User login
My choice? Unvaccinated pose outsize risk to vaccinated
according to a mathematical modeling study.
The study, which simulated patterns of infection among vaccinated and unvaccinated populations, showed that, as the populations mixed less, attack rates decreased among vaccinated people (from 15% to 10%) and increased among unvaccinated people (from 62% to 79%). The unvaccinated increasingly became the source of infection, however.
“When the vaccinated and unvaccinated mix, indirect protection is conferred upon the unvaccinated by the buffering effect of vaccinated individuals, and by contrast, risk in the vaccinated goes up,” lead author David Fisman, MD, professor of epidemiology at the University of Toronto, told this news organization.
As the groups mix less and less, the size of the epidemic increases among the unvaccinated and decreases among the vaccinated. “But the impact of the unvaccinated on risk in the vaccinated is disproportionate to the numbers of contacts between the two groups,” said Dr. Fisman.
The study was published online in the Canadian Medical Association Journal.
Relative contributions to risk
The researchers used a model of a respiratory viral disease “similar to SARS-CoV-2 infection with Delta variant.” They included reproduction values to capture the dynamics of the Omicron variant, which was emerging at the time. In the study, vaccines ranged in effectiveness from 40% to 80%. The study incorporated various levels of mixing between a partially vaccinated and an unvaccinated population. The mixing ranged from random mixing to like-with-like mixing (“assortativity”). There were three possible “compartments” of people in the model: those considered susceptible to infection, those considered infected and infectious, and those considered immune because of recovery.
The model showed that, as mixing between the vaccinated and the unvaccinated populations increased, case numbers rose, “with cases in the unvaccinated subpopulation accounting for a substantial proportion of infections.” However, as mixing between the populations decreased, the final attack rate decreased among vaccinated people, but the relative “contribution of risk to vaccinated people caused by infection acquired from contact with unvaccinated people ... increased.”
When the vaccination rate was increased in the model, case numbers among the vaccinated declined “as expected, owing to indirect protective effects,” the researchers noted. But this also “further increased the relative contribution to risk in vaccinated people by those who were unvaccinated.”
Self-regarding risk?
The findings show that “choices made by people who forgo vaccination contribute disproportionately to risk among those who do get vaccinated,” the researchers wrote. “Although risk associated with avoiding vaccination during a virulent pandemic accrues chiefly to those who are unvaccinated, the choice of some individuals to refuse vaccination is likely to affect the health and safety of vaccinated people in a manner disproportionate to the fraction of unvaccinated people in the population.”
The fact that like-with-like mixing cannot mitigate the risk to vaccinated people “undermines the assertion that vaccine choice is best left to the individual and supports strong public actions aimed at enhancing vaccine uptake and limiting access to public spaces for unvaccinated people,” they wrote.
Mandates and passports
“Our model provides support for vaccine mandates and passports during epidemics, such that vaccination is required for people to take part in nonessential activities,” said Dr. Fisman. The choice to not be vaccinated against COVID-19 should not be considered “self-regarding,” he added. “Risk is self-regarding when it only impacts the person engaging in the activity. Something like smoking cigarettes (alone, without others around) creates a lot of risk over time, but if nobody is breathing your secondhand smoke, you’re only creating risk for yourself. By contrast, we regulate, in Ontario, your right to smoke in public indoor spaces such as restaurants, because once other people are around, the risk isn’t self-regarding anymore. You’re creating risk for others.”
The authors also noted that the risks created by the unvaccinated extend beyond those of infection by “creating a risk that those around them may not be able to obtain the care they need.” They recommended that considerations of equity and justice for people who do choose to be vaccinated, as well as those who choose not to be, need to be included in formulating vaccination policy.
Illuminating the discussion
Asked to comment on the study, Matthew Oughton, MD, assistant professor of medicine at McGill University, Montreal, said: “It is easy to dismiss a mathematical model as a series of assumptions that leads to an implausible conclusion. ... However, they can serve to illustrate and, to an extent, quantify the results of complex interactions, and this study does just that.” Dr. Oughton was not involved in the research.
During the past 2 years, the scientific press and the general press have often discussed the individual and collective effects of disease-prevention methods, including nonpharmaceutical interventions. “Models like this can help illuminate those discussions by highlighting important consequences of preventive measures,” said Dr. Oughton, who also works in the division of infectious diseases at the Jewish General Hospital, Montreal.
It’s worth noting that the authors modeled vaccine effectiveness against all infection, “rather than the generally greater and more durable effects we have seen for vaccines in prevention of severe infection,” said Dr. Oughton. He added that the authors did not include the effect of vaccination in reducing forward transmission. “Inclusion of this effect would presumably have reduced overall infectious burden in mixed populations and increased the difference between groups at lower levels of mixing between populations.”
The research was supported by a grant from the Canadian Institutes of Health Research. Dr. Fisman has served on advisory boards related to influenza and SARS-CoV-2 vaccines for Seqirus, Pfizer, AstraZeneca, and Sanofi-Pasteur Vaccines and has served as a legal expert on issues related to COVID-19 epidemiology for the Elementary Teachers Federation of Ontario and the Registered Nurses Association of Ontario. Dr. Oughton disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a mathematical modeling study.
The study, which simulated patterns of infection among vaccinated and unvaccinated populations, showed that, as the populations mixed less, attack rates decreased among vaccinated people (from 15% to 10%) and increased among unvaccinated people (from 62% to 79%). The unvaccinated increasingly became the source of infection, however.
“When the vaccinated and unvaccinated mix, indirect protection is conferred upon the unvaccinated by the buffering effect of vaccinated individuals, and by contrast, risk in the vaccinated goes up,” lead author David Fisman, MD, professor of epidemiology at the University of Toronto, told this news organization.
As the groups mix less and less, the size of the epidemic increases among the unvaccinated and decreases among the vaccinated. “But the impact of the unvaccinated on risk in the vaccinated is disproportionate to the numbers of contacts between the two groups,” said Dr. Fisman.
The study was published online in the Canadian Medical Association Journal.
Relative contributions to risk
The researchers used a model of a respiratory viral disease “similar to SARS-CoV-2 infection with Delta variant.” They included reproduction values to capture the dynamics of the Omicron variant, which was emerging at the time. In the study, vaccines ranged in effectiveness from 40% to 80%. The study incorporated various levels of mixing between a partially vaccinated and an unvaccinated population. The mixing ranged from random mixing to like-with-like mixing (“assortativity”). There were three possible “compartments” of people in the model: those considered susceptible to infection, those considered infected and infectious, and those considered immune because of recovery.
The model showed that, as mixing between the vaccinated and the unvaccinated populations increased, case numbers rose, “with cases in the unvaccinated subpopulation accounting for a substantial proportion of infections.” However, as mixing between the populations decreased, the final attack rate decreased among vaccinated people, but the relative “contribution of risk to vaccinated people caused by infection acquired from contact with unvaccinated people ... increased.”
When the vaccination rate was increased in the model, case numbers among the vaccinated declined “as expected, owing to indirect protective effects,” the researchers noted. But this also “further increased the relative contribution to risk in vaccinated people by those who were unvaccinated.”
Self-regarding risk?
The findings show that “choices made by people who forgo vaccination contribute disproportionately to risk among those who do get vaccinated,” the researchers wrote. “Although risk associated with avoiding vaccination during a virulent pandemic accrues chiefly to those who are unvaccinated, the choice of some individuals to refuse vaccination is likely to affect the health and safety of vaccinated people in a manner disproportionate to the fraction of unvaccinated people in the population.”
The fact that like-with-like mixing cannot mitigate the risk to vaccinated people “undermines the assertion that vaccine choice is best left to the individual and supports strong public actions aimed at enhancing vaccine uptake and limiting access to public spaces for unvaccinated people,” they wrote.
Mandates and passports
“Our model provides support for vaccine mandates and passports during epidemics, such that vaccination is required for people to take part in nonessential activities,” said Dr. Fisman. The choice to not be vaccinated against COVID-19 should not be considered “self-regarding,” he added. “Risk is self-regarding when it only impacts the person engaging in the activity. Something like smoking cigarettes (alone, without others around) creates a lot of risk over time, but if nobody is breathing your secondhand smoke, you’re only creating risk for yourself. By contrast, we regulate, in Ontario, your right to smoke in public indoor spaces such as restaurants, because once other people are around, the risk isn’t self-regarding anymore. You’re creating risk for others.”
The authors also noted that the risks created by the unvaccinated extend beyond those of infection by “creating a risk that those around them may not be able to obtain the care they need.” They recommended that considerations of equity and justice for people who do choose to be vaccinated, as well as those who choose not to be, need to be included in formulating vaccination policy.
Illuminating the discussion
Asked to comment on the study, Matthew Oughton, MD, assistant professor of medicine at McGill University, Montreal, said: “It is easy to dismiss a mathematical model as a series of assumptions that leads to an implausible conclusion. ... However, they can serve to illustrate and, to an extent, quantify the results of complex interactions, and this study does just that.” Dr. Oughton was not involved in the research.
During the past 2 years, the scientific press and the general press have often discussed the individual and collective effects of disease-prevention methods, including nonpharmaceutical interventions. “Models like this can help illuminate those discussions by highlighting important consequences of preventive measures,” said Dr. Oughton, who also works in the division of infectious diseases at the Jewish General Hospital, Montreal.
It’s worth noting that the authors modeled vaccine effectiveness against all infection, “rather than the generally greater and more durable effects we have seen for vaccines in prevention of severe infection,” said Dr. Oughton. He added that the authors did not include the effect of vaccination in reducing forward transmission. “Inclusion of this effect would presumably have reduced overall infectious burden in mixed populations and increased the difference between groups at lower levels of mixing between populations.”
The research was supported by a grant from the Canadian Institutes of Health Research. Dr. Fisman has served on advisory boards related to influenza and SARS-CoV-2 vaccines for Seqirus, Pfizer, AstraZeneca, and Sanofi-Pasteur Vaccines and has served as a legal expert on issues related to COVID-19 epidemiology for the Elementary Teachers Federation of Ontario and the Registered Nurses Association of Ontario. Dr. Oughton disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a mathematical modeling study.
The study, which simulated patterns of infection among vaccinated and unvaccinated populations, showed that, as the populations mixed less, attack rates decreased among vaccinated people (from 15% to 10%) and increased among unvaccinated people (from 62% to 79%). The unvaccinated increasingly became the source of infection, however.
“When the vaccinated and unvaccinated mix, indirect protection is conferred upon the unvaccinated by the buffering effect of vaccinated individuals, and by contrast, risk in the vaccinated goes up,” lead author David Fisman, MD, professor of epidemiology at the University of Toronto, told this news organization.
As the groups mix less and less, the size of the epidemic increases among the unvaccinated and decreases among the vaccinated. “But the impact of the unvaccinated on risk in the vaccinated is disproportionate to the numbers of contacts between the two groups,” said Dr. Fisman.
The study was published online in the Canadian Medical Association Journal.
Relative contributions to risk
The researchers used a model of a respiratory viral disease “similar to SARS-CoV-2 infection with Delta variant.” They included reproduction values to capture the dynamics of the Omicron variant, which was emerging at the time. In the study, vaccines ranged in effectiveness from 40% to 80%. The study incorporated various levels of mixing between a partially vaccinated and an unvaccinated population. The mixing ranged from random mixing to like-with-like mixing (“assortativity”). There were three possible “compartments” of people in the model: those considered susceptible to infection, those considered infected and infectious, and those considered immune because of recovery.
The model showed that, as mixing between the vaccinated and the unvaccinated populations increased, case numbers rose, “with cases in the unvaccinated subpopulation accounting for a substantial proportion of infections.” However, as mixing between the populations decreased, the final attack rate decreased among vaccinated people, but the relative “contribution of risk to vaccinated people caused by infection acquired from contact with unvaccinated people ... increased.”
When the vaccination rate was increased in the model, case numbers among the vaccinated declined “as expected, owing to indirect protective effects,” the researchers noted. But this also “further increased the relative contribution to risk in vaccinated people by those who were unvaccinated.”
Self-regarding risk?
The findings show that “choices made by people who forgo vaccination contribute disproportionately to risk among those who do get vaccinated,” the researchers wrote. “Although risk associated with avoiding vaccination during a virulent pandemic accrues chiefly to those who are unvaccinated, the choice of some individuals to refuse vaccination is likely to affect the health and safety of vaccinated people in a manner disproportionate to the fraction of unvaccinated people in the population.”
The fact that like-with-like mixing cannot mitigate the risk to vaccinated people “undermines the assertion that vaccine choice is best left to the individual and supports strong public actions aimed at enhancing vaccine uptake and limiting access to public spaces for unvaccinated people,” they wrote.
Mandates and passports
“Our model provides support for vaccine mandates and passports during epidemics, such that vaccination is required for people to take part in nonessential activities,” said Dr. Fisman. The choice to not be vaccinated against COVID-19 should not be considered “self-regarding,” he added. “Risk is self-regarding when it only impacts the person engaging in the activity. Something like smoking cigarettes (alone, without others around) creates a lot of risk over time, but if nobody is breathing your secondhand smoke, you’re only creating risk for yourself. By contrast, we regulate, in Ontario, your right to smoke in public indoor spaces such as restaurants, because once other people are around, the risk isn’t self-regarding anymore. You’re creating risk for others.”
The authors also noted that the risks created by the unvaccinated extend beyond those of infection by “creating a risk that those around them may not be able to obtain the care they need.” They recommended that considerations of equity and justice for people who do choose to be vaccinated, as well as those who choose not to be, need to be included in formulating vaccination policy.
Illuminating the discussion
Asked to comment on the study, Matthew Oughton, MD, assistant professor of medicine at McGill University, Montreal, said: “It is easy to dismiss a mathematical model as a series of assumptions that leads to an implausible conclusion. ... However, they can serve to illustrate and, to an extent, quantify the results of complex interactions, and this study does just that.” Dr. Oughton was not involved in the research.
During the past 2 years, the scientific press and the general press have often discussed the individual and collective effects of disease-prevention methods, including nonpharmaceutical interventions. “Models like this can help illuminate those discussions by highlighting important consequences of preventive measures,” said Dr. Oughton, who also works in the division of infectious diseases at the Jewish General Hospital, Montreal.
It’s worth noting that the authors modeled vaccine effectiveness against all infection, “rather than the generally greater and more durable effects we have seen for vaccines in prevention of severe infection,” said Dr. Oughton. He added that the authors did not include the effect of vaccination in reducing forward transmission. “Inclusion of this effect would presumably have reduced overall infectious burden in mixed populations and increased the difference between groups at lower levels of mixing between populations.”
The research was supported by a grant from the Canadian Institutes of Health Research. Dr. Fisman has served on advisory boards related to influenza and SARS-CoV-2 vaccines for Seqirus, Pfizer, AstraZeneca, and Sanofi-Pasteur Vaccines and has served as a legal expert on issues related to COVID-19 epidemiology for the Elementary Teachers Federation of Ontario and the Registered Nurses Association of Ontario. Dr. Oughton disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE CANADIAN MEDICAL ASSOCIATION JOURNAL
Drug combo holds promise as on-demand contraceptive: Study
A combination of ulipristal acetate (UA) and a cyclo-oxygenase-2 (COX-2) inhibitor holds promise as a pericoital, “on- demand” female oral contraceptive, taken only when needed, according to an exploratory study published in BMJ Sexual & Reproductive Health.
The prospective, open-label, pilot study showed that UA and meloxicam successfully disrupted ovulation at “the peak of luteal surge, when conception risk is highest,” reported lead author Erica P Cahill, MD, of Stanford (Calif.) University, and colleagues.
“There are many people who report being interested in preventing pregnancy who are not using contraception,” Dr. Cahill said in an interview. The ideal is to be able to take a medication to prevent ovulation and know that you wouldn’t ovulate or be able to become pregnant for the next 3-5 days. These would be pericoital contraceptive pills that one could take prior to or immediately after intercourse that would expand the contraceptive options available and meet some of this need, she said.
Dr. Cahill said currently approved emergency contraceptives containing ulipristal acetate or levonorgestrel “work by inhibiting ovulation at the level of the luteal surge, the pituitary signal that starts the ovulation cascade. Because of this mechanism, they are only effective when taken prior to that signal. If they are taken near or after ovulation has occurred, they are not effective.” She said combining meloxicam with UA could address this because meloxicam “has been shown to prevent some of the later steps of ovulation just prior to the egg being released.”
The study included nine healthy women, with a mean age of 31.4 years, and a mean body mass index of 24.5 ± 3.9 kg/m2. All subjects had no exposure to hormonal medication, pregnancy, or lactation in the prior 3 months.
Each participant was followed for two cycles: The first without treatment, to establish normal ovulatory function; and the second during treatment with a one-time dose of UA 30 mg and meloxicam 30 mg during the “fertile window.” This window was defined as when the lead ovarian follicle had a mean diameter of 18 mm, and was determined via thrice-weekly ultrasounds, as well as luteinizing hormone (LH) measurements.
