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Depression as a terminal illness
Is there a place for palliative care?
In 2020, there were 5,224 suicide deaths registered in England and Wales.1 The Mental Health Foundation, a London-based charitable organization, reports that approximately 70% of such deaths are in patients with depression.2 The number of attempted suicides is much higher – the South West London and St. George’s Mental Health Trust estimates that at least 140,000 people attempt suicide in England and Wales every year.3
In suicidal depression, the psychological pain is often unbearable and feels overwhelmingly incompatible with life. One is no longer living but merely surviving, and eventually the exhaustion will lead to decompensation. This is marked by suicide. The goal is to end the suffering permanently and this is achieved through death.
Depression, like all other physical and mental illnesses, runs a course. This is highly variable between individuals and can be the case even between separate relapse episodes in the same patient. Like many diagnoses, depression is known to lead to death in a significant number of people. Many suicidally depressed patients feel that death will be an inevitable result of the illness.
Suicide is often viewed as a symptom of severe depression, but what if we considered death as part of the disease process itself? Consequently, would it be justifiable to consider depression in these patients as a form of terminal illness, since without treatment, the condition would lead to death? Accordingly, could there be a place for palliative care in a small minority of suicidally depressed patients? Taking such a perspective would mean that instead of placing the focus on the prevention of deaths and prolonging of lifespan, the focus would be on making the patients comfortable as the disease progresses, maintaining their dignity, and promoting autonomy.
Suicidal depression and rights
The rationale for this is that psychiatric patients do not have the capacity to make such decisions in the acute setting, because of the direct effects of the unwell mind on their decision-making processes and cognitive faculties. While this may be true in some cases, there is limited evidence that this applies to all suicidally depressed patients in all cases.
Another argument against allowing suicidally depressed patients to decline treatment is the notion that the episode of depression can be successfully treated, and the patients can return to their normal level of functioning. However, in individuals with a previous history of severe depression, it is possible that they will relapse again at some point. In the same way, a cancer can be treated, and patients could return to their baseline level of functioning, only for the cancer to then return later in life. In both cases, these relapses are emotionally and physically exhausting and painful to get through. The difference is that a cancer patient can decline further treatment and opt for no treatment or for palliative treatment, knowing that the disease will shorten life expectancy. For suicidal depression, this is not an option. Such patients may be sectioned, admitted, and treated against their will. Suicide, which could be considered a natural endpoint of the depressive illness, is unacceptable.
Is it fair to confiscate one’s right to decline treatment, solely because that person suffers from a mental illness, as opposed to a physical one? Numerous studies have demonstrated clear structural, neurological, and neurochemical changes in suicidal depression. This is evidence that such a condition encompasses a clear physical property. Other conditions, such as dementia and chronic pain, have previously been accepted for euthanasia in certain countries. Pain is a subjective experience of nociceptive and neurochemical signaling. In the same way, depression is a subjective experience involving aberrant neurochemical signaling. The difference is that physical pain can often be localized. However, patients with suicidal depression often experience very severe and tangible pain that can be difficult to articulate and for others to understand if they have never experienced it themselves.
Like distinct forms of physical pain, suicidal depression creates a different form of pain, but it is pain, nonetheless. Is it therefore fair for suicidally depressed patients to be given lesser rights than those suffering from physical illnesses in determining their fate?
Suicidal depression and capacity
A patient is assumed to have capacity unless proven otherwise. This is often the reverse when managing psychiatric patients. However, if patients are able to fulfill all criteria required for demonstrating capacity (understanding the information, retaining, weighing up, and communicating the decision), surely they have demonstrated capacity to make their decisions, whether that is to receive or to refuse treatment.
For physical illnesses, adults with capacity are permitted to make decisions that their treating teams may not agree with, but this disagreement alone is generally insufficient to override the decisions. These patients, unlike in suicidal depression, have the right to refuse lifesaving or life-prolonging treatment.
An argument for this is that in terminal physical illnesses, death is a passive process and neither the patient nor the physician are actively causing it. However, in many palliative settings, patients can be given medications and treatment for symptomatic relief, even if these may hasten their death. The principle that makes this permissible is that the primary aim is to improve the symptoms and ensure comfort. The unintended effect includes side effects and hastened death. Similarly, in suicidal depression, one could argue that the patient should be permitted medications that may hasten or lead to death, so long as the primary aim is to improve the symptoms of the unbearable mental pain and suffering.
Let us consider an alternative scenario. What if previously suicidal patients are currently in remission from depression and make advanced directives? In their current healthy state, they assert that if, in the future, they were to relapse, they would not want any form of treatment. Instead, they wish for the disease to run its course, which may end in death through suicide.
In this case, the circumstances in which the statement was made would be entirely valid – the patients at that moment have capacity, are not under coercion, are able to articulate logical thought processes, and their reasoning would not be affected by a concurrent psychiatric pathology. Furthermore, they can demonstrate that suicide is not an impulsive decision and have considered the consequences of suicide on themselves and others. If the patients can demonstrate all the above, what would the ethical grounds be for refusing this advanced directive?
Medical ethics
Below, I consider this debate in the context of four pillars of medical ethics.
Non-maleficence
To determine whether an action is in line with non-maleficence, one must ask whether the proposed treatment will improve or resolve one’s condition. In the case of severe suicidal depression, the treatment may help patients in the short term, but what happens if or when they relapse? The treatment will likely prolong life, but also inadvertently prolong suffering. What if the patients do not wish to go through this again? The treatment regime can be profoundly taxing for the patients, the loved ones, and sometimes even for the treating team. Are we doing more harm by forcing these patients to stay alive against their will?
Beneficence
Beneficence is the moral duty to promote the action that is in the patient’s best interest. But who should determine what the patient’s best interests are if the patient and the doctor disagree? Usually, this decision is made by the treating doctor, who considers the patient’s past and present wishes, beliefs and values, and capacity assessment. Supposing that the law was not a restriction, could one’s psychiatrist ever agree on psychiatric grounds alone that it is indeed in the patient’s best interests to die?
Doctors play a central role in the duty of care. But care does not always mean active treatment. Caring encompasses physical, psychological, and spiritual welfare and includes considering an individual patient’s dignity, personal circumstances, and wishes. In certain circumstances, keeping patients with capacity alive against their wishes could be more harmful than caring.
Autonomy
Autonomy gives the patients ultimate decision-making responsibility for their own lives. It allows patients with capacity to decline treatment that is recommended by their physicians and to make decisions regarding their own death. However, in suicidally depressed patients, this autonomy is confiscated. Severely unwell patients, at high risk of committing suicide, are not permitted the autonomy to make the decision regarding their treatment, suicide, and death.
Justice
A justice-orientated and utilitarian view questions whether spending resources on these patients wastes time, resources, and expertise, and whether resources should instead be spent on patients who do want treatment.
For example, the British National Health Service holds an outstanding debt of £13.4 billion.4 The financial cost of treating mental illness in 2020/2021 was £14.31 billion.5 The NHS estimates that wider costs to national economy, including welfare benefits, housing support, social workers, community support, lost productivity at work, etc., amounts to approximately £77 billion annually.6 Many severely depressed patients are so unwell that their ability to contribute to society, financially, socially, and otherwise, is minimal. If patients with capacity genuinely want to die and society would benefit from a reduction in the pressures on health and social care services, would it not be in both their best interests to allow them to die? This way, resources could be redirected to service users who would appreciate and benefit from them the most.
A consequentialist view focuses on whether the action will benefit the patient overall; the action itself is not so relevant. According to this view, keeping suicidally depressed patients alive against their wishes would be ethical if the patients lack capacity. Keeping them safe and treating them until they are better would overall be in the patients’ best interests. However, if the patients do have capacity and wish to die, forcing them to stay alive and undergo treatment against their wishes would merely prolong their suffering and thus could be considered unethical.
When enough is enough
In suicidal treatment-resistant depression, where the patient has tried multiple treatments over time and carefully considered alternatives, when is it time to stop trying? For physical illness, patients can refuse treatment provided they can demonstrate capacity. In depression, they can refuse treatment only if they can demonstrate that they are not at serious risk to themselves or others. Most societies consider suicide as a serious risk to self and therefore unacceptable. However, if we considered suicide as a natural endpoint of the disease process, should the patient have the right to refuse treatment and allow the disease to progress to death?
The treatment regime can be a lengthy process and the repeated failures to improve can be physically and mentally exhausting and further compound the hopelessness. Treatments often have side effects, which further erode the patient’s physical and mental wellbeing. Is there a time when giving up and withdrawing active treatment is in the patient’s best interests, especially if that is what the patient wants?
Terminal diseases are incurable and likely to hasten one’s death. Severe suicidal treatment-resistant depression conforms to both conditions – it is unresponsive to treatment and has a high likelihood of precipitating premature death through suicide. Most terminal illnesses can be managed with palliative treatment. In the context of severe suicidal depression, euthanasia and assisted suicide could be considered as means of palliative care.
Palliative care involves managing the patient’s symptomatology, dignity, and comfort. Euthanasia and assisted suicide help to address all of these. Like palliative care, euthanasia and assisted suicide aim to improve symptoms of depression by alleviating pain and suffering, even if they may hasten death.
Euthanasia and assisted suicide in severe depression
Euthanasia and assisted suicide are legal in seven countries. Two countries (Belgium and the Netherlands) permit euthanasia for psychiatric illnesses. Passive euthanasia is practiced in most countries, e.g., withholding artificial life support. In suicidal depression, it could be considered that this withholding of treatment may directly lead to death by suicide.
In active euthanasia and assisted suicide, the patient is given a chemical that will directly lead to death. Euthanasia and assisted suicide allow individuals to die with dignity in a controlled and organized manner. It ends the patients’ suffering and allows them to finally find peace. The difficulties that led them to seek euthanasia/assisted suicide indicate a loss of control of the pain and suffering in life, and euthanasia allows them to regain this control and autonomy through death. It allows these individuals to properly say goodbye to their loved ones, and a chance to share their thoughts and feelings.
In contrast, suicide is often covert, clandestine, and planned in secret, and it frequently requires individuals to be dishonest with their closest loved ones. The suicide often comes as a shock to the loved ones and profound grief, questions, anger, pain, sorrow, and guilt follow. These are due to questions that have been left unanswered, thoughts that were never shared, regret that they had not done more to help, and anguish knowing that their loved one died alone, in unbearable mental agony, unable to speak to anyone about this final hurdle.
Euthanasia and assisted suicide provide a path to overcome all these issues. They encourage open conversations between the patients, their loved ones, and the treating team. They promote transparency, mutual support, and help prepare the loved ones for the death. In this way, euthanasia and assisted suicide can benefit both the patient and the loved ones.
A significant proportion of severely suicidally depressed patients will eventually go on to commit or attempt suicide. Thus, giving them the autonomy to choose euthanasia or assisted suicide could be considered a kind, fair, and compassionate course of action, as it respects their wishes, and allows them to escape their suffering and to die with dignity.
Conclusion
Depression has historically never been considered a terminal illness, but there is undeniable evidence that a significant number of deaths every year are directly caused by depression. Should we therefore shift the focus from lifesaving and life-prolonging treatment to ensuring comfort and maintaining dignity by exploring palliative options for extremely suicidally depressed patients with capacity, who are adamant on ending their lives?
Euthanasia and assisted suicide for depression pose a profound paradox when viewed through a deontological lens. According to this, the correct course of action directly corresponds to what the most “moral” action would be. The moral stance would be to help those who are suffering. But what exactly constitutes “help”? Are euthanasia and assisted suicide helping or harming? Likewise, is keeping patients with capacity alive against their wishes helping or harming? Many believe that euthanasia, assisted suicide, and suicide itself are intrinsically and morally wrong. But this poses another clear impasse. Who should be the ones to decide whether an action is moral or not? Should it be the individual? The treating physician? Or society?
Dr. Chang graduated from Imperial College London with an MBBS (medicine and surgery) and a BSc (gastroenterology and hepatology) degree.
References
1. Office for National Statistics. Suicides in England and Wales – Office for National Statistics, 2021.
2. Faulkner, A. Suicide and Deliberate Self Harm: The Fundamental Facts. Mental Health Foundation; 1997.
3. NHS. Suicide Factsheet. Southwest London and St. George’s Mental Health NHS Trust [ebook], 2022.
4. The King’s Fund. Financial debts and loans in the NHS. 2020.
5. NHS England. Mental Health Five Year Forward View Dashboard. 2018.
6. National Mental Health, Policy into Practice. The costs of mental ill health.
Is there a place for palliative care?
Is there a place for palliative care?
In 2020, there were 5,224 suicide deaths registered in England and Wales.1 The Mental Health Foundation, a London-based charitable organization, reports that approximately 70% of such deaths are in patients with depression.2 The number of attempted suicides is much higher – the South West London and St. George’s Mental Health Trust estimates that at least 140,000 people attempt suicide in England and Wales every year.3
In suicidal depression, the psychological pain is often unbearable and feels overwhelmingly incompatible with life. One is no longer living but merely surviving, and eventually the exhaustion will lead to decompensation. This is marked by suicide. The goal is to end the suffering permanently and this is achieved through death.
Depression, like all other physical and mental illnesses, runs a course. This is highly variable between individuals and can be the case even between separate relapse episodes in the same patient. Like many diagnoses, depression is known to lead to death in a significant number of people. Many suicidally depressed patients feel that death will be an inevitable result of the illness.
Suicide is often viewed as a symptom of severe depression, but what if we considered death as part of the disease process itself? Consequently, would it be justifiable to consider depression in these patients as a form of terminal illness, since without treatment, the condition would lead to death? Accordingly, could there be a place for palliative care in a small minority of suicidally depressed patients? Taking such a perspective would mean that instead of placing the focus on the prevention of deaths and prolonging of lifespan, the focus would be on making the patients comfortable as the disease progresses, maintaining their dignity, and promoting autonomy.
Suicidal depression and rights
The rationale for this is that psychiatric patients do not have the capacity to make such decisions in the acute setting, because of the direct effects of the unwell mind on their decision-making processes and cognitive faculties. While this may be true in some cases, there is limited evidence that this applies to all suicidally depressed patients in all cases.
Another argument against allowing suicidally depressed patients to decline treatment is the notion that the episode of depression can be successfully treated, and the patients can return to their normal level of functioning. However, in individuals with a previous history of severe depression, it is possible that they will relapse again at some point. In the same way, a cancer can be treated, and patients could return to their baseline level of functioning, only for the cancer to then return later in life. In both cases, these relapses are emotionally and physically exhausting and painful to get through. The difference is that a cancer patient can decline further treatment and opt for no treatment or for palliative treatment, knowing that the disease will shorten life expectancy. For suicidal depression, this is not an option. Such patients may be sectioned, admitted, and treated against their will. Suicide, which could be considered a natural endpoint of the depressive illness, is unacceptable.
Is it fair to confiscate one’s right to decline treatment, solely because that person suffers from a mental illness, as opposed to a physical one? Numerous studies have demonstrated clear structural, neurological, and neurochemical changes in suicidal depression. This is evidence that such a condition encompasses a clear physical property. Other conditions, such as dementia and chronic pain, have previously been accepted for euthanasia in certain countries. Pain is a subjective experience of nociceptive and neurochemical signaling. In the same way, depression is a subjective experience involving aberrant neurochemical signaling. The difference is that physical pain can often be localized. However, patients with suicidal depression often experience very severe and tangible pain that can be difficult to articulate and for others to understand if they have never experienced it themselves.
Like distinct forms of physical pain, suicidal depression creates a different form of pain, but it is pain, nonetheless. Is it therefore fair for suicidally depressed patients to be given lesser rights than those suffering from physical illnesses in determining their fate?
Suicidal depression and capacity
A patient is assumed to have capacity unless proven otherwise. This is often the reverse when managing psychiatric patients. However, if patients are able to fulfill all criteria required for demonstrating capacity (understanding the information, retaining, weighing up, and communicating the decision), surely they have demonstrated capacity to make their decisions, whether that is to receive or to refuse treatment.
For physical illnesses, adults with capacity are permitted to make decisions that their treating teams may not agree with, but this disagreement alone is generally insufficient to override the decisions. These patients, unlike in suicidal depression, have the right to refuse lifesaving or life-prolonging treatment.
An argument for this is that in terminal physical illnesses, death is a passive process and neither the patient nor the physician are actively causing it. However, in many palliative settings, patients can be given medications and treatment for symptomatic relief, even if these may hasten their death. The principle that makes this permissible is that the primary aim is to improve the symptoms and ensure comfort. The unintended effect includes side effects and hastened death. Similarly, in suicidal depression, one could argue that the patient should be permitted medications that may hasten or lead to death, so long as the primary aim is to improve the symptoms of the unbearable mental pain and suffering.
Let us consider an alternative scenario. What if previously suicidal patients are currently in remission from depression and make advanced directives? In their current healthy state, they assert that if, in the future, they were to relapse, they would not want any form of treatment. Instead, they wish for the disease to run its course, which may end in death through suicide.
In this case, the circumstances in which the statement was made would be entirely valid – the patients at that moment have capacity, are not under coercion, are able to articulate logical thought processes, and their reasoning would not be affected by a concurrent psychiatric pathology. Furthermore, they can demonstrate that suicide is not an impulsive decision and have considered the consequences of suicide on themselves and others. If the patients can demonstrate all the above, what would the ethical grounds be for refusing this advanced directive?
Medical ethics
Below, I consider this debate in the context of four pillars of medical ethics.
Non-maleficence
To determine whether an action is in line with non-maleficence, one must ask whether the proposed treatment will improve or resolve one’s condition. In the case of severe suicidal depression, the treatment may help patients in the short term, but what happens if or when they relapse? The treatment will likely prolong life, but also inadvertently prolong suffering. What if the patients do not wish to go through this again? The treatment regime can be profoundly taxing for the patients, the loved ones, and sometimes even for the treating team. Are we doing more harm by forcing these patients to stay alive against their will?
Beneficence
Beneficence is the moral duty to promote the action that is in the patient’s best interest. But who should determine what the patient’s best interests are if the patient and the doctor disagree? Usually, this decision is made by the treating doctor, who considers the patient’s past and present wishes, beliefs and values, and capacity assessment. Supposing that the law was not a restriction, could one’s psychiatrist ever agree on psychiatric grounds alone that it is indeed in the patient’s best interests to die?
Doctors play a central role in the duty of care. But care does not always mean active treatment. Caring encompasses physical, psychological, and spiritual welfare and includes considering an individual patient’s dignity, personal circumstances, and wishes. In certain circumstances, keeping patients with capacity alive against their wishes could be more harmful than caring.
Autonomy
Autonomy gives the patients ultimate decision-making responsibility for their own lives. It allows patients with capacity to decline treatment that is recommended by their physicians and to make decisions regarding their own death. However, in suicidally depressed patients, this autonomy is confiscated. Severely unwell patients, at high risk of committing suicide, are not permitted the autonomy to make the decision regarding their treatment, suicide, and death.
Justice
A justice-orientated and utilitarian view questions whether spending resources on these patients wastes time, resources, and expertise, and whether resources should instead be spent on patients who do want treatment.
For example, the British National Health Service holds an outstanding debt of £13.4 billion.4 The financial cost of treating mental illness in 2020/2021 was £14.31 billion.5 The NHS estimates that wider costs to national economy, including welfare benefits, housing support, social workers, community support, lost productivity at work, etc., amounts to approximately £77 billion annually.6 Many severely depressed patients are so unwell that their ability to contribute to society, financially, socially, and otherwise, is minimal. If patients with capacity genuinely want to die and society would benefit from a reduction in the pressures on health and social care services, would it not be in both their best interests to allow them to die? This way, resources could be redirected to service users who would appreciate and benefit from them the most.
A consequentialist view focuses on whether the action will benefit the patient overall; the action itself is not so relevant. According to this view, keeping suicidally depressed patients alive against their wishes would be ethical if the patients lack capacity. Keeping them safe and treating them until they are better would overall be in the patients’ best interests. However, if the patients do have capacity and wish to die, forcing them to stay alive and undergo treatment against their wishes would merely prolong their suffering and thus could be considered unethical.
When enough is enough
In suicidal treatment-resistant depression, where the patient has tried multiple treatments over time and carefully considered alternatives, when is it time to stop trying? For physical illness, patients can refuse treatment provided they can demonstrate capacity. In depression, they can refuse treatment only if they can demonstrate that they are not at serious risk to themselves or others. Most societies consider suicide as a serious risk to self and therefore unacceptable. However, if we considered suicide as a natural endpoint of the disease process, should the patient have the right to refuse treatment and allow the disease to progress to death?
The treatment regime can be a lengthy process and the repeated failures to improve can be physically and mentally exhausting and further compound the hopelessness. Treatments often have side effects, which further erode the patient’s physical and mental wellbeing. Is there a time when giving up and withdrawing active treatment is in the patient’s best interests, especially if that is what the patient wants?
Terminal diseases are incurable and likely to hasten one’s death. Severe suicidal treatment-resistant depression conforms to both conditions – it is unresponsive to treatment and has a high likelihood of precipitating premature death through suicide. Most terminal illnesses can be managed with palliative treatment. In the context of severe suicidal depression, euthanasia and assisted suicide could be considered as means of palliative care.
