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Misoprostol effective in healing aspirin-induced small bowel bleeding
CHICAGO – , a small study showed.
Compared with placebo, it was superior in healing small bowel ulcers. A total of 12 patients who received misoprostol had complete healing at 8 weeks, compared with 4 in the placebo group (P = .017).
“Among patients with overt bleeding or anemia from small bowel lesions who receive continuous aspirin therapy, misoprostol is superior to placebo in achieving complete mucosal healing,” said lead author Francis Chan, MD, professor of gastroenterology and hepatology at the Chinese University of Hong Kong, who presented the findings at the annual Digestive Disease Week®.
Millions of individuals use low-dose aspirin daily to lower their risk of stroke and cardiovascular events, but they face a risk of gastrointestinal bleeding. In fact, Dr. Chan pointed out, continuous aspirin use has been associated with a threefold risk of a lower GI bleed.
“But to date, there is no effective pharmacological treatment for small bowel ulcers that are associated with use of low-dose aspirin,” he said.
Misoprostol is a synthetic prostaglandin E1 analog that is indicated for reducing the risk of NSAID–induced gastric ulcers in individuals who are at high risk of complications from gastric ulcers. In their study, Dr. Chan and his colleagues assessed the efficacy of misoprostol for healing small bowel ulcers in patients with GI bleeding who were using continuous aspirin therapy.
The primary endpoint was complete mucosal healing in 8 weeks, and secondary endpoints included changes in the number of GI erosions.
The double-blind, randomized, placebo-controlled trial included 35 patients assigned to misoprostol and 37 to placebo. All patients were on regular aspirin (at least 160 mg/day) for established cardiothrombotic diseases and had either overt bleeding of the small bowel or anemia. No bleeding source was identified on gastroscopy and colonoscopy. They had a score of 3 (more than four erosions) or 4 (large erosion or ulcer) that was confirmed by capsule endoscopy.
Those randomized to the active therapy arm received 200 mg misoprostol four times daily, and all patients continued aspirin 80 mg/day for the duration of the trial. During the study period, concomitant NSAIDs, proton pump inhibitors, sucralfate, rebamipide, antibiotics, corticosteroids, or iron supplement was prohibited.
A follow-up capsule endoscopy was performed at 8 weeks to assess mucosal healing, and all images were evaluated by a blinded panel.
The intention-to-treat population included all patients who took at least one dose of the study drug and returned for follow-up capsule endoscopy (n = 72).
In this population, 33% of patients in the misoprostol group and 10.5% on placebo had complete mucosal healing at 8 weeks.
“For the secondary endpoint of changes in small bowel erosions, there was a significant difference between the misoprostol group and placebo group with a P value of .025,” said Dr. Chan.
The study was supported by a competitive grant from the Research Grant Council of Hong Kong. Dr. Chan reported relationships with AstraZeneca, Eisai, Pfizer, and Takeda.
CHICAGO – , a small study showed.
Compared with placebo, it was superior in healing small bowel ulcers. A total of 12 patients who received misoprostol had complete healing at 8 weeks, compared with 4 in the placebo group (P = .017).
“Among patients with overt bleeding or anemia from small bowel lesions who receive continuous aspirin therapy, misoprostol is superior to placebo in achieving complete mucosal healing,” said lead author Francis Chan, MD, professor of gastroenterology and hepatology at the Chinese University of Hong Kong, who presented the findings at the annual Digestive Disease Week®.
Millions of individuals use low-dose aspirin daily to lower their risk of stroke and cardiovascular events, but they face a risk of gastrointestinal bleeding. In fact, Dr. Chan pointed out, continuous aspirin use has been associated with a threefold risk of a lower GI bleed.
“But to date, there is no effective pharmacological treatment for small bowel ulcers that are associated with use of low-dose aspirin,” he said.
Misoprostol is a synthetic prostaglandin E1 analog that is indicated for reducing the risk of NSAID–induced gastric ulcers in individuals who are at high risk of complications from gastric ulcers. In their study, Dr. Chan and his colleagues assessed the efficacy of misoprostol for healing small bowel ulcers in patients with GI bleeding who were using continuous aspirin therapy.
The primary endpoint was complete mucosal healing in 8 weeks, and secondary endpoints included changes in the number of GI erosions.
The double-blind, randomized, placebo-controlled trial included 35 patients assigned to misoprostol and 37 to placebo. All patients were on regular aspirin (at least 160 mg/day) for established cardiothrombotic diseases and had either overt bleeding of the small bowel or anemia. No bleeding source was identified on gastroscopy and colonoscopy. They had a score of 3 (more than four erosions) or 4 (large erosion or ulcer) that was confirmed by capsule endoscopy.
Those randomized to the active therapy arm received 200 mg misoprostol four times daily, and all patients continued aspirin 80 mg/day for the duration of the trial. During the study period, concomitant NSAIDs, proton pump inhibitors, sucralfate, rebamipide, antibiotics, corticosteroids, or iron supplement was prohibited.
A follow-up capsule endoscopy was performed at 8 weeks to assess mucosal healing, and all images were evaluated by a blinded panel.
The intention-to-treat population included all patients who took at least one dose of the study drug and returned for follow-up capsule endoscopy (n = 72).
In this population, 33% of patients in the misoprostol group and 10.5% on placebo had complete mucosal healing at 8 weeks.
“For the secondary endpoint of changes in small bowel erosions, there was a significant difference between the misoprostol group and placebo group with a P value of .025,” said Dr. Chan.
The study was supported by a competitive grant from the Research Grant Council of Hong Kong. Dr. Chan reported relationships with AstraZeneca, Eisai, Pfizer, and Takeda.
CHICAGO – , a small study showed.
Compared with placebo, it was superior in healing small bowel ulcers. A total of 12 patients who received misoprostol had complete healing at 8 weeks, compared with 4 in the placebo group (P = .017).
“Among patients with overt bleeding or anemia from small bowel lesions who receive continuous aspirin therapy, misoprostol is superior to placebo in achieving complete mucosal healing,” said lead author Francis Chan, MD, professor of gastroenterology and hepatology at the Chinese University of Hong Kong, who presented the findings at the annual Digestive Disease Week®.
Millions of individuals use low-dose aspirin daily to lower their risk of stroke and cardiovascular events, but they face a risk of gastrointestinal bleeding. In fact, Dr. Chan pointed out, continuous aspirin use has been associated with a threefold risk of a lower GI bleed.
“But to date, there is no effective pharmacological treatment for small bowel ulcers that are associated with use of low-dose aspirin,” he said.
Misoprostol is a synthetic prostaglandin E1 analog that is indicated for reducing the risk of NSAID–induced gastric ulcers in individuals who are at high risk of complications from gastric ulcers. In their study, Dr. Chan and his colleagues assessed the efficacy of misoprostol for healing small bowel ulcers in patients with GI bleeding who were using continuous aspirin therapy.
The primary endpoint was complete mucosal healing in 8 weeks, and secondary endpoints included changes in the number of GI erosions.
The double-blind, randomized, placebo-controlled trial included 35 patients assigned to misoprostol and 37 to placebo. All patients were on regular aspirin (at least 160 mg/day) for established cardiothrombotic diseases and had either overt bleeding of the small bowel or anemia. No bleeding source was identified on gastroscopy and colonoscopy. They had a score of 3 (more than four erosions) or 4 (large erosion or ulcer) that was confirmed by capsule endoscopy.
Those randomized to the active therapy arm received 200 mg misoprostol four times daily, and all patients continued aspirin 80 mg/day for the duration of the trial. During the study period, concomitant NSAIDs, proton pump inhibitors, sucralfate, rebamipide, antibiotics, corticosteroids, or iron supplement was prohibited.
A follow-up capsule endoscopy was performed at 8 weeks to assess mucosal healing, and all images were evaluated by a blinded panel.
The intention-to-treat population included all patients who took at least one dose of the study drug and returned for follow-up capsule endoscopy (n = 72).
In this population, 33% of patients in the misoprostol group and 10.5% on placebo had complete mucosal healing at 8 weeks.
“For the secondary endpoint of changes in small bowel erosions, there was a significant difference between the misoprostol group and placebo group with a P value of .025,” said Dr. Chan.
The study was supported by a competitive grant from the Research Grant Council of Hong Kong. Dr. Chan reported relationships with AstraZeneca, Eisai, Pfizer, and Takeda.
AT DDW
Key clinical point: Misoprostol was more effective than placebo in healing small bowel ulcers in patients who used daily low-dose aspirin.
Major finding: 33% of patients in the misoprostol group and 10.5% on placebo had complete mucosal healing at 8 weeks.
Data source: An 8-week, double-blind, randomized placebo-controlled trial of 72 patients that assessed misoprostol vs. placebo for healing small bowel ulcers.
Disclosures: The study was supported by a competitive grant from the Research Grant Council of Hong Kong. Dr. Chan reported relationships with AstraZeneca, Eisai, Pfizer, and Takeda.
Determining patients’ decisional capacity
Question: Mrs. Wong, age 80 years, has vascular dementia, and for the last 2 years has lived in a nursing home. She is forgetful and disoriented to time, person, and place, and totally dependent on others for all of her daily living needs. But she remains verbal and recognizes family members.
Recently, her glomerular filtration rate declined to less than 10% normal, and she has developed symptoms of uremia, i.e., nausea, vomiting, and intractable hiccups. The nephrologist has diagnosed end-stage renal failure and recommends hemodialysis, which will improve her renal symptoms and may extend her life by 1-2 years. But it will do nothing for her underlying dementia, which is progressive and irreversible.
Should she undergo hemodialysis? Choose the best single answer:
A. Mrs. Wong definitely lacks the capacity to decide whether to undergo hemodialysis.
B. A court-appointed guardian should make the decision.
C. Hemodialysis is futile and is medically contraindicated, inhumane, and unethical.
D. Hemodialysis is a life-extending form of comfort care, and therefore cannot be withheld.
E. The choice is hers if she understands the procedure and the consequences of her decision.
Answer: E. The terms competence and capacity are often used interchangeably in the health care context, although there are distinctions. Technically, a patient remains competent until a court says otherwise. On the other hand, the determination of medical decision-making capacity can be made by the attending physician and does not ordinarily require a court hearing.
Medical capacity can be determined by the use of the four-point test, which asks whether:
1. The patient understands the nature of the intervention.
2. The patient understands the consequences of the decision (especially refusal of treatment).
3. The patient is able to communicate his/her wishes.
4. Those wishes are compatible with the patient’s known values.
Courts tend to rule in favor of a finding of capacity. In one case, the court found no evidence that the patient’s “forgetfulness and confusion cause, or relate in any way to, impairment of her ability to understand that, in rejecting the amputation, she is, in effect, choosing death over life.”1
In another, the court opined, “However humble the background, sad and deprived the way of life, each individual should have the choice as to what is done to his body, if he is capable of understanding the consequences. This patient, although suffering from an organic brain disease, in the court’s opinion understands the consequences of his refusal. … I find that he has sufficient capacity and competence to consent to or refuse the proposed surgery.”2
Sometimes capacity is truly lacking. In a Tennessee case, Mary Northern, an elderly woman, refused amputation, denying that gangrene had caused her feet to be “dead, black, shriveled, rotting, and stinking.”3 Instead, she believed that they were merely blackened by soot or dust.
The court declared her incompetent, because she was “incapable of recognizing facts which would be obvious to a person of normal perception.” The court said that if she had acknowledged that her legs were gangrenous but refused amputation because she preferred death to the loss of her feet, she would have been considered competent to refuse surgery.
When the patient lacks capacity, a surrogate steps in. This may be a person previously designated by the patient as having durable power of attorney for health care decisions, and he/she is obligated to give voice to what the patient would have wanted. This is called substituted judgment.
Often, no surrogate has been formally mentioned, and a family member assumes the role; rarely, a court-appointed guardian takes over. When there is no knowledge of the patient’s wishes, the decision is then made in the patient’s best interests.
