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Semaglutide shows promise in NASH phase 2 study
according to a phase 2, double-blind, randomized, placebo-controlled trial published in the New England Journal of Medicine and presented at the 2020 American Association for the Study of Liver Diseases (AASLD) meeting.
“This bodes well for further study of semaglutide and is supported further by marked improvements in weight, glycemic control and lipid profile,” commented the study’s senior author Philip N. Newsome, PhD, FRCPE, of the University of Birmingham (England), in an interview.
The highest daily dose (0.4 mg) of the glucagonlike peptide-1 (GLP-1) receptor agonist, semaglutide, which is approved for the treatment of type 2 diabetes, led to levels of NASH resolution “which are higher than any previously demonstrated,” noted Dr. Newsome. “This was also accompanied by improvement in noninvasive markers of liver fibrosis and also less fibrosis progression, compared to placebo.”
“I think this represents an exciting advance and will, if confirmed in further studies, mark a step-change in our management of patients with NASH,” he added.
The multicenter study, conducted at 143 sites in 16 countries, included 320 patients, aged 18-75 years, with or without type 2 diabetes, who had histologic evidence of NASH and stage 1-3 liver fibrosis.
They were randomized in a 3:3:3:1:1:1 ratio to receive once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg, or placebo for 72 weeks.
The primary endpoint was resolution of NASH and no worsening of fibrosis, with a secondary endpoint being improvement of fibrosis by at least one stage without worsening of NASH.
The study found 40% of patients in the 0.1-mg semaglutide group, 36% in the 0.2-mg group, and 59% in the 0.4-mg group achieved NASH resolution with no worsening of fibrosis, compared with 17% of the placebo group (odds ratio, 6.87; P < .001 for the highest semaglutide dose). However, the treatment did not lead to significant between-group differences in the secondary endpoint, which occurred in 43% of patients on the highest semaglutide dose compared to 33% in the placebo group (OR, 1.42; P = .48).
Treatment with semaglutide also resulted in dose-dependent reductions in body weight, as well as in glycated hemoglobin levels. Bodyweight was reduced by a mean of 5% in the 0.1-mg semaglutide group, followed by mean reductions of 9% and 13% in the 0.2-mg and 0.4-mg groups respectively. This compared to a mean reduction of 1% in the placebo group.
Similarly, glycated hemoglobin levels among patients with type 2 diabetes dropped by 0.63, 1.07, and 1.15 percentage points in the 0.1-mg, 0.2-mg, and 0.4-mg semaglutide groups respectively, compared with a drop of 0.01 percentage point in the placebo group.
“The fact that the percentage of patients who had an improvement in fibrosis stage was not significantly higher with semaglutide than with placebo – despite a greater benefit with respect to NASH resolution and dose-dependent weight loss – was unexpected, given that previous studies have suggested that resolution of NASH and improvements in activity scores for the components of nonalcoholic fatty liver disease are associated with regression of fibrosis,” wrote the authors. “However, the temporal association among NASH resolution, weight loss, and improvement in fibrosis stage is not fully understood. It is possible that the current trial was not of sufficient duration for improvements in fibrosis stage to become apparent.”
The authors also noted that the safety profile of semaglutide was “consistent with that observed in patients with type 2 diabetes in other trials and with the known effects of GLP-1 receptor agonists,” with gastrointestinal disorders being the most commonly reported.
Nausea, constipation, and vomiting were reported more often in the 0.4-mg semaglutide group than in the placebo group (nausea, 42% vs. 11%; constipation, 22% vs. 12%; and vomiting, 15% vs. 2%).
The overall incidence of benign, malignant, or unspecified neoplasms was 15% in the treatment groups versus 8% in the placebo group.
Rowen K. Zetterman, MD, who was not involved with the study, noted that “treatment of NASH is currently limited, and no therapies have yet been approved by the Food and Drug Administration.”
The findings are “important but not yet exciting,” added Dr. Zetterman, who is professor emeritus of internal medicine and associate vice chancellor for strategic planning for the University of Nebraska Medical Center, Omaha.
“Though reversal of liver fibrosis was not noted, the resolution of hepatic inflammation and liver cell injury by semaglutide suggests it may be slowing disease progression,” said Dr. Zetterman, who also serves on the editorial advisory board of Internal Medicine News. This “warrants additional studies where longer treatment with semaglutide may prove reversal of fibrosis and/or prevention of progression to cirrhosis.”
The study was sponsored by Novo Nordisk. Dr. Newsome reported disclosures related to Novo Nordisk during the conduct of the study, and to Boehringer Ingelheim, Bristol-Myers Squibb, Echosens, Gilead, Pfizer, Pharmaxis, and Poxel. Several of the other study authors reported receiving fees and grants from various pharmaceutical companies, including Novo Nordisk One author reported pending patents for the use of semaglutide. Dr. Zetterman had no relevant disclosures.
SOURCE: Newsome PN et al. N Engl J Med. 2020 Nov 13. doi: 10.1056/NEJMoa2028395.
according to a phase 2, double-blind, randomized, placebo-controlled trial published in the New England Journal of Medicine and presented at the 2020 American Association for the Study of Liver Diseases (AASLD) meeting.
“This bodes well for further study of semaglutide and is supported further by marked improvements in weight, glycemic control and lipid profile,” commented the study’s senior author Philip N. Newsome, PhD, FRCPE, of the University of Birmingham (England), in an interview.
The highest daily dose (0.4 mg) of the glucagonlike peptide-1 (GLP-1) receptor agonist, semaglutide, which is approved for the treatment of type 2 diabetes, led to levels of NASH resolution “which are higher than any previously demonstrated,” noted Dr. Newsome. “This was also accompanied by improvement in noninvasive markers of liver fibrosis and also less fibrosis progression, compared to placebo.”
“I think this represents an exciting advance and will, if confirmed in further studies, mark a step-change in our management of patients with NASH,” he added.
The multicenter study, conducted at 143 sites in 16 countries, included 320 patients, aged 18-75 years, with or without type 2 diabetes, who had histologic evidence of NASH and stage 1-3 liver fibrosis.
They were randomized in a 3:3:3:1:1:1 ratio to receive once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg, or placebo for 72 weeks.
The primary endpoint was resolution of NASH and no worsening of fibrosis, with a secondary endpoint being improvement of fibrosis by at least one stage without worsening of NASH.
The study found 40% of patients in the 0.1-mg semaglutide group, 36% in the 0.2-mg group, and 59% in the 0.4-mg group achieved NASH resolution with no worsening of fibrosis, compared with 17% of the placebo group (odds ratio, 6.87; P < .001 for the highest semaglutide dose). However, the treatment did not lead to significant between-group differences in the secondary endpoint, which occurred in 43% of patients on the highest semaglutide dose compared to 33% in the placebo group (OR, 1.42; P = .48).
Treatment with semaglutide also resulted in dose-dependent reductions in body weight, as well as in glycated hemoglobin levels. Bodyweight was reduced by a mean of 5% in the 0.1-mg semaglutide group, followed by mean reductions of 9% and 13% in the 0.2-mg and 0.4-mg groups respectively. This compared to a mean reduction of 1% in the placebo group.
Similarly, glycated hemoglobin levels among patients with type 2 diabetes dropped by 0.63, 1.07, and 1.15 percentage points in the 0.1-mg, 0.2-mg, and 0.4-mg semaglutide groups respectively, compared with a drop of 0.01 percentage point in the placebo group.
“The fact that the percentage of patients who had an improvement in fibrosis stage was not significantly higher with semaglutide than with placebo – despite a greater benefit with respect to NASH resolution and dose-dependent weight loss – was unexpected, given that previous studies have suggested that resolution of NASH and improvements in activity scores for the components of nonalcoholic fatty liver disease are associated with regression of fibrosis,” wrote the authors. “However, the temporal association among NASH resolution, weight loss, and improvement in fibrosis stage is not fully understood. It is possible that the current trial was not of sufficient duration for improvements in fibrosis stage to become apparent.”
The authors also noted that the safety profile of semaglutide was “consistent with that observed in patients with type 2 diabetes in other trials and with the known effects of GLP-1 receptor agonists,” with gastrointestinal disorders being the most commonly reported.
Nausea, constipation, and vomiting were reported more often in the 0.4-mg semaglutide group than in the placebo group (nausea, 42% vs. 11%; constipation, 22% vs. 12%; and vomiting, 15% vs. 2%).
The overall incidence of benign, malignant, or unspecified neoplasms was 15% in the treatment groups versus 8% in the placebo group.
Rowen K. Zetterman, MD, who was not involved with the study, noted that “treatment of NASH is currently limited, and no therapies have yet been approved by the Food and Drug Administration.”
The findings are “important but not yet exciting,” added Dr. Zetterman, who is professor emeritus of internal medicine and associate vice chancellor for strategic planning for the University of Nebraska Medical Center, Omaha.
“Though reversal of liver fibrosis was not noted, the resolution of hepatic inflammation and liver cell injury by semaglutide suggests it may be slowing disease progression,” said Dr. Zetterman, who also serves on the editorial advisory board of Internal Medicine News. This “warrants additional studies where longer treatment with semaglutide may prove reversal of fibrosis and/or prevention of progression to cirrhosis.”
The study was sponsored by Novo Nordisk. Dr. Newsome reported disclosures related to Novo Nordisk during the conduct of the study, and to Boehringer Ingelheim, Bristol-Myers Squibb, Echosens, Gilead, Pfizer, Pharmaxis, and Poxel. Several of the other study authors reported receiving fees and grants from various pharmaceutical companies, including Novo Nordisk One author reported pending patents for the use of semaglutide. Dr. Zetterman had no relevant disclosures.
SOURCE: Newsome PN et al. N Engl J Med. 2020 Nov 13. doi: 10.1056/NEJMoa2028395.
according to a phase 2, double-blind, randomized, placebo-controlled trial published in the New England Journal of Medicine and presented at the 2020 American Association for the Study of Liver Diseases (AASLD) meeting.
“This bodes well for further study of semaglutide and is supported further by marked improvements in weight, glycemic control and lipid profile,” commented the study’s senior author Philip N. Newsome, PhD, FRCPE, of the University of Birmingham (England), in an interview.
The highest daily dose (0.4 mg) of the glucagonlike peptide-1 (GLP-1) receptor agonist, semaglutide, which is approved for the treatment of type 2 diabetes, led to levels of NASH resolution “which are higher than any previously demonstrated,” noted Dr. Newsome. “This was also accompanied by improvement in noninvasive markers of liver fibrosis and also less fibrosis progression, compared to placebo.”
“I think this represents an exciting advance and will, if confirmed in further studies, mark a step-change in our management of patients with NASH,” he added.
The multicenter study, conducted at 143 sites in 16 countries, included 320 patients, aged 18-75 years, with or without type 2 diabetes, who had histologic evidence of NASH and stage 1-3 liver fibrosis.
They were randomized in a 3:3:3:1:1:1 ratio to receive once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg, or placebo for 72 weeks.
The primary endpoint was resolution of NASH and no worsening of fibrosis, with a secondary endpoint being improvement of fibrosis by at least one stage without worsening of NASH.
The study found 40% of patients in the 0.1-mg semaglutide group, 36% in the 0.2-mg group, and 59% in the 0.4-mg group achieved NASH resolution with no worsening of fibrosis, compared with 17% of the placebo group (odds ratio, 6.87; P < .001 for the highest semaglutide dose). However, the treatment did not lead to significant between-group differences in the secondary endpoint, which occurred in 43% of patients on the highest semaglutide dose compared to 33% in the placebo group (OR, 1.42; P = .48).
Treatment with semaglutide also resulted in dose-dependent reductions in body weight, as well as in glycated hemoglobin levels. Bodyweight was reduced by a mean of 5% in the 0.1-mg semaglutide group, followed by mean reductions of 9% and 13% in the 0.2-mg and 0.4-mg groups respectively. This compared to a mean reduction of 1% in the placebo group.
Similarly, glycated hemoglobin levels among patients with type 2 diabetes dropped by 0.63, 1.07, and 1.15 percentage points in the 0.1-mg, 0.2-mg, and 0.4-mg semaglutide groups respectively, compared with a drop of 0.01 percentage point in the placebo group.
“The fact that the percentage of patients who had an improvement in fibrosis stage was not significantly higher with semaglutide than with placebo – despite a greater benefit with respect to NASH resolution and dose-dependent weight loss – was unexpected, given that previous studies have suggested that resolution of NASH and improvements in activity scores for the components of nonalcoholic fatty liver disease are associated with regression of fibrosis,” wrote the authors. “However, the temporal association among NASH resolution, weight loss, and improvement in fibrosis stage is not fully understood. It is possible that the current trial was not of sufficient duration for improvements in fibrosis stage to become apparent.”
The authors also noted that the safety profile of semaglutide was “consistent with that observed in patients with type 2 diabetes in other trials and with the known effects of GLP-1 receptor agonists,” with gastrointestinal disorders being the most commonly reported.
Nausea, constipation, and vomiting were reported more often in the 0.4-mg semaglutide group than in the placebo group (nausea, 42% vs. 11%; constipation, 22% vs. 12%; and vomiting, 15% vs. 2%).
The overall incidence of benign, malignant, or unspecified neoplasms was 15% in the treatment groups versus 8% in the placebo group.
Rowen K. Zetterman, MD, who was not involved with the study, noted that “treatment of NASH is currently limited, and no therapies have yet been approved by the Food and Drug Administration.”
The findings are “important but not yet exciting,” added Dr. Zetterman, who is professor emeritus of internal medicine and associate vice chancellor for strategic planning for the University of Nebraska Medical Center, Omaha.
“Though reversal of liver fibrosis was not noted, the resolution of hepatic inflammation and liver cell injury by semaglutide suggests it may be slowing disease progression,” said Dr. Zetterman, who also serves on the editorial advisory board of Internal Medicine News. This “warrants additional studies where longer treatment with semaglutide may prove reversal of fibrosis and/or prevention of progression to cirrhosis.”
The study was sponsored by Novo Nordisk. Dr. Newsome reported disclosures related to Novo Nordisk during the conduct of the study, and to Boehringer Ingelheim, Bristol-Myers Squibb, Echosens, Gilead, Pfizer, Pharmaxis, and Poxel. Several of the other study authors reported receiving fees and grants from various pharmaceutical companies, including Novo Nordisk One author reported pending patents for the use of semaglutide. Dr. Zetterman had no relevant disclosures.
SOURCE: Newsome PN et al. N Engl J Med. 2020 Nov 13. doi: 10.1056/NEJMoa2028395.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Proposed withdrawal of approval of preterm drug: Two opposing views
The Oct. 5, 2020 move by the Food and Drug Administration’s Center for Drug Evaluation and Research (CDER) suggesting the withdrawal of the approval of Makena incited some opposition.
Amag Pharmaceuticals’ 17 alpha-hydroxyprogesterone caproate (17OHP) injection received accelerated approval in 2011 to reduce the risk of recurrent preterm birth in women with previous unexplained preterm birth. Makena is the only drug approved for preventing recurrent preterm birth.
The back story
The approval was based on findings from a randomized, placebo-controlled trial that demonstrated a 34% relative risk reduction in births before 37 weeks – from 55% in the placebo arm to 36% in the 17OHP-treated arm.
The trial was not designed to measure neonatal outcomes, with the surrogate outcome of recurrent preterm birth being determined as “reasonably likely” to predict benefit to the neonate.
Subsequently, results of the required postapproval confirmatory PROLONG trialproduced conflicting results, failing to show a benefit of 17OHP on either preterm birth or neonatal outcome, which prompted the proposed withdrawal of the drug’s approval.
The CDER advisory committee agreed unanimously that the PROLONG trial did not support the clinical benefit of 17OHP, but the committee was not unanimous in deciding what to do. Of the 16 members, 9 voted to withdraw the drug’s approval, while seven voted to retain it and require another confirmatory trial.
When CDER recommends withdrawal, the company can request a public hearing, which it has done. The FDA commissioner will recommend whether to grant this request.
In the meantime, one from a group of three doctors who are against it and the other from the CDER.
Arguments from the opposing views
“We sympathize with women who are at risk for recurrent preterm birth that could result in death or significant lifelong health effects in neonates, but retaining on the market a drug not shown to be effective for this use does not protect or promote their health,” wrote Christina Chang, MD, MPH and associates from CDER.
On the other hand, “the widespread use of 17OHP after accelerated approval has not uncovered important safety signals,” countered Michael F. Greene, MD, from Massachusetts General Hospital, Boston; David Harrington, PhD, from the Harvard T. Chan School of Public Health, Boston; and Mark A. Klebanoff, MD, MPH, who was coauthor on the original preapproval study and is with Nationwide Children’s Hospital, the Ohio State University College of Medicine, and Ohio State University College of Public Health, all in Columbus. “Withdrawal of the approval for 17OHP, as imperfect as it may be, will leave a very vulnerable demographic group of U.S. women at high risk for this complication of pregnancy with absolutely no available therapeutic option.”
While both the preapproval study and postapproval PROLONG trial had the same enrollment criteria – namely women with a singleton pregnancy and previous singleton spontaneous preterm birth – all parties acknowledged that the studies ended up with very different cohorts. Approval of the drug in the United States made it difficult to recruit U.S. participants for the second trial “because of a lack of equipoise perceived by health care providers and patients,” noted Dr. Greene and associates, resulting in 75% of the PROLONG study’s cohort coming from Europe. This meant that 59% of those in the first study were non-Hispanic black compared with just 6.6% in the PROLONG study, a difference that is important because of the increased risk of preterm birth in Black women.
“Black women are generally underrepresented in U.S. clinical trials, and they are clearly underrepresented in the PROLONG study,” noted Dr. Greene and colleagues, adding that “the total number of qualifying composite neonatal outcome events among Blacks or African Americans in the entire PROLONG study population of 1,700 participants was 9 (6 of 69 in the 17OHP group and 3 of 40 in the placebo group). This is not a robust database from which to conclude that there is no effect in Black women.”
But, Dr. Chang and the CDER group argued, while the first study showed 17OHP “reduced the risk of recurrent preterm birth in both Black and non-Black participants, the lack of even a trend toward efficacy among either Black or non-Black women in [the PROLONG study] argues that the smaller proportion of Black women [in the PROLONG study] does not explain the lack of efficacy.”
In addition to race, there were other risk factors for preterm birth, such as tobacco, alcohol, and street drug use; marital status; and age that differed between the two study cohorts. Even after subcategorizing PROLONG trial participants into higher or lower risk for preterm birth based on these risk factors, Dr. Chang and associates still found no evidence of benefit to 17OHP treatment in any risk group.
Withdrawing approval of 17OHP for a recurrent preterm indication would still allow off-label prescribing, but would most likely end insurance coverage and eventually manufacturing of the drug, noted Dr. Greene and associates.
“When the majority of a population achieves little benefit from a drug, but a minority demographic group at greatest risk for a serious medical problem appears to obtain significant benefit, any decision that will ultimately make it impossible to obtain the drug should be undertaken cautiously,” they warned. “This issue is particularly pressing when that minority group may be the least able to find and financially afford work-arounds to obtain the needed medication in our complex medical system that has a history of failing to serve them well.”
Dr. Chang and associates reported they had no relevant financial disclosures. Dr. Greene and associates reported that they had no relevant conflicts of interest or financial disclosures. Dr. Greene reported he is employed by the New England Journal of Medicine as associate editor. Dr. Harrington reported being employed by the journal as statistical consultant. Dr. Klebanoff reported he was an author of the original article about 17OHP published in the journal and referenced in this article.
The Oct. 5, 2020 move by the Food and Drug Administration’s Center for Drug Evaluation and Research (CDER) suggesting the withdrawal of the approval of Makena incited some opposition.