The primary outcome of the study was ovulation disruption, defined as unruptured dominant follicle for 5 days, a blunted LH peak, defined as <15 IU/L, and a nonovulatory luteal phase progesterone level, defined as <3 ng/mL.
Ovulation disruption was achieved in six subjects (67.7%), with eight subjects (88.9%) meeting some criteria.
“When we compare ovulation disruption rates in our study with the previous studies on which our protocol is based, the combination of UA and meloxicam disrupted ovulation at each phase of the fertile window more than any other medication previously studied,” the researchers wrote. “This medication combination is an important candidate to evaluate as oral pericoital contraception.”
When comparing subjects’ baseline cycles with their treatment cycles, the latter were approximately 3 days longer, although there was no difference in endometrial stripe thickness or irregular bleeding.
“Cycle length changes are an important parameter as people interested in oral, on-demand contraception may also be using fertility awareness methods which can be affected by cycle length changes.”
The authors noted that measures of full efficacy and side effects were beyond the scope of the study and would require repeat dosing. Similarly, liver enzymes were not measured, because there was only one dose of study medication, but “given the potential impact of repeat UA on liver enzymes, this measurement is critical for future studies.”
Asked to comment on the study, Eve Espey, MD, said that although it was limited in size and the use of an “intermediate outcome” of ovulation disruption, “the combination does show some promise as a focus of future research.” However, Dr. Espey, distinguished professor and chair in the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, said it is too early to determine the significance of the findings. “But it does point the way to further research,” she noted. “Compared with existing emergency contraception, this study shows that the UA-meloxicam combination disrupts ovulation over a broader mid-cycle time period – [an] extended duration of action [that] could theoretically translate into increased effectiveness as a contraceptive.”
The study was supported by the Society for Family Planning Research Fund. None of the authors, or Dr. Espey, declared competing interests.
A combination of ulipristal acetate (UA) and a cyclo-oxygenase-2 (COX-2) inhibitor holds promise as a pericoital, “on- demand” female oral contraceptive, taken only when needed, according to an exploratory study published in BMJ Sexual & Reproductive Health.
The prospective, open-label, pilot study showed that UA and meloxicam successfully disrupted ovulation at “the peak of luteal surge, when conception risk is highest,” reported lead author Erica P Cahill, MD, of Stanford (Calif.) University, and colleagues.
“There are many people who report being interested in preventing pregnancy who are not using contraception,” Dr. Cahill said in an interview. The ideal is to be able to take a medication to prevent ovulation and know that you wouldn’t ovulate or be able to become pregnant for the next 3-5 days. These would be pericoital contraceptive pills that one could take prior to or immediately after intercourse that would expand the contraceptive options available and meet some of this need, she said.
Dr. Cahill said currently approved emergency contraceptives containing ulipristal acetate or levonorgestrel “work by inhibiting ovulation at the level of the luteal surge, the pituitary signal that starts the ovulation cascade. Because of this mechanism, they are only effective when taken prior to that signal. If they are taken near or after ovulation has occurred, they are not effective.” She said combining meloxicam with UA could address this because meloxicam “has been shown to prevent some of the later steps of ovulation just prior to the egg being released.”
The study included nine healthy women, with a mean age of 31.4 years, and a mean body mass index of 24.5 ± 3.9 kg/m2. All subjects had no exposure to hormonal medication, pregnancy, or lactation in the prior 3 months.
Each participant was followed for two cycles: The first without treatment, to establish normal ovulatory function; and the second during treatment with a one-time dose of UA 30 mg and meloxicam 30 mg during the “fertile window.” This window was defined as when the lead ovarian follicle had a mean diameter of 18 mm, and was determined via thrice-weekly ultrasounds, as well as luteinizing hormone (LH) measurements.
The primary outcome of the study was ovulation disruption, defined as unruptured dominant follicle for 5 days, a blunted LH peak, defined as <15 IU/L, and a nonovulatory luteal phase progesterone level, defined as <3 ng/mL.
Ovulation disruption was achieved in six subjects (67.7%), with eight subjects (88.9%) meeting some criteria.
“When we compare ovulation disruption rates in our study with the previous studies on which our protocol is based, the combination of UA and meloxicam disrupted ovulation at each phase of the fertile window more than any other medication previously studied,” the researchers wrote. “This medication combination is an important candidate to evaluate as oral pericoital contraception.”
When comparing subjects’ baseline cycles with their treatment cycles, the latter were approximately 3 days longer, although there was no difference in endometrial stripe thickness or irregular bleeding.
“Cycle length changes are an important parameter as people interested in oral, on-demand contraception may also be using fertility awareness methods which can be affected by cycle length changes.”
The authors noted that measures of full efficacy and side effects were beyond the scope of the study and would require repeat dosing. Similarly, liver enzymes were not measured, because there was only one dose of study medication, but “given the potential impact of repeat UA on liver enzymes, this measurement is critical for future studies.”
Asked to comment on the study, Eve Espey, MD, said that although it was limited in size and the use of an “intermediate outcome” of ovulation disruption, “the combination does show some promise as a focus of future research.” However, Dr. Espey, distinguished professor and chair in the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, said it is too early to determine the significance of the findings. “But it does point the way to further research,” she noted. “Compared with existing emergency contraception, this study shows that the UA-meloxicam combination disrupts ovulation over a broader mid-cycle time period – [an] extended duration of action [that] could theoretically translate into increased effectiveness as a contraceptive.”
The study was supported by the Society for Family Planning Research Fund. None of the authors, or Dr. Espey, declared competing interests.
A combination of ulipristal acetate (UA) and a cyclo-oxygenase-2 (COX-2) inhibitor holds promise as a pericoital, “on- demand” female oral contraceptive, taken only when needed, according to an exploratory study published in BMJ Sexual & Reproductive Health.
The prospective, open-label, pilot study showed that UA and meloxicam successfully disrupted ovulation at “the peak of luteal surge, when conception risk is highest,” reported lead author Erica P Cahill, MD, of Stanford (Calif.) University, and colleagues.
“There are many people who report being interested in preventing pregnancy who are not using contraception,” Dr. Cahill said in an interview. The ideal is to be able to take a medication to prevent ovulation and know that you wouldn’t ovulate or be able to become pregnant for the next 3-5 days. These would be pericoital contraceptive pills that one could take prior to or immediately after intercourse that would expand the contraceptive options available and meet some of this need, she said.
Dr. Cahill said currently approved emergency contraceptives containing ulipristal acetate or levonorgestrel “work by inhibiting ovulation at the level of the luteal surge, the pituitary signal that starts the ovulation cascade. Because of this mechanism, they are only effective when taken prior to that signal. If they are taken near or after ovulation has occurred, they are not effective.” She said combining meloxicam with UA could address this because meloxicam “has been shown to prevent some of the later steps of ovulation just prior to the egg being released.”
The study included nine healthy women, with a mean age of 31.4 years, and a mean body mass index of 24.5 ± 3.9 kg/m2. All subjects had no exposure to hormonal medication, pregnancy, or lactation in the prior 3 months.
Each participant was followed for two cycles: The first without treatment, to establish normal ovulatory function; and the second during treatment with a one-time dose of UA 30 mg and meloxicam 30 mg during the “fertile window.” This window was defined as when the lead ovarian follicle had a mean diameter of 18 mm, and was determined via thrice-weekly ultrasounds, as well as luteinizing hormone (LH) measurements.
The primary outcome of the study was ovulation disruption, defined as unruptured dominant follicle for 5 days, a blunted LH peak, defined as <15 IU/L, and a nonovulatory luteal phase progesterone level, defined as <3 ng/mL.
Ovulation disruption was achieved in six subjects (67.7%), with eight subjects (88.9%) meeting some criteria.
“When we compare ovulation disruption rates in our study with the previous studies on which our protocol is based, the combination of UA and meloxicam disrupted ovulation at each phase of the fertile window more than any other medication previously studied,” the researchers wrote. “This medication combination is an important candidate to evaluate as oral pericoital contraception.”
When comparing subjects’ baseline cycles with their treatment cycles, the latter were approximately 3 days longer, although there was no difference in endometrial stripe thickness or irregular bleeding.
“Cycle length changes are an important parameter as people interested in oral, on-demand contraception may also be using fertility awareness methods which can be affected by cycle length changes.”
The authors noted that measures of full efficacy and side effects were beyond the scope of the study and would require repeat dosing. Similarly, liver enzymes were not measured, because there was only one dose of study medication, but “given the potential impact of repeat UA on liver enzymes, this measurement is critical for future studies.”
Asked to comment on the study, Eve Espey, MD, said that although it was limited in size and the use of an “intermediate outcome” of ovulation disruption, “the combination does show some promise as a focus of future research.” However, Dr. Espey, distinguished professor and chair in the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, said it is too early to determine the significance of the findings. “But it does point the way to further research,” she noted. “Compared with existing emergency contraception, this study shows that the UA-meloxicam combination disrupts ovulation over a broader mid-cycle time period – [an] extended duration of action [that] could theoretically translate into increased effectiveness as a contraceptive.”
The study was supported by the Society for Family Planning Research Fund. None of the authors, or Dr. Espey, declared competing interests.
FROM BMJ SEXUAL & REPRODUCTIVE HEALTH
Three symptoms suggest higher risk for self-injury in cancer
, according to a Canadian study.
In a population-based, case-control study, each of these symptoms was associated with an increase of at least 60% in the risk for NFSI in the following 180 days, the investigators report.
“Clinicians should know that self-injury is a real problem after a cancer diagnosis,” lead investigator Julie Hallet, MD, an associate scientist at Sunnybrook Health Sciences Centre in Toronto, told this news organization.
Self-injury “does not necessarily represent an attempted suicide,” she added. “While our data do not allow us to know what the intent was, we know from other work that the repercussions of distress in patients with cancer are much broader than suicide. Self-injury can be a means to cope with psychological difficulties for some patients, without intent for suicide.”
The study was published online in JAMA Oncology.
Nine common symptoms
The study included adults who were diagnosed with cancer between Jan. 1, 2007, and March 31, 2019, and had completed the Edmonton Symptom Assessment System (ESAS) evaluation within 36 months of their index cancer diagnosis. ESAS evaluates nine common cancer-associated symptoms, including pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being, and shortness of breath, on a patient-reported scale of 0 (absence of symptom) to 10 (worst possible symptom).
The analysis included 406 patients who had visited an emergency department for an NFSI within 180 days of their ESAS evaluation, as well as 1,624 matched control patients with cancer who did not have an NFSI. Case patients and control patients were matched according to age at cancer diagnosis, sex, prior self-injury within 5 years of being diagnosed with cancer, and cancer type. Nonmatched covariates included psychiatric illness and therapy received before NFSI, comorbidity burden, material deprivation, and cancer stage.
Toward tailored intervention
A higher proportion of case patients than control patients reported moderate to severe scores for all nine ESAS symptoms. In an adjusted analysis, moderate to severe anxiety (odds ratio, 1.61), depression (OR, 1.66), and shortness of breath (OR, 1.65) were independently associated with higher odds of subsequent NFSI. Each 10-point increase in total ESAS score also was associated with increased risk (OR, 1.51).
“These findings are important to enhance the use of screening ESAS scores to better support patients,” say the authors. “Scores from ESAS assessments can be used to identify patients at higher risk of NFSI, indicating higher level of distress, and help direct tailored assessment and intervention.”
In prior work, Dr. Hallet’s group showed that NFSI occurs in 3 of every 1,000 patients with cancer. NFSI is more frequent among younger patients and those with a history of prior mental illness. “Identifying patients at risk in clinical practice requires you to inquire about a patient’s prior history, identify high symptom scores and ask about them, and trigger intervention pathways when risk is identified,” said Dr. Hallet.
“For example, a young patient with head and neck cancer and a prior history of mental illness who reports high scores for anxiety and drowsiness would be at high risk of self-injury,” she added. Such a patient should be referred to psycho-oncology, psychiatry, or social work. “To facilitate this, we are working on prognostic scores that can be integrated in clinical practice, such as an electronic medical record, to flag patients at risk,” said Dr. Hallet. “Future work will also need to identify the optimal care pathways for at-risk patients.”
Self-injury vs. suicidality
Commenting on the study for this news organization, Madeline Li, MD, PhD, a psychiatrist and clinician-scientist at Toronto’s Princess Margaret Cancer Centre, said that the findings are “underwhelming” because they tell us what is already known – that “NFSI is associated with distress, and cancer is a stressor.” It would have been more interesting to ask how to distinguish patients at risk for suicide from those at risk for self-harm without suicide, she added.
“The way these authors formulated NFSI included both self-harm intent and suicidal intent,” she explained. The researchers compared patients who were at risk for these two types of events with patients without NFSI. “When we see self-harm without suicidal intent in the emergency room, it’s mostly people making cries for help,” said Dr. Li. “These are people who cut their wrists or take small overdoses on purpose without the intent to die. It would have been more interesting to see if there are different risk factors for people who are just going to self-harm vs. those who are actually going to attempt suicide.”
The study’s identification of risk factors for NSFI is important because “it does tell us that when there’s anxiety, depression, and shortness of breath, we should pay attention to these patients and do something about it,” said Dr. Li. Still, research in cancer psychiatry needs to shift its focus from identifying and addressing existing risk factors to preventing them from developing, she added.
“We need to move earlier and provide emotional and mental health support to cancer patients to prevent them from becoming suicidal, rather than intervening when somebody already is,” Dr. Li concluded.
The study was funded by the Hanna Research Award from the division of surgical oncology at the Odette Cancer Centre–Sunnybrook Health Sciences Centre and by a Sunnybrook Health Sciences Centre Alternate Funding Plan Innovation grant. It was also supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. Dr. Hallet has received personal fees from Ipsen Biopharmaceuticals Canada and AAA outside the submitted work. Dr. Li reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, according to a Canadian study.
In a population-based, case-control study, each of these symptoms was associated with an increase of at least 60% in the risk for NFSI in the following 180 days, the investigators report.
“Clinicians should know that self-injury is a real problem after a cancer diagnosis,” lead investigator Julie Hallet, MD, an associate scientist at Sunnybrook Health Sciences Centre in Toronto, told this news organization.
Self-injury “does not necessarily represent an attempted suicide,” she added. “While our data do not allow us to know what the intent was, we know from other work that the repercussions of distress in patients with cancer are much broader than suicide. Self-injury can be a means to cope with psychological difficulties for some patients, without intent for suicide.”
The study was published online in JAMA Oncology.
Nine common symptoms
The study included adults who were diagnosed with cancer between Jan. 1, 2007, and March 31, 2019, and had completed the Edmonton Symptom Assessment System (ESAS) evaluation within 36 months of their index cancer diagnosis. ESAS evaluates nine common cancer-associated symptoms, including pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being, and shortness of breath, on a patient-reported scale of 0 (absence of symptom) to 10 (worst possible symptom).
The analysis included 406 patients who had visited an emergency department for an NFSI within 180 days of their ESAS evaluation, as well as 1,624 matched control patients with cancer who did not have an NFSI. Case patients and control patients were matched according to age at cancer diagnosis, sex, prior self-injury within 5 years of being diagnosed with cancer, and cancer type. Nonmatched covariates included psychiatric illness and therapy received before NFSI, comorbidity burden, material deprivation, and cancer stage.
Toward tailored intervention
A higher proportion of case patients than control patients reported moderate to severe scores for all nine ESAS symptoms. In an adjusted analysis, moderate to severe anxiety (odds ratio, 1.61), depression (OR, 1.66), and shortness of breath (OR, 1.65) were independently associated with higher odds of subsequent NFSI. Each 10-point increase in total ESAS score also was associated with increased risk (OR, 1.51).
“These findings are important to enhance the use of screening ESAS scores to better support patients,” say the authors. “Scores from ESAS assessments can be used to identify patients at higher risk of NFSI, indicating higher level of distress, and help direct tailored assessment and intervention.”
In prior work, Dr. Hallet’s group showed that NFSI occurs in 3 of every 1,000 patients with cancer. NFSI is more frequent among younger patients and those with a history of prior mental illness. “Identifying patients at risk in clinical practice requires you to inquire about a patient’s prior history, identify high symptom scores and ask about them, and trigger intervention pathways when risk is identified,” said Dr. Hallet.
“For example, a young patient with head and neck cancer and a prior history of mental illness who reports high scores for anxiety and drowsiness would be at high risk of self-injury,” she added. Such a patient should be referred to psycho-oncology, psychiatry, or social work. “To facilitate this, we are working on prognostic scores that can be integrated in clinical practice, such as an electronic medical record, to flag patients at risk,” said Dr. Hallet. “Future work will also need to identify the optimal care pathways for at-risk patients.”