That a surrogate can make life and death decisions was first enunciated in the seminal case of Karen Ann Quinlan, where the New Jersey Supreme Court famously wrote, “The sad truth, however, is that she is grossly incompetent, and we cannot discern her supposed choice based on the testimony of her previous conversations with friends, where such testimony is without sufficient probative weight. Nevertheless, we have concluded that Karen’s right of privacy may be asserted on her behalf by her guardian under the peculiar circumstances here present.”4
The U.S. Supreme Court in Cruzan v. Director Missouri Department of Health has similarly held that an “incompetent person is not able to make an informed and voluntary choice to exercise a hypothetical right to refuse treatment or any other right. Such a ‘right’ must be exercised for her, if at all, by some sort of surrogate.”5 The court also opined that a state – in this case, Missouri – may apply a clear and convincing evidentiary standard in proceedings where a guardian seeks to discontinue nutrition and hydration.
Clear and convincing evidence is said to exist where there is a finding of high probability, based on evidence “so clear as to leave no substantial doubt” and “sufficiently strong to command the unhesitating assent of every reasonable mind.”
However, where a patient’s wishes are not clear and convincing, a court will be reluctant to order cessation of treatment, as in the landmark case of Wendland v. Wendland, where the California Supreme Court unanimously disallowed the discontinuation of a patient’s tube feedings.6
The patient, Robert Wendland, had regained consciousness after 14 months in a coma, but was left hemiparetic and incontinent, and could not feed by mouth or dress, bathe, and communicate consistently. He did not have an advance directive, but had made statements to the effect he would not want to live in a vegetative state.
His wife, Rose, refused to authorize reinsertion of his dislodged feeding tube, believing that Robert would not have wanted it replaced. The patient’s daughter and brother, as well as the hospital’s ethics committee, county ombudsman, and a court-appointed counsel, all agreed with the decision.
But the patient’s mother, Florence, went to court to block the action. The court determined that Robert’s statements were not clear and convincing, because they did not address his current condition, were not sufficiently specific, and were not necessarily intended to direct his medical care. Further, the patient’s spouse had failed to provide sufficient evidence that her decision was in her husband’s best interests.
Issues surrounding treatment at the end of life can be difficult and elusive. Even where there is an advance medical directive, statements made by patients in the document do not always comport with their eventual treatment decisions.
In a telling study, the authors found that only two-thirds of the time were decisions consistent.7 One-third of patients changed their preferences in the face of actual illness, usually in favor of treatments rejected in advance. Surrogate agreement was only 58%, and surrogates tended to overestimate their loved one’s desire for treatment.
The designation of who may be the legitimate alternative decision maker is another contentious issue, with laws varying widely from state to state.8
All of this may have in part prompted Singapore’s newly enacted Mental Capacity Act,9 which permits a surrogate to make wide-ranging decisions on behalf of an incapacitated person, to specifically exclude decisions regarding life-sustaining treatment and any measure that the physician “reasonably believes is necessary to prevent a serious deterioration” in the patient’s condition.
The decisional responsibility resides in the treating physician, who is obligated by law to make an effort to assist the patient to come to a decision, failing which it is made in the patient’s best interests.
Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. For additional information, readers may contact the author at [email protected].
References
1. Lane v. Candura, 6 Mass. App. 377 (1978).
2. Matter of Roosevelt Hospital, N.Y.L.J. 13 Jan 1977 p. 7 (Sup. Ct., New York Co.).
3. State Dept Human Resources v. Northern, 563 SW 2d 197 (Tenn. Ct. App., 1978).
4. In the matter of Karen Quinlan, 355 A.2d 647 (N.J., 1976).
5. Cruzan v. Director Missouri Department of Health, 110 S. Ct. 2841 (1990).
6. Wendland v. Wendland, 28 P.3d 151 (Cal., 2001).
7. J Clin Ethics. 1998 Fall;9(3):258-62.
8. N Engl J Med. 2017 Apr 13;376(15):1478-82.
9. Singapore’s Mental Capacity Act (Chapter 177A).
Question: Mrs. Wong, age 80 years, has vascular dementia, and for the last 2 years has lived in a nursing home. She is forgetful and disoriented to time, person, and place, and totally dependent on others for all of her daily living needs. But she remains verbal and recognizes family members.
Recently, her glomerular filtration rate declined to less than 10% normal, and she has developed symptoms of uremia, i.e., nausea, vomiting, and intractable hiccups. The nephrologist has diagnosed end-stage renal failure and recommends hemodialysis, which will improve her renal symptoms and may extend her life by 1-2 years. But it will do nothing for her underlying dementia, which is progressive and irreversible.
Should she undergo hemodialysis? Choose the best single answer:
A. Mrs. Wong definitely lacks the capacity to decide whether to undergo hemodialysis.
B. A court-appointed guardian should make the decision.
C. Hemodialysis is futile and is medically contraindicated, inhumane, and unethical.
D. Hemodialysis is a life-extending form of comfort care, and therefore cannot be withheld.
E. The choice is hers if she understands the procedure and the consequences of her decision.
Answer: E. The terms competence and capacity are often used interchangeably in the health care context, although there are distinctions. Technically, a patient remains competent until a court says otherwise. On the other hand, the determination of medical decision-making capacity can be made by the attending physician and does not ordinarily require a court hearing.
Medical capacity can be determined by the use of the four-point test, which asks whether:
1. The patient understands the nature of the intervention.
2. The patient understands the consequences of the decision (especially refusal of treatment).
3. The patient is able to communicate his/her wishes.
4. Those wishes are compatible with the patient’s known values.
Courts tend to rule in favor of a finding of capacity. In one case, the court found no evidence that the patient’s “forgetfulness and confusion cause, or relate in any way to, impairment of her ability to understand that, in rejecting the amputation, she is, in effect, choosing death over life.”1
In another, the court opined, “However humble the background, sad and deprived the way of life, each individual should have the choice as to what is done to his body, if he is capable of understanding the consequences. This patient, although suffering from an organic brain disease, in the court’s opinion understands the consequences of his refusal. … I find that he has sufficient capacity and competence to consent to or refuse the proposed surgery.”2
Sometimes capacity is truly lacking. In a Tennessee case, Mary Northern, an elderly woman, refused amputation, denying that gangrene had caused her feet to be “dead, black, shriveled, rotting, and stinking.”3 Instead, she believed that they were merely blackened by soot or dust.
The court declared her incompetent, because she was “incapable of recognizing facts which would be obvious to a person of normal perception.” The court said that if she had acknowledged that her legs were gangrenous but refused amputation because she preferred death to the loss of her feet, she would have been considered competent to refuse surgery.
When the patient lacks capacity, a surrogate steps in. This may be a person previously designated by the patient as having durable power of attorney for health care decisions, and he/she is obligated to give voice to what the patient would have wanted. This is called substituted judgment.
Often, no surrogate has been formally mentioned, and a family member assumes the role; rarely, a court-appointed guardian takes over. When there is no knowledge of the patient’s wishes, the decision is then made in the patient’s best interests.
That a surrogate can make life and death decisions was first enunciated in the seminal case of Karen Ann Quinlan, where the New Jersey Supreme Court famously wrote, “The sad truth, however, is that she is grossly incompetent, and we cannot discern her supposed choice based on the testimony of her previous conversations with friends, where such testimony is without sufficient probative weight. Nevertheless, we have concluded that Karen’s right of privacy may be asserted on her behalf by her guardian under the peculiar circumstances here present.”4
The U.S. Supreme Court in Cruzan v. Director Missouri Department of Health has similarly held that an “incompetent person is not able to make an informed and voluntary choice to exercise a hypothetical right to refuse treatment or any other right. Such a ‘right’ must be exercised for her, if at all, by some sort of surrogate.”5 The court also opined that a state – in this case, Missouri – may apply a clear and convincing evidentiary standard in proceedings where a guardian seeks to discontinue nutrition and hydration.
Clear and convincing evidence is said to exist where there is a finding of high probability, based on evidence “so clear as to leave no substantial doubt” and “sufficiently strong to command the unhesitating assent of every reasonable mind.”
However, where a patient’s wishes are not clear and convincing, a court will be reluctant to order cessation of treatment, as in the landmark case of Wendland v. Wendland, where the California Supreme Court unanimously disallowed the discontinuation of a patient’s tube feedings.6
The patient, Robert Wendland, had regained consciousness after 14 months in a coma, but was left hemiparetic and incontinent, and could not feed by mouth or dress, bathe, and communicate consistently. He did not have an advance directive, but had made statements to the effect he would not want to live in a vegetative state.
His wife, Rose, refused to authorize reinsertion of his dislodged feeding tube, believing that Robert would not have wanted it replaced. The patient’s daughter and brother, as well as the hospital’s ethics committee, county ombudsman, and a court-appointed counsel, all agreed with the decision.
But the patient’s mother, Florence, went to court to block the action. The court determined that Robert’s statements were not clear and convincing, because they did not address his current condition, were not sufficiently specific, and were not necessarily intended to direct his medical care. Further, the patient’s spouse had failed to provide sufficient evidence that her decision was in her husband’s best interests.
Issues surrounding treatment at the end of life can be difficult and elusive. Even where there is an advance medical directive, statements made by patients in the document do not always comport with their eventual treatment decisions.
In a telling study, the authors found that only two-thirds of the time were decisions consistent.7 One-third of patients changed their preferences in the face of actual illness, usually in favor of treatments rejected in advance. Surrogate agreement was only 58%, and surrogates tended to overestimate their loved one’s desire for treatment.
The designation of who may be the legitimate alternative decision maker is another contentious issue, with laws varying widely from state to state.8
All of this may have in part prompted Singapore’s newly enacted Mental Capacity Act,9 which permits a surrogate to make wide-ranging decisions on behalf of an incapacitated person, to specifically exclude decisions regarding life-sustaining treatment and any measure that the physician “reasonably believes is necessary to prevent a serious deterioration” in the patient’s condition.
The decisional responsibility resides in the treating physician, who is obligated by law to make an effort to assist the patient to come to a decision, failing which it is made in the patient’s best interests.
Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. For additional information, readers may contact the author at [email protected].
References
1. Lane v. Candura, 6 Mass. App. 377 (1978).
2. Matter of Roosevelt Hospital, N.Y.L.J. 13 Jan 1977 p. 7 (Sup. Ct., New York Co.).
3. State Dept Human Resources v. Northern, 563 SW 2d 197 (Tenn. Ct. App., 1978).
4. In the matter of Karen Quinlan, 355 A.2d 647 (N.J., 1976).
5. Cruzan v. Director Missouri Department of Health, 110 S. Ct. 2841 (1990).
6. Wendland v. Wendland, 28 P.3d 151 (Cal., 2001).
7. J Clin Ethics. 1998 Fall;9(3):258-62.
8. N Engl J Med. 2017 Apr 13;376(15):1478-82.
9. Singapore’s Mental Capacity Act (Chapter 177A).
Question: Mrs. Wong, age 80 years, has vascular dementia, and for the last 2 years has lived in a nursing home. She is forgetful and disoriented to time, person, and place, and totally dependent on others for all of her daily living needs. But she remains verbal and recognizes family members.
Recently, her glomerular filtration rate declined to less than 10% normal, and she has developed symptoms of uremia, i.e., nausea, vomiting, and intractable hiccups. The nephrologist has diagnosed end-stage renal failure and recommends hemodialysis, which will improve her renal symptoms and may extend her life by 1-2 years. But it will do nothing for her underlying dementia, which is progressive and irreversible.
Should she undergo hemodialysis? Choose the best single answer:
A. Mrs. Wong definitely lacks the capacity to decide whether to undergo hemodialysis.
B. A court-appointed guardian should make the decision.
C. Hemodialysis is futile and is medically contraindicated, inhumane, and unethical.
D. Hemodialysis is a life-extending form of comfort care, and therefore cannot be withheld.
E. The choice is hers if she understands the procedure and the consequences of her decision.
Answer: E. The terms competence and capacity are often used interchangeably in the health care context, although there are distinctions. Technically, a patient remains competent until a court says otherwise. On the other hand, the determination of medical decision-making capacity can be made by the attending physician and does not ordinarily require a court hearing.