Amag Pharmaceuticals’ 17 alpha-hydroxyprogesterone caproate (17OHP) injection received accelerated approval in 2011 to reduce the risk of recurrent preterm birth in women with previous unexplained preterm birth. Makena is the only drug approved for preventing recurrent preterm birth.
The back story
The approval was based on findings from a randomized, placebo-controlled trial that demonstrated a 34% relative risk reduction in births before 37 weeks – from 55% in the placebo arm to 36% in the 17OHP-treated arm.
The trial was not designed to measure neonatal outcomes, with the surrogate outcome of recurrent preterm birth being determined as “reasonably likely” to predict benefit to the neonate.
Subsequently, results of the required postapproval confirmatory PROLONG trialproduced conflicting results, failing to show a benefit of 17OHP on either preterm birth or neonatal outcome, which prompted the proposed withdrawal of the drug’s approval.
The CDER advisory committee agreed unanimously that the PROLONG trial did not support the clinical benefit of 17OHP, but the committee was not unanimous in deciding what to do. Of the 16 members, 9 voted to withdraw the drug’s approval, while seven voted to retain it and require another confirmatory trial.
When CDER recommends withdrawal, the company can request a public hearing, which it has done. The FDA commissioner will recommend whether to grant this request.
In the meantime, one from a group of three doctors who are against it and the other from the CDER.
Arguments from the opposing views
“We sympathize with women who are at risk for recurrent preterm birth that could result in death or significant lifelong health effects in neonates, but retaining on the market a drug not shown to be effective for this use does not protect or promote their health,” wrote Christina Chang, MD, MPH and associates from CDER.
On the other hand, “the widespread use of 17OHP after accelerated approval has not uncovered important safety signals,” countered Michael F. Greene, MD, from Massachusetts General Hospital, Boston; David Harrington, PhD, from the Harvard T. Chan School of Public Health, Boston; and Mark A. Klebanoff, MD, MPH, who was coauthor on the original preapproval study and is with Nationwide Children’s Hospital, the Ohio State University College of Medicine, and Ohio State University College of Public Health, all in Columbus. “Withdrawal of the approval for 17OHP, as imperfect as it may be, will leave a very vulnerable demographic group of U.S. women at high risk for this complication of pregnancy with absolutely no available therapeutic option.”
While both the preapproval study and postapproval PROLONG trial had the same enrollment criteria – namely women with a singleton pregnancy and previous singleton spontaneous preterm birth – all parties acknowledged that the studies ended up with very different cohorts. Approval of the drug in the United States made it difficult to recruit U.S. participants for the second trial “because of a lack of equipoise perceived by health care providers and patients,” noted Dr. Greene and associates, resulting in 75% of the PROLONG study’s cohort coming from Europe. This meant that 59% of those in the first study were non-Hispanic black compared with just 6.6% in the PROLONG study, a difference that is important because of the increased risk of preterm birth in Black women.
“Black women are generally underrepresented in U.S. clinical trials, and they are clearly underrepresented in the PROLONG study,” noted Dr. Greene and colleagues, adding that “the total number of qualifying composite neonatal outcome events among Blacks or African Americans in the entire PROLONG study population of 1,700 participants was 9 (6 of 69 in the 17OHP group and 3 of 40 in the placebo group). This is not a robust database from which to conclude that there is no effect in Black women.”
But, Dr. Chang and the CDER group argued, while the first study showed 17OHP “reduced the risk of recurrent preterm birth in both Black and non-Black participants, the lack of even a trend toward efficacy among either Black or non-Black women in [the PROLONG study] argues that the smaller proportion of Black women [in the PROLONG study] does not explain the lack of efficacy.”
In addition to race, there were other risk factors for preterm birth, such as tobacco, alcohol, and street drug use; marital status; and age that differed between the two study cohorts. Even after subcategorizing PROLONG trial participants into higher or lower risk for preterm birth based on these risk factors, Dr. Chang and associates still found no evidence of benefit to 17OHP treatment in any risk group.
Withdrawing approval of 17OHP for a recurrent preterm indication would still allow off-label prescribing, but would most likely end insurance coverage and eventually manufacturing of the drug, noted Dr. Greene and associates.
“When the majority of a population achieves little benefit from a drug, but a minority demographic group at greatest risk for a serious medical problem appears to obtain significant benefit, any decision that will ultimately make it impossible to obtain the drug should be undertaken cautiously,” they warned. “This issue is particularly pressing when that minority group may be the least able to find and financially afford work-arounds to obtain the needed medication in our complex medical system that has a history of failing to serve them well.”
Dr. Chang and associates reported they had no relevant financial disclosures. Dr. Greene and associates reported that they had no relevant conflicts of interest or financial disclosures. Dr. Greene reported he is employed by the New England Journal of Medicine as associate editor. Dr. Harrington reported being employed by the journal as statistical consultant. Dr. Klebanoff reported he was an author of the original article about 17OHP published in the journal and referenced in this article.
The Oct. 5, 2020 move by the Food and Drug Administration’s Center for Drug Evaluation and Research (CDER) suggesting the withdrawal of the approval of Makena incited some opposition.
Amag Pharmaceuticals’ 17 alpha-hydroxyprogesterone caproate (17OHP) injection received accelerated approval in 2011 to reduce the risk of recurrent preterm birth in women with previous unexplained preterm birth. Makena is the only drug approved for preventing recurrent preterm birth.
The back story
The approval was based on findings from a randomized, placebo-controlled trial that demonstrated a 34% relative risk reduction in births before 37 weeks – from 55% in the placebo arm to 36% in the 17OHP-treated arm.
The trial was not designed to measure neonatal outcomes, with the surrogate outcome of recurrent preterm birth being determined as “reasonably likely” to predict benefit to the neonate.
Subsequently, results of the required postapproval confirmatory PROLONG trialproduced conflicting results, failing to show a benefit of 17OHP on either preterm birth or neonatal outcome, which prompted the proposed withdrawal of the drug’s approval.
The CDER advisory committee agreed unanimously that the PROLONG trial did not support the clinical benefit of 17OHP, but the committee was not unanimous in deciding what to do. Of the 16 members, 9 voted to withdraw the drug’s approval, while seven voted to retain it and require another confirmatory trial.
When CDER recommends withdrawal, the company can request a public hearing, which it has done. The FDA commissioner will recommend whether to grant this request.
In the meantime, one from a group of three doctors who are against it and the other from the CDER.
Arguments from the opposing views
“We sympathize with women who are at risk for recurrent preterm birth that could result in death or significant lifelong health effects in neonates, but retaining on the market a drug not shown to be effective for this use does not protect or promote their health,” wrote Christina Chang, MD, MPH and associates from CDER.
On the other hand, “the widespread use of 17OHP after accelerated approval has not uncovered important safety signals,” countered Michael F. Greene, MD, from Massachusetts General Hospital, Boston; David Harrington, PhD, from the Harvard T. Chan School of Public Health, Boston; and Mark A. Klebanoff, MD, MPH, who was coauthor on the original preapproval study and is with Nationwide Children’s Hospital, the Ohio State University College of Medicine, and Ohio State University College of Public Health, all in Columbus. “Withdrawal of the approval for 17OHP, as imperfect as it may be, will leave a very vulnerable demographic group of U.S. women at high risk for this complication of pregnancy with absolutely no available therapeutic option.”
While both the preapproval study and postapproval PROLONG trial had the same enrollment criteria – namely women with a singleton pregnancy and previous singleton spontaneous preterm birth – all parties acknowledged that the studies ended up with very different cohorts. Approval of the drug in the United States made it difficult to recruit U.S. participants for the second trial “because of a lack of equipoise perceived by health care providers and patients,” noted Dr. Greene and associates, resulting in 75% of the PROLONG study’s cohort coming from Europe. This meant that 59% of those in the first study were non-Hispanic black compared with just 6.6% in the PROLONG study, a difference that is important because of the increased risk of preterm birth in Black women.
“Black women are generally underrepresented in U.S. clinical trials, and they are clearly underrepresented in the PROLONG study,” noted Dr. Greene and colleagues, adding that “the total number of qualifying composite neonatal outcome events among Blacks or African Americans in the entire PROLONG study population of 1,700 participants was 9 (6 of 69 in the 17OHP group and 3 of 40 in the placebo group). This is not a robust database from which to conclude that there is no effect in Black women.”
But, Dr. Chang and the CDER group argued, while the first study showed 17OHP “reduced the risk of recurrent preterm birth in both Black and non-Black participants, the lack of even a trend toward efficacy among either Black or non-Black women in [the PROLONG study] argues that the smaller proportion of Black women [in the PROLONG study] does not explain the lack of efficacy.”
In addition to race, there were other risk factors for preterm birth, such as tobacco, alcohol, and street drug use; marital status; and age that differed between the two study cohorts. Even after subcategorizing PROLONG trial participants into higher or lower risk for preterm birth based on these risk factors, Dr. Chang and associates still found no evidence of benefit to 17OHP treatment in any risk group.
Withdrawing approval of 17OHP for a recurrent preterm indication would still allow off-label prescribing, but would most likely end insurance coverage and eventually manufacturing of the drug, noted Dr. Greene and associates.
“When the majority of a population achieves little benefit from a drug, but a minority demographic group at greatest risk for a serious medical problem appears to obtain significant benefit, any decision that will ultimately make it impossible to obtain the drug should be undertaken cautiously,” they warned. “This issue is particularly pressing when that minority group may be the least able to find and financially afford work-arounds to obtain the needed medication in our complex medical system that has a history of failing to serve them well.”
Dr. Chang and associates reported they had no relevant financial disclosures. Dr. Greene and associates reported that they had no relevant conflicts of interest or financial disclosures. Dr. Greene reported he is employed by the New England Journal of Medicine as associate editor. Dr. Harrington reported being employed by the journal as statistical consultant. Dr. Klebanoff reported he was an author of the original article about 17OHP published in the journal and referenced in this article.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Study: 10% of pregnant women test positive for COVID-19, with most asymptomatic
according to a living systematic review from the PregCOV-19 Living Systematic Review Consortium.
The study, published in BMJ, shows an increased risk of preterm delivery, as well as the need for invasive ventilation in these women, wrote John Allotey, PhD, of the University of Birmingham (England) and colleagues. The findings “will produce a strong evidence base for living guidelines on COVID-19 and pregnancy,” they noted.
The systematic review included 77 studies, one-third each from the United States and China, with the remaining studies from Belgium, Brazil, Denmark, France, Israel, Italy, Japan, Mexico, the Netherlands Portugal, Spain, and the United Kingdom.
The studies included women with COVID-19, of whom 13,118 were either pregnant or in the postpartum or postabortion period and 83,486 were of reproductive age but not pregnant. Some studies also included healthy pregnant women for comparison.
In the pregnant and recently pregnant women, the most common COVID-19 symptoms were fever (40%) and cough (39%), with lymphopenia (35%) and raised C reactive protein levels (49%) being the most common laboratory findings. Pregnant and recently pregnant women with COVID-19 were less likely to have fever (odds ratio, 0.43) and myalgia (OR, 0.48), compared with nonpregnant women of reproductive age with COVID-19, reported the authors.
The overall preterm and spontaneous preterm birth rates in the COVID-19–positive women were 17% and 6% respectively. Dr. Allotey and authors noted that “these preterm births could be medically indicated, as the overall rates of spontaneous preterm births in pregnant women with COVID-19 was broadly similar to those observed in the pre-pandemic period.” There were 18 stillbirths and 6 neonatal deaths in the COVID-19 cohort.
Overall, 73 (0.1%) of pregnant women with confirmed COVID-19 died from any cause, and severe COVID-19 infection was diagnosed in 13%. Maternal risk factors associated with severe infection included older age (OR, 1.78), high body mass index (OR, 2.3), chronic hypertension (OR, 2.0), and preexisting diabetes (OR, 2.51). Compared with nonpregnant women with COVID-19, pregnant or recently pregnant women with the infection were at increased risk of admission to intensive care (OR, 1.62) and needing invasive ventilation (OR, 1.88).
The report included studies published between December 1, 2019, and June 26, 2020, but the living systematic review will involve weekly search updates, with analysis performed every 2-4 weeks and reported through a dedicated website.
The value of a living meta-analysis
Asked to comment on the findings, Torri Metz, MD, a maternal-fetal medicine subspecialist at the University of Utah, Salt Lake City, expressed surprise at the 10% rate of infection in the pregnant or recently pregnant population. “This is higher than currently observed at many hospitals in the United States,” she said in an interview. “This may overestimate the actual risk as many of these studies were published early in the pandemic and did not universally sample women who were pregnant for SARS-CoV-2.”
She noted the value of a living meta-analysis in that it will be updated on a regular basis as new evidence emerges. “During this time of rapidly accumulating publications about COVID-19 infection, clinicians will find it useful to have a resource in which the available data can be combined in one source.”
And there are still some outstanding questions that new studies hopefully will shed light on, she added. “The authors found that many of the risk factors for severe disease, like diabetes, obesity and high blood pressure, in nonpregnant adults are the same in the pregnant population. What remains unknown is if pregnant patients with COVID-19 infection are at higher risk than those who are not pregnant. The authors note that this information is still limited and largely influenced in this published analysis by a CDC [Centers for Disease Control and Prevention] study in which the majority of patients had unknown pregnancy status. We also do not know if COVID-19 infection is associated with any birth defects since the majority of women with COVID-19 infection in the first trimester have not yet delivered.”
Malavika Prabhu, MD, an obstetetrician/gyneologist at Weill Cornell Medicine in New York City added that “this systematic review and meta analysis, which is a compilation of other studies done around the globe, confirms that pregnant women with preexisting medical conditions such as diabetes, hypertension, and obesity, are at increased risk of severe COVID-19 and that pregnant women with COVID-19 are at increased risk of invasive ventilation, compared to nonpregnant women with COVID-19, particularly if they have a preexisting medical condition.”
She said the preterm delivery rate of COVID-positive women is “challenging to interpret given that the total preterm birth rate potentially included many medically indicated preterm deliveries – which is to be expected – and there is no comparison group for spontaneous preterm birth presented”.
Other outstanding questions about COVID-19 pregnancies include whether they are associated with preeclampsia or smaller/growth restricted infants and why the cesarean delivery rate is high, she said. “But some of these questions are tough to answer with this data because it primarily reflects a COVID infection close to the delivery, not one that occurred several months prior to a delivery.”
Deborah Money, MD, professor of obstetrics and gynecology, medicine, and the school of population and public health, University of British Columbia, Vancouver, commented that “this is a group that have been doing ongoing living systematic reviews of the literature scanning for pregnancy outcomes. They post their information in real time on their website, so many of us in this area follow these postings as their methodology is robust and they work hard to only include high-quality literature and avoid duplication of cases in multiple papers. There has been a problem of re-reporting the same severe cases of COVID-19 in the literature.”
This “amplifies the importance of collecting Canadian-specific data to ensure that we understand if these kind of outcomes will also be found in Canada. The data presented in this paper represent outcomes from a broad range of countries with different methods of collecting information on pregnancy and highly variable prenatal care systems. This makes our pan-Canadian study of outcomes of COVID-19 for pregnant women and their infants, CANCOVID-Preg, even more important,” she said.
“Globally, we all must continue to monitor outcomes of COVID-19 in pregnancy to minimize adverse impact on women and their infants,” said Dr. Money, who was not involved in the study.
The study was partially funded by the World Health Organization and supported by Katie’s Team, a dedicated patient and public involvement group in Women’s Health. Dr. Metz is principal investigator for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network COVID-19 study; the study is funded by NICHD and enrollment is ongoing. Dr. Prabhu had no relevant financial disclosures. Dr. Money received funding from the Canadian Institutes for Health Research and the Public Health Agency of Canada and received a small grant from theBC Women’s Foundation for COVID-19 in pregnancy research.
SOURCE: Allotey J et al. BMJ. 2020;370:m3320.
according to a living systematic review from the PregCOV-19 Living Systematic Review Consortium.
The study, published in BMJ, shows an increased risk of preterm delivery, as well as the need for invasive ventilation in these women, wrote John Allotey, PhD, of the University of Birmingham (England) and colleagues. The findings “will produce a strong evidence base for living guidelines on COVID-19 and pregnancy,” they noted.
The systematic review included 77 studies, one-third each from the United States and China, with the remaining studies from Belgium, Brazil, Denmark, France, Israel, Italy, Japan, Mexico, the Netherlands Portugal, Spain, and the United Kingdom.
The studies included women with COVID-19, of whom 13,118 were either pregnant or in the postpartum or postabortion period and 83,486 were of reproductive age but not pregnant. Some studies also included healthy pregnant women for comparison.
In the pregnant and recently pregnant women, the most common COVID-19 symptoms were fever (40%) and cough (39%), with lymphopenia (35%) and raised C reactive protein levels (49%) being the most common laboratory findings. Pregnant and recently pregnant women with COVID-19 were less likely to have fever (odds ratio, 0.43) and myalgia (OR, 0.48), compared with nonpregnant women of reproductive age with COVID-19, reported the authors.
The overall preterm and spontaneous preterm birth rates in the COVID-19–positive women were 17% and 6% respectively. Dr. Allotey and authors noted that “these preterm births could be medically indicated, as the overall rates of spontaneous preterm births in pregnant women with COVID-19 was broadly similar to those observed in the pre-pandemic period.” There were 18 stillbirths and 6 neonatal deaths in the COVID-19 cohort.
Overall, 73 (0.1%) of pregnant women with confirmed COVID-19 died from any cause, and severe COVID-19 infection was diagnosed in 13%. Maternal risk factors associated with severe infection included older age (OR, 1.78), high body mass index (OR, 2.3), chronic hypertension (OR, 2.0), and preexisting diabetes (OR, 2.51). Compared with nonpregnant women with COVID-19, pregnant or recently pregnant women with the infection were at increased risk of admission to intensive care (OR, 1.62) and needing invasive ventilation (OR, 1.88).
The report included studies published between December 1, 2019, and June 26, 2020, but the living systematic review will involve weekly search updates, with analysis performed every 2-4 weeks and reported through a dedicated website.
The value of a living meta-analysis
Asked to comment on the findings, Torri Metz, MD, a maternal-fetal medicine subspecialist at the University of Utah, Salt Lake City, expressed surprise at the 10% rate of infection in the pregnant or recently pregnant population. “This is higher than currently observed at many hospitals in the United States,” she said in an interview. “This may overestimate the actual risk as many of these studies were published early in the pandemic and did not universally sample women who were pregnant for SARS-CoV-2.”
She noted the value of a living meta-analysis in that it will be updated on a regular basis as new evidence emerges. “During this time of rapidly accumulating publications about COVID-19 infection, clinicians will find it useful to have a resource in which the available data can be combined in one source.”
And there are still some outstanding questions that new studies hopefully will shed light on, she added. “The authors found that many of the risk factors for severe disease, like diabetes, obesity and high blood pressure, in nonpregnant adults are the same in the pregnant population. What remains unknown is if pregnant patients with COVID-19 infection are at higher risk than those who are not pregnant. The authors note that this information is still limited and largely influenced in this published analysis by a CDC [Centers for Disease Control and Prevention] study in which the majority of patients had unknown pregnancy status. We also do not know if COVID-19 infection is associated with any birth defects since the majority of women with COVID-19 infection in the first trimester have not yet delivered.”
Malavika Prabhu, MD, an obstetetrician/gyneologist at Weill Cornell Medicine in New York City added that “this systematic review and meta analysis, which is a compilation of other studies done around the globe, confirms that pregnant women with preexisting medical conditions such as diabetes, hypertension, and obesity, are at increased risk of severe COVID-19 and that pregnant women with COVID-19 are at increased risk of invasive ventilation, compared to nonpregnant women with COVID-19, particularly if they have a preexisting medical condition.”
She said the preterm delivery rate of COVID-positive women is “challenging to interpret given that the total preterm birth rate potentially included many medically indicated preterm deliveries – which is to be expected – and there is no comparison group for spontaneous preterm birth presented”.
Other outstanding questions about COVID-19 pregnancies include whether they are associated with preeclampsia or smaller/growth restricted infants and why the cesarean delivery rate is high, she said. “But some of these questions are tough to answer with this data because it primarily reflects a COVID infection close to the delivery, not one that occurred several months prior to a delivery.”
Deborah Money, MD, professor of obstetrics and gynecology, medicine, and the school of population and public health, University of British Columbia, Vancouver, commented that “this is a group that have been doing ongoing living systematic reviews of the literature scanning for pregnancy outcomes. They post their information in real time on their website, so many of us in this area follow these postings as their methodology is robust and they work hard to only include high-quality literature and avoid duplication of cases in multiple papers. There has been a problem of re-reporting the same severe cases of COVID-19 in the literature.”
This “amplifies the importance of collecting Canadian-specific data to ensure that we understand if these kind of outcomes will also be found in Canada. The data presented in this paper represent outcomes from a broad range of countries with different methods of collecting information on pregnancy and highly variable prenatal care systems. This makes our pan-Canadian study of outcomes of COVID-19 for pregnant women and their infants, CANCOVID-Preg, even more important,” she said.
“Globally, we all must continue to monitor outcomes of COVID-19 in pregnancy to minimize adverse impact on women and their infants,” said Dr. Money, who was not involved in the study.
The study was partially funded by the World Health Organization and supported by Katie’s Team, a dedicated patient and public involvement group in Women’s Health. Dr. Metz is principal investigator for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network COVID-19 study; the study is funded by NICHD and enrollment is ongoing. Dr. Prabhu had no relevant financial disclosures. Dr. Money received funding from the Canadian Institutes for Health Research and the Public Health Agency of Canada and received a small grant from theBC Women’s Foundation for COVID-19 in pregnancy research.
SOURCE: Allotey J et al. BMJ. 2020;370:m3320.
according to a living systematic review from the PregCOV-19 Living Systematic Review Consortium.
The study, published in BMJ, shows an increased risk of preterm delivery, as well as the need for invasive ventilation in these women, wrote John Allotey, PhD, of the University of Birmingham (England) and colleagues. The findings “will produce a strong evidence base for living guidelines on COVID-19 and pregnancy,” they noted.
The systematic review included 77 studies, one-third each from the United States and China, with the remaining studies from Belgium, Brazil, Denmark, France, Israel, Italy, Japan, Mexico, the Netherlands Portugal, Spain, and the United Kingdom.
The studies included women with COVID-19, of whom 13,118 were either pregnant or in the postpartum or postabortion period and 83,486 were of reproductive age but not pregnant. Some studies also included healthy pregnant women for comparison.
In the pregnant and recently pregnant women, the most common COVID-19 symptoms were fever (40%) and cough (39%), with lymphopenia (35%) and raised C reactive protein levels (49%) being the most common laboratory findings. Pregnant and recently pregnant women with COVID-19 were less likely to have fever (odds ratio, 0.43) and myalgia (OR, 0.48), compared with nonpregnant women of reproductive age with COVID-19, reported the authors.
The overall preterm and spontaneous preterm birth rates in the COVID-19–positive women were 17% and 6% respectively. Dr. Allotey and authors noted that “these preterm births could be medically indicated, as the overall rates of spontaneous preterm births in pregnant women with COVID-19 was broadly similar to those observed in the pre-pandemic period.” There were 18 stillbirths and 6 neonatal deaths in the COVID-19 cohort.
Overall, 73 (0.1%) of pregnant women with confirmed COVID-19 died from any cause, and severe COVID-19 infection was diagnosed in 13%. Maternal risk factors associated with severe infection included older age (OR, 1.78), high body mass index (OR, 2.3), chronic hypertension (OR, 2.0), and preexisting diabetes (OR, 2.51). Compared with nonpregnant women with COVID-19, pregnant or recently pregnant women with the infection were at increased risk of admission to intensive care (OR, 1.62) and needing invasive ventilation (OR, 1.88).
The report included studies published between December 1, 2019, and June 26, 2020, but the living systematic review will involve weekly search updates, with analysis performed every 2-4 weeks and reported through a dedicated website.
The value of a living meta-analysis
Asked to comment on the findings, Torri Metz, MD, a maternal-fetal medicine subspecialist at the University of Utah, Salt Lake City, expressed surprise at the 10% rate of infection in the pregnant or recently pregnant population. “This is higher than currently observed at many hospitals in the United States,” she said in an interview. “This may overestimate the actual risk as many of these studies were published early in the pandemic and did not universally sample women who were pregnant for SARS-CoV-2.”
She noted the value of a living meta-analysis in that it will be updated on a regular basis as new evidence emerges. “During this time of rapidly accumulating publications about COVID-19 infection, clinicians will find it useful to have a resource in which the available data can be combined in one source.”
And there are still some outstanding questions that new studies hopefully will shed light on, she added. “The authors found that many of the risk factors for severe disease, like diabetes, obesity and high blood pressure, in nonpregnant adults are the same in the pregnant population. What remains unknown is if pregnant patients with COVID-19 infection are at higher risk than those who are not pregnant. The authors note that this information is still limited and largely influenced in this published analysis by a CDC [Centers for Disease Control and Prevention] study in which the majority of patients had unknown pregnancy status. We also do not know if COVID-19 infection is associated with any birth defects since the majority of women with COVID-19 infection in the first trimester have not yet delivered.”
Malavika Prabhu, MD, an obstetetrician/gyneologist at Weill Cornell Medicine in New York City added that “this systematic review and meta analysis, which is a compilation of other studies done around the globe, confirms that pregnant women with preexisting medical conditions such as diabetes, hypertension, and obesity, are at increased risk of severe COVID-19 and that pregnant women with COVID-19 are at increased risk of invasive ventilation, compared to nonpregnant women with COVID-19, particularly if they have a preexisting medical condition.”
She said the preterm delivery rate of COVID-positive women is “challenging to interpret given that the total preterm birth rate potentially included many medically indicated preterm deliveries – which is to be expected – and there is no comparison group for spontaneous preterm birth presented”.
Other outstanding questions about COVID-19 pregnancies include whether they are associated with preeclampsia or smaller/growth restricted infants and why the cesarean delivery rate is high, she said. “But some of these questions are tough to answer with this data because it primarily reflects a COVID infection close to the delivery, not one that occurred several months prior to a delivery.”
Deborah Money, MD, professor of obstetrics and gynecology, medicine, and the school of population and public health, University of British Columbia, Vancouver, commented that “this is a group that have been doing ongoing living systematic reviews of the literature scanning for pregnancy outcomes. They post their information in real time on their website, so many of us in this area follow these postings as their methodology is robust and they work hard to only include high-quality literature and avoid duplication of cases in multiple papers. There has been a problem of re-reporting the same severe cases of COVID-19 in the literature.”
This “amplifies the importance of collecting Canadian-specific data to ensure that we understand if these kind of outcomes will also be found in Canada. The data presented in this paper represent outcomes from a broad range of countries with different methods of collecting information on pregnancy and highly variable prenatal care systems. This makes our pan-Canadian study of outcomes of COVID-19 for pregnant women and their infants, CANCOVID-Preg, even more important,” she said.
“Globally, we all must continue to monitor outcomes of COVID-19 in pregnancy to minimize adverse impact on women and their infants,” said Dr. Money, who was not involved in the study.
The study was partially funded by the World Health Organization and supported by Katie’s Team, a dedicated patient and public involvement group in Women’s Health. Dr. Metz is principal investigator for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network COVID-19 study; the study is funded by NICHD and enrollment is ongoing. Dr. Prabhu had no relevant financial disclosures. Dr. Money received funding from the Canadian Institutes for Health Research and the Public Health Agency of Canada and received a small grant from theBC Women’s Foundation for COVID-19 in pregnancy research.
SOURCE: Allotey J et al. BMJ. 2020;370:m3320.
FROM BMJ
Tailored messaging needed to get cancer screening back on track
In late June, Lisa Richardson, MD, emerged from Atlanta, Georgia’s initial COVID-19 lockdown, and “got back out there” for some overdue doctor’s appointments, including a mammogram.
The mammogram was a particular priority for her, since she is director of the CDC’s Division of Cancer Prevention and Control. But she knows that cancer screening is going to be a much tougher sell for the average person going forward in the pandemic era.
“It really is a challenge trying to get people to feel comfortable coming back in to be screened,” she said. Richardson was speaking recently at the AACR virtual meeting: COVID-19 and Cancer, a virtual symposium on cancer prevention and early detection in the COVID-19 pandemic organized by the American Association for Cancer Research.
While health service shutdowns and stay-at-home orders forced the country’s initial precipitous decline in cancer screening, fear of contracting COVID-19 is a big part of what is preventing patients from returning.
“We’ve known even pre-pandemic that people were hesitant to do cancer screening and in some ways this has really given them an out to say, ‘Well, I’m going to hold off on that colonoscopy,’ ” Amy Leader, MD, from Thomas Jefferson University’s Kimmel Cancer Center in Philadelphia, Pennsylvania, said during the symposium.
Estimating the pandemic’s impact on cancer care
While the impact of the pandemic on cancer can only be estimated at the moment, the prospects are already daunting, said Richardson, speculating that the hard-won 26% drop in cancer mortality over the past two decades “may be put on hold or reversed” by COVID-19.
There could be as many as 10,000 excess deaths in the US from colorectal and breast cancer alone because of COVID-19 delays, predicted Norman E. Sharpless, director of the US National Cancer Institute in Bethesda, Maryland.
But even Sharpless acknowledges that his modeling gives a conservative estimate, “as it does not consider other cancer types, it does not account for the additional nonlethal morbidity from upstaging, and it assumes a moderate disruption in care that completely resolves after 6 months.”
With still no end to the pandemic in sight, the true scope of cancer screening and treatment disruptions will take a long time to assess, but several studies presented during the symposium revealed some early indications.
A national survey launched in mid-May, which involved 534 women either diagnosed with breast cancer or undergoing screening or diagnostic evaluation for it, found that delays in screening were reported by 31.7% of those with breast cancer, and 26.7% of those without. Additionally, 21% of those on active treatment for breast cancer reported treatment delays.
“It’s going to be really important to implement strategies to help patients return to care ... creating a culture and a feeling of safety among patients and communicating through the uncertainty that exists in the pandemic,” said study investigator Erica T. Warner, ScD MPH, from Massachusetts General Hospital, Boston.
Screening for prostate cancer (via prostate-specific antigen testing) also declined, though not as dramatically as that for breast cancer, noted Mara Epstein, ScD, from The Meyers Primary Care Institute, University of Massachusetts Medical School, Worcester. Her study at a large healthcare provider group compared rates of both screening and diagnostic mammographies, and also PSA testing, as well as breast and prostate biopsies in the first five months of 2020 vs the same months in 2019.
While a decrease from 2019 to 2020 was seen in all procedures over the entire study period, the greatest decline was seen in April for screening mammography (down 98%), and tomosynthesis (down 96%), as well as PSA testing (down 83%), she said.
More recent figures are hard to come by, but a recent weekly survey from the Primary Care Collaborative shows 46% of practices are offering preventive and chronic care management visits, but patients are not scheduling them, and 44% report that in-person visit volume is between 30%-50% below normal over the last 4 weeks.
Will COVID-19 exacerbate racial disparities in cancer?
Neither of the studies presented at the symposium analyzed cancer care disruptions by race, but there was concern among some panelists that cancer care disparities that existed before the pandemic will be magnified further.
“Over the next several months and into the next year there’s going to be some catch-up in screening and treatment, and one of my concerns is minority and underserved populations will not partake in that catch-up the way many middle-class Americans will,” said Otis Brawley, MD, from Johns Hopkins University, Baltimore, Maryland.
There is ample evidence that minority populations have been disproportionately hit by COVID-19, job losses, and lost health insurance, said the CDC’s Richardson, and all these factors could widen the cancer gap.
“It’s not a race thing, it’s a ‘what do you do thing,’ and an access to care thing, and what your socioeconomic status is,” Richardson said in an interview. “People who didn’t have sick leave before the pandemic still don’t have sick leave; if they didn’t have time to get their mammogram they still don’t have time.”
But she acknowledges that evidence is still lacking. Could some minority populations actually be less fearful of medical encounters because their work has already prevented them from sheltering in place? “It could go either way,” she said. “They might be less wary of venturing out into the clinic, but they also might reason that they’ve exposed themselves enough already at work and don’t want any additional exposure.”
In that regard, Richardson suggests population-specific messaging will be an important way of communicating with under-served populations to restart screening.
“We’re struggling at CDC with how to develop messages that resonate within different communities, because we’re missing the point of actually speaking to people within their culture and within the places that they live,” she said. “Just saying the same thing and putting a black face on it is not going to make a difference; you actually have to speak the language of the people you’re trying to reach — the same message in different packages.”
To that end, even before the pandemic, the CDC supported the development of Make It Your Own, a website that uses “evidence-based strategies” to assist healthcare organizations in customizing health information “by race, ethnicity, age, gender and location”, and target messages to “specific populations, cultural groups and languages”.
But Mass General’s Warner says she’s not sure she would argue for messages to be tailored by race, “at least not without evidence that values and priorities regarding returning to care differ between racial/ethnic groups.”
“Tailoring in the absence of data requires assumptions that may or may not be correct and ignores within-group heterogeneity,” Warner told Medscape Medical News. “However, I do believe that messaging about return to cancer screening and care should be multifaceted and use diverse imagery. This recognizes that some messages will resonate more or less with individuals based on their own characteristics, of which race may be one.”
Warner does believe in the power of tailored messaging though. “Part of the onus for healthcare institutions and providers is to make some decisions about who it is really important to bring back in soonest,” she said.
“Those are the ones we want to prioritize, as opposed to those who we want to get back into care but we don’t need to get them in right now,” Warner emphasized. “As they are balancing all the needs of their family and their community and their other needs, messaging that adds additional stress, worry, anxiety and shame is not what we want to do. So really we need to distinguish between these populations, identify the priorities, hit the hard message to people who really need it now, and encourage others to come back in as they can.”
Building trust
All the panelists agreed that building trust with the public will be key to getting cancer care back on track.
“I don’t think anyone trusts the healthcare community right now, but we already had this baseline distrust of healthcare among many minority communities, and now with COVID-19, the African American community in particular is seeing people go into the hospital and never come back,” said Richardson.
For Warner, the onus really falls on healthcare institutions. “We have to be proactive and not leave the burden of deciding when and how to return to care up to patients,” she said.
“What we need to focus on as much as possible is to get people to realize it is safe to come see the doctor,” said Johns Hopkins oncologist Brawley. “We have to make it safe for them to come see us, and then we have to convince them it is safe to come see us.”
Venturing out to her mammography appointment in early June, Richardson said she felt safe. “Everything was just the way it was supposed to be, everyone was masked, everyone was washing their hands,” she said.
Yet, by mid-June she had contracted COVID-19. “I don’t know where I got it,” she said. “No matter how careful you are, understand that if you’re in a total red spot, as I am, you can just get it.”
This article first appeared on Medscape.com.
In late June, Lisa Richardson, MD, emerged from Atlanta, Georgia’s initial COVID-19 lockdown, and “got back out there” for some overdue doctor’s appointments, including a mammogram.
The mammogram was a particular priority for her, since she is director of the CDC’s Division of Cancer Prevention and Control. But she knows that cancer screening is going to be a much tougher sell for the average person going forward in the pandemic era.
“It really is a challenge trying to get people to feel comfortable coming back in to be screened,” she said. Richardson was speaking recently at the AACR virtual meeting: COVID-19 and Cancer, a virtual symposium on cancer prevention and early detection in the COVID-19 pandemic organized by the American Association for Cancer Research.
While health service shutdowns and stay-at-home orders forced the country’s initial precipitous decline in cancer screening, fear of contracting COVID-19 is a big part of what is preventing patients from returning.
“We’ve known even pre-pandemic that people were hesitant to do cancer screening and in some ways this has really given them an out to say, ‘Well, I’m going to hold off on that colonoscopy,’ ” Amy Leader, MD, from Thomas Jefferson University’s Kimmel Cancer Center in Philadelphia, Pennsylvania, said during the symposium.
Estimating the pandemic’s impact on cancer care
While the impact of the pandemic on cancer can only be estimated at the moment, the prospects are already daunting, said Richardson, speculating that the hard-won 26% drop in cancer mortality over the past two decades “may be put on hold or reversed” by COVID-19.
There could be as many as 10,000 excess deaths in the US from colorectal and breast cancer alone because of COVID-19 delays, predicted Norman E. Sharpless, director of the US National Cancer Institute in Bethesda, Maryland.
But even Sharpless acknowledges that his modeling gives a conservative estimate, “as it does not consider other cancer types, it does not account for the additional nonlethal morbidity from upstaging, and it assumes a moderate disruption in care that completely resolves after 6 months.”
With still no end to the pandemic in sight, the true scope of cancer screening and treatment disruptions will take a long time to assess, but several studies presented during the symposium revealed some early indications.
A national survey launched in mid-May, which involved 534 women either diagnosed with breast cancer or undergoing screening or diagnostic evaluation for it, found that delays in screening were reported by 31.7% of those with breast cancer, and 26.7% of those without. Additionally, 21% of those on active treatment for breast cancer reported treatment delays.
“It’s going to be really important to implement strategies to help patients return to care ... creating a culture and a feeling of safety among patients and communicating through the uncertainty that exists in the pandemic,” said study investigator Erica T. Warner, ScD MPH, from Massachusetts General Hospital, Boston.
Screening for prostate cancer (via prostate-specific antigen testing) also declined, though not as dramatically as that for breast cancer, noted Mara Epstein, ScD, from The Meyers Primary Care Institute, University of Massachusetts Medical School, Worcester. Her study at a large healthcare provider group compared rates of both screening and diagnostic mammographies, and also PSA testing, as well as breast and prostate biopsies in the first five months of 2020 vs the same months in 2019.
While a decrease from 2019 to 2020 was seen in all procedures over the entire study period, the greatest decline was seen in April for screening mammography (down 98%), and tomosynthesis (down 96%), as well as PSA testing (down 83%), she said.
More recent figures are hard to come by, but a recent weekly survey from the Primary Care Collaborative shows 46% of practices are offering preventive and chronic care management visits, but patients are not scheduling them, and 44% report that in-person visit volume is between 30%-50% below normal over the last 4 weeks.
Will COVID-19 exacerbate racial disparities in cancer?
Neither of the studies presented at the symposium analyzed cancer care disruptions by race, but there was concern among some panelists that cancer care disparities that existed before the pandemic will be magnified further.
“Over the next several months and into the next year there’s going to be some catch-up in screening and treatment, and one of my concerns is minority and underserved populations will not partake in that catch-up the way many middle-class Americans will,” said Otis Brawley, MD, from Johns Hopkins University, Baltimore, Maryland.
There is ample evidence that minority populations have been disproportionately hit by COVID-19, job losses, and lost health insurance, said the CDC’s Richardson, and all these factors could widen the cancer gap.
“It’s not a race thing, it’s a ‘what do you do thing,’ and an access to care thing, and what your socioeconomic status is,” Richardson said in an interview. “People who didn’t have sick leave before the pandemic still don’t have sick leave; if they didn’t have time to get their mammogram they still don’t have time.”
But she acknowledges that evidence is still lacking. Could some minority populations actually be less fearful of medical encounters because their work has already prevented them from sheltering in place? “It could go either way,” she said. “They might be less wary of venturing out into the clinic, but they also might reason that they’ve exposed themselves enough already at work and don’t want any additional exposure.”
In that regard, Richardson suggests population-specific messaging will be an important way of communicating with under-served populations to restart screening.
“We’re struggling at CDC with how to develop messages that resonate within different communities, because we’re missing the point of actually speaking to people within their culture and within the places that they live,” she said. “Just saying the same thing and putting a black face on it is not going to make a difference; you actually have to speak the language of the people you’re trying to reach — the same message in different packages.”
To that end, even before the pandemic, the CDC supported the development of Make It Your Own, a website that uses “evidence-based strategies” to assist healthcare organizations in customizing health information “by race, ethnicity, age, gender and location”, and target messages to “specific populations, cultural groups and languages”.
But Mass General’s Warner says she’s not sure she would argue for messages to be tailored by race, “at least not without evidence that values and priorities regarding returning to care differ between racial/ethnic groups.”
“Tailoring in the absence of data requires assumptions that may or may not be correct and ignores within-group heterogeneity,” Warner told Medscape Medical News. “However, I do believe that messaging about return to cancer screening and care should be multifaceted and use diverse imagery. This recognizes that some messages will resonate more or less with individuals based on their own characteristics, of which race may be one.”
Warner does believe in the power of tailored messaging though. “Part of the onus for healthcare institutions and providers is to make some decisions about who it is really important to bring back in soonest,” she said.
“Those are the ones we want to prioritize, as opposed to those who we want to get back into care but we don’t need to get them in right now,” Warner emphasized. “As they are balancing all the needs of their family and their community and their other needs, messaging that adds additional stress, worry, anxiety and shame is not what we want to do. So really we need to distinguish between these populations, identify the priorities, hit the hard message to people who really need it now, and encourage others to come back in as they can.”
Building trust
All the panelists agreed that building trust with the public will be key to getting cancer care back on track.
“I don’t think anyone trusts the healthcare community right now, but we already had this baseline distrust of healthcare among many minority communities, and now with COVID-19, the African American community in particular is seeing people go into the hospital and never come back,” said Richardson.
For Warner, the onus really falls on healthcare institutions. “We have to be proactive and not leave the burden of deciding when and how to return to care up to patients,” she said.
“What we need to focus on as much as possible is to get people to realize it is safe to come see the doctor,” said Johns Hopkins oncologist Brawley. “We have to make it safe for them to come see us, and then we have to convince them it is safe to come see us.”
Venturing out to her mammography appointment in early June, Richardson said she felt safe. “Everything was just the way it was supposed to be, everyone was masked, everyone was washing their hands,” she said.
Yet, by mid-June she had contracted COVID-19. “I don’t know where I got it,” she said. “No matter how careful you are, understand that if you’re in a total red spot, as I am, you can just get it.”
This article first appeared on Medscape.com.
In late June, Lisa Richardson, MD, emerged from Atlanta, Georgia’s initial COVID-19 lockdown, and “got back out there” for some overdue doctor’s appointments, including a mammogram.
The mammogram was a particular priority for her, since she is director of the CDC’s Division of Cancer Prevention and Control. But she knows that cancer screening is going to be a much tougher sell for the average person going forward in the pandemic era.
“It really is a challenge trying to get people to feel comfortable coming back in to be screened,” she said. Richardson was speaking recently at the AACR virtual meeting: COVID-19 and Cancer, a virtual symposium on cancer prevention and early detection in the COVID-19 pandemic organized by the American Association for Cancer Research.
While health service shutdowns and stay-at-home orders forced the country’s initial precipitous decline in cancer screening, fear of contracting COVID-19 is a big part of what is preventing patients from returning.
“We’ve known even pre-pandemic that people were hesitant to do cancer screening and in some ways this has really given them an out to say, ‘Well, I’m going to hold off on that colonoscopy,’ ” Amy Leader, MD, from Thomas Jefferson University’s Kimmel Cancer Center in Philadelphia, Pennsylvania, said during the symposium.
Estimating the pandemic’s impact on cancer care
While the impact of the pandemic on cancer can only be estimated at the moment, the prospects are already daunting, said Richardson, speculating that the hard-won 26% drop in cancer mortality over the past two decades “may be put on hold or reversed” by COVID-19.
There could be as many as 10,000 excess deaths in the US from colorectal and breast cancer alone because of COVID-19 delays, predicted Norman E. Sharpless, director of the US National Cancer Institute in Bethesda, Maryland.
But even Sharpless acknowledges that his modeling gives a conservative estimate, “as it does not consider other cancer types, it does not account for the additional nonlethal morbidity from upstaging, and it assumes a moderate disruption in care that completely resolves after 6 months.”
With still no end to the pandemic in sight, the true scope of cancer screening and treatment disruptions will take a long time to assess, but several studies presented during the symposium revealed some early indications.
A national survey launched in mid-May, which involved 534 women either diagnosed with breast cancer or undergoing screening or diagnostic evaluation for it, found that delays in screening were reported by 31.7% of those with breast cancer, and 26.7% of those without. Additionally, 21% of those on active treatment for breast cancer reported treatment delays.
“It’s going to be really important to implement strategies to help patients return to care ... creating a culture and a feeling of safety among patients and communicating through the uncertainty that exists in the pandemic,” said study investigator Erica T. Warner, ScD MPH, from Massachusetts General Hospital, Boston.
Screening for prostate cancer (via prostate-specific antigen testing) also declined, though not as dramatically as that for breast cancer, noted Mara Epstein, ScD, from The Meyers Primary Care Institute, University of Massachusetts Medical School, Worcester. Her study at a large healthcare provider group compared rates of both screening and diagnostic mammographies, and also PSA testing, as well as breast and prostate biopsies in the first five months of 2020 vs the same months in 2019.
While a decrease from 2019 to 2020 was seen in all procedures over the entire study period, the greatest decline was seen in April for screening mammography (down 98%), and tomosynthesis (down 96%), as well as PSA testing (down 83%), she said.
More recent figures are hard to come by, but a recent weekly survey from the Primary Care Collaborative shows 46% of practices are offering preventive and chronic care management visits, but patients are not scheduling them, and 44% report that in-person visit volume is between 30%-50% below normal over the last 4 weeks.
Will COVID-19 exacerbate racial disparities in cancer?
Neither of the studies presented at the symposium analyzed cancer care disruptions by race, but there was concern among some panelists that cancer care disparities that existed before the pandemic will be magnified further.
“Over the next several months and into the next year there’s going to be some catch-up in screening and treatment, and one of my concerns is minority and underserved populations will not partake in that catch-up the way many middle-class Americans will,” said Otis Brawley, MD, from Johns Hopkins University, Baltimore, Maryland.
There is ample evidence that minority populations have been disproportionately hit by COVID-19, job losses, and lost health insurance, said the CDC’s Richardson, and all these factors could widen the cancer gap.
“It’s not a race thing, it’s a ‘what do you do thing,’ and an access to care thing, and what your socioeconomic status is,” Richardson said in an interview. “People who didn’t have sick leave before the pandemic still don’t have sick leave; if they didn’t have time to get their mammogram they still don’t have time.”
But she acknowledges that evidence is still lacking. Could some minority populations actually be less fearful of medical encounters because their work has already prevented them from sheltering in place? “It could go either way,” she said. “They might be less wary of venturing out into the clinic, but they also might reason that they’ve exposed themselves enough already at work and don’t want any additional exposure.”
In that regard, Richardson suggests population-specific messaging will be an important way of communicating with under-served populations to restart screening.
“We’re struggling at CDC with how to develop messages that resonate within different communities, because we’re missing the point of actually speaking to people within their culture and within the places that they live,” she said. “Just saying the same thing and putting a black face on it is not going to make a difference; you actually have to speak the language of the people you’re trying to reach — the same message in different packages.”
To that end, even before the pandemic, the CDC supported the development of Make It Your Own, a website that uses “evidence-based strategies” to assist healthcare organizations in customizing health information “by race, ethnicity, age, gender and location”, and target messages to “specific populations, cultural groups and languages”.
But Mass General’s Warner says she’s not sure she would argue for messages to be tailored by race, “at least not without evidence that values and priorities regarding returning to care differ between racial/ethnic groups.”
“Tailoring in the absence of data requires assumptions that may or may not be correct and ignores within-group heterogeneity,” Warner told Medscape Medical News. “However, I do believe that messaging about return to cancer screening and care should be multifaceted and use diverse imagery. This recognizes that some messages will resonate more or less with individuals based on their own characteristics, of which race may be one.”
Warner does believe in the power of tailored messaging though. “Part of the onus for healthcare institutions and providers is to make some decisions about who it is really important to bring back in soonest,” she said.
“Those are the ones we want to prioritize, as opposed to those who we want to get back into care but we don’t need to get them in right now,” Warner emphasized. “As they are balancing all the needs of their family and their community and their other needs, messaging that adds additional stress, worry, anxiety and shame is not what we want to do. So really we need to distinguish between these populations, identify the priorities, hit the hard message to people who really need it now, and encourage others to come back in as they can.”
Building trust
All the panelists agreed that building trust with the public will be key to getting cancer care back on track.
“I don’t think anyone trusts the healthcare community right now, but we already had this baseline distrust of healthcare among many minority communities, and now with COVID-19, the African American community in particular is seeing people go into the hospital and never come back,” said Richardson.
For Warner, the onus really falls on healthcare institutions. “We have to be proactive and not leave the burden of deciding when and how to return to care up to patients,” she said.
“What we need to focus on as much as possible is to get people to realize it is safe to come see the doctor,” said Johns Hopkins oncologist Brawley. “We have to make it safe for them to come see us, and then we have to convince them it is safe to come see us.”
Venturing out to her mammography appointment in early June, Richardson said she felt safe. “Everything was just the way it was supposed to be, everyone was masked, everyone was washing their hands,” she said.
Yet, by mid-June she had contracted COVID-19. “I don’t know where I got it,” she said. “No matter how careful you are, understand that if you’re in a total red spot, as I am, you can just get it.”
This article first appeared on Medscape.com.
Does stirrup choice influence vaginal surgery outcome?
according to the first randomized controlled trial comparing both types of lithotomy stirrups.
“Participants positioned in candy cane stirrups had greater hip abduction than those positioned in boot stirrups, which could provide a rationale for our findings,” suggested Ankita Gupta, MD, MPH, of the University of Louisville (Ky.), and colleagues. Their report is in Obstetrics & Gynecology.
But one expert questions this interpretation, calling it a major limitation of the study.
“The only difference between the two arms of the study is associated with the angles between the femurs,” said Rosanne M. Kho, MD, a gynecologic surgeon at Cleveland Clinic, who was not involved in the study. “The difference of the angles at the femur is not inherent to the type of stirrup but in the method in which the patients were positioned using the two different types of stirrups,” she said. “The same wide angle between the femurs can be attained with the boot stirrups if the patient is not positioned properly. To determine if the same benefit in physical function is achieved with a lesser angle between the femur, the investigators should use only one type of stirrup (whether the candy cane or the boot stirrups) and change only the angles of the femur.”
The study was a single-masked, randomized controlled trial of women undergoing vaginal surgery at the University of Louisville’s division of urogynecology between March 2018 and Oct. 2019. Surgeries included any combination of vaginal hysterectomy, vaginal vault suspension (uterosacral or sacrospinous ligament fixation), vaginectomy (partial or total), mid-urethral slings, or other surgeries such as urethral diverticulectomy, fistula repair, or mesh excision.
Among the 138 women included in the intention-to-treat analysis, 72 were randomized to candy cane, and 66 to boot (Yellofin) stirrups. They were positioned in the assigned stirrup by the attending surgeon, with assistance from the surgical team, after administration of anesthesia and were not informed of their allocation until the end of the study at 6 weeks post surgery.
On day 1 post surgery, a 100-point visual analog scale (VAS) questionnaire was administered for pain in the lower back, hips, buttocks, thighs, knees, calves, and feet, followed by a series of questionnaires at 6 weeks post surgery, including the PROMIS (Patient-Reported Outcomes Measurement Information System) forms on physical function, pain intensity, and pain interference, as well as the Pelvic Floor Disability Index (PFDI-20) and the Patient Global Impression of Improvement forms.
While the authors acknowledged that neurologic injuries following vaginal surgery are rare, and therefore difficult to measure, physical function is a “prudent” alternative measurement.
Although the study was designed to compare lithotomy stirrups, patient positioning also was measured. Once the patient was anesthetized, the surgeon used a goniometer to measure flexion at the hip and knee joints, the angle of abduction and external rotation at the hip. The “angle between the femurs” was measured by placing the fulcrum of the goniometer at the anal opening.
While the angles of flexion at the hips and knees were similar between groups, the study found a significant difference between groups in the angle between the femurs (mean ± standard deviation, 88.7 ± 13.4 candy cane vs. 77.2 ± 13.3 boot, P < .01).
In addition, the primary outcome, change in physical function based on the PROMIS physical function shortform-20a, was significantly different between the two groups: While subjects in the candy cane group demonstrated a decline of 1.9 in mean physical function score at 6 weeks compared to baseline, those in the boot stirrup group showed an increase of 1.9 from baseline. The mean 6-week postoperative scores were 45.8 versus 49.8 for the candy cane and boot stirrup groups respectively (P < .01).
Although it was “well executed by a well-respected group of vaginal surgeons at a major academic institution,” the study has other limitations, noted Dr. Kho.
“Though the measurements were obtained with the goniometer at the beginning of the surgery, it does not appear that a repeat measurement was performed at the end of the case. Is it possible that positioning could have shifted and resulted in further change in the angle of the femur/hip/knees compared to the beginning of the surgery?” she asked.
In addition, “compared to the candy canes, the boot stirrup has bulky boots that could limit opportunities for bedside assistants who were standing next to the primary surgeon to lean against the patient’s thighs during the surgery. Were there measures done to ensure that assistants were not leaning against the [candy cane] patients?”
In terms of the 6-week outcome measure, Dr. Kho suggested PROMIS outcomes measured at 2 weeks and at 4 or 6 weeks “would have provided greater insight to the study question.
“The authors acknowledge that neuropathies due to patient positioning manifest soon after surgery and tend to be transient. Incidence of neuropathy is extremely low in both groups and is equivalent. Factors that could impair quick return to normal activity as a result of the neuromuscular effects due to patient positioning should have been measured earlier,” she suggested.
Finally, Dr. Kho noted that the authors “fail to provide any likely rationale for the impaired physical function measured at 6 weeks that can be attributed to the difference in the angles at the femur. The findings of decreased physical function at 6 weeks in the candy cane group may be incidental, and may be different if measured at an earlier time (which would be more pertinent for this study) or at a later time such as 3 months.”
Individual authors acknowledged personal funds from Society of Gynecologic Surgeons, Elsevier publishing, RBI Medical, and AMAG Pharmaceuticals. Dr. Kho had no relevant financial disclosures.
SOURCE: Gupta A et al. Obstet Gynecol. 2020 July 8. doi: 10.1097/AOG.0000000000003954.
according to the first randomized controlled trial comparing both types of lithotomy stirrups.
“Participants positioned in candy cane stirrups had greater hip abduction than those positioned in boot stirrups, which could provide a rationale for our findings,” suggested Ankita Gupta, MD, MPH, of the University of Louisville (Ky.), and colleagues. Their report is in Obstetrics & Gynecology.
But one expert questions this interpretation, calling it a major limitation of the study.
“The only difference between the two arms of the study is associated with the angles between the femurs,” said Rosanne M. Kho, MD, a gynecologic surgeon at Cleveland Clinic, who was not involved in the study. “The difference of the angles at the femur is not inherent to the type of stirrup but in the method in which the patients were positioned using the two different types of stirrups,” she said. “The same wide angle between the femurs can be attained with the boot stirrups if the patient is not positioned properly. To determine if the same benefit in physical function is achieved with a lesser angle between the femur, the investigators should use only one type of stirrup (whether the candy cane or the boot stirrups) and change only the angles of the femur.”
The study was a single-masked, randomized controlled trial of women undergoing vaginal surgery at the University of Louisville’s division of urogynecology between March 2018 and Oct. 2019. Surgeries included any combination of vaginal hysterectomy, vaginal vault suspension (uterosacral or sacrospinous ligament fixation), vaginectomy (partial or total), mid-urethral slings, or other surgeries such as urethral diverticulectomy, fistula repair, or mesh excision.
Among the 138 women included in the intention-to-treat analysis, 72 were randomized to candy cane, and 66 to boot (Yellofin) stirrups. They were positioned in the assigned stirrup by the attending surgeon, with assistance from the surgical team, after administration of anesthesia and were not informed of their allocation until the end of the study at 6 weeks post surgery.
On day 1 post surgery, a 100-point visual analog scale (VAS) questionnaire was administered for pain in the lower back, hips, buttocks, thighs, knees, calves, and feet, followed by a series of questionnaires at 6 weeks post surgery, including the PROMIS (Patient-Reported Outcomes Measurement Information System) forms on physical function, pain intensity, and pain interference, as well as the Pelvic Floor Disability Index (PFDI-20) and the Patient Global Impression of Improvement forms.
While the authors acknowledged that neurologic injuries following vaginal surgery are rare, and therefore difficult to measure, physical function is a “prudent” alternative measurement.
Although the study was designed to compare lithotomy stirrups, patient positioning also was measured. Once the patient was anesthetized, the surgeon used a goniometer to measure flexion at the hip and knee joints, the angle of abduction and external rotation at the hip. The “angle between the femurs” was measured by placing the fulcrum of the goniometer at the anal opening.
While the angles of flexion at the hips and knees were similar between groups, the study found a significant difference between groups in the angle between the femurs (mean ± standard deviation, 88.7 ± 13.4 candy cane vs. 77.2 ± 13.3 boot, P < .01).
In addition, the primary outcome, change in physical function based on the PROMIS physical function shortform-20a, was significantly different between the two groups: While subjects in the candy cane group demonstrated a decline of 1.9 in mean physical function score at 6 weeks compared to baseline, those in the boot stirrup group showed an increase of 1.9 from baseline. The mean 6-week postoperative scores were 45.8 versus 49.8 for the candy cane and boot stirrup groups respectively (P < .01).
Although it was “well executed by a well-respected group of vaginal surgeons at a major academic institution,” the study has other limitations, noted Dr. Kho.
“Though the measurements were obtained with the goniometer at the beginning of the surgery, it does not appear that a repeat measurement was performed at the end of the case. Is it possible that positioning could have shifted and resulted in further change in the angle of the femur/hip/knees compared to the beginning of the surgery?” she asked.
In addition, “compared to the candy canes, the boot stirrup has bulky boots that could limit opportunities for bedside assistants who were standing next to the primary surgeon to lean against the patient’s thighs during the surgery. Were there measures done to ensure that assistants were not leaning against the [candy cane] patients?”
In terms of the 6-week outcome measure, Dr. Kho suggested PROMIS outcomes measured at 2 weeks and at 4 or 6 weeks “would have provided greater insight to the study question.
“The authors acknowledge that neuropathies due to patient positioning manifest soon after surgery and tend to be transient. Incidence of neuropathy is extremely low in both groups and is equivalent. Factors that could impair quick return to normal activity as a result of the neuromuscular effects due to patient positioning should have been measured earlier,” she suggested.
Finally, Dr. Kho noted that the authors “fail to provide any likely rationale for the impaired physical function measured at 6 weeks that can be attributed to the difference in the angles at the femur. The findings of decreased physical function at 6 weeks in the candy cane group may be incidental, and may be different if measured at an earlier time (which would be more pertinent for this study) or at a later time such as 3 months.”
Individual authors acknowledged personal funds from Society of Gynecologic Surgeons, Elsevier publishing, RBI Medical, and AMAG Pharmaceuticals. Dr. Kho had no relevant financial disclosures.
SOURCE: Gupta A et al. Obstet Gynecol. 2020 July 8. doi: 10.1097/AOG.0000000000003954.
according to the first randomized controlled trial comparing both types of lithotomy stirrups.
“Participants positioned in candy cane stirrups had greater hip abduction than those positioned in boot stirrups, which could provide a rationale for our findings,” suggested Ankita Gupta, MD, MPH, of the University of Louisville (Ky.), and colleagues. Their report is in Obstetrics & Gynecology.
But one expert questions this interpretation, calling it a major limitation of the study.
“The only difference between the two arms of the study is associated with the angles between the femurs,” said Rosanne M. Kho, MD, a gynecologic surgeon at Cleveland Clinic, who was not involved in the study. “The difference of the angles at the femur is not inherent to the type of stirrup but in the method in which the patients were positioned using the two different types of stirrups,” she said. “The same wide angle between the femurs can be attained with the boot stirrups if the patient is not positioned properly. To determine if the same benefit in physical function is achieved with a lesser angle between the femur, the investigators should use only one type of stirrup (whether the candy cane or the boot stirrups) and change only the angles of the femur.”
The study was a single-masked, randomized controlled trial of women undergoing vaginal surgery at the University of Louisville’s division of urogynecology between March 2018 and Oct. 2019. Surgeries included any combination of vaginal hysterectomy, vaginal vault suspension (uterosacral or sacrospinous ligament fixation), vaginectomy (partial or total), mid-urethral slings, or other surgeries such as urethral diverticulectomy, fistula repair, or mesh excision.
Among the 138 women included in the intention-to-treat analysis, 72 were randomized to candy cane, and 66 to boot (Yellofin) stirrups. They were positioned in the assigned stirrup by the attending surgeon, with assistance from the surgical team, after administration of anesthesia and were not informed of their allocation until the end of the study at 6 weeks post surgery.
On day 1 post surgery, a 100-point visual analog scale (VAS) questionnaire was administered for pain in the lower back, hips, buttocks, thighs, knees, calves, and feet, followed by a series of questionnaires at 6 weeks post surgery, including the PROMIS (Patient-Reported Outcomes Measurement Information System) forms on physical function, pain intensity, and pain interference, as well as the Pelvic Floor Disability Index (PFDI-20) and the Patient Global Impression of Improvement forms.
While the authors acknowledged that neurologic injuries following vaginal surgery are rare, and therefore difficult to measure, physical function is a “prudent” alternative measurement.
Although the study was designed to compare lithotomy stirrups, patient positioning also was measured. Once the patient was anesthetized, the surgeon used a goniometer to measure flexion at the hip and knee joints, the angle of abduction and external rotation at the hip. The “angle between the femurs” was measured by placing the fulcrum of the goniometer at the anal opening.
While the angles of flexion at the hips and knees were similar between groups, the study found a significant difference between groups in the angle between the femurs (mean ± standard deviation, 88.7 ± 13.4 candy cane vs. 77.2 ± 13.3 boot, P < .01).
In addition, the primary outcome, change in physical function based on the PROMIS physical function shortform-20a, was significantly different between the two groups: While subjects in the candy cane group demonstrated a decline of 1.9 in mean physical function score at 6 weeks compared to baseline, those in the boot stirrup group showed an increase of 1.9 from baseline. The mean 6-week postoperative scores were 45.8 versus 49.8 for the candy cane and boot stirrup groups respectively (P < .01).
Although it was “well executed by a well-respected group of vaginal surgeons at a major academic institution,” the study has other limitations, noted Dr. Kho.
“Though the measurements were obtained with the goniometer at the beginning of the surgery, it does not appear that a repeat measurement was performed at the end of the case. Is it possible that positioning could have shifted and resulted in further change in the angle of the femur/hip/knees compared to the beginning of the surgery?” she asked.
In addition, “compared to the candy canes, the boot stirrup has bulky boots that could limit opportunities for bedside assistants who were standing next to the primary surgeon to lean against the patient’s thighs during the surgery. Were there measures done to ensure that assistants were not leaning against the [candy cane] patients?”
In terms of the 6-week outcome measure, Dr. Kho suggested PROMIS outcomes measured at 2 weeks and at 4 or 6 weeks “would have provided greater insight to the study question.
“The authors acknowledge that neuropathies due to patient positioning manifest soon after surgery and tend to be transient. Incidence of neuropathy is extremely low in both groups and is equivalent. Factors that could impair quick return to normal activity as a result of the neuromuscular effects due to patient positioning should have been measured earlier,” she suggested.
Finally, Dr. Kho noted that the authors “fail to provide any likely rationale for the impaired physical function measured at 6 weeks that can be attributed to the difference in the angles at the femur. The findings of decreased physical function at 6 weeks in the candy cane group may be incidental, and may be different if measured at an earlier time (which would be more pertinent for this study) or at a later time such as 3 months.”
Individual authors acknowledged personal funds from Society of Gynecologic Surgeons, Elsevier publishing, RBI Medical, and AMAG Pharmaceuticals. Dr. Kho had no relevant financial disclosures.
SOURCE: Gupta A et al. Obstet Gynecol. 2020 July 8. doi: 10.1097/AOG.0000000000003954.
FROM OBSTETRICS & GYNECOLOGY
Postpartum tubal ligation safe in obese women
Women with a high body mass index who request tubal ligation immediately post partum face no increased risk of complications, compared with normal-weight woman, according to a large, single-institution, retrospective study.
“Our study underscores the overall safety of postpartum tubal ligation among overweight and obese women,” John J. Byrne, MD, MPH, and colleagues at the University of Texas, Dallas, reported in Obstetrics & Gynecology.
“Even among women in the highest BMI category, this procedure is safe and effective,” they noted, despite previous studies identifying body mass index (BMI) higher than 40 kg/m2 “as a significant barrier to this procedure.”
“For the woman who is appropriately counseled and desires permanent contraception, BMI should not impede her access to the procedure,” Dr. Byrne and associates said.
The study included 3,670 women undergoing postpartum tubal ligation after a vaginal delivery between August 2015 and March 2019 at Parkland Hospital, which is operated by the Dallas County Hospital District.
The method used was the Parkland-type tubal ligation – a bilateral midsegment partial salpingectomy performed through a 2-3 cm infraumbilical incision. Women were excluded if they were planning additional surgery, such as ovarian cyst removal or hernia repair at the same time.
Comparing a composite outcome of surgical complications and subsequent pregnancies over a 5-year follow-up, the study found no differences across all maternal BMI categories, which were stratified as: underweight or normal weight (BMI, 24.9 or lower), overweight (25-29.9), class I obesity (30-34.9), class II obesity (35-39.9), and class III obesity (40 or higher).
A full breakdown of the composite morbidity included “blood transfusion, aborted procedure, intraoperative complications (bleeding requiring additional surgery, extension of incision), anesthetic complication (high spinal, bronchospasm, postdural puncture headaches requiring blood patch, and allergic reaction to anesthetic), postoperative complication (deep wound infection, venous thromboembolism, ileus, small bowel obstruction, acute intestinal herniation, peritonitis), return to operating room, incomplete transection of fallopian tube, and subsequent pregnancy,” they reported.
Among the study subjects, the mean BMI was 32.2, with 263 being underweight or normal weight at the time of admission, 1,044 being overweight, 1,371 having class I obesity, 689 having class II obesity, 303 having class III obesity, and 11 patients classified as supermorbidly obese (a BMI of 50 or higher).
Overall, “composite morbidity occurred in 49 (1.3%) women and was not significantly different across BMI categories (P = .07),” noted the authors.
More specifically, there were 19 (1.5%) composite morbidity events in the nonobese cohort and 30 (1.3%) in the obese cohort. “Even among women who had undergone prior abdominal surgery, there was no association of BMI with the rate of procedural complication,” Dr. Byrne and associates added.
The subsequent pregnancy rate was 1.63 per 1,000 procedures performed, which is “significantly lower than previously reported estimates,” they noted. In total, there were six subsequent pregnancies in the cohort: three full term, two ectopic, and one of unknown location.
“Although there was variability in operative time in all BMI categories, this is likely not clinically relevant as the range in operative time overlapped across groups,” reported the authors. “Other surgical metrics, such as estimated blood loss and length of hospitalization after tubal ligation, were found to be no different between BMI categories.”
Their findings “can be generalized to other tubal ligation forms, such as modified Pomeroy and even possibly salpingectomy, if the minilaparotomy incision is the same,” Dr. Byrne and colleagues suggested.
“This innovative study adds an important practical perspective to the literature on postpartum permanent contraception – a finding that should be reassuring for obstetrician/gynecologists,” commented Eve Espey, MD MPH, who was not involved in the research.
“Women with high BMI are significantly less likely to receive desired postvaginal delivery tubal ligation, compared to lower-BMI women, as documented in several prior studies,” said Dr. Espey, who is professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque.
“Although those studies did not explore the reasons for nonfulfillment, intuitively concerns about complications or inability to complete the procedure are the most likely explanations,” she added.
“Although this study is limited by its retrospective nature, the smaller number of women in the highest BMI category, and lack of information on patients with unfulfilled requests for tubal ligation, it is overall well designed and should serve to encourage physicians to proceed with postvaginal delivery tubal ligation in patients across all BMI categories,” Dr. Espey concluded.
The study received no external funding; Dr. Byrne and associates reported no relevant financial disclosures. Dr. Espey is a member of the Ob.Gyn. News editorial advisory board, and said she has no relevant financial disclosures.
SOURCE: Byrne JJ et al. Obstet Gynecol. 2020;136:342-8.
Women with a high body mass index who request tubal ligation immediately post partum face no increased risk of complications, compared with normal-weight woman, according to a large, single-institution, retrospective study.
“Our study underscores the overall safety of postpartum tubal ligation among overweight and obese women,” John J. Byrne, MD, MPH, and colleagues at the University of Texas, Dallas, reported in Obstetrics & Gynecology.
“Even among women in the highest BMI category, this procedure is safe and effective,” they noted, despite previous studies identifying body mass index (BMI) higher than 40 kg/m2 “as a significant barrier to this procedure.”
“For the woman who is appropriately counseled and desires permanent contraception, BMI should not impede her access to the procedure,” Dr. Byrne and associates said.
The study included 3,670 women undergoing postpartum tubal ligation after a vaginal delivery between August 2015 and March 2019 at Parkland Hospital, which is operated by the Dallas County Hospital District.
The method used was the Parkland-type tubal ligation – a bilateral midsegment partial salpingectomy performed through a 2-3 cm infraumbilical incision. Women were excluded if they were planning additional surgery, such as ovarian cyst removal or hernia repair at the same time.
Comparing a composite outcome of surgical complications and subsequent pregnancies over a 5-year follow-up, the study found no differences across all maternal BMI categories, which were stratified as: underweight or normal weight (BMI, 24.9 or lower), overweight (25-29.9), class I obesity (30-34.9), class II obesity (35-39.9), and class III obesity (40 or higher).
A full breakdown of the composite morbidity included “blood transfusion, aborted procedure, intraoperative complications (bleeding requiring additional surgery, extension of incision), anesthetic complication (high spinal, bronchospasm, postdural puncture headaches requiring blood patch, and allergic reaction to anesthetic), postoperative complication (deep wound infection, venous thromboembolism, ileus, small bowel obstruction, acute intestinal herniation, peritonitis), return to operating room, incomplete transection of fallopian tube, and subsequent pregnancy,” they reported.
Among the study subjects, the mean BMI was 32.2, with 263 being underweight or normal weight at the time of admission, 1,044 being overweight, 1,371 having class I obesity, 689 having class II obesity, 303 having class III obesity, and 11 patients classified as supermorbidly obese (a BMI of 50 or higher).
Overall, “composite morbidity occurred in 49 (1.3%) women and was not significantly different across BMI categories (P = .07),” noted the authors.
More specifically, there were 19 (1.5%) composite morbidity events in the nonobese cohort and 30 (1.3%) in the obese cohort. “Even among women who had undergone prior abdominal surgery, there was no association of BMI with the rate of procedural complication,” Dr. Byrne and associates added.
The subsequent pregnancy rate was 1.63 per 1,000 procedures performed, which is “significantly lower than previously reported estimates,” they noted. In total, there were six subsequent pregnancies in the cohort: three full term, two ectopic, and one of unknown location.
“Although there was variability in operative time in all BMI categories, this is likely not clinically relevant as the range in operative time overlapped across groups,” reported the authors. “Other surgical metrics, such as estimated blood loss and length of hospitalization after tubal ligation, were found to be no different between BMI categories.”
Their findings “can be generalized to other tubal ligation forms, such as modified Pomeroy and even possibly salpingectomy, if the minilaparotomy incision is the same,” Dr. Byrne and colleagues suggested.
“This innovative study adds an important practical perspective to the literature on postpartum permanent contraception – a finding that should be reassuring for obstetrician/gynecologists,” commented Eve Espey, MD MPH, who was not involved in the research.
“Women with high BMI are significantly less likely to receive desired postvaginal delivery tubal ligation, compared to lower-BMI women, as documented in several prior studies,” said Dr. Espey, who is professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque.
“Although those studies did not explore the reasons for nonfulfillment, intuitively concerns about complications or inability to complete the procedure are the most likely explanations,” she added.
“Although this study is limited by its retrospective nature, the smaller number of women in the highest BMI category, and lack of information on patients with unfulfilled requests for tubal ligation, it is overall well designed and should serve to encourage physicians to proceed with postvaginal delivery tubal ligation in patients across all BMI categories,” Dr. Espey concluded.
The study received no external funding; Dr. Byrne and associates reported no relevant financial disclosures. Dr. Espey is a member of the Ob.Gyn. News editorial advisory board, and said she has no relevant financial disclosures.
SOURCE: Byrne JJ et al. Obstet Gynecol. 2020;136:342-8.
Women with a high body mass index who request tubal ligation immediately post partum face no increased risk of complications, compared with normal-weight woman, according to a large, single-institution, retrospective study.
“Our study underscores the overall safety of postpartum tubal ligation among overweight and obese women,” John J. Byrne, MD, MPH, and colleagues at the University of Texas, Dallas, reported in Obstetrics & Gynecology.
“Even among women in the highest BMI category, this procedure is safe and effective,” they noted, despite previous studies identifying body mass index (BMI) higher than 40 kg/m2 “as a significant barrier to this procedure.”
“For the woman who is appropriately counseled and desires permanent contraception, BMI should not impede her access to the procedure,” Dr. Byrne and associates said.
The study included 3,670 women undergoing postpartum tubal ligation after a vaginal delivery between August 2015 and March 2019 at Parkland Hospital, which is operated by the Dallas County Hospital District.
The method used was the Parkland-type tubal ligation – a bilateral midsegment partial salpingectomy performed through a 2-3 cm infraumbilical incision. Women were excluded if they were planning additional surgery, such as ovarian cyst removal or hernia repair at the same time.
Comparing a composite outcome of surgical complications and subsequent pregnancies over a 5-year follow-up, the study found no differences across all maternal BMI categories, which were stratified as: underweight or normal weight (BMI, 24.9 or lower), overweight (25-29.9), class I obesity (30-34.9), class II obesity (35-39.9), and class III obesity (40 or higher).
A full breakdown of the composite morbidity included “blood transfusion, aborted procedure, intraoperative complications (bleeding requiring additional surgery, extension of incision), anesthetic complication (high spinal, bronchospasm, postdural puncture headaches requiring blood patch, and allergic reaction to anesthetic), postoperative complication (deep wound infection, venous thromboembolism, ileus, small bowel obstruction, acute intestinal herniation, peritonitis), return to operating room, incomplete transection of fallopian tube, and subsequent pregnancy,” they reported.
Among the study subjects, the mean BMI was 32.2, with 263 being underweight or normal weight at the time of admission, 1,044 being overweight, 1,371 having class I obesity, 689 having class II obesity, 303 having class III obesity, and 11 patients classified as supermorbidly obese (a BMI of 50 or higher).
Overall, “composite morbidity occurred in 49 (1.3%) women and was not significantly different across BMI categories (P = .07),” noted the authors.
More specifically, there were 19 (1.5%) composite morbidity events in the nonobese cohort and 30 (1.3%) in the obese cohort. “Even among women who had undergone prior abdominal surgery, there was no association of BMI with the rate of procedural complication,” Dr. Byrne and associates added.
The subsequent pregnancy rate was 1.63 per 1,000 procedures performed, which is “significantly lower than previously reported estimates,” they noted. In total, there were six subsequent pregnancies in the cohort: three full term, two ectopic, and one of unknown location.
“Although there was variability in operative time in all BMI categories, this is likely not clinically relevant as the range in operative time overlapped across groups,” reported the authors. “Other surgical metrics, such as estimated blood loss and length of hospitalization after tubal ligation, were found to be no different between BMI categories.”
Their findings “can be generalized to other tubal ligation forms, such as modified Pomeroy and even possibly salpingectomy, if the minilaparotomy incision is the same,” Dr. Byrne and colleagues suggested.
“This innovative study adds an important practical perspective to the literature on postpartum permanent contraception – a finding that should be reassuring for obstetrician/gynecologists,” commented Eve Espey, MD MPH, who was not involved in the research.
“Women with high BMI are significantly less likely to receive desired postvaginal delivery tubal ligation, compared to lower-BMI women, as documented in several prior studies,” said Dr. Espey, who is professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque.
“Although those studies did not explore the reasons for nonfulfillment, intuitively concerns about complications or inability to complete the procedure are the most likely explanations,” she added.
“Although this study is limited by its retrospective nature, the smaller number of women in the highest BMI category, and lack of information on patients with unfulfilled requests for tubal ligation, it is overall well designed and should serve to encourage physicians to proceed with postvaginal delivery tubal ligation in patients across all BMI categories,” Dr. Espey concluded.
The study received no external funding; Dr. Byrne and associates reported no relevant financial disclosures. Dr. Espey is a member of the Ob.Gyn. News editorial advisory board, and said she has no relevant financial disclosures.
SOURCE: Byrne JJ et al. Obstet Gynecol. 2020;136:342-8.
FROM OBSTETRICS & GYNECOLOGY
Small NY study: Mother-baby transmission of COVID-19 not seen
according to a study out of New York-Presbyterian Hospital.
“It is suggested in the cumulative data that the virus does not confer additional risk to the fetus during labor or during the early postnatal period in both preterm and term infants,” concluded Jeffrey Perlman, MB ChB, and colleagues in Pediatrics.
But other experts suggest substantial gaps remain in our understanding of maternal transmission of SARS-CoV-2.
“Much more needs to be known,” Munish Gupta, MD, and colleagues from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, said in an accompanying editorial.
The prospective study is the first to describe a cohort of U.S. COVID-19–related deliveries, with the prior neonatal impact of COVID-19 “almost exclusively” reported from China, noted the authors. They included a cohort of 326 women who were tested for SARS-CoV-2 on admission to labor and delivery at New York-Presbyterian Hospital between March 22 and April 15th, 2020. Of the 31 (10%) mothers who tested positive, 15 (48%) were asymptomatic and 16 (52%) were symptomatic.
Two babies were born prematurely (one by Cesarean) and were isolated in negative pressure rooms with continuous positive airway pressure. Both were moved out of isolation after two negative test results and “have exhibited an unremarkable clinical course,” the authors reported.
The other 29 term babies were cared for in their mothers’ rooms, with breastfeeding allowed, if desired. These babies and their mothers were discharged from the hospital between 24 and 48 hours after delivery.
“Visitor restriction for mothers who were positive for COVID-19 included 14 days of no visitation from the start of symptoms,” noted the team.
They added “since the prepublication release there have been a total of 47 mothers positive for COVID-19, resulting in 47 infants; 4 have been admitted to neonatal intensive care. In addition, 32 other infants have been tested for a variety of indications within the unit. All infants test results have been negative.”
The brief report outlined the institution’s checklist for delivery preparedness in either the operating room or labor delivery room, including personal protective equipment, resuscitation, transportation to the neonatal intensive care unit, and early postresuscitation care. “Suspected or confirmed COVID-19 alone in an otherwise uncomplicated pregnancy is not an indication for the resuscitation team or the neonatal fellow,” they noted, adding delivery room preparation and management should include contact precautions. “With scrupulous attention to infectious precautions, horizontal viral transmission should be minimized,” they advised.
Dr. Perlman and associates emphasized that rapid turnaround SARSCoV-2 testing is “crucial to minimize the likelihood of a provider becoming infected and/or infecting the infant.”
Although the findings are “clearly reassuring,” Dr. Gupta and colleagues have reservations. “To what extent does this report address concerns for infection risk with a rooming-in approach to care?” they asked in their accompanying editorial. “The answer is likely some, but not much.”
Many questions remain, they said, including: “What precautions were used to minimize infection risk during the postbirth hospital course? What was the approach to skin-to-skin care and direct mother-newborn contact? Were restrictions placed on family members? Were changes made to routine interventions such as hearing screens or circumcisions? What practices were in place around environmental cleaning? Most important, how did the newborns do after discharge?”
The current uncertainty around neonatal COVID-19 infection risk has led to “disparate” variations in care recommendations, they pointed out. Whereas China’s consensus guidelines recommend a 14-day separation of COVID-19–positive mothers from their healthy infants, a practice supported by the American Academy of Pediatrics “when possible,” the Italian Society of Neonatology, the Royal College of Paediatrics and Child Health, and the Canadian Paediatric Society advise “rooming-in and breastfeeding with appropriate infection prevention measures.”
Dr. Gupta and colleagues pointed to the following as at least three “critical and time-sensitive needs for research around neonatal care and outcomes related to COVID-19”:
- Studies need to have much larger sample sizes and include diverse populations. This will allow for reliable measurement of outcomes.
- Descriptions of care practices must be in detail, especially about infection prevention; these should be presented in a way to compare the efficacy of different approaches.
- There needs to be follow-up information on outcomes of both the mother and the neonate after the birth hospitalization.
Asked to comment, Lillian Beard, MD, of George Washington University in Washington welcomed the data as “good news.”
“Although small, the study was done during a 3-week peak period at the hottest spot of the pandemic in the United States during that period. It illustrates how delivery room preparedness, adequate personal protective equipment, and carefully planned infection control precautions can positively impact outcomes even during a seemingly impossible period,” she said.
“Although there are many uncertainties about maternal COVID-19 transmission and neonatal infection risks ... in my opinion, during the after birth hospitalization, the inherent benefits of rooming in for breast feeding and the opportunities for the demonstration and teaching of infection prevention practices for the family home, far outweigh the risks of disease transmission,” said Dr. Beard, who was not involved with the study.
The study and the commentary emphasize the likely low risk of vertical transmission of the virus, with horizontal transmission being the greater risk. However, cases of transplacental transmission have been reported, and the lead investigator of one recent placental study cautions against complacency.
“Neonates can get infected in both ways. The majority of cases seem to be horizontal, but those who have been infected or highly suspected to be vertically infected are not a small percentage either,” said Daniele de Luca, MD, PhD, president-elect of the European Society for Pediatric and Neonatal Intensive Care (ESPNIC) and a neonatologist at Antoine Béclère Hospital in Clamart, France.
“Perlman’s data are interesting and consistent with other reports around the world. However, two things must be remembered,” he said in an interview. “First, newborn infants are at relatively low risk from SARS-CoV-2 infections, but this is very far from zero risk. Neonatal SARS-CoV-2 infections do exist and have been described around the world. While they have a mild course in the majority of cases, neonatologists should not forget them and should be prepared to offer the best care to these babies.”
“Second, how this can be balanced with the need to promote breastfeeding and avoid overtreatment or separation from the mother is a question far from being answered. Gupta et al. in their commentary are right in saying that we have more questions than answers. While waiting for the results of large initiatives (such as the ESPNIC EPICENTRE Registry that they cite) to answer these open points, the best we can do is to provide a personalised case by case approach, transparent information to parents, and an open counselling informing clinical decisions.”
The study received no external funding. Dr. Perlman and associates had no financial disclosures. Dr. Gupta and colleagues had no relevant financial disclosures. Neither Dr. Beard nor Dr. de Luca had any relevant financial disclosures.
SOURCE: Perlman J et al. Pediatrics. 2020;146(2):e20201567.
according to a study out of New York-Presbyterian Hospital.
“It is suggested in the cumulative data that the virus does not confer additional risk to the fetus during labor or during the early postnatal period in both preterm and term infants,” concluded Jeffrey Perlman, MB ChB, and colleagues in Pediatrics.
But other experts suggest substantial gaps remain in our understanding of maternal transmission of SARS-CoV-2.
“Much more needs to be known,” Munish Gupta, MD, and colleagues from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, said in an accompanying editorial.
The prospective study is the first to describe a cohort of U.S. COVID-19–related deliveries, with the prior neonatal impact of COVID-19 “almost exclusively” reported from China, noted the authors. They included a cohort of 326 women who were tested for SARS-CoV-2 on admission to labor and delivery at New York-Presbyterian Hospital between March 22 and April 15th, 2020. Of the 31 (10%) mothers who tested positive, 15 (48%) were asymptomatic and 16 (52%) were symptomatic.
Two babies were born prematurely (one by Cesarean) and were isolated in negative pressure rooms with continuous positive airway pressure. Both were moved out of isolation after two negative test results and “have exhibited an unremarkable clinical course,” the authors reported.
The other 29 term babies were cared for in their mothers’ rooms, with breastfeeding allowed, if desired. These babies and their mothers were discharged from the hospital between 24 and 48 hours after delivery.
“Visitor restriction for mothers who were positive for COVID-19 included 14 days of no visitation from the start of symptoms,” noted the team.
They added “since the prepublication release there have been a total of 47 mothers positive for COVID-19, resulting in 47 infants; 4 have been admitted to neonatal intensive care. In addition, 32 other infants have been tested for a variety of indications within the unit. All infants test results have been negative.”
The brief report outlined the institution’s checklist for delivery preparedness in either the operating room or labor delivery room, including personal protective equipment, resuscitation, transportation to the neonatal intensive care unit, and early postresuscitation care. “Suspected or confirmed COVID-19 alone in an otherwise uncomplicated pregnancy is not an indication for the resuscitation team or the neonatal fellow,” they noted, adding delivery room preparation and management should include contact precautions. “With scrupulous attention to infectious precautions, horizontal viral transmission should be minimized,” they advised.
Dr. Perlman and associates emphasized that rapid turnaround SARSCoV-2 testing is “crucial to minimize the likelihood of a provider becoming infected and/or infecting the infant.”
Although the findings are “clearly reassuring,” Dr. Gupta and colleagues have reservations. “To what extent does this report address concerns for infection risk with a rooming-in approach to care?” they asked in their accompanying editorial. “The answer is likely some, but not much.”
Many questions remain, they said, including: “What precautions were used to minimize infection risk during the postbirth hospital course? What was the approach to skin-to-skin care and direct mother-newborn contact? Were restrictions placed on family members? Were changes made to routine interventions such as hearing screens or circumcisions? What practices were in place around environmental cleaning? Most important, how did the newborns do after discharge?”
The current uncertainty around neonatal COVID-19 infection risk has led to “disparate” variations in care recommendations, they pointed out. Whereas China’s consensus guidelines recommend a 14-day separation of COVID-19–positive mothers from their healthy infants, a practice supported by the American Academy of Pediatrics “when possible,” the Italian Society of Neonatology, the Royal College of Paediatrics and Child Health, and the Canadian Paediatric Society advise “rooming-in and breastfeeding with appropriate infection prevention measures.”
Dr. Gupta and colleagues pointed to the following as at least three “critical and time-sensitive needs for research around neonatal care and outcomes related to COVID-19”:
- Studies need to have much larger sample sizes and include diverse populations. This will allow for reliable measurement of outcomes.
- Descriptions of care practices must be in detail, especially about infection prevention; these should be presented in a way to compare the efficacy of different approaches.
- There needs to be follow-up information on outcomes of both the mother and the neonate after the birth hospitalization.
Asked to comment, Lillian Beard, MD, of George Washington University in Washington welcomed the data as “good news.”
“Although small, the study was done during a 3-week peak period at the hottest spot of the pandemic in the United States during that period. It illustrates how delivery room preparedness, adequate personal protective equipment, and carefully planned infection control precautions can positively impact outcomes even during a seemingly impossible period,” she said.
“Although there are many uncertainties about maternal COVID-19 transmission and neonatal infection risks ... in my opinion, during the after birth hospitalization, the inherent benefits of rooming in for breast feeding and the opportunities for the demonstration and teaching of infection prevention practices for the family home, far outweigh the risks of disease transmission,” said Dr. Beard, who was not involved with the study.
The study and the commentary emphasize the likely low risk of vertical transmission of the virus, with horizontal transmission being the greater risk. However, cases of transplacental transmission have been reported, and the lead investigator of one recent placental study cautions against complacency.
“Neonates can get infected in both ways. The majority of cases seem to be horizontal, but those who have been infected or highly suspected to be vertically infected are not a small percentage either,” said Daniele de Luca, MD, PhD, president-elect of the European Society for Pediatric and Neonatal Intensive Care (ESPNIC) and a neonatologist at Antoine Béclère Hospital in Clamart, France.
“Perlman’s data are interesting and consistent with other reports around the world. However, two things must be remembered,” he said in an interview. “First, newborn infants are at relatively low risk from SARS-CoV-2 infections, but this is very far from zero risk. Neonatal SARS-CoV-2 infections do exist and have been described around the world. While they have a mild course in the majority of cases, neonatologists should not forget them and should be prepared to offer the best care to these babies.”
“Second, how this can be balanced with the need to promote breastfeeding and avoid overtreatment or separation from the mother is a question far from being answered. Gupta et al. in their commentary are right in saying that we have more questions than answers. While waiting for the results of large initiatives (such as the ESPNIC EPICENTRE Registry that they cite) to answer these open points, the best we can do is to provide a personalised case by case approach, transparent information to parents, and an open counselling informing clinical decisions.”
The study received no external funding. Dr. Perlman and associates had no financial disclosures. Dr. Gupta and colleagues had no relevant financial disclosures. Neither Dr. Beard nor Dr. de Luca had any relevant financial disclosures.
SOURCE: Perlman J et al. Pediatrics. 2020;146(2):e20201567.
according to a study out of New York-Presbyterian Hospital.
“It is suggested in the cumulative data that the virus does not confer additional risk to the fetus during labor or during the early postnatal period in both preterm and term infants,” concluded Jeffrey Perlman, MB ChB, and colleagues in Pediatrics.
But other experts suggest substantial gaps remain in our understanding of maternal transmission of SARS-CoV-2.
“Much more needs to be known,” Munish Gupta, MD, and colleagues from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, said in an accompanying editorial.
The prospective study is the first to describe a cohort of U.S. COVID-19–related deliveries, with the prior neonatal impact of COVID-19 “almost exclusively” reported from China, noted the authors. They included a cohort of 326 women who were tested for SARS-CoV-2 on admission to labor and delivery at New York-Presbyterian Hospital between March 22 and April 15th, 2020. Of the 31 (10%) mothers who tested positive, 15 (48%) were asymptomatic and 16 (52%) were symptomatic.
Two babies were born prematurely (one by Cesarean) and were isolated in negative pressure rooms with continuous positive airway pressure. Both were moved out of isolation after two negative test results and “have exhibited an unremarkable clinical course,” the authors reported.
The other 29 term babies were cared for in their mothers’ rooms, with breastfeeding allowed, if desired. These babies and their mothers were discharged from the hospital between 24 and 48 hours after delivery.
“Visitor restriction for mothers who were positive for COVID-19 included 14 days of no visitation from the start of symptoms,” noted the team.
They added “since the prepublication release there have been a total of 47 mothers positive for COVID-19, resulting in 47 infants; 4 have been admitted to neonatal intensive care. In addition, 32 other infants have been tested for a variety of indications within the unit. All infants test results have been negative.”
The brief report outlined the institution’s checklist for delivery preparedness in either the operating room or labor delivery room, including personal protective equipment, resuscitation, transportation to the neonatal intensive care unit, and early postresuscitation care. “Suspected or confirmed COVID-19 alone in an otherwise uncomplicated pregnancy is not an indication for the resuscitation team or the neonatal fellow,” they noted, adding delivery room preparation and management should include contact precautions. “With scrupulous attention to infectious precautions, horizontal viral transmission should be minimized,” they advised.
Dr. Perlman and associates emphasized that rapid turnaround SARSCoV-2 testing is “crucial to minimize the likelihood of a provider becoming infected and/or infecting the infant.”
Although the findings are “clearly reassuring,” Dr. Gupta and colleagues have reservations. “To what extent does this report address concerns for infection risk with a rooming-in approach to care?” they asked in their accompanying editorial. “The answer is likely some, but not much.”
Many questions remain, they said, including: “What precautions were used to minimize infection risk during the postbirth hospital course? What was the approach to skin-to-skin care and direct mother-newborn contact? Were restrictions placed on family members? Were changes made to routine interventions such as hearing screens or circumcisions? What practices were in place around environmental cleaning? Most important, how did the newborns do after discharge?”
The current uncertainty around neonatal COVID-19 infection risk has led to “disparate” variations in care recommendations, they pointed out. Whereas China’s consensus guidelines recommend a 14-day separation of COVID-19–positive mothers from their healthy infants, a practice supported by the American Academy of Pediatrics “when possible,” the Italian Society of Neonatology, the Royal College of Paediatrics and Child Health, and the Canadian Paediatric Society advise “rooming-in and breastfeeding with appropriate infection prevention measures.”
Dr. Gupta and colleagues pointed to the following as at least three “critical and time-sensitive needs for research around neonatal care and outcomes related to COVID-19”:
- Studies need to have much larger sample sizes and include diverse populations. This will allow for reliable measurement of outcomes.
- Descriptions of care practices must be in detail, especially about infection prevention; these should be presented in a way to compare the efficacy of different approaches.
- There needs to be follow-up information on outcomes of both the mother and the neonate after the birth hospitalization.
Asked to comment, Lillian Beard, MD, of George Washington University in Washington welcomed the data as “good news.”
“Although small, the study was done during a 3-week peak period at the hottest spot of the pandemic in the United States during that period. It illustrates how delivery room preparedness, adequate personal protective equipment, and carefully planned infection control precautions can positively impact outcomes even during a seemingly impossible period,” she said.
“Although there are many uncertainties about maternal COVID-19 transmission and neonatal infection risks ... in my opinion, during the after birth hospitalization, the inherent benefits of rooming in for breast feeding and the opportunities for the demonstration and teaching of infection prevention practices for the family home, far outweigh the risks of disease transmission,” said Dr. Beard, who was not involved with the study.
The study and the commentary emphasize the likely low risk of vertical transmission of the virus, with horizontal transmission being the greater risk. However, cases of transplacental transmission have been reported, and the lead investigator of one recent placental study cautions against complacency.
“Neonates can get infected in both ways. The majority of cases seem to be horizontal, but those who have been infected or highly suspected to be vertically infected are not a small percentage either,” said Daniele de Luca, MD, PhD, president-elect of the European Society for Pediatric and Neonatal Intensive Care (ESPNIC) and a neonatologist at Antoine Béclère Hospital in Clamart, France.
“Perlman’s data are interesting and consistent with other reports around the world. However, two things must be remembered,” he said in an interview. “First, newborn infants are at relatively low risk from SARS-CoV-2 infections, but this is very far from zero risk. Neonatal SARS-CoV-2 infections do exist and have been described around the world. While they have a mild course in the majority of cases, neonatologists should not forget them and should be prepared to offer the best care to these babies.”
“Second, how this can be balanced with the need to promote breastfeeding and avoid overtreatment or separation from the mother is a question far from being answered. Gupta et al. in their commentary are right in saying that we have more questions than answers. While waiting for the results of large initiatives (such as the ESPNIC EPICENTRE Registry that they cite) to answer these open points, the best we can do is to provide a personalised case by case approach, transparent information to parents, and an open counselling informing clinical decisions.”
The study received no external funding. Dr. Perlman and associates had no financial disclosures. Dr. Gupta and colleagues had no relevant financial disclosures. Neither Dr. Beard nor Dr. de Luca had any relevant financial disclosures.
SOURCE: Perlman J et al. Pediatrics. 2020;146(2):e20201567.
FROM PEDIATRICS
Higher stroke rates seen among patients with COVID-19 compared with influenza
, according to a retrospective cohort study conducted at New York–Presbyterian Hospital and Weill Cornell Medicine, New York. “These findings suggest that clinicians should be vigilant for symptoms and signs of acute ischemic stroke in patients with COVID-19 so that time-sensitive interventions, such as thrombolysis and thrombectomy, can be instituted if possible to reduce the burden of long-term disability,” wrote Alexander E. Merkler and colleagues. Their report is in JAMA Neurology.
While several recent publications have “raised the possibility” of this link, none have had an appropriate control group, noted Dr. Merkler of the department of neurology, Weill Cornell Medicine. “Further elucidation of thrombotic mechanisms in patients with COVID-19 may yield better strategies to prevent disabling thrombotic complications like ischemic stroke,” he added.
An increased risk of stroke
The study included 1,916 adults with confirmed COVID-19 (median age 64 years) who were either hospitalized or visited an emergency department between March 4 and May 2, 2020. These cases were compared with a historical cohort of 1,486 patients (median age 62 years) who were hospitalized with laboratory-confirmed influenza A or B between January 1, 2016, and May 31, 2018.
Among the patients with COVID-19, a diagnosis of cerebrovascular disease during hospitalization, a brain computed tomography (CT), or brain magnetic resonance imaging (MRI) was an indication of possible ischemic stroke. These records were then independently reviewed by two board-certified attending neurologists (with a third resolving any disagreement) to adjudicate a final stroke diagnosis. In the influenza cohort, the Cornell Acute Stroke Academic Registry (CAESAR) was used to ascertain ischemic strokes.
The study identified 31 patients with stroke among the COVID-19 cohort (1.6%; 95% confidence interval, 1.1%-2.3%) and 3 in the influenza cohort (0.2%; 95% CI, 0.0%-0.6%). After adjustment for age, sex, and race, stroke risk was almost 8 times higher in the COVID-19 cohort (OR, 7.6; 95% CI, 2.3-25.2).
This association “persisted across multiple sensitivity analyses, with the magnitude of relative associations ranging from 4.0 to 9,” wrote the authors. “This included a sensitivity analysis that adjusted for the number of vascular risk factors and ICU admissions (OR, 4.6; 95% CI, 1.4-15.7).”
The median age of patients with COVID-19 and stroke was 69 years, and the median duration of COVID-19 symptom onset to stroke diagnosis was 16 days. Stroke symptoms were the presenting complaint in only 26% of the patients, while the remainder developing stroke while hospitalized, and more than a third (35%) of all strokes occurred in patients who were mechanically ventilated with severe COVID-19. Inpatient mortality was considerably higher among patients with COVID-19 with stroke versus without (32% vs. 14%; P = .003).
In patients with COVID-19 “most ischemic strokes occurred in older age groups, those with traditional stroke risk factors, and people of color,” wrote the authors. “We also noted that initial plasma D-dimer levels were nearly 3-fold higher in those who received a diagnosis of ischemic stroke than in those who did not” (1.930 mcg/mL vs. 0.682 mcg/mL).
The authors suggested several possible explanations for the elevated risk of stroke in COVID-19. Acute viral illnesses are known to trigger inflammation, and COVID-19 in particular is associated with “a vigorous inflammatory response accompanied by coagulopathy, with elevated D-dimer levels and the frequent presence of antiphospholipid antibodies,” they wrote. The infection is also associated with more severe respiratory syndrome compared with influenza, as well as a heightened risk for complications such as atrial arrhythmias, myocardial infarction, heart failure, myocarditis, and venous thromboses, all of which likely contribute to the risk of ischemic stroke.”
COVID or conventional risk factors?