Self-injury vs. suicidality
Commenting on the study for this news organization, Madeline Li, MD, PhD, a psychiatrist and clinician-scientist at Toronto’s Princess Margaret Cancer Centre, said that the findings are “underwhelming” because they tell us what is already known – that “NFSI is associated with distress, and cancer is a stressor.” It would have been more interesting to ask how to distinguish patients at risk for suicide from those at risk for self-harm without suicide, she added.
“The way these authors formulated NFSI included both self-harm intent and suicidal intent,” she explained. The researchers compared patients who were at risk for these two types of events with patients without NFSI. “When we see self-harm without suicidal intent in the emergency room, it’s mostly people making cries for help,” said Dr. Li. “These are people who cut their wrists or take small overdoses on purpose without the intent to die. It would have been more interesting to see if there are different risk factors for people who are just going to self-harm vs. those who are actually going to attempt suicide.”
The study’s identification of risk factors for NSFI is important because “it does tell us that when there’s anxiety, depression, and shortness of breath, we should pay attention to these patients and do something about it,” said Dr. Li. Still, research in cancer psychiatry needs to shift its focus from identifying and addressing existing risk factors to preventing them from developing, she added.
“We need to move earlier and provide emotional and mental health support to cancer patients to prevent them from becoming suicidal, rather than intervening when somebody already is,” Dr. Li concluded.
The study was funded by the Hanna Research Award from the division of surgical oncology at the Odette Cancer Centre–Sunnybrook Health Sciences Centre and by a Sunnybrook Health Sciences Centre Alternate Funding Plan Innovation grant. It was also supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. Dr. Hallet has received personal fees from Ipsen Biopharmaceuticals Canada and AAA outside the submitted work. Dr. Li reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, according to a Canadian study.
In a population-based, case-control study, each of these symptoms was associated with an increase of at least 60% in the risk for NFSI in the following 180 days, the investigators report.
“Clinicians should know that self-injury is a real problem after a cancer diagnosis,” lead investigator Julie Hallet, MD, an associate scientist at Sunnybrook Health Sciences Centre in Toronto, told this news organization.
Self-injury “does not necessarily represent an attempted suicide,” she added. “While our data do not allow us to know what the intent was, we know from other work that the repercussions of distress in patients with cancer are much broader than suicide. Self-injury can be a means to cope with psychological difficulties for some patients, without intent for suicide.”
The study was published online in JAMA Oncology.
Nine common symptoms
The study included adults who were diagnosed with cancer between Jan. 1, 2007, and March 31, 2019, and had completed the Edmonton Symptom Assessment System (ESAS) evaluation within 36 months of their index cancer diagnosis. ESAS evaluates nine common cancer-associated symptoms, including pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being, and shortness of breath, on a patient-reported scale of 0 (absence of symptom) to 10 (worst possible symptom).
The analysis included 406 patients who had visited an emergency department for an NFSI within 180 days of their ESAS evaluation, as well as 1,624 matched control patients with cancer who did not have an NFSI. Case patients and control patients were matched according to age at cancer diagnosis, sex, prior self-injury within 5 years of being diagnosed with cancer, and cancer type. Nonmatched covariates included psychiatric illness and therapy received before NFSI, comorbidity burden, material deprivation, and cancer stage.
Toward tailored intervention
A higher proportion of case patients than control patients reported moderate to severe scores for all nine ESAS symptoms. In an adjusted analysis, moderate to severe anxiety (odds ratio, 1.61), depression (OR, 1.66), and shortness of breath (OR, 1.65) were independently associated with higher odds of subsequent NFSI. Each 10-point increase in total ESAS score also was associated with increased risk (OR, 1.51).
“These findings are important to enhance the use of screening ESAS scores to better support patients,” say the authors. “Scores from ESAS assessments can be used to identify patients at higher risk of NFSI, indicating higher level of distress, and help direct tailored assessment and intervention.”
In prior work, Dr. Hallet’s group showed that NFSI occurs in 3 of every 1,000 patients with cancer. NFSI is more frequent among younger patients and those with a history of prior mental illness. “Identifying patients at risk in clinical practice requires you to inquire about a patient’s prior history, identify high symptom scores and ask about them, and trigger intervention pathways when risk is identified,” said Dr. Hallet.
“For example, a young patient with head and neck cancer and a prior history of mental illness who reports high scores for anxiety and drowsiness would be at high risk of self-injury,” she added. Such a patient should be referred to psycho-oncology, psychiatry, or social work. “To facilitate this, we are working on prognostic scores that can be integrated in clinical practice, such as an electronic medical record, to flag patients at risk,” said Dr. Hallet. “Future work will also need to identify the optimal care pathways for at-risk patients.”
Self-injury vs. suicidality
Commenting on the study for this news organization, Madeline Li, MD, PhD, a psychiatrist and clinician-scientist at Toronto’s Princess Margaret Cancer Centre, said that the findings are “underwhelming” because they tell us what is already known – that “NFSI is associated with distress, and cancer is a stressor.” It would have been more interesting to ask how to distinguish patients at risk for suicide from those at risk for self-harm without suicide, she added.
“The way these authors formulated NFSI included both self-harm intent and suicidal intent,” she explained. The researchers compared patients who were at risk for these two types of events with patients without NFSI. “When we see self-harm without suicidal intent in the emergency room, it’s mostly people making cries for help,” said Dr. Li. “These are people who cut their wrists or take small overdoses on purpose without the intent to die. It would have been more interesting to see if there are different risk factors for people who are just going to self-harm vs. those who are actually going to attempt suicide.”
The study’s identification of risk factors for NSFI is important because “it does tell us that when there’s anxiety, depression, and shortness of breath, we should pay attention to these patients and do something about it,” said Dr. Li. Still, research in cancer psychiatry needs to shift its focus from identifying and addressing existing risk factors to preventing them from developing, she added.
“We need to move earlier and provide emotional and mental health support to cancer patients to prevent them from becoming suicidal, rather than intervening when somebody already is,” Dr. Li concluded.
The study was funded by the Hanna Research Award from the division of surgical oncology at the Odette Cancer Centre–Sunnybrook Health Sciences Centre and by a Sunnybrook Health Sciences Centre Alternate Funding Plan Innovation grant. It was also supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. Dr. Hallet has received personal fees from Ipsen Biopharmaceuticals Canada and AAA outside the submitted work. Dr. Li reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA ONCOLOGY
Age and ferritin levels may predict MIS-C severity
, according to a Canadian multicenter cohort study.
The adjusted absolute risk for admission to an intensive care unit was 43.6% among children aged 6 years and older and 46.2% in children aged 13 to 17 years, compared with 18.4% in children aged 5 years or younger.
“We do not understand why teens get more severe MIS-C than younger children,” senior author Joan Robinson, MD, of the University of Alberta, Edmonton, told this news organization. “It is possible that more exposures to other coronaviruses in the past result in them having a more robust immune response to SARS-CoV-2, which results in more inflammation.”
The data were published in the Canadian Medical Association Journal.
A multinational study
The study included data on 232 children admitted with probable or confirmed MIS-C at 15 hospitals in Canada, Iran, and Costa Rica between March 1, 2020, and March 7, 2021. The median age of the children was 5.8 years, 56.0% were boys, and 21.6% had comorbidities.
Although cardiac involvement was common (58.6%), and almost one-third of the cohort (31.5%) was admitted to an ICU, “recovery was typically rapid, with 85% of patients discharged within 10 days,” said Dr. Robinson, for the Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC).
Older age as a risk
The results suggest that older age is associated with increased risk of severe MIS-C. “However, one would then predict that adults would be at even higher risk than teens, whereas the same syndrome in adults (MIS-A) is very, very rare,” said Dr. Robinson.
The study also found that children admitted with ferritin levels greater than 500 μg/L, signaling greater inflammation, also had an increased risk for ICU admission, compared with those with lower levels (adjusted risk difference, 18.4%; relative risk, 1.69). “This is presumably because the more inflammation that the child has, the more likely they are to have inflammation of the heart, which can lead to low blood pressure,” said Dr. Robinson.
Features of MIS-C
Among all patients with MIS-C, gastrointestinal involvement was common (89.2%), as were mucocutaneous findings (84.5%). Children with MIS-C had fever for a median duration of 6 days. “Clinicians who see children in their practice commonly have to determine why a child is febrile. Our study shows that one mainly has to consider MIS-C if febrile children have a rash and one or more of vomiting, diarrhea, or abdominal pain,” said Dr. Robinson.
The study also found that patients with MIS-C who were admitted to the hospital in the latter part of the study period (Nov. 1, 2020, to March 7, 2021) were slightly more likely to require ICU admission, compared with those admitted between March 1 and Oct. 31, 2020. “We cannot provide a clear explanation [for this],” the authors noted. “The features of severe MIS-C were widely publicized by May 2020, so it seems unlikely that severe cases were missed early in the study period. SARS-CoV-2 variants of concern have replaced the wild-type virus. It is possible that the immune response to circulating variants alters the severity of COVID-19 and MIS-C, when compared with wild-type virus.”
Despite initial concerns that pediatric COVID-19 vaccines might cause MIS-C, Dr. Robinson says data suggest this is rarely, if ever, the case, and that vaccines actually prevent the syndrome. She says further studies will be needed to assess MIS-C risk following reinfection with SARS-CoV-2. “I am an optimistic person, and it is my hope that MIS-C following reinfection is rare,” she said. “If this is the case, perhaps we will see very few cases once almost all children have been immunized and/or had SARS-CoV-2 infection.”
‘Differences across countries’
Adrienne Randolph, MD, a pediatrician at Harvard Medical School, Boston, and senior author of a large case series of patients with MIS-C, said that the Canadian study is valuable because it includes children from three countries. “It’s very interesting that there are differences across countries,” she said. “The patients in Iran had the highest percentage (58.7%) going into the ICU, whereas Costa Rica had the lowest percentage (9.2%), and the percentage going to the ICU in Canada (34.7%) was less than the percentages we see in the U.S. – which is pretty consistently about 60% to 70% of MIS-C patients going into the ICU.” Dr. Randolph was not involved in the current study.
Reasons for differences in the rates of ICU visits will be important to explore in the effort to standardize diagnostic criteria, stratification of severity, and recommendations for treatment of MIS-C, said Dr. Randolph.
“What is consistent is that the younger kids, zero to 5 years, in general are less ill,” she said. “That’s been consistent across multiple countries.” It’s unclear whether the cause of this difference is that parents observe younger patients more closely than they do teenagers, or whether other aspects of adolescence, such as prevalence of obesity and attendant inflammation, are at work, said Dr. Randolph.
What is also unclear is why hospitalized patients with MIS-C had higher percentages of ICU admission in the latter part of the study period, compared with the earlier period. “Did the patients change, or did practice change as we got to understand the disease process?” asked Dr. Randolph. “It could be that they got better at the diagnosis and were weeding out some of the patients who they realized didn’t need to be hospitalized. At the very beginning, we had a very low threshold to admit patients, because we didn’t know, and then, over time, people understood what was going on and felt more comfortable monitoring them as outpatients.”
This study was partially funded by a Janeway Foundation Research Grant to support data collection. Dr. Robinson disclosed no conflicts of interest. Dr. Randolph reported receiving royalties from UpToDate and personal fees from the La Jolla Pharmaceutical Company.
A version of this article first appeared on Medscape.com.
, according to a Canadian multicenter cohort study.
The adjusted absolute risk for admission to an intensive care unit was 43.6% among children aged 6 years and older and 46.2% in children aged 13 to 17 years, compared with 18.4% in children aged 5 years or younger.
“We do not understand why teens get more severe MIS-C than younger children,” senior author Joan Robinson, MD, of the University of Alberta, Edmonton, told this news organization. “It is possible that more exposures to other coronaviruses in the past result in them having a more robust immune response to SARS-CoV-2, which results in more inflammation.”
The data were published in the Canadian Medical Association Journal.
A multinational study
The study included data on 232 children admitted with probable or confirmed MIS-C at 15 hospitals in Canada, Iran, and Costa Rica between March 1, 2020, and March 7, 2021. The median age of the children was 5.8 years, 56.0% were boys, and 21.6% had comorbidities.
Although cardiac involvement was common (58.6%), and almost one-third of the cohort (31.5%) was admitted to an ICU, “recovery was typically rapid, with 85% of patients discharged within 10 days,” said Dr. Robinson, for the Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC).
Older age as a risk
The results suggest that older age is associated with increased risk of severe MIS-C. “However, one would then predict that adults would be at even higher risk than teens, whereas the same syndrome in adults (MIS-A) is very, very rare,” said Dr. Robinson.
The study also found that children admitted with ferritin levels greater than 500 μg/L, signaling greater inflammation, also had an increased risk for ICU admission, compared with those with lower levels (adjusted risk difference, 18.4%; relative risk, 1.69). “This is presumably because the more inflammation that the child has, the more likely they are to have inflammation of the heart, which can lead to low blood pressure,” said Dr. Robinson.
Features of MIS-C
Among all patients with MIS-C, gastrointestinal involvement was common (89.2%), as were mucocutaneous findings (84.5%). Children with MIS-C had fever for a median duration of 6 days. “Clinicians who see children in their practice commonly have to determine why a child is febrile. Our study shows that one mainly has to consider MIS-C if febrile children have a rash and one or more of vomiting, diarrhea, or abdominal pain,” said Dr. Robinson.
The study also found that patients with MIS-C who were admitted to the hospital in the latter part of the study period (Nov. 1, 2020, to March 7, 2021) were slightly more likely to require ICU admission, compared with those admitted between March 1 and Oct. 31, 2020. “We cannot provide a clear explanation [for this],” the authors noted. “The features of severe MIS-C were widely publicized by May 2020, so it seems unlikely that severe cases were missed early in the study period. SARS-CoV-2 variants of concern have replaced the wild-type virus. It is possible that the immune response to circulating variants alters the severity of COVID-19 and MIS-C, when compared with wild-type virus.”
Despite initial concerns that pediatric COVID-19 vaccines might cause MIS-C, Dr. Robinson says data suggest this is rarely, if ever, the case, and that vaccines actually prevent the syndrome. She says further studies will be needed to assess MIS-C risk following reinfection with SARS-CoV-2. “I am an optimistic person, and it is my hope that MIS-C following reinfection is rare,” she said. “If this is the case, perhaps we will see very few cases once almost all children have been immunized and/or had SARS-CoV-2 infection.”
‘Differences across countries’
Adrienne Randolph, MD, a pediatrician at Harvard Medical School, Boston, and senior author of a large case series of patients with MIS-C, said that the Canadian study is valuable because it includes children from three countries. “It’s very interesting that there are differences across countries,” she said. “The patients in Iran had the highest percentage (58.7%) going into the ICU, whereas Costa Rica had the lowest percentage (9.2%), and the percentage going to the ICU in Canada (34.7%) was less than the percentages we see in the U.S. – which is pretty consistently about 60% to 70% of MIS-C patients going into the ICU.” Dr. Randolph was not involved in the current study.
Reasons for differences in the rates of ICU visits will be important to explore in the effort to standardize diagnostic criteria, stratification of severity, and recommendations for treatment of MIS-C, said Dr. Randolph.
“What is consistent is that the younger kids, zero to 5 years, in general are less ill,” she said. “That’s been consistent across multiple countries.” It’s unclear whether the cause of this difference is that parents observe younger patients more closely than they do teenagers, or whether other aspects of adolescence, such as prevalence of obesity and attendant inflammation, are at work, said Dr. Randolph.
What is also unclear is why hospitalized patients with MIS-C had higher percentages of ICU admission in the latter part of the study period, compared with the earlier period. “Did the patients change, or did practice change as we got to understand the disease process?” asked Dr. Randolph. “It could be that they got better at the diagnosis and were weeding out some of the patients who they realized didn’t need to be hospitalized. At the very beginning, we had a very low threshold to admit patients, because we didn’t know, and then, over time, people understood what was going on and felt more comfortable monitoring them as outpatients.”
This study was partially funded by a Janeway Foundation Research Grant to support data collection. Dr. Robinson disclosed no conflicts of interest. Dr. Randolph reported receiving royalties from UpToDate and personal fees from the La Jolla Pharmaceutical Company.
A version of this article first appeared on Medscape.com.
, according to a Canadian multicenter cohort study.
The adjusted absolute risk for admission to an intensive care unit was 43.6% among children aged 6 years and older and 46.2% in children aged 13 to 17 years, compared with 18.4% in children aged 5 years or younger.
“We do not understand why teens get more severe MIS-C than younger children,” senior author Joan Robinson, MD, of the University of Alberta, Edmonton, told this news organization. “It is possible that more exposures to other coronaviruses in the past result in them having a more robust immune response to SARS-CoV-2, which results in more inflammation.”
The data were published in the Canadian Medical Association Journal.
