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extacy
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A peer-reviewed clinical journal serving healthcare professionals working with the Department of Veterans Affairs, the Department of Defense, and the Public Health Service.
Abstracts Presented at the 2020 AVAHO Annual Meeting (Digital Edition)
Mounting data support COVID-19 acute pancreatitis
Mounting data support acute pancreatitis as one possible GI manifestation of COVID-19, according to investigators.
While previous case reports suggested that infection with SARS-CoV2 may lead to pancreatitis, this retrospective analysis, which is the largest to date, is the first to offer substantial evidence for this claim, reported lead author Sumant Inamdar, MBBS, of the University of Arkansas, Little Rock, and colleagues.
“It has become increasingly clear that COVID-19 has systemic effects that also includes the gastrointestinal and pancreaticobiliary systems,” the investigators wrote in Gastroenterology. “As islet cells of the pancreas contain ACE2 receptor proteins, SARS-CoV2 can bind to these receptors and cause pancreatic injury.”
For the present analysis, Dr. Inamdar and colleagues reviewed charts from 48,012 patients who were hospitalized in New York between March and June of this year. While pancreatitis is usually diagnosed based on two out of three criteria, disease classification in the study required all three: characteristic upper abdominal pain upon admission, lipase greater than three times the upper limit of normal, and evidence of pancreatitis on cross-sectional imaging.
“[B]y including all three criteria for pancreatitis in our definition, we may be underestimating the rate of pancreatitis,” the investigators wrote. “However, we felt including diagnostic lipase levels and imaging was important for the accuracy of the diagnosis.”
Primary outcomes included mechanical ventilation, length of stay, development of pancreatic necrosis, and mortality. Outcomes were compared between patients with and without COVID-19.
Out of 48,012 hospitalized patients, 11,883 (24.75%) tested positive for SARS-CoV2. Across the entire population, 189 patients had pancreatitis (0.39%), and of these, 32 (17%) also had COVID-19. This translates to a point prevalence for pancreatitis of 0.27% for patients hospitalized with COVID-19.
Among patients with pancreatitis who did not have COVID-19, the most common etiologies for pancreatitis were gallstones (34%) and alcohol (37%), compared with just 16% and 6% of SARS-CoV2-positive cases of pancreatitis, respectively. Idiopathic pancreatitis was significantly more common among patients with COVID-19 than those without (69% vs 21%; P less than .0001).
Black or Hispanic patients with pancreatitis were 4-5 times more likely to have COVID-19 than patients with pancreatitis who were white. Across all races/ethnicities, patients with pancreatitis and COVID-19 more often required mechanical ventilation (odds ratio [OR], 5.65) and longer hospital stays (OR, 3.22), compared with those who had pancreatitis alone. While rates of mortality and pancreatic necrosis showed similar trends, associations with COVID-19 were not statistically significant.
“These findings support the notion that pancreatitis should be included in the list of GI manifestations of COVID-19,” the investigators wrote.
When caring for patients with COVID-19, Dr. Inamdar and colleagues recommended that clinicians pay close attention to any history of abdominal pain, and consider testing serum lipase levels.
“Further large studies are needed to confirm our findings,” they concluded.
Gyanprakash Avinash Ketwaroo, MD, of Baylor College of Medicine in Houston, agreed that more work is needed; in the meantime, he suggested that evidence is now strong enough for clinicians to take notice.
“Overall, this study adds further weight to COVID-19 acute pancreatitis,” he said. “Larger studies, and convincing pathophysiologic data, will be needed to confirm COVID-19 as a cause of acute pancreatitis. However, there appears to be enough circumstantial evidence to consider a COVID-19 diagnosis in patients presenting with acute pancreatitis.”
He noted that the new clinical evidence also stands on a solid theoretical foundation.
“Viruses, especially mumps and measles, have long been known to cause acute pancreatitis,” he said. “Additionally, the ACE2 receptor is present on pancreatic beta-cells and may mediate COVID-19 induced pancreatitis.”
Along with larger observational studies, Dr. Ketwaroo suggested that a number of interventional questions remain unanswered.
“While most acute pancreatitis is treated with supportive care, could proven therapies for COVID-19, such as steroids, also mitigate COVID-19 acute pancreatitis?” he asked. “Is COVID-19 a cofactor for acute pancreatitis caused by alcohol or endoscopic retrograde cholangiopancreatography? We await further information from an active area of research.”
The investigators disclosed relationships with Boston Scientific, Olympus, Fujifilm, and others.
SOURCE: Inamdar S et al. Gastroenterology. 2020 Aug 26. doi: 10.1053/j.gastro.2020.08.044.
Mounting data support acute pancreatitis as one possible GI manifestation of COVID-19, according to investigators.
While previous case reports suggested that infection with SARS-CoV2 may lead to pancreatitis, this retrospective analysis, which is the largest to date, is the first to offer substantial evidence for this claim, reported lead author Sumant Inamdar, MBBS, of the University of Arkansas, Little Rock, and colleagues.
“It has become increasingly clear that COVID-19 has systemic effects that also includes the gastrointestinal and pancreaticobiliary systems,” the investigators wrote in Gastroenterology. “As islet cells of the pancreas contain ACE2 receptor proteins, SARS-CoV2 can bind to these receptors and cause pancreatic injury.”
For the present analysis, Dr. Inamdar and colleagues reviewed charts from 48,012 patients who were hospitalized in New York between March and June of this year. While pancreatitis is usually diagnosed based on two out of three criteria, disease classification in the study required all three: characteristic upper abdominal pain upon admission, lipase greater than three times the upper limit of normal, and evidence of pancreatitis on cross-sectional imaging.
“[B]y including all three criteria for pancreatitis in our definition, we may be underestimating the rate of pancreatitis,” the investigators wrote. “However, we felt including diagnostic lipase levels and imaging was important for the accuracy of the diagnosis.”
Primary outcomes included mechanical ventilation, length of stay, development of pancreatic necrosis, and mortality. Outcomes were compared between patients with and without COVID-19.
Out of 48,012 hospitalized patients, 11,883 (24.75%) tested positive for SARS-CoV2. Across the entire population, 189 patients had pancreatitis (0.39%), and of these, 32 (17%) also had COVID-19. This translates to a point prevalence for pancreatitis of 0.27% for patients hospitalized with COVID-19.
Among patients with pancreatitis who did not have COVID-19, the most common etiologies for pancreatitis were gallstones (34%) and alcohol (37%), compared with just 16% and 6% of SARS-CoV2-positive cases of pancreatitis, respectively. Idiopathic pancreatitis was significantly more common among patients with COVID-19 than those without (69% vs 21%; P less than .0001).
Black or Hispanic patients with pancreatitis were 4-5 times more likely to have COVID-19 than patients with pancreatitis who were white. Across all races/ethnicities, patients with pancreatitis and COVID-19 more often required mechanical ventilation (odds ratio [OR], 5.65) and longer hospital stays (OR, 3.22), compared with those who had pancreatitis alone. While rates of mortality and pancreatic necrosis showed similar trends, associations with COVID-19 were not statistically significant.
“These findings support the notion that pancreatitis should be included in the list of GI manifestations of COVID-19,” the investigators wrote.
When caring for patients with COVID-19, Dr. Inamdar and colleagues recommended that clinicians pay close attention to any history of abdominal pain, and consider testing serum lipase levels.
“Further large studies are needed to confirm our findings,” they concluded.
Gyanprakash Avinash Ketwaroo, MD, of Baylor College of Medicine in Houston, agreed that more work is needed; in the meantime, he suggested that evidence is now strong enough for clinicians to take notice.
“Overall, this study adds further weight to COVID-19 acute pancreatitis,” he said. “Larger studies, and convincing pathophysiologic data, will be needed to confirm COVID-19 as a cause of acute pancreatitis. However, there appears to be enough circumstantial evidence to consider a COVID-19 diagnosis in patients presenting with acute pancreatitis.”
He noted that the new clinical evidence also stands on a solid theoretical foundation.
“Viruses, especially mumps and measles, have long been known to cause acute pancreatitis,” he said. “Additionally, the ACE2 receptor is present on pancreatic beta-cells and may mediate COVID-19 induced pancreatitis.”
Along with larger observational studies, Dr. Ketwaroo suggested that a number of interventional questions remain unanswered.
“While most acute pancreatitis is treated with supportive care, could proven therapies for COVID-19, such as steroids, also mitigate COVID-19 acute pancreatitis?” he asked. “Is COVID-19 a cofactor for acute pancreatitis caused by alcohol or endoscopic retrograde cholangiopancreatography? We await further information from an active area of research.”
The investigators disclosed relationships with Boston Scientific, Olympus, Fujifilm, and others.
SOURCE: Inamdar S et al. Gastroenterology. 2020 Aug 26. doi: 10.1053/j.gastro.2020.08.044.
Mounting data support acute pancreatitis as one possible GI manifestation of COVID-19, according to investigators.
While previous case reports suggested that infection with SARS-CoV2 may lead to pancreatitis, this retrospective analysis, which is the largest to date, is the first to offer substantial evidence for this claim, reported lead author Sumant Inamdar, MBBS, of the University of Arkansas, Little Rock, and colleagues.
“It has become increasingly clear that COVID-19 has systemic effects that also includes the gastrointestinal and pancreaticobiliary systems,” the investigators wrote in Gastroenterology. “As islet cells of the pancreas contain ACE2 receptor proteins, SARS-CoV2 can bind to these receptors and cause pancreatic injury.”
For the present analysis, Dr. Inamdar and colleagues reviewed charts from 48,012 patients who were hospitalized in New York between March and June of this year. While pancreatitis is usually diagnosed based on two out of three criteria, disease classification in the study required all three: characteristic upper abdominal pain upon admission, lipase greater than three times the upper limit of normal, and evidence of pancreatitis on cross-sectional imaging.
“[B]y including all three criteria for pancreatitis in our definition, we may be underestimating the rate of pancreatitis,” the investigators wrote. “However, we felt including diagnostic lipase levels and imaging was important for the accuracy of the diagnosis.”
Primary outcomes included mechanical ventilation, length of stay, development of pancreatic necrosis, and mortality. Outcomes were compared between patients with and without COVID-19.
Out of 48,012 hospitalized patients, 11,883 (24.75%) tested positive for SARS-CoV2. Across the entire population, 189 patients had pancreatitis (0.39%), and of these, 32 (17%) also had COVID-19. This translates to a point prevalence for pancreatitis of 0.27% for patients hospitalized with COVID-19.
Among patients with pancreatitis who did not have COVID-19, the most common etiologies for pancreatitis were gallstones (34%) and alcohol (37%), compared with just 16% and 6% of SARS-CoV2-positive cases of pancreatitis, respectively. Idiopathic pancreatitis was significantly more common among patients with COVID-19 than those without (69% vs 21%; P less than .0001).
Black or Hispanic patients with pancreatitis were 4-5 times more likely to have COVID-19 than patients with pancreatitis who were white. Across all races/ethnicities, patients with pancreatitis and COVID-19 more often required mechanical ventilation (odds ratio [OR], 5.65) and longer hospital stays (OR, 3.22), compared with those who had pancreatitis alone. While rates of mortality and pancreatic necrosis showed similar trends, associations with COVID-19 were not statistically significant.
“These findings support the notion that pancreatitis should be included in the list of GI manifestations of COVID-19,” the investigators wrote.
When caring for patients with COVID-19, Dr. Inamdar and colleagues recommended that clinicians pay close attention to any history of abdominal pain, and consider testing serum lipase levels.
“Further large studies are needed to confirm our findings,” they concluded.
Gyanprakash Avinash Ketwaroo, MD, of Baylor College of Medicine in Houston, agreed that more work is needed; in the meantime, he suggested that evidence is now strong enough for clinicians to take notice.
“Overall, this study adds further weight to COVID-19 acute pancreatitis,” he said. “Larger studies, and convincing pathophysiologic data, will be needed to confirm COVID-19 as a cause of acute pancreatitis. However, there appears to be enough circumstantial evidence to consider a COVID-19 diagnosis in patients presenting with acute pancreatitis.”
He noted that the new clinical evidence also stands on a solid theoretical foundation.
“Viruses, especially mumps and measles, have long been known to cause acute pancreatitis,” he said. “Additionally, the ACE2 receptor is present on pancreatic beta-cells and may mediate COVID-19 induced pancreatitis.”
Along with larger observational studies, Dr. Ketwaroo suggested that a number of interventional questions remain unanswered.
“While most acute pancreatitis is treated with supportive care, could proven therapies for COVID-19, such as steroids, also mitigate COVID-19 acute pancreatitis?” he asked. “Is COVID-19 a cofactor for acute pancreatitis caused by alcohol or endoscopic retrograde cholangiopancreatography? We await further information from an active area of research.”
The investigators disclosed relationships with Boston Scientific, Olympus, Fujifilm, and others.
SOURCE: Inamdar S et al. Gastroenterology. 2020 Aug 26. doi: 10.1053/j.gastro.2020.08.044.
FROM GASTROENTEROLOGY
Five reasons why medical meetings will never be the same
In the wake of the COVID-19 pandemic, the virtual medical meeting is now the norm. And while it’s admirable that key data are being disseminated (often for free), there is no escaping the fact that it is a fundamentally different and lesser experience.
Watching from home, most of us split our attention between live streams of the meeting and work and family obligations. There is far less urgency when early live presentations are recorded and can be viewed later.
In terms of discussing the data, Twitter may offer broader participation than a live meeting, yet only a small number of attendees actively engage online.
And the exhibit halls for these online meetings? With neither free coffee nor company-branded tchotchkes, I expect that they have virtual tumbleweeds blowing through and crickets chirping.
Even still, the virtual meeting experience, while inferior to the live one, is a tremendous advance. It should never be banished as a historical footnote but rather should remain an option. It’s analogous to watching the Super Bowl at home: Obviously, it’s not the same as being there, but it’s a terrific alternative. Like telemedicine, this pandemic has provided a critical proof of concept that there is a better model.
Reshaping the medical meeting
Let’s consider five reasons why medical meetings should be permanently reshaped by this pandemic.
This pandemic isn’t going away in 2020. While nearly every country has done a far better job than the United States of containing COVID-19 thus far, outbreaks remain a problem wherever crowds assemble. You’d be hard-pressed to devise a setting more conducive to mass spread than a conference of 20,000 attendees from all over the world sitting alongside each other cheek to jowl for 5 days. Worse yet is the thought of them returning home and infecting their patients, families, and friends. What medical society wants to be remembered for creating a COVID-19 superspreader event? Professional medical societies will need to offer this option as the safest alternative moving forward.
Virtual learning still conveys the most important content. Despite the many social benefits of a live meeting, its core purpose is to disseminate new research and current and emerging treatment options. Virtual meetings have proven that this format can effectively deliver the content, and not as a secondary offering but as the sole platform in real time.
Virtual learning levels the playing field. Traveling to attend conferences typically costs thousands of dollars, accounting for the registration fees, inflated hotel rates, ground transportation, and meals out for days on end. Most meetings also demand several days away from our work and families, forcing many of us to work extra in the days before we leave and upon our return. Parents and those with commitments at home also face special challenges. For international participants, the financial and time costs are even greater. A virtual meeting helps overcome these hurdles and erases barriers that have long precluded many from attending a conference.
Virtual learning is efficient and comfortable. Virtual meetings over the past 6 months have given us a glimpse of an astonishingly more efficient form. If the content seems of a lower magnitude without the fanfare of a live conference, it is in part because so much of a live meeting is spent walking a mile between session rooms, waiting in concession or taxi lines, sitting in traffic between venues, or simply waiting for a session to begin. All of that has been replaced with time that you can use productively in between video sessions viewed either live or on demand. And with a virtual meeting, you can comfortably watch the sessions. There’s no need to stand along the back wall of an overcrowded room or step over 10 people to squeeze into an open middle seat. You can be focused, rather than having an end-of-day presentation wash over you as your eyes cross because you’ve been running around for the past 12 hours.
Virtual learning and social media will only improve. While virtual meetings unquestionably have limitations, it’s important to acknowledge that the successes thus far still represent only the earliest forays into this endeavor. In-person meetings evolved to their present form over centuries. In contrast, virtual meetings are being cobbled together within a few weeks or months. They can only be expected to improve as presenters adapt their skills to the online audience and new tools improve virtual discussions.