Palliative care involves managing the patient’s symptomatology, dignity, and comfort. Euthanasia and assisted suicide help to address all of these. Like palliative care, euthanasia and assisted suicide aim to improve symptoms of depression by alleviating pain and suffering, even if they may hasten death.
Euthanasia and assisted suicide in severe depression
Euthanasia and assisted suicide are legal in seven countries. Two countries (Belgium and the Netherlands) permit euthanasia for psychiatric illnesses. Passive euthanasia is practiced in most countries, e.g., withholding artificial life support. In suicidal depression, it could be considered that this withholding of treatment may directly lead to death by suicide.
In active euthanasia and assisted suicide, the patient is given a chemical that will directly lead to death. Euthanasia and assisted suicide allow individuals to die with dignity in a controlled and organized manner. It ends the patients’ suffering and allows them to finally find peace. The difficulties that led them to seek euthanasia/assisted suicide indicate a loss of control of the pain and suffering in life, and euthanasia allows them to regain this control and autonomy through death. It allows these individuals to properly say goodbye to their loved ones, and a chance to share their thoughts and feelings.
In contrast, suicide is often covert, clandestine, and planned in secret, and it frequently requires individuals to be dishonest with their closest loved ones. The suicide often comes as a shock to the loved ones and profound grief, questions, anger, pain, sorrow, and guilt follow. These are due to questions that have been left unanswered, thoughts that were never shared, regret that they had not done more to help, and anguish knowing that their loved one died alone, in unbearable mental agony, unable to speak to anyone about this final hurdle.
Euthanasia and assisted suicide provide a path to overcome all these issues. They encourage open conversations between the patients, their loved ones, and the treating team. They promote transparency, mutual support, and help prepare the loved ones for the death. In this way, euthanasia and assisted suicide can benefit both the patient and the loved ones.
A significant proportion of severely suicidally depressed patients will eventually go on to commit or attempt suicide. Thus, giving them the autonomy to choose euthanasia or assisted suicide could be considered a kind, fair, and compassionate course of action, as it respects their wishes, and allows them to escape their suffering and to die with dignity.
Conclusion
Depression has historically never been considered a terminal illness, but there is undeniable evidence that a significant number of deaths every year are directly caused by depression. Should we therefore shift the focus from lifesaving and life-prolonging treatment to ensuring comfort and maintaining dignity by exploring palliative options for extremely suicidally depressed patients with capacity, who are adamant on ending their lives?
Euthanasia and assisted suicide for depression pose a profound paradox when viewed through a deontological lens. According to this, the correct course of action directly corresponds to what the most “moral” action would be. The moral stance would be to help those who are suffering. But what exactly constitutes “help”? Are euthanasia and assisted suicide helping or harming? Likewise, is keeping patients with capacity alive against their wishes helping or harming? Many believe that euthanasia, assisted suicide, and suicide itself are intrinsically and morally wrong. But this poses another clear impasse. Who should be the ones to decide whether an action is moral or not? Should it be the individual? The treating physician? Or society?
Dr. Chang graduated from Imperial College London with an MBBS (medicine and surgery) and a BSc (gastroenterology and hepatology) degree.
References
1. Office for National Statistics. Suicides in England and Wales – Office for National Statistics, 2021.
2. Faulkner, A. Suicide and Deliberate Self Harm: The Fundamental Facts. Mental Health Foundation; 1997.
3. NHS. Suicide Factsheet. Southwest London and St. George’s Mental Health NHS Trust [ebook], 2022.
4. The King’s Fund. Financial debts and loans in the NHS. 2020.
5. NHS England. Mental Health Five Year Forward View Dashboard. 2018.
6. National Mental Health, Policy into Practice. The costs of mental ill health.
In 2020, there were 5,224 suicide deaths registered in England and Wales.1 The Mental Health Foundation, a London-based charitable organization, reports that approximately 70% of such deaths are in patients with depression.2 The number of attempted suicides is much higher – the South West London and St. George’s Mental Health Trust estimates that at least 140,000 people attempt suicide in England and Wales every year.3
In suicidal depression, the psychological pain is often unbearable and feels overwhelmingly incompatible with life. One is no longer living but merely surviving, and eventually the exhaustion will lead to decompensation. This is marked by suicide. The goal is to end the suffering permanently and this is achieved through death.
Depression, like all other physical and mental illnesses, runs a course. This is highly variable between individuals and can be the case even between separate relapse episodes in the same patient. Like many diagnoses, depression is known to lead to death in a significant number of people. Many suicidally depressed patients feel that death will be an inevitable result of the illness.
Suicide is often viewed as a symptom of severe depression, but what if we considered death as part of the disease process itself? Consequently, would it be justifiable to consider depression in these patients as a form of terminal illness, since without treatment, the condition would lead to death? Accordingly, could there be a place for palliative care in a small minority of suicidally depressed patients? Taking such a perspective would mean that instead of placing the focus on the prevention of deaths and prolonging of lifespan, the focus would be on making the patients comfortable as the disease progresses, maintaining their dignity, and promoting autonomy.
Suicidal depression and rights
The rationale for this is that psychiatric patients do not have the capacity to make such decisions in the acute setting, because of the direct effects of the unwell mind on their decision-making processes and cognitive faculties. While this may be true in some cases, there is limited evidence that this applies to all suicidally depressed patients in all cases.
Another argument against allowing suicidally depressed patients to decline treatment is the notion that the episode of depression can be successfully treated, and the patients can return to their normal level of functioning. However, in individuals with a previous history of severe depression, it is possible that they will relapse again at some point. In the same way, a cancer can be treated, and patients could return to their baseline level of functioning, only for the cancer to then return later in life. In both cases, these relapses are emotionally and physically exhausting and painful to get through. The difference is that a cancer patient can decline further treatment and opt for no treatment or for palliative treatment, knowing that the disease will shorten life expectancy. For suicidal depression, this is not an option. Such patients may be sectioned, admitted, and treated against their will. Suicide, which could be considered a natural endpoint of the depressive illness, is unacceptable.
Is it fair to confiscate one’s right to decline treatment, solely because that person suffers from a mental illness, as opposed to a physical one? Numerous studies have demonstrated clear structural, neurological, and neurochemical changes in suicidal depression. This is evidence that such a condition encompasses a clear physical property. Other conditions, such as dementia and chronic pain, have previously been accepted for euthanasia in certain countries. Pain is a subjective experience of nociceptive and neurochemical signaling. In the same way, depression is a subjective experience involving aberrant neurochemical signaling. The difference is that physical pain can often be localized. However, patients with suicidal depression often experience very severe and tangible pain that can be difficult to articulate and for others to understand if they have never experienced it themselves.
Like distinct forms of physical pain, suicidal depression creates a different form of pain, but it is pain, nonetheless. Is it therefore fair for suicidally depressed patients to be given lesser rights than those suffering from physical illnesses in determining their fate?
Suicidal depression and capacity
A patient is assumed to have capacity unless proven otherwise. This is often the reverse when managing psychiatric patients. However, if patients are able to fulfill all criteria required for demonstrating capacity (understanding the information, retaining, weighing up, and communicating the decision), surely they have demonstrated capacity to make their decisions, whether that is to receive or to refuse treatment.
For physical illnesses, adults with capacity are permitted to make decisions that their treating teams may not agree with, but this disagreement alone is generally insufficient to override the decisions. These patients, unlike in suicidal depression, have the right to refuse lifesaving or life-prolonging treatment.
An argument for this is that in terminal physical illnesses, death is a passive process and neither the patient nor the physician are actively causing it. However, in many palliative settings, patients can be given medications and treatment for symptomatic relief, even if these may hasten their death. The principle that makes this permissible is that the primary aim is to improve the symptoms and ensure comfort. The unintended effect includes side effects and hastened death. Similarly, in suicidal depression, one could argue that the patient should be permitted medications that may hasten or lead to death, so long as the primary aim is to improve the symptoms of the unbearable mental pain and suffering.
Let us consider an alternative scenario. What if previously suicidal patients are currently in remission from depression and make advanced directives? In their current healthy state, they assert that if, in the future, they were to relapse, they would not want any form of treatment. Instead, they wish for the disease to run its course, which may end in death through suicide.
In this case, the circumstances in which the statement was made would be entirely valid – the patients at that moment have capacity, are not under coercion, are able to articulate logical thought processes, and their reasoning would not be affected by a concurrent psychiatric pathology. Furthermore, they can demonstrate that suicide is not an impulsive decision and have considered the consequences of suicide on themselves and others. If the patients can demonstrate all the above, what would the ethical grounds be for refusing this advanced directive?
Medical ethics
Below, I consider this debate in the context of four pillars of medical ethics.
Non-maleficence
To determine whether an action is in line with non-maleficence, one must ask whether the proposed treatment will improve or resolve one’s condition. In the case of severe suicidal depression, the treatment may help patients in the short term, but what happens if or when they relapse? The treatment will likely prolong life, but also inadvertently prolong suffering. What if the patients do not wish to go through this again? The treatment regime can be profoundly taxing for the patients, the loved ones, and sometimes even for the treating team. Are we doing more harm by forcing these patients to stay alive against their will?
Beneficence
Beneficence is the moral duty to promote the action that is in the patient’s best interest. But who should determine what the patient’s best interests are if the patient and the doctor disagree? Usually, this decision is made by the treating doctor, who considers the patient’s past and present wishes, beliefs and values, and capacity assessment. Supposing that the law was not a restriction, could one’s psychiatrist ever agree on psychiatric grounds alone that it is indeed in the patient’s best interests to die?
Doctors play a central role in the duty of care. But care does not always mean active treatment. Caring encompasses physical, psychological, and spiritual welfare and includes considering an individual patient’s dignity, personal circumstances, and wishes. In certain circumstances, keeping patients with capacity alive against their wishes could be more harmful than caring.
Autonomy
Autonomy gives the patients ultimate decision-making responsibility for their own lives. It allows patients with capacity to decline treatment that is recommended by their physicians and to make decisions regarding their own death. However, in suicidally depressed patients, this autonomy is confiscated. Severely unwell patients, at high risk of committing suicide, are not permitted the autonomy to make the decision regarding their treatment, suicide, and death.
Justice
A justice-orientated and utilitarian view questions whether spending resources on these patients wastes time, resources, and expertise, and whether resources should instead be spent on patients who do want treatment.
For example, the British National Health Service holds an outstanding debt of £13.4 billion.4 The financial cost of treating mental illness in 2020/2021 was £14.31 billion.5 The NHS estimates that wider costs to national economy, including welfare benefits, housing support, social workers, community support, lost productivity at work, etc., amounts to approximately £77 billion annually.6 Many severely depressed patients are so unwell that their ability to contribute to society, financially, socially, and otherwise, is minimal. If patients with capacity genuinely want to die and society would benefit from a reduction in the pressures on health and social care services, would it not be in both their best interests to allow them to die? This way, resources could be redirected to service users who would appreciate and benefit from them the most.
A consequentialist view focuses on whether the action will benefit the patient overall; the action itself is not so relevant. According to this view, keeping suicidally depressed patients alive against their wishes would be ethical if the patients lack capacity. Keeping them safe and treating them until they are better would overall be in the patients’ best interests. However, if the patients do have capacity and wish to die, forcing them to stay alive and undergo treatment against their wishes would merely prolong their suffering and thus could be considered unethical.
When enough is enough
In suicidal treatment-resistant depression, where the patient has tried multiple treatments over time and carefully considered alternatives, when is it time to stop trying? For physical illness, patients can refuse treatment provided they can demonstrate capacity. In depression, they can refuse treatment only if they can demonstrate that they are not at serious risk to themselves or others. Most societies consider suicide as a serious risk to self and therefore unacceptable. However, if we considered suicide as a natural endpoint of the disease process, should the patient have the right to refuse treatment and allow the disease to progress to death?
The treatment regime can be a lengthy process and the repeated failures to improve can be physically and mentally exhausting and further compound the hopelessness. Treatments often have side effects, which further erode the patient’s physical and mental wellbeing. Is there a time when giving up and withdrawing active treatment is in the patient’s best interests, especially if that is what the patient wants?
Terminal diseases are incurable and likely to hasten one’s death. Severe suicidal treatment-resistant depression conforms to both conditions – it is unresponsive to treatment and has a high likelihood of precipitating premature death through suicide. Most terminal illnesses can be managed with palliative treatment. In the context of severe suicidal depression, euthanasia and assisted suicide could be considered as means of palliative care.
Palliative care involves managing the patient’s symptomatology, dignity, and comfort. Euthanasia and assisted suicide help to address all of these. Like palliative care, euthanasia and assisted suicide aim to improve symptoms of depression by alleviating pain and suffering, even if they may hasten death.
Euthanasia and assisted suicide in severe depression
Euthanasia and assisted suicide are legal in seven countries. Two countries (Belgium and the Netherlands) permit euthanasia for psychiatric illnesses. Passive euthanasia is practiced in most countries, e.g., withholding artificial life support. In suicidal depression, it could be considered that this withholding of treatment may directly lead to death by suicide.
In active euthanasia and assisted suicide, the patient is given a chemical that will directly lead to death. Euthanasia and assisted suicide allow individuals to die with dignity in a controlled and organized manner. It ends the patients’ suffering and allows them to finally find peace. The difficulties that led them to seek euthanasia/assisted suicide indicate a loss of control of the pain and suffering in life, and euthanasia allows them to regain this control and autonomy through death. It allows these individuals to properly say goodbye to their loved ones, and a chance to share their thoughts and feelings.
In contrast, suicide is often covert, clandestine, and planned in secret, and it frequently requires individuals to be dishonest with their closest loved ones. The suicide often comes as a shock to the loved ones and profound grief, questions, anger, pain, sorrow, and guilt follow. These are due to questions that have been left unanswered, thoughts that were never shared, regret that they had not done more to help, and anguish knowing that their loved one died alone, in unbearable mental agony, unable to speak to anyone about this final hurdle.
Euthanasia and assisted suicide provide a path to overcome all these issues. They encourage open conversations between the patients, their loved ones, and the treating team. They promote transparency, mutual support, and help prepare the loved ones for the death. In this way, euthanasia and assisted suicide can benefit both the patient and the loved ones.
A significant proportion of severely suicidally depressed patients will eventually go on to commit or attempt suicide. Thus, giving them the autonomy to choose euthanasia or assisted suicide could be considered a kind, fair, and compassionate course of action, as it respects their wishes, and allows them to escape their suffering and to die with dignity.
Conclusion
Depression has historically never been considered a terminal illness, but there is undeniable evidence that a significant number of deaths every year are directly caused by depression. Should we therefore shift the focus from lifesaving and life-prolonging treatment to ensuring comfort and maintaining dignity by exploring palliative options for extremely suicidally depressed patients with capacity, who are adamant on ending their lives?
Euthanasia and assisted suicide for depression pose a profound paradox when viewed through a deontological lens. According to this, the correct course of action directly corresponds to what the most “moral” action would be. The moral stance would be to help those who are suffering. But what exactly constitutes “help”? Are euthanasia and assisted suicide helping or harming? Likewise, is keeping patients with capacity alive against their wishes helping or harming? Many believe that euthanasia, assisted suicide, and suicide itself are intrinsically and morally wrong. But this poses another clear impasse. Who should be the ones to decide whether an action is moral or not? Should it be the individual? The treating physician? Or society?
Dr. Chang graduated from Imperial College London with an MBBS (medicine and surgery) and a BSc (gastroenterology and hepatology) degree.
References
1. Office for National Statistics. Suicides in England and Wales – Office for National Statistics, 2021.
2. Faulkner, A. Suicide and Deliberate Self Harm: The Fundamental Facts. Mental Health Foundation; 1997.
3. NHS. Suicide Factsheet. Southwest London and St. George’s Mental Health NHS Trust [ebook], 2022.
4. The King’s Fund. Financial debts and loans in the NHS. 2020.
5. NHS England. Mental Health Five Year Forward View Dashboard. 2018.
6. National Mental Health, Policy into Practice. The costs of mental ill health.
Inhaled vasodilator type has no impact on outcomes
based on data from more than 11,000 patients.
Mechanically ventilated patients with severe acute respiratory failure may be treated with inhaled vasodilators using nitric oxide or epoprostenol to improve oxygenation, but data on practice patterns and head-to-head comparisons of effectiveness for the two options are limited, wrote Nicholas A. Bosch, MD, of Boston University, and colleagues.
In a study published in the journal Chest, the researchers used the Premier Healthcare Database to emulate a cluster randomized trial. The study population included 11,200 patients aged 18 years and older who were hospitalized at one of 303 hospitals with acute respiratory failure or acute respiratory distress between 2016 and 2020.
The patients received either nitric oxide (iNO) or epoprostenol (iEpo) during a hospital stay. A total of 6,366 patients received iNO first, 4,720 received iEpo first, and 114 received both on the same day. The median age of the patients was 58 years, and 64.6% of patients received neuromuscular blockades on the day they began vasodilator therapy. The primary outcome for effectiveness was successful extubation within 28 days of receiving a vasodilator. The outcomes for evaluating practice patterns included the choice of first inhaled vasodilator, days of invasive mechanical ventilation before starting a vasodilator, duration of use, proportion of patients who switched between iNO and iEpo, and the proportion who received each type of vasodilator.
A total of 104 hospitals (34.3%) used iNO exclusively, and 118 hospitals (38.9%) used iEpo exclusively. No differences in successful extubation rates appeared between these iNO and iEpo groups (37.0% vs. 34.7%; hazard ratio, 0.97). In addition, no differences were observed between the iNO and iEpo hospitals in total hospital costs or patient deaths or discharge to hospice, and the results persisted in a multivariate analysis.
Overall, the results were similar in a subgroup analysis, although patients receiving iNO were more likely to have successful extubation after controlling for organ dysfunction, the researchers noted.
“Our study provides stronger and more robust evidence that there are no differences in patient outcomes based on inhaled vasodilator type,” and suggest that either type may be used for patients whom clinicians think would benefit, the researchers wrote in their discussion. However, neither vasodilator type has been shown to significantly improve mortality, they noted.
The findings were limited by several factors including the observational design, lack of data on medication dose, and the use of nonrandom samples of hospitalizations and patients with laboratory and vital signs data, the researchers noted. The study also did not identify the specific indication for inhaled vasodilator therapy, and did not adjust for other therapies such as prone positioning or adherence to lung protective ventilation, they said.
However, the results were strengthened by the large sample size and more precise estimates of effectiveness than previous smaller studies, and suggest similar outcomes for patients and costs for hospitals, they concluded.
The study was funded by the National Institutes of Health National Center for Advancing Translational Sciences. Lead author Dr. Bosch also was supported by NIH/NCATS, the National Heart, Lung, and Blood Institute, and the Department of Defense. The researchers had no financial conflicts to disclose.
based on data from more than 11,000 patients.
Mechanically ventilated patients with severe acute respiratory failure may be treated with inhaled vasodilators using nitric oxide or epoprostenol to improve oxygenation, but data on practice patterns and head-to-head comparisons of effectiveness for the two options are limited, wrote Nicholas A. Bosch, MD, of Boston University, and colleagues.
In a study published in the journal Chest, the researchers used the Premier Healthcare Database to emulate a cluster randomized trial. The study population included 11,200 patients aged 18 years and older who were hospitalized at one of 303 hospitals with acute respiratory failure or acute respiratory distress between 2016 and 2020.
The patients received either nitric oxide (iNO) or epoprostenol (iEpo) during a hospital stay. A total of 6,366 patients received iNO first, 4,720 received iEpo first, and 114 received both on the same day. The median age of the patients was 58 years, and 64.6% of patients received neuromuscular blockades on the day they began vasodilator therapy. The primary outcome for effectiveness was successful extubation within 28 days of receiving a vasodilator. The outcomes for evaluating practice patterns included the choice of first inhaled vasodilator, days of invasive mechanical ventilation before starting a vasodilator, duration of use, proportion of patients who switched between iNO and iEpo, and the proportion who received each type of vasodilator.
A total of 104 hospitals (34.3%) used iNO exclusively, and 118 hospitals (38.9%) used iEpo exclusively. No differences in successful extubation rates appeared between these iNO and iEpo groups (37.0% vs. 34.7%; hazard ratio, 0.97). In addition, no differences were observed between the iNO and iEpo hospitals in total hospital costs or patient deaths or discharge to hospice, and the results persisted in a multivariate analysis.
Overall, the results were similar in a subgroup analysis, although patients receiving iNO were more likely to have successful extubation after controlling for organ dysfunction, the researchers noted.
“Our study provides stronger and more robust evidence that there are no differences in patient outcomes based on inhaled vasodilator type,” and suggest that either type may be used for patients whom clinicians think would benefit, the researchers wrote in their discussion. However, neither vasodilator type has been shown to significantly improve mortality, they noted.
The findings were limited by several factors including the observational design, lack of data on medication dose, and the use of nonrandom samples of hospitalizations and patients with laboratory and vital signs data, the researchers noted. The study also did not identify the specific indication for inhaled vasodilator therapy, and did not adjust for other therapies such as prone positioning or adherence to lung protective ventilation, they said.
However, the results were strengthened by the large sample size and more precise estimates of effectiveness than previous smaller studies, and suggest similar outcomes for patients and costs for hospitals, they concluded.
