beamer reported no relevant financial relationships.
FROM JAMA NETWORK OPEN
One in five female oncologists considering leaving academia, survey finds
More than half of respondents in academic medicine said they believe their gender adversely affects their likelihood for promotion, and 1 in 5 said they were considering leaving academia in the next 5 years.
Given the percentage of female oncologists planning to exit academia, “gender inequality is at high risk of continuing if the culture is not addressed,” write the authors in their study, published online Dec. 30 in JAMA Network Open.
Although women currently outnumber men in U.S. medical schools – a shift that first occurred in 2019 – female representation in academic oncology dwindles at more senior levels. Women represent 45% of hematology and oncology residents, only about 36% of academic faculty, and an even smaller percentage of leadership positions in academic medicine. Women, for instance, occupy about 31% of the chair positions in medical oncology, 17.4% in radiation oncology, and 11% in surgical oncology.
A team of researchers led by Emily C. Merfeld, MD, of the University of Wisconsin Hospitals and Clinics, Madison, set out to understand the factors influencing female oncologists’ decisions to pursue academic versus nonacademic career paths.
Dr. Merfeld and colleagues analyzed survey responses from 667 female oncologists between August 1 and Oct. 31, 2020 – 422 (63.2%) in academic medicine and 245 (36.8%) in nonacademic practice.
Overall, 1 in 4 oncologists said their spouse or partner and family “extremely or moderately” affected their decision to pursue academic practice.
Almost 43% of academic oncologists perceived time spent with loved ones as the biggest sacrifice related to pursuing a career in academic medicine. Approximately the same percentage (41.6%) of nonacademic oncologists perceived the pressure to achieve academic promotion as the most significant sacrifice associated with academic oncology, whereas only 22.4% perceived less time with loved ones as the biggest sacrifice.
“Although work-life balance was a concern for academic oncologists and may be a factor in female oncologists leaving academia, survey data suggested that women in nonacademic practice faced similar challenges,” the authors write.
More specifically, women in academic oncology reported working 2 more hours on the weekends compared to women not in academic medicine; however, both groups worked a similar number of hours during the week.
On the hiring front, almost 24% of academic oncologists said their gender had a “negative or somewhat negative” impact on their ability to get a job, compared with 21% of nonacademic oncologists. Conversely, nearly 28% of academic oncologists said their gender had a “positive or somewhat positive” influence on whether they were hired compared with 41.2% of nonacademic oncologists.
Respondents, however, perceived that gender strongly influenced promotion opportunities. More than half of the respondents – 54.6% of academic oncologists and 50.6% of nonacademic oncologists – believed they were less likely to be promoted than their male colleagues.
This perception aligns with findings from prior studies, which “found women were less likely than men to be promoted to associate professor, full professor, or department chair positions,” the authors write.
Overall, most respondents in each group – 71.3% in academic medicine and 68.6% in nonacademic practice – said they would choose the same career path again. But almost 22% of those in academia said they were “likely or very likely” to leave academic oncology in the next 5 years. Of these women, 28.2% said they would switch to industry employment and 25% would move to community practice.
“Contrary to popular assumptions,” the researchers note, “a spouse or partner and/or family were not a major factor in female oncologists favoring nonacademic careers, because this factor was similarly important to both academic and nonacademic oncologists.”
However, they note, “the increased financial compensation in nonacademic oncology may play a large role in some women’s career decisions.”
Making headway on gender equality?
In 2013, oncologist Katherine Reeder-Hayes, MD, MBA, now an associate at the University of North Carolina, Chapel Hill, published a study on gender equality in oncology in which she concluded that despite “an increasingly significant presence in the oncology physician workforce” women remained “under-represented in leadership positions and at the senior levels of academic medicine.”
Since then, Dr. Reeder-Hayes says that she has seen progress but recognizes the need for more.
“To some extent, I think that representation is improving over time due to factors outside the workplace – women are entering medical school in large numbers and may have more supportive partners and more social support for pursuing a professional career in general, [compared with] a decade or two ago,” Dr. Reeder-Hayes told this news organization.
On a personal level, she noted, “I do see many midcareer women assuming key leadership roles in my own institution.” However, she added, “I think the translation of those good candidates into increased representation in leadership probably varies widely across different institutions.”
In a 2019 editorial, researchers highlighted this variation while calling attention to the “notable progress” made by the American Association for Cancer Research (AACR). Specifically, the editorialists reported that women represent 40% of AACR members, 45% of the AACR Board of Directors, and half of the last 10 association presidents.
Editorial coauthor Elizabeth Jaffee, MD, deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, and former AACR president, told this news organization that she attributes this progress to “concrete measures to ensure equality throughout the organization,” which include gender balance on nominating and program committees as well as research meetings and providing opportunities for mentoring, leadership training, and networking.
Despite this positive change, the COVID-19 pandemic threatens to widen the gender imbalance. In a recent article, Julie Silver, MD, an expert in gender equity in medicine, told this news organization that she anticipates trouble ahead.
“There are many indications that women are leaving medicine in disproportionately high numbers,” said Dr. Silver, associate chair and director of cancer rehabilitation in the department of physical medicine and rehabilitation at Harvard Medical School, Boston. “A lack of fair pay and promotion opportunities that were present before COVID-19 are now combined with a host of pandemic-related challenges.”