Asked to comment on the study, Benedict Michael, MBChB (Hons), MRCP (Neurol), PhD, from the United Kingdom’s Coronerve Studies Group, a collaborative initiative to study the neurological features of COVID-19, said in an interview that “this study suggests many cases of stroke are occurring in older patients with multiple existing conventional and well recognized risks for stroke, and may simply represent decompensation during sepsis.”
Dr. Michael, a senior clinician scientist fellow at the University of Liverpool and an honorary consultant neurologist at the Walton Centre, was the senior author on a recently published UK-wide surveillance study on the neurological and neuropsychiatric complications of COVID-19 (Lancet Psychiatry. 2020 Jun 25. doi: 10.1016/S2215-0366[20]30287-X).
He said among patients in the New York study, “those with COVID and a stroke appeared to have many conventional risk factors for stroke (and often at higher percentages than COVID patients without a stroke), e.g. hypertension, overweight, diabetes, hyperlipidemia, existing vascular disease affecting the coronary arteries and atrial fibrillation. To establish evidence-based treatment pathways, clearly further studies are needed to determine the biological mechanisms underlying the seemingly higher rate of stroke with COVID-19 than influenza; but this must especially focus on those younger patients without conventional risk factors for stroke (which are largely not included in this study).”
SOURCE: Merkler AE et al. JAMA Neurol. doi: 10.1001/jamaneurol.2020.2730.
, according to a retrospective cohort study conducted at New York–Presbyterian Hospital and Weill Cornell Medicine, New York. “These findings suggest that clinicians should be vigilant for symptoms and signs of acute ischemic stroke in patients with COVID-19 so that time-sensitive interventions, such as thrombolysis and thrombectomy, can be instituted if possible to reduce the burden of long-term disability,” wrote Alexander E. Merkler and colleagues. Their report is in JAMA Neurology.
While several recent publications have “raised the possibility” of this link, none have had an appropriate control group, noted Dr. Merkler of the department of neurology, Weill Cornell Medicine. “Further elucidation of thrombotic mechanisms in patients with COVID-19 may yield better strategies to prevent disabling thrombotic complications like ischemic stroke,” he added.
An increased risk of stroke
The study included 1,916 adults with confirmed COVID-19 (median age 64 years) who were either hospitalized or visited an emergency department between March 4 and May 2, 2020. These cases were compared with a historical cohort of 1,486 patients (median age 62 years) who were hospitalized with laboratory-confirmed influenza A or B between January 1, 2016, and May 31, 2018.
Among the patients with COVID-19, a diagnosis of cerebrovascular disease during hospitalization, a brain computed tomography (CT), or brain magnetic resonance imaging (MRI) was an indication of possible ischemic stroke. These records were then independently reviewed by two board-certified attending neurologists (with a third resolving any disagreement) to adjudicate a final stroke diagnosis. In the influenza cohort, the Cornell Acute Stroke Academic Registry (CAESAR) was used to ascertain ischemic strokes.
The study identified 31 patients with stroke among the COVID-19 cohort (1.6%; 95% confidence interval, 1.1%-2.3%) and 3 in the influenza cohort (0.2%; 95% CI, 0.0%-0.6%). After adjustment for age, sex, and race, stroke risk was almost 8 times higher in the COVID-19 cohort (OR, 7.6; 95% CI, 2.3-25.2).
This association “persisted across multiple sensitivity analyses, with the magnitude of relative associations ranging from 4.0 to 9,” wrote the authors. “This included a sensitivity analysis that adjusted for the number of vascular risk factors and ICU admissions (OR, 4.6; 95% CI, 1.4-15.7).”
The median age of patients with COVID-19 and stroke was 69 years, and the median duration of COVID-19 symptom onset to stroke diagnosis was 16 days. Stroke symptoms were the presenting complaint in only 26% of the patients, while the remainder developing stroke while hospitalized, and more than a third (35%) of all strokes occurred in patients who were mechanically ventilated with severe COVID-19. Inpatient mortality was considerably higher among patients with COVID-19 with stroke versus without (32% vs. 14%; P = .003).
In patients with COVID-19 “most ischemic strokes occurred in older age groups, those with traditional stroke risk factors, and people of color,” wrote the authors. “We also noted that initial plasma D-dimer levels were nearly 3-fold higher in those who received a diagnosis of ischemic stroke than in those who did not” (1.930 mcg/mL vs. 0.682 mcg/mL).
The authors suggested several possible explanations for the elevated risk of stroke in COVID-19. Acute viral illnesses are known to trigger inflammation, and COVID-19 in particular is associated with “a vigorous inflammatory response accompanied by coagulopathy, with elevated D-dimer levels and the frequent presence of antiphospholipid antibodies,” they wrote. The infection is also associated with more severe respiratory syndrome compared with influenza, as well as a heightened risk for complications such as atrial arrhythmias, myocardial infarction, heart failure, myocarditis, and venous thromboses, all of which likely contribute to the risk of ischemic stroke.”
COVID or conventional risk factors?
Asked to comment on the study, Benedict Michael, MBChB (Hons), MRCP (Neurol), PhD, from the United Kingdom’s Coronerve Studies Group, a collaborative initiative to study the neurological features of COVID-19, said in an interview that “this study suggests many cases of stroke are occurring in older patients with multiple existing conventional and well recognized risks for stroke, and may simply represent decompensation during sepsis.”
Dr. Michael, a senior clinician scientist fellow at the University of Liverpool and an honorary consultant neurologist at the Walton Centre, was the senior author on a recently published UK-wide surveillance study on the neurological and neuropsychiatric complications of COVID-19 (Lancet Psychiatry. 2020 Jun 25. doi: 10.1016/S2215-0366[20]30287-X).
He said among patients in the New York study, “those with COVID and a stroke appeared to have many conventional risk factors for stroke (and often at higher percentages than COVID patients without a stroke), e.g. hypertension, overweight, diabetes, hyperlipidemia, existing vascular disease affecting the coronary arteries and atrial fibrillation. To establish evidence-based treatment pathways, clearly further studies are needed to determine the biological mechanisms underlying the seemingly higher rate of stroke with COVID-19 than influenza; but this must especially focus on those younger patients without conventional risk factors for stroke (which are largely not included in this study).”
SOURCE: Merkler AE et al. JAMA Neurol. doi: 10.1001/jamaneurol.2020.2730.
, according to a retrospective cohort study conducted at New York–Presbyterian Hospital and Weill Cornell Medicine, New York. “These findings suggest that clinicians should be vigilant for symptoms and signs of acute ischemic stroke in patients with COVID-19 so that time-sensitive interventions, such as thrombolysis and thrombectomy, can be instituted if possible to reduce the burden of long-term disability,” wrote Alexander E. Merkler and colleagues. Their report is in JAMA Neurology.
While several recent publications have “raised the possibility” of this link, none have had an appropriate control group, noted Dr. Merkler of the department of neurology, Weill Cornell Medicine. “Further elucidation of thrombotic mechanisms in patients with COVID-19 may yield better strategies to prevent disabling thrombotic complications like ischemic stroke,” he added.
An increased risk of stroke
The study included 1,916 adults with confirmed COVID-19 (median age 64 years) who were either hospitalized or visited an emergency department between March 4 and May 2, 2020. These cases were compared with a historical cohort of 1,486 patients (median age 62 years) who were hospitalized with laboratory-confirmed influenza A or B between January 1, 2016, and May 31, 2018.
Among the patients with COVID-19, a diagnosis of cerebrovascular disease during hospitalization, a brain computed tomography (CT), or brain magnetic resonance imaging (MRI) was an indication of possible ischemic stroke. These records were then independently reviewed by two board-certified attending neurologists (with a third resolving any disagreement) to adjudicate a final stroke diagnosis. In the influenza cohort, the Cornell Acute Stroke Academic Registry (CAESAR) was used to ascertain ischemic strokes.
The study identified 31 patients with stroke among the COVID-19 cohort (1.6%; 95% confidence interval, 1.1%-2.3%) and 3 in the influenza cohort (0.2%; 95% CI, 0.0%-0.6%). After adjustment for age, sex, and race, stroke risk was almost 8 times higher in the COVID-19 cohort (OR, 7.6; 95% CI, 2.3-25.2).
This association “persisted across multiple sensitivity analyses, with the magnitude of relative associations ranging from 4.0 to 9,” wrote the authors. “This included a sensitivity analysis that adjusted for the number of vascular risk factors and ICU admissions (OR, 4.6; 95% CI, 1.4-15.7).”
The median age of patients with COVID-19 and stroke was 69 years, and the median duration of COVID-19 symptom onset to stroke diagnosis was 16 days. Stroke symptoms were the presenting complaint in only 26% of the patients, while the remainder developing stroke while hospitalized, and more than a third (35%) of all strokes occurred in patients who were mechanically ventilated with severe COVID-19. Inpatient mortality was considerably higher among patients with COVID-19 with stroke versus without (32% vs. 14%; P = .003).
In patients with COVID-19 “most ischemic strokes occurred in older age groups, those with traditional stroke risk factors, and people of color,” wrote the authors. “We also noted that initial plasma D-dimer levels were nearly 3-fold higher in those who received a diagnosis of ischemic stroke than in those who did not” (1.930 mcg/mL vs. 0.682 mcg/mL).
The authors suggested several possible explanations for the elevated risk of stroke in COVID-19. Acute viral illnesses are known to trigger inflammation, and COVID-19 in particular is associated with “a vigorous inflammatory response accompanied by coagulopathy, with elevated D-dimer levels and the frequent presence of antiphospholipid antibodies,” they wrote. The infection is also associated with more severe respiratory syndrome compared with influenza, as well as a heightened risk for complications such as atrial arrhythmias, myocardial infarction, heart failure, myocarditis, and venous thromboses, all of which likely contribute to the risk of ischemic stroke.”
COVID or conventional risk factors?
Asked to comment on the study, Benedict Michael, MBChB (Hons), MRCP (Neurol), PhD, from the United Kingdom’s Coronerve Studies Group, a collaborative initiative to study the neurological features of COVID-19, said in an interview that “this study suggests many cases of stroke are occurring in older patients with multiple existing conventional and well recognized risks for stroke, and may simply represent decompensation during sepsis.”
Dr. Michael, a senior clinician scientist fellow at the University of Liverpool and an honorary consultant neurologist at the Walton Centre, was the senior author on a recently published UK-wide surveillance study on the neurological and neuropsychiatric complications of COVID-19 (Lancet Psychiatry. 2020 Jun 25. doi: 10.1016/S2215-0366[20]30287-X).
He said among patients in the New York study, “those with COVID and a stroke appeared to have many conventional risk factors for stroke (and often at higher percentages than COVID patients without a stroke), e.g. hypertension, overweight, diabetes, hyperlipidemia, existing vascular disease affecting the coronary arteries and atrial fibrillation. To establish evidence-based treatment pathways, clearly further studies are needed to determine the biological mechanisms underlying the seemingly higher rate of stroke with COVID-19 than influenza; but this must especially focus on those younger patients without conventional risk factors for stroke (which are largely not included in this study).”
SOURCE: Merkler AE et al. JAMA Neurol. doi: 10.1001/jamaneurol.2020.2730.
FROM JAMA NEUROLOGY
Can an app guide cancer treatment decisions during the pandemic?
Deciding which cancer patients need immediate treatment and who can safely wait is an uncomfortable assessment for cancer clinicians during the COVID-19 pandemic.
In early April, as the COVID-19 surge was bearing down on New York City, those treatment decisions were “a juggling act every single day,” Jonathan Yang, MD, PhD, a radiation oncologist from New York’s Memorial Sloan Kettering Cancer Center, told Medscape Medical News.
Eventually, a glut of guidelines, recommendations, and expert opinions aimed at helping oncologists emerged. The tools help navigate the complicated risk-benefit analysis of their patient’s risk of infection by SARS-CoV-2 and delaying therapy.
Now, a new tool, which appears to be the first of its kind, quantifies that risk-benefit analysis. But its presence immediately raises the question: can it help?
Three-Tier Systems Are Not Very Sophisticated
OncCOVID, a free tool that was launched May 26 by the University of Michigan, allows physicians to individualize risk estimates for delaying treatment of up to 25 early- to late-stage cancers. It includes more than 45 patient characteristics, such as age, location, cancer type, cancer stage, treatment plan, underlying medical conditions, and proposed length of delay in care.
Combining these personal details with data from the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) registry and the National Cancer Database, the Michigan app then estimates a patient’s 5- or 10-year survival with immediate vs delayed treatment and weighs that against their risk for COVID-19 using data from the Johns Hopkins Coronavirus Resource Center.
“We thought, isn’t it better to at least provide some evidence-based quantification, rather than a back-of-the-envelope three-tier system that is just sort of ‘made up’?“ explained one of the developers, Daniel Spratt, MD, associate professor of radiation oncology at Michigan Medicine.
Spratt explained that almost every organization, professional society, and government has created something like a three-tier system. Tier 1 represents urgent cases and patients who need immediate treatment. For tier 2, treatment can be delayed weeks or a month, and with tier 3, it can be delayed until the pandemic is over or it’s deemed safe.
“[This system] sounds good at first glance, but in cancer, we’re always talking about personalized medicine, and it’s mind-blowing that these tier systems are only based on urgency and prognosis,” he told Medscape Medical News.
Spratt offered an example. Consider a patient with a very aggressive brain tumor ― that patient is in tier 1 and should undergo treatment immediately. But will the treatment actually help? And how helpful would the procedure be if, say, the patient is 80 years old and, if infected, would have a 30% to 50% chance of dying from the coronavirus?
“If the model says this guy has a 5% harm and this one has 30% harm, you can use that to help prioritize,” summarized Spratt.
The app can generate risk estimates for patients living anywhere in the world and has already been accessed by people from 37 countries. However, Spratt cautions that it is primarily “designed and calibrated for the US.
“The estimates are based on very large US registries, and though it’s probably somewhat similar across much of the world, there’s probably certain cancer types that are more region specific ― especially something like stomach cancer or certain types of head and neck cancer in parts of Asia, for example,” he said.
Although the app’s COVID-19 data are specific to the county level in the United States, elsewhere in the world, it is only country specific.
“We’re using the best data we have for coronavirus, but everyone knows we still have large data gaps,” he acknowledged.
How Accurate?
Asked to comment on the app, Richard Bleicher, MD, leader of the Breast Cancer Program at Fox Chase Cancer Center, Philadelphia, praised the effort and the goal but had some concerns.
“Several questions arise, most important of which is, How accurate is this, and how has this been validated, if at all ― especially as it is too soon to see the outcomes of patients affected in this pandemic?” he told Medscape Medical News.
“We are imposing delays on a broad scale because of the coronavirus, and we are getting continuously changing data as we test more patients. But both situations are novel and may not be accurately represented by the data being pulled, because the datasets use patients from a few years ago, and confounders in these datasets may not apply to this situation,” Bleicher continued.
Although acknowledging the “value in delineating the risk of dying from cancer vs the risk of dying from the SARS-CoV-2 pandemic,” Bleicher urged caution in using the tool to make individual patient decisions.
“We need to remember that the best of modeling ... can be wildly inaccurate and needs to be validated using patients having the circumstances in question. ... This won’t be possible until long after the pandemic is completed, and so the model’s accuracy remains unknown.”
That sentiment was echoed by Giampaolo Bianchini, MD, head of the Breast Cancer Group, Department of Medical Oncology, Ospedale San Raffaele, in Milan, Italy.
“Arbitrarily postponing and modifying treatment strategies including surgery, radiation therapy, and medical therapy without properly balancing the risk/benefit ratio may lead to significantly worse cancer-related outcomes, which largely exceed the actual risks for COVID,” he wrote in an email.
“The OncCOVID app is a remarkable attempt to fill the gap between perception and estimation,” he said. The app provides side by side the COVID-19 risk estimation and the consequences of arbitrary deviation from the standard of care, observed Bianchini.
However, he pointed out weaknesses, including the fact that the “data generated in literature are not always of high quality and do not take into consideration relevant characteristics of the disease and treatment benefit. It should for sure be used, but then also interpreted with caution.”
Another Italian group responded more positively.
“In our opinion, it could be a useful tool for clinicians,” wrote colleagues Alessio Cortelinni and Giampiero Porzio, both medical oncologists at San Salvatore Hospital and the University of L’Aquila, in Italy. “This Web app might assist clinicians in balancing the risk/benefit ratio of being treated and/or access to the outpatient cancer center for each kind of patient (both early and advanced stages), in order to make a more tailored counseling,” they wrote in an email. “Importantly, the Web app might help those clinicians who work ‘alone,’ in peripheral centers, without resources, colleagues, and multidisciplinary tumor boards on whom they can rely.”
Bleicher, who was involved in the COVID-19 Breast Cancer Consortium’s recommendations for prioritizing breast cancer treatment, summarized that the app “may end up being close or accurate, but we won’t know except in hindsight.”
This article first appeared on Medscape.com.
Deciding which cancer patients need immediate treatment and who can safely wait is an uncomfortable assessment for cancer clinicians during the COVID-19 pandemic.
In early April, as the COVID-19 surge was bearing down on New York City, those treatment decisions were “a juggling act every single day,” Jonathan Yang, MD, PhD, a radiation oncologist from New York’s Memorial Sloan Kettering Cancer Center, told Medscape Medical News.
Eventually, a glut of guidelines, recommendations, and expert opinions aimed at helping oncologists emerged. The tools help navigate the complicated risk-benefit analysis of their patient’s risk of infection by SARS-CoV-2 and delaying therapy.
Now, a new tool, which appears to be the first of its kind, quantifies that risk-benefit analysis. But its presence immediately raises the question: can it help?
Three-Tier Systems Are Not Very Sophisticated
OncCOVID, a free tool that was launched May 26 by the University of Michigan, allows physicians to individualize risk estimates for delaying treatment of up to 25 early- to late-stage cancers. It includes more than 45 patient characteristics, such as age, location, cancer type, cancer stage, treatment plan, underlying medical conditions, and proposed length of delay in care.
Combining these personal details with data from the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) registry and the National Cancer Database, the Michigan app then estimates a patient’s 5- or 10-year survival with immediate vs delayed treatment and weighs that against their risk for COVID-19 using data from the Johns Hopkins Coronavirus Resource Center.
“We thought, isn’t it better to at least provide some evidence-based quantification, rather than a back-of-the-envelope three-tier system that is just sort of ‘made up’?“ explained one of the developers, Daniel Spratt, MD, associate professor of radiation oncology at Michigan Medicine.
Spratt explained that almost every organization, professional society, and government has created something like a three-tier system. Tier 1 represents urgent cases and patients who need immediate treatment. For tier 2, treatment can be delayed weeks or a month, and with tier 3, it can be delayed until the pandemic is over or it’s deemed safe.
“[This system] sounds good at first glance, but in cancer, we’re always talking about personalized medicine, and it’s mind-blowing that these tier systems are only based on urgency and prognosis,” he told Medscape Medical News.
Spratt offered an example. Consider a patient with a very aggressive brain tumor ― that patient is in tier 1 and should undergo treatment immediately. But will the treatment actually help? And how helpful would the procedure be if, say, the patient is 80 years old and, if infected, would have a 30% to 50% chance of dying from the coronavirus?
“If the model says this guy has a 5% harm and this one has 30% harm, you can use that to help prioritize,” summarized Spratt.
The app can generate risk estimates for patients living anywhere in the world and has already been accessed by people from 37 countries. However, Spratt cautions that it is primarily “designed and calibrated for the US.
“The estimates are based on very large US registries, and though it’s probably somewhat similar across much of the world, there’s probably certain cancer types that are more region specific ― especially something like stomach cancer or certain types of head and neck cancer in parts of Asia, for example,” he said.
Although the app’s COVID-19 data are specific to the county level in the United States, elsewhere in the world, it is only country specific.
“We’re using the best data we have for coronavirus, but everyone knows we still have large data gaps,” he acknowledged.