Medical capacity can be determined by the use of the four-point test, which asks whether:
1. The patient understands the nature of the intervention.
2. The patient understands the consequences of the decision (especially refusal of treatment).
3. The patient is able to communicate his/her wishes.
4. Those wishes are compatible with the patient’s known values.
Courts tend to rule in favor of a finding of capacity. In one case, the court found no evidence that the patient’s “forgetfulness and confusion cause, or relate in any way to, impairment of her ability to understand that, in rejecting the amputation, she is, in effect, choosing death over life.”1
In another, the court opined, “However humble the background, sad and deprived the way of life, each individual should have the choice as to what is done to his body, if he is capable of understanding the consequences. This patient, although suffering from an organic brain disease, in the court’s opinion understands the consequences of his refusal. … I find that he has sufficient capacity and competence to consent to or refuse the proposed surgery.”2
Sometimes capacity is truly lacking. In a Tennessee case, Mary Northern, an elderly woman, refused amputation, denying that gangrene had caused her feet to be “dead, black, shriveled, rotting, and stinking.”3 Instead, she believed that they were merely blackened by soot or dust.
The court declared her incompetent, because she was “incapable of recognizing facts which would be obvious to a person of normal perception.” The court said that if she had acknowledged that her legs were gangrenous but refused amputation because she preferred death to the loss of her feet, she would have been considered competent to refuse surgery.
When the patient lacks capacity, a surrogate steps in. This may be a person previously designated by the patient as having durable power of attorney for health care decisions, and he/she is obligated to give voice to what the patient would have wanted. This is called substituted judgment.
Often, no surrogate has been formally mentioned, and a family member assumes the role; rarely, a court-appointed guardian takes over. When there is no knowledge of the patient’s wishes, the decision is then made in the patient’s best interests.
That a surrogate can make life and death decisions was first enunciated in the seminal case of Karen Ann Quinlan, where the New Jersey Supreme Court famously wrote, “The sad truth, however, is that she is grossly incompetent, and we cannot discern her supposed choice based on the testimony of her previous conversations with friends, where such testimony is without sufficient probative weight. Nevertheless, we have concluded that Karen’s right of privacy may be asserted on her behalf by her guardian under the peculiar circumstances here present.”4
The U.S. Supreme Court in Cruzan v. Director Missouri Department of Health has similarly held that an “incompetent person is not able to make an informed and voluntary choice to exercise a hypothetical right to refuse treatment or any other right. Such a ‘right’ must be exercised for her, if at all, by some sort of surrogate.”5 The court also opined that a state – in this case, Missouri – may apply a clear and convincing evidentiary standard in proceedings where a guardian seeks to discontinue nutrition and hydration.
Clear and convincing evidence is said to exist where there is a finding of high probability, based on evidence “so clear as to leave no substantial doubt” and “sufficiently strong to command the unhesitating assent of every reasonable mind.”
However, where a patient’s wishes are not clear and convincing, a court will be reluctant to order cessation of treatment, as in the landmark case of Wendland v. Wendland, where the California Supreme Court unanimously disallowed the discontinuation of a patient’s tube feedings.6
The patient, Robert Wendland, had regained consciousness after 14 months in a coma, but was left hemiparetic and incontinent, and could not feed by mouth or dress, bathe, and communicate consistently. He did not have an advance directive, but had made statements to the effect he would not want to live in a vegetative state.
His wife, Rose, refused to authorize reinsertion of his dislodged feeding tube, believing that Robert would not have wanted it replaced. The patient’s daughter and brother, as well as the hospital’s ethics committee, county ombudsman, and a court-appointed counsel, all agreed with the decision.
But the patient’s mother, Florence, went to court to block the action. The court determined that Robert’s statements were not clear and convincing, because they did not address his current condition, were not sufficiently specific, and were not necessarily intended to direct his medical care. Further, the patient’s spouse had failed to provide sufficient evidence that her decision was in her husband’s best interests.
Issues surrounding treatment at the end of life can be difficult and elusive. Even where there is an advance medical directive, statements made by patients in the document do not always comport with their eventual treatment decisions.
In a telling study, the authors found that only two-thirds of the time were decisions consistent.7 One-third of patients changed their preferences in the face of actual illness, usually in favor of treatments rejected in advance. Surrogate agreement was only 58%, and surrogates tended to overestimate their loved one’s desire for treatment.
The designation of who may be the legitimate alternative decision maker is another contentious issue, with laws varying widely from state to state.8
All of this may have in part prompted Singapore’s newly enacted Mental Capacity Act,9 which permits a surrogate to make wide-ranging decisions on behalf of an incapacitated person, to specifically exclude decisions regarding life-sustaining treatment and any measure that the physician “reasonably believes is necessary to prevent a serious deterioration” in the patient’s condition.
The decisional responsibility resides in the treating physician, who is obligated by law to make an effort to assist the patient to come to a decision, failing which it is made in the patient’s best interests.
Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. For additional information, readers may contact the author at [email protected].
References
1. Lane v. Candura, 6 Mass. App. 377 (1978).
2. Matter of Roosevelt Hospital, N.Y.L.J. 13 Jan 1977 p. 7 (Sup. Ct., New York Co.).
3. State Dept Human Resources v. Northern, 563 SW 2d 197 (Tenn. Ct. App., 1978).
4. In the matter of Karen Quinlan, 355 A.2d 647 (N.J., 1976).
5. Cruzan v. Director Missouri Department of Health, 110 S. Ct. 2841 (1990).
6. Wendland v. Wendland, 28 P.3d 151 (Cal., 2001).
7. J Clin Ethics. 1998 Fall;9(3):258-62.
8. N Engl J Med. 2017 Apr 13;376(15):1478-82.
9. Singapore’s Mental Capacity Act (Chapter 177A).
Muscle-related AEs reported in statin trial suggest ‘nocebo’ effect
Patients are more likely to report muscle-related adverse events (AEs) with statin therapy if a trial is unblinded, according to an analysis of a large clinical trial.
In the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes trial (ASCOT-LLA), 10,180 patients were randomized 1:1 to atorvastatin 10 mg daily or matching placebo for a median for 3.3 years. After the trial was terminated for efficacy, all patients were offered open-label atorvastatin, with 6,409 users and 3,490 nonusers then followed for a median of 2.3 years.
However, during the nonblinded, nonrandomized phase, the rate of muscle-related adverse events was 41% higher in individuals taking atorvastatin, compared with nonusers (1.26% vs. 1% per annum, P = .006). This was despite the fact that patients who reported muscle-related adverse events during the blinded phase were less likely to remain on a statin during the nonblinded phase, compared with those who had not reported this adverse event (Lancet. 2017 May 2. doi: 10.1016/S0140-6736[17]31075-9).
“This observation is consistent with a nocebo effect, whereby subjective AEs (e.g., symptoms reported by patients) can be more likely to be attributed to a treatment thought to cause some particular side effect,” wrote Ajay Gupta, MD, of the National Heart and Lung Institute at Imperial College London and his coauthors.
Musculoskeletal and connective tissue disorders and blood and lymphatic system disorders were also reported more commonly among those taking statins, compared with those not in the nonblinded phase. Apart from these, there were no other significant differences in the rate of other adverse events.
In the blinded phase, patients taking atorvastatin reported significantly lower rates of sleep disturbance, compared with those on placebo, but there was a significant 23% higher rate of renal and urinary adverse events in the atorvastatin arm, compared with the placebo arm. Researchers were not able to draw any conclusions about the incidence of cognitive impairment because there were too few cases.
“We hope that the demonstration in the ASCOT-LLA, of not only the absence of adverse effects of statin therapy on muscle-related and other AEs but also the effect of ascertainment bias in nonblinding studies (which have been the basis of many of the misleading claims), will help to counter the adverse effect on public health of exaggerated claims about statin side effects,” the authors wrote.
The study was funded by Pfizer, Servier Research Group, and Leo Laboratories. Four authors declared personal fees, funding, or speakers honoraria from pharmaceutical companies, including Pfizer. One author was also noted for having sought retraction of papers published about the side-effects of statin therapy. No other conflicts of interest were declared.
Patients are more likely to report muscle-related adverse events (AEs) with statin therapy if a trial is unblinded, according to an analysis of a large clinical trial.
In the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes trial (ASCOT-LLA), 10,180 patients were randomized 1:1 to atorvastatin 10 mg daily or matching placebo for a median for 3.3 years. After the trial was terminated for efficacy, all patients were offered open-label atorvastatin, with 6,409 users and 3,490 nonusers then followed for a median of 2.3 years.
However, during the nonblinded, nonrandomized phase, the rate of muscle-related adverse events was 41% higher in individuals taking atorvastatin, compared with nonusers (1.26% vs. 1% per annum, P = .006). This was despite the fact that patients who reported muscle-related adverse events during the blinded phase were less likely to remain on a statin during the nonblinded phase, compared with those who had not reported this adverse event (Lancet. 2017 May 2. doi: 10.1016/S0140-6736[17]31075-9).
“This observation is consistent with a nocebo effect, whereby subjective AEs (e.g., symptoms reported by patients) can be more likely to be attributed to a treatment thought to cause some particular side effect,” wrote Ajay Gupta, MD, of the National Heart and Lung Institute at Imperial College London and his coauthors.
Musculoskeletal and connective tissue disorders and blood and lymphatic system disorders were also reported more commonly among those taking statins, compared with those not in the nonblinded phase. Apart from these, there were no other significant differences in the rate of other adverse events.
In the blinded phase, patients taking atorvastatin reported significantly lower rates of sleep disturbance, compared with those on placebo, but there was a significant 23% higher rate of renal and urinary adverse events in the atorvastatin arm, compared with the placebo arm. Researchers were not able to draw any conclusions about the incidence of cognitive impairment because there were too few cases.
“We hope that the demonstration in the ASCOT-LLA, of not only the absence of adverse effects of statin therapy on muscle-related and other AEs but also the effect of ascertainment bias in nonblinding studies (which have been the basis of many of the misleading claims), will help to counter the adverse effect on public health of exaggerated claims about statin side effects,” the authors wrote.
The study was funded by Pfizer, Servier Research Group, and Leo Laboratories. Four authors declared personal fees, funding, or speakers honoraria from pharmaceutical companies, including Pfizer. One author was also noted for having sought retraction of papers published about the side-effects of statin therapy. No other conflicts of interest were declared.
Patients are more likely to report muscle-related adverse events (AEs) with statin therapy if a trial is unblinded, according to an analysis of a large clinical trial.
In the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes trial (ASCOT-LLA), 10,180 patients were randomized 1:1 to atorvastatin 10 mg daily or matching placebo for a median for 3.3 years. After the trial was terminated for efficacy, all patients were offered open-label atorvastatin, with 6,409 users and 3,490 nonusers then followed for a median of 2.3 years.
However, during the nonblinded, nonrandomized phase, the rate of muscle-related adverse events was 41% higher in individuals taking atorvastatin, compared with nonusers (1.26% vs. 1% per annum, P = .006). This was despite the fact that patients who reported muscle-related adverse events during the blinded phase were less likely to remain on a statin during the nonblinded phase, compared with those who had not reported this adverse event (Lancet. 2017 May 2. doi: 10.1016/S0140-6736[17]31075-9).
“This observation is consistent with a nocebo effect, whereby subjective AEs (e.g., symptoms reported by patients) can be more likely to be attributed to a treatment thought to cause some particular side effect,” wrote Ajay Gupta, MD, of the National Heart and Lung Institute at Imperial College London and his coauthors.
Musculoskeletal and connective tissue disorders and blood and lymphatic system disorders were also reported more commonly among those taking statins, compared with those not in the nonblinded phase. Apart from these, there were no other significant differences in the rate of other adverse events.