The study was funded by the National Institutes of Health National Center for Advancing Translational Sciences. Lead author Dr. Bosch also was supported by NIH/NCATS, the National Heart, Lung, and Blood Institute, and the Department of Defense. The researchers had no financial conflicts to disclose.
based on data from more than 11,000 patients.
Mechanically ventilated patients with severe acute respiratory failure may be treated with inhaled vasodilators using nitric oxide or epoprostenol to improve oxygenation, but data on practice patterns and head-to-head comparisons of effectiveness for the two options are limited, wrote Nicholas A. Bosch, MD, of Boston University, and colleagues.
In a study published in the journal Chest, the researchers used the Premier Healthcare Database to emulate a cluster randomized trial. The study population included 11,200 patients aged 18 years and older who were hospitalized at one of 303 hospitals with acute respiratory failure or acute respiratory distress between 2016 and 2020.
The patients received either nitric oxide (iNO) or epoprostenol (iEpo) during a hospital stay. A total of 6,366 patients received iNO first, 4,720 received iEpo first, and 114 received both on the same day. The median age of the patients was 58 years, and 64.6% of patients received neuromuscular blockades on the day they began vasodilator therapy. The primary outcome for effectiveness was successful extubation within 28 days of receiving a vasodilator. The outcomes for evaluating practice patterns included the choice of first inhaled vasodilator, days of invasive mechanical ventilation before starting a vasodilator, duration of use, proportion of patients who switched between iNO and iEpo, and the proportion who received each type of vasodilator.
A total of 104 hospitals (34.3%) used iNO exclusively, and 118 hospitals (38.9%) used iEpo exclusively. No differences in successful extubation rates appeared between these iNO and iEpo groups (37.0% vs. 34.7%; hazard ratio, 0.97). In addition, no differences were observed between the iNO and iEpo hospitals in total hospital costs or patient deaths or discharge to hospice, and the results persisted in a multivariate analysis.
Overall, the results were similar in a subgroup analysis, although patients receiving iNO were more likely to have successful extubation after controlling for organ dysfunction, the researchers noted.
“Our study provides stronger and more robust evidence that there are no differences in patient outcomes based on inhaled vasodilator type,” and suggest that either type may be used for patients whom clinicians think would benefit, the researchers wrote in their discussion. However, neither vasodilator type has been shown to significantly improve mortality, they noted.
The findings were limited by several factors including the observational design, lack of data on medication dose, and the use of nonrandom samples of hospitalizations and patients with laboratory and vital signs data, the researchers noted. The study also did not identify the specific indication for inhaled vasodilator therapy, and did not adjust for other therapies such as prone positioning or adherence to lung protective ventilation, they said.
However, the results were strengthened by the large sample size and more precise estimates of effectiveness than previous smaller studies, and suggest similar outcomes for patients and costs for hospitals, they concluded.
The study was funded by the National Institutes of Health National Center for Advancing Translational Sciences. Lead author Dr. Bosch also was supported by NIH/NCATS, the National Heart, Lung, and Blood Institute, and the Department of Defense. The researchers had no financial conflicts to disclose.
FROM CHEST
Time to cancer diagnoses in U.S. averages 5 months
Time to diagnosis is a crucial factor in cancer. Delays can lead to diagnosis at later stages and prevent optimal therapeutic strategies, both of which have the potential to reduce survival. An estimated 63%-82% of cancers get diagnosed as a result of symptom presentation, and delays in diagnosis can hamper treatment efforts. Diagnosis can be challenging because common symptoms – such as weight loss, weakness, poor appetite, and shortness of breath – are nonspecific.
A new analysis of U.S.-based data shows that the average time to diagnosis is 5.2 months for patients with solid tumors. The authors of the study call for better cancer diagnosis pathways in the U.S.
“Several countries, including the UK, Denmark, Sweden, Canada and Australia, have identified the importance and potential impact of more timely diagnosis by establishing national guidelines, special programs, and treatment pathways. However, in the U.S., there’s relatively little research and effort focused on streamlining the diagnostic pathway. Currently, the U.S. does not have established cancer diagnostic pathways that are used consistently,” Matthew Gitlin, PharmD, said during a presentation at the annual meeting of the European Society for Medical Oncology.
“That is often associated with worse clinical outcomes, increased economic burden, and decreased health related quality of life,” said Dr. Gitlin, founder and managing director of the health economics consulting firm BluePath Solutions, which conducted the analysis.
The study retrospectively examined administrative billing data drawn from the Clinformatics for Managed Markets longitudinal database. The data represent individuals in Medicare Advantage and a large, U.S.-based private insurance plan. Between 2018 and 2019, there were 458,818 cancer diagnoses. The mean age was 70.6 years and 49.6% of the patients were female. Sixty-five percent were White, 11.1% Black, 8.3% Hispanic, and 2.5% Asian. No race data were available for 13.2%. Medicare Advantage was the primary insurance carrier for 74.0%, and 24.0% had a commercial plan.
The mean time to diagnosis across all tumors was 5.2 months (standard deviation, 5.5 months). There was significant variation across different tumor types, as well as within the same tumor type. The median value was 3.9 months (interquartile range, 1.1-7.2 months).
Mean time to diagnosis ranged from 121.6 days for bladder cancer to as high as 229 days for multiple myeloma. Standard deviations were nearly as large or even larger than the mean values. The study showed that 15.8% of patients waited 6 months or longer for a diagnosis. Delays were most common in kidney cancer, colorectal cancer, gallbladder cancer, esophageal cancer, stomach cancer, lymphoma, and multiple myeloma: More than 25% of patients had a time to diagnosis of at least 6 months in these tumors.
“Although there is limited research in the published literature, our findings are consistent with that literature that does exist. Development or modification of policies, guidelines or medical interventions that streamline the diagnostic pathway are needed to optimize patient outcomes and reduce resource burden and cost to the health care system,” Dr. Gitlin said.
Previous literature on this topic has seen wide variation in how time to diagnosis is defined, and most research is conducted in high-income countries, according to Felipe Roitberg, PhD, who served as a discussant during the session. “Most of the countries and patients in need are localized in low- and middle-income countries, so that is a call to action (for more research),” said Dr. Roitberg, a clinical oncologist at Hospital Sírio Libanês in São Paulo, Brazil.
The study did not look at the associations between race and time to diagnosis. “This is a source of analysis could further be explored,” said Dr. Roitberg.
He noted that the ABC-DO prospective cohort study in sub-Saharan Africa found large variations in breast cancer survival by country, and its authors predicted that downstaging and improvements in treatment could prevent up to one-third of projected breast cancer deaths over the next decade. “So these are the drivers of populational gain in terms of overall survival – not more drugs, not more services available, but coordination of services and making sure the patient has a right pathway (to diagnosis and treatment),” Dr. Roitberg said.
Dr. Gitlin has received consulting fees from GRAIL LLC, which is a subsidiary of Illumina. Dr. Roitberg has received honoraria from Boehringer Ingelheim, Sanofi, Roche, MSD Oncology, AstraZeneca, Nestle Health Science, Dr Reddy’s, and Oncologia Brazil. He has consulted for MSD Oncology. He has received research funding from Roche, Boehringer Ingelheim, MSD, Bayer, AstraZeneca, and Takeda.
Time to diagnosis is a crucial factor in cancer. Delays can lead to diagnosis at later stages and prevent optimal therapeutic strategies, both of which have the potential to reduce survival. An estimated 63%-82% of cancers get diagnosed as a result of symptom presentation, and delays in diagnosis can hamper treatment efforts. Diagnosis can be challenging because common symptoms – such as weight loss, weakness, poor appetite, and shortness of breath – are nonspecific.
A new analysis of U.S.-based data shows that the average time to diagnosis is 5.2 months for patients with solid tumors. The authors of the study call for better cancer diagnosis pathways in the U.S.
“Several countries, including the UK, Denmark, Sweden, Canada and Australia, have identified the importance and potential impact of more timely diagnosis by establishing national guidelines, special programs, and treatment pathways. However, in the U.S., there’s relatively little research and effort focused on streamlining the diagnostic pathway. Currently, the U.S. does not have established cancer diagnostic pathways that are used consistently,” Matthew Gitlin, PharmD, said during a presentation at the annual meeting of the European Society for Medical Oncology.
“That is often associated with worse clinical outcomes, increased economic burden, and decreased health related quality of life,” said Dr. Gitlin, founder and managing director of the health economics consulting firm BluePath Solutions, which conducted the analysis.
The study retrospectively examined administrative billing data drawn from the Clinformatics for Managed Markets longitudinal database. The data represent individuals in Medicare Advantage and a large, U.S.-based private insurance plan. Between 2018 and 2019, there were 458,818 cancer diagnoses. The mean age was 70.6 years and 49.6% of the patients were female. Sixty-five percent were White, 11.1% Black, 8.3% Hispanic, and 2.5% Asian. No race data were available for 13.2%. Medicare Advantage was the primary insurance carrier for 74.0%, and 24.0% had a commercial plan.
The mean time to diagnosis across all tumors was 5.2 months (standard deviation, 5.5 months). There was significant variation across different tumor types, as well as within the same tumor type. The median value was 3.9 months (interquartile range, 1.1-7.2 months).
Mean time to diagnosis ranged from 121.6 days for bladder cancer to as high as 229 days for multiple myeloma. Standard deviations were nearly as large or even larger than the mean values. The study showed that 15.8% of patients waited 6 months or longer for a diagnosis. Delays were most common in kidney cancer, colorectal cancer, gallbladder cancer, esophageal cancer, stomach cancer, lymphoma, and multiple myeloma: More than 25% of patients had a time to diagnosis of at least 6 months in these tumors.
“Although there is limited research in the published literature, our findings are consistent with that literature that does exist. Development or modification of policies, guidelines or medical interventions that streamline the diagnostic pathway are needed to optimize patient outcomes and reduce resource burden and cost to the health care system,” Dr. Gitlin said.
Previous literature on this topic has seen wide variation in how time to diagnosis is defined, and most research is conducted in high-income countries, according to Felipe Roitberg, PhD, who served as a discussant during the session. “Most of the countries and patients in need are localized in low- and middle-income countries, so that is a call to action (for more research),” said Dr. Roitberg, a clinical oncologist at Hospital Sírio Libanês in São Paulo, Brazil.
The study did not look at the associations between race and time to diagnosis. “This is a source of analysis could further be explored,” said Dr. Roitberg.
He noted that the ABC-DO prospective cohort study in sub-Saharan Africa found large variations in breast cancer survival by country, and its authors predicted that downstaging and improvements in treatment could prevent up to one-third of projected breast cancer deaths over the next decade. “So these are the drivers of populational gain in terms of overall survival – not more drugs, not more services available, but coordination of services and making sure the patient has a right pathway (to diagnosis and treatment),” Dr. Roitberg said.
Dr. Gitlin has received consulting fees from GRAIL LLC, which is a subsidiary of Illumina. Dr. Roitberg has received honoraria from Boehringer Ingelheim, Sanofi, Roche, MSD Oncology, AstraZeneca, Nestle Health Science, Dr Reddy’s, and Oncologia Brazil. He has consulted for MSD Oncology. He has received research funding from Roche, Boehringer Ingelheim, MSD, Bayer, AstraZeneca, and Takeda.
Time to diagnosis is a crucial factor in cancer. Delays can lead to diagnosis at later stages and prevent optimal therapeutic strategies, both of which have the potential to reduce survival. An estimated 63%-82% of cancers get diagnosed as a result of symptom presentation, and delays in diagnosis can hamper treatment efforts. Diagnosis can be challenging because common symptoms – such as weight loss, weakness, poor appetite, and shortness of breath – are nonspecific.
A new analysis of U.S.-based data shows that the average time to diagnosis is 5.2 months for patients with solid tumors. The authors of the study call for better cancer diagnosis pathways in the U.S.
“Several countries, including the UK, Denmark, Sweden, Canada and Australia, have identified the importance and potential impact of more timely diagnosis by establishing national guidelines, special programs, and treatment pathways. However, in the U.S., there’s relatively little research and effort focused on streamlining the diagnostic pathway. Currently, the U.S. does not have established cancer diagnostic pathways that are used consistently,” Matthew Gitlin, PharmD, said during a presentation at the annual meeting of the European Society for Medical Oncology.
“That is often associated with worse clinical outcomes, increased economic burden, and decreased health related quality of life,” said Dr. Gitlin, founder and managing director of the health economics consulting firm BluePath Solutions, which conducted the analysis.
The study retrospectively examined administrative billing data drawn from the Clinformatics for Managed Markets longitudinal database. The data represent individuals in Medicare Advantage and a large, U.S.-based private insurance plan. Between 2018 and 2019, there were 458,818 cancer diagnoses. The mean age was 70.6 years and 49.6% of the patients were female. Sixty-five percent were White, 11.1% Black, 8.3% Hispanic, and 2.5% Asian. No race data were available for 13.2%. Medicare Advantage was the primary insurance carrier for 74.0%, and 24.0% had a commercial plan.
The mean time to diagnosis across all tumors was 5.2 months (standard deviation, 5.5 months). There was significant variation across different tumor types, as well as within the same tumor type. The median value was 3.9 months (interquartile range, 1.1-7.2 months).
Mean time to diagnosis ranged from 121.6 days for bladder cancer to as high as 229 days for multiple myeloma. Standard deviations were nearly as large or even larger than the mean values. The study showed that 15.8% of patients waited 6 months or longer for a diagnosis. Delays were most common in kidney cancer, colorectal cancer, gallbladder cancer, esophageal cancer, stomach cancer, lymphoma, and multiple myeloma: More than 25% of patients had a time to diagnosis of at least 6 months in these tumors.
“Although there is limited research in the published literature, our findings are consistent with that literature that does exist. Development or modification of policies, guidelines or medical interventions that streamline the diagnostic pathway are needed to optimize patient outcomes and reduce resource burden and cost to the health care system,” Dr. Gitlin said.
Previous literature on this topic has seen wide variation in how time to diagnosis is defined, and most research is conducted in high-income countries, according to Felipe Roitberg, PhD, who served as a discussant during the session. “Most of the countries and patients in need are localized in low- and middle-income countries, so that is a call to action (for more research),” said Dr. Roitberg, a clinical oncologist at Hospital Sírio Libanês in São Paulo, Brazil.
The study did not look at the associations between race and time to diagnosis. “This is a source of analysis could further be explored,” said Dr. Roitberg.
He noted that the ABC-DO prospective cohort study in sub-Saharan Africa found large variations in breast cancer survival by country, and its authors predicted that downstaging and improvements in treatment could prevent up to one-third of projected breast cancer deaths over the next decade. “So these are the drivers of populational gain in terms of overall survival – not more drugs, not more services available, but coordination of services and making sure the patient has a right pathway (to diagnosis and treatment),” Dr. Roitberg said.
Dr. Gitlin has received consulting fees from GRAIL LLC, which is a subsidiary of Illumina. Dr. Roitberg has received honoraria from Boehringer Ingelheim, Sanofi, Roche, MSD Oncology, AstraZeneca, Nestle Health Science, Dr Reddy’s, and Oncologia Brazil. He has consulted for MSD Oncology. He has received research funding from Roche, Boehringer Ingelheim, MSD, Bayer, AstraZeneca, and Takeda.
FROM ESMO CONGRESS 2022
Newborns get routine heel blood tests, but should states keep those samples?
Close to 4 million babies are born in the United States every year, and within their first 48 hours nearly all are pricked in the heel so their blood can be tested for dozens of life-threatening genetic and metabolic problems. The heel-stick test is considered such a crucial public health measure that states typically require it and parents aren’t asked for their permission before it’s done.
But the lab tests for newborn screenings generally don’t use all of the half-dozen or so drops of blood collected on filter paper cards. So states hold on to the leftover “dried blood spots,” as they’re called, often without parents’ knowledge or consent. In recent years, privacy-related concerns have grown about the sometimes decades-long storage and use of the material.
Some states allow the blood spots to be used in research studies, sometimes by third parties for a fee, or provided to law enforcement personnel investigating a crime. Permitting these or other uses without parents’ informed consent that they understand and agree to the use has prompted lawsuits from parents who want to make those decisions themselves and who seek to protect their children’s medical and genetic information.
In May, Michigan officials reportedly agreed to destroy more than 3 million blood spots as a partial settlement in a lawsuit brought by parents who said they didn’t receive enough clear information to provide informed consent for the blood to be used in research the state might conduct. The fate of millions of additional blood spots stored by the state will be determined at trial.
Philip L. Ellison, an attorney in Hemlock, Mich., who is spearheading the suit, said he became aware of the issue when his son was born 5 years ago. Mr. Ellison’s son, Patton, spent his first days in the neonatal intensive care unit after his blood sugar levels dropped precipitously after birth. The next morning, Mr. Ellison said, he was approached by a hospital staffer who asked whether he wanted to sign a consent form allowing the blood from Patton’s heel-stick test to be donated for research.
The unexpected request set off alarm bells for Mr. Ellison.
“We don’t know what the future will bring in terms of information that can be extracted from our blood,” he said. How the rules for using that blood might evolve over time is difficult to know. “A program that first starts out for one purpose, to test for disease, has now crept into medical research and then to law enforcement.”
Michigan is the rare state that asks parents for permission to use leftover newborn blood spots in research. Most do not, experts said. The state screens newborns for more than 50 diseases, such as cystic fibrosis and congenital hypothyroidism, because identifying and treating such illnesses early in a child’s life are crucial.
Afterward, whatever is left over is stored for up to 100 years and, if parents agree to it, may be used in research approved by the Michigan Department of Health and Human Services. Some recent studies have used deidentified blood spots to study the relationship between viral infection at birth and the development of autism later in life, as well as the impact of maternal exposure to manufactured chemicals known as PFAS on health outcomes.
Parents have also asked that their children’s blood spots be sent to researchers to help diagnose a disorder or to try to find a reason for a child’s death, said Chelsea Wuth, a spokesperson for the Michigan Department of Health and Human Services.
Michigan parents can request that the state destroy the leftover blood spots if they don’t want the state to hold on to them.
Since the 1960s, states have screened newborn blood for conditions that can lead to devastating physical or mental disabilities or death if they are not diagnosed and treated. The federal government recommends that roughly three dozen screening tests be performed, but some states conduct many more. Every year, an estimated 13,000 infants with serious medical conditions are identified through newborn screening programs, according to data published by the federal Centers for Disease Control and Prevention.
Many public health experts strongly support mandatory newborn screening as a critical component of infants’ clinical care. But some are receptive to giving parents a say in what happens to the blood after the screening.
“I have always believed that parents should be able to have the opportunity to say ‘yes’ or ‘no’ ” to having their newborns’ leftover blood used in research, said Beth Tarini, MD, a pediatrician and the associate director of the Center for Translational Research at Children’s National Research Institute in Washington, D.C. “Since it is not part of the clinical care, it is a different standard of engagement with the parents.”
In Michigan, 64% of parents consented to participate, according to court documents in Mr. Ellison’s case.
Encouraging people to participate is important, some public health experts say, because the blood spot repositories provide a rare opportunity for population-level research. People of European descent are often overrepresented in genetic databases, which can skew the results of studies. But the newborn screening program includes virtually everyone born in the United States.
“There’s strong evidence that research conducted on samples of white people creates disparities in the benefits of biomedical research for people who are not white,” said Kyle Brothers, MD, PhD, a pediatrician and bioethicist at Norton Children’s Research Institute in Louisville, Ky.
After privacy-related lawsuits were brought in 2009 and 2011 by parents in Texas and Minnesota, respectively, millions of blood spots were destroyed.
Brothers said an unwillingness to participate in research programs reflects larger trends, including more emphasis on the individual and less on contributing to the general good.
To those who might argue that parents’ privacy concerns are overblown, a recent lawsuit in New Jersey raises troubling questions.
In a public records lawsuit, the New Jersey Office of the Public Defender and the New Jersey Monitor, a nonprofit news site, charge that the state police used a subpoena to obtain an infant blood spot of a child who is now 9 years old from the state’s newborn screening laboratory. The lawsuit says a DNA analysis was conducted on the blood spot so evidence could be gathered against the child’s father, who was being represented by the public defender’s office, in connection with a sexual assault committed in 1996. The effort allowed police to get the DNA information without having to show a court probable cause, the suit alleges.
The lawsuit seeks to find out how often in the past 5 years New Jersey law enforcement agencies have used the newborn screening lab as a tool in investigations and subjected defendants to “warrantless searches and seizures.”
New Jersey keeps the records on file for 23 years, said CJ Griffin, a lawyer representing the public defender’s office and the New Jersey Monitor in the lawsuit.
Ms. Griffin said her clients aren’t challenging the program to test newborn blood for diseases. “It’s more the lack of transparency, and safeguards, and information about storage, and we don’t have any information about appropriate use.”
The New Jersey Department of Health doesn’t comment on pending litigation, spokesperson Nancy Kearney said. Ms. Kearney didn’t respond to a request for information about the state’s practices and policies related to the newborn screening program.
A recent Texas Law Review article found that more than a quarter of states lack policies on law enforcement access to newborn blood spot samples and related information and that nearly a third may allow access in certain circumstances.
In Michigan, the state gives law enforcement agencies dried blood spots only to identify the victim of a crime, Ms. Wuth said. “Typically, this means someone has been killed or gone missing,” she added.
Many clinicians and bioethicists say that standards for the use of blood spots need to be set.