A multinational study
The study included data on 232 children admitted with probable or confirmed MIS-C at 15 hospitals in Canada, Iran, and Costa Rica between March 1, 2020, and March 7, 2021. The median age of the children was 5.8 years, 56.0% were boys, and 21.6% had comorbidities.
Although cardiac involvement was common (58.6%), and almost one-third of the cohort (31.5%) was admitted to an ICU, “recovery was typically rapid, with 85% of patients discharged within 10 days,” said Dr. Robinson, for the Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC).
Older age as a risk
The results suggest that older age is associated with increased risk of severe MIS-C. “However, one would then predict that adults would be at even higher risk than teens, whereas the same syndrome in adults (MIS-A) is very, very rare,” said Dr. Robinson.
The study also found that children admitted with ferritin levels greater than 500 μg/L, signaling greater inflammation, also had an increased risk for ICU admission, compared with those with lower levels (adjusted risk difference, 18.4%; relative risk, 1.69). “This is presumably because the more inflammation that the child has, the more likely they are to have inflammation of the heart, which can lead to low blood pressure,” said Dr. Robinson.
Features of MIS-C
Among all patients with MIS-C, gastrointestinal involvement was common (89.2%), as were mucocutaneous findings (84.5%). Children with MIS-C had fever for a median duration of 6 days. “Clinicians who see children in their practice commonly have to determine why a child is febrile. Our study shows that one mainly has to consider MIS-C if febrile children have a rash and one or more of vomiting, diarrhea, or abdominal pain,” said Dr. Robinson.
The study also found that patients with MIS-C who were admitted to the hospital in the latter part of the study period (Nov. 1, 2020, to March 7, 2021) were slightly more likely to require ICU admission, compared with those admitted between March 1 and Oct. 31, 2020. “We cannot provide a clear explanation [for this],” the authors noted. “The features of severe MIS-C were widely publicized by May 2020, so it seems unlikely that severe cases were missed early in the study period. SARS-CoV-2 variants of concern have replaced the wild-type virus. It is possible that the immune response to circulating variants alters the severity of COVID-19 and MIS-C, when compared with wild-type virus.”
Despite initial concerns that pediatric COVID-19 vaccines might cause MIS-C, Dr. Robinson says data suggest this is rarely, if ever, the case, and that vaccines actually prevent the syndrome. She says further studies will be needed to assess MIS-C risk following reinfection with SARS-CoV-2. “I am an optimistic person, and it is my hope that MIS-C following reinfection is rare,” she said. “If this is the case, perhaps we will see very few cases once almost all children have been immunized and/or had SARS-CoV-2 infection.”
‘Differences across countries’
Adrienne Randolph, MD, a pediatrician at Harvard Medical School, Boston, and senior author of a large case series of patients with MIS-C, said that the Canadian study is valuable because it includes children from three countries. “It’s very interesting that there are differences across countries,” she said. “The patients in Iran had the highest percentage (58.7%) going into the ICU, whereas Costa Rica had the lowest percentage (9.2%), and the percentage going to the ICU in Canada (34.7%) was less than the percentages we see in the U.S. – which is pretty consistently about 60% to 70% of MIS-C patients going into the ICU.” Dr. Randolph was not involved in the current study.
Reasons for differences in the rates of ICU visits will be important to explore in the effort to standardize diagnostic criteria, stratification of severity, and recommendations for treatment of MIS-C, said Dr. Randolph.
“What is consistent is that the younger kids, zero to 5 years, in general are less ill,” she said. “That’s been consistent across multiple countries.” It’s unclear whether the cause of this difference is that parents observe younger patients more closely than they do teenagers, or whether other aspects of adolescence, such as prevalence of obesity and attendant inflammation, are at work, said Dr. Randolph.
What is also unclear is why hospitalized patients with MIS-C had higher percentages of ICU admission in the latter part of the study period, compared with the earlier period. “Did the patients change, or did practice change as we got to understand the disease process?” asked Dr. Randolph. “It could be that they got better at the diagnosis and were weeding out some of the patients who they realized didn’t need to be hospitalized. At the very beginning, we had a very low threshold to admit patients, because we didn’t know, and then, over time, people understood what was going on and felt more comfortable monitoring them as outpatients.”
This study was partially funded by a Janeway Foundation Research Grant to support data collection. Dr. Robinson disclosed no conflicts of interest. Dr. Randolph reported receiving royalties from UpToDate and personal fees from the La Jolla Pharmaceutical Company.
A version of this article first appeared on Medscape.com.
Surgeons in China ‘are the executioners,’ procuring organs before brain death
In a deep dive into obscure Chinese language transplant journals, a pair of researchers from Australia and Israel have added a new layer of horror to what’s already known about forced organ harvesting in China.
Searching for documentation that vital organs are being harvested from nonconsenting executed prisoners, a practice that the China Tribunal confirmed “beyond any reasonable doubt” in 2020, Jacob Lavee, MD, an Israeli heart transplant surgeon, and Matthew Roberston, a PhD student at Australian National University, uncovered something even more shocking: that vital organs are being explanted from patients who are still alive.
“We have shown for the first time that the transplant surgeons are the executioners – that the mode of execution is organ procurement. These are self-admissions of executing the patient,” Dr. Lavee told this news organization. “Up until now, there has been what we call circumstantial evidence of this, but our paper is what you’d call the smoking gun, because it’s in the words of the physicians themselves that they are doing it. In the words of these surgeons, intubation was done only after the beginning of surgery, which means the patients were breathing spontaneously up until the moment the operation started ... meaning they were not brain dead.”
The research, published in the American Journal of Transplantation, involved intricate analysis of thousands of Chinese language transplant articles and identified 71 articles in which transplant surgeons describe starting organ procurement surgery before declaring their patients brain dead.
“What we found were improper, illegitimate, nonexistent, or false declarations of brain death,” Mr. Robertson said in an interview. He explained that this violates what’s known as the dead donor rule, which is fundamental in transplant ethics. “The surgeons wrote that the donor was brain dead, but according to everything we know about medical science, they could not possibly have been brain dead because there was no apnea test performed. Brain death is not just something you say, there’s this whole battery of tests, and the key is the apnea test, [in which] the patient is already intubated and ventilated, they turn the machine off, and they’re looking for carbon dioxide in the blood above a certain level.”
Mr. Robertson and Dr. Lavee have painstakingly documented “incriminating sentences” in each of the 71 articles proving that brain death had not occurred before the organ explantation procedure began. “There were two criteria by which we claimed a problematic brain death declaration,” said Mr. Robertson, who translated the Chinese. “One was where the patient was not ventilated and was only intubated after they were declared brain dead; the other was that the intubation took place immediately prior to the surgery beginning.”
“It was mind-boggling,” said Dr. Lavee, from Tel Aviv University. “When I first started reading, my initial reaction is, ‘This can’t be.’ I read it once, and again, and I insisted that Matt get another independent translation of the Chinese just to be sure. I told him, ‘There’s no way a physician, a surgeon could write this – it doesn’t make sense.’ But the more of these papers we read, we saw it was a pattern – and they didn’t come out of a single medical center, they are spread all over China.”
For the analysis, Mr. Robertson wrote code and customized an algorithm to examine 124,770 medical articles from official Chinese databases between 1980 and 2020. The 71 articles revealing cases involving problematic brain death came from 56 hospitals (of which 12 were military) in 33 cities across 15 provinces, they report. In total, 348 surgeons, nurses, anesthesiologists, and other medical workers or researchers were listed as authors of these publications.
Why would these medical personnel write such self-incriminating evidence? The researchers say it’s unclear. “They don’t think anyone’s reading this stuff,” Mr. Robertson suggests. “Sometimes it’s revealed in just five or six characters in a paper of eight pages.” Dr. Lavee wonders if it’s also ignorance. “If this has been a practice for 20 or 30 years in China, I guess nobody at that time was aware they were doing something wrong, although how to declare brain death is something that is known in China. They’ve published a lot about it.”
The article is “evidence that this barbarity continues and is a very valuable contribution that continues to bring attention to an enormous human rights violation,” said Arthur Caplan, PhD, head of the Division of Medical Ethics at New York University’s Grossman School of Medicine. “What they’ve reported has been going on for many, many years, the data are very clear that China’s doing many more transplants than they have cadaver organ donors,” he said, adding that the country’s well-documented and lucrative involvement in transplant tourism “means you have to have a donor ready when the would-be recipient appears; you have to have a matched organ available, and that’s hard to do waiting on a cadaver donor.”
Although the researchers found no incriminating publications after 2015, they speculate that this is likely due to growing awareness among Chinese surgeons that publishing the information would attract international condemnation. “We think these practices are continuing to go on,” said Dr. Lavee. He acknowledged that a voluntary organ donation program is slowly developing in parallel to this. He said, given China’s place as the world’s second largest transplant country behind the U.S., as well as its low rate of voluntary donation, it’s reasonable to conclude that the main source of organs remains prisoners on death row.
Dr. Caplan and the researchers have called for academic institutions and medical journals to resume their previous boycotts of Chinese transplant publications and speakers, but as long as China denies the practices, economic and political leaders will turn a blind eye. “In the past, I don’t think the question of China’s medical professional involvement in the execution of donors has been taken as seriously as it should have,” said Mr. Robertson. “I certainly hope that with the publication of this paper in the leading journal in the field, this will change.”
The study was supported by the Google Cloud Research Credits program, the Australian Government Research Training Program Scholarship, and the Victims of Communism Memorial Foundation. Mr. Robertson, Dr. Lavee, and Dr. Caplan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a deep dive into obscure Chinese language transplant journals, a pair of researchers from Australia and Israel have added a new layer of horror to what’s already known about forced organ harvesting in China.
Searching for documentation that vital organs are being harvested from nonconsenting executed prisoners, a practice that the China Tribunal confirmed “beyond any reasonable doubt” in 2020, Jacob Lavee, MD, an Israeli heart transplant surgeon, and Matthew Roberston, a PhD student at Australian National University, uncovered something even more shocking: that vital organs are being explanted from patients who are still alive.
“We have shown for the first time that the transplant surgeons are the executioners – that the mode of execution is organ procurement. These are self-admissions of executing the patient,” Dr. Lavee told this news organization. “Up until now, there has been what we call circumstantial evidence of this, but our paper is what you’d call the smoking gun, because it’s in the words of the physicians themselves that they are doing it. In the words of these surgeons, intubation was done only after the beginning of surgery, which means the patients were breathing spontaneously up until the moment the operation started ... meaning they were not brain dead.”
The research, published in the American Journal of Transplantation, involved intricate analysis of thousands of Chinese language transplant articles and identified 71 articles in which transplant surgeons describe starting organ procurement surgery before declaring their patients brain dead.
“What we found were improper, illegitimate, nonexistent, or false declarations of brain death,” Mr. Robertson said in an interview. He explained that this violates what’s known as the dead donor rule, which is fundamental in transplant ethics. “The surgeons wrote that the donor was brain dead, but according to everything we know about medical science, they could not possibly have been brain dead because there was no apnea test performed. Brain death is not just something you say, there’s this whole battery of tests, and the key is the apnea test, [in which] the patient is already intubated and ventilated, they turn the machine off, and they’re looking for carbon dioxide in the blood above a certain level.”
Mr. Robertson and Dr. Lavee have painstakingly documented “incriminating sentences” in each of the 71 articles proving that brain death had not occurred before the organ explantation procedure began. “There were two criteria by which we claimed a problematic brain death declaration,” said Mr. Robertson, who translated the Chinese. “One was where the patient was not ventilated and was only intubated after they were declared brain dead; the other was that the intubation took place immediately prior to the surgery beginning.”
“It was mind-boggling,” said Dr. Lavee, from Tel Aviv University. “When I first started reading, my initial reaction is, ‘This can’t be.’ I read it once, and again, and I insisted that Matt get another independent translation of the Chinese just to be sure. I told him, ‘There’s no way a physician, a surgeon could write this – it doesn’t make sense.’ But the more of these papers we read, we saw it was a pattern – and they didn’t come out of a single medical center, they are spread all over China.”
For the analysis, Mr. Robertson wrote code and customized an algorithm to examine 124,770 medical articles from official Chinese databases between 1980 and 2020. The 71 articles revealing cases involving problematic brain death came from 56 hospitals (of which 12 were military) in 33 cities across 15 provinces, they report. In total, 348 surgeons, nurses, anesthesiologists, and other medical workers or researchers were listed as authors of these publications.
Why would these medical personnel write such self-incriminating evidence? The researchers say it’s unclear. “They don’t think anyone’s reading this stuff,” Mr. Robertson suggests. “Sometimes it’s revealed in just five or six characters in a paper of eight pages.” Dr. Lavee wonders if it’s also ignorance. “If this has been a practice for 20 or 30 years in China, I guess nobody at that time was aware they were doing something wrong, although how to declare brain death is something that is known in China. They’ve published a lot about it.”
The article is “evidence that this barbarity continues and is a very valuable contribution that continues to bring attention to an enormous human rights violation,” said Arthur Caplan, PhD, head of the Division of Medical Ethics at New York University’s Grossman School of Medicine. “What they’ve reported has been going on for many, many years, the data are very clear that China’s doing many more transplants than they have cadaver organ donors,” he said, adding that the country’s well-documented and lucrative involvement in transplant tourism “means you have to have a donor ready when the would-be recipient appears; you have to have a matched organ available, and that’s hard to do waiting on a cadaver donor.”
Although the researchers found no incriminating publications after 2015, they speculate that this is likely due to growing awareness among Chinese surgeons that publishing the information would attract international condemnation. “We think these practices are continuing to go on,” said Dr. Lavee. He acknowledged that a voluntary organ donation program is slowly developing in parallel to this. He said, given China’s place as the world’s second largest transplant country behind the U.S., as well as its low rate of voluntary donation, it’s reasonable to conclude that the main source of organs remains prisoners on death row.
Dr. Caplan and the researchers have called for academic institutions and medical journals to resume their previous boycotts of Chinese transplant publications and speakers, but as long as China denies the practices, economic and political leaders will turn a blind eye. “In the past, I don’t think the question of China’s medical professional involvement in the execution of donors has been taken as seriously as it should have,” said Mr. Robertson. “I certainly hope that with the publication of this paper in the leading journal in the field, this will change.”
The study was supported by the Google Cloud Research Credits program, the Australian Government Research Training Program Scholarship, and the Victims of Communism Memorial Foundation. Mr. Robertson, Dr. Lavee, and Dr. Caplan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a deep dive into obscure Chinese language transplant journals, a pair of researchers from Australia and Israel have added a new layer of horror to what’s already known about forced organ harvesting in China.
Searching for documentation that vital organs are being harvested from nonconsenting executed prisoners, a practice that the China Tribunal confirmed “beyond any reasonable doubt” in 2020, Jacob Lavee, MD, an Israeli heart transplant surgeon, and Matthew Roberston, a PhD student at Australian National University, uncovered something even more shocking: that vital organs are being explanted from patients who are still alive.
“We have shown for the first time that the transplant surgeons are the executioners – that the mode of execution is organ procurement. These are self-admissions of executing the patient,” Dr. Lavee told this news organization. “Up until now, there has been what we call circumstantial evidence of this, but our paper is what you’d call the smoking gun, because it’s in the words of the physicians themselves that they are doing it. In the words of these surgeons, intubation was done only after the beginning of surgery, which means the patients were breathing spontaneously up until the moment the operation started ... meaning they were not brain dead.”
The research, published in the American Journal of Transplantation, involved intricate analysis of thousands of Chinese language transplant articles and identified 71 articles in which transplant surgeons describe starting organ procurement surgery before declaring their patients brain dead.
“What we found were improper, illegitimate, nonexistent, or false declarations of brain death,” Mr. Robertson said in an interview. He explained that this violates what’s known as the dead donor rule, which is fundamental in transplant ethics. “The surgeons wrote that the donor was brain dead, but according to everything we know about medical science, they could not possibly have been brain dead because there was no apnea test performed. Brain death is not just something you say, there’s this whole battery of tests, and the key is the apnea test, [in which] the patient is already intubated and ventilated, they turn the machine off, and they’re looking for carbon dioxide in the blood above a certain level.”
Mr. Robertson and Dr. Lavee have painstakingly documented “incriminating sentences” in each of the 71 articles proving that brain death had not occurred before the organ explantation procedure began. “There were two criteria by which we claimed a problematic brain death declaration,” said Mr. Robertson, who translated the Chinese. “One was where the patient was not ventilated and was only intubated after they were declared brain dead; the other was that the intubation took place immediately prior to the surgery beginning.”
“It was mind-boggling,” said Dr. Lavee, from Tel Aviv University. “When I first started reading, my initial reaction is, ‘This can’t be.’ I read it once, and again, and I insisted that Matt get another independent translation of the Chinese just to be sure. I told him, ‘There’s no way a physician, a surgeon could write this – it doesn’t make sense.’ But the more of these papers we read, we saw it was a pattern – and they didn’t come out of a single medical center, they are spread all over China.”