I am not implying that live meetings will or should be replaced by virtual ones. We still need that experience of trainees and experts presenting to a live audience and discussing the results together, all while sharing the energy of the moment. But there should be room for both a live conference and a virtual version.
Practically speaking, it is unclear whether professional societies could forgo the revenue they receive from registration fees, meeting sponsorships, and corporate exhibits. Yet, there are certainly ways to obtain sponsorship revenue for a virtual program. Even if the virtual version of a conference costs far less than attending in person, there is plenty of room between that number and free. It costs remarkably little for a professional society to share its content, and virtual offerings further the mission of distributing this content broadly.
We should not rush to return to the previous status quo. Despite their limitations, virtual meetings have brought a new, higher standard of access and efficiency for sharing important new data and treatment options in medicine.
H. Jack West, MD, associate clinical professor and executive director of employer services at City of Hope Comprehensive Cancer Center in Duarte, Calif., regularly comments on lung cancer for Medscape. West serves as web editor for JAMA Oncology, edits and writes several sections on lung cancer for UpToDate, and leads a wide range of continuing education programs and other educational programs, including hosting the audio podcast West Wind.
This article first appeared on Medscape.com.
In the wake of the COVID-19 pandemic, the virtual medical meeting is now the norm. And while it’s admirable that key data are being disseminated (often for free), there is no escaping the fact that it is a fundamentally different and lesser experience.
Watching from home, most of us split our attention between live streams of the meeting and work and family obligations. There is far less urgency when early live presentations are recorded and can be viewed later.
In terms of discussing the data, Twitter may offer broader participation than a live meeting, yet only a small number of attendees actively engage online.
And the exhibit halls for these online meetings? With neither free coffee nor company-branded tchotchkes, I expect that they have virtual tumbleweeds blowing through and crickets chirping.
Even still, the virtual meeting experience, while inferior to the live one, is a tremendous advance. It should never be banished as a historical footnote but rather should remain an option. It’s analogous to watching the Super Bowl at home: Obviously, it’s not the same as being there, but it’s a terrific alternative. Like telemedicine, this pandemic has provided a critical proof of concept that there is a better model.
Reshaping the medical meeting
Let’s consider five reasons why medical meetings should be permanently reshaped by this pandemic.
This pandemic isn’t going away in 2020. While nearly every country has done a far better job than the United States of containing COVID-19 thus far, outbreaks remain a problem wherever crowds assemble. You’d be hard-pressed to devise a setting more conducive to mass spread than a conference of 20,000 attendees from all over the world sitting alongside each other cheek to jowl for 5 days. Worse yet is the thought of them returning home and infecting their patients, families, and friends. What medical society wants to be remembered for creating a COVID-19 superspreader event? Professional medical societies will need to offer this option as the safest alternative moving forward.
Virtual learning still conveys the most important content. Despite the many social benefits of a live meeting, its core purpose is to disseminate new research and current and emerging treatment options. Virtual meetings have proven that this format can effectively deliver the content, and not as a secondary offering but as the sole platform in real time.
Virtual learning levels the playing field. Traveling to attend conferences typically costs thousands of dollars, accounting for the registration fees, inflated hotel rates, ground transportation, and meals out for days on end. Most meetings also demand several days away from our work and families, forcing many of us to work extra in the days before we leave and upon our return. Parents and those with commitments at home also face special challenges. For international participants, the financial and time costs are even greater. A virtual meeting helps overcome these hurdles and erases barriers that have long precluded many from attending a conference.
Virtual learning is efficient and comfortable. Virtual meetings over the past 6 months have given us a glimpse of an astonishingly more efficient form. If the content seems of a lower magnitude without the fanfare of a live conference, it is in part because so much of a live meeting is spent walking a mile between session rooms, waiting in concession or taxi lines, sitting in traffic between venues, or simply waiting for a session to begin. All of that has been replaced with time that you can use productively in between video sessions viewed either live or on demand. And with a virtual meeting, you can comfortably watch the sessions. There’s no need to stand along the back wall of an overcrowded room or step over 10 people to squeeze into an open middle seat. You can be focused, rather than having an end-of-day presentation wash over you as your eyes cross because you’ve been running around for the past 12 hours.
Virtual learning and social media will only improve. While virtual meetings unquestionably have limitations, it’s important to acknowledge that the successes thus far still represent only the earliest forays into this endeavor. In-person meetings evolved to their present form over centuries. In contrast, virtual meetings are being cobbled together within a few weeks or months. They can only be expected to improve as presenters adapt their skills to the online audience and new tools improve virtual discussions.
I am not implying that live meetings will or should be replaced by virtual ones. We still need that experience of trainees and experts presenting to a live audience and discussing the results together, all while sharing the energy of the moment. But there should be room for both a live conference and a virtual version.
Practically speaking, it is unclear whether professional societies could forgo the revenue they receive from registration fees, meeting sponsorships, and corporate exhibits. Yet, there are certainly ways to obtain sponsorship revenue for a virtual program. Even if the virtual version of a conference costs far less than attending in person, there is plenty of room between that number and free. It costs remarkably little for a professional society to share its content, and virtual offerings further the mission of distributing this content broadly.
We should not rush to return to the previous status quo. Despite their limitations, virtual meetings have brought a new, higher standard of access and efficiency for sharing important new data and treatment options in medicine.
H. Jack West, MD, associate clinical professor and executive director of employer services at City of Hope Comprehensive Cancer Center in Duarte, Calif., regularly comments on lung cancer for Medscape. West serves as web editor for JAMA Oncology, edits and writes several sections on lung cancer for UpToDate, and leads a wide range of continuing education programs and other educational programs, including hosting the audio podcast West Wind.
This article first appeared on Medscape.com.
In the wake of the COVID-19 pandemic, the virtual medical meeting is now the norm. And while it’s admirable that key data are being disseminated (often for free), there is no escaping the fact that it is a fundamentally different and lesser experience.
Watching from home, most of us split our attention between live streams of the meeting and work and family obligations. There is far less urgency when early live presentations are recorded and can be viewed later.
In terms of discussing the data, Twitter may offer broader participation than a live meeting, yet only a small number of attendees actively engage online.
And the exhibit halls for these online meetings? With neither free coffee nor company-branded tchotchkes, I expect that they have virtual tumbleweeds blowing through and crickets chirping.
Even still, the virtual meeting experience, while inferior to the live one, is a tremendous advance. It should never be banished as a historical footnote but rather should remain an option. It’s analogous to watching the Super Bowl at home: Obviously, it’s not the same as being there, but it’s a terrific alternative. Like telemedicine, this pandemic has provided a critical proof of concept that there is a better model.
Reshaping the medical meeting
Let’s consider five reasons why medical meetings should be permanently reshaped by this pandemic.
This pandemic isn’t going away in 2020. While nearly every country has done a far better job than the United States of containing COVID-19 thus far, outbreaks remain a problem wherever crowds assemble. You’d be hard-pressed to devise a setting more conducive to mass spread than a conference of 20,000 attendees from all over the world sitting alongside each other cheek to jowl for 5 days. Worse yet is the thought of them returning home and infecting their patients, families, and friends. What medical society wants to be remembered for creating a COVID-19 superspreader event? Professional medical societies will need to offer this option as the safest alternative moving forward.
Virtual learning still conveys the most important content. Despite the many social benefits of a live meeting, its core purpose is to disseminate new research and current and emerging treatment options. Virtual meetings have proven that this format can effectively deliver the content, and not as a secondary offering but as the sole platform in real time.
Virtual learning levels the playing field. Traveling to attend conferences typically costs thousands of dollars, accounting for the registration fees, inflated hotel rates, ground transportation, and meals out for days on end. Most meetings also demand several days away from our work and families, forcing many of us to work extra in the days before we leave and upon our return. Parents and those with commitments at home also face special challenges. For international participants, the financial and time costs are even greater. A virtual meeting helps overcome these hurdles and erases barriers that have long precluded many from attending a conference.
Virtual learning is efficient and comfortable. Virtual meetings over the past 6 months have given us a glimpse of an astonishingly more efficient form. If the content seems of a lower magnitude without the fanfare of a live conference, it is in part because so much of a live meeting is spent walking a mile between session rooms, waiting in concession or taxi lines, sitting in traffic between venues, or simply waiting for a session to begin. All of that has been replaced with time that you can use productively in between video sessions viewed either live or on demand. And with a virtual meeting, you can comfortably watch the sessions. There’s no need to stand along the back wall of an overcrowded room or step over 10 people to squeeze into an open middle seat. You can be focused, rather than having an end-of-day presentation wash over you as your eyes cross because you’ve been running around for the past 12 hours.
Virtual learning and social media will only improve. While virtual meetings unquestionably have limitations, it’s important to acknowledge that the successes thus far still represent only the earliest forays into this endeavor. In-person meetings evolved to their present form over centuries. In contrast, virtual meetings are being cobbled together within a few weeks or months. They can only be expected to improve as presenters adapt their skills to the online audience and new tools improve virtual discussions.
I am not implying that live meetings will or should be replaced by virtual ones. We still need that experience of trainees and experts presenting to a live audience and discussing the results together, all while sharing the energy of the moment. But there should be room for both a live conference and a virtual version.
Practically speaking, it is unclear whether professional societies could forgo the revenue they receive from registration fees, meeting sponsorships, and corporate exhibits. Yet, there are certainly ways to obtain sponsorship revenue for a virtual program. Even if the virtual version of a conference costs far less than attending in person, there is plenty of room between that number and free. It costs remarkably little for a professional society to share its content, and virtual offerings further the mission of distributing this content broadly.
We should not rush to return to the previous status quo. Despite their limitations, virtual meetings have brought a new, higher standard of access and efficiency for sharing important new data and treatment options in medicine.
H. Jack West, MD, associate clinical professor and executive director of employer services at City of Hope Comprehensive Cancer Center in Duarte, Calif., regularly comments on lung cancer for Medscape. West serves as web editor for JAMA Oncology, edits and writes several sections on lung cancer for UpToDate, and leads a wide range of continuing education programs and other educational programs, including hosting the audio podcast West Wind.
This article first appeared on Medscape.com.
Deaths sky high in hospitalized COVID patients with kidney injury
More evidence indicates that the development of acute kidney injury
“This ... is the first study in the United States to report the persistence of kidney dysfunction (lack of recovery) in survivors of COVID-19–associated AKI [and] this is in marked contrast to other forms of AKI where over 80% of patients recover their renal function by 10 days,” Lili Chan, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues observed.
The research is a retrospective, observational cohort study published online Sept. 3 in the Journal of the American Society of Nephrology
“We may be facing an epidemic of post–COVID-19 kidney disease and that, in turn, could mean much greater numbers of patients who require kidney dialysis and even transplants,” said senior author Girish Nadkarni, MD, a nephrologist, in a statement from Mount Sinai.
Nephrologists will need to prepare for a significant uptick in patients with chronic kidney disease as a result of exposure to the SARS-CoV-2 virus that causes COVID-19, the researchers warned.
“These findings may help centers with resource planning and preparing for the increased load resulting from survivors of COVID-19–associated AKI who do not experience recovery of kidney function,” they added.
Analysis of patients from February to end of May 2020
“AKI among hospitalized patients with COVID-19 in the United States is not well described,” they noted in their article.
And so they analyzed data from five major hospitals in the Mount Sinai Health System between Feb. 27 and May 30 of this year, during which 3,993 patients were hospitalized within the system for COVID-19. The MSHS has a patient population of racially and ethnically diverse citizens from New York.
AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. AKI occurred in 46% of the overall cohort of patients, 19% of whom required dialysis.
However, among those patients who required admission to the ICU, over three-quarters (76%) developed AKI and almost one-third of ICU patients required dialysis, the investigators said.
“The median time from hospital admission until AKI diagnoses was 1 day and the median time from AKI diagnosis to dialysis was 3 days,” they explain.
The proportion of patients with stages 1, 2, or 3 AKI among those admitted to hospital were 39%, 19%, and 42%, respectively. In patients requiring admission to ICU, 28% had stage 1 AKI, 17% had stage 2, and 56% had stage 3.
And among those who required dialysis for AKI, the median peak serum creatinine was 8.2 mg/dL, compared with 2.2 mg/dL for those who did not require dialysis.
Predictors of AKI: male sex, potassium levels, and preexisting CKD
Almost two thirds of patients (65%) had recovered from their kidney injury by the time they left hospital but 35% had acute kidney disease. Of this latter group, on follow-up, 36% had recovered from it, the investigators noted.
Conversely, of those patients who had recovered from AKI by hospital discharge, 14% went on to develop acute kidney disease at the time of follow-up.
And 30% of patients who had required dialysis at some point during their hospital care required dialysis again within 72 hours of being discharged, the investigators noted.
Predictors of severe AKI included male sex (adjusted odds ratio, 1.46), potassium levels on admission (aOR, 1.7), and preexisting chronic kidney disease (CKD) (aOR, 2.8).
Most compellingly, “in-hospital mortality in patients who experienced AKI was 50% [versus] 8% in patients without AKI (P < .001),” Dr. Nadkarni and colleagues reported.
Among those who required ICU care, 42% of patients with AKI died, compared with 7% of those in ICU who did not develop AKI, while in patients cared for outside of ICU, 62% with AKI died compared with only 13% of those who did not develop AKI.
And after adjusting for demographics, comorbidities, and laboratory values, the aOR for death was 11.4 times higher for ICU patients with AKI, compared with ICU patients without AKI, the authors emphasize.
In all patients who developed AKI, the aOR for mortality was 9.2, compared with patients who did not develop AKI, they added.
Perhaps predictably, the risk of death rose with increasing stage of AKI, and patients with stage 3 AKI who required dialysis were at highest risk of death, the authors observe.
Sheer number of AKI cases, need for dialysis unprecedented
“The sheer number of AKI cases and the overwhelming need for dialysis that we are seeing in the context of COVID-19 is unprecedented,” Dr. Nadkarni said.
“These findings bring clinical evidence to the hypothesis of lingering organ dysfunction among patients recovering from COVID-19 and serve as a reminder to hospitals around the country to be very strategic in the allocation of resources to care for patients who experience AKI,” he cautioned.
“We are grappling with a great deal of uncertainty as to how the virus will impact the kidneys in the long haul,” Dr. Nadkarni added. “We may be facing an epidemic of post–COVID-19 kidney disease, and that, in turn, could mean much greater numbers of patients who require kidney dialysis and even transplants.”
Dr. Nadkarni reported serving as a consultant and advisory board member for RenalytixAI and owns equity in the company.
This article first appeared on Medscape.com.
More evidence indicates that the development of acute kidney injury
“This ... is the first study in the United States to report the persistence of kidney dysfunction (lack of recovery) in survivors of COVID-19–associated AKI [and] this is in marked contrast to other forms of AKI where over 80% of patients recover their renal function by 10 days,” Lili Chan, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues observed.
The research is a retrospective, observational cohort study published online Sept. 3 in the Journal of the American Society of Nephrology
“We may be facing an epidemic of post–COVID-19 kidney disease and that, in turn, could mean much greater numbers of patients who require kidney dialysis and even transplants,” said senior author Girish Nadkarni, MD, a nephrologist, in a statement from Mount Sinai.
Nephrologists will need to prepare for a significant uptick in patients with chronic kidney disease as a result of exposure to the SARS-CoV-2 virus that causes COVID-19, the researchers warned.
“These findings may help centers with resource planning and preparing for the increased load resulting from survivors of COVID-19–associated AKI who do not experience recovery of kidney function,” they added.
Analysis of patients from February to end of May 2020
“AKI among hospitalized patients with COVID-19 in the United States is not well described,” they noted in their article.
And so they analyzed data from five major hospitals in the Mount Sinai Health System between Feb. 27 and May 30 of this year, during which 3,993 patients were hospitalized within the system for COVID-19. The MSHS has a patient population of racially and ethnically diverse citizens from New York.
AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. AKI occurred in 46% of the overall cohort of patients, 19% of whom required dialysis.
However, among those patients who required admission to the ICU, over three-quarters (76%) developed AKI and almost one-third of ICU patients required dialysis, the investigators said.