“It’s nearly impossible for us to monitor the potential uses of our data,” said Andrew Crawford, senior policy counsel for the privacy and data project at the Center for Democracy and Technology. “That’s why need to put limitations on the use.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Close to 4 million babies are born in the United States every year, and within their first 48 hours nearly all are pricked in the heel so their blood can be tested for dozens of life-threatening genetic and metabolic problems. The heel-stick test is considered such a crucial public health measure that states typically require it and parents aren’t asked for their permission before it’s done.
But the lab tests for newborn screenings generally don’t use all of the half-dozen or so drops of blood collected on filter paper cards. So states hold on to the leftover “dried blood spots,” as they’re called, often without parents’ knowledge or consent. In recent years, privacy-related concerns have grown about the sometimes decades-long storage and use of the material.
Some states allow the blood spots to be used in research studies, sometimes by third parties for a fee, or provided to law enforcement personnel investigating a crime. Permitting these or other uses without parents’ informed consent that they understand and agree to the use has prompted lawsuits from parents who want to make those decisions themselves and who seek to protect their children’s medical and genetic information.
In May, Michigan officials reportedly agreed to destroy more than 3 million blood spots as a partial settlement in a lawsuit brought by parents who said they didn’t receive enough clear information to provide informed consent for the blood to be used in research the state might conduct. The fate of millions of additional blood spots stored by the state will be determined at trial.
Philip L. Ellison, an attorney in Hemlock, Mich., who is spearheading the suit, said he became aware of the issue when his son was born 5 years ago. Mr. Ellison’s son, Patton, spent his first days in the neonatal intensive care unit after his blood sugar levels dropped precipitously after birth. The next morning, Mr. Ellison said, he was approached by a hospital staffer who asked whether he wanted to sign a consent form allowing the blood from Patton’s heel-stick test to be donated for research.
The unexpected request set off alarm bells for Mr. Ellison.
“We don’t know what the future will bring in terms of information that can be extracted from our blood,” he said. How the rules for using that blood might evolve over time is difficult to know. “A program that first starts out for one purpose, to test for disease, has now crept into medical research and then to law enforcement.”
Michigan is the rare state that asks parents for permission to use leftover newborn blood spots in research. Most do not, experts said. The state screens newborns for more than 50 diseases, such as cystic fibrosis and congenital hypothyroidism, because identifying and treating such illnesses early in a child’s life are crucial.
Afterward, whatever is left over is stored for up to 100 years and, if parents agree to it, may be used in research approved by the Michigan Department of Health and Human Services. Some recent studies have used deidentified blood spots to study the relationship between viral infection at birth and the development of autism later in life, as well as the impact of maternal exposure to manufactured chemicals known as PFAS on health outcomes.
Parents have also asked that their children’s blood spots be sent to researchers to help diagnose a disorder or to try to find a reason for a child’s death, said Chelsea Wuth, a spokesperson for the Michigan Department of Health and Human Services.
Michigan parents can request that the state destroy the leftover blood spots if they don’t want the state to hold on to them.
Since the 1960s, states have screened newborn blood for conditions that can lead to devastating physical or mental disabilities or death if they are not diagnosed and treated. The federal government recommends that roughly three dozen screening tests be performed, but some states conduct many more. Every year, an estimated 13,000 infants with serious medical conditions are identified through newborn screening programs, according to data published by the federal Centers for Disease Control and Prevention.
Many public health experts strongly support mandatory newborn screening as a critical component of infants’ clinical care. But some are receptive to giving parents a say in what happens to the blood after the screening.
“I have always believed that parents should be able to have the opportunity to say ‘yes’ or ‘no’ ” to having their newborns’ leftover blood used in research, said Beth Tarini, MD, a pediatrician and the associate director of the Center for Translational Research at Children’s National Research Institute in Washington, D.C. “Since it is not part of the clinical care, it is a different standard of engagement with the parents.”
In Michigan, 64% of parents consented to participate, according to court documents in Mr. Ellison’s case.
Encouraging people to participate is important, some public health experts say, because the blood spot repositories provide a rare opportunity for population-level research. People of European descent are often overrepresented in genetic databases, which can skew the results of studies. But the newborn screening program includes virtually everyone born in the United States.
“There’s strong evidence that research conducted on samples of white people creates disparities in the benefits of biomedical research for people who are not white,” said Kyle Brothers, MD, PhD, a pediatrician and bioethicist at Norton Children’s Research Institute in Louisville, Ky.
After privacy-related lawsuits were brought in 2009 and 2011 by parents in Texas and Minnesota, respectively, millions of blood spots were destroyed.
Brothers said an unwillingness to participate in research programs reflects larger trends, including more emphasis on the individual and less on contributing to the general good.
To those who might argue that parents’ privacy concerns are overblown, a recent lawsuit in New Jersey raises troubling questions.
In a public records lawsuit, the New Jersey Office of the Public Defender and the New Jersey Monitor, a nonprofit news site, charge that the state police used a subpoena to obtain an infant blood spot of a child who is now 9 years old from the state’s newborn screening laboratory. The lawsuit says a DNA analysis was conducted on the blood spot so evidence could be gathered against the child’s father, who was being represented by the public defender’s office, in connection with a sexual assault committed in 1996. The effort allowed police to get the DNA information without having to show a court probable cause, the suit alleges.
The lawsuit seeks to find out how often in the past 5 years New Jersey law enforcement agencies have used the newborn screening lab as a tool in investigations and subjected defendants to “warrantless searches and seizures.”
New Jersey keeps the records on file for 23 years, said CJ Griffin, a lawyer representing the public defender’s office and the New Jersey Monitor in the lawsuit.
Ms. Griffin said her clients aren’t challenging the program to test newborn blood for diseases. “It’s more the lack of transparency, and safeguards, and information about storage, and we don’t have any information about appropriate use.”
The New Jersey Department of Health doesn’t comment on pending litigation, spokesperson Nancy Kearney said. Ms. Kearney didn’t respond to a request for information about the state’s practices and policies related to the newborn screening program.
A recent Texas Law Review article found that more than a quarter of states lack policies on law enforcement access to newborn blood spot samples and related information and that nearly a third may allow access in certain circumstances.
In Michigan, the state gives law enforcement agencies dried blood spots only to identify the victim of a crime, Ms. Wuth said. “Typically, this means someone has been killed or gone missing,” she added.
Many clinicians and bioethicists say that standards for the use of blood spots need to be set.
“It’s nearly impossible for us to monitor the potential uses of our data,” said Andrew Crawford, senior policy counsel for the privacy and data project at the Center for Democracy and Technology. “That’s why need to put limitations on the use.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Close to 4 million babies are born in the United States every year, and within their first 48 hours nearly all are pricked in the heel so their blood can be tested for dozens of life-threatening genetic and metabolic problems. The heel-stick test is considered such a crucial public health measure that states typically require it and parents aren’t asked for their permission before it’s done.
But the lab tests for newborn screenings generally don’t use all of the half-dozen or so drops of blood collected on filter paper cards. So states hold on to the leftover “dried blood spots,” as they’re called, often without parents’ knowledge or consent. In recent years, privacy-related concerns have grown about the sometimes decades-long storage and use of the material.
Some states allow the blood spots to be used in research studies, sometimes by third parties for a fee, or provided to law enforcement personnel investigating a crime. Permitting these or other uses without parents’ informed consent that they understand and agree to the use has prompted lawsuits from parents who want to make those decisions themselves and who seek to protect their children’s medical and genetic information.
In May, Michigan officials reportedly agreed to destroy more than 3 million blood spots as a partial settlement in a lawsuit brought by parents who said they didn’t receive enough clear information to provide informed consent for the blood to be used in research the state might conduct. The fate of millions of additional blood spots stored by the state will be determined at trial.
Philip L. Ellison, an attorney in Hemlock, Mich., who is spearheading the suit, said he became aware of the issue when his son was born 5 years ago. Mr. Ellison’s son, Patton, spent his first days in the neonatal intensive care unit after his blood sugar levels dropped precipitously after birth. The next morning, Mr. Ellison said, he was approached by a hospital staffer who asked whether he wanted to sign a consent form allowing the blood from Patton’s heel-stick test to be donated for research.
The unexpected request set off alarm bells for Mr. Ellison.
“We don’t know what the future will bring in terms of information that can be extracted from our blood,” he said. How the rules for using that blood might evolve over time is difficult to know. “A program that first starts out for one purpose, to test for disease, has now crept into medical research and then to law enforcement.”
Michigan is the rare state that asks parents for permission to use leftover newborn blood spots in research. Most do not, experts said. The state screens newborns for more than 50 diseases, such as cystic fibrosis and congenital hypothyroidism, because identifying and treating such illnesses early in a child’s life are crucial.
Afterward, whatever is left over is stored for up to 100 years and, if parents agree to it, may be used in research approved by the Michigan Department of Health and Human Services. Some recent studies have used deidentified blood spots to study the relationship between viral infection at birth and the development of autism later in life, as well as the impact of maternal exposure to manufactured chemicals known as PFAS on health outcomes.
Parents have also asked that their children’s blood spots be sent to researchers to help diagnose a disorder or to try to find a reason for a child’s death, said Chelsea Wuth, a spokesperson for the Michigan Department of Health and Human Services.
Michigan parents can request that the state destroy the leftover blood spots if they don’t want the state to hold on to them.
Since the 1960s, states have screened newborn blood for conditions that can lead to devastating physical or mental disabilities or death if they are not diagnosed and treated. The federal government recommends that roughly three dozen screening tests be performed, but some states conduct many more. Every year, an estimated 13,000 infants with serious medical conditions are identified through newborn screening programs, according to data published by the federal Centers for Disease Control and Prevention.
Many public health experts strongly support mandatory newborn screening as a critical component of infants’ clinical care. But some are receptive to giving parents a say in what happens to the blood after the screening.
“I have always believed that parents should be able to have the opportunity to say ‘yes’ or ‘no’ ” to having their newborns’ leftover blood used in research, said Beth Tarini, MD, a pediatrician and the associate director of the Center for Translational Research at Children’s National Research Institute in Washington, D.C. “Since it is not part of the clinical care, it is a different standard of engagement with the parents.”
In Michigan, 64% of parents consented to participate, according to court documents in Mr. Ellison’s case.
Encouraging people to participate is important, some public health experts say, because the blood spot repositories provide a rare opportunity for population-level research. People of European descent are often overrepresented in genetic databases, which can skew the results of studies. But the newborn screening program includes virtually everyone born in the United States.
“There’s strong evidence that research conducted on samples of white people creates disparities in the benefits of biomedical research for people who are not white,” said Kyle Brothers, MD, PhD, a pediatrician and bioethicist at Norton Children’s Research Institute in Louisville, Ky.
After privacy-related lawsuits were brought in 2009 and 2011 by parents in Texas and Minnesota, respectively, millions of blood spots were destroyed.
Brothers said an unwillingness to participate in research programs reflects larger trends, including more emphasis on the individual and less on contributing to the general good.
To those who might argue that parents’ privacy concerns are overblown, a recent lawsuit in New Jersey raises troubling questions.
In a public records lawsuit, the New Jersey Office of the Public Defender and the New Jersey Monitor, a nonprofit news site, charge that the state police used a subpoena to obtain an infant blood spot of a child who is now 9 years old from the state’s newborn screening laboratory. The lawsuit says a DNA analysis was conducted on the blood spot so evidence could be gathered against the child’s father, who was being represented by the public defender’s office, in connection with a sexual assault committed in 1996. The effort allowed police to get the DNA information without having to show a court probable cause, the suit alleges.
The lawsuit seeks to find out how often in the past 5 years New Jersey law enforcement agencies have used the newborn screening lab as a tool in investigations and subjected defendants to “warrantless searches and seizures.”
New Jersey keeps the records on file for 23 years, said CJ Griffin, a lawyer representing the public defender’s office and the New Jersey Monitor in the lawsuit.
Ms. Griffin said her clients aren’t challenging the program to test newborn blood for diseases. “It’s more the lack of transparency, and safeguards, and information about storage, and we don’t have any information about appropriate use.”
The New Jersey Department of Health doesn’t comment on pending litigation, spokesperson Nancy Kearney said. Ms. Kearney didn’t respond to a request for information about the state’s practices and policies related to the newborn screening program.
A recent Texas Law Review article found that more than a quarter of states lack policies on law enforcement access to newborn blood spot samples and related information and that nearly a third may allow access in certain circumstances.
In Michigan, the state gives law enforcement agencies dried blood spots only to identify the victim of a crime, Ms. Wuth said. “Typically, this means someone has been killed or gone missing,” she added.
Many clinicians and bioethicists say that standards for the use of blood spots need to be set.
“It’s nearly impossible for us to monitor the potential uses of our data,” said Andrew Crawford, senior policy counsel for the privacy and data project at the Center for Democracy and Technology. “That’s why need to put limitations on the use.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Two states aim to curb diet pill sales to minors
California and New York are on the cusp of going further than the Food and Drug Administration in restricting the sale of nonprescription diet pills to minors as pediatricians and public health advocates try to protect kids from extreme weight-loss gimmicks online.
A bill before Gov. Gavin Newsom would bar anyone under 18 in California from buying over-the-counter weight-loss supplements – whether online or in shops – without a prescription. A similar bill passed by New York lawmakers is on Gov. Kathy Hochul’s desk. Neither Democrat has indicated how he or she will act.
If both bills are signed into law, proponents hope the momentum will build to restrict diet pill sales to children in more states. Massachusetts, New Jersey, and Missouri have introduced similar bills and backers plan to continue their push next year.
Nearly 30 million people in the United States will have an eating disorder in their lifetime; 95% of them are aged between 12 and 25, according to Johns Hopkins All Children’s Hospital. The hospital added that eating disorders pose the highest risk of mortality of any mental health disorder. And it has become easier than ever for minors to get pills that are sold online or on drugstore shelves. All dietary supplements, which include those for weight loss, accounted for nearly 35% of the $63 billion over-the-counter health products industry in 2021, according to Vision Research Reports, a market research firm.
Dietary supplements, which encompass a broad range of vitamins, herbs, and minerals, are classified by the FDA as food and don’t undergo scientific and safety testing as prescription drugs and over-the-counter medicines do.
Public health advocates want to keep weight-loss products – with ads that may promise to “Drop 5 pounds a week!” and pill names like Slim Sense – away from young people, particularly girls, since some research has linked some products to eating disorders. A study in the American Journal of Public Health, which followed more than 10,000 women aged 14-36 over 15 years, found that “those who used diet pills had more than 5 times higher adjusted odds of receiving an eating disorder diagnosis from a health care provider within 1-3 years than those who did not.”
Many pills have been found tainted with banned and dangerous ingredients that may cause cancer, heart attacks, strokes, and other ailments. For example, the FDA advised the public to avoid Slim Sense by Dr. Reade because it contains lorcaserin, which has been found to cause psychiatric disturbances and impairments in attention or memory. The FDA ordered it discontinued and the company couldn’t be reached for comment.
“Unscrupulous manufacturers are willing to take risks with consumers’ health – and they are lacing their products with illegal pharmaceuticals, banned pharmaceuticals, steroids, excessive stimulants, even experimental stimulants,” said S. Bryn Austin, ScD, founding director of the Strategic Training Initiative for the Prevention of Eating Disorders, or STRIPED, which supports the restrictions. “Consumers have no idea that this is what’s in these types of products.”
STRIPED is a public health initiative based at the Harvard School of Public Health, Boston, and Boston Children’s Hospital.
An industry trade group, the Natural Products Association, disputes that diet pills cause eating disorders, citing the lack of consumer complaints to the FDA of adverse events from their members’ products. “According to FDA data, there is no association between the two,” said Kyle Turk, the association’s director of government affairs.
The association contends that its members adhere to safe manufacturing processes, random product testing, and appropriate marketing guidelines. Representatives also worry that if minors can’t buy supplements over the counter, they may buy them from “crooks” on the black market and undermine the integrity of the industry. Under the bills, minors purchasing weight-loss products must show identification along with a prescription.
Not all business groups oppose the ban. The American Herbal Products Association, a trade group representing dietary supplement manufacturers and retailers, dropped its opposition to California’s bill once it was amended to remove ingredient categories that are found in non-diet supplements and vitamins, according to Robert Marriott, director of regulatory affairs.
Children’s advocates have found worrisome trends among young people who envision their ideal body type based on what they see on social media. According to a study commissioned by Fairplay, a nonprofit that seeks to stop harmful marketing practices targeting children, kids as young as 9 were found to be following three or more eating disorder accounts on Instagram, while the median age was 19. The authors called it a “pro–eating disorder bubble.”
Meta, which owns Instagram and Facebook, said the report lacks nuance, such as recognizing the human need to share life’s difficult moments. The company argues that blanket censorship isn’t the answer. “Experts and safety organizations have told us it’s important to strike a balance and allow people to share their personal stories while removing any content that encourages or promotes eating disorders,” Liza Crenshaw, a Meta spokesperson, said in an email.
Jason Nagata, MD, a pediatrician who cares for children and young adults with life-threatening eating disorders, believes that easy access to diet pills contributes to his patients’ conditions at UCSF Benioff Children’s Hospital in San Francisco. That was the case for one of his patients, an emaciated 11-year-old girl.
“She had basically entered a starvation state because she was not getting enough nutrition,” said Dr. Nagata, who provided supporting testimony for the California bill. “She was taking these pills and using other kinds of extreme behaviors to lose weight.”
Dr. Nagata said the number of patients he sees with eating disorders has tripled since the pandemic began. They are desperate to get diet pills, some with modest results. “We’ve had patients who have been so dependent on these products that they will be hospitalized and they’re still ordering these products on Amazon,” he said.
Public health advocates turned to state legislatures in response to the federal government’s limited authority to regulate diet pills. Under a 1994 federal law known as the Dietary Supplement Health and Education Act, the FDA “cannot step in until after there is a clear issue of harm to consumers,” said Dr. Austin.
No match for the supplement industry’s heavy lobbying on Capitol Hill, public health advocates shifted to a state-by-state approach.
There is, however, a push for the FDA to improve oversight of what goes into diet pills. Sen. Dick Durbin (D-Ill.) in April introduced a bill that would require dietary supplement manufacturers to register their products – along with the ingredients – with the regulator.
Proponents say the change is needed because manufacturers have been known to include dangerous ingredients. C. Michael White, PharmD, of the University of Connecticut, Storrs, found 35% of tainted health products came from weight-loss supplements in a review of a health fraud database.
A few ingredients have been banned, including sibutramine, a stimulant. “It was a very commonly used weight-loss supplement that ended up being removed from the U.S. market because of its elevated risk of causing things like heart attacks, strokes, and arrhythmias,” Dr. White said.
Another ingredient was phenolphthalein, which was used in laxatives until it was identified as a suspected carcinogen and banned in 1999. “To think,” he said, “that that product would still be on the U.S. market is just unconscionable.”
This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
California and New York are on the cusp of going further than the Food and Drug Administration in restricting the sale of nonprescription diet pills to minors as pediatricians and public health advocates try to protect kids from extreme weight-loss gimmicks online.
A bill before Gov. Gavin Newsom would bar anyone under 18 in California from buying over-the-counter weight-loss supplements – whether online or in shops – without a prescription. A similar bill passed by New York lawmakers is on Gov. Kathy Hochul’s desk. Neither Democrat has indicated how he or she will act.
If both bills are signed into law, proponents hope the momentum will build to restrict diet pill sales to children in more states. Massachusetts, New Jersey, and Missouri have introduced similar bills and backers plan to continue their push next year.
Nearly 30 million people in the United States will have an eating disorder in their lifetime; 95% of them are aged between 12 and 25, according to Johns Hopkins All Children’s Hospital. The hospital added that eating disorders pose the highest risk of mortality of any mental health disorder. And it has become easier than ever for minors to get pills that are sold online or on drugstore shelves. All dietary supplements, which include those for weight loss, accounted for nearly 35% of the $63 billion over-the-counter health products industry in 2021, according to Vision Research Reports, a market research firm.
Dietary supplements, which encompass a broad range of vitamins, herbs, and minerals, are classified by the FDA as food and don’t undergo scientific and safety testing as prescription drugs and over-the-counter medicines do.
Public health advocates want to keep weight-loss products – with ads that may promise to “Drop 5 pounds a week!” and pill names like Slim Sense – away from young people, particularly girls, since some research has linked some products to eating disorders. A study in the American Journal of Public Health, which followed more than 10,000 women aged 14-36 over 15 years, found that “those who used diet pills had more than 5 times higher adjusted odds of receiving an eating disorder diagnosis from a health care provider within 1-3 years than those who did not.”
Many pills have been found tainted with banned and dangerous ingredients that may cause cancer, heart attacks, strokes, and other ailments. For example, the FDA advised the public to avoid Slim Sense by Dr. Reade because it contains lorcaserin, which has been found to cause psychiatric disturbances and impairments in attention or memory. The FDA ordered it discontinued and the company couldn’t be reached for comment.
“Unscrupulous manufacturers are willing to take risks with consumers’ health – and they are lacing their products with illegal pharmaceuticals, banned pharmaceuticals, steroids, excessive stimulants, even experimental stimulants,” said S. Bryn Austin, ScD, founding director of the Strategic Training Initiative for the Prevention of Eating Disorders, or STRIPED, which supports the restrictions. “Consumers have no idea that this is what’s in these types of products.”