For the analysis, Mr. Robertson wrote code and customized an algorithm to examine 124,770 medical articles from official Chinese databases between 1980 and 2020. The 71 articles revealing cases involving problematic brain death came from 56 hospitals (of which 12 were military) in 33 cities across 15 provinces, they report. In total, 348 surgeons, nurses, anesthesiologists, and other medical workers or researchers were listed as authors of these publications.
Why would these medical personnel write such self-incriminating evidence? The researchers say it’s unclear. “They don’t think anyone’s reading this stuff,” Mr. Robertson suggests. “Sometimes it’s revealed in just five or six characters in a paper of eight pages.” Dr. Lavee wonders if it’s also ignorance. “If this has been a practice for 20 or 30 years in China, I guess nobody at that time was aware they were doing something wrong, although how to declare brain death is something that is known in China. They’ve published a lot about it.”
The article is “evidence that this barbarity continues and is a very valuable contribution that continues to bring attention to an enormous human rights violation,” said Arthur Caplan, PhD, head of the Division of Medical Ethics at New York University’s Grossman School of Medicine. “What they’ve reported has been going on for many, many years, the data are very clear that China’s doing many more transplants than they have cadaver organ donors,” he said, adding that the country’s well-documented and lucrative involvement in transplant tourism “means you have to have a donor ready when the would-be recipient appears; you have to have a matched organ available, and that’s hard to do waiting on a cadaver donor.”
Although the researchers found no incriminating publications after 2015, they speculate that this is likely due to growing awareness among Chinese surgeons that publishing the information would attract international condemnation. “We think these practices are continuing to go on,” said Dr. Lavee. He acknowledged that a voluntary organ donation program is slowly developing in parallel to this. He said, given China’s place as the world’s second largest transplant country behind the U.S., as well as its low rate of voluntary donation, it’s reasonable to conclude that the main source of organs remains prisoners on death row.
Dr. Caplan and the researchers have called for academic institutions and medical journals to resume their previous boycotts of Chinese transplant publications and speakers, but as long as China denies the practices, economic and political leaders will turn a blind eye. “In the past, I don’t think the question of China’s medical professional involvement in the execution of donors has been taken as seriously as it should have,” said Mr. Robertson. “I certainly hope that with the publication of this paper in the leading journal in the field, this will change.”
The study was supported by the Google Cloud Research Credits program, the Australian Government Research Training Program Scholarship, and the Victims of Communism Memorial Foundation. Mr. Robertson, Dr. Lavee, and Dr. Caplan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
False-positive breast cancer screening likely over 10-year period
Breast cancer screening modality has less effect on the probability of false-positive results than screening interval, patient age, and breast density according to a new study comparing digital breast tomosynthesis (DBT) with digital mammography.
Although DBT was associated with a modest improvement in recalls for false-positive results compared with mammography, about half of women in both groups received at least one false-positive result over a 10-year period of annual screening, reported senior author Diana L. Miglioretti, PhD, from the University of California, Davis, and colleagues.
By contrast, the authors reported “substantial reductions” in false-positive recalls with biennial screening. Specifically, while annual mammography and DBT resulted in cumulative 10-year false-positive recall rates of 56.3% and 49.6% respectively, biennial rates were 38.1% and 35.7%.
The comparative effectiveness study, published in JAMA Network Open, included 903,495 women who underwent 10 years of breast cancer screening at 126 radiology facilities in the Breast Cancer Surveillance Consortium. The mean age of participants was 57.6 years, and 46% of them had dense breasts. A total of 2,969,055 screening exams were performed (15% DBT), with each woman receiving a mean of 3.3 exams over 10 years. Most participants (71.8%) had annual exams, while 16.8% had biennial, with the remainder being performed at intervals of 3 years or more.
Investigators looked at the cumulative rate of three kinds of false-positive results over 10 years: false-positive recalls for further imaging, false-positive short-interval follow-up recommendations, and false-positive biopsy recommendations. A result was considered false positive if there was no diagnosis of invasive carcinoma or ductal carcinoma in situ within 1 year of the screening examination and before the next screening examination.
Overall, across all screening intervals, and after adjusting for age and breast density, the percentage of false-positive results was slightly lower for DBT vs. mammography: 7.6% vs. 9.0%, respectively, for false-positive recalls; 1.8% vs. 2.1%, respectively, for false-positive short-interval follow-up recommendations; and 1.1% vs. 1.2% for false-positive biopsy recommendations. “We did not observe consistent clinically meaningful differences in the cumulative probabilities of false-positive short-interval follow-up or biopsy recommendation by screening modality,” they noted, adding that, although DBT provided “modest” reductions in false-positive recalls, compared with mammography (2.4% less for biennial screening and 6.7% less for annual screening), “nonetheless, this percentage equates to many thousands of individuals in absolute numbers, especially for annual screening, which is the dominant practice in the U.S.”
The authors also noted that, regardless of screening modality, all three types of false-positive results were substantially lower for biennial versus annual mammograph, and depended on age and breast density. The highest cumulative rates of false-positive results occurred in women aged 40-49 years (68.0% with annual digital mammography and 60.8% with annual DBT). Women with extremely dense breasts had the highest probability of all three types of false positive, which “may be due to the lack of interspersed fat within dense fibroglandular tissue, with the contrast between the fat and tissue being a requirement for more accurate detection of suspicious features by interpreting radiologists.”
The study findings “offer new information about the potential harms of repeated screening, which may be used to inform screening guidelines and decision-making between individuals and their physicians. However, it is important to weigh these and other potential harms with potential benefits of earlier diagnosis. … Women at high risk of an advanced cancer under biennial screening, including some women with dense breasts, may reduce their risk with annual screening,” they suggested.
Although DBT is now widely used in the United States, amid growing optimism about its superiority over digital mammography, this study reminds clinicians to counsel patients appropriately, according to Lydia E. Pace, MD, from Brigham and Women’s Hospital in Boston. “Unfortunately, the growing availability of DBT does not substantially change the likelihood that women will experience a false-positive result over years of regular mammograms,” she wrote in an invited commentary published with the study. She noted that, although many women tolerate false-positive results, “they are associated with at least transient anxiety as well as time, inconvenience, and expense. More information is needed to understand the association of DBT with overdiagnosis, which is the more clinically important harm of screening.”
The study was funded by the National Cancer Institute. Dr. Miglioretti and Dr. Pace reported no conflicts of interest. One coauthor of the study is an unpaid consultant for Grail, for the STRIVE study, and another coauthor receives personal fees from Grail for work on a data safety monitoring board. No other disclosures were reported.
Breast cancer screening modality has less effect on the probability of false-positive results than screening interval, patient age, and breast density according to a new study comparing digital breast tomosynthesis (DBT) with digital mammography.
Although DBT was associated with a modest improvement in recalls for false-positive results compared with mammography, about half of women in both groups received at least one false-positive result over a 10-year period of annual screening, reported senior author Diana L. Miglioretti, PhD, from the University of California, Davis, and colleagues.
By contrast, the authors reported “substantial reductions” in false-positive recalls with biennial screening. Specifically, while annual mammography and DBT resulted in cumulative 10-year false-positive recall rates of 56.3% and 49.6% respectively, biennial rates were 38.1% and 35.7%.
The comparative effectiveness study, published in JAMA Network Open, included 903,495 women who underwent 10 years of breast cancer screening at 126 radiology facilities in the Breast Cancer Surveillance Consortium. The mean age of participants was 57.6 years, and 46% of them had dense breasts. A total of 2,969,055 screening exams were performed (15% DBT), with each woman receiving a mean of 3.3 exams over 10 years. Most participants (71.8%) had annual exams, while 16.8% had biennial, with the remainder being performed at intervals of 3 years or more.
Investigators looked at the cumulative rate of three kinds of false-positive results over 10 years: false-positive recalls for further imaging, false-positive short-interval follow-up recommendations, and false-positive biopsy recommendations. A result was considered false positive if there was no diagnosis of invasive carcinoma or ductal carcinoma in situ within 1 year of the screening examination and before the next screening examination.
Overall, across all screening intervals, and after adjusting for age and breast density, the percentage of false-positive results was slightly lower for DBT vs. mammography: 7.6% vs. 9.0%, respectively, for false-positive recalls; 1.8% vs. 2.1%, respectively, for false-positive short-interval follow-up recommendations; and 1.1% vs. 1.2% for false-positive biopsy recommendations. “We did not observe consistent clinically meaningful differences in the cumulative probabilities of false-positive short-interval follow-up or biopsy recommendation by screening modality,” they noted, adding that, although DBT provided “modest” reductions in false-positive recalls, compared with mammography (2.4% less for biennial screening and 6.7% less for annual screening), “nonetheless, this percentage equates to many thousands of individuals in absolute numbers, especially for annual screening, which is the dominant practice in the U.S.”
The authors also noted that, regardless of screening modality, all three types of false-positive results were substantially lower for biennial versus annual mammograph, and depended on age and breast density. The highest cumulative rates of false-positive results occurred in women aged 40-49 years (68.0% with annual digital mammography and 60.8% with annual DBT). Women with extremely dense breasts had the highest probability of all three types of false positive, which “may be due to the lack of interspersed fat within dense fibroglandular tissue, with the contrast between the fat and tissue being a requirement for more accurate detection of suspicious features by interpreting radiologists.”
The study findings “offer new information about the potential harms of repeated screening, which may be used to inform screening guidelines and decision-making between individuals and their physicians. However, it is important to weigh these and other potential harms with potential benefits of earlier diagnosis. … Women at high risk of an advanced cancer under biennial screening, including some women with dense breasts, may reduce their risk with annual screening,” they suggested.
Although DBT is now widely used in the United States, amid growing optimism about its superiority over digital mammography, this study reminds clinicians to counsel patients appropriately, according to Lydia E. Pace, MD, from Brigham and Women’s Hospital in Boston. “Unfortunately, the growing availability of DBT does not substantially change the likelihood that women will experience a false-positive result over years of regular mammograms,” she wrote in an invited commentary published with the study. She noted that, although many women tolerate false-positive results, “they are associated with at least transient anxiety as well as time, inconvenience, and expense. More information is needed to understand the association of DBT with overdiagnosis, which is the more clinically important harm of screening.”
The study was funded by the National Cancer Institute. Dr. Miglioretti and Dr. Pace reported no conflicts of interest. One coauthor of the study is an unpaid consultant for Grail, for the STRIVE study, and another coauthor receives personal fees from Grail for work on a data safety monitoring board. No other disclosures were reported.
Breast cancer screening modality has less effect on the probability of false-positive results than screening interval, patient age, and breast density according to a new study comparing digital breast tomosynthesis (DBT) with digital mammography.
Although DBT was associated with a modest improvement in recalls for false-positive results compared with mammography, about half of women in both groups received at least one false-positive result over a 10-year period of annual screening, reported senior author Diana L. Miglioretti, PhD, from the University of California, Davis, and colleagues.
By contrast, the authors reported “substantial reductions” in false-positive recalls with biennial screening. Specifically, while annual mammography and DBT resulted in cumulative 10-year false-positive recall rates of 56.3% and 49.6% respectively, biennial rates were 38.1% and 35.7%.
The comparative effectiveness study, published in JAMA Network Open, included 903,495 women who underwent 10 years of breast cancer screening at 126 radiology facilities in the Breast Cancer Surveillance Consortium. The mean age of participants was 57.6 years, and 46% of them had dense breasts. A total of 2,969,055 screening exams were performed (15% DBT), with each woman receiving a mean of 3.3 exams over 10 years. Most participants (71.8%) had annual exams, while 16.8% had biennial, with the remainder being performed at intervals of 3 years or more.
Investigators looked at the cumulative rate of three kinds of false-positive results over 10 years: false-positive recalls for further imaging, false-positive short-interval follow-up recommendations, and false-positive biopsy recommendations. A result was considered false positive if there was no diagnosis of invasive carcinoma or ductal carcinoma in situ within 1 year of the screening examination and before the next screening examination.
Overall, across all screening intervals, and after adjusting for age and breast density, the percentage of false-positive results was slightly lower for DBT vs. mammography: 7.6% vs. 9.0%, respectively, for false-positive recalls; 1.8% vs. 2.1%, respectively, for false-positive short-interval follow-up recommendations; and 1.1% vs. 1.2% for false-positive biopsy recommendations. “We did not observe consistent clinically meaningful differences in the cumulative probabilities of false-positive short-interval follow-up or biopsy recommendation by screening modality,” they noted, adding that, although DBT provided “modest” reductions in false-positive recalls, compared with mammography (2.4% less for biennial screening and 6.7% less for annual screening), “nonetheless, this percentage equates to many thousands of individuals in absolute numbers, especially for annual screening, which is the dominant practice in the U.S.”
The authors also noted that, regardless of screening modality, all three types of false-positive results were substantially lower for biennial versus annual mammograph, and depended on age and breast density. The highest cumulative rates of false-positive results occurred in women aged 40-49 years (68.0% with annual digital mammography and 60.8% with annual DBT). Women with extremely dense breasts had the highest probability of all three types of false positive, which “may be due to the lack of interspersed fat within dense fibroglandular tissue, with the contrast between the fat and tissue being a requirement for more accurate detection of suspicious features by interpreting radiologists.”
The study findings “offer new information about the potential harms of repeated screening, which may be used to inform screening guidelines and decision-making between individuals and their physicians. However, it is important to weigh these and other potential harms with potential benefits of earlier diagnosis. … Women at high risk of an advanced cancer under biennial screening, including some women with dense breasts, may reduce their risk with annual screening,” they suggested.
Although DBT is now widely used in the United States, amid growing optimism about its superiority over digital mammography, this study reminds clinicians to counsel patients appropriately, according to Lydia E. Pace, MD, from Brigham and Women’s Hospital in Boston. “Unfortunately, the growing availability of DBT does not substantially change the likelihood that women will experience a false-positive result over years of regular mammograms,” she wrote in an invited commentary published with the study. She noted that, although many women tolerate false-positive results, “they are associated with at least transient anxiety as well as time, inconvenience, and expense. More information is needed to understand the association of DBT with overdiagnosis, which is the more clinically important harm of screening.”
The study was funded by the National Cancer Institute. Dr. Miglioretti and Dr. Pace reported no conflicts of interest. One coauthor of the study is an unpaid consultant for Grail, for the STRIVE study, and another coauthor receives personal fees from Grail for work on a data safety monitoring board. No other disclosures were reported.
JAMA NETWORK OPEN
Coordinating cancer care for patients displaced by war
across the border into neighboring countries, which makes the role of oncology groups vitally important.
“They’re trying to deal with an extremely vulnerable and traumatized population – children who’ve lost their families, elderly who are confused and potentially abandoned,” commented Richard Sullivan, MD, PhD.
“The triage that’s happening on the border is not focusing on noncommunicable diseases,” he continued. “We know from previous crises that many cancer patients are lost; they simply do not present with their symptoms once they become refugees, and that’s going to become a really big issue.”
Oncology groups are needed to “provide the navigation, the treatment, and also the intelligence to ensure we deliver excellent cancer care where it’s needed for our Ukrainian friends,” he added. Dr. Sullivan is a member of the World Health Organization’s Emergency Committee and is director of the Institute of Cancer Policy at King’s College London.
He was speaking at a virtual briefing organized by the American Society of Clinical Oncology (ASCO) and the European Cancer Organisation (ECO), which have joined forces to centralize cancer care efforts.
With an estimated 3.3 million refugees having already crossed Ukraine’s borders, neighboring countries are experiencing an approximately 5% increase in their overall populations, making increased demand for cancer care inevitable, said Dr. Sullivan.
“Suggestions are that with 4 million refugees, you’re going to be looking at an increase of 13,000-16,000 cancer patients per month. ... But it will take time for the issue to evolve. At the moment, people are not being overwhelmed ... but there’s no doubt cancer care capacity for host countries is going to be an issue in the future.”
So far, about 2 million refugees are in Poland, where cancer centers have experienced a 10% increase in new patients since the war started, said Piotr Rutkowski, MD, PhD, professor of surgical oncology at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw.
“Of course, our resources are limited,” he said, adding that efforts are underway to accredit Ukrainian health care workers to work in Poland. “It’s unpredictable how the health care system in Europe can overcome these difficulties.”
“Until now, I don’t think any cancer patients have not received care, so still, we are in a positive situation, but the waiting list can enlarge in the near future,” Dr. Rutkowsli commented.
Indeed, the anticipated increase will “likely exceed the possibilities of the Polish health system” soon, warned Jacek Jassem, MD, PhD, professor of clinical oncology and radiotherapy and the head of the department of oncology and radiotherapy at the Medical University of Gdansk, Poland.