“The median time from hospital admission until AKI diagnoses was 1 day and the median time from AKI diagnosis to dialysis was 3 days,” they explain.
The proportion of patients with stages 1, 2, or 3 AKI among those admitted to hospital were 39%, 19%, and 42%, respectively. In patients requiring admission to ICU, 28% had stage 1 AKI, 17% had stage 2, and 56% had stage 3.
And among those who required dialysis for AKI, the median peak serum creatinine was 8.2 mg/dL, compared with 2.2 mg/dL for those who did not require dialysis.
Predictors of AKI: male sex, potassium levels, and preexisting CKD
Almost two thirds of patients (65%) had recovered from their kidney injury by the time they left hospital but 35% had acute kidney disease. Of this latter group, on follow-up, 36% had recovered from it, the investigators noted.
Conversely, of those patients who had recovered from AKI by hospital discharge, 14% went on to develop acute kidney disease at the time of follow-up.
And 30% of patients who had required dialysis at some point during their hospital care required dialysis again within 72 hours of being discharged, the investigators noted.
Predictors of severe AKI included male sex (adjusted odds ratio, 1.46), potassium levels on admission (aOR, 1.7), and preexisting chronic kidney disease (CKD) (aOR, 2.8).
Most compellingly, “in-hospital mortality in patients who experienced AKI was 50% [versus] 8% in patients without AKI (P < .001),” Dr. Nadkarni and colleagues reported.
Among those who required ICU care, 42% of patients with AKI died, compared with 7% of those in ICU who did not develop AKI, while in patients cared for outside of ICU, 62% with AKI died compared with only 13% of those who did not develop AKI.
And after adjusting for demographics, comorbidities, and laboratory values, the aOR for death was 11.4 times higher for ICU patients with AKI, compared with ICU patients without AKI, the authors emphasize.
In all patients who developed AKI, the aOR for mortality was 9.2, compared with patients who did not develop AKI, they added.
Perhaps predictably, the risk of death rose with increasing stage of AKI, and patients with stage 3 AKI who required dialysis were at highest risk of death, the authors observe.
Sheer number of AKI cases, need for dialysis unprecedented
“The sheer number of AKI cases and the overwhelming need for dialysis that we are seeing in the context of COVID-19 is unprecedented,” Dr. Nadkarni said.
“These findings bring clinical evidence to the hypothesis of lingering organ dysfunction among patients recovering from COVID-19 and serve as a reminder to hospitals around the country to be very strategic in the allocation of resources to care for patients who experience AKI,” he cautioned.
“We are grappling with a great deal of uncertainty as to how the virus will impact the kidneys in the long haul,” Dr. Nadkarni added. “We may be facing an epidemic of post–COVID-19 kidney disease, and that, in turn, could mean much greater numbers of patients who require kidney dialysis and even transplants.”
Dr. Nadkarni reported serving as a consultant and advisory board member for RenalytixAI and owns equity in the company.
This article first appeared on Medscape.com.
More evidence indicates that the development of acute kidney injury
“This ... is the first study in the United States to report the persistence of kidney dysfunction (lack of recovery) in survivors of COVID-19–associated AKI [and] this is in marked contrast to other forms of AKI where over 80% of patients recover their renal function by 10 days,” Lili Chan, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues observed.
The research is a retrospective, observational cohort study published online Sept. 3 in the Journal of the American Society of Nephrology
“We may be facing an epidemic of post–COVID-19 kidney disease and that, in turn, could mean much greater numbers of patients who require kidney dialysis and even transplants,” said senior author Girish Nadkarni, MD, a nephrologist, in a statement from Mount Sinai.
Nephrologists will need to prepare for a significant uptick in patients with chronic kidney disease as a result of exposure to the SARS-CoV-2 virus that causes COVID-19, the researchers warned.
“These findings may help centers with resource planning and preparing for the increased load resulting from survivors of COVID-19–associated AKI who do not experience recovery of kidney function,” they added.
Analysis of patients from February to end of May 2020
“AKI among hospitalized patients with COVID-19 in the United States is not well described,” they noted in their article.
And so they analyzed data from five major hospitals in the Mount Sinai Health System between Feb. 27 and May 30 of this year, during which 3,993 patients were hospitalized within the system for COVID-19. The MSHS has a patient population of racially and ethnically diverse citizens from New York.
AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. AKI occurred in 46% of the overall cohort of patients, 19% of whom required dialysis.
However, among those patients who required admission to the ICU, over three-quarters (76%) developed AKI and almost one-third of ICU patients required dialysis, the investigators said.
“The median time from hospital admission until AKI diagnoses was 1 day and the median time from AKI diagnosis to dialysis was 3 days,” they explain.
The proportion of patients with stages 1, 2, or 3 AKI among those admitted to hospital were 39%, 19%, and 42%, respectively. In patients requiring admission to ICU, 28% had stage 1 AKI, 17% had stage 2, and 56% had stage 3.
And among those who required dialysis for AKI, the median peak serum creatinine was 8.2 mg/dL, compared with 2.2 mg/dL for those who did not require dialysis.
Predictors of AKI: male sex, potassium levels, and preexisting CKD
Almost two thirds of patients (65%) had recovered from their kidney injury by the time they left hospital but 35% had acute kidney disease. Of this latter group, on follow-up, 36% had recovered from it, the investigators noted.
Conversely, of those patients who had recovered from AKI by hospital discharge, 14% went on to develop acute kidney disease at the time of follow-up.
And 30% of patients who had required dialysis at some point during their hospital care required dialysis again within 72 hours of being discharged, the investigators noted.
Predictors of severe AKI included male sex (adjusted odds ratio, 1.46), potassium levels on admission (aOR, 1.7), and preexisting chronic kidney disease (CKD) (aOR, 2.8).
Most compellingly, “in-hospital mortality in patients who experienced AKI was 50% [versus] 8% in patients without AKI (P < .001),” Dr. Nadkarni and colleagues reported.
Among those who required ICU care, 42% of patients with AKI died, compared with 7% of those in ICU who did not develop AKI, while in patients cared for outside of ICU, 62% with AKI died compared with only 13% of those who did not develop AKI.
And after adjusting for demographics, comorbidities, and laboratory values, the aOR for death was 11.4 times higher for ICU patients with AKI, compared with ICU patients without AKI, the authors emphasize.
In all patients who developed AKI, the aOR for mortality was 9.2, compared with patients who did not develop AKI, they added.
Perhaps predictably, the risk of death rose with increasing stage of AKI, and patients with stage 3 AKI who required dialysis were at highest risk of death, the authors observe.
Sheer number of AKI cases, need for dialysis unprecedented
“The sheer number of AKI cases and the overwhelming need for dialysis that we are seeing in the context of COVID-19 is unprecedented,” Dr. Nadkarni said.
“These findings bring clinical evidence to the hypothesis of lingering organ dysfunction among patients recovering from COVID-19 and serve as a reminder to hospitals around the country to be very strategic in the allocation of resources to care for patients who experience AKI,” he cautioned.
“We are grappling with a great deal of uncertainty as to how the virus will impact the kidneys in the long haul,” Dr. Nadkarni added. “We may be facing an epidemic of post–COVID-19 kidney disease, and that, in turn, could mean much greater numbers of patients who require kidney dialysis and even transplants.”
Dr. Nadkarni reported serving as a consultant and advisory board member for RenalytixAI and owns equity in the company.
This article first appeared on Medscape.com.
Unexpected results in new COVID-19 ‘cytokine storm’ data
The immune system overactivation known as a “cytokine storm” does not play a major role in more severe COVID-19 outcomes, according to unexpected findings in new research. The findings stand in direct contrast to many previous reports.
“We were indeed surprised by the results of our study,” senior study author Peter Pickkers, MD, PhD, said in an interview.
In a unique approach, Dr. Pickkers and colleagues compared cytokine levels in critically ill people with COVID-19 with those in patients with bacterial sepsis, trauma, and after cardiac arrest.
“For the first time, we measured the cytokines in different diseases using the same methods. Our results convincingly show that the circulating cytokine concentrations are not higher, but lower, compared to other diseases,” said Dr. Pickkers, who is affiliated with the department of intensive care medicine at Radboud University Medical Center in Nijmegen, the Netherlands.
The team’s research was published online on Sept. 3 in a letter in JAMA.
Cytokines lower than expected
Normally, cytokines trigger inflammation and promote healing after trauma, infection, or other conditions.
Although a cytokine storm remains ill defined, the authors noted, many researchers have implicated a hyperinflammatory response involving these small proteins in the pathophysiology of COVID-19.
The question remains, however, whether all cytokine storms strike people with different conditions the same way.
Dr. Pickkers, lead author Matthijs Kox, PhD, and colleagues studied 46 people with COVID-19 and acute respiratory distress syndrome (ARDS) who were admitted to the ICU at Radboud University Medical Center. All participants underwent mechanical ventilation and were treated between March 11 and April 27, 2020.
The investigators measured plasma levels of cytokines, including tumor necrosis factor (TNF), interleukin-6, and IL-8. They compared results in this group with those in 51 patients who experienced septic shock and ARDS, 15 patients with septic shock without ARDS, 30 people with out-of-hospital cardiac arrest, and 62 people who experienced multiple traumas. They used historical data for the non–COVID-19 cohorts.
Conditional findings
Compared with patients with septic shock and ARDS, the COVID-19 cohort had lower levels of TNF, IL-6, and IL-8. The differences were statistically significant for TNF (P < .01), as well as for IL-6 and IL-8 concentrations (for both, P < .001).
In addition, the COVID-19 group had significantly lower IL-6 and IL-8 concentrations compared with the patients who had septic shock without ARDS.
The researchers likewise found lower concentrations of IL-8 in patients with COVID-19, compared with the out-of-hospital cardiac arrest patients. IL-8 levels did not differ between the COVID-19 and trauma groups.
Furthermore, the researchers found no differences in IL-6 concentrations between patients with COVID-19 and those who experienced out-of-hospital cardiac arrest or trauma.
However, levels of TNF in people with COVID-19 were higher than in trauma patients.
The small sample sizes and single-center study design are limitations.
“The findings of this preliminary analysis suggest COVID-19 may not be characterized by cytokine storm,” the researchers noted. However, they added, “whether anticytokine therapies will benefit patients with COVID-19 remains to be determined.”
Going forward, Dr. Pickkers and colleagues are investigating the effectiveness of different treatments to lower cytokine levels. They are treating people with COVID-19, for example, with the IL-1 cytokine inhibitor anakinra and steroids.
They also plan to assess the long-term effects of COVID-19 on the immune system. “Following an infection, it is known that the immune system may be suppressed for a longer period of time, and we are determining to what extent this is also present in COVID-19 patients,” Dr. Pickkers said.
Enough to cause a storm?
The study “is quite interesting, and data in this paper are consistent with our data,” Tadamitsu Kishimoto, MD, PhD, of the department of immune regulation at the Immunology Frontier Research Center at Osaka (Japan) University, said in an interview.
His study, published online August 21 in PNAS, also revealed lower serum IL-6 levels among people with COVID-19, compared with patients with bacterial ARDS or sepsis.
Dr. Kishimoto drew a distinction, however: COVID-19 patients can develop severe respiratory failure, suggesting a distinct immune reaction, compared with patients with bacterial sepsis. SARS-CoV-2 directly infects and activates endothelial cells rather than macrophages, as occurs in sepsis.
For this reason, Dr. Kishimoto said, “SARS-CoV-2 infection causes critical illness and severe dysfunction in respiratory organs and induces a cytokine storm,” even in the setting of lower but still elevated serum IL-6 levels.
Dr. Pickkers and Dr. Kishimoto reported no relevant financial relationships.
This story first appeared on Medscape.com.
The immune system overactivation known as a “cytokine storm” does not play a major role in more severe COVID-19 outcomes, according to unexpected findings in new research. The findings stand in direct contrast to many previous reports.
“We were indeed surprised by the results of our study,” senior study author Peter Pickkers, MD, PhD, said in an interview.
In a unique approach, Dr. Pickkers and colleagues compared cytokine levels in critically ill people with COVID-19 with those in patients with bacterial sepsis, trauma, and after cardiac arrest.
“For the first time, we measured the cytokines in different diseases using the same methods. Our results convincingly show that the circulating cytokine concentrations are not higher, but lower, compared to other diseases,” said Dr. Pickkers, who is affiliated with the department of intensive care medicine at Radboud University Medical Center in Nijmegen, the Netherlands.
The team’s research was published online on Sept. 3 in a letter in JAMA.
Cytokines lower than expected
Normally, cytokines trigger inflammation and promote healing after trauma, infection, or other conditions.
Although a cytokine storm remains ill defined, the authors noted, many researchers have implicated a hyperinflammatory response involving these small proteins in the pathophysiology of COVID-19.
The question remains, however, whether all cytokine storms strike people with different conditions the same way.
Dr. Pickkers, lead author Matthijs Kox, PhD, and colleagues studied 46 people with COVID-19 and acute respiratory distress syndrome (ARDS) who were admitted to the ICU at Radboud University Medical Center. All participants underwent mechanical ventilation and were treated between March 11 and April 27, 2020.
The investigators measured plasma levels of cytokines, including tumor necrosis factor (TNF), interleukin-6, and IL-8. They compared results in this group with those in 51 patients who experienced septic shock and ARDS, 15 patients with septic shock without ARDS, 30 people with out-of-hospital cardiac arrest, and 62 people who experienced multiple traumas. They used historical data for the non–COVID-19 cohorts.
Conditional findings
Compared with patients with septic shock and ARDS, the COVID-19 cohort had lower levels of TNF, IL-6, and IL-8. The differences were statistically significant for TNF (P < .01), as well as for IL-6 and IL-8 concentrations (for both, P < .001).
In addition, the COVID-19 group had significantly lower IL-6 and IL-8 concentrations compared with the patients who had septic shock without ARDS.
The researchers likewise found lower concentrations of IL-8 in patients with COVID-19, compared with the out-of-hospital cardiac arrest patients. IL-8 levels did not differ between the COVID-19 and trauma groups.
Furthermore, the researchers found no differences in IL-6 concentrations between patients with COVID-19 and those who experienced out-of-hospital cardiac arrest or trauma.
However, levels of TNF in people with COVID-19 were higher than in trauma patients.
The small sample sizes and single-center study design are limitations.
“The findings of this preliminary analysis suggest COVID-19 may not be characterized by cytokine storm,” the researchers noted. However, they added, “whether anticytokine therapies will benefit patients with COVID-19 remains to be determined.”
Going forward, Dr. Pickkers and colleagues are investigating the effectiveness of different treatments to lower cytokine levels. They are treating people with COVID-19, for example, with the IL-1 cytokine inhibitor anakinra and steroids.
They also plan to assess the long-term effects of COVID-19 on the immune system. “Following an infection, it is known that the immune system may be suppressed for a longer period of time, and we are determining to what extent this is also present in COVID-19 patients,” Dr. Pickkers said.
Enough to cause a storm?
The study “is quite interesting, and data in this paper are consistent with our data,” Tadamitsu Kishimoto, MD, PhD, of the department of immune regulation at the Immunology Frontier Research Center at Osaka (Japan) University, said in an interview.
His study, published online August 21 in PNAS, also revealed lower serum IL-6 levels among people with COVID-19, compared with patients with bacterial ARDS or sepsis.
Dr. Kishimoto drew a distinction, however: COVID-19 patients can develop severe respiratory failure, suggesting a distinct immune reaction, compared with patients with bacterial sepsis. SARS-CoV-2 directly infects and activates endothelial cells rather than macrophages, as occurs in sepsis.
For this reason, Dr. Kishimoto said, “SARS-CoV-2 infection causes critical illness and severe dysfunction in respiratory organs and induces a cytokine storm,” even in the setting of lower but still elevated serum IL-6 levels.
Dr. Pickkers and Dr. Kishimoto reported no relevant financial relationships.
This story first appeared on Medscape.com.
The immune system overactivation known as a “cytokine storm” does not play a major role in more severe COVID-19 outcomes, according to unexpected findings in new research. The findings stand in direct contrast to many previous reports.
“We were indeed surprised by the results of our study,” senior study author Peter Pickkers, MD, PhD, said in an interview.