In addition to salary and promotion disparities, the U.S. continues to suffer from “a chronic shortage of available, affordable, and high-quality childcare and a lack of federal-level policy initiatives or employer initiatives to broaden paid family leave and develop childcare infrastructure and workforce,” Dr. Reeder-Hayes said. Providing extended leave for new parents and on-site childcare could go a long way to improving this problem, she said.
However, Dr. Reeder-Hayes noted that perhaps the “leaky pipeline” problem in oncology highlights the fact that women “are making good decisions that reflect balanced life priorities, [and that] if we don’t structure job responsibilities, childcare, and pacing of promotion and tenure in ways that allow people to nurture other parts of their lives, employees will feel they’re being asked to sacrifice key things.”
In other words, she said, “it’s the workplace that needs to change if we’re going to convince [women], and many men with similar values, to stay.”
A version of this article first appeared on Medscape.com.
More than half of respondents in academic medicine said they believe their gender adversely affects their likelihood for promotion, and 1 in 5 said they were considering leaving academia in the next 5 years.
Given the percentage of female oncologists planning to exit academia, “gender inequality is at high risk of continuing if the culture is not addressed,” write the authors in their study, published online Dec. 30 in JAMA Network Open.
Although women currently outnumber men in U.S. medical schools – a shift that first occurred in 2019 – female representation in academic oncology dwindles at more senior levels. Women represent 45% of hematology and oncology residents, only about 36% of academic faculty, and an even smaller percentage of leadership positions in academic medicine. Women, for instance, occupy about 31% of the chair positions in medical oncology, 17.4% in radiation oncology, and 11% in surgical oncology.
A team of researchers led by Emily C. Merfeld, MD, of the University of Wisconsin Hospitals and Clinics, Madison, set out to understand the factors influencing female oncologists’ decisions to pursue academic versus nonacademic career paths.
Dr. Merfeld and colleagues analyzed survey responses from 667 female oncologists between August 1 and Oct. 31, 2020 – 422 (63.2%) in academic medicine and 245 (36.8%) in nonacademic practice.
Overall, 1 in 4 oncologists said their spouse or partner and family “extremely or moderately” affected their decision to pursue academic practice.
Almost 43% of academic oncologists perceived time spent with loved ones as the biggest sacrifice related to pursuing a career in academic medicine. Approximately the same percentage (41.6%) of nonacademic oncologists perceived the pressure to achieve academic promotion as the most significant sacrifice associated with academic oncology, whereas only 22.4% perceived less time with loved ones as the biggest sacrifice.
“Although work-life balance was a concern for academic oncologists and may be a factor in female oncologists leaving academia, survey data suggested that women in nonacademic practice faced similar challenges,” the authors write.
More specifically, women in academic oncology reported working 2 more hours on the weekends compared to women not in academic medicine; however, both groups worked a similar number of hours during the week.
On the hiring front, almost 24% of academic oncologists said their gender had a “negative or somewhat negative” impact on their ability to get a job, compared with 21% of nonacademic oncologists. Conversely, nearly 28% of academic oncologists said their gender had a “positive or somewhat positive” influence on whether they were hired compared with 41.2% of nonacademic oncologists.
Respondents, however, perceived that gender strongly influenced promotion opportunities. More than half of the respondents – 54.6% of academic oncologists and 50.6% of nonacademic oncologists – believed they were less likely to be promoted than their male colleagues.
This perception aligns with findings from prior studies, which “found women were less likely than men to be promoted to associate professor, full professor, or department chair positions,” the authors write.
Overall, most respondents in each group – 71.3% in academic medicine and 68.6% in nonacademic practice – said they would choose the same career path again. But almost 22% of those in academia said they were “likely or very likely” to leave academic oncology in the next 5 years. Of these women, 28.2% said they would switch to industry employment and 25% would move to community practice.
“Contrary to popular assumptions,” the researchers note, “a spouse or partner and/or family were not a major factor in female oncologists favoring nonacademic careers, because this factor was similarly important to both academic and nonacademic oncologists.”
However, they note, “the increased financial compensation in nonacademic oncology may play a large role in some women’s career decisions.”
Making headway on gender equality?
In 2013, oncologist Katherine Reeder-Hayes, MD, MBA, now an associate at the University of North Carolina, Chapel Hill, published a study on gender equality in oncology in which she concluded that despite “an increasingly significant presence in the oncology physician workforce” women remained “under-represented in leadership positions and at the senior levels of academic medicine.”
Since then, Dr. Reeder-Hayes says that she has seen progress but recognizes the need for more.
“To some extent, I think that representation is improving over time due to factors outside the workplace – women are entering medical school in large numbers and may have more supportive partners and more social support for pursuing a professional career in general, [compared with] a decade or two ago,” Dr. Reeder-Hayes told this news organization.
On a personal level, she noted, “I do see many midcareer women assuming key leadership roles in my own institution.” However, she added, “I think the translation of those good candidates into increased representation in leadership probably varies widely across different institutions.”
In a 2019 editorial, researchers highlighted this variation while calling attention to the “notable progress” made by the American Association for Cancer Research (AACR). Specifically, the editorialists reported that women represent 40% of AACR members, 45% of the AACR Board of Directors, and half of the last 10 association presidents.
Editorial coauthor Elizabeth Jaffee, MD, deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, and former AACR president, told this news organization that she attributes this progress to “concrete measures to ensure equality throughout the organization,” which include gender balance on nominating and program committees as well as research meetings and providing opportunities for mentoring, leadership training, and networking.
Despite this positive change, the COVID-19 pandemic threatens to widen the gender imbalance. In a recent article, Julie Silver, MD, an expert in gender equity in medicine, told this news organization that she anticipates trouble ahead.