In the blinded phase, patients taking atorvastatin reported significantly lower rates of sleep disturbance, compared with those on placebo, but there was a significant 23% higher rate of renal and urinary adverse events in the atorvastatin arm, compared with the placebo arm. Researchers were not able to draw any conclusions about the incidence of cognitive impairment because there were too few cases.
“We hope that the demonstration in the ASCOT-LLA, of not only the absence of adverse effects of statin therapy on muscle-related and other AEs but also the effect of ascertainment bias in nonblinding studies (which have been the basis of many of the misleading claims), will help to counter the adverse effect on public health of exaggerated claims about statin side effects,” the authors wrote.
The study was funded by Pfizer, Servier Research Group, and Leo Laboratories. Four authors declared personal fees, funding, or speakers honoraria from pharmaceutical companies, including Pfizer. One author was also noted for having sought retraction of papers published about the side-effects of statin therapy. No other conflicts of interest were declared.
FROM THE LANCET
Key clinical point: Patient reports of muscle-related adverse events related to statin use increases significantly after unblinding.
Major finding: The rate of muscle-related adverse events was 41% higher in individuals taking atorvastatin than in nonusers in the nonblinded phase of a trial, compared with no significant difference between arms in the blinded phase.
Data source: The lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LLA) involving 10,180 patients.
Disclosures: The study was funded by Pfizer, Servier Research Group, and Leo Laboratories. Four authors declared personal fees, funding, or speakers honoraria from pharmaceutical companies, including Pfizer. One author was also noted for having sought retraction of papers published about the side effects of statin therapy. No other conflicts of interest were declared.
Time to therapy for gram-positive bacteremia reduced from 60 hours to 4 hours
SAN FRANCISCO – Implementation of sample testing using a molecular approach, combined with coordinated and multidisciplinary notification of clinicians, has reduced the time to deliver adequate antibiotic therapy for bacteremia caused by gram-positive cocci including methicillin-resistant Staphylococcus aureus (MRSA) from 60 hours to 4 hours.
“We observed a significant decrease in the time to adequate antibiotics, significant decrease in time to first negative blood culture, and decreased variation in both measures,” Michael Tchou, MD, of the division of hospital medicine at Cincinnati Children’s Hospital Medical Center (CCHMC), reported at the Pediatric Academic Societies meeting.
Speeding up the time to delivery of adequate antibiotics is a must, Dr. Tchou emphasized.
CCHMC initiated the use of a multiplex polymerase chain reaction (PCR)–based identification protocol in mid-2013. Multiplex PCR targets specific regions of genetic material. In the protocol, empiric antibiotics are administered. At the same time, multiplex PCR is done. Blood culture and subsequent Gram staining of the bacteria in the colonies that grow also are done. PCR-based species identification and determination of probable antibiotic resistance, which takes about 3 hours, can be used to shift antibiotic therapy to adequate therapy, which is defined as the necessary antimicrobial therapy, even if it is still too broad. The growth-based results available the next day help fine-tune the therapy.
The use of multiplex PCR speeds the time to an “actionable result” – the time to recognize that the empiric antibiotic therapy is not the best, Dr. Tchou said.
At CCHMC, an actionable result is obtained for about 1 of every 40 cases of bloodstream infection determined to be caused by gram-positive cocci. The delay in switching to adequate antibiotic coverage used to average 60 hours.
In an effort to do better, Dr. Tchou and colleagues set a goal of reducing the time to adequate antibiotic therapy for gram-positive bacteremia from 60 to 12 hours within 6 months.
The effort necessitated the coordinated involvement of a multidisciplinary team, with a rapid system of clinician notification, and the real-time software-based monitoring of results. In the system, an actionable result triggers a text message to the on-call antibiotic stewardship contact, who in turn notifies the primary care team.
The multidisciplinary system was rolled out first for MRSA. The effort was even more successful than they hoped for. Delivery of appropriate antibiotics for MRSA infections dropped from about 60 hours to 13 hours within a few months, with a further decrease to 4 hours within another few months. Roll out of the initiative to all gram-positive cocci including coagulase-negative staphylococci, Streptococcus pyogenes, Enterococcus faecalis, and E. faecium similarly achieved the 4-hour target within months.
And preliminary results not presented by Dr. Tchou indicate an earlier resolution of bacteremia.
Next steps include modifying the decision support software to allow direct paging of providers instead of using text messages, expansion of the antibiotic coverage, and achieving similar improved treatment time for gram-negative bloodstream infections.
The study was sponsored by Cincinnati Children’s Hospital and was not funded. Dr. Tchou reported having no relevant financial disclosures.
SAN FRANCISCO – Implementation of sample testing using a molecular approach, combined with coordinated and multidisciplinary notification of clinicians, has reduced the time to deliver adequate antibiotic therapy for bacteremia caused by gram-positive cocci including methicillin-resistant Staphylococcus aureus (MRSA) from 60 hours to 4 hours.
“We observed a significant decrease in the time to adequate antibiotics, significant decrease in time to first negative blood culture, and decreased variation in both measures,” Michael Tchou, MD, of the division of hospital medicine at Cincinnati Children’s Hospital Medical Center (CCHMC), reported at the Pediatric Academic Societies meeting.
Speeding up the time to delivery of adequate antibiotics is a must, Dr. Tchou emphasized.
CCHMC initiated the use of a multiplex polymerase chain reaction (PCR)–based identification protocol in mid-2013. Multiplex PCR targets specific regions of genetic material. In the protocol, empiric antibiotics are administered. At the same time, multiplex PCR is done. Blood culture and subsequent Gram staining of the bacteria in the colonies that grow also are done. PCR-based species identification and determination of probable antibiotic resistance, which takes about 3 hours, can be used to shift antibiotic therapy to adequate therapy, which is defined as the necessary antimicrobial therapy, even if it is still too broad. The growth-based results available the next day help fine-tune the therapy.
The use of multiplex PCR speeds the time to an “actionable result” – the time to recognize that the empiric antibiotic therapy is not the best, Dr. Tchou said.
At CCHMC, an actionable result is obtained for about 1 of every 40 cases of bloodstream infection determined to be caused by gram-positive cocci. The delay in switching to adequate antibiotic coverage used to average 60 hours.
In an effort to do better, Dr. Tchou and colleagues set a goal of reducing the time to adequate antibiotic therapy for gram-positive bacteremia from 60 to 12 hours within 6 months.
The effort necessitated the coordinated involvement of a multidisciplinary team, with a rapid system of clinician notification, and the real-time software-based monitoring of results. In the system, an actionable result triggers a text message to the on-call antibiotic stewardship contact, who in turn notifies the primary care team.
The multidisciplinary system was rolled out first for MRSA. The effort was even more successful than they hoped for. Delivery of appropriate antibiotics for MRSA infections dropped from about 60 hours to 13 hours within a few months, with a further decrease to 4 hours within another few months. Roll out of the initiative to all gram-positive cocci including coagulase-negative staphylococci, Streptococcus pyogenes, Enterococcus faecalis, and E. faecium similarly achieved the 4-hour target within months.
And preliminary results not presented by Dr. Tchou indicate an earlier resolution of bacteremia.
Next steps include modifying the decision support software to allow direct paging of providers instead of using text messages, expansion of the antibiotic coverage, and achieving similar improved treatment time for gram-negative bloodstream infections.
The study was sponsored by Cincinnati Children’s Hospital and was not funded. Dr. Tchou reported having no relevant financial disclosures.
SAN FRANCISCO – Implementation of sample testing using a molecular approach, combined with coordinated and multidisciplinary notification of clinicians, has reduced the time to deliver adequate antibiotic therapy for bacteremia caused by gram-positive cocci including methicillin-resistant Staphylococcus aureus (MRSA) from 60 hours to 4 hours.
“We observed a significant decrease in the time to adequate antibiotics, significant decrease in time to first negative blood culture, and decreased variation in both measures,” Michael Tchou, MD, of the division of hospital medicine at Cincinnati Children’s Hospital Medical Center (CCHMC), reported at the Pediatric Academic Societies meeting.
Speeding up the time to delivery of adequate antibiotics is a must, Dr. Tchou emphasized.
CCHMC initiated the use of a multiplex polymerase chain reaction (PCR)–based identification protocol in mid-2013. Multiplex PCR targets specific regions of genetic material. In the protocol, empiric antibiotics are administered. At the same time, multiplex PCR is done. Blood culture and subsequent Gram staining of the bacteria in the colonies that grow also are done. PCR-based species identification and determination of probable antibiotic resistance, which takes about 3 hours, can be used to shift antibiotic therapy to adequate therapy, which is defined as the necessary antimicrobial therapy, even if it is still too broad. The growth-based results available the next day help fine-tune the therapy.
The use of multiplex PCR speeds the time to an “actionable result” – the time to recognize that the empiric antibiotic therapy is not the best, Dr. Tchou said.
At CCHMC, an actionable result is obtained for about 1 of every 40 cases of bloodstream infection determined to be caused by gram-positive cocci. The delay in switching to adequate antibiotic coverage used to average 60 hours.
In an effort to do better, Dr. Tchou and colleagues set a goal of reducing the time to adequate antibiotic therapy for gram-positive bacteremia from 60 to 12 hours within 6 months.
The effort necessitated the coordinated involvement of a multidisciplinary team, with a rapid system of clinician notification, and the real-time software-based monitoring of results. In the system, an actionable result triggers a text message to the on-call antibiotic stewardship contact, who in turn notifies the primary care team.
The multidisciplinary system was rolled out first for MRSA. The effort was even more successful than they hoped for. Delivery of appropriate antibiotics for MRSA infections dropped from about 60 hours to 13 hours within a few months, with a further decrease to 4 hours within another few months. Roll out of the initiative to all gram-positive cocci including coagulase-negative staphylococci, Streptococcus pyogenes, Enterococcus faecalis, and E. faecium similarly achieved the 4-hour target within months.
And preliminary results not presented by Dr. Tchou indicate an earlier resolution of bacteremia.
Next steps include modifying the decision support software to allow direct paging of providers instead of using text messages, expansion of the antibiotic coverage, and achieving similar improved treatment time for gram-negative bloodstream infections.
The study was sponsored by Cincinnati Children’s Hospital and was not funded. Dr. Tchou reported having no relevant financial disclosures.
AT PAS 2017
Key clinical point: Multiplex PCR and a revamped system of notification reduced the time to deliver adequate antibiotic therapy for bacteremia caused by gram-positive cocci from 60 hours to 4 hours within 6 months of implementation.
Major finding: and other gram-positive cocci-related infections.
Data source: A retrospective review of hospital records including patient data prior to and following implementation of multiplex PCR testing at one hospital.
Disclosures: The study was sponsored by Cincinnati Children’s Hospital and was not funded. Dr. Tchou reported having no relevant financial disclosures.
Using telemedicine to improve maternal safety
SAN DIEGO – Utah hospitals reported improved implementation of an obstetrics hemorrhage bundle following a series of teleconferencing sessions.
“There is an increasing body of evidence to support the use of protocols and bundles in obstetrics to improve outcomes for pregnant women and their babies,” Brett D. Einerson, MD, MPH, lead study author, said in an interview. “In Utah and throughout the Mountain West, we face the unique challenge of disseminating information and education on the latest evidence-based treatments to smaller rural hospitals that still need to be prepared for events like severe postpartum hemorrhage but do not have the volume, or sometime the resources, to be adequately prepared.”
“Telehealth allowed us to reach providers who otherwise could not travel the distance to attend frequent training sessions and gave the whole state access to expertise at the region’s large tertiary care hospitals,” Dr. Einerson said. “As far as we know, this is one of the first uses of telehealth as a tool for disseminating patient safety and quality improvement education for health care providers on a statewide scale.”
Dr. Einerson and his associates invited all Utah hospitals to participate in the Obstetric Hemorrhage Collaborative, an evidence-based educational program aimed at facilitating implementation of the obstetric hemorrhage bundle. The program involved two in-person training meetings and twice-monthly teleconferencing with expert mentorship over 6 months. In-person sessions consisted of hands-on training and strategy building, while telehealth sessions were led by regional and national leaders in the field of obstetric hemorrhage.
A statewide self-assessment survey of 38 bundle elements was administered before initiation of the project and after completion. The researchers used modified Likert scales to describe participant responses. Means and proportions were compared before and after the training.
Of Utah’s obstetric hospitals, representing every hospital system in the state, 27 (61%) completed the needs-assessment survey, and 15 (34%) participated in the Obstetric Hemorrhage Collaborative, which included four bundle domains:
- Recognition and Prevention: Conducting a risk assessment and active management of the Third Stage of labor.
- Response: Creating a checklist and a rapid response team.
- Readiness: Establishing a blood bank, hemorrhage cart, and conducting simulation/team drills.
- Reporting and Learning: Fostering a culture of debriefing, conducting a multidisciplinary review, and measuring outcomes and processes.
Hospitals reported implementation, or progress toward implementation, of significantly more elements of the bundle after the educational program, compared with before the collaborative (a mean of 33.3 vs. 19 bundle elements; P less than 0.001). Hospitals reported increased implementation of elements in all four bundle domains. All participants (100%) reported that teleconferencing sessions were “very helpful,” and 14 (93%) said that they were “very satisfied” with the collaborative.
“Hospitals in the state of Utah generally had the right tools to treat and prevent obstetric hemorrhage but did not have the systems in place to be sure that the tools were used correctly,” Dr. Einerson said. “For instance, 80% of hospitals had access to a cart with supplies for treating bleeding, but less than 15% were systematically measuring blood loss after delivery. What surprised me most, however, was that most hospitals did not track their rates of postpartum bleeding. In my mind, you can’t set goals for treatment until you know how good – or bad – you are doing. Knowing your baseline rate of outcomes can help set goals and measure progress toward achieving them. Before training, less than 50% of Utah hospitals knew their own rate of hemorrhage, but all participating hospitals reported tracking their rates after the intervention.”
He acknowledged certain limitations of the study, including the fact that it did not measure obstetric outcomes. “We are in the process of measuring the effectiveness of our telehealth intervention by monitoring hemorrhage rates and complications over time,” Dr. Einerson said. “This survey of participants in the statewide telehealth bundle program is the first step.”
Dr. Einerson reported having no financial disclosures.
SAN DIEGO – Utah hospitals reported improved implementation of an obstetrics hemorrhage bundle following a series of teleconferencing sessions.
“There is an increasing body of evidence to support the use of protocols and bundles in obstetrics to improve outcomes for pregnant women and their babies,” Brett D. Einerson, MD, MPH, lead study author, said in an interview. “In Utah and throughout the Mountain West, we face the unique challenge of disseminating information and education on the latest evidence-based treatments to smaller rural hospitals that still need to be prepared for events like severe postpartum hemorrhage but do not have the volume, or sometime the resources, to be adequately prepared.”
“Telehealth allowed us to reach providers who otherwise could not travel the distance to attend frequent training sessions and gave the whole state access to expertise at the region’s large tertiary care hospitals,” Dr. Einerson said. “As far as we know, this is one of the first uses of telehealth as a tool for disseminating patient safety and quality improvement education for health care providers on a statewide scale.”
Dr. Einerson and his associates invited all Utah hospitals to participate in the Obstetric Hemorrhage Collaborative, an evidence-based educational program aimed at facilitating implementation of the obstetric hemorrhage bundle. The program involved two in-person training meetings and twice-monthly teleconferencing with expert mentorship over 6 months. In-person sessions consisted of hands-on training and strategy building, while telehealth sessions were led by regional and national leaders in the field of obstetric hemorrhage.
A statewide self-assessment survey of 38 bundle elements was administered before initiation of the project and after completion. The researchers used modified Likert scales to describe participant responses. Means and proportions were compared before and after the training.
Of Utah’s obstetric hospitals, representing every hospital system in the state, 27 (61%) completed the needs-assessment survey, and 15 (34%) participated in the Obstetric Hemorrhage Collaborative, which included four bundle domains:
- Recognition and Prevention: Conducting a risk assessment and active management of the Third Stage of labor.
- Response: Creating a checklist and a rapid response team.
- Readiness: Establishing a blood bank, hemorrhage cart, and conducting simulation/team drills.
- Reporting and Learning: Fostering a culture of debriefing, conducting a multidisciplinary review, and measuring outcomes and processes.
Hospitals reported implementation, or progress toward implementation, of significantly more elements of the bundle after the educational program, compared with before the collaborative (a mean of 33.3 vs. 19 bundle elements; P less than 0.001). Hospitals reported increased implementation of elements in all four bundle domains. All participants (100%) reported that teleconferencing sessions were “very helpful,” and 14 (93%) said that they were “very satisfied” with the collaborative.
“Hospitals in the state of Utah generally had the right tools to treat and prevent obstetric hemorrhage but did not have the systems in place to be sure that the tools were used correctly,” Dr. Einerson said. “For instance, 80% of hospitals had access to a cart with supplies for treating bleeding, but less than 15% were systematically measuring blood loss after delivery. What surprised me most, however, was that most hospitals did not track their rates of postpartum bleeding. In my mind, you can’t set goals for treatment until you know how good – or bad – you are doing. Knowing your baseline rate of outcomes can help set goals and measure progress toward achieving them. Before training, less than 50% of Utah hospitals knew their own rate of hemorrhage, but all participating hospitals reported tracking their rates after the intervention.”
He acknowledged certain limitations of the study, including the fact that it did not measure obstetric outcomes. “We are in the process of measuring the effectiveness of our telehealth intervention by monitoring hemorrhage rates and complications over time,” Dr. Einerson said. “This survey of participants in the statewide telehealth bundle program is the first step.”
Dr. Einerson reported having no financial disclosures.
SAN DIEGO – Utah hospitals reported improved implementation of an obstetrics hemorrhage bundle following a series of teleconferencing sessions.
“There is an increasing body of evidence to support the use of protocols and bundles in obstetrics to improve outcomes for pregnant women and their babies,” Brett D. Einerson, MD, MPH, lead study author, said in an interview. “In Utah and throughout the Mountain West, we face the unique challenge of disseminating information and education on the latest evidence-based treatments to smaller rural hospitals that still need to be prepared for events like severe postpartum hemorrhage but do not have the volume, or sometime the resources, to be adequately prepared.”
“Telehealth allowed us to reach providers who otherwise could not travel the distance to attend frequent training sessions and gave the whole state access to expertise at the region’s large tertiary care hospitals,” Dr. Einerson said. “As far as we know, this is one of the first uses of telehealth as a tool for disseminating patient safety and quality improvement education for health care providers on a statewide scale.”
Dr. Einerson and his associates invited all Utah hospitals to participate in the Obstetric Hemorrhage Collaborative, an evidence-based educational program aimed at facilitating implementation of the obstetric hemorrhage bundle. The program involved two in-person training meetings and twice-monthly teleconferencing with expert mentorship over 6 months. In-person sessions consisted of hands-on training and strategy building, while telehealth sessions were led by regional and national leaders in the field of obstetric hemorrhage.
A statewide self-assessment survey of 38 bundle elements was administered before initiation of the project and after completion. The researchers used modified Likert scales to describe participant responses. Means and proportions were compared before and after the training.
Of Utah’s obstetric hospitals, representing every hospital system in the state, 27 (61%) completed the needs-assessment survey, and 15 (34%) participated in the Obstetric Hemorrhage Collaborative, which included four bundle domains:
- Recognition and Prevention: Conducting a risk assessment and active management of the Third Stage of labor.
- Response: Creating a checklist and a rapid response team.
- Readiness: Establishing a blood bank, hemorrhage cart, and conducting simulation/team drills.
- Reporting and Learning: Fostering a culture of debriefing, conducting a multidisciplinary review, and measuring outcomes and processes.
Hospitals reported implementation, or progress toward implementation, of significantly more elements of the bundle after the educational program, compared with before the collaborative (a mean of 33.3 vs. 19 bundle elements; P less than 0.001). Hospitals reported increased implementation of elements in all four bundle domains. All participants (100%) reported that teleconferencing sessions were “very helpful,” and 14 (93%) said that they were “very satisfied” with the collaborative.
“Hospitals in the state of Utah generally had the right tools to treat and prevent obstetric hemorrhage but did not have the systems in place to be sure that the tools were used correctly,” Dr. Einerson said. “For instance, 80% of hospitals had access to a cart with supplies for treating bleeding, but less than 15% were systematically measuring blood loss after delivery. What surprised me most, however, was that most hospitals did not track their rates of postpartum bleeding. In my mind, you can’t set goals for treatment until you know how good – or bad – you are doing. Knowing your baseline rate of outcomes can help set goals and measure progress toward achieving them. Before training, less than 50% of Utah hospitals knew their own rate of hemorrhage, but all participating hospitals reported tracking their rates after the intervention.”
He acknowledged certain limitations of the study, including the fact that it did not measure obstetric outcomes. “We are in the process of measuring the effectiveness of our telehealth intervention by monitoring hemorrhage rates and complications over time,” Dr. Einerson said. “This survey of participants in the statewide telehealth bundle program is the first step.”
Dr. Einerson reported having no financial disclosures.
AT ACOG 2017
Key clinical point:
Major finding: Hospitals reported implementation, or progress toward implementation, of significantly more elements of the bundle after the educational program, compared with before the collaborative (a mean of 33.3 vs. 19 bundle elements; P less than 0.001).
Data source: Results from 15 Utah hospitals that participated in the Obstetric Hemorrhage Collaborative.
Disclosures: The researchers reported having no financial disclosures.
More than one-third of genetic tests misordered, study finds
SAN DIEGO – A review of genetic tests ordered during a 3-month period found that more than one-third were misordered, leading to more than $20,000 in unnecessary health care costs, results from a single-center quality improvement project showed.
“We know there is an ever-expanding number of genetic tests available for clinicians to order, and there is more direct marketing to the patient,” Kathleen Ruzzo, MD, the lead study author, said in an interview prior to the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “It can be difficult to stay on top of that as we have so many different clinical responsibilities.”
Of genetic tests ordered for the 114 patients, 44 (39%) were deemed to be misordered based on published clinical practice guidelines. Of the rest, 24 tests were misordered/not indicated, 8 tests were misordered/false reassurance, and 12 tests were misordered/inadequate.
The costs of ordered genetic testing totaled approximately $75,000, while the cost of recommended testing following the chart review was approximately $54,000, a difference of more than $20,000.
When Dr. Ruzzo shared results of the study with her colleagues at Naval Medical Center San Diego, “I think it opened a lot of people’s eyes … to be more meticulous about [genetic] testing and to ask for help when you need help,” she said. “Having trained individuals, reviewing genetic tests could save money in the health care system more broadly. We could also approve the appropriate testing for the patient.”
She acknowledged certain limitations of the study, including the fact that it “reviewed a very narrow scope of [genetic] tests for a short amount of time, so we think we underestimated the appropriate health care expenditures. Additionally, we didn’t focus on the clinical ramifications of the misordering for patients.”
Study coauthor Monica A. Lutgendorf, MD, a maternal-fetal medicine physician at the medical center, characterized the study findings as “a call to action in general for ob.gyns. to get additional training and resources to handle the ever-expanding number of [genetic] tests,” she said. “I don’t think that this is unique to any specific institution. I think this is part of the new environment of practice that we’re in.”
Physicians can learn more about genetic testing from ACOG and from the Perinatal Quality Foundation, Dr. Lutgendorf said. The study won first prize among oral abstracts presented at the ACOG meeting. The researchers reported having no financial disclosures.
SAN DIEGO – A review of genetic tests ordered during a 3-month period found that more than one-third were misordered, leading to more than $20,000 in unnecessary health care costs, results from a single-center quality improvement project showed.
“We know there is an ever-expanding number of genetic tests available for clinicians to order, and there is more direct marketing to the patient,” Kathleen Ruzzo, MD, the lead study author, said in an interview prior to the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “It can be difficult to stay on top of that as we have so many different clinical responsibilities.”
Of genetic tests ordered for the 114 patients, 44 (39%) were deemed to be misordered based on published clinical practice guidelines. Of the rest, 24 tests were misordered/not indicated, 8 tests were misordered/false reassurance, and 12 tests were misordered/inadequate.
The costs of ordered genetic testing totaled approximately $75,000, while the cost of recommended testing following the chart review was approximately $54,000, a difference of more than $20,000.
When Dr. Ruzzo shared results of the study with her colleagues at Naval Medical Center San Diego, “I think it opened a lot of people’s eyes … to be more meticulous about [genetic] testing and to ask for help when you need help,” she said. “Having trained individuals, reviewing genetic tests could save money in the health care system more broadly. We could also approve the appropriate testing for the patient.”
She acknowledged certain limitations of the study, including the fact that it “reviewed a very narrow scope of [genetic] tests for a short amount of time, so we think we underestimated the appropriate health care expenditures. Additionally, we didn’t focus on the clinical ramifications of the misordering for patients.”
Study coauthor Monica A. Lutgendorf, MD, a maternal-fetal medicine physician at the medical center, characterized the study findings as “a call to action in general for ob.gyns. to get additional training and resources to handle the ever-expanding number of [genetic] tests,” she said. “I don’t think that this is unique to any specific institution. I think this is part of the new environment of practice that we’re in.”
Physicians can learn more about genetic testing from ACOG and from the Perinatal Quality Foundation, Dr. Lutgendorf said. The study won first prize among oral abstracts presented at the ACOG meeting. The researchers reported having no financial disclosures.
SAN DIEGO – A review of genetic tests ordered during a 3-month period found that more than one-third were misordered, leading to more than $20,000 in unnecessary health care costs, results from a single-center quality improvement project showed.
“We know there is an ever-expanding number of genetic tests available for clinicians to order, and there is more direct marketing to the patient,” Kathleen Ruzzo, MD, the lead study author, said in an interview prior to the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “It can be difficult to stay on top of that as we have so many different clinical responsibilities.”
Of genetic tests ordered for the 114 patients, 44 (39%) were deemed to be misordered based on published clinical practice guidelines. Of the rest, 24 tests were misordered/not indicated, 8 tests were misordered/false reassurance, and 12 tests were misordered/inadequate.
The costs of ordered genetic testing totaled approximately $75,000, while the cost of recommended testing following the chart review was approximately $54,000, a difference of more than $20,000.
When Dr. Ruzzo shared results of the study with her colleagues at Naval Medical Center San Diego, “I think it opened a lot of people’s eyes … to be more meticulous about [genetic] testing and to ask for help when you need help,” she said. “Having trained individuals, reviewing genetic tests could save money in the health care system more broadly. We could also approve the appropriate testing for the patient.”
She acknowledged certain limitations of the study, including the fact that it “reviewed a very narrow scope of [genetic] tests for a short amount of time, so we think we underestimated the appropriate health care expenditures. Additionally, we didn’t focus on the clinical ramifications of the misordering for patients.”
Study coauthor Monica A. Lutgendorf, MD, a maternal-fetal medicine physician at the medical center, characterized the study findings as “a call to action in general for ob.gyns. to get additional training and resources to handle the ever-expanding number of [genetic] tests,” she said. “I don’t think that this is unique to any specific institution. I think this is part of the new environment of practice that we’re in.”
Physicians can learn more about genetic testing from ACOG and from the Perinatal Quality Foundation, Dr. Lutgendorf said. The study won first prize among oral abstracts presented at the ACOG meeting. The researchers reported having no financial disclosures.
AT ACOG 2017
Key clinical point:
Major finding: Of genetic tests ordered by clinicians, 39% were deemed to be misordered.
Data source: A review of 114 genetic tests ordered over a 3-month period at a single center.
Disclosures: The researchers reported having no financial disclosures.
Adult vaccination is low, with minimal improvement in recent years
Only minimal improvements have been made in vaccination coverage among U.S. adults in recent years, reported Walter W. Williams, MD, of the National Center for Immunization and Respiratory Diseases, Atlanta, and his associates.
In an analysis of data from the 2015 National Health Interview Survey, the researchers looked at adult vaccine coverage for influenza, pneumococcal, tetanus, hepatitis A, hepatitis B, herpes zoster, and human papillomavirus. Although vaccine coverage rose in several of the seven vaccines studied from 2014 to 2015, these were small increases, they noted (MMWR Surveill Summ. 2017 May 5;66[11]:1-28).
Two or more doses of hepatitis A vaccination coverage in 2015 was 9% for adults aged 19 years or older, similar to the estimate for 2014. Three or more doses of hepatitis B vaccination coverage among adults was 24.6% for adults aged 19 years or older in 2015, similar to that in 2014. However, hepatitis B vaccination coverage among health care providers aged 19 years and older was 64.7%, a 4.1% increase compared with 2014.
In women aged 19-26 years, 41.6% received at least 1 dose of human papillomavirus vaccine in 2015, similar to that reported for 2014. In adults aged 60 years and older, 30.6% reported receiving herpes zoster vaccination to prevent shingles in 2015, 2.7% higher than in 2014.
The results showed that racial and ethnic differences in vaccine coverage persisted for all vaccines researched in this report, with higher coverage for whites compared with most other groups such as African Americans and Hispanics. The differences widened for vaccines such as pneumococcal and herpes zoster. Whites also reported receiving vaccinations more often than other groups, the researchers said.
The data in this report are subject to some limitations, such as exclusion of people in the military and those residing in institutions. Self-report of vaccination may be subject to recall bias, as young adults likely are not able to remember accurately the number of vaccines they’ve received as children or as adults, the researchers noted.
The awareness of the need for vaccines by adults is low among the general population. Health care provider recommendations for vaccinations are strongly associated with a patient’s receiving vaccines. Integrating assessment of adult patients’ vaccination needs, recommendations, and offers of vaccination as a part of routine adult clinical care could greatly improve the adult vaccination rate, according Dr. Williams and his associates.
No conflict of interest was reported.
Only minimal improvements have been made in vaccination coverage among U.S. adults in recent years, reported Walter W. Williams, MD, of the National Center for Immunization and Respiratory Diseases, Atlanta, and his associates.
In an analysis of data from the 2015 National Health Interview Survey, the researchers looked at adult vaccine coverage for influenza, pneumococcal, tetanus, hepatitis A, hepatitis B, herpes zoster, and human papillomavirus. Although vaccine coverage rose in several of the seven vaccines studied from 2014 to 2015, these were small increases, they noted (MMWR Surveill Summ. 2017 May 5;66[11]:1-28).
Two or more doses of hepatitis A vaccination coverage in 2015 was 9% for adults aged 19 years or older, similar to the estimate for 2014. Three or more doses of hepatitis B vaccination coverage among adults was 24.6% for adults aged 19 years or older in 2015, similar to that in 2014. However, hepatitis B vaccination coverage among health care providers aged 19 years and older was 64.7%, a 4.1% increase compared with 2014.
In women aged 19-26 years, 41.6% received at least 1 dose of human papillomavirus vaccine in 2015, similar to that reported for 2014. In adults aged 60 years and older, 30.6% reported receiving herpes zoster vaccination to prevent shingles in 2015, 2.7% higher than in 2014.
The results showed that racial and ethnic differences in vaccine coverage persisted for all vaccines researched in this report, with higher coverage for whites compared with most other groups such as African Americans and Hispanics. The differences widened for vaccines such as pneumococcal and herpes zoster. Whites also reported receiving vaccinations more often than other groups, the researchers said.
The data in this report are subject to some limitations, such as exclusion of people in the military and those residing in institutions. Self-report of vaccination may be subject to recall bias, as young adults likely are not able to remember accurately the number of vaccines they’ve received as children or as adults, the researchers noted.
The awareness of the need for vaccines by adults is low among the general population. Health care provider recommendations for vaccinations are strongly associated with a patient’s receiving vaccines. Integrating assessment of adult patients’ vaccination needs, recommendations, and offers of vaccination as a part of routine adult clinical care could greatly improve the adult vaccination rate, according Dr. Williams and his associates.
No conflict of interest was reported.
Only minimal improvements have been made in vaccination coverage among U.S. adults in recent years, reported Walter W. Williams, MD, of the National Center for Immunization and Respiratory Diseases, Atlanta, and his associates.
In an analysis of data from the 2015 National Health Interview Survey, the researchers looked at adult vaccine coverage for influenza, pneumococcal, tetanus, hepatitis A, hepatitis B, herpes zoster, and human papillomavirus. Although vaccine coverage rose in several of the seven vaccines studied from 2014 to 2015, these were small increases, they noted (MMWR Surveill Summ. 2017 May 5;66[11]:1-28).
Two or more doses of hepatitis A vaccination coverage in 2015 was 9% for adults aged 19 years or older, similar to the estimate for 2014. Three or more doses of hepatitis B vaccination coverage among adults was 24.6% for adults aged 19 years or older in 2015, similar to that in 2014. However, hepatitis B vaccination coverage among health care providers aged 19 years and older was 64.7%, a 4.1% increase compared with 2014.
In women aged 19-26 years, 41.6% received at least 1 dose of human papillomavirus vaccine in 2015, similar to that reported for 2014. In adults aged 60 years and older, 30.6% reported receiving herpes zoster vaccination to prevent shingles in 2015, 2.7% higher than in 2014.
The results showed that racial and ethnic differences in vaccine coverage persisted for all vaccines researched in this report, with higher coverage for whites compared with most other groups such as African Americans and Hispanics. The differences widened for vaccines such as pneumococcal and herpes zoster. Whites also reported receiving vaccinations more often than other groups, the researchers said.
The data in this report are subject to some limitations, such as exclusion of people in the military and those residing in institutions. Self-report of vaccination may be subject to recall bias, as young adults likely are not able to remember accurately the number of vaccines they’ve received as children or as adults, the researchers noted.
The awareness of the need for vaccines by adults is low among the general population. Health care provider recommendations for vaccinations are strongly associated with a patient’s receiving vaccines. Integrating assessment of adult patients’ vaccination needs, recommendations, and offers of vaccination as a part of routine adult clinical care could greatly improve the adult vaccination rate, according Dr. Williams and his associates.
No conflict of interest was reported.
FROM MMWR
CAR T-cell data expected soon in mantle cell lymphoma
Final data collection for primary outcome measures is anticipated in September for ZUMA-2, a Phase II multicenter study of the chimeric antigen receptor (CAR) T-cell product KTE-C19 in patients with relapsed/refractory mantle cell lymphoma.
ZUMA-2 (NCT02601313), with a planned enrollment of 70 patients, is expected to release the overall response rate at 12 months. Secondary outcome measures include duration of response, best objective response, and progression-free survival.
Subjects can have up to five prior regimens, which must include anthracycline or bendamustine-containing chemotherapy, anti-CD20 monoclonal antibody therapy, and ibrutinib. Study subjects cannot have received allogeneic stem cell transplantation, prior CD19 targeted therapy, or prior CAR or other genetically modified T cell therapy.
Trial participants must be adults with an Eastern cooperative oncology group (ECOG) performance status of 0 or 1, an absolute neutrophil count of at least 1000/µL, and a platelet count of at least 50,000/µL. All need to have adequate renal function, defined as a serum creatinine of 1.5 mg/dL or less; adequate hepatic function, defined as a serum ALT/AST of 2.5 the upper limit of normal or less; and a total bilirubin of 1.5 mg/dL or less (except in subjects with Gilbert’s syndrome), and adequate cardiac function, defined as a cardiac ejection fraction of 50% or more with no evidence of pericardial effusion.
Exclusion criteria include a history of another cancer other than nonmelanomatous skin cancer or carcinoma in situ (for example, cervix, bladder, breast) unless disease free for at least 3 years, known infection with HIV or hepatitis B or C virus, metastases in cerebrospinal fluid or brain, and a history of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
The study is sponsored by Kite Pharma, the makers of KTE-C19.
Final data collection for primary outcome measures is anticipated in September for ZUMA-2, a Phase II multicenter study of the chimeric antigen receptor (CAR) T-cell product KTE-C19 in patients with relapsed/refractory mantle cell lymphoma.
ZUMA-2 (NCT02601313), with a planned enrollment of 70 patients, is expected to release the overall response rate at 12 months. Secondary outcome measures include duration of response, best objective response, and progression-free survival.
Subjects can have up to five prior regimens, which must include anthracycline or bendamustine-containing chemotherapy, anti-CD20 monoclonal antibody therapy, and ibrutinib. Study subjects cannot have received allogeneic stem cell transplantation, prior CD19 targeted therapy, or prior CAR or other genetically modified T cell therapy.
Trial participants must be adults with an Eastern cooperative oncology group (ECOG) performance status of 0 or 1, an absolute neutrophil count of at least 1000/µL, and a platelet count of at least 50,000/µL. All need to have adequate renal function, defined as a serum creatinine of 1.5 mg/dL or less; adequate hepatic function, defined as a serum ALT/AST of 2.5 the upper limit of normal or less; and a total bilirubin of 1.5 mg/dL or less (except in subjects with Gilbert’s syndrome), and adequate cardiac function, defined as a cardiac ejection fraction of 50% or more with no evidence of pericardial effusion.
Exclusion criteria include a history of another cancer other than nonmelanomatous skin cancer or carcinoma in situ (for example, cervix, bladder, breast) unless disease free for at least 3 years, known infection with HIV or hepatitis B or C virus, metastases in cerebrospinal fluid or brain, and a history of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
The study is sponsored by Kite Pharma, the makers of KTE-C19.
Final data collection for primary outcome measures is anticipated in September for ZUMA-2, a Phase II multicenter study of the chimeric antigen receptor (CAR) T-cell product KTE-C19 in patients with relapsed/refractory mantle cell lymphoma.
ZUMA-2 (NCT02601313), with a planned enrollment of 70 patients, is expected to release the overall response rate at 12 months. Secondary outcome measures include duration of response, best objective response, and progression-free survival.
Subjects can have up to five prior regimens, which must include anthracycline or bendamustine-containing chemotherapy, anti-CD20 monoclonal antibody therapy, and ibrutinib. Study subjects cannot have received allogeneic stem cell transplantation, prior CD19 targeted therapy, or prior CAR or other genetically modified T cell therapy.
Trial participants must be adults with an Eastern cooperative oncology group (ECOG) performance status of 0 or 1, an absolute neutrophil count of at least 1000/µL, and a platelet count of at least 50,000/µL. All need to have adequate renal function, defined as a serum creatinine of 1.5 mg/dL or less; adequate hepatic function, defined as a serum ALT/AST of 2.5 the upper limit of normal or less; and a total bilirubin of 1.5 mg/dL or less (except in subjects with Gilbert’s syndrome), and adequate cardiac function, defined as a cardiac ejection fraction of 50% or more with no evidence of pericardial effusion.
Exclusion criteria include a history of another cancer other than nonmelanomatous skin cancer or carcinoma in situ (for example, cervix, bladder, breast) unless disease free for at least 3 years, known infection with HIV or hepatitis B or C virus, metastases in cerebrospinal fluid or brain, and a history of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
The study is sponsored by Kite Pharma, the makers of KTE-C19.
SUMMARY FROM CLINICALTRIALS.GOV
Isothiazolinone allergy frequent and underdiagnosed in children
Sensitization to the isothiazolinones MCI (methylchloroisothiazolinone) and MI (methylisothiazolinone), which are used as preservatives in a wide variety of personal and household products, is both frequent and underdiagnosed in U.S. children, according to a report published in Pediatric Dermatology.
These agents are compatible with surfactants and emulsifiers, and because they maintain biocidal activity across a broad range of pH levels they are frequently used as preservatives in products such as wet wipes; shampoos and hair conditioners; soaps, cleansers, and disinfectants; and laundry products. However, they are known to cause contact dermatitis very frequently, and are among the top five contact allergens identified in infants’ patch tests.
A recent survey showed that among 152 pediatric skin care products available at major retail stores, 20% contained MI. These were specifically targeted to infants and children, advertised as being “hypoallergenic,” “natural,” good for “sensitive” skin, and containing “gentle ingredients,” said Alina Goldenberg, MD, of the department of dermatology at the University of California, San Diego, and her associates.
During the past 10 years, only 35 U.S. cases of a positive patch-test reaction to MCI and/or MI have been reported in the literature. To get a more accurate estimate of the true prevalence of pediatric sensitization to MCI and MI, the investigators analyzed information in a database of patch-test results, the Provider Contact Dermatitis Registry. They focused on 1,056 patch tests performed during a 1-year period.
They found 37 positive reactions to combined MCI/MI and another 39 reactions that were negative to combined MCI/MI but positive to MI alone. This shows how important it is to test for sensitization to both formulations separately, Dr. Goldenberg and her associates noted (Pediatr Dermatol. 2017 Mar;34[2]:138-43).
In stark contrast to the reported 35 cases across the entire country during a 10-year period, the investigators found 76 cases (1%) in 1,056 patch tests during a 1-year period.
When test results for MCI/MI and MI alone were compared with those for all other allergens, children sensitized to the isothiazolinones showed marked differences: They were significantly younger, and the location of their dermatitis was more likely to involve the groin and buttocks. This probably is due to the increased use of wet wipes containing MCI and MI being used to clean up urinary and fecal accidents in young children, the researchers said.
The Society for Pediatric Dermatology supported the work. Dr. Goldenberg reported having no relevant financial disclosures; an associate reported serving as a consultant for Johnson & Johnson.
Sensitization to the isothiazolinones MCI (methylchloroisothiazolinone) and MI (methylisothiazolinone), which are used as preservatives in a wide variety of personal and household products, is both frequent and underdiagnosed in U.S. children, according to a report published in Pediatric Dermatology.
These agents are compatible with surfactants and emulsifiers, and because they maintain biocidal activity across a broad range of pH levels they are frequently used as preservatives in products such as wet wipes; shampoos and hair conditioners; soaps, cleansers, and disinfectants; and laundry products. However, they are known to cause contact dermatitis very frequently, and are among the top five contact allergens identified in infants’ patch tests.
A recent survey showed that among 152 pediatric skin care products available at major retail stores, 20% contained MI. These were specifically targeted to infants and children, advertised as being “hypoallergenic,” “natural,” good for “sensitive” skin, and containing “gentle ingredients,” said Alina Goldenberg, MD, of the department of dermatology at the University of California, San Diego, and her associates.
During the past 10 years, only 35 U.S. cases of a positive patch-test reaction to MCI and/or MI have been reported in the literature. To get a more accurate estimate of the true prevalence of pediatric sensitization to MCI and MI, the investigators analyzed information in a database of patch-test results, the Provider Contact Dermatitis Registry. They focused on 1,056 patch tests performed during a 1-year period.
They found 37 positive reactions to combined MCI/MI and another 39 reactions that were negative to combined MCI/MI but positive to MI alone. This shows how important it is to test for sensitization to both formulations separately, Dr. Goldenberg and her associates noted (Pediatr Dermatol. 2017 Mar;34[2]:138-43).
In stark contrast to the reported 35 cases across the entire country during a 10-year period, the investigators found 76 cases (1%) in 1,056 patch tests during a 1-year period.
When test results for MCI/MI and MI alone were compared with those for all other allergens, children sensitized to the isothiazolinones showed marked differences: They were significantly younger, and the location of their dermatitis was more likely to involve the groin and buttocks. This probably is due to the increased use of wet wipes containing MCI and MI being used to clean up urinary and fecal accidents in young children, the researchers said.
The Society for Pediatric Dermatology supported the work. Dr. Goldenberg reported having no relevant financial disclosures; an associate reported serving as a consultant for Johnson & Johnson.
Sensitization to the isothiazolinones MCI (methylchloroisothiazolinone) and MI (methylisothiazolinone), which are used as preservatives in a wide variety of personal and household products, is both frequent and underdiagnosed in U.S. children, according to a report published in Pediatric Dermatology.
These agents are compatible with surfactants and emulsifiers, and because they maintain biocidal activity across a broad range of pH levels they are frequently used as preservatives in products such as wet wipes; shampoos and hair conditioners; soaps, cleansers, and disinfectants; and laundry products. However, they are known to cause contact dermatitis very frequently, and are among the top five contact allergens identified in infants’ patch tests.
A recent survey showed that among 152 pediatric skin care products available at major retail stores, 20% contained MI. These were specifically targeted to infants and children, advertised as being “hypoallergenic,” “natural,” good for “sensitive” skin, and containing “gentle ingredients,” said Alina Goldenberg, MD, of the department of dermatology at the University of California, San Diego, and her associates.
During the past 10 years, only 35 U.S. cases of a positive patch-test reaction to MCI and/or MI have been reported in the literature. To get a more accurate estimate of the true prevalence of pediatric sensitization to MCI and MI, the investigators analyzed information in a database of patch-test results, the Provider Contact Dermatitis Registry. They focused on 1,056 patch tests performed during a 1-year period.
They found 37 positive reactions to combined MCI/MI and another 39 reactions that were negative to combined MCI/MI but positive to MI alone. This shows how important it is to test for sensitization to both formulations separately, Dr. Goldenberg and her associates noted (Pediatr Dermatol. 2017 Mar;34[2]:138-43).
In stark contrast to the reported 35 cases across the entire country during a 10-year period, the investigators found 76 cases (1%) in 1,056 patch tests during a 1-year period.
When test results for MCI/MI and MI alone were compared with those for all other allergens, children sensitized to the isothiazolinones showed marked differences: They were significantly younger, and the location of their dermatitis was more likely to involve the groin and buttocks. This probably is due to the increased use of wet wipes containing MCI and MI being used to clean up urinary and fecal accidents in young children, the researchers said.
The Society for Pediatric Dermatology supported the work. Dr. Goldenberg reported having no relevant financial disclosures; an associate reported serving as a consultant for Johnson & Johnson.
FROM PEDIATRIC DERMATOLOGY
Key clinical point:
Major finding: There were 37 positive patch-test reactions to combined MCI/MI and another 39 reactions that were negative to combined MCI/MI but positive to MI alone.
Data source: An analysis of 1,056 patch-test results recorded in a database by clinicians during a 1-year period.
Disclosures: The Society for Pediatric Dermatology supported the work. Dr. Goldenberg reported having no relevant financial disclosures; an associate reported serving as a consultant for Johnson & Johnson.
G-CSF safe, but antibiotics are more concerning in SCLC
GENEVA – In patients with limited stage–small cell lung cancer (LS-SCLC) treated with concurrent chemotherapy and radiation, the use of antibiotics to prevent febrile neutropenia was associated with worse outcomes, but granulocyte-colony stimulating factor (G-CSF) prescribed for the same purposes appeared to be safe, reported investigators.
In a subanalysis of data on patients with early SCLC enrolled in the phase III CONVERT trial comparing chemotherapy with concurrent once-daily vs. twice-daily radiation, the use of antibiotic prophylaxis of neutropenia was associated with worse overall survival (OS) and progression-free survival, (PFS) compared with no antibiotics, reported Fabio Gomes, MD, from the Christie NHS Foundation Trust Hospital in Manchester, England.
The use of G-CSF was, however, associated with higher rates of grade 3 or 4 thrombocytopenia and anemia, requiring supportive measures, he acknowledged.
The role of G-CSF with concurrent thoracic radiotherapy is controversial because of safety concerns, but data are scarce, Dr. Gomes said. He noted that the American Society of Clinical Oncology guidelines on the use of white blood cell growth factors recommend against their routine use.
However, some of those concerns arose in the mid-1990s when granulocyt macrophage–stimulating colony factor (GM-CSF) was used, rather than G-CSF, which acts on only a single blood lineage, namely neutrophils. Additionally, modern radiology techniques are more precise than they were 20 years ago, reducing the risk of toxicity, he noted.
In the CONVERT trial, 547 patients with LS-SCLC were randomly assigned to receive four to six cycles of cisplatin and etoposide chemotherapy concurrently with either once daily thoracic radiation for a total dose of 66 Gy divided into 33 fractions delivered over 45 days or to twice-daily radiation at a total dose of 45 Gy divided into 30 fractions delivered over 19 days.
There was no difference between the groups in the primary endpoint of overall survival.
In the subanalysis reported here, Gomes et al. looked at the use of G-CSF, delivered at the investigator’s discretion, in 487 patients. Approximately 40% of patients in the subanalysis received G-CSF during at least one treatment cycle.
Prophylactic antibiotics were recommended by the investigators for use in association with at least one chemotherapy cycle, and 49% of patients in the subanalysis received them during at least one cycle.
Hematological toxicities included grade 3 or 4 thrombocytopenia occurring in 29.9% of patients who received G-CSF, vs. 13.3% of those who did not (P less than .001). The rates were similar between the once-daily and twice-daily radiation groups.
Grade 3 or 4 anemia occurred in 16.9% of patients who received G-CSF, vs. 10.7% of those who didn’t (P = .027). The difference was significant only among patients in the twice-daily radiation arm (20.9% vs. 8.3%, respectively; P = .004).
Patients in the twice-daily radiation arms who received G-CSF also required more platelet transfusion, compared with the once-daily arm (P less than .001), and, in both arms, G-CSF was associated with more red-cell transfusions (P = .007 for once-daily and .001 for twice daily).
G-CSF was not associated with either pneumonitis or esophagitis, and there were no differences in treatment-related deaths with either G-CSF or antibiotics.
Median OS by G-CSF use was 29 months with and 27 months without, a difference that was not significant (P = .08). Median PFS also did not differ by G-CSF use or nonuse.
When it came to antibiotic prophylaxis, however, both median OS and PFS were significant worse with antibiotic use (OS, 24 months with vs. 33 months without; P = .016; PFS, P = .03).
“We are very reassured that there are no significant additional toxicities [with G-CSF] from radiation in the acute setting,” commented Sanjay Popat, FRCP, PhD, from the Royal Marsden Hospital in London, the invited discussant.
“However, we have no data as yet on the impact of G-CSF usage on febrile neutropenia, which is of course the fundamental that we’re aiming to improve in the hope that this will contribute to [lowering] costs,” he added.
The study was sponsored by the Christie Hospital National Health Service Foundation Trust, Cancer Research UK, EORTC, GECP, GFPC, and IFCT. Dr. Gomes reported no relevant disclosures. Dr. Popat reported consultation, honoraria, travel expenses, and institutional research from multiple entities.
GENEVA – In patients with limited stage–small cell lung cancer (LS-SCLC) treated with concurrent chemotherapy and radiation, the use of antibiotics to prevent febrile neutropenia was associated with worse outcomes, but granulocyte-colony stimulating factor (G-CSF) prescribed for the same purposes appeared to be safe, reported investigators.
In a subanalysis of data on patients with early SCLC enrolled in the phase III CONVERT trial comparing chemotherapy with concurrent once-daily vs. twice-daily radiation, the use of antibiotic prophylaxis of neutropenia was associated with worse overall survival (OS) and progression-free survival, (PFS) compared with no antibiotics, reported Fabio Gomes, MD, from the Christie NHS Foundation Trust Hospital in Manchester, England.
The use of G-CSF was, however, associated with higher rates of grade 3 or 4 thrombocytopenia and anemia, requiring supportive measures, he acknowledged.
The role of G-CSF with concurrent thoracic radiotherapy is controversial because of safety concerns, but data are scarce, Dr. Gomes said. He noted that the American Society of Clinical Oncology guidelines on the use of white blood cell growth factors recommend against their routine use.
However, some of those concerns arose in the mid-1990s when granulocyt macrophage–stimulating colony factor (GM-CSF) was used, rather than G-CSF, which acts on only a single blood lineage, namely neutrophils. Additionally, modern radiology techniques are more precise than they were 20 years ago, reducing the risk of toxicity, he noted.
In the CONVERT trial, 547 patients with LS-SCLC were randomly assigned to receive four to six cycles of cisplatin and etoposide chemotherapy concurrently with either once daily thoracic radiation for a total dose of 66 Gy divided into 33 fractions delivered over 45 days or to twice-daily radiation at a total dose of 45 Gy divided into 30 fractions delivered over 19 days.
There was no difference between the groups in the primary endpoint of overall survival.
In the subanalysis reported here, Gomes et al. looked at the use of G-CSF, delivered at the investigator’s discretion, in 487 patients. Approximately 40% of patients in the subanalysis received G-CSF during at least one treatment cycle.
Prophylactic antibiotics were recommended by the investigators for use in association with at least one chemotherapy cycle, and 49% of patients in the subanalysis received them during at least one cycle.
Hematological toxicities included grade 3 or 4 thrombocytopenia occurring in 29.9% of patients who received G-CSF, vs. 13.3% of those who did not (P less than .001). The rates were similar between the once-daily and twice-daily radiation groups.
Grade 3 or 4 anemia occurred in 16.9% of patients who received G-CSF, vs. 10.7% of those who didn’t (P = .027). The difference was significant only among patients in the twice-daily radiation arm (20.9% vs. 8.3%, respectively; P = .004).
Patients in the twice-daily radiation arms who received G-CSF also required more platelet transfusion, compared with the once-daily arm (P less than .001), and, in both arms, G-CSF was associated with more red-cell transfusions (P = .007 for once-daily and .001 for twice daily).
G-CSF was not associated with either pneumonitis or esophagitis, and there were no differences in treatment-related deaths with either G-CSF or antibiotics.
Median OS by G-CSF use was 29 months with and 27 months without, a difference that was not significant (P = .08). Median PFS also did not differ by G-CSF use or nonuse.
When it came to antibiotic prophylaxis, however, both median OS and PFS were significant worse with antibiotic use (OS, 24 months with vs. 33 months without; P = .016; PFS, P = .03).
“We are very reassured that there are no significant additional toxicities [with G-CSF] from radiation in the acute setting,” commented Sanjay Popat, FRCP, PhD, from the Royal Marsden Hospital in London, the invited discussant.
“However, we have no data as yet on the impact of G-CSF usage on febrile neutropenia, which is of course the fundamental that we’re aiming to improve in the hope that this will contribute to [lowering] costs,” he added.
The study was sponsored by the Christie Hospital National Health Service Foundation Trust, Cancer Research UK, EORTC, GECP, GFPC, and IFCT. Dr. Gomes reported no relevant disclosures. Dr. Popat reported consultation, honoraria, travel expenses, and institutional research from multiple entities.
GENEVA – In patients with limited stage–small cell lung cancer (LS-SCLC) treated with concurrent chemotherapy and radiation, the use of antibiotics to prevent febrile neutropenia was associated with worse outcomes, but granulocyte-colony stimulating factor (G-CSF) prescribed for the same purposes appeared to be safe, reported investigators.
In a subanalysis of data on patients with early SCLC enrolled in the phase III CONVERT trial comparing chemotherapy with concurrent once-daily vs. twice-daily radiation, the use of antibiotic prophylaxis of neutropenia was associated with worse overall survival (OS) and progression-free survival, (PFS) compared with no antibiotics, reported Fabio Gomes, MD, from the Christie NHS Foundation Trust Hospital in Manchester, England.
The use of G-CSF was, however, associated with higher rates of grade 3 or 4 thrombocytopenia and anemia, requiring supportive measures, he acknowledged.
The role of G-CSF with concurrent thoracic radiotherapy is controversial because of safety concerns, but data are scarce, Dr. Gomes said. He noted that the American Society of Clinical Oncology guidelines on the use of white blood cell growth factors recommend against their routine use.
However, some of those concerns arose in the mid-1990s when granulocyt macrophage–stimulating colony factor (GM-CSF) was used, rather than G-CSF, which acts on only a single blood lineage, namely neutrophils. Additionally, modern radiology techniques are more precise than they were 20 years ago, reducing the risk of toxicity, he noted.
In the CONVERT trial, 547 patients with LS-SCLC were randomly assigned to receive four to six cycles of cisplatin and etoposide chemotherapy concurrently with either once daily thoracic radiation for a total dose of 66 Gy divided into 33 fractions delivered over 45 days or to twice-daily radiation at a total dose of 45 Gy divided into 30 fractions delivered over 19 days.
There was no difference between the groups in the primary endpoint of overall survival.
In the subanalysis reported here, Gomes et al. looked at the use of G-CSF, delivered at the investigator’s discretion, in 487 patients. Approximately 40% of patients in the subanalysis received G-CSF during at least one treatment cycle.
Prophylactic antibiotics were recommended by the investigators for use in association with at least one chemotherapy cycle, and 49% of patients in the subanalysis received them during at least one cycle.
Hematological toxicities included grade 3 or 4 thrombocytopenia occurring in 29.9% of patients who received G-CSF, vs. 13.3% of those who did not (P less than .001). The rates were similar between the once-daily and twice-daily radiation groups.
Grade 3 or 4 anemia occurred in 16.9% of patients who received G-CSF, vs. 10.7% of those who didn’t (P = .027). The difference was significant only among patients in the twice-daily radiation arm (20.9% vs. 8.3%, respectively; P = .004).
Patients in the twice-daily radiation arms who received G-CSF also required more platelet transfusion, compared with the once-daily arm (P less than .001), and, in both arms, G-CSF was associated with more red-cell transfusions (P = .007 for once-daily and .001 for twice daily).
G-CSF was not associated with either pneumonitis or esophagitis, and there were no differences in treatment-related deaths with either G-CSF or antibiotics.
Median OS by G-CSF use was 29 months with and 27 months without, a difference that was not significant (P = .08). Median PFS also did not differ by G-CSF use or nonuse.
When it came to antibiotic prophylaxis, however, both median OS and PFS were significant worse with antibiotic use (OS, 24 months with vs. 33 months without; P = .016; PFS, P = .03).
“We are very reassured that there are no significant additional toxicities [with G-CSF] from radiation in the acute setting,” commented Sanjay Popat, FRCP, PhD, from the Royal Marsden Hospital in London, the invited discussant.
“However, we have no data as yet on the impact of G-CSF usage on febrile neutropenia, which is of course the fundamental that we’re aiming to improve in the hope that this will contribute to [lowering] costs,” he added.
The study was sponsored by the Christie Hospital National Health Service Foundation Trust, Cancer Research UK, EORTC, GECP, GFPC, and IFCT. Dr. Gomes reported no relevant disclosures. Dr. Popat reported consultation, honoraria, travel expenses, and institutional research from multiple entities.
FROM ELCC
Key clinical point: Febrile neutropenia prophylaxis with G-CSF was safe, but prophylactic antibiotics were associated with worse overall survival in patients with limited stage–small cell lung cancer.
Major finding: Both median overall and progression-free survival were lower among patients who received prophylactic antibiotics. There were no differences in survival by G-CSF use.
Data source: Subanalysis of data on 487 patients in the phase III CONVERT trial comparing once-daily and twice daily radiation concurrent with chemotherapy in LS-SCLC.
Disclosures: The study was sponsored by the Christie Hospital National Health Service Foundation Trust, Cancer Research UK, EORTC, GECP, GFPC, and IFCT. Dr. Gomes reported no relevant disclosures. Dr. Popat reported consultation, honoraria, travel expenses, and institutional research from multiple entities.