In a unique approach, Dr. Pickkers and colleagues compared cytokine levels in critically ill people with COVID-19 with those in patients with bacterial sepsis, trauma, and after cardiac arrest.
“For the first time, we measured the cytokines in different diseases using the same methods. Our results convincingly show that the circulating cytokine concentrations are not higher, but lower, compared to other diseases,” said Dr. Pickkers, who is affiliated with the department of intensive care medicine at Radboud University Medical Center in Nijmegen, the Netherlands.
The team’s research was published online on Sept. 3 in a letter in JAMA.
Cytokines lower than expected
Normally, cytokines trigger inflammation and promote healing after trauma, infection, or other conditions.
Although a cytokine storm remains ill defined, the authors noted, many researchers have implicated a hyperinflammatory response involving these small proteins in the pathophysiology of COVID-19.
The question remains, however, whether all cytokine storms strike people with different conditions the same way.
Dr. Pickkers, lead author Matthijs Kox, PhD, and colleagues studied 46 people with COVID-19 and acute respiratory distress syndrome (ARDS) who were admitted to the ICU at Radboud University Medical Center. All participants underwent mechanical ventilation and were treated between March 11 and April 27, 2020.
The investigators measured plasma levels of cytokines, including tumor necrosis factor (TNF), interleukin-6, and IL-8. They compared results in this group with those in 51 patients who experienced septic shock and ARDS, 15 patients with septic shock without ARDS, 30 people with out-of-hospital cardiac arrest, and 62 people who experienced multiple traumas. They used historical data for the non–COVID-19 cohorts.
Conditional findings
Compared with patients with septic shock and ARDS, the COVID-19 cohort had lower levels of TNF, IL-6, and IL-8. The differences were statistically significant for TNF (P < .01), as well as for IL-6 and IL-8 concentrations (for both, P < .001).
In addition, the COVID-19 group had significantly lower IL-6 and IL-8 concentrations compared with the patients who had septic shock without ARDS.
The researchers likewise found lower concentrations of IL-8 in patients with COVID-19, compared with the out-of-hospital cardiac arrest patients. IL-8 levels did not differ between the COVID-19 and trauma groups.
Furthermore, the researchers found no differences in IL-6 concentrations between patients with COVID-19 and those who experienced out-of-hospital cardiac arrest or trauma.
However, levels of TNF in people with COVID-19 were higher than in trauma patients.
The small sample sizes and single-center study design are limitations.
“The findings of this preliminary analysis suggest COVID-19 may not be characterized by cytokine storm,” the researchers noted. However, they added, “whether anticytokine therapies will benefit patients with COVID-19 remains to be determined.”
Going forward, Dr. Pickkers and colleagues are investigating the effectiveness of different treatments to lower cytokine levels. They are treating people with COVID-19, for example, with the IL-1 cytokine inhibitor anakinra and steroids.
They also plan to assess the long-term effects of COVID-19 on the immune system. “Following an infection, it is known that the immune system may be suppressed for a longer period of time, and we are determining to what extent this is also present in COVID-19 patients,” Dr. Pickkers said.
Enough to cause a storm?
The study “is quite interesting, and data in this paper are consistent with our data,” Tadamitsu Kishimoto, MD, PhD, of the department of immune regulation at the Immunology Frontier Research Center at Osaka (Japan) University, said in an interview.
His study, published online August 21 in PNAS, also revealed lower serum IL-6 levels among people with COVID-19, compared with patients with bacterial ARDS or sepsis.
Dr. Kishimoto drew a distinction, however: COVID-19 patients can develop severe respiratory failure, suggesting a distinct immune reaction, compared with patients with bacterial sepsis. SARS-CoV-2 directly infects and activates endothelial cells rather than macrophages, as occurs in sepsis.
For this reason, Dr. Kishimoto said, “SARS-CoV-2 infection causes critical illness and severe dysfunction in respiratory organs and induces a cytokine storm,” even in the setting of lower but still elevated serum IL-6 levels.
Dr. Pickkers and Dr. Kishimoto reported no relevant financial relationships.
This story first appeared on Medscape.com.
More U.S. states cap insulin cost, but activists will ‘fight harder’
Twelve U.S. states have now passed laws aimed at making insulin more affordable – and more than 30 are considering such legislation – but they all have gaps that still put the cost of this basic and essential medication out of reach for many with diabetes.
The laws only apply to health insurance through state-regulated plans, and not to the majority of health plans that cover most Americans: Medicare, Medicaid, the Veterans Affairs health system, or self-funded employer-sponsored plans.
Overall, Hannah Crabtree, an activist who writes the blog Data for Insulin, estimates state laws that limit copays, deductibles, or other out-of-pocket costs for insulin cover an average of 27% of people with diabetes across the United States.
And while diabetes activists have applauded state actions, most want more help for the under- and uninsured.
“Our chapter will be fighting harder next legislative session for the uninsured,” said Mindie Hooley, the leader of the Utah #insulin4all chapter, which successfully lobbied legislators to pass a bill signed by the state’s governor on March 30.
“With so many losing their jobs because of the pandemic, there’s no better time than now to fight for these patients who don’t have insurance,” Ms. Hooley said in an interview.
The American Diabetes Association has also been lobbying for state caps as one of many avenues for making insulin more affordable, said Stephen Habbe, the ADA’s director for state government affairs.
One in four insulin users report rationing the medication, Mr. Habbe said.
The state laws “can really provide important relief in terms of affordability for their insulin costs, which we know can be critical in terms of preserving their life and helping to prevent complications that can potentially be disabling or even deadly,” he said in an interview.
Activists with T1 International, which created the #insulin4all campaign, are working nationwide to convince state legislators to back measures that limit out-of-pocket costs for insulin, or for other diabetes medications and supplies.
Colorado, Connecticut, Delaware, Illinois, Maine, New Hampshire, New Mexico, New York, Utah, Virginia, Washington, and West Virginia have enacted such limits, with caps ranging from $25 to $100.
Insulin makers unfazed, blame insurers, PBMs for high prices
The three insulin manufacturers in the United States – Eli Lilly, Novo Nordisk, and Sanofi– have not overtly fought against the laws, although in July, the Pharmaceutical Research and Manufacturers of America did sue to block a related Minnesota law that provides a free emergency supply of insulin.
And the nonprofit news organization FairWarning reported in August that a lobbyist from Eli Lilly had attempted to push a Tennessee legislator to keep the uninsured from being eligible for any out-of-pocket limits.
The insulin makers have also not lowered prices in response to the mounting number of state laws.
They see no need, said Tara O’Neill Hayes, director of human welfare policy at the American Action Forum, a center right–leaning Washington, D.C., think tank.
“You’re going to do what you can get away with,” Ms. O’Neill Hayes said in an interview. “To the extent that they can keep their prices high and people are still buying, they have limited incentives to lower those costs.”
The insulin market is dysfunctional, she added. “The increasing cost of insulin seems primarily to be the result of a lack of competition in the market and convoluted drug pricing and insurance practices,” Ms. O’Neill Hayes and colleagues wrote in a report in April on federal and state attempts to address insulin affordability.
Novo Nordisk, however, maintains that drugmakers are not solely to blame.
“Everyone in the health care system has a role to play in affordability,” said Ken Inchausti, Novo Nordisk’s senior director for corporate communications. State legislation “attempts to address a systemic issue in [U.S.] health care: How benefit design can make medicines unaffordable for many, especially for those in high-deductible health plans,” he said in an interview.
“Efforts to place copay caps on insurance plans covering insulin can certainly help lower out-of-pocket costs,” said Mr. Inchausti.
Sanofi spokesperson Jon Florio said the company supports actions that increase affordable access to insulin. However, “while we support capped copays, we feel this should not be limited to just one class of medicines,” he said. Mr. Florio also noted that Sanofi provides out-of-pocket caps to anyone with commercial insurance and that anyone without insurance can buy one or multiple Sanofi insulins for a fixed price of $99 per month, up to 10 boxes of pens and/or 10-mL vials.
And Sanofi will take part in the Centers for Medicare & Medicaid Services’ new insulin demonstration program. Starting in 2021, CMS will cap insulin copays at $35 for people in Part D plans that participate.
Eli Lilly spokesperson Brad Jacklin said the company “believes in the common goal of ensuring affordable access to insulin and other life-saving medicines because nobody should have to forgo or ration because of cost.”
Lilly supports efforts “that more directly affect patients’ cost-sharing based on their health care coverage,” he said. Insurers and pharmacy benefit managers (PBMs) should pass savings on to patients, Mr. Jacklin urged. Lilly caps some insulins at $35 for the uninsured or commercially insured. The company will also participate in the CMS program.
Meanwhile, a PhRMA-sponsored website www.letstalkaboutcost.org said that, because they do not share savings, insurers and PBMs are responsible for high insulin costs.
Manufacturer assistance programs for patients with diabetes and other chronic diseases, on the other hand, can save individuals $300-$500 a year, PhRMA said in August.
PBMs point back at insulin manufacturers
PBMs, however, point back at drug companies. “PBMs have been able to moderate insulin costs for most consumers with insurance,” said J.C. Scott, president and CEO of the Pharmaceutical Care Management Association, the PBM trade group, in a statement.
The rising cost of insulin is caused by a lack of competition and overuse of patent extensions, PCMA maintains.
Health insurers, which, in tandem with PBMs, give insulins formulary preference based on a discounted price, are most likely to feel the impact of laws limiting out-of-pocket costs.
If they have to make up the shortfall from a patient’s reduced payment for a prescription, they will likely raise premiums, said Ms. O’Neill Hayes.
And if patients pay the same price for insulin – regardless of who makes it – drugmakers won’t have much incentive to offer discounts or rebates for formulary placement, she said. Again, that would likely lead to higher premiums.
David Allen, a spokesperson for America’s Health Insurance Plans, said in an interview that AHIP believes lack of competition has driven up insulin prices.
“High prices for insulin correspond with high health insurance costs for insulin,” he said. When CMS starts requiring drugmakers to discount their insulins for Medicare that will allow “health plans to use those savings to reduce out-of-pocket [costs] for seniors.”
He did not respond to a question as to why health insurers were not already passing savings on to commercially insured patients, especially in states with out-of-pocket limits.
Mr. Allen did say that AHIP’s plans “stand ready to work with state policymakers to remove barriers to lower insulin prices for Americans.”
Utah savings hopefully saving lives already
In Utah, legislators tuned out the blame game, and instead were keen to listen to patients, who had many stories about how the high cost of insulin had hurt them, said Ms. Hooley.
She noted an estimated 50,000 Utahans rely on insulin to stay alive.
Ms. Hooley and her chapter convinced legislators to pass a bill that gives insurers the option to cap patient copays at $30 per month, or to put insulin on its lowest formulary tier and waive any patient deductible. That aspect of the law does not go into effect until January 2021, but insurers are already starting to move insulin to the lowest formulary tier.
That has helped some people immediately. One state resident said her most recent insulin prescription cost $7 – instead of the usual $200.
The uninsured are not left totally high and dry either. Starting June 1, anyone in the state could buy through a state bulk-purchasing program, which guaranteed a 60% discount.
Ms. Hooley said she’d recently heard about a patient who usually spent $300 per prescription but was able to buy insulin for $100 through the program.
“Although $100 is still too much, it is nice knowing the Utah Insulin Savings Program is saving lives,” Ms. Hooley concluded.
A version of this article originally appeared on Medscape.com.
Twelve U.S. states have now passed laws aimed at making insulin more affordable – and more than 30 are considering such legislation – but they all have gaps that still put the cost of this basic and essential medication out of reach for many with diabetes.
The laws only apply to health insurance through state-regulated plans, and not to the majority of health plans that cover most Americans: Medicare, Medicaid, the Veterans Affairs health system, or self-funded employer-sponsored plans.
Overall, Hannah Crabtree, an activist who writes the blog Data for Insulin, estimates state laws that limit copays, deductibles, or other out-of-pocket costs for insulin cover an average of 27% of people with diabetes across the United States.
And while diabetes activists have applauded state actions, most want more help for the under- and uninsured.
“Our chapter will be fighting harder next legislative session for the uninsured,” said Mindie Hooley, the leader of the Utah #insulin4all chapter, which successfully lobbied legislators to pass a bill signed by the state’s governor on March 30.
“With so many losing their jobs because of the pandemic, there’s no better time than now to fight for these patients who don’t have insurance,” Ms. Hooley said in an interview.
The American Diabetes Association has also been lobbying for state caps as one of many avenues for making insulin more affordable, said Stephen Habbe, the ADA’s director for state government affairs.
One in four insulin users report rationing the medication, Mr. Habbe said.
The state laws “can really provide important relief in terms of affordability for their insulin costs, which we know can be critical in terms of preserving their life and helping to prevent complications that can potentially be disabling or even deadly,” he said in an interview.
Activists with T1 International, which created the #insulin4all campaign, are working nationwide to convince state legislators to back measures that limit out-of-pocket costs for insulin, or for other diabetes medications and supplies.
Colorado, Connecticut, Delaware, Illinois, Maine, New Hampshire, New Mexico, New York, Utah, Virginia, Washington, and West Virginia have enacted such limits, with caps ranging from $25 to $100.
Insulin makers unfazed, blame insurers, PBMs for high prices
The three insulin manufacturers in the United States – Eli Lilly, Novo Nordisk, and Sanofi– have not overtly fought against the laws, although in July, the Pharmaceutical Research and Manufacturers of America did sue to block a related Minnesota law that provides a free emergency supply of insulin.
And the nonprofit news organization FairWarning reported in August that a lobbyist from Eli Lilly had attempted to push a Tennessee legislator to keep the uninsured from being eligible for any out-of-pocket limits.
The insulin makers have also not lowered prices in response to the mounting number of state laws.
They see no need, said Tara O’Neill Hayes, director of human welfare policy at the American Action Forum, a center right–leaning Washington, D.C., think tank.
“You’re going to do what you can get away with,” Ms. O’Neill Hayes said in an interview. “To the extent that they can keep their prices high and people are still buying, they have limited incentives to lower those costs.”
The insulin market is dysfunctional, she added. “The increasing cost of insulin seems primarily to be the result of a lack of competition in the market and convoluted drug pricing and insurance practices,” Ms. O’Neill Hayes and colleagues wrote in a report in April on federal and state attempts to address insulin affordability.
Novo Nordisk, however, maintains that drugmakers are not solely to blame.
“Everyone in the health care system has a role to play in affordability,” said Ken Inchausti, Novo Nordisk’s senior director for corporate communications. State legislation “attempts to address a systemic issue in [U.S.] health care: How benefit design can make medicines unaffordable for many, especially for those in high-deductible health plans,” he said in an interview.
“Efforts to place copay caps on insurance plans covering insulin can certainly help lower out-of-pocket costs,” said Mr. Inchausti.
Sanofi spokesperson Jon Florio said the company supports actions that increase affordable access to insulin. However, “while we support capped copays, we feel this should not be limited to just one class of medicines,” he said. Mr. Florio also noted that Sanofi provides out-of-pocket caps to anyone with commercial insurance and that anyone without insurance can buy one or multiple Sanofi insulins for a fixed price of $99 per month, up to 10 boxes of pens and/or 10-mL vials.
And Sanofi will take part in the Centers for Medicare & Medicaid Services’ new insulin demonstration program. Starting in 2021, CMS will cap insulin copays at $35 for people in Part D plans that participate.
Eli Lilly spokesperson Brad Jacklin said the company “believes in the common goal of ensuring affordable access to insulin and other life-saving medicines because nobody should have to forgo or ration because of cost.”
Lilly supports efforts “that more directly affect patients’ cost-sharing based on their health care coverage,” he said. Insurers and pharmacy benefit managers (PBMs) should pass savings on to patients, Mr. Jacklin urged. Lilly caps some insulins at $35 for the uninsured or commercially insured. The company will also participate in the CMS program.
Meanwhile, a PhRMA-sponsored website www.letstalkaboutcost.org said that, because they do not share savings, insurers and PBMs are responsible for high insulin costs.
Manufacturer assistance programs for patients with diabetes and other chronic diseases, on the other hand, can save individuals $300-$500 a year, PhRMA said in August.