“There are many indications that women are leaving medicine in disproportionately high numbers,” said Dr. Silver, associate chair and director of cancer rehabilitation in the department of physical medicine and rehabilitation at Harvard Medical School, Boston. “A lack of fair pay and promotion opportunities that were present before COVID-19 are now combined with a host of pandemic-related challenges.”
In addition to salary and promotion disparities, the U.S. continues to suffer from “a chronic shortage of available, affordable, and high-quality childcare and a lack of federal-level policy initiatives or employer initiatives to broaden paid family leave and develop childcare infrastructure and workforce,” Dr. Reeder-Hayes said. Providing extended leave for new parents and on-site childcare could go a long way to improving this problem, she said.
However, Dr. Reeder-Hayes noted that perhaps the “leaky pipeline” problem in oncology highlights the fact that women “are making good decisions that reflect balanced life priorities, [and that] if we don’t structure job responsibilities, childcare, and pacing of promotion and tenure in ways that allow people to nurture other parts of their lives, employees will feel they’re being asked to sacrifice key things.”
In other words, she said, “it’s the workplace that needs to change if we’re going to convince [women], and many men with similar values, to stay.”
A version of this article first appeared on Medscape.com.
More than half of respondents in academic medicine said they believe their gender adversely affects their likelihood for promotion, and 1 in 5 said they were considering leaving academia in the next 5 years.
Given the percentage of female oncologists planning to exit academia, “gender inequality is at high risk of continuing if the culture is not addressed,” write the authors in their study, published online Dec. 30 in JAMA Network Open.
Although women currently outnumber men in U.S. medical schools – a shift that first occurred in 2019 – female representation in academic oncology dwindles at more senior levels. Women represent 45% of hematology and oncology residents, only about 36% of academic faculty, and an even smaller percentage of leadership positions in academic medicine. Women, for instance, occupy about 31% of the chair positions in medical oncology, 17.4% in radiation oncology, and 11% in surgical oncology.
A team of researchers led by Emily C. Merfeld, MD, of the University of Wisconsin Hospitals and Clinics, Madison, set out to understand the factors influencing female oncologists’ decisions to pursue academic versus nonacademic career paths.
Dr. Merfeld and colleagues analyzed survey responses from 667 female oncologists between August 1 and Oct. 31, 2020 – 422 (63.2%) in academic medicine and 245 (36.8%) in nonacademic practice.
Overall, 1 in 4 oncologists said their spouse or partner and family “extremely or moderately” affected their decision to pursue academic practice.
Almost 43% of academic oncologists perceived time spent with loved ones as the biggest sacrifice related to pursuing a career in academic medicine. Approximately the same percentage (41.6%) of nonacademic oncologists perceived the pressure to achieve academic promotion as the most significant sacrifice associated with academic oncology, whereas only 22.4% perceived less time with loved ones as the biggest sacrifice.
“Although work-life balance was a concern for academic oncologists and may be a factor in female oncologists leaving academia, survey data suggested that women in nonacademic practice faced similar challenges,” the authors write.
More specifically, women in academic oncology reported working 2 more hours on the weekends compared to women not in academic medicine; however, both groups worked a similar number of hours during the week.
On the hiring front, almost 24% of academic oncologists said their gender had a “negative or somewhat negative” impact on their ability to get a job, compared with 21% of nonacademic oncologists. Conversely, nearly 28% of academic oncologists said their gender had a “positive or somewhat positive” influence on whether they were hired compared with 41.2% of nonacademic oncologists.
Respondents, however, perceived that gender strongly influenced promotion opportunities. More than half of the respondents – 54.6% of academic oncologists and 50.6% of nonacademic oncologists – believed they were less likely to be promoted than their male colleagues.
This perception aligns with findings from prior studies, which “found women were less likely than men to be promoted to associate professor, full professor, or department chair positions,” the authors write.
Overall, most respondents in each group – 71.3% in academic medicine and 68.6% in nonacademic practice – said they would choose the same career path again. But almost 22% of those in academia said they were “likely or very likely” to leave academic oncology in the next 5 years. Of these women, 28.2% said they would switch to industry employment and 25% would move to community practice.
“Contrary to popular assumptions,” the researchers note, “a spouse or partner and/or family were not a major factor in female oncologists favoring nonacademic careers, because this factor was similarly important to both academic and nonacademic oncologists.”
However, they note, “the increased financial compensation in nonacademic oncology may play a large role in some women’s career decisions.”
Making headway on gender equality?
In 2013, oncologist Katherine Reeder-Hayes, MD, MBA, now an associate at the University of North Carolina, Chapel Hill, published a study on gender equality in oncology in which she concluded that despite “an increasingly significant presence in the oncology physician workforce” women remained “under-represented in leadership positions and at the senior levels of academic medicine.”
Since then, Dr. Reeder-Hayes says that she has seen progress but recognizes the need for more.
“To some extent, I think that representation is improving over time due to factors outside the workplace – women are entering medical school in large numbers and may have more supportive partners and more social support for pursuing a professional career in general, [compared with] a decade or two ago,” Dr. Reeder-Hayes told this news organization.
On a personal level, she noted, “I do see many midcareer women assuming key leadership roles in my own institution.” However, she added, “I think the translation of those good candidates into increased representation in leadership probably varies widely across different institutions.”