STRIPED is a public health initiative based at the Harvard School of Public Health, Boston, and Boston Children’s Hospital.
An industry trade group, the Natural Products Association, disputes that diet pills cause eating disorders, citing the lack of consumer complaints to the FDA of adverse events from their members’ products. “According to FDA data, there is no association between the two,” said Kyle Turk, the association’s director of government affairs.
The association contends that its members adhere to safe manufacturing processes, random product testing, and appropriate marketing guidelines. Representatives also worry that if minors can’t buy supplements over the counter, they may buy them from “crooks” on the black market and undermine the integrity of the industry. Under the bills, minors purchasing weight-loss products must show identification along with a prescription.
Not all business groups oppose the ban. The American Herbal Products Association, a trade group representing dietary supplement manufacturers and retailers, dropped its opposition to California’s bill once it was amended to remove ingredient categories that are found in non-diet supplements and vitamins, according to Robert Marriott, director of regulatory affairs.
Children’s advocates have found worrisome trends among young people who envision their ideal body type based on what they see on social media. According to a study commissioned by Fairplay, a nonprofit that seeks to stop harmful marketing practices targeting children, kids as young as 9 were found to be following three or more eating disorder accounts on Instagram, while the median age was 19. The authors called it a “pro–eating disorder bubble.”
Meta, which owns Instagram and Facebook, said the report lacks nuance, such as recognizing the human need to share life’s difficult moments. The company argues that blanket censorship isn’t the answer. “Experts and safety organizations have told us it’s important to strike a balance and allow people to share their personal stories while removing any content that encourages or promotes eating disorders,” Liza Crenshaw, a Meta spokesperson, said in an email.
Jason Nagata, MD, a pediatrician who cares for children and young adults with life-threatening eating disorders, believes that easy access to diet pills contributes to his patients’ conditions at UCSF Benioff Children’s Hospital in San Francisco. That was the case for one of his patients, an emaciated 11-year-old girl.
“She had basically entered a starvation state because she was not getting enough nutrition,” said Dr. Nagata, who provided supporting testimony for the California bill. “She was taking these pills and using other kinds of extreme behaviors to lose weight.”
Dr. Nagata said the number of patients he sees with eating disorders has tripled since the pandemic began. They are desperate to get diet pills, some with modest results. “We’ve had patients who have been so dependent on these products that they will be hospitalized and they’re still ordering these products on Amazon,” he said.
Public health advocates turned to state legislatures in response to the federal government’s limited authority to regulate diet pills. Under a 1994 federal law known as the Dietary Supplement Health and Education Act, the FDA “cannot step in until after there is a clear issue of harm to consumers,” said Dr. Austin.
No match for the supplement industry’s heavy lobbying on Capitol Hill, public health advocates shifted to a state-by-state approach.
There is, however, a push for the FDA to improve oversight of what goes into diet pills. Sen. Dick Durbin (D-Ill.) in April introduced a bill that would require dietary supplement manufacturers to register their products – along with the ingredients – with the regulator.
Proponents say the change is needed because manufacturers have been known to include dangerous ingredients. C. Michael White, PharmD, of the University of Connecticut, Storrs, found 35% of tainted health products came from weight-loss supplements in a review of a health fraud database.
A few ingredients have been banned, including sibutramine, a stimulant. “It was a very commonly used weight-loss supplement that ended up being removed from the U.S. market because of its elevated risk of causing things like heart attacks, strokes, and arrhythmias,” Dr. White said.
Another ingredient was phenolphthalein, which was used in laxatives until it was identified as a suspected carcinogen and banned in 1999. “To think,” he said, “that that product would still be on the U.S. market is just unconscionable.”
This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
California and New York are on the cusp of going further than the Food and Drug Administration in restricting the sale of nonprescription diet pills to minors as pediatricians and public health advocates try to protect kids from extreme weight-loss gimmicks online.
A bill before Gov. Gavin Newsom would bar anyone under 18 in California from buying over-the-counter weight-loss supplements – whether online or in shops – without a prescription. A similar bill passed by New York lawmakers is on Gov. Kathy Hochul’s desk. Neither Democrat has indicated how he or she will act.
If both bills are signed into law, proponents hope the momentum will build to restrict diet pill sales to children in more states. Massachusetts, New Jersey, and Missouri have introduced similar bills and backers plan to continue their push next year.
Nearly 30 million people in the United States will have an eating disorder in their lifetime; 95% of them are aged between 12 and 25, according to Johns Hopkins All Children’s Hospital. The hospital added that eating disorders pose the highest risk of mortality of any mental health disorder. And it has become easier than ever for minors to get pills that are sold online or on drugstore shelves. All dietary supplements, which include those for weight loss, accounted for nearly 35% of the $63 billion over-the-counter health products industry in 2021, according to Vision Research Reports, a market research firm.
Dietary supplements, which encompass a broad range of vitamins, herbs, and minerals, are classified by the FDA as food and don’t undergo scientific and safety testing as prescription drugs and over-the-counter medicines do.
Public health advocates want to keep weight-loss products – with ads that may promise to “Drop 5 pounds a week!” and pill names like Slim Sense – away from young people, particularly girls, since some research has linked some products to eating disorders. A study in the American Journal of Public Health, which followed more than 10,000 women aged 14-36 over 15 years, found that “those who used diet pills had more than 5 times higher adjusted odds of receiving an eating disorder diagnosis from a health care provider within 1-3 years than those who did not.”
Many pills have been found tainted with banned and dangerous ingredients that may cause cancer, heart attacks, strokes, and other ailments. For example, the FDA advised the public to avoid Slim Sense by Dr. Reade because it contains lorcaserin, which has been found to cause psychiatric disturbances and impairments in attention or memory. The FDA ordered it discontinued and the company couldn’t be reached for comment.
“Unscrupulous manufacturers are willing to take risks with consumers’ health – and they are lacing their products with illegal pharmaceuticals, banned pharmaceuticals, steroids, excessive stimulants, even experimental stimulants,” said S. Bryn Austin, ScD, founding director of the Strategic Training Initiative for the Prevention of Eating Disorders, or STRIPED, which supports the restrictions. “Consumers have no idea that this is what’s in these types of products.”
STRIPED is a public health initiative based at the Harvard School of Public Health, Boston, and Boston Children’s Hospital.
An industry trade group, the Natural Products Association, disputes that diet pills cause eating disorders, citing the lack of consumer complaints to the FDA of adverse events from their members’ products. “According to FDA data, there is no association between the two,” said Kyle Turk, the association’s director of government affairs.
The association contends that its members adhere to safe manufacturing processes, random product testing, and appropriate marketing guidelines. Representatives also worry that if minors can’t buy supplements over the counter, they may buy them from “crooks” on the black market and undermine the integrity of the industry. Under the bills, minors purchasing weight-loss products must show identification along with a prescription.
Not all business groups oppose the ban. The American Herbal Products Association, a trade group representing dietary supplement manufacturers and retailers, dropped its opposition to California’s bill once it was amended to remove ingredient categories that are found in non-diet supplements and vitamins, according to Robert Marriott, director of regulatory affairs.
Children’s advocates have found worrisome trends among young people who envision their ideal body type based on what they see on social media. According to a study commissioned by Fairplay, a nonprofit that seeks to stop harmful marketing practices targeting children, kids as young as 9 were found to be following three or more eating disorder accounts on Instagram, while the median age was 19. The authors called it a “pro–eating disorder bubble.”
Meta, which owns Instagram and Facebook, said the report lacks nuance, such as recognizing the human need to share life’s difficult moments. The company argues that blanket censorship isn’t the answer. “Experts and safety organizations have told us it’s important to strike a balance and allow people to share their personal stories while removing any content that encourages or promotes eating disorders,” Liza Crenshaw, a Meta spokesperson, said in an email.
Jason Nagata, MD, a pediatrician who cares for children and young adults with life-threatening eating disorders, believes that easy access to diet pills contributes to his patients’ conditions at UCSF Benioff Children’s Hospital in San Francisco. That was the case for one of his patients, an emaciated 11-year-old girl.
“She had basically entered a starvation state because she was not getting enough nutrition,” said Dr. Nagata, who provided supporting testimony for the California bill. “She was taking these pills and using other kinds of extreme behaviors to lose weight.”
Dr. Nagata said the number of patients he sees with eating disorders has tripled since the pandemic began. They are desperate to get diet pills, some with modest results. “We’ve had patients who have been so dependent on these products that they will be hospitalized and they’re still ordering these products on Amazon,” he said.
Public health advocates turned to state legislatures in response to the federal government’s limited authority to regulate diet pills. Under a 1994 federal law known as the Dietary Supplement Health and Education Act, the FDA “cannot step in until after there is a clear issue of harm to consumers,” said Dr. Austin.
No match for the supplement industry’s heavy lobbying on Capitol Hill, public health advocates shifted to a state-by-state approach.
There is, however, a push for the FDA to improve oversight of what goes into diet pills. Sen. Dick Durbin (D-Ill.) in April introduced a bill that would require dietary supplement manufacturers to register their products – along with the ingredients – with the regulator.
Proponents say the change is needed because manufacturers have been known to include dangerous ingredients. C. Michael White, PharmD, of the University of Connecticut, Storrs, found 35% of tainted health products came from weight-loss supplements in a review of a health fraud database.
A few ingredients have been banned, including sibutramine, a stimulant. “It was a very commonly used weight-loss supplement that ended up being removed from the U.S. market because of its elevated risk of causing things like heart attacks, strokes, and arrhythmias,” Dr. White said.
Another ingredient was phenolphthalein, which was used in laxatives until it was identified as a suspected carcinogen and banned in 1999. “To think,” he said, “that that product would still be on the U.S. market is just unconscionable.”
This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Health Care Foundation. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
BRAF/MEK combo shows long-term efficacy in melanoma
, according to 5-year follow-up data from the COLUMBUS trial. Among patients with advanced unresectable or metastatic disease who were untreated or who had progressed following immunotherapy, the regimen of encorafenib plus binimetinib produced impressive gains in progression-free and overall survival, compared with historical controls, and are in line with other BRAF/MEK inhibitor combinations. It also outperformed encorafenib and vemurafenib monotherapy regimens.
The findings present good news, but the combination still doesn’t represent the best first-line option, according to Ryan Sullivan, MD, who wrote an accompanying editorial. He pointed out that the previously published DREAMSeq trial showed that a combination of immune checkpoint inhibitors (ICIs) ipilimumab and nivolumab produced a 2-year survival of 72%, compared with 52% for a BRAF inhibitor combination of dabrafenib plus trametinib (P = .0095).
There are three combinations of BRAF and MEK inhibitors that are approved for BRAF mutant melanoma, and any of the seven individual agents and six combinations that are approved by the U.S. Food and Drug Administration- for melanoma can be used in BRAFV600 patients. “The standard of care for most patients with newly diagnosed BRAF mutant melanoma is ... immune checkpoint inhibition, either with anti–PD-1 inhibitor or a combination of immunotherapy with an anti–PD-1 inhibitor. The optimal use of BRAF targeted therapy is unknown but some data supports its use earlier in the disease course (adjuvant setting) or after progression following anti–PD-1 therapy in the advanced disease setting,” wrote Dr. Sullivan in an email. He is associate director of the melanoma program at Massachusetts General Hospital, Boston.
The new study was published online in the Journal of Clinical Oncology.
In his editorial, Dr. Sullivan wrote that anti–PD-1 monoclonal antibodies alone or in combination with anti-CTLA4 receptor therapies is likely the best front-line therapy for BRAFV600 mutant advanced melanoma, with long-term survival ranging from 40% to 50%.
Still, the efficacy of BRAF-targeted therapy makes it important to explore ways to strengthen it further. One possibility is to use it in the front-line setting when a patient is at high risk of rapid progression and death, since analysis from DREAMSeq showed that BRAF-targeted therapy had a better overall survival than immunotherapy during the first 10 months after random assignment. It was only after this time point that the curves reversed and pointed to greater efficacy for immunotherapy. An option would be to treat to maximum tumor regression with BRAF-targeted therapy and then switch to immunotherapy, according to Dr. Sullivan. That point was echoed by study author Paolo Ascierto, MD, in an email exchange. “For patients with symptomatic disease or very high tumor burden, BRAF/MEK inhibitor should be used first,” said Dr. Ascierto, who is director of the melanoma cancer immunotherapy innovative therapy unit of the National Tumor Institute in Naples, Italy.
BRAF inhibitors as second- or later-line therapy
Aside from that exception, BRAF inhibitors should generally be reserved for second- or later-line therapy, according to Dr. Sullivan. Retrospective data indicate that response to BRAF inhibitors is preserved following immunotherapy, although the duration of benefit is reduced. Unfortunately, that strategy limits BRAF inhibitors to a setting in which they’re less likely to be maximally effective.
To improve matters, Dr. Sullivan suggested that they could be used in the adjuvant setting, where disease burden is lower. He noted that dabrafenib and trametinib are approved for resected stage 3 melanoma and showed similar efficacy to immunotherapy in that setting. Immunotherapy retains efficacy after BRAF-targeted therapy.
Another potential strategy is to come up with 3- or even 4-drug combinations employing BRAF/MEK inhibitors in the second-line setting. A few trials have already begun to investigate this possibility.
The COLUMBUS trial included 192 patients who received encorafenib plus binimetinib (E+B), 191 who received vemurafenib and 194 who received encorafenib. Five-year progression-free survival (PFS) was 23% in the E+B group, and 31% in those with normal lactate dehydrogenase levels. Five-year PFS was 10% with vemurafenib alone (12% with normal lactate dehydrogenase). Progression free survival (PFS) was 19% in the encorafenib group. Five-year overall survival (OS) followed a similar trend: 35% (45% with normal lactate dehydrogenase) in the E+B group, and 21% (28%) in the vemurafenib group. E+B had a median duration of response of 18.6 months, and a disease control rate of 92.2%, compared with 12.3 months and 81.2% with vemurafenib. Median duration of response was 15.5 months in the encorafenib monotherapy group.
The COLUMBUS trial was sponsored by Array BioPharma, which was acquired by Pfizer in July 2019.
Dr. Sullivan has consulted or advised Novartis, Merck, Replimune, Asana Biosciences, Alkermes, Eisai, Pfizer, Iovance Biotherapeutics, OncoSec, AstraZeneca, and Bristol Myers Squibb. Dr. Ascierto has stock or an ownership position in PrimeVax. He has consulted or advised for Bristol Myers Squibb, Roche/Genentech, Merck Sharp & Dohme, Novartis, Array BioPharma, Merck Serono, Pierre Fabre, Incyte, MedImmune, AstraZeneca, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, Nektar, Boehringer Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, OncoSec, Nouscom, Takis Biotech, Lunaphore Technologies, Seattle Genetics, ITeos Therapeutics, Medicenna, and Bio-Al Health.
, according to 5-year follow-up data from the COLUMBUS trial. Among patients with advanced unresectable or metastatic disease who were untreated or who had progressed following immunotherapy, the regimen of encorafenib plus binimetinib produced impressive gains in progression-free and overall survival, compared with historical controls, and are in line with other BRAF/MEK inhibitor combinations. It also outperformed encorafenib and vemurafenib monotherapy regimens.
The findings present good news, but the combination still doesn’t represent the best first-line option, according to Ryan Sullivan, MD, who wrote an accompanying editorial. He pointed out that the previously published DREAMSeq trial showed that a combination of immune checkpoint inhibitors (ICIs) ipilimumab and nivolumab produced a 2-year survival of 72%, compared with 52% for a BRAF inhibitor combination of dabrafenib plus trametinib (P = .0095).
There are three combinations of BRAF and MEK inhibitors that are approved for BRAF mutant melanoma, and any of the seven individual agents and six combinations that are approved by the U.S. Food and Drug Administration- for melanoma can be used in BRAFV600 patients. “The standard of care for most patients with newly diagnosed BRAF mutant melanoma is ... immune checkpoint inhibition, either with anti–PD-1 inhibitor or a combination of immunotherapy with an anti–PD-1 inhibitor. The optimal use of BRAF targeted therapy is unknown but some data supports its use earlier in the disease course (adjuvant setting) or after progression following anti–PD-1 therapy in the advanced disease setting,” wrote Dr. Sullivan in an email. He is associate director of the melanoma program at Massachusetts General Hospital, Boston.
The new study was published online in the Journal of Clinical Oncology.
In his editorial, Dr. Sullivan wrote that anti–PD-1 monoclonal antibodies alone or in combination with anti-CTLA4 receptor therapies is likely the best front-line therapy for BRAFV600 mutant advanced melanoma, with long-term survival ranging from 40% to 50%.
Still, the efficacy of BRAF-targeted therapy makes it important to explore ways to strengthen it further. One possibility is to use it in the front-line setting when a patient is at high risk of rapid progression and death, since analysis from DREAMSeq showed that BRAF-targeted therapy had a better overall survival than immunotherapy during the first 10 months after random assignment. It was only after this time point that the curves reversed and pointed to greater efficacy for immunotherapy. An option would be to treat to maximum tumor regression with BRAF-targeted therapy and then switch to immunotherapy, according to Dr. Sullivan. That point was echoed by study author Paolo Ascierto, MD, in an email exchange. “For patients with symptomatic disease or very high tumor burden, BRAF/MEK inhibitor should be used first,” said Dr. Ascierto, who is director of the melanoma cancer immunotherapy innovative therapy unit of the National Tumor Institute in Naples, Italy.
BRAF inhibitors as second- or later-line therapy
Aside from that exception, BRAF inhibitors should generally be reserved for second- or later-line therapy, according to Dr. Sullivan. Retrospective data indicate that response to BRAF inhibitors is preserved following immunotherapy, although the duration of benefit is reduced. Unfortunately, that strategy limits BRAF inhibitors to a setting in which they’re less likely to be maximally effective.
To improve matters, Dr. Sullivan suggested that they could be used in the adjuvant setting, where disease burden is lower. He noted that dabrafenib and trametinib are approved for resected stage 3 melanoma and showed similar efficacy to immunotherapy in that setting. Immunotherapy retains efficacy after BRAF-targeted therapy.
Another potential strategy is to come up with 3- or even 4-drug combinations employing BRAF/MEK inhibitors in the second-line setting. A few trials have already begun to investigate this possibility.
The COLUMBUS trial included 192 patients who received encorafenib plus binimetinib (E+B), 191 who received vemurafenib and 194 who received encorafenib. Five-year progression-free survival (PFS) was 23% in the E+B group, and 31% in those with normal lactate dehydrogenase levels. Five-year PFS was 10% with vemurafenib alone (12% with normal lactate dehydrogenase). Progression free survival (PFS) was 19% in the encorafenib group. Five-year overall survival (OS) followed a similar trend: 35% (45% with normal lactate dehydrogenase) in the E+B group, and 21% (28%) in the vemurafenib group. E+B had a median duration of response of 18.6 months, and a disease control rate of 92.2%, compared with 12.3 months and 81.2% with vemurafenib. Median duration of response was 15.5 months in the encorafenib monotherapy group.
The COLUMBUS trial was sponsored by Array BioPharma, which was acquired by Pfizer in July 2019.
Dr. Sullivan has consulted or advised Novartis, Merck, Replimune, Asana Biosciences, Alkermes, Eisai, Pfizer, Iovance Biotherapeutics, OncoSec, AstraZeneca, and Bristol Myers Squibb. Dr. Ascierto has stock or an ownership position in PrimeVax. He has consulted or advised for Bristol Myers Squibb, Roche/Genentech, Merck Sharp & Dohme, Novartis, Array BioPharma, Merck Serono, Pierre Fabre, Incyte, MedImmune, AstraZeneca, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, Nektar, Boehringer Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, OncoSec, Nouscom, Takis Biotech, Lunaphore Technologies, Seattle Genetics, ITeos Therapeutics, Medicenna, and Bio-Al Health.
, according to 5-year follow-up data from the COLUMBUS trial. Among patients with advanced unresectable or metastatic disease who were untreated or who had progressed following immunotherapy, the regimen of encorafenib plus binimetinib produced impressive gains in progression-free and overall survival, compared with historical controls, and are in line with other BRAF/MEK inhibitor combinations. It also outperformed encorafenib and vemurafenib monotherapy regimens.
The findings present good news, but the combination still doesn’t represent the best first-line option, according to Ryan Sullivan, MD, who wrote an accompanying editorial. He pointed out that the previously published DREAMSeq trial showed that a combination of immune checkpoint inhibitors (ICIs) ipilimumab and nivolumab produced a 2-year survival of 72%, compared with 52% for a BRAF inhibitor combination of dabrafenib plus trametinib (P = .0095).
There are three combinations of BRAF and MEK inhibitors that are approved for BRAF mutant melanoma, and any of the seven individual agents and six combinations that are approved by the U.S. Food and Drug Administration- for melanoma can be used in BRAFV600 patients. “The standard of care for most patients with newly diagnosed BRAF mutant melanoma is ... immune checkpoint inhibition, either with anti–PD-1 inhibitor or a combination of immunotherapy with an anti–PD-1 inhibitor. The optimal use of BRAF targeted therapy is unknown but some data supports its use earlier in the disease course (adjuvant setting) or after progression following anti–PD-1 therapy in the advanced disease setting,” wrote Dr. Sullivan in an email. He is associate director of the melanoma program at Massachusetts General Hospital, Boston.