PBMs point back at insulin manufacturers
PBMs, however, point back at drug companies. “PBMs have been able to moderate insulin costs for most consumers with insurance,” said J.C. Scott, president and CEO of the Pharmaceutical Care Management Association, the PBM trade group, in a statement.
The rising cost of insulin is caused by a lack of competition and overuse of patent extensions, PCMA maintains.
Health insurers, which, in tandem with PBMs, give insulins formulary preference based on a discounted price, are most likely to feel the impact of laws limiting out-of-pocket costs.
If they have to make up the shortfall from a patient’s reduced payment for a prescription, they will likely raise premiums, said Ms. O’Neill Hayes.
And if patients pay the same price for insulin – regardless of who makes it – drugmakers won’t have much incentive to offer discounts or rebates for formulary placement, she said. Again, that would likely lead to higher premiums.
David Allen, a spokesperson for America’s Health Insurance Plans, said in an interview that AHIP believes lack of competition has driven up insulin prices.
“High prices for insulin correspond with high health insurance costs for insulin,” he said. When CMS starts requiring drugmakers to discount their insulins for Medicare that will allow “health plans to use those savings to reduce out-of-pocket [costs] for seniors.”
He did not respond to a question as to why health insurers were not already passing savings on to commercially insured patients, especially in states with out-of-pocket limits.
Mr. Allen did say that AHIP’s plans “stand ready to work with state policymakers to remove barriers to lower insulin prices for Americans.”
Utah savings hopefully saving lives already
In Utah, legislators tuned out the blame game, and instead were keen to listen to patients, who had many stories about how the high cost of insulin had hurt them, said Ms. Hooley.
She noted an estimated 50,000 Utahans rely on insulin to stay alive.
Ms. Hooley and her chapter convinced legislators to pass a bill that gives insurers the option to cap patient copays at $30 per month, or to put insulin on its lowest formulary tier and waive any patient deductible. That aspect of the law does not go into effect until January 2021, but insurers are already starting to move insulin to the lowest formulary tier.
That has helped some people immediately. One state resident said her most recent insulin prescription cost $7 – instead of the usual $200.
The uninsured are not left totally high and dry either. Starting June 1, anyone in the state could buy through a state bulk-purchasing program, which guaranteed a 60% discount.
Ms. Hooley said she’d recently heard about a patient who usually spent $300 per prescription but was able to buy insulin for $100 through the program.
“Although $100 is still too much, it is nice knowing the Utah Insulin Savings Program is saving lives,” Ms. Hooley concluded.
A version of this article originally appeared on Medscape.com.
Twelve U.S. states have now passed laws aimed at making insulin more affordable – and more than 30 are considering such legislation – but they all have gaps that still put the cost of this basic and essential medication out of reach for many with diabetes.
The laws only apply to health insurance through state-regulated plans, and not to the majority of health plans that cover most Americans: Medicare, Medicaid, the Veterans Affairs health system, or self-funded employer-sponsored plans.
Overall, Hannah Crabtree, an activist who writes the blog Data for Insulin, estimates state laws that limit copays, deductibles, or other out-of-pocket costs for insulin cover an average of 27% of people with diabetes across the United States.
And while diabetes activists have applauded state actions, most want more help for the under- and uninsured.
“Our chapter will be fighting harder next legislative session for the uninsured,” said Mindie Hooley, the leader of the Utah #insulin4all chapter, which successfully lobbied legislators to pass a bill signed by the state’s governor on March 30.
“With so many losing their jobs because of the pandemic, there’s no better time than now to fight for these patients who don’t have insurance,” Ms. Hooley said in an interview.
The American Diabetes Association has also been lobbying for state caps as one of many avenues for making insulin more affordable, said Stephen Habbe, the ADA’s director for state government affairs.
One in four insulin users report rationing the medication, Mr. Habbe said.
The state laws “can really provide important relief in terms of affordability for their insulin costs, which we know can be critical in terms of preserving their life and helping to prevent complications that can potentially be disabling or even deadly,” he said in an interview.
Activists with T1 International, which created the #insulin4all campaign, are working nationwide to convince state legislators to back measures that limit out-of-pocket costs for insulin, or for other diabetes medications and supplies.
Colorado, Connecticut, Delaware, Illinois, Maine, New Hampshire, New Mexico, New York, Utah, Virginia, Washington, and West Virginia have enacted such limits, with caps ranging from $25 to $100.
Insulin makers unfazed, blame insurers, PBMs for high prices
The three insulin manufacturers in the United States – Eli Lilly, Novo Nordisk, and Sanofi– have not overtly fought against the laws, although in July, the Pharmaceutical Research and Manufacturers of America did sue to block a related Minnesota law that provides a free emergency supply of insulin.
And the nonprofit news organization FairWarning reported in August that a lobbyist from Eli Lilly had attempted to push a Tennessee legislator to keep the uninsured from being eligible for any out-of-pocket limits.
The insulin makers have also not lowered prices in response to the mounting number of state laws.
They see no need, said Tara O’Neill Hayes, director of human welfare policy at the American Action Forum, a center right–leaning Washington, D.C., think tank.
“You’re going to do what you can get away with,” Ms. O’Neill Hayes said in an interview. “To the extent that they can keep their prices high and people are still buying, they have limited incentives to lower those costs.”
The insulin market is dysfunctional, she added. “The increasing cost of insulin seems primarily to be the result of a lack of competition in the market and convoluted drug pricing and insurance practices,” Ms. O’Neill Hayes and colleagues wrote in a report in April on federal and state attempts to address insulin affordability.
Novo Nordisk, however, maintains that drugmakers are not solely to blame.
“Everyone in the health care system has a role to play in affordability,” said Ken Inchausti, Novo Nordisk’s senior director for corporate communications. State legislation “attempts to address a systemic issue in [U.S.] health care: How benefit design can make medicines unaffordable for many, especially for those in high-deductible health plans,” he said in an interview.
“Efforts to place copay caps on insurance plans covering insulin can certainly help lower out-of-pocket costs,” said Mr. Inchausti.
Sanofi spokesperson Jon Florio said the company supports actions that increase affordable access to insulin. However, “while we support capped copays, we feel this should not be limited to just one class of medicines,” he said. Mr. Florio also noted that Sanofi provides out-of-pocket caps to anyone with commercial insurance and that anyone without insurance can buy one or multiple Sanofi insulins for a fixed price of $99 per month, up to 10 boxes of pens and/or 10-mL vials.
And Sanofi will take part in the Centers for Medicare & Medicaid Services’ new insulin demonstration program. Starting in 2021, CMS will cap insulin copays at $35 for people in Part D plans that participate.
Eli Lilly spokesperson Brad Jacklin said the company “believes in the common goal of ensuring affordable access to insulin and other life-saving medicines because nobody should have to forgo or ration because of cost.”
Lilly supports efforts “that more directly affect patients’ cost-sharing based on their health care coverage,” he said. Insurers and pharmacy benefit managers (PBMs) should pass savings on to patients, Mr. Jacklin urged. Lilly caps some insulins at $35 for the uninsured or commercially insured. The company will also participate in the CMS program.
Meanwhile, a PhRMA-sponsored website www.letstalkaboutcost.org said that, because they do not share savings, insurers and PBMs are responsible for high insulin costs.
Manufacturer assistance programs for patients with diabetes and other chronic diseases, on the other hand, can save individuals $300-$500 a year, PhRMA said in August.
PBMs point back at insulin manufacturers
PBMs, however, point back at drug companies. “PBMs have been able to moderate insulin costs for most consumers with insurance,” said J.C. Scott, president and CEO of the Pharmaceutical Care Management Association, the PBM trade group, in a statement.
The rising cost of insulin is caused by a lack of competition and overuse of patent extensions, PCMA maintains.
Health insurers, which, in tandem with PBMs, give insulins formulary preference based on a discounted price, are most likely to feel the impact of laws limiting out-of-pocket costs.
If they have to make up the shortfall from a patient’s reduced payment for a prescription, they will likely raise premiums, said Ms. O’Neill Hayes.
And if patients pay the same price for insulin – regardless of who makes it – drugmakers won’t have much incentive to offer discounts or rebates for formulary placement, she said. Again, that would likely lead to higher premiums.
David Allen, a spokesperson for America’s Health Insurance Plans, said in an interview that AHIP believes lack of competition has driven up insulin prices.
“High prices for insulin correspond with high health insurance costs for insulin,” he said. When CMS starts requiring drugmakers to discount their insulins for Medicare that will allow “health plans to use those savings to reduce out-of-pocket [costs] for seniors.”
He did not respond to a question as to why health insurers were not already passing savings on to commercially insured patients, especially in states with out-of-pocket limits.
Mr. Allen did say that AHIP’s plans “stand ready to work with state policymakers to remove barriers to lower insulin prices for Americans.”
Utah savings hopefully saving lives already
In Utah, legislators tuned out the blame game, and instead were keen to listen to patients, who had many stories about how the high cost of insulin had hurt them, said Ms. Hooley.
She noted an estimated 50,000 Utahans rely on insulin to stay alive.
Ms. Hooley and her chapter convinced legislators to pass a bill that gives insurers the option to cap patient copays at $30 per month, or to put insulin on its lowest formulary tier and waive any patient deductible. That aspect of the law does not go into effect until January 2021, but insurers are already starting to move insulin to the lowest formulary tier.
That has helped some people immediately. One state resident said her most recent insulin prescription cost $7 – instead of the usual $200.
The uninsured are not left totally high and dry either. Starting June 1, anyone in the state could buy through a state bulk-purchasing program, which guaranteed a 60% discount.
Ms. Hooley said she’d recently heard about a patient who usually spent $300 per prescription but was able to buy insulin for $100 through the program.
“Although $100 is still too much, it is nice knowing the Utah Insulin Savings Program is saving lives,” Ms. Hooley concluded.
A version of this article originally appeared on Medscape.com.
HHS plan to improve rural health focuses on better broadband, telehealth services
Even before the coronavirus pandemic reached into the nation’s less-populated regions, rural Americans were sicker, poorer, and older than the rest of the country. Hospitals are shuttering at record rates, and health care experts have long called for changes.
The new plan, released by the Department of Health & Human Services Secretary Alex M. Azar, II, acknowledges the gaps in health care and other problems facing rural America. It lists a litany of projects and directives, with many already underway or announced within federal agencies.
“We cannot just tinker around the edges of a rural healthcare system that has struggled for too long,” Azar said in a prepared statement.
Yet, that is exactly what experts say the administration continues to do.
“They tinker around the edges,” said Tommy Barnhart, former president of the National Rural Health Association. And he added, “there’s a lot of political hype” that has happened under President Trump, as well as previous presidents.
In the past few months, rural health care has increasingly become a focus for Mr. Trump, whose polling numbers are souring as COVID-19 kills hundreds of Americans every day, drives down restaurant demand for some farm products, and spreads through meatpacking plants. Rural states including Iowa and the Dakotas are reporting the latest surges in cases.
This announcement comes in response to Mr. Trump’s executive order last month calling for improved rural health and telehealth access. Earlier this week, three federal agencies also announced they would team up to address gaps in rural broadband service – a key need because large portions of the plan seek to expand telehealth.
The plan is more than 70 pages long and the word “telehealth” appears more than 90 times, with a focus on projects across HHS, including the Health Resources and Services Administration and the Centers for Medicare & Medicaid Services.
Mr. Barnhart said CMS has passed some public health emergency waivers since the beginning of the pandemic that helped rural facilities get more funding, including one that specifically was designed to provide additional money for telehealth services. However, those waivers are set to expire when the coronavirus emergency ends. Officials have not yet set a date for when the federal emergency will end.
Andrew Jay Schwartzman, senior counselor to the Benton Institute for Broadband & Society, a private foundation that works to ensure greater Internet access, said there are multiple challenges with implementing telehealth across the nation. Many initiatives for robust telehealth programs need fast bandwidth, yet getting the money and setting up the necessary infrastructure is very difficult, he said.
“It will be a long time before this kind of technology will be readily available to much of the country,” he said.
Ge Bai, associate professor of accounting and health policy at Johns Hopkins University in Baltimore, noted that telehealth was short on funding in the HHS initiative. However, she said, the focus on telehealth, as well as a proposed shift in payment for small rural hospitals and changing workforce licensing requirements, had good potential.
“We are so close to the election that this is probably more of a messaging issue to cater to rural residents,” Ms. Bai said. “But it doesn’t matter who will be president. This report will give the next administration useful guidance.”
The American Hospital Association, representing 5,000 hospitals nationwide, sent a letter to Mr. Trump last week recommending a host of steps the administration could take. As of late Thursday, AHA was still reviewing the HHS plan but said it was “encouraged by the increased attention on rural health care.”
Buried within the HHS announcement are technical initiatives, such as a contract to help clinics and hospitals integrate care, and detailed efforts to address gaps in care, including a proposal to increase funding for school-based mental health programs in the president’s 2021 budget.
A senior HHS official said that, while some actions have been taken in recent months to improve rural health — such as the $11 billion provided to rural hospitals through coronavirus relief funding — more is needed.
“We’re putting our stake in the ground that the time for talk is over,” he said. “We’re going to move forward.”
Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.
Even before the coronavirus pandemic reached into the nation’s less-populated regions, rural Americans were sicker, poorer, and older than the rest of the country. Hospitals are shuttering at record rates, and health care experts have long called for changes.
The new plan, released by the Department of Health & Human Services Secretary Alex M. Azar, II, acknowledges the gaps in health care and other problems facing rural America. It lists a litany of projects and directives, with many already underway or announced within federal agencies.
“We cannot just tinker around the edges of a rural healthcare system that has struggled for too long,” Azar said in a prepared statement.
Yet, that is exactly what experts say the administration continues to do.
“They tinker around the edges,” said Tommy Barnhart, former president of the National Rural Health Association. And he added, “there’s a lot of political hype” that has happened under President Trump, as well as previous presidents.
In the past few months, rural health care has increasingly become a focus for Mr. Trump, whose polling numbers are souring as COVID-19 kills hundreds of Americans every day, drives down restaurant demand for some farm products, and spreads through meatpacking plants. Rural states including Iowa and the Dakotas are reporting the latest surges in cases.
This announcement comes in response to Mr. Trump’s executive order last month calling for improved rural health and telehealth access. Earlier this week, three federal agencies also announced they would team up to address gaps in rural broadband service – a key need because large portions of the plan seek to expand telehealth.
The plan is more than 70 pages long and the word “telehealth” appears more than 90 times, with a focus on projects across HHS, including the Health Resources and Services Administration and the Centers for Medicare & Medicaid Services.
Mr. Barnhart said CMS has passed some public health emergency waivers since the beginning of the pandemic that helped rural facilities get more funding, including one that specifically was designed to provide additional money for telehealth services. However, those waivers are set to expire when the coronavirus emergency ends. Officials have not yet set a date for when the federal emergency will end.
Andrew Jay Schwartzman, senior counselor to the Benton Institute for Broadband & Society, a private foundation that works to ensure greater Internet access, said there are multiple challenges with implementing telehealth across the nation. Many initiatives for robust telehealth programs need fast bandwidth, yet getting the money and setting up the necessary infrastructure is very difficult, he said.
“It will be a long time before this kind of technology will be readily available to much of the country,” he said.
Ge Bai, associate professor of accounting and health policy at Johns Hopkins University in Baltimore, noted that telehealth was short on funding in the HHS initiative. However, she said, the focus on telehealth, as well as a proposed shift in payment for small rural hospitals and changing workforce licensing requirements, had good potential.
“We are so close to the election that this is probably more of a messaging issue to cater to rural residents,” Ms. Bai said. “But it doesn’t matter who will be president. This report will give the next administration useful guidance.”
The American Hospital Association, representing 5,000 hospitals nationwide, sent a letter to Mr. Trump last week recommending a host of steps the administration could take. As of late Thursday, AHA was still reviewing the HHS plan but said it was “encouraged by the increased attention on rural health care.”
Buried within the HHS announcement are technical initiatives, such as a contract to help clinics and hospitals integrate care, and detailed efforts to address gaps in care, including a proposal to increase funding for school-based mental health programs in the president’s 2021 budget.