In a 2019 editorial, researchers highlighted this variation while calling attention to the “notable progress” made by the American Association for Cancer Research (AACR). Specifically, the editorialists reported that women represent 40% of AACR members, 45% of the AACR Board of Directors, and half of the last 10 association presidents.
Editorial coauthor Elizabeth Jaffee, MD, deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, and former AACR president, told this news organization that she attributes this progress to “concrete measures to ensure equality throughout the organization,” which include gender balance on nominating and program committees as well as research meetings and providing opportunities for mentoring, leadership training, and networking.
Despite this positive change, the COVID-19 pandemic threatens to widen the gender imbalance. In a recent article, Julie Silver, MD, an expert in gender equity in medicine, told this news organization that she anticipates trouble ahead.
“There are many indications that women are leaving medicine in disproportionately high numbers,” said Dr. Silver, associate chair and director of cancer rehabilitation in the department of physical medicine and rehabilitation at Harvard Medical School, Boston. “A lack of fair pay and promotion opportunities that were present before COVID-19 are now combined with a host of pandemic-related challenges.”
In addition to salary and promotion disparities, the U.S. continues to suffer from “a chronic shortage of available, affordable, and high-quality childcare and a lack of federal-level policy initiatives or employer initiatives to broaden paid family leave and develop childcare infrastructure and workforce,” Dr. Reeder-Hayes said. Providing extended leave for new parents and on-site childcare could go a long way to improving this problem, she said.
However, Dr. Reeder-Hayes noted that perhaps the “leaky pipeline” problem in oncology highlights the fact that women “are making good decisions that reflect balanced life priorities, [and that] if we don’t structure job responsibilities, childcare, and pacing of promotion and tenure in ways that allow people to nurture other parts of their lives, employees will feel they’re being asked to sacrifice key things.”
In other words, she said, “it’s the workplace that needs to change if we’re going to convince [women], and many men with similar values, to stay.”
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Dairy intake may increase risk of Parkinson’s disease in men
according to investigators. Men of European ancestry with a genetic marker predicting dairy consumption had significantly greater risk of Parkinson’s disease than individuals without the marker, suggesting a causal relationship between dairy intake and Parkinson’s disease, lead author Cloé Domenighetti, MSc, a PhD student at UVSQ, Université Paris Sud, and colleagues reported.
“Previous studies highlighted dairy intake as a risk factor of Parkinson’s disease,” the investigators wrote in Movement Disorders. “A meta-analysis of prospective studies reported a 40% increased Parkinson’s disease risk in participants with the highest intake. It is unclear whether the association is causal or explained by confounding or reverse causation, given the long prodromal phase of Parkinson’s disease.”
A Mendelian randomization study
The investigators evaluated this link by comparing 9,823 cases of Parkinson’s disease with 8,376 controls, all individuals of European ancestry from the Courage-Parkinson’s disease consortium, comprising 23 studies. Data were analyzed by two-sample Mendelian randomization, a technique that uses genotype to predict behavior, thereby replacing conventional methods of capturing behavior, such as questionnaires. In this case, the investigators screened all participants for rs4988235, a single-nucleotide polymorphism (SNP) upstream of the lactase gene that is well documented to predict dairy intake among individuals of European ancestry.
“Mendelian randomization uses genetic variants associated with exposures as instrumental variables to estimate causal relationships between exposures and outcomes,” the investigators wrote. “Mendelian randomization analyses are less likely to be biased by confounding or reverse causation than observational studies if a set of assumptions are met.”
The approach uncovered a significant association between rs4988235 and Parkinson’s disease, with a 70% increase in disease risk per one serving of dairy per day (odds ratio, 1.70; 95% confidence interval, 1.12-2.60; P = .013). Further analysis revealed that this finding was driven by men, who had a 2.5-fold increased risk of Parkinson’s disease per one serving per day (OR, 2.50; 95% CI, 1.37-4.56; P = .003) versus women, among whom there was no significant association (OR, 1.04; 95% CI, 0.56-1.92; P = .91). No significant associations were observed among individuals grouped by age or Parkinson’s disease duration.
“Our findings suggest that dairy intake increases Parkinson’s disease risk,” the investigators concluded. “Therefore, diets with limited milk intake (e.g., Mediterranean diet) may be beneficial with respect to Parkinson’s disease.”
Further evidence supporting a link between diet and Parkinson’s disease
According to Silke Appel-Cresswell, MD, Marg Meikle Professor for Parkinson’s Research at the University of British Columbia, Vancouver, the findings align with previous prospective cohort studies demonstrating an increased risk of Parkinson’s disease with greater consumption of dairy.
“What the current study adds,” Dr. Appel-Cresswell said, “is a complementary approach to assess the association where the risk of reverse causation and of confounding are minimized. Like in some of the previous studies, the authors find sex differences with an increased risk for men but not women.”
Dr. Appel-Cresswell noted that an increasing body of evidence supports a link between diet and Parkinson’s disease, including a study of her own published last year, which showed later onset of Parkinson’s disease among individuals with a Mediterranean-style diet.
“We are accumulating evidence for a role of diet (or more broadly, the food exposome) for the risk to develop Parkinson’s disease,” Dr. Appel-Cresswell said, noting that “key pieces are still missing, including mechanisms underlying associations, clinical trials in individuals with established Parkinson’s disease and – eventually – preventive interventions. This research is urgently needed and analyses will need to take sex differences and a large range of potential other factors into account.”
A ‘modest’ contributing factor?