Although there is an EU international agreement for a more widespread allocation of cancer patients, “when they come to Poland, many of them want to be treated in Poland, because they have family here, the language is more familiar.”
Dr. Jassem suggests the best way to avoid overwhelming host cancer centers is to triage patients directly from Ukraine. “Some therapies shouldn’t be interrupted. So, for example, radiotherapy started in Ukraine should be continued there, but otherwise, chemotherapy can be continued elsewhere, surgery may be postponed and done elsewhere. These are the decisions that should be considered in Ukraine, and then patients who are selected for particular therapies should be reallocated to other countries,” he suggested.
Romania has seen an influx of about 400,000 refugees, including cancer patients seeking systemic therapy, radiotherapy, or follow-up, said Nicoleta Antone, MD, a medical oncologist at the Cancer Institute of Ion Chiricuta in Cluj-Napoca, Romania. “We have seen patients mainly with breast cancer because most of the refugees [with cancer] are women looking for systemic therapy, but also all the other tumor types, both solid and hematologic tumors.”
Dr. Sullivan says attempts by EU member states to address cancer needs are complicated by the fact that many refugees are still on the move. They have been passing through their initial host countries and moving on to Greece, Slovenia, Austria, Germany, Italy, and Turkey, “making the therapeutic geographies at any potential time quite challenging to keep an eye on.” Other countries, such as Moldova, are not part of the EU, “so we dealing with some really quite complex political and financial issues.”
The situation calls for a broader approach to refugees generally, he added. “We’re talking free cancer care for Ukrainian patients, but there’s also, of course, this dialogue of ensuring there’s free care for all refugees. Europe already has a large refugee contingent from other countries, so there’s no doubt this is an opportunity to talk more broadly about cancer care for refugees and also progressive universalism.
“You can’t have rules for one set of patients and a different set of rules for another set of patients, so there’s going to be a real issue around fairness and equity which Europe is going to have to address,” he said.
In an attempt, ASCO and ECO have joined forces in a special network, noted Julie Gralow, MD, chief medical officer at ASCO.
“The ECO/ASCO Special Network is all about collaboration and coordination across professional societies, across cancer patient groups, across academic and other clinical centers. We’re providing information in the various national languages and trying to amplify the work that each of us is doing. ... We’re sharing intelligence, regular reports from the field, information, experience, and most of all, contacts. We’re all being approached individually about people who need help or people who want to help, and we’re trying to bring this all together in a focused way.”
Separately, there is also an ASCO resource page, as well as an ECO resource page.
The American Cancer Society also has patient resources on their site, including a 24-hour international call center in multiple languages and a Volunteer Corp of Clinicians, which currently has 123 active volunteers (and another 300 applicants) available to answer questions.
Europe and other countries must consider both a medium and a long-term commitment to refugees with cancer, said Dr. Sullivan. “Because even if the war stopped tomorrow, it’s going to take between a year and a year and a half to rebuild cancer care in Ukraine.”
A version of this article first appeared on Medscape.com.
across the border into neighboring countries, which makes the role of oncology groups vitally important.
“They’re trying to deal with an extremely vulnerable and traumatized population – children who’ve lost their families, elderly who are confused and potentially abandoned,” commented Richard Sullivan, MD, PhD.
“The triage that’s happening on the border is not focusing on noncommunicable diseases,” he continued. “We know from previous crises that many cancer patients are lost; they simply do not present with their symptoms once they become refugees, and that’s going to become a really big issue.”
Oncology groups are needed to “provide the navigation, the treatment, and also the intelligence to ensure we deliver excellent cancer care where it’s needed for our Ukrainian friends,” he added. Dr. Sullivan is a member of the World Health Organization’s Emergency Committee and is director of the Institute of Cancer Policy at King’s College London.
He was speaking at a virtual briefing organized by the American Society of Clinical Oncology (ASCO) and the European Cancer Organisation (ECO), which have joined forces to centralize cancer care efforts.
With an estimated 3.3 million refugees having already crossed Ukraine’s borders, neighboring countries are experiencing an approximately 5% increase in their overall populations, making increased demand for cancer care inevitable, said Dr. Sullivan.
“Suggestions are that with 4 million refugees, you’re going to be looking at an increase of 13,000-16,000 cancer patients per month. ... But it will take time for the issue to evolve. At the moment, people are not being overwhelmed ... but there’s no doubt cancer care capacity for host countries is going to be an issue in the future.”
So far, about 2 million refugees are in Poland, where cancer centers have experienced a 10% increase in new patients since the war started, said Piotr Rutkowski, MD, PhD, professor of surgical oncology at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw.
“Of course, our resources are limited,” he said, adding that efforts are underway to accredit Ukrainian health care workers to work in Poland. “It’s unpredictable how the health care system in Europe can overcome these difficulties.”
“Until now, I don’t think any cancer patients have not received care, so still, we are in a positive situation, but the waiting list can enlarge in the near future,” Dr. Rutkowsli commented.
Indeed, the anticipated increase will “likely exceed the possibilities of the Polish health system” soon, warned Jacek Jassem, MD, PhD, professor of clinical oncology and radiotherapy and the head of the department of oncology and radiotherapy at the Medical University of Gdansk, Poland.
Although there is an EU international agreement for a more widespread allocation of cancer patients, “when they come to Poland, many of them want to be treated in Poland, because they have family here, the language is more familiar.”
Dr. Jassem suggests the best way to avoid overwhelming host cancer centers is to triage patients directly from Ukraine. “Some therapies shouldn’t be interrupted. So, for example, radiotherapy started in Ukraine should be continued there, but otherwise, chemotherapy can be continued elsewhere, surgery may be postponed and done elsewhere. These are the decisions that should be considered in Ukraine, and then patients who are selected for particular therapies should be reallocated to other countries,” he suggested.
Romania has seen an influx of about 400,000 refugees, including cancer patients seeking systemic therapy, radiotherapy, or follow-up, said Nicoleta Antone, MD, a medical oncologist at the Cancer Institute of Ion Chiricuta in Cluj-Napoca, Romania. “We have seen patients mainly with breast cancer because most of the refugees [with cancer] are women looking for systemic therapy, but also all the other tumor types, both solid and hematologic tumors.”
Dr. Sullivan says attempts by EU member states to address cancer needs are complicated by the fact that many refugees are still on the move. They have been passing through their initial host countries and moving on to Greece, Slovenia, Austria, Germany, Italy, and Turkey, “making the therapeutic geographies at any potential time quite challenging to keep an eye on.” Other countries, such as Moldova, are not part of the EU, “so we dealing with some really quite complex political and financial issues.”
The situation calls for a broader approach to refugees generally, he added. “We’re talking free cancer care for Ukrainian patients, but there’s also, of course, this dialogue of ensuring there’s free care for all refugees. Europe already has a large refugee contingent from other countries, so there’s no doubt this is an opportunity to talk more broadly about cancer care for refugees and also progressive universalism.
“You can’t have rules for one set of patients and a different set of rules for another set of patients, so there’s going to be a real issue around fairness and equity which Europe is going to have to address,” he said.
In an attempt, ASCO and ECO have joined forces in a special network, noted Julie Gralow, MD, chief medical officer at ASCO.
“The ECO/ASCO Special Network is all about collaboration and coordination across professional societies, across cancer patient groups, across academic and other clinical centers. We’re providing information in the various national languages and trying to amplify the work that each of us is doing. ... We’re sharing intelligence, regular reports from the field, information, experience, and most of all, contacts. We’re all being approached individually about people who need help or people who want to help, and we’re trying to bring this all together in a focused way.”
Separately, there is also an ASCO resource page, as well as an ECO resource page.
The American Cancer Society also has patient resources on their site, including a 24-hour international call center in multiple languages and a Volunteer Corp of Clinicians, which currently has 123 active volunteers (and another 300 applicants) available to answer questions.
Europe and other countries must consider both a medium and a long-term commitment to refugees with cancer, said Dr. Sullivan. “Because even if the war stopped tomorrow, it’s going to take between a year and a year and a half to rebuild cancer care in Ukraine.”
A version of this article first appeared on Medscape.com.
across the border into neighboring countries, which makes the role of oncology groups vitally important.
“They’re trying to deal with an extremely vulnerable and traumatized population – children who’ve lost their families, elderly who are confused and potentially abandoned,” commented Richard Sullivan, MD, PhD.
“The triage that’s happening on the border is not focusing on noncommunicable diseases,” he continued. “We know from previous crises that many cancer patients are lost; they simply do not present with their symptoms once they become refugees, and that’s going to become a really big issue.”
Oncology groups are needed to “provide the navigation, the treatment, and also the intelligence to ensure we deliver excellent cancer care where it’s needed for our Ukrainian friends,” he added. Dr. Sullivan is a member of the World Health Organization’s Emergency Committee and is director of the Institute of Cancer Policy at King’s College London.
He was speaking at a virtual briefing organized by the American Society of Clinical Oncology (ASCO) and the European Cancer Organisation (ECO), which have joined forces to centralize cancer care efforts.
With an estimated 3.3 million refugees having already crossed Ukraine’s borders, neighboring countries are experiencing an approximately 5% increase in their overall populations, making increased demand for cancer care inevitable, said Dr. Sullivan.
“Suggestions are that with 4 million refugees, you’re going to be looking at an increase of 13,000-16,000 cancer patients per month. ... But it will take time for the issue to evolve. At the moment, people are not being overwhelmed ... but there’s no doubt cancer care capacity for host countries is going to be an issue in the future.”
So far, about 2 million refugees are in Poland, where cancer centers have experienced a 10% increase in new patients since the war started, said Piotr Rutkowski, MD, PhD, professor of surgical oncology at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw.
“Of course, our resources are limited,” he said, adding that efforts are underway to accredit Ukrainian health care workers to work in Poland. “It’s unpredictable how the health care system in Europe can overcome these difficulties.”
“Until now, I don’t think any cancer patients have not received care, so still, we are in a positive situation, but the waiting list can enlarge in the near future,” Dr. Rutkowsli commented.
Indeed, the anticipated increase will “likely exceed the possibilities of the Polish health system” soon, warned Jacek Jassem, MD, PhD, professor of clinical oncology and radiotherapy and the head of the department of oncology and radiotherapy at the Medical University of Gdansk, Poland.
Although there is an EU international agreement for a more widespread allocation of cancer patients, “when they come to Poland, many of them want to be treated in Poland, because they have family here, the language is more familiar.”
Dr. Jassem suggests the best way to avoid overwhelming host cancer centers is to triage patients directly from Ukraine. “Some therapies shouldn’t be interrupted. So, for example, radiotherapy started in Ukraine should be continued there, but otherwise, chemotherapy can be continued elsewhere, surgery may be postponed and done elsewhere. These are the decisions that should be considered in Ukraine, and then patients who are selected for particular therapies should be reallocated to other countries,” he suggested.
Romania has seen an influx of about 400,000 refugees, including cancer patients seeking systemic therapy, radiotherapy, or follow-up, said Nicoleta Antone, MD, a medical oncologist at the Cancer Institute of Ion Chiricuta in Cluj-Napoca, Romania. “We have seen patients mainly with breast cancer because most of the refugees [with cancer] are women looking for systemic therapy, but also all the other tumor types, both solid and hematologic tumors.”
Dr. Sullivan says attempts by EU member states to address cancer needs are complicated by the fact that many refugees are still on the move. They have been passing through their initial host countries and moving on to Greece, Slovenia, Austria, Germany, Italy, and Turkey, “making the therapeutic geographies at any potential time quite challenging to keep an eye on.” Other countries, such as Moldova, are not part of the EU, “so we dealing with some really quite complex political and financial issues.”
The situation calls for a broader approach to refugees generally, he added. “We’re talking free cancer care for Ukrainian patients, but there’s also, of course, this dialogue of ensuring there’s free care for all refugees. Europe already has a large refugee contingent from other countries, so there’s no doubt this is an opportunity to talk more broadly about cancer care for refugees and also progressive universalism.
“You can’t have rules for one set of patients and a different set of rules for another set of patients, so there’s going to be a real issue around fairness and equity which Europe is going to have to address,” he said.
In an attempt, ASCO and ECO have joined forces in a special network, noted Julie Gralow, MD, chief medical officer at ASCO.
“The ECO/ASCO Special Network is all about collaboration and coordination across professional societies, across cancer patient groups, across academic and other clinical centers. We’re providing information in the various national languages and trying to amplify the work that each of us is doing. ... We’re sharing intelligence, regular reports from the field, information, experience, and most of all, contacts. We’re all being approached individually about people who need help or people who want to help, and we’re trying to bring this all together in a focused way.”
Separately, there is also an ASCO resource page, as well as an ECO resource page.
The American Cancer Society also has patient resources on their site, including a 24-hour international call center in multiple languages and a Volunteer Corp of Clinicians, which currently has 123 active volunteers (and another 300 applicants) available to answer questions.
Europe and other countries must consider both a medium and a long-term commitment to refugees with cancer, said Dr. Sullivan. “Because even if the war stopped tomorrow, it’s going to take between a year and a year and a half to rebuild cancer care in Ukraine.”
A version of this article first appeared on Medscape.com.
Hands trained for surgery now on machine gun: Kyiv oncologist
The pediatric oncology unit in Kyiv’s National Cancer Institute is empty, with all the children evacuated to safer hospitals in Western Ukraine or further, making it a good place to talk on Zoom.
Against a backdrop of colorful animals painted on the wall, Oleksandr Stakhovskyi, MD, PhD, speaks optimistically about the future of his city, his country, and even his patients, despite acknowledging that his surgical hands are now trained to use a machine gun.
“It’s not as bad as last week,” he laughs, explaining that residents of Kyiv are more relaxed now, despite the air raid sirens, because the city’s anti-missile system has thus far kept them safe.
Even still, missiles have continued hitting civilian residences and Dr. Stakhovskyi, a urologic-oncology surgeon, has evacuated his wife and children out of the country, as have 70% of his colleagues. But for those who stayed in Kyiv, there is a strong resolve.
“People working in IT, in law, in other professions — they just took the guns and stayed in Kyiv,” he said in an interview. “They are just civilians, armed, trying to protect and fortify Kyiv — to make it unbreakable.”
Dr. Stakhovskyi doesn’t have a background in the military, but he now knows how to use a machine gun. “I am a super-specialized oncologist, [but] I realize if I leave right now it will give the Russians momentum to come in. The longer it takes, the weaker the opponent army will become, and we are more and more optimistic,” he said.
In Kyiv, Dr. Stakhovskyi is working half the time at the cancer hospital and the other half at the nearby military hospital, but he said so far war casualties are minimal within the city, and even the flow of patients with cancer has reduced.
“I had my surgeries planned up until the end of March, but when the war started, they were all postponed,” he said. Emergency cancer surgeries have continued, and now there is talk of resuming some others. “We will stratify patients into categories based on need,” he said. “For those patients whose surgery can basically stop the disease and they don’t need neoadjuvant chemo, we’ll probably be doing those.”
Medical oncology clinics have also resumed, said Dr. Stakhovskyi, but the volume of patients is low, because many have left the city. An estimated 3.3 million people have left Ukraine since the Russian invasion on February 24.
Across the country, in Lviv near the Polish border, another surgical oncologist tells a different story. Andriy Hrynkiv, MD, from Lviv Regional Cancer Center, says his hospital has seen a dramatic increase in patients, displaced internally from areas where the medical infrastructure has collapsed.
“Russian forces have destroyed more than 117 hospitals, 43 ambulances have been shot at, 6 doctors have been killed, and 13 wounded,” Dr. Hrynkiv said. In the city of Mariupol, “doctors and patients have been taken hostage,” he said, used by Russian forces as a human shield. In Kharkiv, with approximately 1.5 million residents, the only oncologic hospital has been destroyed.
There is a shortage and instability of medical supplies including all iodine-containing medications that citizens are stocking up on in the face of a potential nuclear attack, he said.
Dr. Hrynkiv was speaking on a webcast organized by the American Society of Clinical Oncology (ASCO) and European Cancer Organisation (ECO).
The two organizations are collaborating with each other and the World Health Organization to create a special network that is aiming to connect professionals, academic and clinical centers, and patient groups.
Additionally, the Ukranian Society of Clinical Oncology (USCO), cofounded by Dr. Stakhovskyi, is trying to keep patients connected with nongovernment organizations.
“These patient organizations moved west when the war started, but they still use us to help them make contact with foreign doctors,” he said. “We have tried to centralize this process but it’s very difficult because patients and organizations are also calling doctors and centers directly looking for treatment options.”
He says USCO is also coordinating the distribution of a donation of immunotherapy pembrolizumab (Keytruda) from pharmaceutical company Merck Sharp & Dohme. “It’s a huge influx of this drug,” he says. “They’ve promised something like 2,000 doses to cover 230 patients for 3 months at least. Usually this is not an easy drug to access for people in Ukraine because it’s really expensive.”