A senior HHS official said that, while some actions have been taken in recent months to improve rural health — such as the $11 billion provided to rural hospitals through coronavirus relief funding — more is needed.
“We’re putting our stake in the ground that the time for talk is over,” he said. “We’re going to move forward.”
Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.
Even before the coronavirus pandemic reached into the nation’s less-populated regions, rural Americans were sicker, poorer, and older than the rest of the country. Hospitals are shuttering at record rates, and health care experts have long called for changes.
The new plan, released by the Department of Health & Human Services Secretary Alex M. Azar, II, acknowledges the gaps in health care and other problems facing rural America. It lists a litany of projects and directives, with many already underway or announced within federal agencies.
“We cannot just tinker around the edges of a rural healthcare system that has struggled for too long,” Azar said in a prepared statement.
Yet, that is exactly what experts say the administration continues to do.
“They tinker around the edges,” said Tommy Barnhart, former president of the National Rural Health Association. And he added, “there’s a lot of political hype” that has happened under President Trump, as well as previous presidents.
In the past few months, rural health care has increasingly become a focus for Mr. Trump, whose polling numbers are souring as COVID-19 kills hundreds of Americans every day, drives down restaurant demand for some farm products, and spreads through meatpacking plants. Rural states including Iowa and the Dakotas are reporting the latest surges in cases.
This announcement comes in response to Mr. Trump’s executive order last month calling for improved rural health and telehealth access. Earlier this week, three federal agencies also announced they would team up to address gaps in rural broadband service – a key need because large portions of the plan seek to expand telehealth.
The plan is more than 70 pages long and the word “telehealth” appears more than 90 times, with a focus on projects across HHS, including the Health Resources and Services Administration and the Centers for Medicare & Medicaid Services.
Mr. Barnhart said CMS has passed some public health emergency waivers since the beginning of the pandemic that helped rural facilities get more funding, including one that specifically was designed to provide additional money for telehealth services. However, those waivers are set to expire when the coronavirus emergency ends. Officials have not yet set a date for when the federal emergency will end.
Andrew Jay Schwartzman, senior counselor to the Benton Institute for Broadband & Society, a private foundation that works to ensure greater Internet access, said there are multiple challenges with implementing telehealth across the nation. Many initiatives for robust telehealth programs need fast bandwidth, yet getting the money and setting up the necessary infrastructure is very difficult, he said.
“It will be a long time before this kind of technology will be readily available to much of the country,” he said.
Ge Bai, associate professor of accounting and health policy at Johns Hopkins University in Baltimore, noted that telehealth was short on funding in the HHS initiative. However, she said, the focus on telehealth, as well as a proposed shift in payment for small rural hospitals and changing workforce licensing requirements, had good potential.
“We are so close to the election that this is probably more of a messaging issue to cater to rural residents,” Ms. Bai said. “But it doesn’t matter who will be president. This report will give the next administration useful guidance.”
The American Hospital Association, representing 5,000 hospitals nationwide, sent a letter to Mr. Trump last week recommending a host of steps the administration could take. As of late Thursday, AHA was still reviewing the HHS plan but said it was “encouraged by the increased attention on rural health care.”
Buried within the HHS announcement are technical initiatives, such as a contract to help clinics and hospitals integrate care, and detailed efforts to address gaps in care, including a proposal to increase funding for school-based mental health programs in the president’s 2021 budget.
A senior HHS official said that, while some actions have been taken in recent months to improve rural health — such as the $11 billion provided to rural hospitals through coronavirus relief funding — more is needed.
“We’re putting our stake in the ground that the time for talk is over,” he said. “We’re going to move forward.”
Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.
Study: 10% of pregnant women test positive for COVID-19, with most asymptomatic
The study, published in BMJ, shows an increased risk of preterm delivery, as well as the need for invasive ventilation in these women, wrote John Allotey, PhD, of the University of Birmingham (England) and colleagues. The findings “will produce a strong evidence base for living guidelines on COVID-19 and pregnancy,” they noted.
The systematic review included 77 studies, one-third each from the United States and China, with the remaining studies from Belgium, Brazil, Denmark, France, Israel, Italy, Japan, Mexico, the Netherlands Portugal, Spain, and the United Kingdom.
The studies included women with COVID-19, of whom 13,118 were either pregnant or in the postpartum or postabortion period and 83,486 were of reproductive age but not pregnant. Some studies also included healthy pregnant women for comparison.
In the pregnant and recently pregnant women, the most common COVID-19 symptoms were fever (40%) and cough (39%), with lymphopenia (35%) and raised C reactive protein levels (49%) being the most common laboratory findings. Pregnant and recently pregnant women with COVID-19 were less likely to have fever (odds ratio, 0.43) and myalgia (OR, 0.48), compared with nonpregnant women of reproductive age with COVID-19, reported the authors.
The overall preterm and spontaneous preterm birth rates in the COVID-19–positive women were 17% and 6% respectively. Dr. Allotey and authors noted that “these preterm births could be medically indicated, as the overall rates of spontaneous preterm births in pregnant women with COVID-19 was broadly similar to those observed in the pre-pandemic period.” There were 18 stillbirths and 6 neonatal deaths in the COVID-19 cohort.
Overall, 73 (0.1%) of pregnant women with confirmed COVID-19 died from any cause, and severe COVID-19 infection was diagnosed in 13%. Maternal risk factors associated with severe infection included older age (OR, 1.78), high body mass index (OR, 2.3), chronic hypertension (OR, 2.0), and preexisting diabetes (OR, 2.51). Compared with nonpregnant women with COVID-19, pregnant or recently pregnant women with the infection were at increased risk of admission to intensive care (OR, 1.62) and needing invasive ventilation (OR, 1.88).
The report included studies published between December 1, 2019, and June 26, 2020, but the living systematic review will involve weekly search updates, with analysis performed every 2-4 weeks and reported through a dedicated website.
The value of a living meta-analysis
Asked to comment on the findings, Torri Metz, MD, a maternal-fetal medicine subspecialist at the University of Utah, Salt Lake City, expressed surprise at the 10% rate of infection in the pregnant or recently pregnant population. “This is higher than currently observed at many hospitals in the United States,” she said in an interview. “This may overestimate the actual risk as many of these studies were published early in the pandemic and did not universally sample women who were pregnant for SARS-CoV-2.”
She noted the value of a living meta-analysis in that it will be updated on a regular basis as new evidence emerges. “During this time of rapidly accumulating publications about COVID-19 infection, clinicians will find it useful to have a resource in which the available data can be combined in one source.”
And there are still some outstanding questions that new studies hopefully will shed light on, she added. “The authors found that many of the risk factors for severe disease, like diabetes, obesity and high blood pressure, in nonpregnant adults are the same in the pregnant population. What remains unknown is if pregnant patients with COVID-19 infection are at higher risk than those who are not pregnant. The authors note that this information is still limited and largely influenced in this published analysis by a CDC [Centers for Disease Control and Prevention] study in which the majority of patients had unknown pregnancy status. We also do not know if COVID-19 infection is associated with any birth defects since the majority of women with COVID-19 infection in the first trimester have not yet delivered.”
Malavika Prabhu, MD, an obstetetrician/gyneologist at Weill Cornell Medicine in New York City added that “this systematic review and meta analysis, which is a compilation of other studies done around the globe, confirms that pregnant women with preexisting medical conditions such as diabetes, hypertension, and obesity, are at increased risk of severe COVID-19 and that pregnant women with COVID-19 are at increased risk of invasive ventilation, compared to nonpregnant women with COVID-19, particularly if they have a preexisting medical condition.”
She said the preterm delivery rate of COVID-positive women is “challenging to interpret given that the total preterm birth rate potentially included many medically indicated preterm deliveries – which is to be expected – and there is no comparison group for spontaneous preterm birth presented”.
Other outstanding questions about COVID-19 pregnancies include whether they are associated with preeclampsia or smaller/growth restricted infants and why the cesarean delivery rate is high, she said. “But some of these questions are tough to answer with this data because it primarily reflects a COVID infection close to the delivery, not one that occurred several months prior to a delivery.”
Deborah Money, MD, professor of obstetrics and gynecology, medicine, and the school of population and public health, University of British Columbia, Vancouver, commented that “this is a group that have been doing ongoing living systematic reviews of the literature scanning for pregnancy outcomes. They post their information in real time on their website, so many of us in this area follow these postings as their methodology is robust and they work hard to only include high-quality literature and avoid duplication of cases in multiple papers. There has been a problem of re-reporting the same severe cases of COVID-19 in the literature.”
This “amplifies the importance of collecting Canadian-specific data to ensure that we understand if these kind of outcomes will also be found in Canada. The data presented in this paper represent outcomes from a broad range of countries with different methods of collecting information on pregnancy and highly variable prenatal care systems. This makes our pan-Canadian study of outcomes of COVID-19 for pregnant women and their infants, CANCOVID-Preg, even more important,” she said.
“Globally, we all must continue to monitor outcomes of COVID-19 in pregnancy to minimize adverse impact on women and their infants,” said Dr. Money, who was not involved in the study.
The study was partially funded by the World Health Organization and supported by Katie’s Team, a dedicated patient and public involvement group in Women’s Health. Dr. Metz is principal investigator for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network COVID-19 study; the study is funded by NICHD and enrollment is ongoing. Dr. Prabhu had no relevant financial disclosures. Dr. Money received funding from the Canadian Institutes for Health Research and the Public Health Agency of Canada and received a small grant from theBC Women’s Foundation for COVID-19 in pregnancy research.
SOURCE: Allotey J et al. BMJ. 2020;370:m3320.
The study, published in BMJ, shows an increased risk of preterm delivery, as well as the need for invasive ventilation in these women, wrote John Allotey, PhD, of the University of Birmingham (England) and colleagues. The findings “will produce a strong evidence base for living guidelines on COVID-19 and pregnancy,” they noted.
The systematic review included 77 studies, one-third each from the United States and China, with the remaining studies from Belgium, Brazil, Denmark, France, Israel, Italy, Japan, Mexico, the Netherlands Portugal, Spain, and the United Kingdom.
The studies included women with COVID-19, of whom 13,118 were either pregnant or in the postpartum or postabortion period and 83,486 were of reproductive age but not pregnant. Some studies also included healthy pregnant women for comparison.
In the pregnant and recently pregnant women, the most common COVID-19 symptoms were fever (40%) and cough (39%), with lymphopenia (35%) and raised C reactive protein levels (49%) being the most common laboratory findings. Pregnant and recently pregnant women with COVID-19 were less likely to have fever (odds ratio, 0.43) and myalgia (OR, 0.48), compared with nonpregnant women of reproductive age with COVID-19, reported the authors.
The overall preterm and spontaneous preterm birth rates in the COVID-19–positive women were 17% and 6% respectively. Dr. Allotey and authors noted that “these preterm births could be medically indicated, as the overall rates of spontaneous preterm births in pregnant women with COVID-19 was broadly similar to those observed in the pre-pandemic period.” There were 18 stillbirths and 6 neonatal deaths in the COVID-19 cohort.
Overall, 73 (0.1%) of pregnant women with confirmed COVID-19 died from any cause, and severe COVID-19 infection was diagnosed in 13%. Maternal risk factors associated with severe infection included older age (OR, 1.78), high body mass index (OR, 2.3), chronic hypertension (OR, 2.0), and preexisting diabetes (OR, 2.51). Compared with nonpregnant women with COVID-19, pregnant or recently pregnant women with the infection were at increased risk of admission to intensive care (OR, 1.62) and needing invasive ventilation (OR, 1.88).
The report included studies published between December 1, 2019, and June 26, 2020, but the living systematic review will involve weekly search updates, with analysis performed every 2-4 weeks and reported through a dedicated website.
The value of a living meta-analysis
Asked to comment on the findings, Torri Metz, MD, a maternal-fetal medicine subspecialist at the University of Utah, Salt Lake City, expressed surprise at the 10% rate of infection in the pregnant or recently pregnant population. “This is higher than currently observed at many hospitals in the United States,” she said in an interview. “This may overestimate the actual risk as many of these studies were published early in the pandemic and did not universally sample women who were pregnant for SARS-CoV-2.”
She noted the value of a living meta-analysis in that it will be updated on a regular basis as new evidence emerges. “During this time of rapidly accumulating publications about COVID-19 infection, clinicians will find it useful to have a resource in which the available data can be combined in one source.”
And there are still some outstanding questions that new studies hopefully will shed light on, she added. “The authors found that many of the risk factors for severe disease, like diabetes, obesity and high blood pressure, in nonpregnant adults are the same in the pregnant population. What remains unknown is if pregnant patients with COVID-19 infection are at higher risk than those who are not pregnant. The authors note that this information is still limited and largely influenced in this published analysis by a CDC [Centers for Disease Control and Prevention] study in which the majority of patients had unknown pregnancy status. We also do not know if COVID-19 infection is associated with any birth defects since the majority of women with COVID-19 infection in the first trimester have not yet delivered.”
Malavika Prabhu, MD, an obstetetrician/gyneologist at Weill Cornell Medicine in New York City added that “this systematic review and meta analysis, which is a compilation of other studies done around the globe, confirms that pregnant women with preexisting medical conditions such as diabetes, hypertension, and obesity, are at increased risk of severe COVID-19 and that pregnant women with COVID-19 are at increased risk of invasive ventilation, compared to nonpregnant women with COVID-19, particularly if they have a preexisting medical condition.”
She said the preterm delivery rate of COVID-positive women is “challenging to interpret given that the total preterm birth rate potentially included many medically indicated preterm deliveries – which is to be expected – and there is no comparison group for spontaneous preterm birth presented”.
Other outstanding questions about COVID-19 pregnancies include whether they are associated with preeclampsia or smaller/growth restricted infants and why the cesarean delivery rate is high, she said. “But some of these questions are tough to answer with this data because it primarily reflects a COVID infection close to the delivery, not one that occurred several months prior to a delivery.”
Deborah Money, MD, professor of obstetrics and gynecology, medicine, and the school of population and public health, University of British Columbia, Vancouver, commented that “this is a group that have been doing ongoing living systematic reviews of the literature scanning for pregnancy outcomes. They post their information in real time on their website, so many of us in this area follow these postings as their methodology is robust and they work hard to only include high-quality literature and avoid duplication of cases in multiple papers. There has been a problem of re-reporting the same severe cases of COVID-19 in the literature.”
This “amplifies the importance of collecting Canadian-specific data to ensure that we understand if these kind of outcomes will also be found in Canada. The data presented in this paper represent outcomes from a broad range of countries with different methods of collecting information on pregnancy and highly variable prenatal care systems. This makes our pan-Canadian study of outcomes of COVID-19 for pregnant women and their infants, CANCOVID-Preg, even more important,” she said.
“Globally, we all must continue to monitor outcomes of COVID-19 in pregnancy to minimize adverse impact on women and their infants,” said Dr. Money, who was not involved in the study.
The study was partially funded by the World Health Organization and supported by Katie’s Team, a dedicated patient and public involvement group in Women’s Health. Dr. Metz is principal investigator for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network COVID-19 study; the study is funded by NICHD and enrollment is ongoing. Dr. Prabhu had no relevant financial disclosures. Dr. Money received funding from the Canadian Institutes for Health Research and the Public Health Agency of Canada and received a small grant from theBC Women’s Foundation for COVID-19 in pregnancy research.
SOURCE: Allotey J et al. BMJ. 2020;370:m3320.
The study, published in BMJ, shows an increased risk of preterm delivery, as well as the need for invasive ventilation in these women, wrote John Allotey, PhD, of the University of Birmingham (England) and colleagues. The findings “will produce a strong evidence base for living guidelines on COVID-19 and pregnancy,” they noted.
The systematic review included 77 studies, one-third each from the United States and China, with the remaining studies from Belgium, Brazil, Denmark, France, Israel, Italy, Japan, Mexico, the Netherlands Portugal, Spain, and the United Kingdom.
The studies included women with COVID-19, of whom 13,118 were either pregnant or in the postpartum or postabortion period and 83,486 were of reproductive age but not pregnant. Some studies also included healthy pregnant women for comparison.
In the pregnant and recently pregnant women, the most common COVID-19 symptoms were fever (40%) and cough (39%), with lymphopenia (35%) and raised C reactive protein levels (49%) being the most common laboratory findings. Pregnant and recently pregnant women with COVID-19 were less likely to have fever (odds ratio, 0.43) and myalgia (OR, 0.48), compared with nonpregnant women of reproductive age with COVID-19, reported the authors.
The overall preterm and spontaneous preterm birth rates in the COVID-19–positive women were 17% and 6% respectively. Dr. Allotey and authors noted that “these preterm births could be medically indicated, as the overall rates of spontaneous preterm births in pregnant women with COVID-19 was broadly similar to those observed in the pre-pandemic period.” There were 18 stillbirths and 6 neonatal deaths in the COVID-19 cohort.
Overall, 73 (0.1%) of pregnant women with confirmed COVID-19 died from any cause, and severe COVID-19 infection was diagnosed in 13%. Maternal risk factors associated with severe infection included older age (OR, 1.78), high body mass index (OR, 2.3), chronic hypertension (OR, 2.0), and preexisting diabetes (OR, 2.51). Compared with nonpregnant women with COVID-19, pregnant or recently pregnant women with the infection were at increased risk of admission to intensive care (OR, 1.62) and needing invasive ventilation (OR, 1.88).
The report included studies published between December 1, 2019, and June 26, 2020, but the living systematic review will involve weekly search updates, with analysis performed every 2-4 weeks and reported through a dedicated website.
The value of a living meta-analysis
Asked to comment on the findings, Torri Metz, MD, a maternal-fetal medicine subspecialist at the University of Utah, Salt Lake City, expressed surprise at the 10% rate of infection in the pregnant or recently pregnant population. “This is higher than currently observed at many hospitals in the United States,” she said in an interview. “This may overestimate the actual risk as many of these studies were published early in the pandemic and did not universally sample women who were pregnant for SARS-CoV-2.”
She noted the value of a living meta-analysis in that it will be updated on a regular basis as new evidence emerges. “During this time of rapidly accumulating publications about COVID-19 infection, clinicians will find it useful to have a resource in which the available data can be combined in one source.”
And there are still some outstanding questions that new studies hopefully will shed light on, she added. “The authors found that many of the risk factors for severe disease, like diabetes, obesity and high blood pressure, in nonpregnant adults are the same in the pregnant population. What remains unknown is if pregnant patients with COVID-19 infection are at higher risk than those who are not pregnant. The authors note that this information is still limited and largely influenced in this published analysis by a CDC [Centers for Disease Control and Prevention] study in which the majority of patients had unknown pregnancy status. We also do not know if COVID-19 infection is associated with any birth defects since the majority of women with COVID-19 infection in the first trimester have not yet delivered.”
Malavika Prabhu, MD, an obstetetrician/gyneologist at Weill Cornell Medicine in New York City added that “this systematic review and meta analysis, which is a compilation of other studies done around the globe, confirms that pregnant women with preexisting medical conditions such as diabetes, hypertension, and obesity, are at increased risk of severe COVID-19 and that pregnant women with COVID-19 are at increased risk of invasive ventilation, compared to nonpregnant women with COVID-19, particularly if they have a preexisting medical condition.”
She said the preterm delivery rate of COVID-positive women is “challenging to interpret given that the total preterm birth rate potentially included many medically indicated preterm deliveries – which is to be expected – and there is no comparison group for spontaneous preterm birth presented”.
Other outstanding questions about COVID-19 pregnancies include whether they are associated with preeclampsia or smaller/growth restricted infants and why the cesarean delivery rate is high, she said. “But some of these questions are tough to answer with this data because it primarily reflects a COVID infection close to the delivery, not one that occurred several months prior to a delivery.”
Deborah Money, MD, professor of obstetrics and gynecology, medicine, and the school of population and public health, University of British Columbia, Vancouver, commented that “this is a group that have been doing ongoing living systematic reviews of the literature scanning for pregnancy outcomes. They post their information in real time on their website, so many of us in this area follow these postings as their methodology is robust and they work hard to only include high-quality literature and avoid duplication of cases in multiple papers. There has been a problem of re-reporting the same severe cases of COVID-19 in the literature.”
This “amplifies the importance of collecting Canadian-specific data to ensure that we understand if these kind of outcomes will also be found in Canada. The data presented in this paper represent outcomes from a broad range of countries with different methods of collecting information on pregnancy and highly variable prenatal care systems. This makes our pan-Canadian study of outcomes of COVID-19 for pregnant women and their infants, CANCOVID-Preg, even more important,” she said.
“Globally, we all must continue to monitor outcomes of COVID-19 in pregnancy to minimize adverse impact on women and their infants,” said Dr. Money, who was not involved in the study.
The study was partially funded by the World Health Organization and supported by Katie’s Team, a dedicated patient and public involvement group in Women’s Health. Dr. Metz is principal investigator for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network COVID-19 study; the study is funded by NICHD and enrollment is ongoing. Dr. Prabhu had no relevant financial disclosures. Dr. Money received funding from the Canadian Institutes for Health Research and the Public Health Agency of Canada and received a small grant from theBC Women’s Foundation for COVID-19 in pregnancy research.
SOURCE: Allotey J et al. BMJ. 2020;370:m3320.
FROM BMJ
Experts advocate for the elimination of daylight savings time
In the interest of public health and safety,
– a recommendation that has garnered strong support from multiple medical and other high-profile organizations.“Permanent, year-round standard time is the best choice to most closely match our circadian sleep-wake cycle,” M. Adeel Rishi, MD, lead author of the AASM position statement, said in a news release. “Daylight saving time results in more darkness in the morning and more light in the evening, disrupting the body’s natural rhythm,” said Dr. Rishi, of the department of pulmonology, critical care, and sleep medicine, Mayo Clinic, Eau Claire, Wis., and vice chair of the AASM Public Safety Committee.
The position statement was published Aug. 26 in the Journal of Clinical Sleep Medicine to coincide with the virtual annual meeting of the Associated Professional Sleep Societies .
Significant health risks
In the United States, the annual “spring forward” to daylight saving time and “fall back” to standard time is required by law, although under the statute some exceptions are permitted.
There has been intense debate over the last several years about transitioning between standard and daylight saving time. The AASM says there is “an abundance of evidence” to indicate that quick transition from standard time to daylight saving time incurs significant public health and safety risks, including increased risk of heart attack, stroke, mood disorders, and car crashes.
“Although chronic effects of remaining in daylight saving time year-round have not been well-studied, daylight saving time is less aligned with human circadian biology – which, because of the impacts of the delayed natural light/dark cycle on human activity, could result in circadian misalignment, which has been associated in some studies with increased cardiovascular disease risk, metabolic syndrome and other health risks,” the authors wrote.
A recent study also showed an increase in medical errors in the week after switching to daylight saving time.
“Because the adoption of permanent standard time would be beneficial for public health and safety, the AASM will be advocating at the federal level for this legislative change,” said AASM President Kannan Ramar, MBBS, MD, with the Mayo Clinic in Rochester, Minn.
It seems that many Americans are in favor of the change. In July, an AASM survey of roughly 2,000 U.S. adults showed that two-thirds support doing away with the seasonal time change. Only 11% opposed it. In addition, the academy’s 2019 survey showed more than half of adults feel extremely, or somewhat, tired after the springing ahead to daylight saving time.
Strong support
The position statement has been endorsed by 19 organizations, including the American Academy of Cardiovascular Sleep Medicine, American College of Chest Physicians (CHEST), American College of Occupational and Environmental Medicine, National PTA, National Safety Council, Society of Anesthesia and Sleep Medicine, and the Society of Behavioral Sleep Medicine.
Weighing in on the issue, Saul Rothenberg, PhD, from the Sleep Center at Greenwich Hospital, Conn., said the literature on daylight saving time has grown over the past 20 years. He said he was ”humbled” by the research that shows that a “relatively small” misalignment of biological and social clocks has a measurable impact on human health and behavior.
“Because misalignment is associated with negative health and performance outcomes, keeping one set of hours year-round is promoted to minimize misalignment and associated consequences,” he added.
In light of this research, the recommendation to dispense with daylight saving time seems “quite reasonable” from a public health perspective. “I am left with a strengthened view on the importance of regular adequate sleep as a way to enhance health, performance, and quality of life,” he added.
This research had no commercial funding. Dr. Rishi and Dr. Rothenberg have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In the interest of public health and safety,
– a recommendation that has garnered strong support from multiple medical and other high-profile organizations.“Permanent, year-round standard time is the best choice to most closely match our circadian sleep-wake cycle,” M. Adeel Rishi, MD, lead author of the AASM position statement, said in a news release. “Daylight saving time results in more darkness in the morning and more light in the evening, disrupting the body’s natural rhythm,” said Dr. Rishi, of the department of pulmonology, critical care, and sleep medicine, Mayo Clinic, Eau Claire, Wis., and vice chair of the AASM Public Safety Committee.
The position statement was published Aug. 26 in the Journal of Clinical Sleep Medicine to coincide with the virtual annual meeting of the Associated Professional Sleep Societies .
Significant health risks
In the United States, the annual “spring forward” to daylight saving time and “fall back” to standard time is required by law, although under the statute some exceptions are permitted.
There has been intense debate over the last several years about transitioning between standard and daylight saving time. The AASM says there is “an abundance of evidence” to indicate that quick transition from standard time to daylight saving time incurs significant public health and safety risks, including increased risk of heart attack, stroke, mood disorders, and car crashes.
“Although chronic effects of remaining in daylight saving time year-round have not been well-studied, daylight saving time is less aligned with human circadian biology – which, because of the impacts of the delayed natural light/dark cycle on human activity, could result in circadian misalignment, which has been associated in some studies with increased cardiovascular disease risk, metabolic syndrome and other health risks,” the authors wrote.
A recent study also showed an increase in medical errors in the week after switching to daylight saving time.
“Because the adoption of permanent standard time would be beneficial for public health and safety, the AASM will be advocating at the federal level for this legislative change,” said AASM President Kannan Ramar, MBBS, MD, with the Mayo Clinic in Rochester, Minn.
It seems that many Americans are in favor of the change. In July, an AASM survey of roughly 2,000 U.S. adults showed that two-thirds support doing away with the seasonal time change. Only 11% opposed it. In addition, the academy’s 2019 survey showed more than half of adults feel extremely, or somewhat, tired after the springing ahead to daylight saving time.
Strong support
The position statement has been endorsed by 19 organizations, including the American Academy of Cardiovascular Sleep Medicine, American College of Chest Physicians (CHEST), American College of Occupational and Environmental Medicine, National PTA, National Safety Council, Society of Anesthesia and Sleep Medicine, and the Society of Behavioral Sleep Medicine.
Weighing in on the issue, Saul Rothenberg, PhD, from the Sleep Center at Greenwich Hospital, Conn., said the literature on daylight saving time has grown over the past 20 years. He said he was ”humbled” by the research that shows that a “relatively small” misalignment of biological and social clocks has a measurable impact on human health and behavior.
“Because misalignment is associated with negative health and performance outcomes, keeping one set of hours year-round is promoted to minimize misalignment and associated consequences,” he added.
In light of this research, the recommendation to dispense with daylight saving time seems “quite reasonable” from a public health perspective. “I am left with a strengthened view on the importance of regular adequate sleep as a way to enhance health, performance, and quality of life,” he added.
This research had no commercial funding. Dr. Rishi and Dr. Rothenberg have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In the interest of public health and safety,
– a recommendation that has garnered strong support from multiple medical and other high-profile organizations.“Permanent, year-round standard time is the best choice to most closely match our circadian sleep-wake cycle,” M. Adeel Rishi, MD, lead author of the AASM position statement, said in a news release. “Daylight saving time results in more darkness in the morning and more light in the evening, disrupting the body’s natural rhythm,” said Dr. Rishi, of the department of pulmonology, critical care, and sleep medicine, Mayo Clinic, Eau Claire, Wis., and vice chair of the AASM Public Safety Committee.
The position statement was published Aug. 26 in the Journal of Clinical Sleep Medicine to coincide with the virtual annual meeting of the Associated Professional Sleep Societies .
Significant health risks
In the United States, the annual “spring forward” to daylight saving time and “fall back” to standard time is required by law, although under the statute some exceptions are permitted.
There has been intense debate over the last several years about transitioning between standard and daylight saving time. The AASM says there is “an abundance of evidence” to indicate that quick transition from standard time to daylight saving time incurs significant public health and safety risks, including increased risk of heart attack, stroke, mood disorders, and car crashes.
“Although chronic effects of remaining in daylight saving time year-round have not been well-studied, daylight saving time is less aligned with human circadian biology – which, because of the impacts of the delayed natural light/dark cycle on human activity, could result in circadian misalignment, which has been associated in some studies with increased cardiovascular disease risk, metabolic syndrome and other health risks,” the authors wrote.
A recent study also showed an increase in medical errors in the week after switching to daylight saving time.
“Because the adoption of permanent standard time would be beneficial for public health and safety, the AASM will be advocating at the federal level for this legislative change,” said AASM President Kannan Ramar, MBBS, MD, with the Mayo Clinic in Rochester, Minn.
It seems that many Americans are in favor of the change. In July, an AASM survey of roughly 2,000 U.S. adults showed that two-thirds support doing away with the seasonal time change. Only 11% opposed it. In addition, the academy’s 2019 survey showed more than half of adults feel extremely, or somewhat, tired after the springing ahead to daylight saving time.
Strong support
The position statement has been endorsed by 19 organizations, including the American Academy of Cardiovascular Sleep Medicine, American College of Chest Physicians (CHEST), American College of Occupational and Environmental Medicine, National PTA, National Safety Council, Society of Anesthesia and Sleep Medicine, and the Society of Behavioral Sleep Medicine.
Weighing in on the issue, Saul Rothenberg, PhD, from the Sleep Center at Greenwich Hospital, Conn., said the literature on daylight saving time has grown over the past 20 years. He said he was ”humbled” by the research that shows that a “relatively small” misalignment of biological and social clocks has a measurable impact on human health and behavior.
“Because misalignment is associated with negative health and performance outcomes, keeping one set of hours year-round is promoted to minimize misalignment and associated consequences,” he added.
In light of this research, the recommendation to dispense with daylight saving time seems “quite reasonable” from a public health perspective. “I am left with a strengthened view on the importance of regular adequate sleep as a way to enhance health, performance, and quality of life,” he added.
This research had no commercial funding. Dr. Rishi and Dr. Rothenberg have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM SLEEP 2020
An Atypical Long-Term Thiamine Treatment Regimen for Wernicke Encephalopathy
Wernicke-Korsakoff syndrome is a cluster of symptoms attributed to a disorder of vitamin B1 (thiamine) deficiency, manifesting as a combined presentation of alcohol-induced Wernicke encephalopathy (WE) and Korsakoff syndrome (KS).1 While there is consensus on the characteristic presentation and symptoms of WE, there is a lack of agreement on the exact definition of KS. The classic triad describing WE consists of ataxia, ophthalmoplegia, and confusion; however, reports now suggest that a majority of patients exhibit only 1 or 2 of the elements of the triad. KS is often seen as a condition of chronic thiamine deficiency manifesting as memory impairment alongside a cognitive and behavioral decline, with no clear consensus on the sequence of appearance of symptoms. The typical relationship is thought to be a progression of WE to KS if untreated.
From a mental health perspective, WE presents with delirium and confusion whereas KS manifests with irreversible dementia and a cognitive deterioration. Though it is commonly taught that KS-induced memory loss is permanent due to neuronal damage (classically identified as damage to the mammillary bodies - though other structures have been implicated as well), more recent research suggest otherwise.2 A review published in 2018, for example, gathered several case reports and case series that suggest significant improvement in memory and cognition attributed to behavioral and pharmacologic interventions, indicating this as an area deserving of further study.3 About 20% of patients diagnosed with WE by autopsy exhibited none of the classical triad symptoms prior to death.4 Hence, these conditions are surmised to be significantly underdiagnosed and misdiagnosed.