The new study was published online in the Journal of Clinical Oncology.
In his editorial, Dr. Sullivan wrote that anti–PD-1 monoclonal antibodies alone or in combination with anti-CTLA4 receptor therapies is likely the best front-line therapy for BRAFV600 mutant advanced melanoma, with long-term survival ranging from 40% to 50%.
Still, the efficacy of BRAF-targeted therapy makes it important to explore ways to strengthen it further. One possibility is to use it in the front-line setting when a patient is at high risk of rapid progression and death, since analysis from DREAMSeq showed that BRAF-targeted therapy had a better overall survival than immunotherapy during the first 10 months after random assignment. It was only after this time point that the curves reversed and pointed to greater efficacy for immunotherapy. An option would be to treat to maximum tumor regression with BRAF-targeted therapy and then switch to immunotherapy, according to Dr. Sullivan. That point was echoed by study author Paolo Ascierto, MD, in an email exchange. “For patients with symptomatic disease or very high tumor burden, BRAF/MEK inhibitor should be used first,” said Dr. Ascierto, who is director of the melanoma cancer immunotherapy innovative therapy unit of the National Tumor Institute in Naples, Italy.
BRAF inhibitors as second- or later-line therapy
Aside from that exception, BRAF inhibitors should generally be reserved for second- or later-line therapy, according to Dr. Sullivan. Retrospective data indicate that response to BRAF inhibitors is preserved following immunotherapy, although the duration of benefit is reduced. Unfortunately, that strategy limits BRAF inhibitors to a setting in which they’re less likely to be maximally effective.
To improve matters, Dr. Sullivan suggested that they could be used in the adjuvant setting, where disease burden is lower. He noted that dabrafenib and trametinib are approved for resected stage 3 melanoma and showed similar efficacy to immunotherapy in that setting. Immunotherapy retains efficacy after BRAF-targeted therapy.
Another potential strategy is to come up with 3- or even 4-drug combinations employing BRAF/MEK inhibitors in the second-line setting. A few trials have already begun to investigate this possibility.
The COLUMBUS trial included 192 patients who received encorafenib plus binimetinib (E+B), 191 who received vemurafenib and 194 who received encorafenib. Five-year progression-free survival (PFS) was 23% in the E+B group, and 31% in those with normal lactate dehydrogenase levels. Five-year PFS was 10% with vemurafenib alone (12% with normal lactate dehydrogenase). Progression free survival (PFS) was 19% in the encorafenib group. Five-year overall survival (OS) followed a similar trend: 35% (45% with normal lactate dehydrogenase) in the E+B group, and 21% (28%) in the vemurafenib group. E+B had a median duration of response of 18.6 months, and a disease control rate of 92.2%, compared with 12.3 months and 81.2% with vemurafenib. Median duration of response was 15.5 months in the encorafenib monotherapy group.
The COLUMBUS trial was sponsored by Array BioPharma, which was acquired by Pfizer in July 2019.
Dr. Sullivan has consulted or advised Novartis, Merck, Replimune, Asana Biosciences, Alkermes, Eisai, Pfizer, Iovance Biotherapeutics, OncoSec, AstraZeneca, and Bristol Myers Squibb. Dr. Ascierto has stock or an ownership position in PrimeVax. He has consulted or advised for Bristol Myers Squibb, Roche/Genentech, Merck Sharp & Dohme, Novartis, Array BioPharma, Merck Serono, Pierre Fabre, Incyte, MedImmune, AstraZeneca, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, Nektar, Boehringer Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, OncoSec, Nouscom, Takis Biotech, Lunaphore Technologies, Seattle Genetics, ITeos Therapeutics, Medicenna, and Bio-Al Health.
FROM JOURNAL OF CLINICAL ONCOLOGY
Mental health in America: ‘The kids are not alright’
A new report shines a light on the toll the pandemic and other stressors have taken on the mental health of U.S. children and adolescents over the last 6 years.
The report shows a dramatic increase in use of acute care services for depression, anxiety, and other mental health conditions, especially among teens and preteens.
The report – The Kids Are Not Alright: Pediatric Mental Health Care Utilization from 2016-2021 – is the work of researchers at the Clarify Health Institute, the research arm of Clarify Health.
The results are “deeply concerning” and should “spark a conversation” around the need to improve access, utilization, and quality of pediatric behavioral health services, Niall Brennan, chief analytics and privacy officer for the Clarify Health Institute, told this news organization.
‘Startling’ trends
Leveraging an observational, national sample of insurance claims from more than 20 million children aged 1-19 years annually, the researchers observed several disturbing trends in mental health care.
From 2016 to 2021, inpatient (IP) admissions rose 61% (from 30 to 48 visits annually per 1,000) and emergency department visits rose 20% (from 55 to 66 visits annually per 1,000).
Mental health IP admissions ranged from a low of 27% in the West North Central region to a high of 137% in the Middle Atlantic region.
There were substantial increases from 2016 to 2021 in mental health IP admissions among children of all age groups, but particularly among adolescents 12 to 15 years old, increasing 84% among girls and 83% among boys in this age group.
There was also a sharp increase in mental health ED visits among girls and boys aged 12-15 years, increasing 20% overall during the study period.
Mental health IP use grew faster from 2016 to 2021 among children with commercial insurance than among those with Medicaid (103% vs. 40%).
In contrast, mental health–specific ED visits declined 10% among children with commercial insurance and increased by 20% among those with Medicaid.
ED utilization rates in 2021 were nearly twice as high in the Medicaid population, compared with those for children with commercial insurance.
These are “startling” increases, Mr. Brennan said in an interview.
These trends “reinforce health care leaders’ responsibility to address children’s mental health, especially when considering that half of all mental health conditions onset during adolescence and carry into adulthood,” Jean Drouin, MD, Clarify Health’s chief executive office and cofounder, adds in a news release.
“With a growing consensus that mental, behavioral, and physical health intersect, this research report aims to spark a conversation about the overall wellbeing of America’s next generation,” Dr. Drouin says.
Concern for the future
Commenting on the new report, Anish Dube, MD, chair of the American Psychiatric Association’s Council on Children, Adolescents, and their Families, said the findings are “concerning, though unsurprising.”
“They confirm what those of us in clinical practice have experienced in the last several years. The need for mental health services continues to rise every year, while access to adequate help remains lacking,” Dr. Dube said.
“With the recent COVID-19 pandemic, concerns about the effects of climate change, global political uncertainty, and a rapidly changing employment landscape, young people in particular are vulnerable to worries about their future and feelings of helplessness and hopelessness,” he added.
Dr. Dube said there is no one right solution, and addressing this problem must consider individual and local factors.
However, some of the broader interventions needed to tackle the problem include increasing access to care by enforcing mental health parity and increasing the number of trained and qualified mental health professionals, such as child and adolescent psychiatrists, who can assess and treat these conditions in young people before they become major crises and lead to acute interventions like inpatient hospitalization.
“Public health interventions aimed at schools and families in raising awareness of mental health and well-being, and simple, cost-effective interventions to practice mental wellness will also help reduce the burden of mental illness in young people,” Dr. Dube added.
“The APA continues to fight for mental health parity enforcement and for meaningful access to mental health care for children, adolescents, and their families,” Dr. Dube said.
This research was conducted by the Clarify Health Institute. Mr. Brennan and Dr. Dube report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new report shines a light on the toll the pandemic and other stressors have taken on the mental health of U.S. children and adolescents over the last 6 years.
The report shows a dramatic increase in use of acute care services for depression, anxiety, and other mental health conditions, especially among teens and preteens.
The report – The Kids Are Not Alright: Pediatric Mental Health Care Utilization from 2016-2021 – is the work of researchers at the Clarify Health Institute, the research arm of Clarify Health.
The results are “deeply concerning” and should “spark a conversation” around the need to improve access, utilization, and quality of pediatric behavioral health services, Niall Brennan, chief analytics and privacy officer for the Clarify Health Institute, told this news organization.
‘Startling’ trends
Leveraging an observational, national sample of insurance claims from more than 20 million children aged 1-19 years annually, the researchers observed several disturbing trends in mental health care.
From 2016 to 2021, inpatient (IP) admissions rose 61% (from 30 to 48 visits annually per 1,000) and emergency department visits rose 20% (from 55 to 66 visits annually per 1,000).
Mental health IP admissions ranged from a low of 27% in the West North Central region to a high of 137% in the Middle Atlantic region.
There were substantial increases from 2016 to 2021 in mental health IP admissions among children of all age groups, but particularly among adolescents 12 to 15 years old, increasing 84% among girls and 83% among boys in this age group.
There was also a sharp increase in mental health ED visits among girls and boys aged 12-15 years, increasing 20% overall during the study period.
Mental health IP use grew faster from 2016 to 2021 among children with commercial insurance than among those with Medicaid (103% vs. 40%).
In contrast, mental health–specific ED visits declined 10% among children with commercial insurance and increased by 20% among those with Medicaid.
ED utilization rates in 2021 were nearly twice as high in the Medicaid population, compared with those for children with commercial insurance.
These are “startling” increases, Mr. Brennan said in an interview.
These trends “reinforce health care leaders’ responsibility to address children’s mental health, especially when considering that half of all mental health conditions onset during adolescence and carry into adulthood,” Jean Drouin, MD, Clarify Health’s chief executive office and cofounder, adds in a news release.
“With a growing consensus that mental, behavioral, and physical health intersect, this research report aims to spark a conversation about the overall wellbeing of America’s next generation,” Dr. Drouin says.
Concern for the future
Commenting on the new report, Anish Dube, MD, chair of the American Psychiatric Association’s Council on Children, Adolescents, and their Families, said the findings are “concerning, though unsurprising.”
“They confirm what those of us in clinical practice have experienced in the last several years. The need for mental health services continues to rise every year, while access to adequate help remains lacking,” Dr. Dube said.
“With the recent COVID-19 pandemic, concerns about the effects of climate change, global political uncertainty, and a rapidly changing employment landscape, young people in particular are vulnerable to worries about their future and feelings of helplessness and hopelessness,” he added.
Dr. Dube said there is no one right solution, and addressing this problem must consider individual and local factors.
However, some of the broader interventions needed to tackle the problem include increasing access to care by enforcing mental health parity and increasing the number of trained and qualified mental health professionals, such as child and adolescent psychiatrists, who can assess and treat these conditions in young people before they become major crises and lead to acute interventions like inpatient hospitalization.
“Public health interventions aimed at schools and families in raising awareness of mental health and well-being, and simple, cost-effective interventions to practice mental wellness will also help reduce the burden of mental illness in young people,” Dr. Dube added.
“The APA continues to fight for mental health parity enforcement and for meaningful access to mental health care for children, adolescents, and their families,” Dr. Dube said.
This research was conducted by the Clarify Health Institute. Mr. Brennan and Dr. Dube report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new report shines a light on the toll the pandemic and other stressors have taken on the mental health of U.S. children and adolescents over the last 6 years.
The report shows a dramatic increase in use of acute care services for depression, anxiety, and other mental health conditions, especially among teens and preteens.
The report – The Kids Are Not Alright: Pediatric Mental Health Care Utilization from 2016-2021 – is the work of researchers at the Clarify Health Institute, the research arm of Clarify Health.
The results are “deeply concerning” and should “spark a conversation” around the need to improve access, utilization, and quality of pediatric behavioral health services, Niall Brennan, chief analytics and privacy officer for the Clarify Health Institute, told this news organization.
‘Startling’ trends
Leveraging an observational, national sample of insurance claims from more than 20 million children aged 1-19 years annually, the researchers observed several disturbing trends in mental health care.
From 2016 to 2021, inpatient (IP) admissions rose 61% (from 30 to 48 visits annually per 1,000) and emergency department visits rose 20% (from 55 to 66 visits annually per 1,000).
Mental health IP admissions ranged from a low of 27% in the West North Central region to a high of 137% in the Middle Atlantic region.
There were substantial increases from 2016 to 2021 in mental health IP admissions among children of all age groups, but particularly among adolescents 12 to 15 years old, increasing 84% among girls and 83% among boys in this age group.
There was also a sharp increase in mental health ED visits among girls and boys aged 12-15 years, increasing 20% overall during the study period.
Mental health IP use grew faster from 2016 to 2021 among children with commercial insurance than among those with Medicaid (103% vs. 40%).
In contrast, mental health–specific ED visits declined 10% among children with commercial insurance and increased by 20% among those with Medicaid.
ED utilization rates in 2021 were nearly twice as high in the Medicaid population, compared with those for children with commercial insurance.
These are “startling” increases, Mr. Brennan said in an interview.
These trends “reinforce health care leaders’ responsibility to address children’s mental health, especially when considering that half of all mental health conditions onset during adolescence and carry into adulthood,” Jean Drouin, MD, Clarify Health’s chief executive office and cofounder, adds in a news release.
“With a growing consensus that mental, behavioral, and physical health intersect, this research report aims to spark a conversation about the overall wellbeing of America’s next generation,” Dr. Drouin says.
Concern for the future
Commenting on the new report, Anish Dube, MD, chair of the American Psychiatric Association’s Council on Children, Adolescents, and their Families, said the findings are “concerning, though unsurprising.”
“They confirm what those of us in clinical practice have experienced in the last several years. The need for mental health services continues to rise every year, while access to adequate help remains lacking,” Dr. Dube said.
“With the recent COVID-19 pandemic, concerns about the effects of climate change, global political uncertainty, and a rapidly changing employment landscape, young people in particular are vulnerable to worries about their future and feelings of helplessness and hopelessness,” he added.
Dr. Dube said there is no one right solution, and addressing this problem must consider individual and local factors.
However, some of the broader interventions needed to tackle the problem include increasing access to care by enforcing mental health parity and increasing the number of trained and qualified mental health professionals, such as child and adolescent psychiatrists, who can assess and treat these conditions in young people before they become major crises and lead to acute interventions like inpatient hospitalization.
“Public health interventions aimed at schools and families in raising awareness of mental health and well-being, and simple, cost-effective interventions to practice mental wellness will also help reduce the burden of mental illness in young people,” Dr. Dube added.
“The APA continues to fight for mental health parity enforcement and for meaningful access to mental health care for children, adolescents, and their families,” Dr. Dube said.
This research was conducted by the Clarify Health Institute. Mr. Brennan and Dr. Dube report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New ESC guidelines for cutting CV risk in noncardiac surgery
The European Society of Cardiology guidelines on cardiovascular assessment and management of patients undergoing noncardiac surgery have seen extensive revision since the 2014 version.
They still have the same aim – to prevent surgery-related bleeding complications, perioperative myocardial infarction/injury (PMI), stent thrombosis, acute heart failure, arrhythmias, pulmonary embolism, ischemic stroke, and cardiovascular (CV) death.
Cochairpersons Sigrun Halvorsen, MD, PhD, and Julinda Mehilli, MD, presented highlights from the guidelines at the annual congress of the European Society of Cardiology and the document was simultaneously published online in the European Heart Journal.
The document classifies noncardiac surgery into three levels of 30-day risk of CV death, MI, or stroke. Low (< 1%) risk includes eye or thyroid surgery; intermediate (1%-5%) risk includes knee or hip replacement or renal transplant; and high (> 5%) risk includes aortic aneurysm, lung transplant, or pancreatic or bladder cancer surgery (see more examples below).
It classifies patients as low risk if they are younger than 65 without CV disease or CV risk factors (smoking, hypertension, diabetes, dyslipidemia, family history); intermediate risk if they are 65 or older or have CV risk factors; and high risk if they have CVD.
In an interview, Dr. Halvorsen, professor in cardiology, University of Oslo, zeroed in on three important revisions:
First, recommendations for preoperative ECG and biomarkers are more specific, he noted.
The guidelines advise that before intermediate- or high-risk noncardiac surgery, in patients who have known CVD, CV risk factors (including age 65 or older), or symptoms suggestive of CVD:
- It is recommended to obtain a preoperative 12-lead ECG (class I).
- It is recommended to measure high-sensitivity cardiac troponin T (hs-cTn T) or high-sensitivity cardiac troponin I (hs-cTn I). It is also recommended to measure these biomarkers at 24 hours and 48 hours post surgery (class I).
- It should be considered to measure B-type natriuretic peptide or N-terminal of the prohormone BNP (NT-proBNP).
However, for low-risk patients undergoing low- and intermediate-risk noncardiac surgery, it is not recommended to routinely obtain preoperative ECG, hs-cTn T/I, or BNP/NT-proBNP concentrations (class III).
Troponins have a stronger class I recommendation, compared with the IIA recommendation for BNP, because they are useful for preoperative risk stratification and for diagnosis of PMI, Dr. Halvorsen explained. “Patients receive painkillers after surgery and may have no pain,” she noted, but they may have PMI, which has a bad prognosis.
Second, the guidelines recommend that “all patients should stop smoking 4 weeks before noncardiac surgery [class I],” she noted. Clinicians should also “measure hemoglobin, and if the patient is anemic, treat the anemia.”
Third, the sections on antithrombotic treatment have been significantly revised. “Bridging – stopping an oral antithrombotic drug and switching to a subcutaneous or IV drug – has been common,” Dr. Halvorsen said, “but recently we have new evidence that in most cases that increases the risk of bleeding.”
“We are [now] much more restrictive with respect to bridging” with unfractionated heparin or low-molecular-weight heparin, she said. “We recommend against bridging in patients with low to moderate thrombotic risk,” and bridging should only be considered in patients with mechanical prosthetic heart valves or with very high thrombotic risk.
More preoperative recommendations
In the guideline overview session at the congress, Dr. Halverson highlighted some of the new recommendations for preoperative risk assessment.
If time allows, it is recommended to optimize guideline-recommended treatment of CVD and control of CV risk factors including blood pressure, dyslipidemia, and diabetes, before noncardiac surgery (class I).
Patients commonly have “murmurs, chest pain, dyspnea, and edema that may suggest severe CVD, but may also be caused by noncardiac disease,” she noted. The guidelines state that “for patients with a newly detected murmur and symptoms or signs of CVD, transthoracic echocardiography is recommended before noncardiac surgery (class I).
“Many studies have been performed to try to find out if initiation of specific drugs before surgery could reduce the risk of complications,” Dr. Halvorsen noted. However, few have shown any benefit and “the question of presurgery initiation of beta-blockers has been greatly debated,” she said. “We have again reviewed the literature and concluded ‘Routine initiation of beta-blockers perioperatively is not recommended (class IIIA).’ “
“We adhere to the guidelines on acute and chronic coronary syndrome recommending 6-12 months of dual antiplatelet treatment as a standard before elective surgery,” she said. “However, in case of time-sensitive surgery, the duration of that treatment can be shortened down to a minimum of 1 month after elective PCI and a minimum of 3 months after PCI and ACS.”
Patients with specific types of CVD
Dr. Mehilli, a professor at Landshut-Achdorf (Germany) Hospital, highlighted some new guideline recommendations for patients who have specific types of cardiovascular disease.
Coronary artery disease (CAD). “For chronic coronary syndrome, a cardiac workup is recommended only for patients undergoing intermediate risk or high-risk noncardiac surgery.”
“Stress imaging should be considered before any high risk, noncardiac surgery in asymptomatic patients with poor functional capacity and prior PCI or coronary artery bypass graft (new recommendation, class IIa).”
Mitral valve regurgitation. For patients undergoing scheduled noncardiac surgery, who remain symptomatic despite guideline-directed medical treatment for mitral valve regurgitation (including resynchronization and myocardial revascularization), consider a valve intervention – either transcatheter or surgical – before noncardiac surgery in eligible patients with acceptable procedural risk (new recommendation).
Cardiac implantable electronic devices (CIED). For high-risk patients with CIEDs undergoing noncardiac surgery with high probability of electromagnetic interference, a CIED checkup and necessary reprogramming immediately before the procedure should be considered (new recommendation).
Arrhythmias. “I want only to stress,” Dr. Mehilli said, “in patients with atrial fibrillation with acute or worsening hemodynamic instability undergoing noncardiac surgery, an emergency electrical cardioversion is recommended (class I).”
Peripheral artery disease (PAD) and abdominal aortic aneurysm. For these patients “we do not recommend a routine referral for a cardiac workup. But we recommend it for patients with poor functional capacity or with significant risk factors or symptoms (new recommendations).”
Chronic arterial hypertension. “We have modified the recommendation, recommending avoidance of large perioperative fluctuations in blood pressure, and we do not recommend deferring noncardiac surgery in patients with stage 1 or 2 hypertension,” she said.
Postoperative cardiovascular complications
The most frequent postoperative cardiovascular complication is PMI, Dr. Mehilli noted.
“In the BASEL-PMI registry, the incidence of this complication around intermediate or high-risk noncardiac surgery was up to 15% among patients older than 65 years or with a history of CAD or PAD, which makes this kind of complication really important to prevent, to assess, and to know how to treat.”
“It is recommended to have a high awareness for perioperative cardiovascular complications, combined with surveillance for PMI in patients undergoing intermediate- or high-risk noncardiac surgery” based on serial measurements of high-sensitivity cardiac troponin.
The guidelines define PMI as “an increase in the delta of high-sensitivity troponin more than the upper level of normal,” Dr. Mehilli said. “It’s different from the one used in a rule-in algorithm for non-STEMI acute coronary syndrome.”