Dr. Stakhovskyi said the optimism he feels is fueled by the support that Ukrainians feel from the rest of the world.
“We see the reaction of our international colleagues. It is so impressive and touching — lots of my ex-professors are texting me and sending me messages from all over the place, from Germany, from Canada, from France, from the United States,” he said. “And if we can be optimistic for ourselves, definitely that translates to our patients.”
A version of this article first appeared on Medscape.com.
The pediatric oncology unit in Kyiv’s National Cancer Institute is empty, with all the children evacuated to safer hospitals in Western Ukraine or further, making it a good place to talk on Zoom.
Against a backdrop of colorful animals painted on the wall, Oleksandr Stakhovskyi, MD, PhD, speaks optimistically about the future of his city, his country, and even his patients, despite acknowledging that his surgical hands are now trained to use a machine gun.
“It’s not as bad as last week,” he laughs, explaining that residents of Kyiv are more relaxed now, despite the air raid sirens, because the city’s anti-missile system has thus far kept them safe.
Even still, missiles have continued hitting civilian residences and Dr. Stakhovskyi, a urologic-oncology surgeon, has evacuated his wife and children out of the country, as have 70% of his colleagues. But for those who stayed in Kyiv, there is a strong resolve.
“People working in IT, in law, in other professions — they just took the guns and stayed in Kyiv,” he said in an interview. “They are just civilians, armed, trying to protect and fortify Kyiv — to make it unbreakable.”
Dr. Stakhovskyi doesn’t have a background in the military, but he now knows how to use a machine gun. “I am a super-specialized oncologist, [but] I realize if I leave right now it will give the Russians momentum to come in. The longer it takes, the weaker the opponent army will become, and we are more and more optimistic,” he said.
In Kyiv, Dr. Stakhovskyi is working half the time at the cancer hospital and the other half at the nearby military hospital, but he said so far war casualties are minimal within the city, and even the flow of patients with cancer has reduced.
“I had my surgeries planned up until the end of March, but when the war started, they were all postponed,” he said. Emergency cancer surgeries have continued, and now there is talk of resuming some others. “We will stratify patients into categories based on need,” he said. “For those patients whose surgery can basically stop the disease and they don’t need neoadjuvant chemo, we’ll probably be doing those.”
Medical oncology clinics have also resumed, said Dr. Stakhovskyi, but the volume of patients is low, because many have left the city. An estimated 3.3 million people have left Ukraine since the Russian invasion on February 24.
Across the country, in Lviv near the Polish border, another surgical oncologist tells a different story. Andriy Hrynkiv, MD, from Lviv Regional Cancer Center, says his hospital has seen a dramatic increase in patients, displaced internally from areas where the medical infrastructure has collapsed.
“Russian forces have destroyed more than 117 hospitals, 43 ambulances have been shot at, 6 doctors have been killed, and 13 wounded,” Dr. Hrynkiv said. In the city of Mariupol, “doctors and patients have been taken hostage,” he said, used by Russian forces as a human shield. In Kharkiv, with approximately 1.5 million residents, the only oncologic hospital has been destroyed.
There is a shortage and instability of medical supplies including all iodine-containing medications that citizens are stocking up on in the face of a potential nuclear attack, he said.
Dr. Hrynkiv was speaking on a webcast organized by the American Society of Clinical Oncology (ASCO) and European Cancer Organisation (ECO).
The two organizations are collaborating with each other and the World Health Organization to create a special network that is aiming to connect professionals, academic and clinical centers, and patient groups.
Additionally, the Ukranian Society of Clinical Oncology (USCO), cofounded by Dr. Stakhovskyi, is trying to keep patients connected with nongovernment organizations.
“These patient organizations moved west when the war started, but they still use us to help them make contact with foreign doctors,” he said. “We have tried to centralize this process but it’s very difficult because patients and organizations are also calling doctors and centers directly looking for treatment options.”
He says USCO is also coordinating the distribution of a donation of immunotherapy pembrolizumab (Keytruda) from pharmaceutical company Merck Sharp & Dohme. “It’s a huge influx of this drug,” he says. “They’ve promised something like 2,000 doses to cover 230 patients for 3 months at least. Usually this is not an easy drug to access for people in Ukraine because it’s really expensive.”
Dr. Stakhovskyi said the optimism he feels is fueled by the support that Ukrainians feel from the rest of the world.
“We see the reaction of our international colleagues. It is so impressive and touching — lots of my ex-professors are texting me and sending me messages from all over the place, from Germany, from Canada, from France, from the United States,” he said. “And if we can be optimistic for ourselves, definitely that translates to our patients.”
A version of this article first appeared on Medscape.com.
The pediatric oncology unit in Kyiv’s National Cancer Institute is empty, with all the children evacuated to safer hospitals in Western Ukraine or further, making it a good place to talk on Zoom.
Against a backdrop of colorful animals painted on the wall, Oleksandr Stakhovskyi, MD, PhD, speaks optimistically about the future of his city, his country, and even his patients, despite acknowledging that his surgical hands are now trained to use a machine gun.
“It’s not as bad as last week,” he laughs, explaining that residents of Kyiv are more relaxed now, despite the air raid sirens, because the city’s anti-missile system has thus far kept them safe.
Even still, missiles have continued hitting civilian residences and Dr. Stakhovskyi, a urologic-oncology surgeon, has evacuated his wife and children out of the country, as have 70% of his colleagues. But for those who stayed in Kyiv, there is a strong resolve.
“People working in IT, in law, in other professions — they just took the guns and stayed in Kyiv,” he said in an interview. “They are just civilians, armed, trying to protect and fortify Kyiv — to make it unbreakable.”
Dr. Stakhovskyi doesn’t have a background in the military, but he now knows how to use a machine gun. “I am a super-specialized oncologist, [but] I realize if I leave right now it will give the Russians momentum to come in. The longer it takes, the weaker the opponent army will become, and we are more and more optimistic,” he said.
In Kyiv, Dr. Stakhovskyi is working half the time at the cancer hospital and the other half at the nearby military hospital, but he said so far war casualties are minimal within the city, and even the flow of patients with cancer has reduced.
“I had my surgeries planned up until the end of March, but when the war started, they were all postponed,” he said. Emergency cancer surgeries have continued, and now there is talk of resuming some others. “We will stratify patients into categories based on need,” he said. “For those patients whose surgery can basically stop the disease and they don’t need neoadjuvant chemo, we’ll probably be doing those.”
Medical oncology clinics have also resumed, said Dr. Stakhovskyi, but the volume of patients is low, because many have left the city. An estimated 3.3 million people have left Ukraine since the Russian invasion on February 24.
Across the country, in Lviv near the Polish border, another surgical oncologist tells a different story. Andriy Hrynkiv, MD, from Lviv Regional Cancer Center, says his hospital has seen a dramatic increase in patients, displaced internally from areas where the medical infrastructure has collapsed.
“Russian forces have destroyed more than 117 hospitals, 43 ambulances have been shot at, 6 doctors have been killed, and 13 wounded,” Dr. Hrynkiv said. In the city of Mariupol, “doctors and patients have been taken hostage,” he said, used by Russian forces as a human shield. In Kharkiv, with approximately 1.5 million residents, the only oncologic hospital has been destroyed.
There is a shortage and instability of medical supplies including all iodine-containing medications that citizens are stocking up on in the face of a potential nuclear attack, he said.
Dr. Hrynkiv was speaking on a webcast organized by the American Society of Clinical Oncology (ASCO) and European Cancer Organisation (ECO).
The two organizations are collaborating with each other and the World Health Organization to create a special network that is aiming to connect professionals, academic and clinical centers, and patient groups.
Additionally, the Ukranian Society of Clinical Oncology (USCO), cofounded by Dr. Stakhovskyi, is trying to keep patients connected with nongovernment organizations.
“These patient organizations moved west when the war started, but they still use us to help them make contact with foreign doctors,” he said. “We have tried to centralize this process but it’s very difficult because patients and organizations are also calling doctors and centers directly looking for treatment options.”
He says USCO is also coordinating the distribution of a donation of immunotherapy pembrolizumab (Keytruda) from pharmaceutical company Merck Sharp & Dohme. “It’s a huge influx of this drug,” he says. “They’ve promised something like 2,000 doses to cover 230 patients for 3 months at least. Usually this is not an easy drug to access for people in Ukraine because it’s really expensive.”
Dr. Stakhovskyi said the optimism he feels is fueled by the support that Ukrainians feel from the rest of the world.
“We see the reaction of our international colleagues. It is so impressive and touching — lots of my ex-professors are texting me and sending me messages from all over the place, from Germany, from Canada, from France, from the United States,” he said. “And if we can be optimistic for ourselves, definitely that translates to our patients.”
A version of this article first appeared on Medscape.com.
Cancer patients vulnerable to COVID misinformation
For the past 2 years, oncology practitioners around the world have struggled with the same dilemma: how to maintain their patients’ cancer care without exposing them to COVID-19. Regardless of the country, language, or even which wave of the pandemic, the conversations have likely been very similar: weighing risks versuss benefits, and individualizing each patient’s pandemic cancer plan.
But one question most oncologists have probably overlooked in these discussions is about where their patients get their COVID information – or misinformation.
Surprisingly, this seemingly small detail could make a big difference in a patient’s prognosis.
A recent study found that building on an earlier finding of similar vulnerabilities among parents of children with cancer, compared with parents of healthy children.
“It doesn’t matter what you search for, there is an overwhelming level of information online,” the lead author on both studies, Jeanine Guidry, PhD, from Virginia Commonwealth University’s Massey Cancer Center in Richmond, said in an interview. “If misinformation is the first thing you encounter about a topic, you’re much more likely to believe it and it’s going to be very hard to convince you otherwise.”
Before the pandemic, Dr. Guidry, who is director of the Media+Health Lab at VCU, had already been studying vaccine misinformation on Pinterest and Instagram.
So when data coming out at the start of the pandemic suggested that an increase in pediatric cancer mortality might be partially because of COVID-19 misinformation, she jumped on it.
Dr. Guidry and associates designed a questionnaire involving COVID misinformation statements available online and found that parents of children with cancer were significantly more likely to endorse them, compared with parents of healthy children.
“Our advice to clinicians is you may have an issue here,” Dr. Guidry said in an interview. “You may want to check where they get their news, and if there’s any pieces of misinformation that could be harmful.”
Some beliefs, such as eating more garlic protects against COVID, are not particularly harmful, she acknowledged, but others – such as drinking bleach being protective – are quite harmful, and they often stem from the same misinformation sources.
Both of Dr. Guidry’s studies involved surveys of either adult patients with cancer or parents of children with cancer.
The adult patient survey was conducted June 1-15, 2020, and included 897 respondents, of whom 287 were patients in active treatment for cancer, 301 were survivors not currently in treatment, and 309 had no cancer history.
The parents’ survey, conducted in May 2020, included 735 parents of children aged 2-17 years, 315 of whom had children currently undergoing cancer treatment, and 420 of whom had children with no history of cancer.
Among the misinformation they were asked to agree or disagree with were statements such as “it is unsafe to receive mail from China,” “antibiotics can prevent and treat COVID-19,” and “COVID is less deadly than the ‘flu,’ ” among others.
The surveys revealed that the patients in current treatment for cancer and the parents of patients in current treatment were most likely to endorse COVID misinformation. Results from the parents’ survey showed that “believing misinformation was also more likely for fathers, younger parents, and parents with higher perceived stress from COVID-19,” the authors wrote. Among adult patients and controls, patients in active treatment were most likely to believe misinformation, with cancer survivors no longer in treatment being the least likely to believe it, compared with healthy controls who were in between.
Why the difference? The authors suggested that patients in active treatment “may seek out more information on the internet or via social media where they are more exposed to misinformation,” whereas survivors no longer undergoing treatment may be more “media savvy and have learned to be wary of questionable health information.”
In their articles, Dr. Guidry and associates advised oncologists to be aware of their patients’ potential to endorse COVID misinformation and to “proactively address this in routine visits as well as tailored written materials.” This is easier said than done, she commented, acknowledging that keeping up with the latest misinformation is a challenge.
The misinformation statements her group used in their surveys were popular early in the pandemic, but “some of them have shown fairly remarkable staying power and some have been replaced,” she said. She invited interested clinicians to contact her team for guidance on newer misinformation.
Ultimately, she believes most patients with cancer who endorse misinformation are simply afraid, and looking for help. “They’re already dealing with a level of stress from their illness and then they’re thrown into a pandemic,” Dr. Guidry said. “At some point you just want a solution. Hydroxychloroquine? Great! Horse dewormer? Fantastic! Just wanting to control the situation and not having something else to deal with.”
Both studies were funded by the National Cancer Institute at the National Institutes of Health. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
For the past 2 years, oncology practitioners around the world have struggled with the same dilemma: how to maintain their patients’ cancer care without exposing them to COVID-19. Regardless of the country, language, or even which wave of the pandemic, the conversations have likely been very similar: weighing risks versuss benefits, and individualizing each patient’s pandemic cancer plan.
But one question most oncologists have probably overlooked in these discussions is about where their patients get their COVID information – or misinformation.
Surprisingly, this seemingly small detail could make a big difference in a patient’s prognosis.
A recent study found that building on an earlier finding of similar vulnerabilities among parents of children with cancer, compared with parents of healthy children.
“It doesn’t matter what you search for, there is an overwhelming level of information online,” the lead author on both studies, Jeanine Guidry, PhD, from Virginia Commonwealth University’s Massey Cancer Center in Richmond, said in an interview. “If misinformation is the first thing you encounter about a topic, you’re much more likely to believe it and it’s going to be very hard to convince you otherwise.”
Before the pandemic, Dr. Guidry, who is director of the Media+Health Lab at VCU, had already been studying vaccine misinformation on Pinterest and Instagram.
So when data coming out at the start of the pandemic suggested that an increase in pediatric cancer mortality might be partially because of COVID-19 misinformation, she jumped on it.
Dr. Guidry and associates designed a questionnaire involving COVID misinformation statements available online and found that parents of children with cancer were significantly more likely to endorse them, compared with parents of healthy children.
“Our advice to clinicians is you may have an issue here,” Dr. Guidry said in an interview. “You may want to check where they get their news, and if there’s any pieces of misinformation that could be harmful.”
Some beliefs, such as eating more garlic protects against COVID, are not particularly harmful, she acknowledged, but others – such as drinking bleach being protective – are quite harmful, and they often stem from the same misinformation sources.
Both of Dr. Guidry’s studies involved surveys of either adult patients with cancer or parents of children with cancer.
The adult patient survey was conducted June 1-15, 2020, and included 897 respondents, of whom 287 were patients in active treatment for cancer, 301 were survivors not currently in treatment, and 309 had no cancer history.
The parents’ survey, conducted in May 2020, included 735 parents of children aged 2-17 years, 315 of whom had children currently undergoing cancer treatment, and 420 of whom had children with no history of cancer.
Among the misinformation they were asked to agree or disagree with were statements such as “it is unsafe to receive mail from China,” “antibiotics can prevent and treat COVID-19,” and “COVID is less deadly than the ‘flu,’ ” among others.
The surveys revealed that the patients in current treatment for cancer and the parents of patients in current treatment were most likely to endorse COVID misinformation. Results from the parents’ survey showed that “believing misinformation was also more likely for fathers, younger parents, and parents with higher perceived stress from COVID-19,” the authors wrote. Among adult patients and controls, patients in active treatment were most likely to believe misinformation, with cancer survivors no longer in treatment being the least likely to believe it, compared with healthy controls who were in between.
Why the difference? The authors suggested that patients in active treatment “may seek out more information on the internet or via social media where they are more exposed to misinformation,” whereas survivors no longer undergoing treatment may be more “media savvy and have learned to be wary of questionable health information.”
In their articles, Dr. Guidry and associates advised oncologists to be aware of their patients’ potential to endorse COVID misinformation and to “proactively address this in routine visits as well as tailored written materials.” This is easier said than done, she commented, acknowledging that keeping up with the latest misinformation is a challenge.
The misinformation statements her group used in their surveys were popular early in the pandemic, but “some of them have shown fairly remarkable staying power and some have been replaced,” she said. She invited interested clinicians to contact her team for guidance on newer misinformation.
Ultimately, she believes most patients with cancer who endorse misinformation are simply afraid, and looking for help. “They’re already dealing with a level of stress from their illness and then they’re thrown into a pandemic,” Dr. Guidry said. “At some point you just want a solution. Hydroxychloroquine? Great! Horse dewormer? Fantastic! Just wanting to control the situation and not having something else to deal with.”
Both studies were funded by the National Cancer Institute at the National Institutes of Health. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
For the past 2 years, oncology practitioners around the world have struggled with the same dilemma: how to maintain their patients’ cancer care without exposing them to COVID-19. Regardless of the country, language, or even which wave of the pandemic, the conversations have likely been very similar: weighing risks versuss benefits, and individualizing each patient’s pandemic cancer plan.
But one question most oncologists have probably overlooked in these discussions is about where their patients get their COVID information – or misinformation.
Surprisingly, this seemingly small detail could make a big difference in a patient’s prognosis.
A recent study found that building on an earlier finding of similar vulnerabilities among parents of children with cancer, compared with parents of healthy children.
“It doesn’t matter what you search for, there is an overwhelming level of information online,” the lead author on both studies, Jeanine Guidry, PhD, from Virginia Commonwealth University’s Massey Cancer Center in Richmond, said in an interview. “If misinformation is the first thing you encounter about a topic, you’re much more likely to believe it and it’s going to be very hard to convince you otherwise.”
Before the pandemic, Dr. Guidry, who is director of the Media+Health Lab at VCU, had already been studying vaccine misinformation on Pinterest and Instagram.
So when data coming out at the start of the pandemic suggested that an increase in pediatric cancer mortality might be partially because of COVID-19 misinformation, she jumped on it.
Dr. Guidry and associates designed a questionnaire involving COVID misinformation statements available online and found that parents of children with cancer were significantly more likely to endorse them, compared with parents of healthy children.
“Our advice to clinicians is you may have an issue here,” Dr. Guidry said in an interview. “You may want to check where they get their news, and if there’s any pieces of misinformation that could be harmful.”
Some beliefs, such as eating more garlic protects against COVID, are not particularly harmful, she acknowledged, but others – such as drinking bleach being protective – are quite harmful, and they often stem from the same misinformation sources.
Both of Dr. Guidry’s studies involved surveys of either adult patients with cancer or parents of children with cancer.
The adult patient survey was conducted June 1-15, 2020, and included 897 respondents, of whom 287 were patients in active treatment for cancer, 301 were survivors not currently in treatment, and 309 had no cancer history.
The parents’ survey, conducted in May 2020, included 735 parents of children aged 2-17 years, 315 of whom had children currently undergoing cancer treatment, and 420 of whom had children with no history of cancer.
Among the misinformation they were asked to agree or disagree with were statements such as “it is unsafe to receive mail from China,” “antibiotics can prevent and treat COVID-19,” and “COVID is less deadly than the ‘flu,’ ” among others.
The surveys revealed that the patients in current treatment for cancer and the parents of patients in current treatment were most likely to endorse COVID misinformation. Results from the parents’ survey showed that “believing misinformation was also more likely for fathers, younger parents, and parents with higher perceived stress from COVID-19,” the authors wrote. Among adult patients and controls, patients in active treatment were most likely to believe misinformation, with cancer survivors no longer in treatment being the least likely to believe it, compared with healthy controls who were in between.
Why the difference? The authors suggested that patients in active treatment “may seek out more information on the internet or via social media where they are more exposed to misinformation,” whereas survivors no longer undergoing treatment may be more “media savvy and have learned to be wary of questionable health information.”
In their articles, Dr. Guidry and associates advised oncologists to be aware of their patients’ potential to endorse COVID misinformation and to “proactively address this in routine visits as well as tailored written materials.” This is easier said than done, she commented, acknowledging that keeping up with the latest misinformation is a challenge.
The misinformation statements her group used in their surveys were popular early in the pandemic, but “some of them have shown fairly remarkable staying power and some have been replaced,” she said. She invited interested clinicians to contact her team for guidance on newer misinformation.
Ultimately, she believes most patients with cancer who endorse misinformation are simply afraid, and looking for help. “They’re already dealing with a level of stress from their illness and then they’re thrown into a pandemic,” Dr. Guidry said. “At some point you just want a solution. Hydroxychloroquine? Great! Horse dewormer? Fantastic! Just wanting to control the situation and not having something else to deal with.”
Both studies were funded by the National Cancer Institute at the National Institutes of Health. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM PATIENT EDUCATION AND COUNSELING
Targeting the endocannabinoid system in migraine
, according to Italian researchers at the University of Pavia, and the C. Mondino National Institute of Neurology Foundation. “The complexity of the endocannabinoid system calls for accurate biochemical and pharmacological characterization of any new compounds undergoing testing and development,” noted Rosaria Greco, PhD. She and her colleagues authored a review on the topic that was published online Feb. 18, 2022, in Headache.
Although cannabis has been investigated for both the treatment and prevention of migraine, evidence for its benefit is weak because of lack of controlled studies, they explained. Archival data from a large database “showed greater improvements in men than in women and suggested that concentrated preparations were more effective than flower consumption.” In addition, a small single-center study linked nabilone, a synthetic cannabinoid, to reductions in pain duration, intensity, and daily intake of analgesics among patients with medication overuse headache. Finally, a pilot study reported a reduction in pain intensity among patients with chronic migraine treated with a combination of tested a combination of delta-9-tetrahydrocannabinol and cannabidiol. “Methodologically sound studies are now needed to investigate the possible effects of cannabis in migraine treatment and to define strains, formulations, and dosage,” they noted.
Not just cannabis
In addition to exogenous cannabis, there are now preclinical studies suggesting other compounds that interact with the endocannabinoid system “are also able to modulate the pathways involved in migraine-related pain,” the study authors wrote. “But the road ahead is still long. Multiple molecules linked to the endocannabinoid system have emerged as potential therapeutic targets.
The complexity of the system demands caution and precise biochemical and pharmacological characterization of the new compounds to be tested and developed.”
Among these compounds are endogenous ligands such as N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol that specifically target CB1 and CB2 receptors. Additionally, there are endocannabinoid-based drugs that also target the CB1/CB2 receptors, as well as other substances, such as lipids (palmitoylethanolamide [PEA]) and enzymes, that do not bind to the CB1/CB2 receptors but are responsible for endocannabinoid biosynthesis.
There is some evidence that the endocannabinoid system may be dysfunctional in patients with migraine, and the authors noted their work has shown that PEA plasma levels are increased during experimentally triggered migraine-like attacks. Thus, some preclinical and preliminary evidence suggests that administration of PEA or anandamide may have analgesic and anti-inflammatory effects in migraine.
Another approach is the inhibition of endocannabinoid catabolic enzymes, which could circumvent the adverse effects associated with direct activation of CB receptors. “Endocannabinoid tone enhancement has been proposed as an alternative modality of activation of CB receptors and is possibly devoid of the psychotropic effects reported with CB receptor agonists,” noted the authors, who have shown in animal and preclinical studies that inhibition of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase can modulate migraine pain.
Yet another way of indirectly impacting CB receptors is through their allosteric ligands, an approach that “deserves further investigation”, and “might provide interesting leads for clinical development, given that it may have a favorable side-effect profile with limited psychomimetic and depressant effects,” wrote the authors. And finally, inhibition of N-acylethanolamine acid amide hydrolase, the enzyme that preferentially hydrolyzes PEA, might be a promising approach.
“The multiplicity of options and the wealth of data already obtained in animal models underscore the importance of further advancing research in this area,” the authors concluded.
Patients are taking cannabinoids; physicians should learn about them
Commenting on the paper, Alan Rapaport, MD, clinical professor of neurology at the University of California, Los Angeles, said “this well-done paper points out the complexity of the endocannabinoid system and the multiple ways of getting it to work for certain patients. It details some of the studies that show beneficial results in migraine, medication overuse headache, chronic migraine, and pain. Patients with headache, other types of pain, anxiety, nausea, sleep issues, and other symptoms are already taking cannabinoids, usually derived from the marijuana plant, that are not well regulated. A few are prescribed drugs which target CB1 and CB2 receptors. Patients often get relief of some of their symptoms, sometimes getting high and many times not.
“The paper makes the point that previous studies are often small, not carefully controlled, or well documented. We do need to start doing larger, properly designed studies and getting them into the literature. Doctors need to learn more about these treatments. The next step will be to get [Food and Drug Administration]–approved treatments, so physicians and nurses will know exactly what we are giving, the beneficial effects to expect in a certain percentage of patients, and the adverse events to warn our patients about. Cannabinoids have been tried by a large percentage of patients with headache and pain. Now we need to standardize the various treatments that are sure to be suggested in the future.”
The study was funded by the Migraine Research Foundation, and the Italian Ministry of Health. The study authors declared no conflicts of interest.
, according to Italian researchers at the University of Pavia, and the C. Mondino National Institute of Neurology Foundation. “The complexity of the endocannabinoid system calls for accurate biochemical and pharmacological characterization of any new compounds undergoing testing and development,” noted Rosaria Greco, PhD. She and her colleagues authored a review on the topic that was published online Feb. 18, 2022, in Headache.
Although cannabis has been investigated for both the treatment and prevention of migraine, evidence for its benefit is weak because of lack of controlled studies, they explained. Archival data from a large database “showed greater improvements in men than in women and suggested that concentrated preparations were more effective than flower consumption.” In addition, a small single-center study linked nabilone, a synthetic cannabinoid, to reductions in pain duration, intensity, and daily intake of analgesics among patients with medication overuse headache. Finally, a pilot study reported a reduction in pain intensity among patients with chronic migraine treated with a combination of tested a combination of delta-9-tetrahydrocannabinol and cannabidiol. “Methodologically sound studies are now needed to investigate the possible effects of cannabis in migraine treatment and to define strains, formulations, and dosage,” they noted.
Not just cannabis
In addition to exogenous cannabis, there are now preclinical studies suggesting other compounds that interact with the endocannabinoid system “are also able to modulate the pathways involved in migraine-related pain,” the study authors wrote. “But the road ahead is still long. Multiple molecules linked to the endocannabinoid system have emerged as potential therapeutic targets.
The complexity of the system demands caution and precise biochemical and pharmacological characterization of the new compounds to be tested and developed.”
Among these compounds are endogenous ligands such as N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol that specifically target CB1 and CB2 receptors. Additionally, there are endocannabinoid-based drugs that also target the CB1/CB2 receptors, as well as other substances, such as lipids (palmitoylethanolamide [PEA]) and enzymes, that do not bind to the CB1/CB2 receptors but are responsible for endocannabinoid biosynthesis.
There is some evidence that the endocannabinoid system may be dysfunctional in patients with migraine, and the authors noted their work has shown that PEA plasma levels are increased during experimentally triggered migraine-like attacks. Thus, some preclinical and preliminary evidence suggests that administration of PEA or anandamide may have analgesic and anti-inflammatory effects in migraine.
Another approach is the inhibition of endocannabinoid catabolic enzymes, which could circumvent the adverse effects associated with direct activation of CB receptors. “Endocannabinoid tone enhancement has been proposed as an alternative modality of activation of CB receptors and is possibly devoid of the psychotropic effects reported with CB receptor agonists,” noted the authors, who have shown in animal and preclinical studies that inhibition of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase can modulate migraine pain.
Yet another way of indirectly impacting CB receptors is through their allosteric ligands, an approach that “deserves further investigation”, and “might provide interesting leads for clinical development, given that it may have a favorable side-effect profile with limited psychomimetic and depressant effects,” wrote the authors. And finally, inhibition of N-acylethanolamine acid amide hydrolase, the enzyme that preferentially hydrolyzes PEA, might be a promising approach.
“The multiplicity of options and the wealth of data already obtained in animal models underscore the importance of further advancing research in this area,” the authors concluded.
Patients are taking cannabinoids; physicians should learn about them
Commenting on the paper, Alan Rapaport, MD, clinical professor of neurology at the University of California, Los Angeles, said “this well-done paper points out the complexity of the endocannabinoid system and the multiple ways of getting it to work for certain patients. It details some of the studies that show beneficial results in migraine, medication overuse headache, chronic migraine, and pain. Patients with headache, other types of pain, anxiety, nausea, sleep issues, and other symptoms are already taking cannabinoids, usually derived from the marijuana plant, that are not well regulated. A few are prescribed drugs which target CB1 and CB2 receptors. Patients often get relief of some of their symptoms, sometimes getting high and many times not.
“The paper makes the point that previous studies are often small, not carefully controlled, or well documented. We do need to start doing larger, properly designed studies and getting them into the literature. Doctors need to learn more about these treatments. The next step will be to get [Food and Drug Administration]–approved treatments, so physicians and nurses will know exactly what we are giving, the beneficial effects to expect in a certain percentage of patients, and the adverse events to warn our patients about. Cannabinoids have been tried by a large percentage of patients with headache and pain. Now we need to standardize the various treatments that are sure to be suggested in the future.”
The study was funded by the Migraine Research Foundation, and the Italian Ministry of Health. The study authors declared no conflicts of interest.
, according to Italian researchers at the University of Pavia, and the C. Mondino National Institute of Neurology Foundation. “The complexity of the endocannabinoid system calls for accurate biochemical and pharmacological characterization of any new compounds undergoing testing and development,” noted Rosaria Greco, PhD. She and her colleagues authored a review on the topic that was published online Feb. 18, 2022, in Headache.
Although cannabis has been investigated for both the treatment and prevention of migraine, evidence for its benefit is weak because of lack of controlled studies, they explained. Archival data from a large database “showed greater improvements in men than in women and suggested that concentrated preparations were more effective than flower consumption.” In addition, a small single-center study linked nabilone, a synthetic cannabinoid, to reductions in pain duration, intensity, and daily intake of analgesics among patients with medication overuse headache. Finally, a pilot study reported a reduction in pain intensity among patients with chronic migraine treated with a combination of tested a combination of delta-9-tetrahydrocannabinol and cannabidiol. “Methodologically sound studies are now needed to investigate the possible effects of cannabis in migraine treatment and to define strains, formulations, and dosage,” they noted.
Not just cannabis
In addition to exogenous cannabis, there are now preclinical studies suggesting other compounds that interact with the endocannabinoid system “are also able to modulate the pathways involved in migraine-related pain,” the study authors wrote. “But the road ahead is still long. Multiple molecules linked to the endocannabinoid system have emerged as potential therapeutic targets.
The complexity of the system demands caution and precise biochemical and pharmacological characterization of the new compounds to be tested and developed.”
Among these compounds are endogenous ligands such as N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol that specifically target CB1 and CB2 receptors. Additionally, there are endocannabinoid-based drugs that also target the CB1/CB2 receptors, as well as other substances, such as lipids (palmitoylethanolamide [PEA]) and enzymes, that do not bind to the CB1/CB2 receptors but are responsible for endocannabinoid biosynthesis.
There is some evidence that the endocannabinoid system may be dysfunctional in patients with migraine, and the authors noted their work has shown that PEA plasma levels are increased during experimentally triggered migraine-like attacks. Thus, some preclinical and preliminary evidence suggests that administration of PEA or anandamide may have analgesic and anti-inflammatory effects in migraine.
Another approach is the inhibition of endocannabinoid catabolic enzymes, which could circumvent the adverse effects associated with direct activation of CB receptors. “Endocannabinoid tone enhancement has been proposed as an alternative modality of activation of CB receptors and is possibly devoid of the psychotropic effects reported with CB receptor agonists,” noted the authors, who have shown in animal and preclinical studies that inhibition of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase can modulate migraine pain.
Yet another way of indirectly impacting CB receptors is through their allosteric ligands, an approach that “deserves further investigation”, and “might provide interesting leads for clinical development, given that it may have a favorable side-effect profile with limited psychomimetic and depressant effects,” wrote the authors. And finally, inhibition of N-acylethanolamine acid amide hydrolase, the enzyme that preferentially hydrolyzes PEA, might be a promising approach.
“The multiplicity of options and the wealth of data already obtained in animal models underscore the importance of further advancing research in this area,” the authors concluded.
Patients are taking cannabinoids; physicians should learn about them
Commenting on the paper, Alan Rapaport, MD, clinical professor of neurology at the University of California, Los Angeles, said “this well-done paper points out the complexity of the endocannabinoid system and the multiple ways of getting it to work for certain patients. It details some of the studies that show beneficial results in migraine, medication overuse headache, chronic migraine, and pain. Patients with headache, other types of pain, anxiety, nausea, sleep issues, and other symptoms are already taking cannabinoids, usually derived from the marijuana plant, that are not well regulated. A few are prescribed drugs which target CB1 and CB2 receptors. Patients often get relief of some of their symptoms, sometimes getting high and many times not.
“The paper makes the point that previous studies are often small, not carefully controlled, or well documented. We do need to start doing larger, properly designed studies and getting them into the literature. Doctors need to learn more about these treatments. The next step will be to get [Food and Drug Administration]–approved treatments, so physicians and nurses will know exactly what we are giving, the beneficial effects to expect in a certain percentage of patients, and the adverse events to warn our patients about. Cannabinoids have been tried by a large percentage of patients with headache and pain. Now we need to standardize the various treatments that are sure to be suggested in the future.”
The study was funded by the Migraine Research Foundation, and the Italian Ministry of Health. The study authors declared no conflicts of interest.
FROM HEADACHE