Vikas Kotagal, MD, associate professor of neurology at the University of Michigan, Ann Arbor, offered a perspective on the study methodology, and suggested that a causal link between dairy intake and Parkinson’s disease, if present, is likely minimal.
“Limitations to the study include the fact that participants weren’t actually asked or tested for how much dairy they truly consumed,” Dr. Kotagal said*. “Their dairy intake was estimated based on their genetic background – there are certainly many assumptions baked into this analytic approach which may or may not be true. It is also worth noting the fact that this causal association was seen in men and not women, suggesting that even if dairy intake was truly causal, it is likely to be a modest contributing factor and not a significant cause of Parkinson’s disease in the broader population in general.”
Still, Dr. Kotagal agreed with Dr. Appel-Cresswell that underlying mechanisms need further investigation.
“The biggest takeaway here is to heighten the urgency for researchers and funders to explore whether factors that might cluster with dairy intake – including pesticide exposure in milk or even the make-up of bacterial populations in different peoples’ intestines – might deserve closer scrutiny as a missing link connecting dairy consumption to increased Parkinson’s disease risk,” Dr. Kotagal said.
Dietary advice
Considering all available evidence, Dr. Appel-Cresswell offered some dietary advice with benefits that may extend beyond prevention of Parkinson’s disease.
“From a clinical point of view, I suggest to limit dairy intake to a moderate amount,” she said. “Mediterranean diets so far have the best supporting evidence for a lower Parkinson’s disease risk, although data is lacking for benefits in established Parkinson’s disease. Given the low risk of the Mediterranean diet and the established benefits for a host of other medical conditions, this is generally a safe and delicious recommendation whether one is living with Parkinson’s or not.”
The study was supported by the European Union Joint Program for Neurodegenerative Disease Research, the National Centre of Excellence in Research on Parkinson’s Disease, the National Institutes of Health, and others. The investigators disclosed additional relationships with Astellas Pharma, Sanofi, Pfizer, and others. Dr. Kotagal and Dr. Appel-Cresswell reported no relevant conflicts of interest.
*Correction, 2/10/22: An earlier version of this article misstated Dr. Kotagal's name in certain instances, including a photo caption.
according to investigators. Men of European ancestry with a genetic marker predicting dairy consumption had significantly greater risk of Parkinson’s disease than individuals without the marker, suggesting a causal relationship between dairy intake and Parkinson’s disease, lead author Cloé Domenighetti, MSc, a PhD student at UVSQ, Université Paris Sud, and colleagues reported.
“Previous studies highlighted dairy intake as a risk factor of Parkinson’s disease,” the investigators wrote in Movement Disorders. “A meta-analysis of prospective studies reported a 40% increased Parkinson’s disease risk in participants with the highest intake. It is unclear whether the association is causal or explained by confounding or reverse causation, given the long prodromal phase of Parkinson’s disease.”
A Mendelian randomization study
The investigators evaluated this link by comparing 9,823 cases of Parkinson’s disease with 8,376 controls, all individuals of European ancestry from the Courage-Parkinson’s disease consortium, comprising 23 studies. Data were analyzed by two-sample Mendelian randomization, a technique that uses genotype to predict behavior, thereby replacing conventional methods of capturing behavior, such as questionnaires. In this case, the investigators screened all participants for rs4988235, a single-nucleotide polymorphism (SNP) upstream of the lactase gene that is well documented to predict dairy intake among individuals of European ancestry.
“Mendelian randomization uses genetic variants associated with exposures as instrumental variables to estimate causal relationships between exposures and outcomes,” the investigators wrote. “Mendelian randomization analyses are less likely to be biased by confounding or reverse causation than observational studies if a set of assumptions are met.”
The approach uncovered a significant association between rs4988235 and Parkinson’s disease, with a 70% increase in disease risk per one serving of dairy per day (odds ratio, 1.70; 95% confidence interval, 1.12-2.60; P = .013). Further analysis revealed that this finding was driven by men, who had a 2.5-fold increased risk of Parkinson’s disease per one serving per day (OR, 2.50; 95% CI, 1.37-4.56; P = .003) versus women, among whom there was no significant association (OR, 1.04; 95% CI, 0.56-1.92; P = .91). No significant associations were observed among individuals grouped by age or Parkinson’s disease duration.
“Our findings suggest that dairy intake increases Parkinson’s disease risk,” the investigators concluded. “Therefore, diets with limited milk intake (e.g., Mediterranean diet) may be beneficial with respect to Parkinson’s disease.”
Further evidence supporting a link between diet and Parkinson’s disease
According to Silke Appel-Cresswell, MD, Marg Meikle Professor for Parkinson’s Research at the University of British Columbia, Vancouver, the findings align with previous prospective cohort studies demonstrating an increased risk of Parkinson’s disease with greater consumption of dairy.
“What the current study adds,” Dr. Appel-Cresswell said, “is a complementary approach to assess the association where the risk of reverse causation and of confounding are minimized. Like in some of the previous studies, the authors find sex differences with an increased risk for men but not women.”
Dr. Appel-Cresswell noted that an increasing body of evidence supports a link between diet and Parkinson’s disease, including a study of her own published last year, which showed later onset of Parkinson’s disease among individuals with a Mediterranean-style diet.
“We are accumulating evidence for a role of diet (or more broadly, the food exposome) for the risk to develop Parkinson’s disease,” Dr. Appel-Cresswell said, noting that “key pieces are still missing, including mechanisms underlying associations, clinical trials in individuals with established Parkinson’s disease and – eventually – preventive interventions. This research is urgently needed and analyses will need to take sex differences and a large range of potential other factors into account.”
A ‘modest’ contributing factor?
Vikas Kotagal, MD, associate professor of neurology at the University of Michigan, Ann Arbor, offered a perspective on the study methodology, and suggested that a causal link between dairy intake and Parkinson’s disease, if present, is likely minimal.
“Limitations to the study include the fact that participants weren’t actually asked or tested for how much dairy they truly consumed,” Dr. Kotagal said*. “Their dairy intake was estimated based on their genetic background – there are certainly many assumptions baked into this analytic approach which may or may not be true. It is also worth noting the fact that this causal association was seen in men and not women, suggesting that even if dairy intake was truly causal, it is likely to be a modest contributing factor and not a significant cause of Parkinson’s disease in the broader population in general.”
Still, Dr. Kotagal agreed with Dr. Appel-Cresswell that underlying mechanisms need further investigation.
“The biggest takeaway here is to heighten the urgency for researchers and funders to explore whether factors that might cluster with dairy intake – including pesticide exposure in milk or even the make-up of bacterial populations in different peoples’ intestines – might deserve closer scrutiny as a missing link connecting dairy consumption to increased Parkinson’s disease risk,” Dr. Kotagal said.
Dietary advice
Considering all available evidence, Dr. Appel-Cresswell offered some dietary advice with benefits that may extend beyond prevention of Parkinson’s disease.
“From a clinical point of view, I suggest to limit dairy intake to a moderate amount,” she said. “Mediterranean diets so far have the best supporting evidence for a lower Parkinson’s disease risk, although data is lacking for benefits in established Parkinson’s disease. Given the low risk of the Mediterranean diet and the established benefits for a host of other medical conditions, this is generally a safe and delicious recommendation whether one is living with Parkinson’s or not.”
The study was supported by the European Union Joint Program for Neurodegenerative Disease Research, the National Centre of Excellence in Research on Parkinson’s Disease, the National Institutes of Health, and others. The investigators disclosed additional relationships with Astellas Pharma, Sanofi, Pfizer, and others. Dr. Kotagal and Dr. Appel-Cresswell reported no relevant conflicts of interest.
*Correction, 2/10/22: An earlier version of this article misstated Dr. Kotagal's name in certain instances, including a photo caption.
according to investigators. Men of European ancestry with a genetic marker predicting dairy consumption had significantly greater risk of Parkinson’s disease than individuals without the marker, suggesting a causal relationship between dairy intake and Parkinson’s disease, lead author Cloé Domenighetti, MSc, a PhD student at UVSQ, Université Paris Sud, and colleagues reported.
“Previous studies highlighted dairy intake as a risk factor of Parkinson’s disease,” the investigators wrote in Movement Disorders. “A meta-analysis of prospective studies reported a 40% increased Parkinson’s disease risk in participants with the highest intake. It is unclear whether the association is causal or explained by confounding or reverse causation, given the long prodromal phase of Parkinson’s disease.”
A Mendelian randomization study
The investigators evaluated this link by comparing 9,823 cases of Parkinson’s disease with 8,376 controls, all individuals of European ancestry from the Courage-Parkinson’s disease consortium, comprising 23 studies. Data were analyzed by two-sample Mendelian randomization, a technique that uses genotype to predict behavior, thereby replacing conventional methods of capturing behavior, such as questionnaires. In this case, the investigators screened all participants for rs4988235, a single-nucleotide polymorphism (SNP) upstream of the lactase gene that is well documented to predict dairy intake among individuals of European ancestry.
“Mendelian randomization uses genetic variants associated with exposures as instrumental variables to estimate causal relationships between exposures and outcomes,” the investigators wrote. “Mendelian randomization analyses are less likely to be biased by confounding or reverse causation than observational studies if a set of assumptions are met.”
The approach uncovered a significant association between rs4988235 and Parkinson’s disease, with a 70% increase in disease risk per one serving of dairy per day (odds ratio, 1.70; 95% confidence interval, 1.12-2.60; P = .013). Further analysis revealed that this finding was driven by men, who had a 2.5-fold increased risk of Parkinson’s disease per one serving per day (OR, 2.50; 95% CI, 1.37-4.56; P = .003) versus women, among whom there was no significant association (OR, 1.04; 95% CI, 0.56-1.92; P = .91). No significant associations were observed among individuals grouped by age or Parkinson’s disease duration.
“Our findings suggest that dairy intake increases Parkinson’s disease risk,” the investigators concluded. “Therefore, diets with limited milk intake (e.g., Mediterranean diet) may be beneficial with respect to Parkinson’s disease.”
Further evidence supporting a link between diet and Parkinson’s disease
According to Silke Appel-Cresswell, MD, Marg Meikle Professor for Parkinson’s Research at the University of British Columbia, Vancouver, the findings align with previous prospective cohort studies demonstrating an increased risk of Parkinson’s disease with greater consumption of dairy.
“What the current study adds,” Dr. Appel-Cresswell said, “is a complementary approach to assess the association where the risk of reverse causation and of confounding are minimized. Like in some of the previous studies, the authors find sex differences with an increased risk for men but not women.”
Dr. Appel-Cresswell noted that an increasing body of evidence supports a link between diet and Parkinson’s disease, including a study of her own published last year, which showed later onset of Parkinson’s disease among individuals with a Mediterranean-style diet.