Postoperative atrial fibrillation (AFib) is observed in 2%-30% of noncardiac surgery patients in different registries, particularly in patients undergoing intermediate or high-risk noncardiac surgery, she noted.
“We propose an algorithm on how to prevent and treat this complication. I want to highlight that in patients with hemodynamic unstable postoperative AF[ib], an emergency cardioversion is indicated. For the others, a rate control with the target heart rate of less than 110 beats per minute is indicated.”
In patients with postoperative AFib, long-term oral anticoagulation therapy should be considered in all patients at risk for stroke, considering the anticipated net clinical benefit of oral anticoagulation therapy as well as informed patient preference (new recommendations).
Routine use of beta-blockers to prevent postoperative AFib in patients undergoing noncardiac surgery is not recommended.
The document also covers the management of patients with kidney disease, diabetes, cancer, obesity, and COVID-19. In general, elective noncardiac surgery should be postponed after a patient has COVID-19, until he or she recovers completely, and coexisting conditions are optimized.
The guidelines are available from the ESC website in several formats: pocket guidelines, pocket guidelines smartphone app, guidelines slide set, essential messages, and the European Heart Journal article.
Noncardiac surgery risk categories
The guideline includes a table that classifies noncardiac surgeries into three groups, based on the associated 30-day risk of death, MI, or stroke:
- Low (< 1%): breast, dental, eye, thyroid, and minor gynecologic, orthopedic, and urologic surgery.
- Intermediate (1%-5%): carotid surgery, endovascular aortic aneurysm repair, gallbladder surgery, head or neck surgery, hernia repair, peripheral arterial angioplasty, renal transplant, major gynecologic, orthopedic, or neurologic (hip or spine) surgery, or urologic surgery
- High (> 5%): aortic and major vascular surgery (including aortic aneurysm), bladder removal (usually as a result of cancer), limb amputation, lung or liver transplant, pancreatic surgery, or perforated bowel repair.
The guidelines were endorsed by the European Society of Anaesthesiology and Intensive Care. The guideline authors reported numerous disclosures.
A version of this article first appeared on Medscape.com.
The European Society of Cardiology guidelines on cardiovascular assessment and management of patients undergoing noncardiac surgery have seen extensive revision since the 2014 version.
They still have the same aim – to prevent surgery-related bleeding complications, perioperative myocardial infarction/injury (PMI), stent thrombosis, acute heart failure, arrhythmias, pulmonary embolism, ischemic stroke, and cardiovascular (CV) death.
Cochairpersons Sigrun Halvorsen, MD, PhD, and Julinda Mehilli, MD, presented highlights from the guidelines at the annual congress of the European Society of Cardiology and the document was simultaneously published online in the European Heart Journal.
The document classifies noncardiac surgery into three levels of 30-day risk of CV death, MI, or stroke. Low (< 1%) risk includes eye or thyroid surgery; intermediate (1%-5%) risk includes knee or hip replacement or renal transplant; and high (> 5%) risk includes aortic aneurysm, lung transplant, or pancreatic or bladder cancer surgery (see more examples below).
It classifies patients as low risk if they are younger than 65 without CV disease or CV risk factors (smoking, hypertension, diabetes, dyslipidemia, family history); intermediate risk if they are 65 or older or have CV risk factors; and high risk if they have CVD.
In an interview, Dr. Halvorsen, professor in cardiology, University of Oslo, zeroed in on three important revisions:
First, recommendations for preoperative ECG and biomarkers are more specific, he noted.
The guidelines advise that before intermediate- or high-risk noncardiac surgery, in patients who have known CVD, CV risk factors (including age 65 or older), or symptoms suggestive of CVD:
- It is recommended to obtain a preoperative 12-lead ECG (class I).
- It is recommended to measure high-sensitivity cardiac troponin T (hs-cTn T) or high-sensitivity cardiac troponin I (hs-cTn I). It is also recommended to measure these biomarkers at 24 hours and 48 hours post surgery (class I).
- It should be considered to measure B-type natriuretic peptide or N-terminal of the prohormone BNP (NT-proBNP).
However, for low-risk patients undergoing low- and intermediate-risk noncardiac surgery, it is not recommended to routinely obtain preoperative ECG, hs-cTn T/I, or BNP/NT-proBNP concentrations (class III).
Troponins have a stronger class I recommendation, compared with the IIA recommendation for BNP, because they are useful for preoperative risk stratification and for diagnosis of PMI, Dr. Halvorsen explained. “Patients receive painkillers after surgery and may have no pain,” she noted, but they may have PMI, which has a bad prognosis.
Second, the guidelines recommend that “all patients should stop smoking 4 weeks before noncardiac surgery [class I],” she noted. Clinicians should also “measure hemoglobin, and if the patient is anemic, treat the anemia.”
Third, the sections on antithrombotic treatment have been significantly revised. “Bridging – stopping an oral antithrombotic drug and switching to a subcutaneous or IV drug – has been common,” Dr. Halvorsen said, “but recently we have new evidence that in most cases that increases the risk of bleeding.”
“We are [now] much more restrictive with respect to bridging” with unfractionated heparin or low-molecular-weight heparin, she said. “We recommend against bridging in patients with low to moderate thrombotic risk,” and bridging should only be considered in patients with mechanical prosthetic heart valves or with very high thrombotic risk.
More preoperative recommendations
In the guideline overview session at the congress, Dr. Halverson highlighted some of the new recommendations for preoperative risk assessment.
If time allows, it is recommended to optimize guideline-recommended treatment of CVD and control of CV risk factors including blood pressure, dyslipidemia, and diabetes, before noncardiac surgery (class I).
Patients commonly have “murmurs, chest pain, dyspnea, and edema that may suggest severe CVD, but may also be caused by noncardiac disease,” she noted. The guidelines state that “for patients with a newly detected murmur and symptoms or signs of CVD, transthoracic echocardiography is recommended before noncardiac surgery (class I).
“Many studies have been performed to try to find out if initiation of specific drugs before surgery could reduce the risk of complications,” Dr. Halvorsen noted. However, few have shown any benefit and “the question of presurgery initiation of beta-blockers has been greatly debated,” she said. “We have again reviewed the literature and concluded ‘Routine initiation of beta-blockers perioperatively is not recommended (class IIIA).’ “
“We adhere to the guidelines on acute and chronic coronary syndrome recommending 6-12 months of dual antiplatelet treatment as a standard before elective surgery,” she said. “However, in case of time-sensitive surgery, the duration of that treatment can be shortened down to a minimum of 1 month after elective PCI and a minimum of 3 months after PCI and ACS.”
Patients with specific types of CVD
Dr. Mehilli, a professor at Landshut-Achdorf (Germany) Hospital, highlighted some new guideline recommendations for patients who have specific types of cardiovascular disease.
Coronary artery disease (CAD). “For chronic coronary syndrome, a cardiac workup is recommended only for patients undergoing intermediate risk or high-risk noncardiac surgery.”
“Stress imaging should be considered before any high risk, noncardiac surgery in asymptomatic patients with poor functional capacity and prior PCI or coronary artery bypass graft (new recommendation, class IIa).”
Mitral valve regurgitation. For patients undergoing scheduled noncardiac surgery, who remain symptomatic despite guideline-directed medical treatment for mitral valve regurgitation (including resynchronization and myocardial revascularization), consider a valve intervention – either transcatheter or surgical – before noncardiac surgery in eligible patients with acceptable procedural risk (new recommendation).
Cardiac implantable electronic devices (CIED). For high-risk patients with CIEDs undergoing noncardiac surgery with high probability of electromagnetic interference, a CIED checkup and necessary reprogramming immediately before the procedure should be considered (new recommendation).
Arrhythmias. “I want only to stress,” Dr. Mehilli said, “in patients with atrial fibrillation with acute or worsening hemodynamic instability undergoing noncardiac surgery, an emergency electrical cardioversion is recommended (class I).”
Peripheral artery disease (PAD) and abdominal aortic aneurysm. For these patients “we do not recommend a routine referral for a cardiac workup. But we recommend it for patients with poor functional capacity or with significant risk factors or symptoms (new recommendations).”
Chronic arterial hypertension. “We have modified the recommendation, recommending avoidance of large perioperative fluctuations in blood pressure, and we do not recommend deferring noncardiac surgery in patients with stage 1 or 2 hypertension,” she said.
Postoperative cardiovascular complications
The most frequent postoperative cardiovascular complication is PMI, Dr. Mehilli noted.
“In the BASEL-PMI registry, the incidence of this complication around intermediate or high-risk noncardiac surgery was up to 15% among patients older than 65 years or with a history of CAD or PAD, which makes this kind of complication really important to prevent, to assess, and to know how to treat.”
“It is recommended to have a high awareness for perioperative cardiovascular complications, combined with surveillance for PMI in patients undergoing intermediate- or high-risk noncardiac surgery” based on serial measurements of high-sensitivity cardiac troponin.
The guidelines define PMI as “an increase in the delta of high-sensitivity troponin more than the upper level of normal,” Dr. Mehilli said. “It’s different from the one used in a rule-in algorithm for non-STEMI acute coronary syndrome.”
Postoperative atrial fibrillation (AFib) is observed in 2%-30% of noncardiac surgery patients in different registries, particularly in patients undergoing intermediate or high-risk noncardiac surgery, she noted.
“We propose an algorithm on how to prevent and treat this complication. I want to highlight that in patients with hemodynamic unstable postoperative AF[ib], an emergency cardioversion is indicated. For the others, a rate control with the target heart rate of less than 110 beats per minute is indicated.”
In patients with postoperative AFib, long-term oral anticoagulation therapy should be considered in all patients at risk for stroke, considering the anticipated net clinical benefit of oral anticoagulation therapy as well as informed patient preference (new recommendations).
Routine use of beta-blockers to prevent postoperative AFib in patients undergoing noncardiac surgery is not recommended.
The document also covers the management of patients with kidney disease, diabetes, cancer, obesity, and COVID-19. In general, elective noncardiac surgery should be postponed after a patient has COVID-19, until he or she recovers completely, and coexisting conditions are optimized.
The guidelines are available from the ESC website in several formats: pocket guidelines, pocket guidelines smartphone app, guidelines slide set, essential messages, and the European Heart Journal article.
Noncardiac surgery risk categories
The guideline includes a table that classifies noncardiac surgeries into three groups, based on the associated 30-day risk of death, MI, or stroke:
- Low (< 1%): breast, dental, eye, thyroid, and minor gynecologic, orthopedic, and urologic surgery.
- Intermediate (1%-5%): carotid surgery, endovascular aortic aneurysm repair, gallbladder surgery, head or neck surgery, hernia repair, peripheral arterial angioplasty, renal transplant, major gynecologic, orthopedic, or neurologic (hip or spine) surgery, or urologic surgery
- High (> 5%): aortic and major vascular surgery (including aortic aneurysm), bladder removal (usually as a result of cancer), limb amputation, lung or liver transplant, pancreatic surgery, or perforated bowel repair.
The guidelines were endorsed by the European Society of Anaesthesiology and Intensive Care. The guideline authors reported numerous disclosures.
A version of this article first appeared on Medscape.com.
The European Society of Cardiology guidelines on cardiovascular assessment and management of patients undergoing noncardiac surgery have seen extensive revision since the 2014 version.
They still have the same aim – to prevent surgery-related bleeding complications, perioperative myocardial infarction/injury (PMI), stent thrombosis, acute heart failure, arrhythmias, pulmonary embolism, ischemic stroke, and cardiovascular (CV) death.
Cochairpersons Sigrun Halvorsen, MD, PhD, and Julinda Mehilli, MD, presented highlights from the guidelines at the annual congress of the European Society of Cardiology and the document was simultaneously published online in the European Heart Journal.
The document classifies noncardiac surgery into three levels of 30-day risk of CV death, MI, or stroke. Low (< 1%) risk includes eye or thyroid surgery; intermediate (1%-5%) risk includes knee or hip replacement or renal transplant; and high (> 5%) risk includes aortic aneurysm, lung transplant, or pancreatic or bladder cancer surgery (see more examples below).
It classifies patients as low risk if they are younger than 65 without CV disease or CV risk factors (smoking, hypertension, diabetes, dyslipidemia, family history); intermediate risk if they are 65 or older or have CV risk factors; and high risk if they have CVD.
In an interview, Dr. Halvorsen, professor in cardiology, University of Oslo, zeroed in on three important revisions:
First, recommendations for preoperative ECG and biomarkers are more specific, he noted.
The guidelines advise that before intermediate- or high-risk noncardiac surgery, in patients who have known CVD, CV risk factors (including age 65 or older), or symptoms suggestive of CVD:
- It is recommended to obtain a preoperative 12-lead ECG (class I).
- It is recommended to measure high-sensitivity cardiac troponin T (hs-cTn T) or high-sensitivity cardiac troponin I (hs-cTn I). It is also recommended to measure these biomarkers at 24 hours and 48 hours post surgery (class I).
- It should be considered to measure B-type natriuretic peptide or N-terminal of the prohormone BNP (NT-proBNP).
However, for low-risk patients undergoing low- and intermediate-risk noncardiac surgery, it is not recommended to routinely obtain preoperative ECG, hs-cTn T/I, or BNP/NT-proBNP concentrations (class III).
Troponins have a stronger class I recommendation, compared with the IIA recommendation for BNP, because they are useful for preoperative risk stratification and for diagnosis of PMI, Dr. Halvorsen explained. “Patients receive painkillers after surgery and may have no pain,” she noted, but they may have PMI, which has a bad prognosis.
Second, the guidelines recommend that “all patients should stop smoking 4 weeks before noncardiac surgery [class I],” she noted. Clinicians should also “measure hemoglobin, and if the patient is anemic, treat the anemia.”
Third, the sections on antithrombotic treatment have been significantly revised. “Bridging – stopping an oral antithrombotic drug and switching to a subcutaneous or IV drug – has been common,” Dr. Halvorsen said, “but recently we have new evidence that in most cases that increases the risk of bleeding.”
“We are [now] much more restrictive with respect to bridging” with unfractionated heparin or low-molecular-weight heparin, she said. “We recommend against bridging in patients with low to moderate thrombotic risk,” and bridging should only be considered in patients with mechanical prosthetic heart valves or with very high thrombotic risk.
More preoperative recommendations
In the guideline overview session at the congress, Dr. Halverson highlighted some of the new recommendations for preoperative risk assessment.
If time allows, it is recommended to optimize guideline-recommended treatment of CVD and control of CV risk factors including blood pressure, dyslipidemia, and diabetes, before noncardiac surgery (class I).
Patients commonly have “murmurs, chest pain, dyspnea, and edema that may suggest severe CVD, but may also be caused by noncardiac disease,” she noted. The guidelines state that “for patients with a newly detected murmur and symptoms or signs of CVD, transthoracic echocardiography is recommended before noncardiac surgery (class I).
“Many studies have been performed to try to find out if initiation of specific drugs before surgery could reduce the risk of complications,” Dr. Halvorsen noted. However, few have shown any benefit and “the question of presurgery initiation of beta-blockers has been greatly debated,” she said. “We have again reviewed the literature and concluded ‘Routine initiation of beta-blockers perioperatively is not recommended (class IIIA).’ “
“We adhere to the guidelines on acute and chronic coronary syndrome recommending 6-12 months of dual antiplatelet treatment as a standard before elective surgery,” she said. “However, in case of time-sensitive surgery, the duration of that treatment can be shortened down to a minimum of 1 month after elective PCI and a minimum of 3 months after PCI and ACS.”
Patients with specific types of CVD
Dr. Mehilli, a professor at Landshut-Achdorf (Germany) Hospital, highlighted some new guideline recommendations for patients who have specific types of cardiovascular disease.
Coronary artery disease (CAD). “For chronic coronary syndrome, a cardiac workup is recommended only for patients undergoing intermediate risk or high-risk noncardiac surgery.”
“Stress imaging should be considered before any high risk, noncardiac surgery in asymptomatic patients with poor functional capacity and prior PCI or coronary artery bypass graft (new recommendation, class IIa).”
Mitral valve regurgitation. For patients undergoing scheduled noncardiac surgery, who remain symptomatic despite guideline-directed medical treatment for mitral valve regurgitation (including resynchronization and myocardial revascularization), consider a valve intervention – either transcatheter or surgical – before noncardiac surgery in eligible patients with acceptable procedural risk (new recommendation).
Cardiac implantable electronic devices (CIED). For high-risk patients with CIEDs undergoing noncardiac surgery with high probability of electromagnetic interference, a CIED checkup and necessary reprogramming immediately before the procedure should be considered (new recommendation).
Arrhythmias. “I want only to stress,” Dr. Mehilli said, “in patients with atrial fibrillation with acute or worsening hemodynamic instability undergoing noncardiac surgery, an emergency electrical cardioversion is recommended (class I).”
Peripheral artery disease (PAD) and abdominal aortic aneurysm. For these patients “we do not recommend a routine referral for a cardiac workup. But we recommend it for patients with poor functional capacity or with significant risk factors or symptoms (new recommendations).”
Chronic arterial hypertension. “We have modified the recommendation, recommending avoidance of large perioperative fluctuations in blood pressure, and we do not recommend deferring noncardiac surgery in patients with stage 1 or 2 hypertension,” she said.
Postoperative cardiovascular complications
The most frequent postoperative cardiovascular complication is PMI, Dr. Mehilli noted.
“In the BASEL-PMI registry, the incidence of this complication around intermediate or high-risk noncardiac surgery was up to 15% among patients older than 65 years or with a history of CAD or PAD, which makes this kind of complication really important to prevent, to assess, and to know how to treat.”
“It is recommended to have a high awareness for perioperative cardiovascular complications, combined with surveillance for PMI in patients undergoing intermediate- or high-risk noncardiac surgery” based on serial measurements of high-sensitivity cardiac troponin.
The guidelines define PMI as “an increase in the delta of high-sensitivity troponin more than the upper level of normal,” Dr. Mehilli said. “It’s different from the one used in a rule-in algorithm for non-STEMI acute coronary syndrome.”
Postoperative atrial fibrillation (AFib) is observed in 2%-30% of noncardiac surgery patients in different registries, particularly in patients undergoing intermediate or high-risk noncardiac surgery, she noted.
“We propose an algorithm on how to prevent and treat this complication. I want to highlight that in patients with hemodynamic unstable postoperative AF[ib], an emergency cardioversion is indicated. For the others, a rate control with the target heart rate of less than 110 beats per minute is indicated.”
In patients with postoperative AFib, long-term oral anticoagulation therapy should be considered in all patients at risk for stroke, considering the anticipated net clinical benefit of oral anticoagulation therapy as well as informed patient preference (new recommendations).
Routine use of beta-blockers to prevent postoperative AFib in patients undergoing noncardiac surgery is not recommended.
The document also covers the management of patients with kidney disease, diabetes, cancer, obesity, and COVID-19. In general, elective noncardiac surgery should be postponed after a patient has COVID-19, until he or she recovers completely, and coexisting conditions are optimized.
The guidelines are available from the ESC website in several formats: pocket guidelines, pocket guidelines smartphone app, guidelines slide set, essential messages, and the European Heart Journal article.
Noncardiac surgery risk categories
The guideline includes a table that classifies noncardiac surgeries into three groups, based on the associated 30-day risk of death, MI, or stroke:
- Low (< 1%): breast, dental, eye, thyroid, and minor gynecologic, orthopedic, and urologic surgery.
- Intermediate (1%-5%): carotid surgery, endovascular aortic aneurysm repair, gallbladder surgery, head or neck surgery, hernia repair, peripheral arterial angioplasty, renal transplant, major gynecologic, orthopedic, or neurologic (hip or spine) surgery, or urologic surgery
- High (> 5%): aortic and major vascular surgery (including aortic aneurysm), bladder removal (usually as a result of cancer), limb amputation, lung or liver transplant, pancreatic surgery, or perforated bowel repair.
The guidelines were endorsed by the European Society of Anaesthesiology and Intensive Care. The guideline authors reported numerous disclosures.
A version of this article first appeared on Medscape.com.
FROM ESC CONGRESS 2022
Vitamins or cocoa: Which preserves cognition?
Unexpected results from a phase 3 trial exploring the effect of multivitamins and cognition have now been published.
Originally presented last November at the 14th Clinical Trials on Alzheimer’s Disease (CTAD) conference, this is the first large-scale, long-term randomized controlled trial to examine the effects of cocoa extract and multivitamins on global cognition. The trial’s primary focus was on cocoa extract, which earlier studies suggest may preserve cognitive function. Analyzing the effect of multivitamins was a secondary outcome.
Showing vitamins, but not cocoa, were beneficial is the exact opposite of what researchers expected. Still, the results offer an interesting new direction for future study, lead investigator Laura D. Baker, PhD, professor of gerontology and geriatric medicine at Wake Forest University, Winston-Salem, N.C., said in an interview.
“This study made us take notice of a pathway for possible cognitive protection,” Dr. Baker said. “Without this study, we would never have looked down that road.”
The full results were published online in Alzheimer’s and Dementia.
Unexpected effect
The COSMOS-Mind study is a substudy to a larger parent trial called COSMOS. It investigated the effects of cocoa extract and a standard multivitamin-mineral on cardiovascular and cancer outcomes in more than 21,000 older participants.
In COSMOS-Mind, researchers tested whether daily intake of cocoa extract vs. placebo and a multivitamin-mineral vs. placebo improved cognition in older adults.