How Accurate?
Asked to comment on the app, Richard Bleicher, MD, leader of the Breast Cancer Program at Fox Chase Cancer Center, Philadelphia, praised the effort and the goal but had some concerns.
“Several questions arise, most important of which is, How accurate is this, and how has this been validated, if at all ― especially as it is too soon to see the outcomes of patients affected in this pandemic?” he told Medscape Medical News.
“We are imposing delays on a broad scale because of the coronavirus, and we are getting continuously changing data as we test more patients. But both situations are novel and may not be accurately represented by the data being pulled, because the datasets use patients from a few years ago, and confounders in these datasets may not apply to this situation,” Bleicher continued.
Although acknowledging the “value in delineating the risk of dying from cancer vs the risk of dying from the SARS-CoV-2 pandemic,” Bleicher urged caution in using the tool to make individual patient decisions.
“We need to remember that the best of modeling ... can be wildly inaccurate and needs to be validated using patients having the circumstances in question. ... This won’t be possible until long after the pandemic is completed, and so the model’s accuracy remains unknown.”
That sentiment was echoed by Giampaolo Bianchini, MD, head of the Breast Cancer Group, Department of Medical Oncology, Ospedale San Raffaele, in Milan, Italy.
“Arbitrarily postponing and modifying treatment strategies including surgery, radiation therapy, and medical therapy without properly balancing the risk/benefit ratio may lead to significantly worse cancer-related outcomes, which largely exceed the actual risks for COVID,” he wrote in an email.
“The OncCOVID app is a remarkable attempt to fill the gap between perception and estimation,” he said. The app provides side by side the COVID-19 risk estimation and the consequences of arbitrary deviation from the standard of care, observed Bianchini.
However, he pointed out weaknesses, including the fact that the “data generated in literature are not always of high quality and do not take into consideration relevant characteristics of the disease and treatment benefit. It should for sure be used, but then also interpreted with caution.”
Another Italian group responded more positively.
“In our opinion, it could be a useful tool for clinicians,” wrote colleagues Alessio Cortelinni and Giampiero Porzio, both medical oncologists at San Salvatore Hospital and the University of L’Aquila, in Italy. “This Web app might assist clinicians in balancing the risk/benefit ratio of being treated and/or access to the outpatient cancer center for each kind of patient (both early and advanced stages), in order to make a more tailored counseling,” they wrote in an email. “Importantly, the Web app might help those clinicians who work ‘alone,’ in peripheral centers, without resources, colleagues, and multidisciplinary tumor boards on whom they can rely.”
Bleicher, who was involved in the COVID-19 Breast Cancer Consortium’s recommendations for prioritizing breast cancer treatment, summarized that the app “may end up being close or accurate, but we won’t know except in hindsight.”
This article first appeared on Medscape.com.
Deciding which cancer patients need immediate treatment and who can safely wait is an uncomfortable assessment for cancer clinicians during the COVID-19 pandemic.
In early April, as the COVID-19 surge was bearing down on New York City, those treatment decisions were “a juggling act every single day,” Jonathan Yang, MD, PhD, a radiation oncologist from New York’s Memorial Sloan Kettering Cancer Center, told Medscape Medical News.
Eventually, a glut of guidelines, recommendations, and expert opinions aimed at helping oncologists emerged. The tools help navigate the complicated risk-benefit analysis of their patient’s risk of infection by SARS-CoV-2 and delaying therapy.
Now, a new tool, which appears to be the first of its kind, quantifies that risk-benefit analysis. But its presence immediately raises the question: can it help?
Three-Tier Systems Are Not Very Sophisticated
OncCOVID, a free tool that was launched May 26 by the University of Michigan, allows physicians to individualize risk estimates for delaying treatment of up to 25 early- to late-stage cancers. It includes more than 45 patient characteristics, such as age, location, cancer type, cancer stage, treatment plan, underlying medical conditions, and proposed length of delay in care.
Combining these personal details with data from the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) registry and the National Cancer Database, the Michigan app then estimates a patient’s 5- or 10-year survival with immediate vs delayed treatment and weighs that against their risk for COVID-19 using data from the Johns Hopkins Coronavirus Resource Center.
“We thought, isn’t it better to at least provide some evidence-based quantification, rather than a back-of-the-envelope three-tier system that is just sort of ‘made up’?“ explained one of the developers, Daniel Spratt, MD, associate professor of radiation oncology at Michigan Medicine.
Spratt explained that almost every organization, professional society, and government has created something like a three-tier system. Tier 1 represents urgent cases and patients who need immediate treatment. For tier 2, treatment can be delayed weeks or a month, and with tier 3, it can be delayed until the pandemic is over or it’s deemed safe.
“[This system] sounds good at first glance, but in cancer, we’re always talking about personalized medicine, and it’s mind-blowing that these tier systems are only based on urgency and prognosis,” he told Medscape Medical News.
Spratt offered an example. Consider a patient with a very aggressive brain tumor ― that patient is in tier 1 and should undergo treatment immediately. But will the treatment actually help? And how helpful would the procedure be if, say, the patient is 80 years old and, if infected, would have a 30% to 50% chance of dying from the coronavirus?
“If the model says this guy has a 5% harm and this one has 30% harm, you can use that to help prioritize,” summarized Spratt.
The app can generate risk estimates for patients living anywhere in the world and has already been accessed by people from 37 countries. However, Spratt cautions that it is primarily “designed and calibrated for the US.
“The estimates are based on very large US registries, and though it’s probably somewhat similar across much of the world, there’s probably certain cancer types that are more region specific ― especially something like stomach cancer or certain types of head and neck cancer in parts of Asia, for example,” he said.
Although the app’s COVID-19 data are specific to the county level in the United States, elsewhere in the world, it is only country specific.
“We’re using the best data we have for coronavirus, but everyone knows we still have large data gaps,” he acknowledged.
How Accurate?
Asked to comment on the app, Richard Bleicher, MD, leader of the Breast Cancer Program at Fox Chase Cancer Center, Philadelphia, praised the effort and the goal but had some concerns.
“Several questions arise, most important of which is, How accurate is this, and how has this been validated, if at all ― especially as it is too soon to see the outcomes of patients affected in this pandemic?” he told Medscape Medical News.
“We are imposing delays on a broad scale because of the coronavirus, and we are getting continuously changing data as we test more patients. But both situations are novel and may not be accurately represented by the data being pulled, because the datasets use patients from a few years ago, and confounders in these datasets may not apply to this situation,” Bleicher continued.
Although acknowledging the “value in delineating the risk of dying from cancer vs the risk of dying from the SARS-CoV-2 pandemic,” Bleicher urged caution in using the tool to make individual patient decisions.
“We need to remember that the best of modeling ... can be wildly inaccurate and needs to be validated using patients having the circumstances in question. ... This won’t be possible until long after the pandemic is completed, and so the model’s accuracy remains unknown.”
That sentiment was echoed by Giampaolo Bianchini, MD, head of the Breast Cancer Group, Department of Medical Oncology, Ospedale San Raffaele, in Milan, Italy.
“Arbitrarily postponing and modifying treatment strategies including surgery, radiation therapy, and medical therapy without properly balancing the risk/benefit ratio may lead to significantly worse cancer-related outcomes, which largely exceed the actual risks for COVID,” he wrote in an email.
“The OncCOVID app is a remarkable attempt to fill the gap between perception and estimation,” he said. The app provides side by side the COVID-19 risk estimation and the consequences of arbitrary deviation from the standard of care, observed Bianchini.
However, he pointed out weaknesses, including the fact that the “data generated in literature are not always of high quality and do not take into consideration relevant characteristics of the disease and treatment benefit. It should for sure be used, but then also interpreted with caution.”
Another Italian group responded more positively.
“In our opinion, it could be a useful tool for clinicians,” wrote colleagues Alessio Cortelinni and Giampiero Porzio, both medical oncologists at San Salvatore Hospital and the University of L’Aquila, in Italy. “This Web app might assist clinicians in balancing the risk/benefit ratio of being treated and/or access to the outpatient cancer center for each kind of patient (both early and advanced stages), in order to make a more tailored counseling,” they wrote in an email. “Importantly, the Web app might help those clinicians who work ‘alone,’ in peripheral centers, without resources, colleagues, and multidisciplinary tumor boards on whom they can rely.”
Bleicher, who was involved in the COVID-19 Breast Cancer Consortium’s recommendations for prioritizing breast cancer treatment, summarized that the app “may end up being close or accurate, but we won’t know except in hindsight.”
This article first appeared on Medscape.com.
‘A good and peaceful death’: Cancer hospice during the pandemic
Lillie Shockney, RN, MAS, a two-time breast cancer survivor and adjunct professor at Johns Hopkins School of Nursing in Baltimore, Maryland, mourns the many losses that her patients with advanced cancer now face in the midst of the COVID-19 pandemic. But in the void of the usual support networks and treatment plans, she sees the resurgence of something that has recently been crowded out: hospice.
The pandemic has forced patients and their physicians to reassess the risk/benefit balance of continuing or embarking on yet another cancer treatment.
“It’s one of the pearls that we will get out of this nightmare,” said Ms. Shockney, who recently retired as administrative director of the cancer survivorship programs at the Sidney Kimmel Comprehensive Cancer Center.
“Physicians have been taught to treat the disease – so as long as there’s a treatment they give another treatment,” she told Medscape Medical News during a Zoom call from her home. “But for some patients with advanced disease, those treatments were making them very sick, so they were trading longevity over quality of life.”
Of course, longevity has never been a guarantee with cancer treatment, and even less so now, with the risk of COVID-19.
“This is going to bring them to some hard discussions,” says Brenda Nevidjon, RN, MSN, chief executive officer at the Oncology Nursing Society.
“We’ve known for a long time that there are patients who are on third- and fourth-round treatment options that have very little evidence of prolonging life or quality of life,” she told Medscape Medical News. “Do we bring these people out of their home to a setting where there could be a fair number of COVID-positive patients? Do we expose them to that?”
Across the world, these dilemmas are pushing cancer specialists to initiate discussions of hospice sooner with patients who have advanced disease, and with more clarity than before.
One of the reasons such conversations have often been avoided is that the concept of hospice is generally misunderstood, said Ms. Shockney.
“Patients think ‘you’re giving up on me, you’ve abandoned me’, but hospice is all about preserving the remainder of their quality of life and letting them have time with family and time to fulfill those elements of experiencing a good and peaceful death,” she said.
Indeed, hospice is “a benefit meant for somebody with at least a 6-month horizon,” agrees Ms. Nevidjon. Yet the average length of hospice in the United States is just 5 days. “It’s at the very, very end, and yet for some of these patients the 6 months they could get in hospice might be a better quality of life than the 4 months on another whole plan of chemotherapy. I can’t imagine that on the backside of this pandemic we will not have learned and we won’t start to change practices around initiating more of these conversations.”
Silver lining of this pandemic?
It’s too early into the pandemic to have hard data on whether hospice uptake has increased, but “it’s encouraging to hear that hospice is being discussed and offered sooner as an alternative to that third- or fourth-round chemo,” said Lori Bishop, MHA, RN, vice president of palliative and advanced care at the National Hospice and Palliative Care Organization.
“I agree that improving informed-decision discussions and timely access to hospice is a silver lining of the pandemic,” she told Medscape Medical News.
But she points out that today’s hospice looks quite different than it did before the pandemic, with the immediate and very obvious difference being telehealth, which was not widely utilized previously.
In March, the Centers for Medicare & Medicaid Services expanded telehealth options for hospice providers, something that Ms. Bishop and other hospice providers hope will remain in place after the pandemic passes.
“Telehealth visits are offered to replace some in-home visits both to minimize risk of exposure to COVID-19 and reduce the drain on personal protective equipment,” Bishop explained.
“In-patient hospice programs are also finding unique ways to provide support and connect patients to their loved ones: visitors are allowed but limited to one or two. Music and pet therapy are being provided through the window or virtually and devices such as iPads are being used to help patients connect with loved ones,” she said.
Telehealth links patients out of loneliness, but the one thing it cannot do is provide the comfort of touch – an important part of any hospice program.
“Hand-holding ... I miss that a lot,” says Ms. Shockney, her eyes filling with tears. “When you take somebody’s hand, you don’t even have to speak; that connection, and eye contact, is all you need to help that person emotionally heal.”
This article first appeared on Medscape.com.
Lillie Shockney, RN, MAS, a two-time breast cancer survivor and adjunct professor at Johns Hopkins School of Nursing in Baltimore, Maryland, mourns the many losses that her patients with advanced cancer now face in the midst of the COVID-19 pandemic. But in the void of the usual support networks and treatment plans, she sees the resurgence of something that has recently been crowded out: hospice.
The pandemic has forced patients and their physicians to reassess the risk/benefit balance of continuing or embarking on yet another cancer treatment.
“It’s one of the pearls that we will get out of this nightmare,” said Ms. Shockney, who recently retired as administrative director of the cancer survivorship programs at the Sidney Kimmel Comprehensive Cancer Center.
“Physicians have been taught to treat the disease – so as long as there’s a treatment they give another treatment,” she told Medscape Medical News during a Zoom call from her home. “But for some patients with advanced disease, those treatments were making them very sick, so they were trading longevity over quality of life.”
Of course, longevity has never been a guarantee with cancer treatment, and even less so now, with the risk of COVID-19.
“This is going to bring them to some hard discussions,” says Brenda Nevidjon, RN, MSN, chief executive officer at the Oncology Nursing Society.
“We’ve known for a long time that there are patients who are on third- and fourth-round treatment options that have very little evidence of prolonging life or quality of life,” she told Medscape Medical News. “Do we bring these people out of their home to a setting where there could be a fair number of COVID-positive patients? Do we expose them to that?”
Across the world, these dilemmas are pushing cancer specialists to initiate discussions of hospice sooner with patients who have advanced disease, and with more clarity than before.
One of the reasons such conversations have often been avoided is that the concept of hospice is generally misunderstood, said Ms. Shockney.
“Patients think ‘you’re giving up on me, you’ve abandoned me’, but hospice is all about preserving the remainder of their quality of life and letting them have time with family and time to fulfill those elements of experiencing a good and peaceful death,” she said.
Indeed, hospice is “a benefit meant for somebody with at least a 6-month horizon,” agrees Ms. Nevidjon. Yet the average length of hospice in the United States is just 5 days. “It’s at the very, very end, and yet for some of these patients the 6 months they could get in hospice might be a better quality of life than the 4 months on another whole plan of chemotherapy. I can’t imagine that on the backside of this pandemic we will not have learned and we won’t start to change practices around initiating more of these conversations.”
Silver lining of this pandemic?
It’s too early into the pandemic to have hard data on whether hospice uptake has increased, but “it’s encouraging to hear that hospice is being discussed and offered sooner as an alternative to that third- or fourth-round chemo,” said Lori Bishop, MHA, RN, vice president of palliative and advanced care at the National Hospice and Palliative Care Organization.
“I agree that improving informed-decision discussions and timely access to hospice is a silver lining of the pandemic,” she told Medscape Medical News.
But she points out that today’s hospice looks quite different than it did before the pandemic, with the immediate and very obvious difference being telehealth, which was not widely utilized previously.
In March, the Centers for Medicare & Medicaid Services expanded telehealth options for hospice providers, something that Ms. Bishop and other hospice providers hope will remain in place after the pandemic passes.
“Telehealth visits are offered to replace some in-home visits both to minimize risk of exposure to COVID-19 and reduce the drain on personal protective equipment,” Bishop explained.
“In-patient hospice programs are also finding unique ways to provide support and connect patients to their loved ones: visitors are allowed but limited to one or two. Music and pet therapy are being provided through the window or virtually and devices such as iPads are being used to help patients connect with loved ones,” she said.
Telehealth links patients out of loneliness, but the one thing it cannot do is provide the comfort of touch – an important part of any hospice program.
“Hand-holding ... I miss that a lot,” says Ms. Shockney, her eyes filling with tears. “When you take somebody’s hand, you don’t even have to speak; that connection, and eye contact, is all you need to help that person emotionally heal.”
This article first appeared on Medscape.com.
Lillie Shockney, RN, MAS, a two-time breast cancer survivor and adjunct professor at Johns Hopkins School of Nursing in Baltimore, Maryland, mourns the many losses that her patients with advanced cancer now face in the midst of the COVID-19 pandemic. But in the void of the usual support networks and treatment plans, she sees the resurgence of something that has recently been crowded out: hospice.
The pandemic has forced patients and their physicians to reassess the risk/benefit balance of continuing or embarking on yet another cancer treatment.
“It’s one of the pearls that we will get out of this nightmare,” said Ms. Shockney, who recently retired as administrative director of the cancer survivorship programs at the Sidney Kimmel Comprehensive Cancer Center.
“Physicians have been taught to treat the disease – so as long as there’s a treatment they give another treatment,” she told Medscape Medical News during a Zoom call from her home. “But for some patients with advanced disease, those treatments were making them very sick, so they were trading longevity over quality of life.”
Of course, longevity has never been a guarantee with cancer treatment, and even less so now, with the risk of COVID-19.
“This is going to bring them to some hard discussions,” says Brenda Nevidjon, RN, MSN, chief executive officer at the Oncology Nursing Society.
“We’ve known for a long time that there are patients who are on third- and fourth-round treatment options that have very little evidence of prolonging life or quality of life,” she told Medscape Medical News. “Do we bring these people out of their home to a setting where there could be a fair number of COVID-positive patients? Do we expose them to that?”
Across the world, these dilemmas are pushing cancer specialists to initiate discussions of hospice sooner with patients who have advanced disease, and with more clarity than before.
One of the reasons such conversations have often been avoided is that the concept of hospice is generally misunderstood, said Ms. Shockney.
“Patients think ‘you’re giving up on me, you’ve abandoned me’, but hospice is all about preserving the remainder of their quality of life and letting them have time with family and time to fulfill those elements of experiencing a good and peaceful death,” she said.
Indeed, hospice is “a benefit meant for somebody with at least a 6-month horizon,” agrees Ms. Nevidjon. Yet the average length of hospice in the United States is just 5 days. “It’s at the very, very end, and yet for some of these patients the 6 months they could get in hospice might be a better quality of life than the 4 months on another whole plan of chemotherapy. I can’t imagine that on the backside of this pandemic we will not have learned and we won’t start to change practices around initiating more of these conversations.”
Silver lining of this pandemic?
It’s too early into the pandemic to have hard data on whether hospice uptake has increased, but “it’s encouraging to hear that hospice is being discussed and offered sooner as an alternative to that third- or fourth-round chemo,” said Lori Bishop, MHA, RN, vice president of palliative and advanced care at the National Hospice and Palliative Care Organization.
“I agree that improving informed-decision discussions and timely access to hospice is a silver lining of the pandemic,” she told Medscape Medical News.
But she points out that today’s hospice looks quite different than it did before the pandemic, with the immediate and very obvious difference being telehealth, which was not widely utilized previously.
In March, the Centers for Medicare & Medicaid Services expanded telehealth options for hospice providers, something that Ms. Bishop and other hospice providers hope will remain in place after the pandemic passes.
“Telehealth visits are offered to replace some in-home visits both to minimize risk of exposure to COVID-19 and reduce the drain on personal protective equipment,” Bishop explained.
“In-patient hospice programs are also finding unique ways to provide support and connect patients to their loved ones: visitors are allowed but limited to one or two. Music and pet therapy are being provided through the window or virtually and devices such as iPads are being used to help patients connect with loved ones,” she said.
Telehealth links patients out of loneliness, but the one thing it cannot do is provide the comfort of touch – an important part of any hospice program.
“Hand-holding ... I miss that a lot,” says Ms. Shockney, her eyes filling with tears. “When you take somebody’s hand, you don’t even have to speak; that connection, and eye contact, is all you need to help that person emotionally heal.”
This article first appeared on Medscape.com.