“We are accumulating evidence for a role of diet (or more broadly, the food exposome) for the risk to develop Parkinson’s disease,” Dr. Appel-Cresswell said, noting that “key pieces are still missing, including mechanisms underlying associations, clinical trials in individuals with established Parkinson’s disease and – eventually – preventive interventions. This research is urgently needed and analyses will need to take sex differences and a large range of potential other factors into account.”
A ‘modest’ contributing factor?
Vikas Kotagal, MD, associate professor of neurology at the University of Michigan, Ann Arbor, offered a perspective on the study methodology, and suggested that a causal link between dairy intake and Parkinson’s disease, if present, is likely minimal.
“Limitations to the study include the fact that participants weren’t actually asked or tested for how much dairy they truly consumed,” Dr. Kotagal said*. “Their dairy intake was estimated based on their genetic background – there are certainly many assumptions baked into this analytic approach which may or may not be true. It is also worth noting the fact that this causal association was seen in men and not women, suggesting that even if dairy intake was truly causal, it is likely to be a modest contributing factor and not a significant cause of Parkinson’s disease in the broader population in general.”
Still, Dr. Kotagal agreed with Dr. Appel-Cresswell that underlying mechanisms need further investigation.
“The biggest takeaway here is to heighten the urgency for researchers and funders to explore whether factors that might cluster with dairy intake – including pesticide exposure in milk or even the make-up of bacterial populations in different peoples’ intestines – might deserve closer scrutiny as a missing link connecting dairy consumption to increased Parkinson’s disease risk,” Dr. Kotagal said.
Dietary advice
Considering all available evidence, Dr. Appel-Cresswell offered some dietary advice with benefits that may extend beyond prevention of Parkinson’s disease.
“From a clinical point of view, I suggest to limit dairy intake to a moderate amount,” she said. “Mediterranean diets so far have the best supporting evidence for a lower Parkinson’s disease risk, although data is lacking for benefits in established Parkinson’s disease. Given the low risk of the Mediterranean diet and the established benefits for a host of other medical conditions, this is generally a safe and delicious recommendation whether one is living with Parkinson’s or not.”
The study was supported by the European Union Joint Program for Neurodegenerative Disease Research, the National Centre of Excellence in Research on Parkinson’s Disease, the National Institutes of Health, and others. The investigators disclosed additional relationships with Astellas Pharma, Sanofi, Pfizer, and others. Dr. Kotagal and Dr. Appel-Cresswell reported no relevant conflicts of interest.
*Correction, 2/10/22: An earlier version of this article misstated Dr. Kotagal's name in certain instances, including a photo caption.
FROM MOVEMENT DISORDERS
Can immunotherapy replace surgery for stomach cancer?
GERCOR NEONIPIGA was a phase 2 study with no comparator group and only 32 patients, but even so, after a 6-cycle course of nivolumab and ipilimumab, there was no sign of tumor in 17 of the 29 patients (59%) who had surgery specimens evaluable by pathology.
Indeed, two patients refused surgery after their preop endoscopic biopsies came back clear with no tumor cells. Surgery was called off in a third patient who developed metastases beforehand.
After a median of 12 months follow-up, there’s was no recurrence or progression in 30 patients (94%). The remaining two included the metastatic patient and one who died 3 days after surgery from cardiovascular complications.
If the findings pan out with additional research, the approach could be a boon for people who respond. “Avoiding surgery is a dream for these patients,” said lead investigator Thierry Andre, MD, a medical oncology professor at Sorbonne University, Paris, when he presented the findings at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium.
The trial “raises the question whether surgery can be delayed or avoided in some patients with localized” disease. Given the findings, “it seems possible not for all but probably for half, maybe more.” As in the two subjects who opted out of surgery, preop endoscopic biopsies could be used to identify complete responders with active surveillance afterwards, he said.
The study included 16 patients with gastric cancer and 16 with esophagogastric adenocarcinoma. They were mismatch repair deficient, which Dr. Andre said predicts response to immunotherapy.
At baseline, 22 had stage T3 disease and four had stage T2 disease, and stage was not evaluable by echo-endoscopy in 6. Nodal status was unknown, but the patients had no metastases at baseline.
They underwent six nivolumab 240-mg infusions and two ipilimumab 1–mg/kg infusions over 12 weeks, followed by R0 resections a median of 5 weeks after the last nivolumab injection.
Surgical specimens from 17 patients (59%) showed a complete pathological response to neoadjuvant immunotherapy (Becker tumor regression grade (TRG) 1a, ypT0N0). TRG was 1b – less than 10% residual tumor in tumor bed in four patients. TRG was 2 in two patients with 10%-50% of residual tumor remaining, and six had a TRG of 3 with more than half of the tumor remaining after immunotherapy.
Based on tumor response, 25 patients had nine additional nivolumab infusions after surgery with 480 mg infused monthly.
Dr. Andre explained that people want to avoid surgery because of the substantial morbidity that was shown in the study, plus 54% of patients had complications, including anastomotic leaks, pancreatitis, pneumonia, and other problems.
There were no new safety signals with neoadjuvant therapy; 25% of patients had grade 3 or 4 events.
The study was conducted in 10 centers in France. About three-quarters of the subjects were men and the median age was 65 years.
Bristol Meyers Squibb supplied the nivolumab and ipilimumab and partially funded the work. Many of the investigators had ties to the company, including Dr. Andre, who is a consultant for BMS and reported payments from the company.