More than 2,200 participants aged 65 and older were enrolled and followed for 3 years. They completed tests over the telephone at baseline and annually to evaluate memory and other cognitive abilities.
Results showed cocoa extract had no effect on global cognition compared with placebo (mean z-score, 0.03; P = .28). Daily multivitamin use, however, did show significant benefits on global cognition vs. placebo (mean z, 0.07, P = .007).
The beneficial effect was most pronounced in participants with a history of cardiovascular disease (no history 0.06 vs. history 0.14; P = .01).
Researchers found similar protective effects for memory and executive function.
Dr. Baker suggested one possible explanation for the positive effects of multivitamins may be the boost in micronutrients and essential minerals they provided.
“With nutrient-deficient diets plus a high prevalence of cardiovascular disease, diabetes, and other medical comorbidities that we know impact the bioavailability of these nutrients, we are possibly dealing with older adults who are at below optimum in terms of their essential micronutrients and minerals,” she said.
“Even suboptimum levels of micronutrients and essential minerals can have significant consequences for brain health,” she added.
More research needed
Intriguing as the results may be, more work is needed before the findings could affect nutritional guidance, according to Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association.
“While the Alzheimer’s Association is encouraged by these results, we are not ready to recommend widespread use of a multivitamin supplement to reduce risk of cognitive decline in older adults,” Dr. Carrillo said in a statement.
“For now, and until there is more data, people should talk with their health care providers about the benefits and risks of all dietary supplements, including multivitamins,” she added.
Dr. Baker agreed, noting that the study was not designed to measure multivitamin use as a primary outcome. In addition, nearly 90% of the participants were non-Hispanic White, which is not representative of the overall population demographics.
The investigators are now designing another, larger trial that would include a more diverse participant pool. It will be aimed specifically at learning more about how and why multivitamins seem to offer a protective effect on cognition, Dr. Baker noted.
The study was funded by the National Institute on Aging of the National Institutes of Health. Dr. Baker and Dr. Carrillo report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Unexpected results from a phase 3 trial exploring the effect of multivitamins and cognition have now been published.
Originally presented last November at the 14th Clinical Trials on Alzheimer’s Disease (CTAD) conference, this is the first large-scale, long-term randomized controlled trial to examine the effects of cocoa extract and multivitamins on global cognition. The trial’s primary focus was on cocoa extract, which earlier studies suggest may preserve cognitive function. Analyzing the effect of multivitamins was a secondary outcome.
Showing vitamins, but not cocoa, were beneficial is the exact opposite of what researchers expected. Still, the results offer an interesting new direction for future study, lead investigator Laura D. Baker, PhD, professor of gerontology and geriatric medicine at Wake Forest University, Winston-Salem, N.C., said in an interview.
“This study made us take notice of a pathway for possible cognitive protection,” Dr. Baker said. “Without this study, we would never have looked down that road.”
The full results were published online in Alzheimer’s and Dementia.
Unexpected effect
The COSMOS-Mind study is a substudy to a larger parent trial called COSMOS. It investigated the effects of cocoa extract and a standard multivitamin-mineral on cardiovascular and cancer outcomes in more than 21,000 older participants.
In COSMOS-Mind, researchers tested whether daily intake of cocoa extract vs. placebo and a multivitamin-mineral vs. placebo improved cognition in older adults.
More than 2,200 participants aged 65 and older were enrolled and followed for 3 years. They completed tests over the telephone at baseline and annually to evaluate memory and other cognitive abilities.
Results showed cocoa extract had no effect on global cognition compared with placebo (mean z-score, 0.03; P = .28). Daily multivitamin use, however, did show significant benefits on global cognition vs. placebo (mean z, 0.07, P = .007).
The beneficial effect was most pronounced in participants with a history of cardiovascular disease (no history 0.06 vs. history 0.14; P = .01).
Researchers found similar protective effects for memory and executive function.
Dr. Baker suggested one possible explanation for the positive effects of multivitamins may be the boost in micronutrients and essential minerals they provided.
“With nutrient-deficient diets plus a high prevalence of cardiovascular disease, diabetes, and other medical comorbidities that we know impact the bioavailability of these nutrients, we are possibly dealing with older adults who are at below optimum in terms of their essential micronutrients and minerals,” she said.
“Even suboptimum levels of micronutrients and essential minerals can have significant consequences for brain health,” she added.
More research needed
Intriguing as the results may be, more work is needed before the findings could affect nutritional guidance, according to Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association.
“While the Alzheimer’s Association is encouraged by these results, we are not ready to recommend widespread use of a multivitamin supplement to reduce risk of cognitive decline in older adults,” Dr. Carrillo said in a statement.
“For now, and until there is more data, people should talk with their health care providers about the benefits and risks of all dietary supplements, including multivitamins,” she added.
Dr. Baker agreed, noting that the study was not designed to measure multivitamin use as a primary outcome. In addition, nearly 90% of the participants were non-Hispanic White, which is not representative of the overall population demographics.
The investigators are now designing another, larger trial that would include a more diverse participant pool. It will be aimed specifically at learning more about how and why multivitamins seem to offer a protective effect on cognition, Dr. Baker noted.
The study was funded by the National Institute on Aging of the National Institutes of Health. Dr. Baker and Dr. Carrillo report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Unexpected results from a phase 3 trial exploring the effect of multivitamins and cognition have now been published.
Originally presented last November at the 14th Clinical Trials on Alzheimer’s Disease (CTAD) conference, this is the first large-scale, long-term randomized controlled trial to examine the effects of cocoa extract and multivitamins on global cognition. The trial’s primary focus was on cocoa extract, which earlier studies suggest may preserve cognitive function. Analyzing the effect of multivitamins was a secondary outcome.
Showing vitamins, but not cocoa, were beneficial is the exact opposite of what researchers expected. Still, the results offer an interesting new direction for future study, lead investigator Laura D. Baker, PhD, professor of gerontology and geriatric medicine at Wake Forest University, Winston-Salem, N.C., said in an interview.
“This study made us take notice of a pathway for possible cognitive protection,” Dr. Baker said. “Without this study, we would never have looked down that road.”
The full results were published online in Alzheimer’s and Dementia.
Unexpected effect
The COSMOS-Mind study is a substudy to a larger parent trial called COSMOS. It investigated the effects of cocoa extract and a standard multivitamin-mineral on cardiovascular and cancer outcomes in more than 21,000 older participants.
In COSMOS-Mind, researchers tested whether daily intake of cocoa extract vs. placebo and a multivitamin-mineral vs. placebo improved cognition in older adults.
More than 2,200 participants aged 65 and older were enrolled and followed for 3 years. They completed tests over the telephone at baseline and annually to evaluate memory and other cognitive abilities.
Results showed cocoa extract had no effect on global cognition compared with placebo (mean z-score, 0.03; P = .28). Daily multivitamin use, however, did show significant benefits on global cognition vs. placebo (mean z, 0.07, P = .007).
The beneficial effect was most pronounced in participants with a history of cardiovascular disease (no history 0.06 vs. history 0.14; P = .01).
Researchers found similar protective effects for memory and executive function.
Dr. Baker suggested one possible explanation for the positive effects of multivitamins may be the boost in micronutrients and essential minerals they provided.
“With nutrient-deficient diets plus a high prevalence of cardiovascular disease, diabetes, and other medical comorbidities that we know impact the bioavailability of these nutrients, we are possibly dealing with older adults who are at below optimum in terms of their essential micronutrients and minerals,” she said.
“Even suboptimum levels of micronutrients and essential minerals can have significant consequences for brain health,” she added.
More research needed
Intriguing as the results may be, more work is needed before the findings could affect nutritional guidance, according to Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association.
“While the Alzheimer’s Association is encouraged by these results, we are not ready to recommend widespread use of a multivitamin supplement to reduce risk of cognitive decline in older adults,” Dr. Carrillo said in a statement.
“For now, and until there is more data, people should talk with their health care providers about the benefits and risks of all dietary supplements, including multivitamins,” she added.
Dr. Baker agreed, noting that the study was not designed to measure multivitamin use as a primary outcome. In addition, nearly 90% of the participants were non-Hispanic White, which is not representative of the overall population demographics.
The investigators are now designing another, larger trial that would include a more diverse participant pool. It will be aimed specifically at learning more about how and why multivitamins seem to offer a protective effect on cognition, Dr. Baker noted.
The study was funded by the National Institute on Aging of the National Institutes of Health. Dr. Baker and Dr. Carrillo report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ALZHEIMER’S AND DEMENTIA
Cumulative blood pressure load: A better predictor of CV events?
Cumulative systolic blood pressure load, which can be calculated from serial blood pressure measurements, may provide better prediction of major cardiovascular events, compared with traditional blood pressure measures, a new study suggests.
“Our results suggest that cumulative blood pressure load is an independent predictor of cardiovascular events and should be used in future cardiovascular risk prediction algorithms,” the authors, led by Nelson Wang, MD, George Institute for Global Health, Sydney, conclude.
The study was published online in the Journal of the American College of Cardiology.
The researchers explain that the management of hypertension has traditionally centered around blood pressure measurements taken at a single timepoint, with adequate control defined as those measurements being below a predefined target threshold.
However, this approach fails to recognize blood pressure as a continuous measure that fluctuates over time and does not acknowledge that the most recently recorded measurement may not reflect previous blood pressure control.
More recently, studies have defined the time a patient spends below blood pressure target, or TIme at TaRgEt (TITRE), as a novel marker of cardiovascular risk that is independent of mean blood pressure.
Although TITRE has the added advantage of incorporating duration of control, it is unable to characterize the magnitude of blood pressure elevation, the researchers note.
They point out that an optimal measure as a risk factor for cardiovascular disease would account for both the magnitude and duration of elevated blood pressure.
Such a measure is cumulative blood pressure load, defined as the area under the curve (AUC) expressed in units of mm Hg by time.
The only prior study of this measure was small and retrospective and calculated cumulative blood pressure load from ambulatory blood pressure monitoring estimated over a short (24-hour) period.
Therefore, the aim of the current study was to estimate the association between cumulative systolic blood pressure load over a longer period (24 months) and subsequent major cardiovascular events.
To do this, the researchers conducted a post-hoc analysis of 9,338 patients with type 2 diabetes in the ADVANCE-ON study.
Cumulative systolic blood pressure load was defined as the AUC for systolic blood pressure values above 130 mm Hg divided by the AUC for all measured systolic blood pressure values over a 24-month exposure period.
Over a median 7.6 years of follow-up, 1,469 major cardiovascular events, 1,615 deaths, and 660 cardiovascular deaths occurred.
Results showed that each one standard deviation increase in cumulative systolic blood pressure load was associated with a 14% increase in major cardiovascular events, a 13% increase in all-cause mortality, and a 21% increase in cardiovascular death.
Cumulative systolic blood pressure load outperformed mean systolic blood pressure, time-below-target, and visit-to-visit systolic blood pressure variability for the prediction of cardiovascular events and death and also discriminated risk and reclassified more patients’ risk correctly than the other measures.
“Small improvements in risk prediction can have a major impact when scaled up across large high-risk populations. Furthermore, cumulative systolic pressure load may also prove useful to inform the design of future clinical trials,” the researchers say.
Although the present study only assessed cumulative systolic blood pressure load over 24 months, clinicians should recognize the importance of this measure over a lifetime, they note.
“This approach emphasizes the importance of early blood pressure–lowering interventions to reduce the cumulative systolic blood pressure load that each individual experiences over their lifetime,” they conclude.
The researchers suggest that, based on these results, cumulative systolic blood pressure load and visit-to-visit systolic blood pressure variability “should be used in conjunction in future cardiovascular risk prediction algorithms.”
In an accompanying editorial, Donald Lloyd-Jones, MD, Northwestern Feinberg School of Medicine, Chicago, says that before routinely adopting these new measures, several additional questions need to be addressed.
He notes that many patients in the current study already had cardiovascular disease, and it is not known whether the benefit was consistent among those with and without cardiovascular disease. In addition, longer term data using blood pressure measurements in the real-world clinical setting would be desirable, as well as information on whether these new measures add incremental value to existing risk prediction equations.
“Certainly, the next guidelines should reconsider all types of blood pressure measures, and other potential predictors, to optimize risk estimation and identification of patients with greatest net benefit from risk-reducing therapies,” Dr. Lloyd-Jones comments.
“Ultimately, clinicians should leverage as much information on their patients as possible to understand their blood pressure–related cardiovascular risk, to identify those who may be more likely have occult or emerging subclinical target organ damage, and to identify those who may have particular net benefit from earlier or more intensive treatment,” he concludes.
“These opportunities are more readily available with integration of data that allow for visualization of longer-term blood pressure patterns and incorporation of home monitoring and ambulatory monitoring data to monitor out-of-office blood pressure levels and control.”
A version of this article first appeared on Medscape.com.
Cumulative systolic blood pressure load, which can be calculated from serial blood pressure measurements, may provide better prediction of major cardiovascular events, compared with traditional blood pressure measures, a new study suggests.
“Our results suggest that cumulative blood pressure load is an independent predictor of cardiovascular events and should be used in future cardiovascular risk prediction algorithms,” the authors, led by Nelson Wang, MD, George Institute for Global Health, Sydney, conclude.
The study was published online in the Journal of the American College of Cardiology.
The researchers explain that the management of hypertension has traditionally centered around blood pressure measurements taken at a single timepoint, with adequate control defined as those measurements being below a predefined target threshold.
However, this approach fails to recognize blood pressure as a continuous measure that fluctuates over time and does not acknowledge that the most recently recorded measurement may not reflect previous blood pressure control.
More recently, studies have defined the time a patient spends below blood pressure target, or TIme at TaRgEt (TITRE), as a novel marker of cardiovascular risk that is independent of mean blood pressure.
Although TITRE has the added advantage of incorporating duration of control, it is unable to characterize the magnitude of blood pressure elevation, the researchers note.
They point out that an optimal measure as a risk factor for cardiovascular disease would account for both the magnitude and duration of elevated blood pressure.
Such a measure is cumulative blood pressure load, defined as the area under the curve (AUC) expressed in units of mm Hg by time.
The only prior study of this measure was small and retrospective and calculated cumulative blood pressure load from ambulatory blood pressure monitoring estimated over a short (24-hour) period.
Therefore, the aim of the current study was to estimate the association between cumulative systolic blood pressure load over a longer period (24 months) and subsequent major cardiovascular events.
To do this, the researchers conducted a post-hoc analysis of 9,338 patients with type 2 diabetes in the ADVANCE-ON study.
Cumulative systolic blood pressure load was defined as the AUC for systolic blood pressure values above 130 mm Hg divided by the AUC for all measured systolic blood pressure values over a 24-month exposure period.
Over a median 7.6 years of follow-up, 1,469 major cardiovascular events, 1,615 deaths, and 660 cardiovascular deaths occurred.
Results showed that each one standard deviation increase in cumulative systolic blood pressure load was associated with a 14% increase in major cardiovascular events, a 13% increase in all-cause mortality, and a 21% increase in cardiovascular death.
Cumulative systolic blood pressure load outperformed mean systolic blood pressure, time-below-target, and visit-to-visit systolic blood pressure variability for the prediction of cardiovascular events and death and also discriminated risk and reclassified more patients’ risk correctly than the other measures.
“Small improvements in risk prediction can have a major impact when scaled up across large high-risk populations. Furthermore, cumulative systolic pressure load may also prove useful to inform the design of future clinical trials,” the researchers say.
Although the present study only assessed cumulative systolic blood pressure load over 24 months, clinicians should recognize the importance of this measure over a lifetime, they note.
“This approach emphasizes the importance of early blood pressure–lowering interventions to reduce the cumulative systolic blood pressure load that each individual experiences over their lifetime,” they conclude.
The researchers suggest that, based on these results, cumulative systolic blood pressure load and visit-to-visit systolic blood pressure variability “should be used in conjunction in future cardiovascular risk prediction algorithms.”
In an accompanying editorial, Donald Lloyd-Jones, MD, Northwestern Feinberg School of Medicine, Chicago, says that before routinely adopting these new measures, several additional questions need to be addressed.
He notes that many patients in the current study already had cardiovascular disease, and it is not known whether the benefit was consistent among those with and without cardiovascular disease. In addition, longer term data using blood pressure measurements in the real-world clinical setting would be desirable, as well as information on whether these new measures add incremental value to existing risk prediction equations.
“Certainly, the next guidelines should reconsider all types of blood pressure measures, and other potential predictors, to optimize risk estimation and identification of patients with greatest net benefit from risk-reducing therapies,” Dr. Lloyd-Jones comments.
“Ultimately, clinicians should leverage as much information on their patients as possible to understand their blood pressure–related cardiovascular risk, to identify those who may be more likely have occult or emerging subclinical target organ damage, and to identify those who may have particular net benefit from earlier or more intensive treatment,” he concludes.
“These opportunities are more readily available with integration of data that allow for visualization of longer-term blood pressure patterns and incorporation of home monitoring and ambulatory monitoring data to monitor out-of-office blood pressure levels and control.”
A version of this article first appeared on Medscape.com.
Cumulative systolic blood pressure load, which can be calculated from serial blood pressure measurements, may provide better prediction of major cardiovascular events, compared with traditional blood pressure measures, a new study suggests.
“Our results suggest that cumulative blood pressure load is an independent predictor of cardiovascular events and should be used in future cardiovascular risk prediction algorithms,” the authors, led by Nelson Wang, MD, George Institute for Global Health, Sydney, conclude.
The study was published online in the Journal of the American College of Cardiology.
The researchers explain that the management of hypertension has traditionally centered around blood pressure measurements taken at a single timepoint, with adequate control defined as those measurements being below a predefined target threshold.
However, this approach fails to recognize blood pressure as a continuous measure that fluctuates over time and does not acknowledge that the most recently recorded measurement may not reflect previous blood pressure control.
More recently, studies have defined the time a patient spends below blood pressure target, or TIme at TaRgEt (TITRE), as a novel marker of cardiovascular risk that is independent of mean blood pressure.
Although TITRE has the added advantage of incorporating duration of control, it is unable to characterize the magnitude of blood pressure elevation, the researchers note.
They point out that an optimal measure as a risk factor for cardiovascular disease would account for both the magnitude and duration of elevated blood pressure.
Such a measure is cumulative blood pressure load, defined as the area under the curve (AUC) expressed in units of mm Hg by time.
The only prior study of this measure was small and retrospective and calculated cumulative blood pressure load from ambulatory blood pressure monitoring estimated over a short (24-hour) period.
Therefore, the aim of the current study was to estimate the association between cumulative systolic blood pressure load over a longer period (24 months) and subsequent major cardiovascular events.
To do this, the researchers conducted a post-hoc analysis of 9,338 patients with type 2 diabetes in the ADVANCE-ON study.
Cumulative systolic blood pressure load was defined as the AUC for systolic blood pressure values above 130 mm Hg divided by the AUC for all measured systolic blood pressure values over a 24-month exposure period.
Over a median 7.6 years of follow-up, 1,469 major cardiovascular events, 1,615 deaths, and 660 cardiovascular deaths occurred.
Results showed that each one standard deviation increase in cumulative systolic blood pressure load was associated with a 14% increase in major cardiovascular events, a 13% increase in all-cause mortality, and a 21% increase in cardiovascular death.
Cumulative systolic blood pressure load outperformed mean systolic blood pressure, time-below-target, and visit-to-visit systolic blood pressure variability for the prediction of cardiovascular events and death and also discriminated risk and reclassified more patients’ risk correctly than the other measures.
“Small improvements in risk prediction can have a major impact when scaled up across large high-risk populations. Furthermore, cumulative systolic pressure load may also prove useful to inform the design of future clinical trials,” the researchers say.
Although the present study only assessed cumulative systolic blood pressure load over 24 months, clinicians should recognize the importance of this measure over a lifetime, they note.
“This approach emphasizes the importance of early blood pressure–lowering interventions to reduce the cumulative systolic blood pressure load that each individual experiences over their lifetime,” they conclude.
The researchers suggest that, based on these results, cumulative systolic blood pressure load and visit-to-visit systolic blood pressure variability “should be used in conjunction in future cardiovascular risk prediction algorithms.”
In an accompanying editorial, Donald Lloyd-Jones, MD, Northwestern Feinberg School of Medicine, Chicago, says that before routinely adopting these new measures, several additional questions need to be addressed.
He notes that many patients in the current study already had cardiovascular disease, and it is not known whether the benefit was consistent among those with and without cardiovascular disease. In addition, longer term data using blood pressure measurements in the real-world clinical setting would be desirable, as well as information on whether these new measures add incremental value to existing risk prediction equations.
“Certainly, the next guidelines should reconsider all types of blood pressure measures, and other potential predictors, to optimize risk estimation and identification of patients with greatest net benefit from risk-reducing therapies,” Dr. Lloyd-Jones comments.
“Ultimately, clinicians should leverage as much information on their patients as possible to understand their blood pressure–related cardiovascular risk, to identify those who may be more likely have occult or emerging subclinical target organ damage, and to identify those who may have particular net benefit from earlier or more intensive treatment,” he concludes.
“These opportunities are more readily available with integration of data that allow for visualization of longer-term blood pressure patterns and incorporation of home monitoring and ambulatory monitoring data to monitor out-of-office blood pressure levels and control.”
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY