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FDA issues warning on fecal transplant transmission of SARS-CoV-2
and that additional safety procedures may be required.
The risk of SARS-CoV-2 transmission through fecal microbiota transplant is unknown, but “several recent studies have documented the presence of SARS-CoV-2 ribonucleic acid (RNA) and/or SARS-CoV-2 virus in stool of infected individuals,” the FDA said in the press release. The testing of nasopharyngeal specimens from stool donors may not be available, and the availability and sensitivity of direct testing of stool for SARS-CoV-2 is currently unknown.
Because of the risk of serious adverse events, the FDA has issued several recommendations for any medically necessary usage of fecal microbiota transplantation involving stool samples donated after Dec. 1, 2019.
- Donor screening with questions directed at identifying those currently or recently infected with SARS-CoV-2.
- Testing donors and/or donor stool for SARS-CoV-2, as feasible.
- Development of criteria for exclusion of donors and donor stool based on screening and testing.
- Informed consent that includes information about the potential for transmission of SARS-CoV-2 via fecal microbiota transplantation, including transplantation prepared from stool from donors who are asymptomatic for COVID-19.
“As the scientific community learns more about SARS-CoV-2 and COVID-19, FDA will provide further information as warranted,” the agency said.
and that additional safety procedures may be required.
The risk of SARS-CoV-2 transmission through fecal microbiota transplant is unknown, but “several recent studies have documented the presence of SARS-CoV-2 ribonucleic acid (RNA) and/or SARS-CoV-2 virus in stool of infected individuals,” the FDA said in the press release. The testing of nasopharyngeal specimens from stool donors may not be available, and the availability and sensitivity of direct testing of stool for SARS-CoV-2 is currently unknown.
Because of the risk of serious adverse events, the FDA has issued several recommendations for any medically necessary usage of fecal microbiota transplantation involving stool samples donated after Dec. 1, 2019.
- Donor screening with questions directed at identifying those currently or recently infected with SARS-CoV-2.
- Testing donors and/or donor stool for SARS-CoV-2, as feasible.
- Development of criteria for exclusion of donors and donor stool based on screening and testing.
- Informed consent that includes information about the potential for transmission of SARS-CoV-2 via fecal microbiota transplantation, including transplantation prepared from stool from donors who are asymptomatic for COVID-19.
“As the scientific community learns more about SARS-CoV-2 and COVID-19, FDA will provide further information as warranted,” the agency said.
and that additional safety procedures may be required.
The risk of SARS-CoV-2 transmission through fecal microbiota transplant is unknown, but “several recent studies have documented the presence of SARS-CoV-2 ribonucleic acid (RNA) and/or SARS-CoV-2 virus in stool of infected individuals,” the FDA said in the press release. The testing of nasopharyngeal specimens from stool donors may not be available, and the availability and sensitivity of direct testing of stool for SARS-CoV-2 is currently unknown.
Because of the risk of serious adverse events, the FDA has issued several recommendations for any medically necessary usage of fecal microbiota transplantation involving stool samples donated after Dec. 1, 2019.
- Donor screening with questions directed at identifying those currently or recently infected with SARS-CoV-2.
- Testing donors and/or donor stool for SARS-CoV-2, as feasible.
- Development of criteria for exclusion of donors and donor stool based on screening and testing.
- Informed consent that includes information about the potential for transmission of SARS-CoV-2 via fecal microbiota transplantation, including transplantation prepared from stool from donors who are asymptomatic for COVID-19.
“As the scientific community learns more about SARS-CoV-2 and COVID-19, FDA will provide further information as warranted,” the agency said.
COVID-19 critical care guideline offers support for frontline clinicians
The 49 recommendations and statements it included are geared to “support hospital clinicians managing critically ill adults with COVID-19 in the ICU. The target users of this guideline are frontline clinicians, allied health professionals, and policy makers involved in the care of patients with COVID-19 in the ICU,” said the document, written by a panel of 36 experts organized by the Surviving Sepsis Campaign, a joint program of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine.
The document divides the recommendations into four categories: infection control, which includes 3 “best-practice” statements and 5 “weak” recommendations; hemodynamics with 2 “strong” recommendations and 13 weak ones; ventilation, with 1 best-practice statement, 6 strong recommendations, and 12 weak recommendations; and therapy with 7 weak recommendations. The guidelines also included five management questions considered by the writing panel without arriving at a recommendation because of insufficient evidence.
Useful guide nonspecialists
Some critical care medicine physicians saw the new guidelines as offering no surprises, but providing a very useful resource to guide management, especially for clinicians who may become involved in caring for COVID-19 patients despite having little experience caring for patients with acute respiratory distress syndrome (ARDS).
“For those of us who manage ARDS patients all the time, this is not a lot of new information, but many critically ill COVID-19 patients are now being cared for by physicians who have not cared for these patients before,” commented Mangala Narasimhan, DO, FCCP, a critical care medicine physician at Long Island Jewish Medical Center in New Hyde Park, N.Y. In fact, Dr, Narasimhan and associates took the new guidelines soon after their release and used them to create a one-page summary sheet to give to all their colleagues who are now seeing COVID-19 patients, she said in an interview. “The guidelines are very important for clinicians who are suddenly taking care of a roomful of patients with ARDS.”
“A lot of people want to know this information,” agreed David M. Ferraro, MD, FCCP, a pulmonologist and critical care medicine physician at National Jewish Health in Denver.
Perhaps the only potentially controversial aspect of the guidelines are a couple of weak recommendations that suggest using a high-flow nasal cannula (HFNC) rather than noninvasive positive pressure ventilation (NIPPV) in patients with acute hypoxemic respiratory failure who have not fully responded to conventional oxygen therapy. “This is controversial, and some of my colleagues are debating this,” said Dr. Narasimhan, but she noted that her clinic has decided to follow the recommended preference for HFNC, which seemed to have modest advantages over NIPPV in a recent meta-analysis (Intensive Care Med. 2019 May;45[5]:563-72).
Another issue with NIPPV is the higher risk for viral dispersion it seems to have, compared with a HFNC, said Dr. Ferraro. If a patient’s mask comes off during NIPPV, it creates a substantial risk for aerosolization of virus. That risk is likely lower with HFNC, especially a HFNC system that uses a small cannula without heating or humidification of the gas flow. “I’d recommend against NIPPV,” Dr. Ferraro said.
He also highlighted the value of quickly forgoing continued use of either of these ventilatory approaches in a declining patient and having a low threshold to switch to intubation. “Many clinicians now favor erring on the side of early intubation,” he noted, an approach that the new guidelines endorsed in a best-practice statement: “In adults with COVID-19 receiving NIPPV or HFNC we recommend close monitoring for worsening respiratory status and early intubation in a controlled setting if worsening occurs.”
One aspect of the COVID-19 pandemic that the new guidelines don’t address are some of the challenges being faced from skyrocketing numbers of patients and inadequate supplies and manpower to meet their acute clinical needs. “We need recommendations on how systems should manage when they are overwhelmed,” commented Dr. Ferraro, an omission that he also saw in the COVID-19 management guidance released on March 13, 2020, by the World Health Organization.
“Neither document gets into this in depth, but that wasn’t in their scope,” Dr. Ferraro acknowledged. He said that recommendations on how to deal with scarce resources, inadequate staffing, and the health of clinicians are probably best handled on a state or local level rather than trying to create recommendations that are applicable to the entire U.S. health system.
Dr. Narasimhan and Dr. Ferraro reported that they had no disclosures.
The 49 recommendations and statements it included are geared to “support hospital clinicians managing critically ill adults with COVID-19 in the ICU. The target users of this guideline are frontline clinicians, allied health professionals, and policy makers involved in the care of patients with COVID-19 in the ICU,” said the document, written by a panel of 36 experts organized by the Surviving Sepsis Campaign, a joint program of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine.
The document divides the recommendations into four categories: infection control, which includes 3 “best-practice” statements and 5 “weak” recommendations; hemodynamics with 2 “strong” recommendations and 13 weak ones; ventilation, with 1 best-practice statement, 6 strong recommendations, and 12 weak recommendations; and therapy with 7 weak recommendations. The guidelines also included five management questions considered by the writing panel without arriving at a recommendation because of insufficient evidence.
Useful guide nonspecialists
Some critical care medicine physicians saw the new guidelines as offering no surprises, but providing a very useful resource to guide management, especially for clinicians who may become involved in caring for COVID-19 patients despite having little experience caring for patients with acute respiratory distress syndrome (ARDS).
“For those of us who manage ARDS patients all the time, this is not a lot of new information, but many critically ill COVID-19 patients are now being cared for by physicians who have not cared for these patients before,” commented Mangala Narasimhan, DO, FCCP, a critical care medicine physician at Long Island Jewish Medical Center in New Hyde Park, N.Y. In fact, Dr, Narasimhan and associates took the new guidelines soon after their release and used them to create a one-page summary sheet to give to all their colleagues who are now seeing COVID-19 patients, she said in an interview. “The guidelines are very important for clinicians who are suddenly taking care of a roomful of patients with ARDS.”
“A lot of people want to know this information,” agreed David M. Ferraro, MD, FCCP, a pulmonologist and critical care medicine physician at National Jewish Health in Denver.
Perhaps the only potentially controversial aspect of the guidelines are a couple of weak recommendations that suggest using a high-flow nasal cannula (HFNC) rather than noninvasive positive pressure ventilation (NIPPV) in patients with acute hypoxemic respiratory failure who have not fully responded to conventional oxygen therapy. “This is controversial, and some of my colleagues are debating this,” said Dr. Narasimhan, but she noted that her clinic has decided to follow the recommended preference for HFNC, which seemed to have modest advantages over NIPPV in a recent meta-analysis (Intensive Care Med. 2019 May;45[5]:563-72).
Another issue with NIPPV is the higher risk for viral dispersion it seems to have, compared with a HFNC, said Dr. Ferraro. If a patient’s mask comes off during NIPPV, it creates a substantial risk for aerosolization of virus. That risk is likely lower with HFNC, especially a HFNC system that uses a small cannula without heating or humidification of the gas flow. “I’d recommend against NIPPV,” Dr. Ferraro said.
He also highlighted the value of quickly forgoing continued use of either of these ventilatory approaches in a declining patient and having a low threshold to switch to intubation. “Many clinicians now favor erring on the side of early intubation,” he noted, an approach that the new guidelines endorsed in a best-practice statement: “In adults with COVID-19 receiving NIPPV or HFNC we recommend close monitoring for worsening respiratory status and early intubation in a controlled setting if worsening occurs.”
One aspect of the COVID-19 pandemic that the new guidelines don’t address are some of the challenges being faced from skyrocketing numbers of patients and inadequate supplies and manpower to meet their acute clinical needs. “We need recommendations on how systems should manage when they are overwhelmed,” commented Dr. Ferraro, an omission that he also saw in the COVID-19 management guidance released on March 13, 2020, by the World Health Organization.
“Neither document gets into this in depth, but that wasn’t in their scope,” Dr. Ferraro acknowledged. He said that recommendations on how to deal with scarce resources, inadequate staffing, and the health of clinicians are probably best handled on a state or local level rather than trying to create recommendations that are applicable to the entire U.S. health system.
Dr. Narasimhan and Dr. Ferraro reported that they had no disclosures.
The 49 recommendations and statements it included are geared to “support hospital clinicians managing critically ill adults with COVID-19 in the ICU. The target users of this guideline are frontline clinicians, allied health professionals, and policy makers involved in the care of patients with COVID-19 in the ICU,” said the document, written by a panel of 36 experts organized by the Surviving Sepsis Campaign, a joint program of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine.
The document divides the recommendations into four categories: infection control, which includes 3 “best-practice” statements and 5 “weak” recommendations; hemodynamics with 2 “strong” recommendations and 13 weak ones; ventilation, with 1 best-practice statement, 6 strong recommendations, and 12 weak recommendations; and therapy with 7 weak recommendations. The guidelines also included five management questions considered by the writing panel without arriving at a recommendation because of insufficient evidence.
Useful guide nonspecialists
Some critical care medicine physicians saw the new guidelines as offering no surprises, but providing a very useful resource to guide management, especially for clinicians who may become involved in caring for COVID-19 patients despite having little experience caring for patients with acute respiratory distress syndrome (ARDS).
“For those of us who manage ARDS patients all the time, this is not a lot of new information, but many critically ill COVID-19 patients are now being cared for by physicians who have not cared for these patients before,” commented Mangala Narasimhan, DO, FCCP, a critical care medicine physician at Long Island Jewish Medical Center in New Hyde Park, N.Y. In fact, Dr, Narasimhan and associates took the new guidelines soon after their release and used them to create a one-page summary sheet to give to all their colleagues who are now seeing COVID-19 patients, she said in an interview. “The guidelines are very important for clinicians who are suddenly taking care of a roomful of patients with ARDS.”
“A lot of people want to know this information,” agreed David M. Ferraro, MD, FCCP, a pulmonologist and critical care medicine physician at National Jewish Health in Denver.
Perhaps the only potentially controversial aspect of the guidelines are a couple of weak recommendations that suggest using a high-flow nasal cannula (HFNC) rather than noninvasive positive pressure ventilation (NIPPV) in patients with acute hypoxemic respiratory failure who have not fully responded to conventional oxygen therapy. “This is controversial, and some of my colleagues are debating this,” said Dr. Narasimhan, but she noted that her clinic has decided to follow the recommended preference for HFNC, which seemed to have modest advantages over NIPPV in a recent meta-analysis (Intensive Care Med. 2019 May;45[5]:563-72).
Another issue with NIPPV is the higher risk for viral dispersion it seems to have, compared with a HFNC, said Dr. Ferraro. If a patient’s mask comes off during NIPPV, it creates a substantial risk for aerosolization of virus. That risk is likely lower with HFNC, especially a HFNC system that uses a small cannula without heating or humidification of the gas flow. “I’d recommend against NIPPV,” Dr. Ferraro said.
He also highlighted the value of quickly forgoing continued use of either of these ventilatory approaches in a declining patient and having a low threshold to switch to intubation. “Many clinicians now favor erring on the side of early intubation,” he noted, an approach that the new guidelines endorsed in a best-practice statement: “In adults with COVID-19 receiving NIPPV or HFNC we recommend close monitoring for worsening respiratory status and early intubation in a controlled setting if worsening occurs.”
One aspect of the COVID-19 pandemic that the new guidelines don’t address are some of the challenges being faced from skyrocketing numbers of patients and inadequate supplies and manpower to meet their acute clinical needs. “We need recommendations on how systems should manage when they are overwhelmed,” commented Dr. Ferraro, an omission that he also saw in the COVID-19 management guidance released on March 13, 2020, by the World Health Organization.
“Neither document gets into this in depth, but that wasn’t in their scope,” Dr. Ferraro acknowledged. He said that recommendations on how to deal with scarce resources, inadequate staffing, and the health of clinicians are probably best handled on a state or local level rather than trying to create recommendations that are applicable to the entire U.S. health system.
Dr. Narasimhan and Dr. Ferraro reported that they had no disclosures.
Three COVID-19 rapid diagnostic tests get FDA thumbs-up
The first authorization, announced by the agency on March 21, was for the Xpert Xpress SARS-CoV-2 test, a rapid molecular diagnostic test for qualitative detection of SARS-CoV-2, the virus causing COVID-19.
The test, manufactured by Cepheid, has a detection time of 45 minutes and has been designed to operate on any of the company’s more than 23,000 automated GeneXpert Systems worldwide, according to a statement from the company.
The agency said in its EUA approval document the test is for a “qualitative detection of nucleic acid from the SARS-CoV-2 in nasopharyngeal swab and/or nasal wash/aspirate specimens collected from patients who are suspected of having COVID-19 infection.” Positive results are indicative of an infection but do not rule out other potential infections, it noted.
The company plans to roll out the test by March 30, according to the FDA.
Cepheid said in a statement that it has almost 5,000 GeneXpert systems in the United States that are capable of point-of-care testing and ready for use in hospitals. “Our automated systems do not require users to have specialty training to perform testing – they are capable of running 24/7, with many systems already doing so today,” Warren Kocmond, the company’s president, said in the statement.
FDA Commissioner Stephen Hahn, MD said in a statement that the authorization marked “an important step in expanding the availability of testing and, importantly, rapid results. Point-of-care testing means that results are delivered to the patient in the patient-care settings, like hospitals, urgent care centers, and emergency rooms, instead of samples being sent to a laboratory. With today’s authorization, there is now an option for testing at the point of care, which enables patient access to more immediate results.”
On March 23, the agency issued an emergency use authorization to bioMerieux subsidiary BioFire Defense LLC for its BIOFIRE COVID-19 test, which detects SARS-CoV-2 from a nasopharyngeal swab in about 45 minutes.
The test was developed with funding from the U.S. Department of Defense.
“Positive results are indicative of the presence of SARS-CoV-2 RNA; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status,” the agency said in its approval document. It again noted that positive results did not rule out bacterial infection or coinfection with other viruses.
Also on March 23, the agency issued an EUA to Mesa Biotech for its Accula SARS-CoV-2 test, which gives COVID-19 diagnostic results in 30 minutes.
The test is indicated for “qualitative, visual detection of nucleic acid from the SARS-CoV-2 in throat swab and nasal swab specimens combined, collected from patients suspected of COVID-19 by their health care provider,” according to the FDA approval document. “The SARS-CoV-2 nucleic acid is generally detectable in throat and nasal swab specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 nucleic acid; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out bacterial infection or coinfection with other viruses.”
Mesa Biotech said in a statement that the test is designed for point-of-care use, including at temporary screening facilities, physician office labs, urgent care, and long-term nursing facilities.
“Our test will provide a highly accessible means for health care professionals to access laboratory quality results close in their office to aid in the decision to isolate, treat, or dismiss potential carriers of the virus,” Hong Cai, the CEO and cofounder of Mesa Biotech, said in a statement. “The potential to reduce the growing strain on our nation’s hospitals is tremendous.”
In separate letters to the three companies notifying them of the authorizations, the FDA said the emergency use of the products met the criteria for issuances of authorization because the SARS-CoV-2 can cause a serious or life-threatening disease or condition; it was “reasonable to believe
that [the] product may be effective in diagnosing COVID-19; and there is no “adequate, approved, and available alternative” to the emergency use of the three products.
The first authorization, announced by the agency on March 21, was for the Xpert Xpress SARS-CoV-2 test, a rapid molecular diagnostic test for qualitative detection of SARS-CoV-2, the virus causing COVID-19.
The test, manufactured by Cepheid, has a detection time of 45 minutes and has been designed to operate on any of the company’s more than 23,000 automated GeneXpert Systems worldwide, according to a statement from the company.
The agency said in its EUA approval document the test is for a “qualitative detection of nucleic acid from the SARS-CoV-2 in nasopharyngeal swab and/or nasal wash/aspirate specimens collected from patients who are suspected of having COVID-19 infection.” Positive results are indicative of an infection but do not rule out other potential infections, it noted.
The company plans to roll out the test by March 30, according to the FDA.
Cepheid said in a statement that it has almost 5,000 GeneXpert systems in the United States that are capable of point-of-care testing and ready for use in hospitals. “Our automated systems do not require users to have specialty training to perform testing – they are capable of running 24/7, with many systems already doing so today,” Warren Kocmond, the company’s president, said in the statement.
FDA Commissioner Stephen Hahn, MD said in a statement that the authorization marked “an important step in expanding the availability of testing and, importantly, rapid results. Point-of-care testing means that results are delivered to the patient in the patient-care settings, like hospitals, urgent care centers, and emergency rooms, instead of samples being sent to a laboratory. With today’s authorization, there is now an option for testing at the point of care, which enables patient access to more immediate results.”
On March 23, the agency issued an emergency use authorization to bioMerieux subsidiary BioFire Defense LLC for its BIOFIRE COVID-19 test, which detects SARS-CoV-2 from a nasopharyngeal swab in about 45 minutes.
The test was developed with funding from the U.S. Department of Defense.
“Positive results are indicative of the presence of SARS-CoV-2 RNA; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status,” the agency said in its approval document. It again noted that positive results did not rule out bacterial infection or coinfection with other viruses.
Also on March 23, the agency issued an EUA to Mesa Biotech for its Accula SARS-CoV-2 test, which gives COVID-19 diagnostic results in 30 minutes.
The test is indicated for “qualitative, visual detection of nucleic acid from the SARS-CoV-2 in throat swab and nasal swab specimens combined, collected from patients suspected of COVID-19 by their health care provider,” according to the FDA approval document. “The SARS-CoV-2 nucleic acid is generally detectable in throat and nasal swab specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 nucleic acid; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out bacterial infection or coinfection with other viruses.”
Mesa Biotech said in a statement that the test is designed for point-of-care use, including at temporary screening facilities, physician office labs, urgent care, and long-term nursing facilities.
“Our test will provide a highly accessible means for health care professionals to access laboratory quality results close in their office to aid in the decision to isolate, treat, or dismiss potential carriers of the virus,” Hong Cai, the CEO and cofounder of Mesa Biotech, said in a statement. “The potential to reduce the growing strain on our nation’s hospitals is tremendous.”
In separate letters to the three companies notifying them of the authorizations, the FDA said the emergency use of the products met the criteria for issuances of authorization because the SARS-CoV-2 can cause a serious or life-threatening disease or condition; it was “reasonable to believe
that [the] product may be effective in diagnosing COVID-19; and there is no “adequate, approved, and available alternative” to the emergency use of the three products.
The first authorization, announced by the agency on March 21, was for the Xpert Xpress SARS-CoV-2 test, a rapid molecular diagnostic test for qualitative detection of SARS-CoV-2, the virus causing COVID-19.
The test, manufactured by Cepheid, has a detection time of 45 minutes and has been designed to operate on any of the company’s more than 23,000 automated GeneXpert Systems worldwide, according to a statement from the company.
The agency said in its EUA approval document the test is for a “qualitative detection of nucleic acid from the SARS-CoV-2 in nasopharyngeal swab and/or nasal wash/aspirate specimens collected from patients who are suspected of having COVID-19 infection.” Positive results are indicative of an infection but do not rule out other potential infections, it noted.
The company plans to roll out the test by March 30, according to the FDA.
Cepheid said in a statement that it has almost 5,000 GeneXpert systems in the United States that are capable of point-of-care testing and ready for use in hospitals. “Our automated systems do not require users to have specialty training to perform testing – they are capable of running 24/7, with many systems already doing so today,” Warren Kocmond, the company’s president, said in the statement.
FDA Commissioner Stephen Hahn, MD said in a statement that the authorization marked “an important step in expanding the availability of testing and, importantly, rapid results. Point-of-care testing means that results are delivered to the patient in the patient-care settings, like hospitals, urgent care centers, and emergency rooms, instead of samples being sent to a laboratory. With today’s authorization, there is now an option for testing at the point of care, which enables patient access to more immediate results.”
On March 23, the agency issued an emergency use authorization to bioMerieux subsidiary BioFire Defense LLC for its BIOFIRE COVID-19 test, which detects SARS-CoV-2 from a nasopharyngeal swab in about 45 minutes.
The test was developed with funding from the U.S. Department of Defense.
“Positive results are indicative of the presence of SARS-CoV-2 RNA; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status,” the agency said in its approval document. It again noted that positive results did not rule out bacterial infection or coinfection with other viruses.
Also on March 23, the agency issued an EUA to Mesa Biotech for its Accula SARS-CoV-2 test, which gives COVID-19 diagnostic results in 30 minutes.
The test is indicated for “qualitative, visual detection of nucleic acid from the SARS-CoV-2 in throat swab and nasal swab specimens combined, collected from patients suspected of COVID-19 by their health care provider,” according to the FDA approval document. “The SARS-CoV-2 nucleic acid is generally detectable in throat and nasal swab specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 nucleic acid; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out bacterial infection or coinfection with other viruses.”
Mesa Biotech said in a statement that the test is designed for point-of-care use, including at temporary screening facilities, physician office labs, urgent care, and long-term nursing facilities.
“Our test will provide a highly accessible means for health care professionals to access laboratory quality results close in their office to aid in the decision to isolate, treat, or dismiss potential carriers of the virus,” Hong Cai, the CEO and cofounder of Mesa Biotech, said in a statement. “The potential to reduce the growing strain on our nation’s hospitals is tremendous.”
In separate letters to the three companies notifying them of the authorizations, the FDA said the emergency use of the products met the criteria for issuances of authorization because the SARS-CoV-2 can cause a serious or life-threatening disease or condition; it was “reasonable to believe
that [the] product may be effective in diagnosing COVID-19; and there is no “adequate, approved, and available alternative” to the emergency use of the three products.
Reports increasingly suggest anosmia/hyposmia can signal early COVID-19 infection
Unexplained anosmia, hyposmia, and dysgeusia should be added to the list of possible COVID-19 symptoms for screening purposes, and individuals with such symptoms should consider self-isolation, the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) has proposed.
However, a World Health Organization expert said during a March 23 daily briefing on the novel coronavirus pandemic that the jury is still out on that.
The AAO-HNS proposal is based on “rapidly accumulating” anecdotal evidence that such symptoms – in the absence of other symptoms suggestive of COVID-19 – have sometimes preceded a COVID-19 diagnosis.
“ ... anosmia, hyposmia, and dysgeusia in the absence of other respiratory disease such as allergic rhinitis, acute rhinosinusitis, or chronic rhinosinusitis should alert physicians to the possibility of COVID-19 infection and warrant serious consideration for self-isolation and testing of these individuals,” the AAO-HNS said in a statement on the proposal.
ENT UK, an organization representing Ear, Nose, and Throat surgery and its related specialties in the UK, also is emphasizing the potential importance of these symptoms. In a March 21 letter, ENT UK experts cited “good evidence from South Korea, China and Italy that significant numbers of patients with proven COVID-19 infection have developed anosmia/hyposmia.”
Claire Hopkins, BMBCh, president of the British Rhinological Society and a professor of Rhinology at King’s College London, along with ENT UK president Nirmal Kumar, also noted in the letter that two of every three cases in Germany, and 30% of patients testing positive in South Korea, had anosmia as their first symptom.
“While there is a chance the apparent increase in incidence could merely reflect the attention COVID-19 has attracted in the media, and that such cases may be caused by typical rhinovirus and coronavirus strains, it could potentially be used as a screening tool to help identify otherwise asymptomatic patients, who could then be better instructed on self-isolation,” they wrote.
Maria Van Kerkhove, MD, technical lead of the WHO Medical Emergencies Program, acknowledged the anecdotal evidence during the WHO briefing.
“Yes, we’ve seen quite a few reports ... but this is something that we need to look into to really capture if this is one of the early signs and symptoms of COVID-19,” she said, noting that WHO is working with more than a dozen countries that are systematically collecting data using molecular and serological testing to “capture more robustly” the early signs and symptoms, and is “reaching out to a number of countries and looking at the cases that have already been reported to see if [anosmia] is a common feature.”
“We don’t have the answer to that,” she said, adding that, in addition to the major symptoms – including dry cough, fever, and shortness of breath – that are well known at this point, “there are likely to be many signs and symptoms that people have.”
“A loss of smell or a loss of taste is something that we’re looking into, and we’re looking forward to the results of these early investigations ... so that we have a more evidence-based approach and we can add that to the list.”
Unexplained anosmia, hyposmia, and dysgeusia should be added to the list of possible COVID-19 symptoms for screening purposes, and individuals with such symptoms should consider self-isolation, the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) has proposed.
However, a World Health Organization expert said during a March 23 daily briefing on the novel coronavirus pandemic that the jury is still out on that.
The AAO-HNS proposal is based on “rapidly accumulating” anecdotal evidence that such symptoms – in the absence of other symptoms suggestive of COVID-19 – have sometimes preceded a COVID-19 diagnosis.
“ ... anosmia, hyposmia, and dysgeusia in the absence of other respiratory disease such as allergic rhinitis, acute rhinosinusitis, or chronic rhinosinusitis should alert physicians to the possibility of COVID-19 infection and warrant serious consideration for self-isolation and testing of these individuals,” the AAO-HNS said in a statement on the proposal.
ENT UK, an organization representing Ear, Nose, and Throat surgery and its related specialties in the UK, also is emphasizing the potential importance of these symptoms. In a March 21 letter, ENT UK experts cited “good evidence from South Korea, China and Italy that significant numbers of patients with proven COVID-19 infection have developed anosmia/hyposmia.”
Claire Hopkins, BMBCh, president of the British Rhinological Society and a professor of Rhinology at King’s College London, along with ENT UK president Nirmal Kumar, also noted in the letter that two of every three cases in Germany, and 30% of patients testing positive in South Korea, had anosmia as their first symptom.
“While there is a chance the apparent increase in incidence could merely reflect the attention COVID-19 has attracted in the media, and that such cases may be caused by typical rhinovirus and coronavirus strains, it could potentially be used as a screening tool to help identify otherwise asymptomatic patients, who could then be better instructed on self-isolation,” they wrote.
Maria Van Kerkhove, MD, technical lead of the WHO Medical Emergencies Program, acknowledged the anecdotal evidence during the WHO briefing.
“Yes, we’ve seen quite a few reports ... but this is something that we need to look into to really capture if this is one of the early signs and symptoms of COVID-19,” she said, noting that WHO is working with more than a dozen countries that are systematically collecting data using molecular and serological testing to “capture more robustly” the early signs and symptoms, and is “reaching out to a number of countries and looking at the cases that have already been reported to see if [anosmia] is a common feature.”
“We don’t have the answer to that,” she said, adding that, in addition to the major symptoms – including dry cough, fever, and shortness of breath – that are well known at this point, “there are likely to be many signs and symptoms that people have.”
“A loss of smell or a loss of taste is something that we’re looking into, and we’re looking forward to the results of these early investigations ... so that we have a more evidence-based approach and we can add that to the list.”
Unexplained anosmia, hyposmia, and dysgeusia should be added to the list of possible COVID-19 symptoms for screening purposes, and individuals with such symptoms should consider self-isolation, the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) has proposed.
However, a World Health Organization expert said during a March 23 daily briefing on the novel coronavirus pandemic that the jury is still out on that.
The AAO-HNS proposal is based on “rapidly accumulating” anecdotal evidence that such symptoms – in the absence of other symptoms suggestive of COVID-19 – have sometimes preceded a COVID-19 diagnosis.
“ ... anosmia, hyposmia, and dysgeusia in the absence of other respiratory disease such as allergic rhinitis, acute rhinosinusitis, or chronic rhinosinusitis should alert physicians to the possibility of COVID-19 infection and warrant serious consideration for self-isolation and testing of these individuals,” the AAO-HNS said in a statement on the proposal.
ENT UK, an organization representing Ear, Nose, and Throat surgery and its related specialties in the UK, also is emphasizing the potential importance of these symptoms. In a March 21 letter, ENT UK experts cited “good evidence from South Korea, China and Italy that significant numbers of patients with proven COVID-19 infection have developed anosmia/hyposmia.”
Claire Hopkins, BMBCh, president of the British Rhinological Society and a professor of Rhinology at King’s College London, along with ENT UK president Nirmal Kumar, also noted in the letter that two of every three cases in Germany, and 30% of patients testing positive in South Korea, had anosmia as their first symptom.
“While there is a chance the apparent increase in incidence could merely reflect the attention COVID-19 has attracted in the media, and that such cases may be caused by typical rhinovirus and coronavirus strains, it could potentially be used as a screening tool to help identify otherwise asymptomatic patients, who could then be better instructed on self-isolation,” they wrote.
Maria Van Kerkhove, MD, technical lead of the WHO Medical Emergencies Program, acknowledged the anecdotal evidence during the WHO briefing.
“Yes, we’ve seen quite a few reports ... but this is something that we need to look into to really capture if this is one of the early signs and symptoms of COVID-19,” she said, noting that WHO is working with more than a dozen countries that are systematically collecting data using molecular and serological testing to “capture more robustly” the early signs and symptoms, and is “reaching out to a number of countries and looking at the cases that have already been reported to see if [anosmia] is a common feature.”
“We don’t have the answer to that,” she said, adding that, in addition to the major symptoms – including dry cough, fever, and shortness of breath – that are well known at this point, “there are likely to be many signs and symptoms that people have.”
“A loss of smell or a loss of taste is something that we’re looking into, and we’re looking forward to the results of these early investigations ... so that we have a more evidence-based approach and we can add that to the list.”
High rate of asymptomatic COVID-19 seen in cruise ship passengers
The high rate of asymptomatic COVID-19 infections aboard the cruise ship Diamond Princess “could partially explain the high attack rate among” the passengers and crew, according to the Centers for Disease Control and Prevention.
Testing of the 3,711 passengers and crew aboard the ship – the source of the largest outbreak outside of China during the initial stages of the pandemic – revealed that 19.2% were positive for COVID-19, Leah F. Moriarty, MPH, and associates reported in the Morbidity and Mortality Weekly Report.
At the time of testing, 46.5% (331) of the 712 infected individuals were asymptomatic, and “statistical models of the Diamond Princess outbreak suggest that 17.9% of infected persons never developed symptoms,” wrote Ms. Moriarty of the CDC COVID-19 response team, and associates.
RNA from the SARS-CoV-2 virus was found on surfaces in cabins up to 17 days after they had been vacated by passengers but before the cabins had been disinfected, the investigators noted.
The Diamond Princess departed from Yokohama, Japan, on Jan. 20, 2020, and returned on Feb. 3 after making six stops in three countries. The ship was quarantined upon its return because a symptomatic passenger who had departed Jan. 25 in Hong Kong tested positive for SARS-CoV-2, Ms. Moriarty and associates explained.
Of the 381 people from the ship who were symptomatic and tested positive, 37 (9.7%) needed intensive care and 9 (1.3%) died. There were 428 Americans on the ship, of whom 107 (25.0%) tested positive and 11 remained hospitalized in Japan as of March 13, they said.
“Many other cruise ships have since been implicated in SARS-CoV-2 transmission,” the investigators said, including the Grand Princess, which sailed out of San Francisco with 3,571 people on Feb. 21 and returned to Oakland on March 8.
That ship had been the site of virus transmission during its previous voyage from Feb. 11 to Feb. 21, from which more than 20 cases have been identified. During the latter trip, 21 of 45 passengers and crew tested positive before the ship docked. During the subsequent land-based quarantine, there have been 78 positive tests among the 469 people tested as of March 21, a rate of 16.6%, the research team reported.
“Public health responses to cruise ship outbreaks require extensive resources,” they wrote. “These responses required the coordination of stakeholders across multiple sectors, including U.S. government departments and agencies, foreign ministries of health, foreign embassies, state and local public health departments, hospitals, laboratories, and cruise ship companies.”
SOURCE: Moriarty LF et al. MMWR. 2020 Mar 23;69[early release]:1-6.
The high rate of asymptomatic COVID-19 infections aboard the cruise ship Diamond Princess “could partially explain the high attack rate among” the passengers and crew, according to the Centers for Disease Control and Prevention.
Testing of the 3,711 passengers and crew aboard the ship – the source of the largest outbreak outside of China during the initial stages of the pandemic – revealed that 19.2% were positive for COVID-19, Leah F. Moriarty, MPH, and associates reported in the Morbidity and Mortality Weekly Report.
At the time of testing, 46.5% (331) of the 712 infected individuals were asymptomatic, and “statistical models of the Diamond Princess outbreak suggest that 17.9% of infected persons never developed symptoms,” wrote Ms. Moriarty of the CDC COVID-19 response team, and associates.
RNA from the SARS-CoV-2 virus was found on surfaces in cabins up to 17 days after they had been vacated by passengers but before the cabins had been disinfected, the investigators noted.
The Diamond Princess departed from Yokohama, Japan, on Jan. 20, 2020, and returned on Feb. 3 after making six stops in three countries. The ship was quarantined upon its return because a symptomatic passenger who had departed Jan. 25 in Hong Kong tested positive for SARS-CoV-2, Ms. Moriarty and associates explained.
Of the 381 people from the ship who were symptomatic and tested positive, 37 (9.7%) needed intensive care and 9 (1.3%) died. There were 428 Americans on the ship, of whom 107 (25.0%) tested positive and 11 remained hospitalized in Japan as of March 13, they said.
“Many other cruise ships have since been implicated in SARS-CoV-2 transmission,” the investigators said, including the Grand Princess, which sailed out of San Francisco with 3,571 people on Feb. 21 and returned to Oakland on March 8.
That ship had been the site of virus transmission during its previous voyage from Feb. 11 to Feb. 21, from which more than 20 cases have been identified. During the latter trip, 21 of 45 passengers and crew tested positive before the ship docked. During the subsequent land-based quarantine, there have been 78 positive tests among the 469 people tested as of March 21, a rate of 16.6%, the research team reported.
“Public health responses to cruise ship outbreaks require extensive resources,” they wrote. “These responses required the coordination of stakeholders across multiple sectors, including U.S. government departments and agencies, foreign ministries of health, foreign embassies, state and local public health departments, hospitals, laboratories, and cruise ship companies.”
SOURCE: Moriarty LF et al. MMWR. 2020 Mar 23;69[early release]:1-6.
The high rate of asymptomatic COVID-19 infections aboard the cruise ship Diamond Princess “could partially explain the high attack rate among” the passengers and crew, according to the Centers for Disease Control and Prevention.
Testing of the 3,711 passengers and crew aboard the ship – the source of the largest outbreak outside of China during the initial stages of the pandemic – revealed that 19.2% were positive for COVID-19, Leah F. Moriarty, MPH, and associates reported in the Morbidity and Mortality Weekly Report.
At the time of testing, 46.5% (331) of the 712 infected individuals were asymptomatic, and “statistical models of the Diamond Princess outbreak suggest that 17.9% of infected persons never developed symptoms,” wrote Ms. Moriarty of the CDC COVID-19 response team, and associates.
RNA from the SARS-CoV-2 virus was found on surfaces in cabins up to 17 days after they had been vacated by passengers but before the cabins had been disinfected, the investigators noted.
The Diamond Princess departed from Yokohama, Japan, on Jan. 20, 2020, and returned on Feb. 3 after making six stops in three countries. The ship was quarantined upon its return because a symptomatic passenger who had departed Jan. 25 in Hong Kong tested positive for SARS-CoV-2, Ms. Moriarty and associates explained.
Of the 381 people from the ship who were symptomatic and tested positive, 37 (9.7%) needed intensive care and 9 (1.3%) died. There were 428 Americans on the ship, of whom 107 (25.0%) tested positive and 11 remained hospitalized in Japan as of March 13, they said.
“Many other cruise ships have since been implicated in SARS-CoV-2 transmission,” the investigators said, including the Grand Princess, which sailed out of San Francisco with 3,571 people on Feb. 21 and returned to Oakland on March 8.
That ship had been the site of virus transmission during its previous voyage from Feb. 11 to Feb. 21, from which more than 20 cases have been identified. During the latter trip, 21 of 45 passengers and crew tested positive before the ship docked. During the subsequent land-based quarantine, there have been 78 positive tests among the 469 people tested as of March 21, a rate of 16.6%, the research team reported.
“Public health responses to cruise ship outbreaks require extensive resources,” they wrote. “These responses required the coordination of stakeholders across multiple sectors, including U.S. government departments and agencies, foreign ministries of health, foreign embassies, state and local public health departments, hospitals, laboratories, and cruise ship companies.”
SOURCE: Moriarty LF et al. MMWR. 2020 Mar 23;69[early release]:1-6.
FROM MMWR
CDC coronavirus testing decision likely to haunt nation for months to come
As the novel coronavirus snaked its way across the globe, the Centers for Disease Control and Prevention in early February distributed 200 test kits it had produced to more than 100 public health labs run by states and counties nationwide.
Each kit contained material to test a mere 300-400 patients. And labs, whether serving the population of New York or tiny towns in rural America, apparently received the same kits.
The kits were distributed roughly equally to locales in all 50 states. That decision presaged weeks of chaos, in which the availability of COVID-19 tests seemed oddly out of sync with where testing was needed.
A woman in South Dakota with mild symptoms and no fever readily got the test and the results. Meanwhile, political leaders and public officials in places like New York, Boston, Seattle, and the San Francisco Bay area – all in the throes of serious outbreaks – couldn’t get enough tests to screen ill patients or, thereby, the information they needed to protect the general public and stem the outbreak of the virus, whose symptoms mimic those of common respiratory illnesses.
Rapid testing is crucial in the early stages of an outbreak. It allows health workers and families to identify and focus on treating those infected and isolate them.
Yet health officials in New York and such states as New York, Washington, Pennsylvania, and Georgia confirmed that they each initially got one test kit, calling into question whether they would have even stood a chance to contain the outbreaks that would emerge. They would soon discover that the tests they did receive were flawed, lacking critical components, and delivering faulty results.
During those early weeks, the virus took off, infecting thousands of people and leading to nationwide social distancing and sheltering in place. Public health officials are just beginning to grapple with the fallout from that early bungling of testing, which is likely to haunt the country in the months to come.
Too little too late
The first shipment to Washington state arrived more than 2 weeks after officials there announced the first U.S. case of coronavirus, and at a moment when deadly outbreaks of the disease were already festering in places like the Life Care Center in Kirkland. Within weeks, three dozen people infected with COVID-19 would die at the nursing home in the suburbs of Seattle.
The spread of COVID-19 would not take long to overwhelm the state, which as of March 20, 2020, had more than 1,300 cases.
The Trump administration in recent days has attempted to speed testing for the virus after early missteps hampered the government’s response to contain the contagion, and officials have had to respond to a barrage of criticism from public health experts, state officials, and members of Congress.
Federal health officials have eased the process for university and commercial labs to perform their own tests, and they are ramping up their capacity. As of March 16, public and private labs in the United States had the ability to test more than 36,000 people a day, according to estimates compiled by the American Enterprise Institute, a conservative-leaning think tank in Washington, a figure expected to rapidly escalate in coming weeks. That figure, however, can vary considerably by state and does not indicate how many tests are actually given to patients.
“We are now beginning to see that they have spread out in a prioritized way. We asked them to prioritize the regions that were mostly affected,” Deborah Birx, the coronavirus response coordinator for the White House Coronavirus Task Force, said March 18 of private labs’ testing, without elaboration.
The scaling up of testing is set to take place after weeks of faltering and hundreds, if not thousands, of undiagnosed people spreading the virus. For example, New York’s state health department received a faulty CDC test kit on Feb. 8 for 800 patient specimens, an amount that’s consistent with other states, according to a spokesperson. It later began testing patients with a test that state officials developed based on the CDC protocol and has significantly increased testing – as of March 20, more than 7,200 people had tested positive statewide.
In New York City, the first batch was obtained on Feb. 7.
“The other state and local public health laboratories got test kits as they became available,” said Eric Blank, chief program officer of the Association of Public Health Laboratories.
Places in the middle of the country with no outbreaks had the luxury of time to plan. For example, Missouri officials have had about 800 tests to work with, leading to only 395 performed so far in the region by public health labs – 26 of which were positive. When private lab tests are accounted for, as of March 20 there were 47 confirmed cases.
Health care providers and public health staff in the state, however, benefited from the fact that there is less international travel to the region, according to infectious disease expert Steven Lawrence, MD, of Washington University, St. Louis.
“This is very similar to 1918 with the influenza pandemic – St. Louis had more time to prepare and was able to put measures in place to flatten the curve than, say, Philadelphia,” Dr. Lawrence said. “Seattle didn’t have an opportunity to prepare as much in advance.”
While commercial labs are coming online, strict restrictions are limiting testing capabilities, Dr. Lawrence said.
“The state has had their hands tied,” he added.
Waiting And wondering
Because of a widespread lag in testing, it is still a mystery for thousands of people to know whether they’ve come into contact with an infected person until well after it happens. As of March 20, the pandemic had killed more than 11,000 globally. More than 16,000 Americans were confirmed infected and at least 216 have died.
“CDC will distribute tests based on where they can do the most good. But without hospital-based testing and commercial testing, it will not be possible to meet the need,” said Tom Frieden, who led the CDC during President Obama’s administration and is a former commissioner of the New York City Health Department.
In California, public school teacher Claire Dugan, whose state was among the hardest hit in the initial wave of U.S. coronavirus cases, was told she didn’t qualify for testing because she had not traveled abroad to any country with an outbreak of the virus or been in contact with an infected person. Ms. Dugan, who lives in the San Francisco Bay area and is already medically fragile after a stray bullet nearly killed her while driving 4 years ago, sought a test from her doctor after registering a temperature of 100.7° F earlier this month.
“There are a lot of layers as to why this is so messed up,” said Ms. Dugan, who relies on a feeding tube and said she sought a test not only to protect herself but her students. “It’s community spreading right now, so it’s kind of silly we’re still insisting on [the early criteria for testing]. How would I know?”
Since the CDC’s initial distribution, states have been reordering more tests through the office’s International Reagent Resource – a long-standing tool that public health labs have relied on. They have also revised testing protocols to use only one sample per person, which boosts the number of people screened.
Yet problems still abound with tests or other materials needed to be able to detect the virus. California Gov. Gavin Newsom (D) said on March 12 that county public health labs can’t use all of the 8,000 test kits the state has because they are missing key components.
In Pennsylvania, state officials weren’t able to begin testing until March 2 because of problems with the CDC’s initial kit, according to Nate Wardle, a spokesperson at its department of health. New York received two newly manufactured CDC test kits on Feb. 29 and also began performing tests March 2, according to its health department.
“We are still limited on extraction kits,” Mandy Cohen, the Health & Human Services secretary in North Carolina, said in an interview in mid-March. Officials earlier this month could test only 300 patients because of shortages in the extraction materials needed to register whether the novel coronavirus is present.
In North Dakota, Loralyn Hegland wrote her physician’s practice an email on March 10 with the subject line “dry cough,” wondering if she should come in for testing after learning that was one symptom of COVID-19. The recommendation she got echoes those of countless others across the United States, saying her risk of being exposed was very low because she hadn’t traveled outside the United States and had not come into contact with a person who had been “definitely” diagnosed with the virus.
Ms. Hegland, who lives in Fargo, didn’t have a fever but decided to shelter herself, anyway, out of caution.
Would she push to get a test?
“What’s the point?” she said. “You can’t know what you don’t know. It’s just that simple. How else do you explain it to people when you’re not testing?”
KHN Midwest correspondent Lauren Weber in St. Louis contributed to this article.
Kaiser Health News is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.
As the novel coronavirus snaked its way across the globe, the Centers for Disease Control and Prevention in early February distributed 200 test kits it had produced to more than 100 public health labs run by states and counties nationwide.
Each kit contained material to test a mere 300-400 patients. And labs, whether serving the population of New York or tiny towns in rural America, apparently received the same kits.
The kits were distributed roughly equally to locales in all 50 states. That decision presaged weeks of chaos, in which the availability of COVID-19 tests seemed oddly out of sync with where testing was needed.
A woman in South Dakota with mild symptoms and no fever readily got the test and the results. Meanwhile, political leaders and public officials in places like New York, Boston, Seattle, and the San Francisco Bay area – all in the throes of serious outbreaks – couldn’t get enough tests to screen ill patients or, thereby, the information they needed to protect the general public and stem the outbreak of the virus, whose symptoms mimic those of common respiratory illnesses.
Rapid testing is crucial in the early stages of an outbreak. It allows health workers and families to identify and focus on treating those infected and isolate them.
Yet health officials in New York and such states as New York, Washington, Pennsylvania, and Georgia confirmed that they each initially got one test kit, calling into question whether they would have even stood a chance to contain the outbreaks that would emerge. They would soon discover that the tests they did receive were flawed, lacking critical components, and delivering faulty results.
During those early weeks, the virus took off, infecting thousands of people and leading to nationwide social distancing and sheltering in place. Public health officials are just beginning to grapple with the fallout from that early bungling of testing, which is likely to haunt the country in the months to come.
Too little too late
The first shipment to Washington state arrived more than 2 weeks after officials there announced the first U.S. case of coronavirus, and at a moment when deadly outbreaks of the disease were already festering in places like the Life Care Center in Kirkland. Within weeks, three dozen people infected with COVID-19 would die at the nursing home in the suburbs of Seattle.
The spread of COVID-19 would not take long to overwhelm the state, which as of March 20, 2020, had more than 1,300 cases.
The Trump administration in recent days has attempted to speed testing for the virus after early missteps hampered the government’s response to contain the contagion, and officials have had to respond to a barrage of criticism from public health experts, state officials, and members of Congress.
Federal health officials have eased the process for university and commercial labs to perform their own tests, and they are ramping up their capacity. As of March 16, public and private labs in the United States had the ability to test more than 36,000 people a day, according to estimates compiled by the American Enterprise Institute, a conservative-leaning think tank in Washington, a figure expected to rapidly escalate in coming weeks. That figure, however, can vary considerably by state and does not indicate how many tests are actually given to patients.
“We are now beginning to see that they have spread out in a prioritized way. We asked them to prioritize the regions that were mostly affected,” Deborah Birx, the coronavirus response coordinator for the White House Coronavirus Task Force, said March 18 of private labs’ testing, without elaboration.
The scaling up of testing is set to take place after weeks of faltering and hundreds, if not thousands, of undiagnosed people spreading the virus. For example, New York’s state health department received a faulty CDC test kit on Feb. 8 for 800 patient specimens, an amount that’s consistent with other states, according to a spokesperson. It later began testing patients with a test that state officials developed based on the CDC protocol and has significantly increased testing – as of March 20, more than 7,200 people had tested positive statewide.
In New York City, the first batch was obtained on Feb. 7.
“The other state and local public health laboratories got test kits as they became available,” said Eric Blank, chief program officer of the Association of Public Health Laboratories.
Places in the middle of the country with no outbreaks had the luxury of time to plan. For example, Missouri officials have had about 800 tests to work with, leading to only 395 performed so far in the region by public health labs – 26 of which were positive. When private lab tests are accounted for, as of March 20 there were 47 confirmed cases.
Health care providers and public health staff in the state, however, benefited from the fact that there is less international travel to the region, according to infectious disease expert Steven Lawrence, MD, of Washington University, St. Louis.
“This is very similar to 1918 with the influenza pandemic – St. Louis had more time to prepare and was able to put measures in place to flatten the curve than, say, Philadelphia,” Dr. Lawrence said. “Seattle didn’t have an opportunity to prepare as much in advance.”
While commercial labs are coming online, strict restrictions are limiting testing capabilities, Dr. Lawrence said.
“The state has had their hands tied,” he added.
Waiting And wondering
Because of a widespread lag in testing, it is still a mystery for thousands of people to know whether they’ve come into contact with an infected person until well after it happens. As of March 20, the pandemic had killed more than 11,000 globally. More than 16,000 Americans were confirmed infected and at least 216 have died.
“CDC will distribute tests based on where they can do the most good. But without hospital-based testing and commercial testing, it will not be possible to meet the need,” said Tom Frieden, who led the CDC during President Obama’s administration and is a former commissioner of the New York City Health Department.
In California, public school teacher Claire Dugan, whose state was among the hardest hit in the initial wave of U.S. coronavirus cases, was told she didn’t qualify for testing because she had not traveled abroad to any country with an outbreak of the virus or been in contact with an infected person. Ms. Dugan, who lives in the San Francisco Bay area and is already medically fragile after a stray bullet nearly killed her while driving 4 years ago, sought a test from her doctor after registering a temperature of 100.7° F earlier this month.
“There are a lot of layers as to why this is so messed up,” said Ms. Dugan, who relies on a feeding tube and said she sought a test not only to protect herself but her students. “It’s community spreading right now, so it’s kind of silly we’re still insisting on [the early criteria for testing]. How would I know?”
Since the CDC’s initial distribution, states have been reordering more tests through the office’s International Reagent Resource – a long-standing tool that public health labs have relied on. They have also revised testing protocols to use only one sample per person, which boosts the number of people screened.
Yet problems still abound with tests or other materials needed to be able to detect the virus. California Gov. Gavin Newsom (D) said on March 12 that county public health labs can’t use all of the 8,000 test kits the state has because they are missing key components.
In Pennsylvania, state officials weren’t able to begin testing until March 2 because of problems with the CDC’s initial kit, according to Nate Wardle, a spokesperson at its department of health. New York received two newly manufactured CDC test kits on Feb. 29 and also began performing tests March 2, according to its health department.
“We are still limited on extraction kits,” Mandy Cohen, the Health & Human Services secretary in North Carolina, said in an interview in mid-March. Officials earlier this month could test only 300 patients because of shortages in the extraction materials needed to register whether the novel coronavirus is present.
In North Dakota, Loralyn Hegland wrote her physician’s practice an email on March 10 with the subject line “dry cough,” wondering if she should come in for testing after learning that was one symptom of COVID-19. The recommendation she got echoes those of countless others across the United States, saying her risk of being exposed was very low because she hadn’t traveled outside the United States and had not come into contact with a person who had been “definitely” diagnosed with the virus.
Ms. Hegland, who lives in Fargo, didn’t have a fever but decided to shelter herself, anyway, out of caution.
Would she push to get a test?
“What’s the point?” she said. “You can’t know what you don’t know. It’s just that simple. How else do you explain it to people when you’re not testing?”
KHN Midwest correspondent Lauren Weber in St. Louis contributed to this article.
Kaiser Health News is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.
As the novel coronavirus snaked its way across the globe, the Centers for Disease Control and Prevention in early February distributed 200 test kits it had produced to more than 100 public health labs run by states and counties nationwide.
Each kit contained material to test a mere 300-400 patients. And labs, whether serving the population of New York or tiny towns in rural America, apparently received the same kits.
The kits were distributed roughly equally to locales in all 50 states. That decision presaged weeks of chaos, in which the availability of COVID-19 tests seemed oddly out of sync with where testing was needed.
A woman in South Dakota with mild symptoms and no fever readily got the test and the results. Meanwhile, political leaders and public officials in places like New York, Boston, Seattle, and the San Francisco Bay area – all in the throes of serious outbreaks – couldn’t get enough tests to screen ill patients or, thereby, the information they needed to protect the general public and stem the outbreak of the virus, whose symptoms mimic those of common respiratory illnesses.
Rapid testing is crucial in the early stages of an outbreak. It allows health workers and families to identify and focus on treating those infected and isolate them.
Yet health officials in New York and such states as New York, Washington, Pennsylvania, and Georgia confirmed that they each initially got one test kit, calling into question whether they would have even stood a chance to contain the outbreaks that would emerge. They would soon discover that the tests they did receive were flawed, lacking critical components, and delivering faulty results.
During those early weeks, the virus took off, infecting thousands of people and leading to nationwide social distancing and sheltering in place. Public health officials are just beginning to grapple with the fallout from that early bungling of testing, which is likely to haunt the country in the months to come.
Too little too late
The first shipment to Washington state arrived more than 2 weeks after officials there announced the first U.S. case of coronavirus, and at a moment when deadly outbreaks of the disease were already festering in places like the Life Care Center in Kirkland. Within weeks, three dozen people infected with COVID-19 would die at the nursing home in the suburbs of Seattle.
The spread of COVID-19 would not take long to overwhelm the state, which as of March 20, 2020, had more than 1,300 cases.
The Trump administration in recent days has attempted to speed testing for the virus after early missteps hampered the government’s response to contain the contagion, and officials have had to respond to a barrage of criticism from public health experts, state officials, and members of Congress.
Federal health officials have eased the process for university and commercial labs to perform their own tests, and they are ramping up their capacity. As of March 16, public and private labs in the United States had the ability to test more than 36,000 people a day, according to estimates compiled by the American Enterprise Institute, a conservative-leaning think tank in Washington, a figure expected to rapidly escalate in coming weeks. That figure, however, can vary considerably by state and does not indicate how many tests are actually given to patients.
“We are now beginning to see that they have spread out in a prioritized way. We asked them to prioritize the regions that were mostly affected,” Deborah Birx, the coronavirus response coordinator for the White House Coronavirus Task Force, said March 18 of private labs’ testing, without elaboration.
The scaling up of testing is set to take place after weeks of faltering and hundreds, if not thousands, of undiagnosed people spreading the virus. For example, New York’s state health department received a faulty CDC test kit on Feb. 8 for 800 patient specimens, an amount that’s consistent with other states, according to a spokesperson. It later began testing patients with a test that state officials developed based on the CDC protocol and has significantly increased testing – as of March 20, more than 7,200 people had tested positive statewide.
In New York City, the first batch was obtained on Feb. 7.
“The other state and local public health laboratories got test kits as they became available,” said Eric Blank, chief program officer of the Association of Public Health Laboratories.
Places in the middle of the country with no outbreaks had the luxury of time to plan. For example, Missouri officials have had about 800 tests to work with, leading to only 395 performed so far in the region by public health labs – 26 of which were positive. When private lab tests are accounted for, as of March 20 there were 47 confirmed cases.
Health care providers and public health staff in the state, however, benefited from the fact that there is less international travel to the region, according to infectious disease expert Steven Lawrence, MD, of Washington University, St. Louis.
“This is very similar to 1918 with the influenza pandemic – St. Louis had more time to prepare and was able to put measures in place to flatten the curve than, say, Philadelphia,” Dr. Lawrence said. “Seattle didn’t have an opportunity to prepare as much in advance.”
While commercial labs are coming online, strict restrictions are limiting testing capabilities, Dr. Lawrence said.
“The state has had their hands tied,” he added.
Waiting And wondering
Because of a widespread lag in testing, it is still a mystery for thousands of people to know whether they’ve come into contact with an infected person until well after it happens. As of March 20, the pandemic had killed more than 11,000 globally. More than 16,000 Americans were confirmed infected and at least 216 have died.
“CDC will distribute tests based on where they can do the most good. But without hospital-based testing and commercial testing, it will not be possible to meet the need,” said Tom Frieden, who led the CDC during President Obama’s administration and is a former commissioner of the New York City Health Department.
In California, public school teacher Claire Dugan, whose state was among the hardest hit in the initial wave of U.S. coronavirus cases, was told she didn’t qualify for testing because she had not traveled abroad to any country with an outbreak of the virus or been in contact with an infected person. Ms. Dugan, who lives in the San Francisco Bay area and is already medically fragile after a stray bullet nearly killed her while driving 4 years ago, sought a test from her doctor after registering a temperature of 100.7° F earlier this month.
“There are a lot of layers as to why this is so messed up,” said Ms. Dugan, who relies on a feeding tube and said she sought a test not only to protect herself but her students. “It’s community spreading right now, so it’s kind of silly we’re still insisting on [the early criteria for testing]. How would I know?”
Since the CDC’s initial distribution, states have been reordering more tests through the office’s International Reagent Resource – a long-standing tool that public health labs have relied on. They have also revised testing protocols to use only one sample per person, which boosts the number of people screened.
Yet problems still abound with tests or other materials needed to be able to detect the virus. California Gov. Gavin Newsom (D) said on March 12 that county public health labs can’t use all of the 8,000 test kits the state has because they are missing key components.
In Pennsylvania, state officials weren’t able to begin testing until March 2 because of problems with the CDC’s initial kit, according to Nate Wardle, a spokesperson at its department of health. New York received two newly manufactured CDC test kits on Feb. 29 and also began performing tests March 2, according to its health department.
“We are still limited on extraction kits,” Mandy Cohen, the Health & Human Services secretary in North Carolina, said in an interview in mid-March. Officials earlier this month could test only 300 patients because of shortages in the extraction materials needed to register whether the novel coronavirus is present.
In North Dakota, Loralyn Hegland wrote her physician’s practice an email on March 10 with the subject line “dry cough,” wondering if she should come in for testing after learning that was one symptom of COVID-19. The recommendation she got echoes those of countless others across the United States, saying her risk of being exposed was very low because she hadn’t traveled outside the United States and had not come into contact with a person who had been “definitely” diagnosed with the virus.
Ms. Hegland, who lives in Fargo, didn’t have a fever but decided to shelter herself, anyway, out of caution.
Would she push to get a test?
“What’s the point?” she said. “You can’t know what you don’t know. It’s just that simple. How else do you explain it to people when you’re not testing?”
KHN Midwest correspondent Lauren Weber in St. Louis contributed to this article.
Kaiser Health News is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.
How long is it safe to delay gynecologic cancer surgery?
As I write this column, there are more than 25,000 current cases of COVID-19 in the United States with an expected exponential rise in these numbers. Hospitals are issuing directives to cancel or postpone “elective” surgery to preserve the finite essential personal protective equipment (PPE), encourage social distancing, prevent exposure of at-risk patients within the hospital, and ensure bed and ventilator capacity for the impending surge in COVID-19 patients.
Many health systems have defined which surgeries they consider permissible, typically by using time parameters such as would not cause patient harm if not performed within 4 weeks, or 7 days, or 24 hours. This leaves surgeons in the unfamiliar position of rationing health care, a role with which, over the coming months, we may have to become increasingly comfortable. This is an enormous responsibility, the shift of resources between one population in need and another, and decisions should be based on data, not bias or hunch. We know that untreated cancer is life threatening, but there is a difference between untreated and delayed. What is a safe time to wait for gynecologic cancer surgery after diagnosis without negatively affecting survival from that cancer?
As I looked through my own upcoming surgical schedule, I sought guidance from the American College of Surgeons’ website, updated on March 17, 2020. In this site they tabulate an “Elective Surgery Acuity Scale” in which “most cancers” fit into tier 3a, which corresponds to high acuity surgery – “do not postpone.” This definition is fairly generalized and blunt; it does not account for the differences in cancers and occasional voluntary needs to postpone a patient’s cancer surgery for health optimization. There are limited data that measure the impact of surgical wait times on survival from gynecologic cancer. Most of this research is observational, and therefore, is influenced by confounders causing delay in surgery (e.g., comorbid conditions or socioeconomic factors that limit access to care). However, the current enforced delays are involuntary; driven by the system, not the patient; and access is universally restricted.
Endometrial cancer
Most data regarding outcomes and gynecologic cancer delay come from endometrial cancer. In 2016, Shalowitz et al. evaluated 182,000 endometrial cancer cases documented within the National Cancer Database (NCDB), which captures approximately 70% of cancer surgeries in the United States.1 They separated these patients into groups of low-grade (grade 1 and 2 endometrioid) and high-grade (grade 3 endometrioid and nonendometrioid) cancers, and evaluated the groups for their overall survival, stratified by the time period between diagnosis and surgery. Interestingly, those whose surgery was performed under 2 weeks from diagnosis had worse perioperative mortality and long-term survival. This seems to be a function of lack of medical optimization; low-volume, nonspecialized centers having less wait time; and the presentation of more advanced and symptomatic disease demanding a more urgent surgery. After those initial 2 weeks of worse outcomes, there was a period of stable outcomes and safety in waiting that extended up to 8 weeks for patients with low-grade cancers and up to 18 weeks for patients with high-grade cancers.
It may be counterintuitive to think that surgical delay affects patients with high-grade endometrial cancers less. These are more aggressive cancers, and there is patient and provider concern for metastatic spread with time elapsed. But an expedited surgery does not appear to be necessary for this group. The Shalowitz study demonstrated no risk for upstaging with surgical delay, meaning that advanced stage was not more likely to be identified in patients whose surgery was delayed, compared with those performed earlier. This observation suggests that the survival from high-grade endometrial cancers is largely determined by factors that cannot be controlled by the surgeon such as the stage at diagnosis, occult spread, and decreased responsiveness of the tumor to adjuvant therapy. In other words, fast-tracking these patients to surgery has limited influence on the outcomes for high-grade endometrial cancers.
For low-grade cancers, adverse outcomes were seen with a surgical delay of more than 8 weeks. But this may not have been caused by progression of disease (low-grade cancers also were not upstaged with delays), but rather may reflect that, in normal times, elective delays of more than 8 weeks are a function of necessary complex medical optimization of comorbidities (such as obesity-related disease). The survival that is measured by NCDB is not disease specific, and patients with comorbidities will be more likely to have impaired overall survival.
A systematic review of all papers that looked at endometrial cancer outcomes associated with surgical delay determined that it is reasonable to delay surgery for up to 8 weeks.2
Ovarian cancer
The data for ovarian cancer surgery is more limited. Most literature discusses the impact of delay in the time between surgery and the receipt of adjuvant chemotherapy, but there are limited data exploring how a delay in primary debulking negatively affects patients. This is perhaps because advanced ovarian cancer surgery rarely is delayed because of symptoms and apparent advanced stage at diagnosis. When a patient’s surgery does need to be voluntarily delayed, for example for medical optimization, there is the option of neoadjuvant chemotherapy (NACT) in which surgery is performed after three or more cycles of chemotherapy. NACT has been shown in multiple studies to have noninferior cancer outcomes, compared with primary debulking surgery.3,4
Perhaps in this current environment in which access to operating rooms and supplies is rationed, we should consider offering more, or all, patients NACT? Hospital stays after primary cytoreductive surgeries are typically 3-7 days in length, and these patients are at a higher risk, compared with other gynecologic cancer surgeries, of ICU admission and blood transfusions, both limited resources in this current environment. The disadvantage of this approach is that, while chemotherapy can keep patients out of the hospital so that they can practice social distancing, this particular therapy adds to the immunocompromised population. However, even patients who undergo primary surgical cytoreductive surgery will need to rapidly transition to immunosuppressive cytotoxic therapy; therefore it is unlikely that this can be avoided entirely during this time.
Lower genital tract cancers
Surgery for patients with lower genital tract cancers – such as cervical and vulvar cancer – also can probably be safely delayed for a 4-week period, and possibly longer. A Canadian retrospective study looked collectively at cervical, vaginal, and vulvar cancers evaluating for disease progression associated with delay to surgery, using 28 days as a benchmark for delayed surgery.5 They found no significant increased progression associated with surgical delay greater than 28 days. This study evaluated progression of cancer and did not measure cancer survival, although it is unlikely we would see impaired survival without a significant increase in disease progression.
We also can look to outcomes from delayed radical hysterectomy for stage I cervical cancer in pregnancy to provided us with some data. A retrospective cohort study observed no difference in survival when 28 women with early-stage cervical cancer who were diagnosed in pregnancy (average wait time 20 weeks from diagnosis to treatment) were compared with the outcomes of 52 matched nonpregnant control patients (average wait time 8 weeks). Their survival was 89% versus 94% respectively (P = .08).6
Summary
Synthesizing this data, it appears that, in an environment of competing needs and resources, it is reasonable and safe to delay surgery for patients with gynecologic cancers for 4-6 weeks and potentially longer. This includes patients with high-grade endometrial cancers. Clearly, these decisions should be individualized to patients and different health systems. For example, a patient who presents with a cancer-associated life-threatening bowel obstruction or hemorrhage may need an immediate intervention, and communities minimally affected by the coronavirus pandemic may have more allowances for surgery. With respect to patient anxiety, most patients with cancer are keen to have surgery promptly, and breaking the news to them that their surgery may be delayed because of institutional and public health needs will be difficult. However, the data support that this is likely safe.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She had no relevant financial disclosures. Email Dr. Rossi at [email protected].
References
1. Am J Obstet Gynecol 2017;216(3):268 e1-68 e18.
2. Eur J Obstet Gynecol Reprod Biol 2020;246:1-6. doi: 10.1016/j.ejogrb.2020.01.004.
3. N Engl J Med 2010;363(10):943-53.
4. Lancet 2015;386(9990):249-57.
5. J Obstet Gynaecol Can 2015;37(4):338-44.
6. Am J Obstet Gynecol 2017;216(3):276 e1-76 e6. doi: 10.1016/j.ajog.2016.10.034.
As I write this column, there are more than 25,000 current cases of COVID-19 in the United States with an expected exponential rise in these numbers. Hospitals are issuing directives to cancel or postpone “elective” surgery to preserve the finite essential personal protective equipment (PPE), encourage social distancing, prevent exposure of at-risk patients within the hospital, and ensure bed and ventilator capacity for the impending surge in COVID-19 patients.
Many health systems have defined which surgeries they consider permissible, typically by using time parameters such as would not cause patient harm if not performed within 4 weeks, or 7 days, or 24 hours. This leaves surgeons in the unfamiliar position of rationing health care, a role with which, over the coming months, we may have to become increasingly comfortable. This is an enormous responsibility, the shift of resources between one population in need and another, and decisions should be based on data, not bias or hunch. We know that untreated cancer is life threatening, but there is a difference between untreated and delayed. What is a safe time to wait for gynecologic cancer surgery after diagnosis without negatively affecting survival from that cancer?
As I looked through my own upcoming surgical schedule, I sought guidance from the American College of Surgeons’ website, updated on March 17, 2020. In this site they tabulate an “Elective Surgery Acuity Scale” in which “most cancers” fit into tier 3a, which corresponds to high acuity surgery – “do not postpone.” This definition is fairly generalized and blunt; it does not account for the differences in cancers and occasional voluntary needs to postpone a patient’s cancer surgery for health optimization. There are limited data that measure the impact of surgical wait times on survival from gynecologic cancer. Most of this research is observational, and therefore, is influenced by confounders causing delay in surgery (e.g., comorbid conditions or socioeconomic factors that limit access to care). However, the current enforced delays are involuntary; driven by the system, not the patient; and access is universally restricted.
Endometrial cancer
Most data regarding outcomes and gynecologic cancer delay come from endometrial cancer. In 2016, Shalowitz et al. evaluated 182,000 endometrial cancer cases documented within the National Cancer Database (NCDB), which captures approximately 70% of cancer surgeries in the United States.1 They separated these patients into groups of low-grade (grade 1 and 2 endometrioid) and high-grade (grade 3 endometrioid and nonendometrioid) cancers, and evaluated the groups for their overall survival, stratified by the time period between diagnosis and surgery. Interestingly, those whose surgery was performed under 2 weeks from diagnosis had worse perioperative mortality and long-term survival. This seems to be a function of lack of medical optimization; low-volume, nonspecialized centers having less wait time; and the presentation of more advanced and symptomatic disease demanding a more urgent surgery. After those initial 2 weeks of worse outcomes, there was a period of stable outcomes and safety in waiting that extended up to 8 weeks for patients with low-grade cancers and up to 18 weeks for patients with high-grade cancers.
It may be counterintuitive to think that surgical delay affects patients with high-grade endometrial cancers less. These are more aggressive cancers, and there is patient and provider concern for metastatic spread with time elapsed. But an expedited surgery does not appear to be necessary for this group. The Shalowitz study demonstrated no risk for upstaging with surgical delay, meaning that advanced stage was not more likely to be identified in patients whose surgery was delayed, compared with those performed earlier. This observation suggests that the survival from high-grade endometrial cancers is largely determined by factors that cannot be controlled by the surgeon such as the stage at diagnosis, occult spread, and decreased responsiveness of the tumor to adjuvant therapy. In other words, fast-tracking these patients to surgery has limited influence on the outcomes for high-grade endometrial cancers.
For low-grade cancers, adverse outcomes were seen with a surgical delay of more than 8 weeks. But this may not have been caused by progression of disease (low-grade cancers also were not upstaged with delays), but rather may reflect that, in normal times, elective delays of more than 8 weeks are a function of necessary complex medical optimization of comorbidities (such as obesity-related disease). The survival that is measured by NCDB is not disease specific, and patients with comorbidities will be more likely to have impaired overall survival.
A systematic review of all papers that looked at endometrial cancer outcomes associated with surgical delay determined that it is reasonable to delay surgery for up to 8 weeks.2
Ovarian cancer
The data for ovarian cancer surgery is more limited. Most literature discusses the impact of delay in the time between surgery and the receipt of adjuvant chemotherapy, but there are limited data exploring how a delay in primary debulking negatively affects patients. This is perhaps because advanced ovarian cancer surgery rarely is delayed because of symptoms and apparent advanced stage at diagnosis. When a patient’s surgery does need to be voluntarily delayed, for example for medical optimization, there is the option of neoadjuvant chemotherapy (NACT) in which surgery is performed after three or more cycles of chemotherapy. NACT has been shown in multiple studies to have noninferior cancer outcomes, compared with primary debulking surgery.3,4
Perhaps in this current environment in which access to operating rooms and supplies is rationed, we should consider offering more, or all, patients NACT? Hospital stays after primary cytoreductive surgeries are typically 3-7 days in length, and these patients are at a higher risk, compared with other gynecologic cancer surgeries, of ICU admission and blood transfusions, both limited resources in this current environment. The disadvantage of this approach is that, while chemotherapy can keep patients out of the hospital so that they can practice social distancing, this particular therapy adds to the immunocompromised population. However, even patients who undergo primary surgical cytoreductive surgery will need to rapidly transition to immunosuppressive cytotoxic therapy; therefore it is unlikely that this can be avoided entirely during this time.
Lower genital tract cancers
Surgery for patients with lower genital tract cancers – such as cervical and vulvar cancer – also can probably be safely delayed for a 4-week period, and possibly longer. A Canadian retrospective study looked collectively at cervical, vaginal, and vulvar cancers evaluating for disease progression associated with delay to surgery, using 28 days as a benchmark for delayed surgery.5 They found no significant increased progression associated with surgical delay greater than 28 days. This study evaluated progression of cancer and did not measure cancer survival, although it is unlikely we would see impaired survival without a significant increase in disease progression.
We also can look to outcomes from delayed radical hysterectomy for stage I cervical cancer in pregnancy to provided us with some data. A retrospective cohort study observed no difference in survival when 28 women with early-stage cervical cancer who were diagnosed in pregnancy (average wait time 20 weeks from diagnosis to treatment) were compared with the outcomes of 52 matched nonpregnant control patients (average wait time 8 weeks). Their survival was 89% versus 94% respectively (P = .08).6
Summary
Synthesizing this data, it appears that, in an environment of competing needs and resources, it is reasonable and safe to delay surgery for patients with gynecologic cancers for 4-6 weeks and potentially longer. This includes patients with high-grade endometrial cancers. Clearly, these decisions should be individualized to patients and different health systems. For example, a patient who presents with a cancer-associated life-threatening bowel obstruction or hemorrhage may need an immediate intervention, and communities minimally affected by the coronavirus pandemic may have more allowances for surgery. With respect to patient anxiety, most patients with cancer are keen to have surgery promptly, and breaking the news to them that their surgery may be delayed because of institutional and public health needs will be difficult. However, the data support that this is likely safe.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She had no relevant financial disclosures. Email Dr. Rossi at [email protected].
References
1. Am J Obstet Gynecol 2017;216(3):268 e1-68 e18.
2. Eur J Obstet Gynecol Reprod Biol 2020;246:1-6. doi: 10.1016/j.ejogrb.2020.01.004.
3. N Engl J Med 2010;363(10):943-53.
4. Lancet 2015;386(9990):249-57.
5. J Obstet Gynaecol Can 2015;37(4):338-44.
6. Am J Obstet Gynecol 2017;216(3):276 e1-76 e6. doi: 10.1016/j.ajog.2016.10.034.
As I write this column, there are more than 25,000 current cases of COVID-19 in the United States with an expected exponential rise in these numbers. Hospitals are issuing directives to cancel or postpone “elective” surgery to preserve the finite essential personal protective equipment (PPE), encourage social distancing, prevent exposure of at-risk patients within the hospital, and ensure bed and ventilator capacity for the impending surge in COVID-19 patients.
Many health systems have defined which surgeries they consider permissible, typically by using time parameters such as would not cause patient harm if not performed within 4 weeks, or 7 days, or 24 hours. This leaves surgeons in the unfamiliar position of rationing health care, a role with which, over the coming months, we may have to become increasingly comfortable. This is an enormous responsibility, the shift of resources between one population in need and another, and decisions should be based on data, not bias or hunch. We know that untreated cancer is life threatening, but there is a difference between untreated and delayed. What is a safe time to wait for gynecologic cancer surgery after diagnosis without negatively affecting survival from that cancer?
As I looked through my own upcoming surgical schedule, I sought guidance from the American College of Surgeons’ website, updated on March 17, 2020. In this site they tabulate an “Elective Surgery Acuity Scale” in which “most cancers” fit into tier 3a, which corresponds to high acuity surgery – “do not postpone.” This definition is fairly generalized and blunt; it does not account for the differences in cancers and occasional voluntary needs to postpone a patient’s cancer surgery for health optimization. There are limited data that measure the impact of surgical wait times on survival from gynecologic cancer. Most of this research is observational, and therefore, is influenced by confounders causing delay in surgery (e.g., comorbid conditions or socioeconomic factors that limit access to care). However, the current enforced delays are involuntary; driven by the system, not the patient; and access is universally restricted.
Endometrial cancer
Most data regarding outcomes and gynecologic cancer delay come from endometrial cancer. In 2016, Shalowitz et al. evaluated 182,000 endometrial cancer cases documented within the National Cancer Database (NCDB), which captures approximately 70% of cancer surgeries in the United States.1 They separated these patients into groups of low-grade (grade 1 and 2 endometrioid) and high-grade (grade 3 endometrioid and nonendometrioid) cancers, and evaluated the groups for their overall survival, stratified by the time period between diagnosis and surgery. Interestingly, those whose surgery was performed under 2 weeks from diagnosis had worse perioperative mortality and long-term survival. This seems to be a function of lack of medical optimization; low-volume, nonspecialized centers having less wait time; and the presentation of more advanced and symptomatic disease demanding a more urgent surgery. After those initial 2 weeks of worse outcomes, there was a period of stable outcomes and safety in waiting that extended up to 8 weeks for patients with low-grade cancers and up to 18 weeks for patients with high-grade cancers.
It may be counterintuitive to think that surgical delay affects patients with high-grade endometrial cancers less. These are more aggressive cancers, and there is patient and provider concern for metastatic spread with time elapsed. But an expedited surgery does not appear to be necessary for this group. The Shalowitz study demonstrated no risk for upstaging with surgical delay, meaning that advanced stage was not more likely to be identified in patients whose surgery was delayed, compared with those performed earlier. This observation suggests that the survival from high-grade endometrial cancers is largely determined by factors that cannot be controlled by the surgeon such as the stage at diagnosis, occult spread, and decreased responsiveness of the tumor to adjuvant therapy. In other words, fast-tracking these patients to surgery has limited influence on the outcomes for high-grade endometrial cancers.
For low-grade cancers, adverse outcomes were seen with a surgical delay of more than 8 weeks. But this may not have been caused by progression of disease (low-grade cancers also were not upstaged with delays), but rather may reflect that, in normal times, elective delays of more than 8 weeks are a function of necessary complex medical optimization of comorbidities (such as obesity-related disease). The survival that is measured by NCDB is not disease specific, and patients with comorbidities will be more likely to have impaired overall survival.
A systematic review of all papers that looked at endometrial cancer outcomes associated with surgical delay determined that it is reasonable to delay surgery for up to 8 weeks.2
Ovarian cancer
The data for ovarian cancer surgery is more limited. Most literature discusses the impact of delay in the time between surgery and the receipt of adjuvant chemotherapy, but there are limited data exploring how a delay in primary debulking negatively affects patients. This is perhaps because advanced ovarian cancer surgery rarely is delayed because of symptoms and apparent advanced stage at diagnosis. When a patient’s surgery does need to be voluntarily delayed, for example for medical optimization, there is the option of neoadjuvant chemotherapy (NACT) in which surgery is performed after three or more cycles of chemotherapy. NACT has been shown in multiple studies to have noninferior cancer outcomes, compared with primary debulking surgery.3,4
Perhaps in this current environment in which access to operating rooms and supplies is rationed, we should consider offering more, or all, patients NACT? Hospital stays after primary cytoreductive surgeries are typically 3-7 days in length, and these patients are at a higher risk, compared with other gynecologic cancer surgeries, of ICU admission and blood transfusions, both limited resources in this current environment. The disadvantage of this approach is that, while chemotherapy can keep patients out of the hospital so that they can practice social distancing, this particular therapy adds to the immunocompromised population. However, even patients who undergo primary surgical cytoreductive surgery will need to rapidly transition to immunosuppressive cytotoxic therapy; therefore it is unlikely that this can be avoided entirely during this time.
Lower genital tract cancers
Surgery for patients with lower genital tract cancers – such as cervical and vulvar cancer – also can probably be safely delayed for a 4-week period, and possibly longer. A Canadian retrospective study looked collectively at cervical, vaginal, and vulvar cancers evaluating for disease progression associated with delay to surgery, using 28 days as a benchmark for delayed surgery.5 They found no significant increased progression associated with surgical delay greater than 28 days. This study evaluated progression of cancer and did not measure cancer survival, although it is unlikely we would see impaired survival without a significant increase in disease progression.
We also can look to outcomes from delayed radical hysterectomy for stage I cervical cancer in pregnancy to provided us with some data. A retrospective cohort study observed no difference in survival when 28 women with early-stage cervical cancer who were diagnosed in pregnancy (average wait time 20 weeks from diagnosis to treatment) were compared with the outcomes of 52 matched nonpregnant control patients (average wait time 8 weeks). Their survival was 89% versus 94% respectively (P = .08).6
Summary
Synthesizing this data, it appears that, in an environment of competing needs and resources, it is reasonable and safe to delay surgery for patients with gynecologic cancers for 4-6 weeks and potentially longer. This includes patients with high-grade endometrial cancers. Clearly, these decisions should be individualized to patients and different health systems. For example, a patient who presents with a cancer-associated life-threatening bowel obstruction or hemorrhage may need an immediate intervention, and communities minimally affected by the coronavirus pandemic may have more allowances for surgery. With respect to patient anxiety, most patients with cancer are keen to have surgery promptly, and breaking the news to them that their surgery may be delayed because of institutional and public health needs will be difficult. However, the data support that this is likely safe.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She had no relevant financial disclosures. Email Dr. Rossi at [email protected].
References
1. Am J Obstet Gynecol 2017;216(3):268 e1-68 e18.
2. Eur J Obstet Gynecol Reprod Biol 2020;246:1-6. doi: 10.1016/j.ejogrb.2020.01.004.
3. N Engl J Med 2010;363(10):943-53.
4. Lancet 2015;386(9990):249-57.
5. J Obstet Gynaecol Can 2015;37(4):338-44.
6. Am J Obstet Gynecol 2017;216(3):276 e1-76 e6. doi: 10.1016/j.ajog.2016.10.034.
Sleep-disordered breathing linked with Alzheimer’s disease biomarkers in cognitively normal older adults
investigators have found.
Among 127 adults enrolled in a randomized clinical trial of interventions to promote mental well-being in older adults, those with sleep-disordered breathing had significantly greater amyloid burden and gray-matter volume, as well as increased perfusion and metabolism in parietal-occipital regions, reported Claire André, PhD, from the French Institute of Health and Medical Research (INSERM) unit in Caen, and colleagues.
“Our findings highlight the need to treat sleep disorders in the older population, even in the absence of cognitive or behavioral manifestations,” they wrote in a study published in JAMA Neurology.
Previous studies of the possible association between sleep-disordered breathing and dementia risk have shown conflicting or inconsistent results, the authors noted.
“These discrepancies may be explained by the characteristics of patients with sleep-disordered breathing (e.g., recruited from sleep clinics versus from the community, differences in age and disease duration), the scoring criteria of respiratory events, sample sizes, or the lack of controls for possibly biasing covariates,” they wrote.
To see whether they could clear up the confusion, the investigators conducted a retrospective analysis of 127 patients who were enrolled in the Age-Well randomized, controlled trial of the Medit-Ageing European project. The participants were community-dwelling adults (mean age, 69.1 years; 63% women), who were enrolled in the trial and underwent evaluation from 2016 to 2018 at the Cyceron Cancer Center in Caen.
The participants, all of whom were cognitively unimpaired at baseline, underwent neuropsychological assessment, polysomnography, MRI, plus florbetapir- and fluorodeoxyglucose-labeled PET.
The investigators defined sleep-disordered breathing as 15 apnea-hypopnea index events per hour or higher, and compared results between those with sleep-disordered breathing and those without for each imaging modality.
Participants with sleep-disordered breathing has significantly greater amyloid burden (P = .04), gray-matter volume (P = .04), perfusion (P = .04), and metabolism (P = .001), primarily overlapping the posterior cingulate cortex and precuneus, areas known to be significantly involved in Alzheimer’s disease.
When the investigators looked for behavioral and cognitive correlates of sleep-disordered breathing severity with associated brain changes, however, they found no associations with either cognitive performance, self-reported cognitive or sleep difficulties, or symptoms of daytime sleepiness.
“Importantly, to the best of our knowledge, our results show in vivo for the first time that greater amyloid burden colocalizes with greater gray-matter volume, perfusion, and metabolism in older participants with sleep-disordered breathing who are cognitively unimpaired. We believe that these overlapping patterns reinforce the likelihood of common underlying mechanisms,” they wrote.
The Age-Well randomized clinical trial is part of the Medit-Ageing project and is funded through the European Union’s Horizon 2020 Research and Innovation Program, INSERM, and Fondation d’ Entreprise MMA des Entrepreneurs du Futur. Dr. André reported no conflicts of interest to disclose.
SOURCE: André C et al. JAMA Neurol. 2020 Mar 23. doi: 10.1001/jamaneurol.2020.0311.
investigators have found.
Among 127 adults enrolled in a randomized clinical trial of interventions to promote mental well-being in older adults, those with sleep-disordered breathing had significantly greater amyloid burden and gray-matter volume, as well as increased perfusion and metabolism in parietal-occipital regions, reported Claire André, PhD, from the French Institute of Health and Medical Research (INSERM) unit in Caen, and colleagues.
“Our findings highlight the need to treat sleep disorders in the older population, even in the absence of cognitive or behavioral manifestations,” they wrote in a study published in JAMA Neurology.
Previous studies of the possible association between sleep-disordered breathing and dementia risk have shown conflicting or inconsistent results, the authors noted.
“These discrepancies may be explained by the characteristics of patients with sleep-disordered breathing (e.g., recruited from sleep clinics versus from the community, differences in age and disease duration), the scoring criteria of respiratory events, sample sizes, or the lack of controls for possibly biasing covariates,” they wrote.
To see whether they could clear up the confusion, the investigators conducted a retrospective analysis of 127 patients who were enrolled in the Age-Well randomized, controlled trial of the Medit-Ageing European project. The participants were community-dwelling adults (mean age, 69.1 years; 63% women), who were enrolled in the trial and underwent evaluation from 2016 to 2018 at the Cyceron Cancer Center in Caen.
The participants, all of whom were cognitively unimpaired at baseline, underwent neuropsychological assessment, polysomnography, MRI, plus florbetapir- and fluorodeoxyglucose-labeled PET.
The investigators defined sleep-disordered breathing as 15 apnea-hypopnea index events per hour or higher, and compared results between those with sleep-disordered breathing and those without for each imaging modality.
Participants with sleep-disordered breathing has significantly greater amyloid burden (P = .04), gray-matter volume (P = .04), perfusion (P = .04), and metabolism (P = .001), primarily overlapping the posterior cingulate cortex and precuneus, areas known to be significantly involved in Alzheimer’s disease.
When the investigators looked for behavioral and cognitive correlates of sleep-disordered breathing severity with associated brain changes, however, they found no associations with either cognitive performance, self-reported cognitive or sleep difficulties, or symptoms of daytime sleepiness.
“Importantly, to the best of our knowledge, our results show in vivo for the first time that greater amyloid burden colocalizes with greater gray-matter volume, perfusion, and metabolism in older participants with sleep-disordered breathing who are cognitively unimpaired. We believe that these overlapping patterns reinforce the likelihood of common underlying mechanisms,” they wrote.
The Age-Well randomized clinical trial is part of the Medit-Ageing project and is funded through the European Union’s Horizon 2020 Research and Innovation Program, INSERM, and Fondation d’ Entreprise MMA des Entrepreneurs du Futur. Dr. André reported no conflicts of interest to disclose.
SOURCE: André C et al. JAMA Neurol. 2020 Mar 23. doi: 10.1001/jamaneurol.2020.0311.
investigators have found.
Among 127 adults enrolled in a randomized clinical trial of interventions to promote mental well-being in older adults, those with sleep-disordered breathing had significantly greater amyloid burden and gray-matter volume, as well as increased perfusion and metabolism in parietal-occipital regions, reported Claire André, PhD, from the French Institute of Health and Medical Research (INSERM) unit in Caen, and colleagues.
“Our findings highlight the need to treat sleep disorders in the older population, even in the absence of cognitive or behavioral manifestations,” they wrote in a study published in JAMA Neurology.
Previous studies of the possible association between sleep-disordered breathing and dementia risk have shown conflicting or inconsistent results, the authors noted.
“These discrepancies may be explained by the characteristics of patients with sleep-disordered breathing (e.g., recruited from sleep clinics versus from the community, differences in age and disease duration), the scoring criteria of respiratory events, sample sizes, or the lack of controls for possibly biasing covariates,” they wrote.
To see whether they could clear up the confusion, the investigators conducted a retrospective analysis of 127 patients who were enrolled in the Age-Well randomized, controlled trial of the Medit-Ageing European project. The participants were community-dwelling adults (mean age, 69.1 years; 63% women), who were enrolled in the trial and underwent evaluation from 2016 to 2018 at the Cyceron Cancer Center in Caen.
The participants, all of whom were cognitively unimpaired at baseline, underwent neuropsychological assessment, polysomnography, MRI, plus florbetapir- and fluorodeoxyglucose-labeled PET.
The investigators defined sleep-disordered breathing as 15 apnea-hypopnea index events per hour or higher, and compared results between those with sleep-disordered breathing and those without for each imaging modality.
Participants with sleep-disordered breathing has significantly greater amyloid burden (P = .04), gray-matter volume (P = .04), perfusion (P = .04), and metabolism (P = .001), primarily overlapping the posterior cingulate cortex and precuneus, areas known to be significantly involved in Alzheimer’s disease.
When the investigators looked for behavioral and cognitive correlates of sleep-disordered breathing severity with associated brain changes, however, they found no associations with either cognitive performance, self-reported cognitive or sleep difficulties, or symptoms of daytime sleepiness.
“Importantly, to the best of our knowledge, our results show in vivo for the first time that greater amyloid burden colocalizes with greater gray-matter volume, perfusion, and metabolism in older participants with sleep-disordered breathing who are cognitively unimpaired. We believe that these overlapping patterns reinforce the likelihood of common underlying mechanisms,” they wrote.
The Age-Well randomized clinical trial is part of the Medit-Ageing project and is funded through the European Union’s Horizon 2020 Research and Innovation Program, INSERM, and Fondation d’ Entreprise MMA des Entrepreneurs du Futur. Dr. André reported no conflicts of interest to disclose.
SOURCE: André C et al. JAMA Neurol. 2020 Mar 23. doi: 10.1001/jamaneurol.2020.0311.
FROM JAMA NEUROLOGY
Intracranial artery stenting shows promising 1-year results
LOS ANGELES –
One-year after 129 patients received an intracranial stent that’s already on the U.S. market for treating severe atherosclerotic disease following an ischemic stroke, their incidence of death or repeat stroke was 9%, low enough to suggest benefit compared with historic control patients who were medically managed and had a 12% 1-year rate of death or stroke. This signal of incremental benefit from intracranial stenting may help spark renewed interest in an intervention that was largely forsaken in recent years because of safety concerns.
Assessing restenosis frequency
“Stenting seemed to confer some protection against severe or fatal strokes” in a study that provided “the largest 1-year follow-up of stenting” for intracranial atherosclerotic disease, the trigger for roughly 10% of all U.S. stroke cases, Michael J. Alexander, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
What 1-year follow-up highlighted was the restenosis frequency, based on imaging follow-up for 107 of these 129 patients who had received a Wingspan nitinol, self-expanding stent. Seven patients developed symptomatic restenosis in the region of stent placement, and another 11 patients had asymptomatic restenosis that occluded at least 70% of the stented artery, a total 1-year restenosis rate of 18/107 (17%), reported Dr. Alexander, professor of neurosurgery and director of the Neurovascular Center at Cedars-Sinai Medical Center in Los Angeles. The mean time to detection of restenosis was 5 months, with a range of 1-11 months.
Intracranial stenting falls out of favor
The tested Wingspan stent first received Food and Drug Administration approval for intracranial artery placement in 2005, and then in August 2012 the agency tightened the labeled indication to a much smaller, more specifically defined group of patients: those 22-80 years old, with 70%-99% stenosis in a cerebral artery, with a history of at least two strokes, with stent placement timed more than 7 days following the most recent stroke, and refractory to medical therapy. This 2012 label change came in response to a concerning rate of periprocedural complications in patients who received intracrania artery stents as part of a study reported in 2011 that included many patients with clinical characteristics that fell outside the limits the agency later set in 2012. Results from the SAMMPRIS (Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) trial showed that among 451 randomized patients the 224 assigned to stenting had a 15% 30-day rate of death or stroke, compared with a 6% rate among control patients who did not receive a stent, a statistically significant difference that led to early stopping of the trial (New Engl J Med. 2011 Sep 15;365[11]:993-1003). At least half of the patients who received a stent in SAMMPRIS were 7 or fewer days out from their index event, a majority had either a single prior stroke or transient ischemic attack as their index event, and many had not been established as refractory to medical management.
The SAMMPRIS results and the subsequent relabeling of the Wingspan stent by the FDA had two consequences. First came a steep drop in the use of intracranial stenting. After SAMMPRIS, vascular neurologists “abandoned the stent; no one does intracranial stenting” today, commented Louise D. McCullough, MD, professor and chair of neurology at the University of Texas Health Science Center at Houston. The second consequence was an FDA mandate to run a new randomized study to reassess the periprocedural complications when clinicians placed the Wingspan intracranial stent in patients who fully matched the revised 2012 labeling.
That mandated study was the WEAVE (Post Market Surveillance Study of the Wingspan Stent System) trial, which enrolled 152 patients at 24 U.S. sites in a single-arm study, and found a 2.6% rate of death or stroke during the 30 days following intervention that beat the 4% benchmark rate prespecified in the trial’s design (Stroke. 2019 Apr;50[4]:889-94). The WEAVE findings provided even more evidence of the need for the tight labeling the device received in 2012. A safety communication from the FDA in April 2019 noted that an additional 46 patients received an intracranial artery stent during WEAVE despite falling outside the 2012 labeled indications, and this off-label group had a 24% incidence of periprocedural complications, compared with the 2.6% rate in the on-label group. The FDA’s statement reaffirmed the labeling restrictions and highlighted additional cautions and recommendations for using the device.
The WOVEN study
The 1-year follow-up of the WEAVE patients, an extension called the WOVEN (Wingspan One Year Vascular Imaging Events and Neurologic Outcomes) study, was investigator initiated with no commercial funding and included 129 of the original on-label patients (85%) at 15 of the original 24 participating centers.
In addition to the data collected in WOVEN on restenosis rates, follow-up tallied seven patients with a stroke in the vascular territory of the stent during the period that began 30 days after the procedure (when the WEAVE follow-up finished) and continued through 12 months, with no neurologic deaths. When combined with the 4 periprocedural events that occurred during WEAVE, the final WOVEN tally was 11 total events in 129 patients followed for 1 year (9%). Because WEAVE and WOVEN included no control patients, Dr. Alexander compared this 1-year incidence rate with the 12% rate among medically managed control patients in SAMMPRIS.
According to Dr. Alexander, the next step in the path to rehabilitating a clinical role for intracranial stenting is a new randomized study that compares stenting used exclusively to the 2012 labeling with medical management in high-risk patients, those with hemodynamic compromise.
Encouraging data, but is it compelling?
“There may be a benefit” from intracranial stenting, but “we need a larger trial to convince people” said Dr. McCullough. The WEAVE and new WOVEN findings provide a “signal that stenting may be better than medical therapy, but this was only in just over 100 patients. We’ll need a larger study,” she said in an interview. The findings also reinforced that restenosis remains a challenge for intracranial artery stenting.
“Intracranial atherosclerosis is very difficult to treat, and we need new strategies for these patients.” The WEAVE and WOVEN results “suggest that while the restenosis rate may be high, it may also be manageable.” Delaying stent placement to no sooner than 8 days after a stroke may be a key step for improving safety, but new approaches are also need to minimize the restenosis risk, Dr. McCullough noted.
WEAVE was sponsored by Stryker Neurovascular, the company that markets the Wingspan intracranial artery stent. WOVEN received no commercial funding. Dr. Alexander has been a consultant to Stryker Neurovascular. Dr. McCullough had no disclosures.
SOURCE: Alexander MJ et al. International Stroke Conference, Abstract LB4.
LOS ANGELES –
One-year after 129 patients received an intracranial stent that’s already on the U.S. market for treating severe atherosclerotic disease following an ischemic stroke, their incidence of death or repeat stroke was 9%, low enough to suggest benefit compared with historic control patients who were medically managed and had a 12% 1-year rate of death or stroke. This signal of incremental benefit from intracranial stenting may help spark renewed interest in an intervention that was largely forsaken in recent years because of safety concerns.
Assessing restenosis frequency
“Stenting seemed to confer some protection against severe or fatal strokes” in a study that provided “the largest 1-year follow-up of stenting” for intracranial atherosclerotic disease, the trigger for roughly 10% of all U.S. stroke cases, Michael J. Alexander, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
What 1-year follow-up highlighted was the restenosis frequency, based on imaging follow-up for 107 of these 129 patients who had received a Wingspan nitinol, self-expanding stent. Seven patients developed symptomatic restenosis in the region of stent placement, and another 11 patients had asymptomatic restenosis that occluded at least 70% of the stented artery, a total 1-year restenosis rate of 18/107 (17%), reported Dr. Alexander, professor of neurosurgery and director of the Neurovascular Center at Cedars-Sinai Medical Center in Los Angeles. The mean time to detection of restenosis was 5 months, with a range of 1-11 months.
Intracranial stenting falls out of favor
The tested Wingspan stent first received Food and Drug Administration approval for intracranial artery placement in 2005, and then in August 2012 the agency tightened the labeled indication to a much smaller, more specifically defined group of patients: those 22-80 years old, with 70%-99% stenosis in a cerebral artery, with a history of at least two strokes, with stent placement timed more than 7 days following the most recent stroke, and refractory to medical therapy. This 2012 label change came in response to a concerning rate of periprocedural complications in patients who received intracrania artery stents as part of a study reported in 2011 that included many patients with clinical characteristics that fell outside the limits the agency later set in 2012. Results from the SAMMPRIS (Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) trial showed that among 451 randomized patients the 224 assigned to stenting had a 15% 30-day rate of death or stroke, compared with a 6% rate among control patients who did not receive a stent, a statistically significant difference that led to early stopping of the trial (New Engl J Med. 2011 Sep 15;365[11]:993-1003). At least half of the patients who received a stent in SAMMPRIS were 7 or fewer days out from their index event, a majority had either a single prior stroke or transient ischemic attack as their index event, and many had not been established as refractory to medical management.
The SAMMPRIS results and the subsequent relabeling of the Wingspan stent by the FDA had two consequences. First came a steep drop in the use of intracranial stenting. After SAMMPRIS, vascular neurologists “abandoned the stent; no one does intracranial stenting” today, commented Louise D. McCullough, MD, professor and chair of neurology at the University of Texas Health Science Center at Houston. The second consequence was an FDA mandate to run a new randomized study to reassess the periprocedural complications when clinicians placed the Wingspan intracranial stent in patients who fully matched the revised 2012 labeling.
That mandated study was the WEAVE (Post Market Surveillance Study of the Wingspan Stent System) trial, which enrolled 152 patients at 24 U.S. sites in a single-arm study, and found a 2.6% rate of death or stroke during the 30 days following intervention that beat the 4% benchmark rate prespecified in the trial’s design (Stroke. 2019 Apr;50[4]:889-94). The WEAVE findings provided even more evidence of the need for the tight labeling the device received in 2012. A safety communication from the FDA in April 2019 noted that an additional 46 patients received an intracranial artery stent during WEAVE despite falling outside the 2012 labeled indications, and this off-label group had a 24% incidence of periprocedural complications, compared with the 2.6% rate in the on-label group. The FDA’s statement reaffirmed the labeling restrictions and highlighted additional cautions and recommendations for using the device.
The WOVEN study
The 1-year follow-up of the WEAVE patients, an extension called the WOVEN (Wingspan One Year Vascular Imaging Events and Neurologic Outcomes) study, was investigator initiated with no commercial funding and included 129 of the original on-label patients (85%) at 15 of the original 24 participating centers.
In addition to the data collected in WOVEN on restenosis rates, follow-up tallied seven patients with a stroke in the vascular territory of the stent during the period that began 30 days after the procedure (when the WEAVE follow-up finished) and continued through 12 months, with no neurologic deaths. When combined with the 4 periprocedural events that occurred during WEAVE, the final WOVEN tally was 11 total events in 129 patients followed for 1 year (9%). Because WEAVE and WOVEN included no control patients, Dr. Alexander compared this 1-year incidence rate with the 12% rate among medically managed control patients in SAMMPRIS.
According to Dr. Alexander, the next step in the path to rehabilitating a clinical role for intracranial stenting is a new randomized study that compares stenting used exclusively to the 2012 labeling with medical management in high-risk patients, those with hemodynamic compromise.
Encouraging data, but is it compelling?
“There may be a benefit” from intracranial stenting, but “we need a larger trial to convince people” said Dr. McCullough. The WEAVE and new WOVEN findings provide a “signal that stenting may be better than medical therapy, but this was only in just over 100 patients. We’ll need a larger study,” she said in an interview. The findings also reinforced that restenosis remains a challenge for intracranial artery stenting.
“Intracranial atherosclerosis is very difficult to treat, and we need new strategies for these patients.” The WEAVE and WOVEN results “suggest that while the restenosis rate may be high, it may also be manageable.” Delaying stent placement to no sooner than 8 days after a stroke may be a key step for improving safety, but new approaches are also need to minimize the restenosis risk, Dr. McCullough noted.
WEAVE was sponsored by Stryker Neurovascular, the company that markets the Wingspan intracranial artery stent. WOVEN received no commercial funding. Dr. Alexander has been a consultant to Stryker Neurovascular. Dr. McCullough had no disclosures.
SOURCE: Alexander MJ et al. International Stroke Conference, Abstract LB4.
LOS ANGELES –
One-year after 129 patients received an intracranial stent that’s already on the U.S. market for treating severe atherosclerotic disease following an ischemic stroke, their incidence of death or repeat stroke was 9%, low enough to suggest benefit compared with historic control patients who were medically managed and had a 12% 1-year rate of death or stroke. This signal of incremental benefit from intracranial stenting may help spark renewed interest in an intervention that was largely forsaken in recent years because of safety concerns.
Assessing restenosis frequency
“Stenting seemed to confer some protection against severe or fatal strokes” in a study that provided “the largest 1-year follow-up of stenting” for intracranial atherosclerotic disease, the trigger for roughly 10% of all U.S. stroke cases, Michael J. Alexander, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
What 1-year follow-up highlighted was the restenosis frequency, based on imaging follow-up for 107 of these 129 patients who had received a Wingspan nitinol, self-expanding stent. Seven patients developed symptomatic restenosis in the region of stent placement, and another 11 patients had asymptomatic restenosis that occluded at least 70% of the stented artery, a total 1-year restenosis rate of 18/107 (17%), reported Dr. Alexander, professor of neurosurgery and director of the Neurovascular Center at Cedars-Sinai Medical Center in Los Angeles. The mean time to detection of restenosis was 5 months, with a range of 1-11 months.
Intracranial stenting falls out of favor
The tested Wingspan stent first received Food and Drug Administration approval for intracranial artery placement in 2005, and then in August 2012 the agency tightened the labeled indication to a much smaller, more specifically defined group of patients: those 22-80 years old, with 70%-99% stenosis in a cerebral artery, with a history of at least two strokes, with stent placement timed more than 7 days following the most recent stroke, and refractory to medical therapy. This 2012 label change came in response to a concerning rate of periprocedural complications in patients who received intracrania artery stents as part of a study reported in 2011 that included many patients with clinical characteristics that fell outside the limits the agency later set in 2012. Results from the SAMMPRIS (Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) trial showed that among 451 randomized patients the 224 assigned to stenting had a 15% 30-day rate of death or stroke, compared with a 6% rate among control patients who did not receive a stent, a statistically significant difference that led to early stopping of the trial (New Engl J Med. 2011 Sep 15;365[11]:993-1003). At least half of the patients who received a stent in SAMMPRIS were 7 or fewer days out from their index event, a majority had either a single prior stroke or transient ischemic attack as their index event, and many had not been established as refractory to medical management.
The SAMMPRIS results and the subsequent relabeling of the Wingspan stent by the FDA had two consequences. First came a steep drop in the use of intracranial stenting. After SAMMPRIS, vascular neurologists “abandoned the stent; no one does intracranial stenting” today, commented Louise D. McCullough, MD, professor and chair of neurology at the University of Texas Health Science Center at Houston. The second consequence was an FDA mandate to run a new randomized study to reassess the periprocedural complications when clinicians placed the Wingspan intracranial stent in patients who fully matched the revised 2012 labeling.
That mandated study was the WEAVE (Post Market Surveillance Study of the Wingspan Stent System) trial, which enrolled 152 patients at 24 U.S. sites in a single-arm study, and found a 2.6% rate of death or stroke during the 30 days following intervention that beat the 4% benchmark rate prespecified in the trial’s design (Stroke. 2019 Apr;50[4]:889-94). The WEAVE findings provided even more evidence of the need for the tight labeling the device received in 2012. A safety communication from the FDA in April 2019 noted that an additional 46 patients received an intracranial artery stent during WEAVE despite falling outside the 2012 labeled indications, and this off-label group had a 24% incidence of periprocedural complications, compared with the 2.6% rate in the on-label group. The FDA’s statement reaffirmed the labeling restrictions and highlighted additional cautions and recommendations for using the device.
The WOVEN study
The 1-year follow-up of the WEAVE patients, an extension called the WOVEN (Wingspan One Year Vascular Imaging Events and Neurologic Outcomes) study, was investigator initiated with no commercial funding and included 129 of the original on-label patients (85%) at 15 of the original 24 participating centers.
In addition to the data collected in WOVEN on restenosis rates, follow-up tallied seven patients with a stroke in the vascular territory of the stent during the period that began 30 days after the procedure (when the WEAVE follow-up finished) and continued through 12 months, with no neurologic deaths. When combined with the 4 periprocedural events that occurred during WEAVE, the final WOVEN tally was 11 total events in 129 patients followed for 1 year (9%). Because WEAVE and WOVEN included no control patients, Dr. Alexander compared this 1-year incidence rate with the 12% rate among medically managed control patients in SAMMPRIS.
According to Dr. Alexander, the next step in the path to rehabilitating a clinical role for intracranial stenting is a new randomized study that compares stenting used exclusively to the 2012 labeling with medical management in high-risk patients, those with hemodynamic compromise.
Encouraging data, but is it compelling?
“There may be a benefit” from intracranial stenting, but “we need a larger trial to convince people” said Dr. McCullough. The WEAVE and new WOVEN findings provide a “signal that stenting may be better than medical therapy, but this was only in just over 100 patients. We’ll need a larger study,” she said in an interview. The findings also reinforced that restenosis remains a challenge for intracranial artery stenting.
“Intracranial atherosclerosis is very difficult to treat, and we need new strategies for these patients.” The WEAVE and WOVEN results “suggest that while the restenosis rate may be high, it may also be manageable.” Delaying stent placement to no sooner than 8 days after a stroke may be a key step for improving safety, but new approaches are also need to minimize the restenosis risk, Dr. McCullough noted.
WEAVE was sponsored by Stryker Neurovascular, the company that markets the Wingspan intracranial artery stent. WOVEN received no commercial funding. Dr. Alexander has been a consultant to Stryker Neurovascular. Dr. McCullough had no disclosures.
SOURCE: Alexander MJ et al. International Stroke Conference, Abstract LB4.
REPORTING FROM ISC 2020
AMA offers resources for front-line physicians
.
The literature include news, advocacy, and other information to help front-line physicians provide care to patients and keep themselves safe “in a rapidly changing environment,” the organization said in a statement.
“The AMA continues to forcefully advocate for [personal protective equipment] and critical policy and regulatory changes needed to address our public health and health system needs. Because so many of the challenges of the pandemic are felt at a practice level, we are also providing new tools and information to help physicians respond,” AMA President Patrice A. Harris, MD, said in the statement.
The COVID-19 physician and practice resources released by the AMA include:
- A Physicians Guide to COVID-19 .
- An AMA COVID-19 online resource center and a COVID-19 FAQ.
- A Quick Guide to Telemedicine in Practice.
- Ethical guidance for physicians .
- Evidence-based resources from the The JAMA Network COVID-19 Resource Center.
- CME for physicians through the JAMA Network’s JN Learning website.
.
The literature include news, advocacy, and other information to help front-line physicians provide care to patients and keep themselves safe “in a rapidly changing environment,” the organization said in a statement.
“The AMA continues to forcefully advocate for [personal protective equipment] and critical policy and regulatory changes needed to address our public health and health system needs. Because so many of the challenges of the pandemic are felt at a practice level, we are also providing new tools and information to help physicians respond,” AMA President Patrice A. Harris, MD, said in the statement.
The COVID-19 physician and practice resources released by the AMA include:
- A Physicians Guide to COVID-19 .
- An AMA COVID-19 online resource center and a COVID-19 FAQ.
- A Quick Guide to Telemedicine in Practice.
- Ethical guidance for physicians .
- Evidence-based resources from the The JAMA Network COVID-19 Resource Center.
- CME for physicians through the JAMA Network’s JN Learning website.
.
The literature include news, advocacy, and other information to help front-line physicians provide care to patients and keep themselves safe “in a rapidly changing environment,” the organization said in a statement.
“The AMA continues to forcefully advocate for [personal protective equipment] and critical policy and regulatory changes needed to address our public health and health system needs. Because so many of the challenges of the pandemic are felt at a practice level, we are also providing new tools and information to help physicians respond,” AMA President Patrice A. Harris, MD, said in the statement.
The COVID-19 physician and practice resources released by the AMA include:
- A Physicians Guide to COVID-19 .
- An AMA COVID-19 online resource center and a COVID-19 FAQ.
- A Quick Guide to Telemedicine in Practice.
- Ethical guidance for physicians .
- Evidence-based resources from the The JAMA Network COVID-19 Resource Center.
- CME for physicians through the JAMA Network’s JN Learning website.