GERCOR NEONIPIGA was a phase 2 study with no comparator group and only 32 patients, but even so, after a 6-cycle course of nivolumab and ipilimumab, there was no sign of tumor in 17 of the 29 patients (59%) who had surgery specimens evaluable by pathology.
Indeed, two patients refused surgery after their preop endoscopic biopsies came back clear with no tumor cells. Surgery was called off in a third patient who developed metastases beforehand.
After a median of 12 months follow-up, there’s was no recurrence or progression in 30 patients (94%). The remaining two included the metastatic patient and one who died 3 days after surgery from cardiovascular complications.
If the findings pan out with additional research, the approach could be a boon for people who respond. “Avoiding surgery is a dream for these patients,” said lead investigator Thierry Andre, MD, a medical oncology professor at Sorbonne University, Paris, when he presented the findings at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium.
The trial “raises the question whether surgery can be delayed or avoided in some patients with localized” disease. Given the findings, “it seems possible not for all but probably for half, maybe more.” As in the two subjects who opted out of surgery, preop endoscopic biopsies could be used to identify complete responders with active surveillance afterwards, he said.
The study included 16 patients with gastric cancer and 16 with esophagogastric adenocarcinoma. They were mismatch repair deficient, which Dr. Andre said predicts response to immunotherapy.
At baseline, 22 had stage T3 disease and four had stage T2 disease, and stage was not evaluable by echo-endoscopy in 6. Nodal status was unknown, but the patients had no metastases at baseline.
They underwent six nivolumab 240-mg infusions and two ipilimumab 1–mg/kg infusions over 12 weeks, followed by R0 resections a median of 5 weeks after the last nivolumab injection.
Surgical specimens from 17 patients (59%) showed a complete pathological response to neoadjuvant immunotherapy (Becker tumor regression grade (TRG) 1a, ypT0N0). TRG was 1b – less than 10% residual tumor in tumor bed in four patients. TRG was 2 in two patients with 10%-50% of residual tumor remaining, and six had a TRG of 3 with more than half of the tumor remaining after immunotherapy.
Based on tumor response, 25 patients had nine additional nivolumab infusions after surgery with 480 mg infused monthly.
Dr. Andre explained that people want to avoid surgery because of the substantial morbidity that was shown in the study, plus 54% of patients had complications, including anastomotic leaks, pancreatitis, pneumonia, and other problems.
There were no new safety signals with neoadjuvant therapy; 25% of patients had grade 3 or 4 events.
The study was conducted in 10 centers in France. About three-quarters of the subjects were men and the median age was 65 years.
Bristol Meyers Squibb supplied the nivolumab and ipilimumab and partially funded the work. Many of the investigators had ties to the company, including Dr. Andre, who is a consultant for BMS and reported payments from the company.
GERCOR NEONIPIGA was a phase 2 study with no comparator group and only 32 patients, but even so, after a 6-cycle course of nivolumab and ipilimumab, there was no sign of tumor in 17 of the 29 patients (59%) who had surgery specimens evaluable by pathology.
Indeed, two patients refused surgery after their preop endoscopic biopsies came back clear with no tumor cells. Surgery was called off in a third patient who developed metastases beforehand.
After a median of 12 months follow-up, there’s was no recurrence or progression in 30 patients (94%). The remaining two included the metastatic patient and one who died 3 days after surgery from cardiovascular complications.
If the findings pan out with additional research, the approach could be a boon for people who respond. “Avoiding surgery is a dream for these patients,” said lead investigator Thierry Andre, MD, a medical oncology professor at Sorbonne University, Paris, when he presented the findings at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium.
The trial “raises the question whether surgery can be delayed or avoided in some patients with localized” disease. Given the findings, “it seems possible not for all but probably for half, maybe more.” As in the two subjects who opted out of surgery, preop endoscopic biopsies could be used to identify complete responders with active surveillance afterwards, he said.
The study included 16 patients with gastric cancer and 16 with esophagogastric adenocarcinoma. They were mismatch repair deficient, which Dr. Andre said predicts response to immunotherapy.
At baseline, 22 had stage T3 disease and four had stage T2 disease, and stage was not evaluable by echo-endoscopy in 6. Nodal status was unknown, but the patients had no metastases at baseline.
They underwent six nivolumab 240-mg infusions and two ipilimumab 1–mg/kg infusions over 12 weeks, followed by R0 resections a median of 5 weeks after the last nivolumab injection.
Surgical specimens from 17 patients (59%) showed a complete pathological response to neoadjuvant immunotherapy (Becker tumor regression grade (TRG) 1a, ypT0N0). TRG was 1b – less than 10% residual tumor in tumor bed in four patients. TRG was 2 in two patients with 10%-50% of residual tumor remaining, and six had a TRG of 3 with more than half of the tumor remaining after immunotherapy.
Based on tumor response, 25 patients had nine additional nivolumab infusions after surgery with 480 mg infused monthly.
Dr. Andre explained that people want to avoid surgery because of the substantial morbidity that was shown in the study, plus 54% of patients had complications, including anastomotic leaks, pancreatitis, pneumonia, and other problems.
There were no new safety signals with neoadjuvant therapy; 25% of patients had grade 3 or 4 events.
The study was conducted in 10 centers in France. About three-quarters of the subjects were men and the median age was 65 years.
Bristol Meyers Squibb supplied the nivolumab and ipilimumab and partially funded the work. Many of the investigators had ties to the company, including Dr. Andre, who is a consultant for BMS and reported payments from the company.
FROM GI CANCERS SYMPOSIUM 2022