Though consensus regarding the appropriate treatment regimen is lacking for WE, a common protocol consists of high-dose parenteral thiamine for 4 to 7 days.5 This is usually followed by daily oral thiamine repletion until the patient either achieves complete abstinence from alcohol (ideal) or decreases consumption. The goal is to allow thiamine stores to replete and maintain at minimum required body levels moving forward. In this case report, we highlight the utilization of a long-term, unconventional intramuscular (IM) thiamine repletion regimen to ensure maintenance of a patient’s mental status, highlighting discrepancies in our understanding of the mechanisms at play in WE and its treatment.
Case Presentation
A 65-year-old male patient with a more than 3-decade history of daily hard liquor intake, multiple psychiatric hospitalizations for WE, and a prior suicide attempt, presented to the emergency department (ED) with increased frequency of falls, poor oral intake, confabulation, and diminished verbal communication. A chart review revealed memory impairment alongside the diagnoses of schizoaffective disorder and WE, and confusion that was responsive to thiamine administration as well as a history of hypertension, hyperlipidemia, osteoarthritis, and urinary retention secondary to benign prostatic hyperplasia (BPH).
On examination the patient was found to be disoriented with a clouded sensorium. While the history of heavy daily alcohol use was clear in the chart and confirmed by other sources, it appeared unlikely that the patient had been using alcohol in the preceding month due to restricted access in his most recent living environment (a shared apartment with daily nursing assistance). He reported no lightheadedness, dizziness, palpitations, numbness, tingling, or any head trauma. He also negated the presence of active mood symptoms, auditory or visual hallucinations or suicidal ideation (SI)
The patient was admitted to the Internal Medicine Service and received a workup for the causes of delirium, including consideration of normal pressure hydrocephalus (NPH) and other neurologic conditions. Laboratory tests including a comprehensive metabolic panel, thyroid stimulating hormone, urinalysis, urine toxicology screen, and vitamin B12 and folate levels were in normal ranges. Although brain imaging revealed enlarged ventricles, NPH was considered unlikely because of the absence of ophthalmologic abnormalities, like gaze nystagmus, and urinary incontinence; conversely, there was some presence of urinary retention attributed to BPH and required an admission a few months prior. Moreover, magnetic resonance images showed that the ventricles were enlarged slightly out of proportion to the sulci, which can be seen with predominantly central volume loss compared with the pattern typically seen in NPH.
In light of concern for WE and the patient's history, treatment with IV thiamine and IV fluids was initiated and the Liaison Psychiatry Service was consulted for cognitive disability and treatment of his mood. Administration of IV thiamine rapidly restored his sensorium, but he became abruptly disorganized as the IV regimen graduated to an oral thiamine dose of 200 mg 3 times daily. Simultaneously, as medical stabilization was achieved, the patient was transferred to the inpatient psychiatry unit to address the nonresolving cognitive impairment and behavioral disorganization. This specifically involved newly emerging, impulsive, self-harming behaviors like throwing himself on the ground and banging his head on the floor. Such behaviors along with paucity of speech and decreased oral intake, ultimately warranted constant observation, which led to a decrease in self-harming activity. All this behavior was noted even though the patient was adherent to oral administration of thiamine. Throughout this time, the patient underwent several transfers back and forth between the Psychiatry and Internal Medicine services due to ongoing concern for the possibility of delirium or WE. However, the Neurology and Internal Medicine services did not feel that WE would explain the patient’s mental and behavioral status, in part due to his ongoing adherence with daily oral thiamine dosing that was not associated with improvement in mental status.
Recollecting the patient’s improvement with the parenteral thiamine regimen (IV and IM), the psychiatry unit tried a thiamine regimen of 200 mg IM and 100 mg oral 2 times daily. After about 2 weeks on this regimen, the patient subsequently achieved remarkable improvement in his cognitive and behavioral status, with resolution of selfharming behaviors. The patient was noted to be calmer, more linear, and more oriented, though he remained incompletely oriented throughout his hospitalization. As improvement in sensorium was established and the patient’s hospital stay prolonged (Figure), his mood symptoms began manifesting as guilt, low energy, decreased appetite, withdrawal, and passive SI. This was followed by a trial of lithium that was discontinued due to elevated creatine levels. As the patient continued to report depression, a multidrug regimen of divalproex, fluoxetine, and quetiapine was administered, which lead to remarkable improvement.
At this time, it was concluded that the stores of thiamine in the patient’s body may have been replenished, the alcohol intake completely ceased and that he needed to be weaned off of thiamine. The next step taken was reduction of the twice daily 200 mg IM thiamine dose to a once daily regimen, and oral thiamine was put on hold. Over the next 48 hours, the patient became less verbal, more withdrawn, incontinent of urine, and delirious. The twice daily IM 200 mg thiamine was restarted, but this time the patient demonstrated very slow improvement. After 2 weeks, the IM thiamine 200 mg was increased to 3 times daily, and the patient showed marked improvement in recall, mood, and effect.
Several attempts were made to reduce the IM thiamine burden on the patient and/ or transition to an exclusively oral regimen. However, he rapidly decompensated within hours of each attempt to taper the IM dose and required immediate reinstation. On the IM thiamine regimen, he eventually appeared to reach a stable cognitive and affective baseline marked by incomplete orientation but pleasant affect, he reported no mood complaints, behavioral stability, and an ability to comply with care needs and have simple conversations. Some speech content remained disorganized particularly if engaged beyond simple exchanges.
The patient was discharged to a skilled nursing facility after a month of 3 times daily IM administration of thiamine. Within the next 24 hours, the patient returned to the ED with the originally reported symptoms of ataxia, agitation, and confusion. On inquiry, it was revealed that the ordered vials of IM thiamine for injection had not arrived with him at the nursing facility and he had missed 2 doses. The blood laboratory results, scans, and all other parameters were otherwise found to be normal and the patient was adherent to his prescribed antipsychotics and antidepressants. As anticipated, restoration of the IM thiamine regimen revived his baseline within hours. While confusion and delirium resolved completely with treatment, the memory impairments persisted. This patient has been administered a 3 times daily IM dose of 200 mg thiamine for more than 2 years with a stable cognitive clinical picture.
Discussion
According to data from the 2016 National Survey on Drug Use and Health, 16 million individuals in the US aged ≥ 12 years reported heavy alcohol use, which is defined as binge drinking on ≥ 5 days in the past month.6,7 Thiamine deficiency is an alcoholrelated disorder that is frequently encountered in hospital settings. This deficiency can also occur in the context of malabsorption, malnutrition, a prolonged course of vomiting, and bariatric surgery.8,9
The deficiency in thiamine, which is sometimes known as WE, manifests rarely with all 3 of the classic triad of gait disturbances, abnormal eye movements, and mental status changes, with only 16.5% of patients displaying all of the triad.4 Moreover, there may be additional symptoms not listed in this triad, such as memory impairment, bilateral sixth nerve palsy, ptosis, hypotension, and hypothermia.10.11 This inconsistent presentation makes the diagnosis challenging and therefore requires a higher threshold for suspicion. If undiagnosed and/or untreated, WE can lead to chronic thiamine deficiency causing permanent brain damage in the guise of KS. This further increases the importance of timely diagnosis and treatment.
Our case highlights the utilization of an unconventional thiamine regimen that appeared to be temporally associated with mental status improvement. The patient’s clouded sensorium and confusion could not be attributed to metabolic, encephalopathic, or infectious pathologies due to the absence of supportive laboratory evidence. He responded to IV and IM doses of thiamine, but repeated attempts to taper the IM doses with the objective of transitioning to oral thiamine supplementation were followed by immediate decompensations in mental status. This was atypical of WE as the patient seemed adequately replete with thiamine, and missing a few doses should not be enough to deplete his stores. Thus, reflecting a unique case of thiamine-dependent chronically set WE when even a single missed dose of thiamine adversely affected the patient’s cognitive baseline. Interesting to note is this patient’s memory issue, as evident by clinical examination and dating back at least 5 years as per chart review. This premature amnestic component of his presentation indicates a likely parallel running KS component of his presentation. Conversely, the patient’s long history of alcohol use disorder, prior episodes of WE, and ideal response achieved only on parenteral thiamine repletion further supported the diagnosis of WE and our impression of the scenario.
Even though this patient had prior episodes of WE, there remained diagnostic uncertainty regarding his altered mental status for some time before the nonoral thiamine repletion treatment was implemented. Particularly in this admission, the patient’s mental status frequently waxed and waned and there was the additional confusion of whether a potential psychiatric etiology contributed to some of the elements of his presentation, such as his impulsive self-harm behaviors. This behavior led to recurrent transfers among the Psychiatry Service, Internal Medicine Service, and the ED.
The patient’s presentation did not reflect the classical triad of WE, and while this is consistent with the majority of clinical manifestations, various services were reluctant to attribute his symptoms to WE. Once the threshold of suspicion of thiamine deficiency was lowered and the deficit treated more aggressively, the patient seemed to improve tremendously. Presence of memory problems and confabulation, both of which this patient exhibited, are suggestive of KS and are not expected to recover with treatment, yet for this patient there did seem to be some improvement—though not complete resolution. This is consistent with newer evidence suggesting that some recovery from the deficits seen in KS is possible.3
Once diagnosed, the treatment objective is the replenishment of thiamine stores and optimization of the metabolic scenario of the body to prevent recurrence. For acute WE symptoms, many regimens call for 250 to 500 mg of IV thiamine supplementation 2 to 3 times daily for 3 to 5 days. High dose IV thiamine (≥ 500 mg daily) has been proposed to be efficacious and free of considerable adverse effects.12 A study conducted at the University of North Carolina described thiamine prescribing practices in a large academic hospital, analyzing data with the objective of assessing outcomes of ordering high-dose IV thiamine (HDIV, ≥ 200 mg IV twice daily) to patients with encephalopathy. 13 The researchers concluded that HDIV, even though rarely prescribed, was associated with decreased inpatient mortality in bivariable models. However, in multivariable analyses this decrease was found to be clinically insignificant. Our patient benefitted from both IV and IM delivery.
Ideally, after the initial IV thiamine dose, oral administration of thiamine 250 to 1,000 mg is continued until a reduction, if not abstinence, from alcohol use is achieved.5 Many patients are discharged on an oral maintenance dose of thiamine 100 mg. Oral thiamine is poorly absorbed and less effective in both prophylaxis and treatment of newly diagnosed WE; therefore, it is typically used only after IM or IV replenishment. It remains unclear why this patient required IM thiamine multiple times per day to maintain his mental status, and why he would present with selfinjurious behaviors after missing doses. The patient’s response can be attributed to late-onset defects in oral thiamine absorption at the carrier protein level of the brush border and basolateral membranes of his jejunum; however, an invasive procedure like a jejunal biopsy to establish the definitive etiology was neither necessary nor practical once treatment response was observed. 14 Other possible explanations include rapid thiamine metabolism, poor gastrointestinal absorption and a late-onset deficit in the thiamine diffusion mechanisms, and active transport systems (thiamine utilization depends on active transport in low availability states and passive transport when readily available). The nature of these mechanisms deserves further study. Less data have been reported on the administration and utility of IM thiamine for chronic WE; hence, our case report is one of the first illustrating the role of this method for sustained repletion.
Conclusions
This case presented a clinical dilemma because the conventional treatment regimen for WE didn’t yield the desired outcome until the mode and duration of thiamine administration were adjusted. It illustrates the utility of a sustained intensive thiamine regimen irrespective of sobriety status, as opposed to the traditional regimen of parenteral (primarily IV) thiamine for 3 to 7 days, followed by oral repletion until the patient achieves sustained abstinence. In this patient’s case, access to nursing care postdischarge facilitated his continued adherence to IM thiamine therapy.
The longitudinal time course of this case suggests a relationship between this route of administration and improvement in symptom burden and indicates that this patient may have a long-term need for IM thiamine to maintain his baseline mental status. Of great benefit in such patients would be the availability of a long-acting IM thiamine therapy. Risk of overdose is unlikely due to the water solubility of B group vitamins.
This case report highlights the importance of setting a high clinical suspicion for WE due to its ever-increasing incidence in these times. We also wish to direct researchers to consider other out-of-the-box treatment options in case of failure of the conventional regime. In documenting this patient report, we invite more medical providers to investigate and explore other therapeutic options for WE treatment with the aim of decreasing both morbidity and mortality secondary to the condition.
1. Lough ME. Wernicke’s encephalopathy: expanding the diagnostic toolbox. Neuropsychol Rev. 2012;22(2):181-194. doi:10.1007/s11065-012-9200-7
2. Arts NJ, Walvoort SJ, Kessels RP. Korsakoff’s syndrome: a critical review. Neuropsychiatr Dis Treat. 2017;13:2875- 2890. Published 2017 Nov 27. doi:10.2147/NDT.S130078
3. Johnson JM, Fox V. Beyond thiamine: treatment for cognitive impairment in Korsakoff’s syndrome. Psychosomatics. 2018;59(4):311-317. doi:10.1016/j.psym.2018.03.011
4. Harper CG, Giles M, Finlay-Jones R. Clinical signs in the Wernicke-Korsakoff complex: a retrospective analysis of 131 cases diagnosed at necropsy. J Neurol Neurosurg Psychiatry. 1986;49(4):341-345. doi:10.1136/ jnnp.49.4.341
5. Xiong GL, Kenedl, CA. Wernicke-Korsakoff syndrome. https://emedicine.medscape.com/article/288379-overview. Updated May 16, 2018, Accessed July 24, 2020.
6. Ahrnsbrak R, Bose J, Hedden SL, Lipari RN, Park-Lee E. Results from the 2016 National Survey on Drug Use and Health. https://www.samhsa.gov/data/sites/default/files /NSDUH-FFR1-2016/NSDUH-FFR1-2016.htm. Accessed July 22, 2020.
7. National Institute on Alcohol Abuse and Alcoholism. Drinking Levels Defined. https://www.niaaa.nih.gov /alcohol-health/overview-alcohol-consumption/moderate -binge-drinking Accessed July 24, 2020.
8. Heye N, Terstegge K, Sirtl C, McMonagle U, Schreiber K, Meyer-Gessner M. Wernicke’s encephalopathy--causes to consider. Intensive Care Med. 1994;20(4):282-286. doi:10.1007/BF01708966
9. Aasheim ET. Wernicke encephalopathy after bariatric surgery: a systematic review. Ann Surg. 2008;248(5):714-720. doi:10.1097/SLA.0b013e3181884308
10. Victor M, Adams RD, Collins GH. The Wernicke-Korsakoff Syndrome and Related Neurologic Disorders Due to Alcoholism and Malnutrition. Philadelphia, PA: FA Davis; 1989.
11. Thomson AD, Cook CC, Touquet R, Henry JA; Royal College of Physicians, London. The Royal College of Physicians report on alcohol: guidelines for managing Wernicke’s encephalopathy in the accident and Emergency Department [published correction appears in Alcohol Alcohol. 2003 May-Jun;38(3):291]. Alcohol Alcohol. 2002;37(6):513-521. doi:10.1093/alcalc/37.6.513
12. Nishimoto A, Usery J, Winton JC, Twilla J. High-dose parenteral thiamine in treatment of Wernicke’s encephalopathy: case series and review of the literature. In Vivo. 2017;31(1):121-124. doi:10.21873/invivo.11034
13. Nakamura ZM, Tatreau JR, Rosenstein DL, Park EM. Clinical characteristics and outcomes associated with highdose intravenous thiamine administration in patients with encephalopathy. Psychosomatics. 2018;59(4):379-387. doi:10.1016/j.psym.2018.01.004
14. Subramanya SB, Subramanian VS, Said HM. Chronic alcohol consumption and intestinal thiamin absorption: effects on physiological and molecular parameters of the uptake process. Am J Physiol Gastrointest Liver Physiol. 2010;299(1):G23-G31. doi:10.1152/ajpgi.00132.2010
Wernicke-Korsakoff syndrome is a cluster of symptoms attributed to a disorder of vitamin B1 (thiamine) deficiency, manifesting as a combined presentation of alcohol-induced Wernicke encephalopathy (WE) and Korsakoff syndrome (KS).1 While there is consensus on the characteristic presentation and symptoms of WE, there is a lack of agreement on the exact definition of KS. The classic triad describing WE consists of ataxia, ophthalmoplegia, and confusion; however, reports now suggest that a majority of patients exhibit only 1 or 2 of the elements of the triad. KS is often seen as a condition of chronic thiamine deficiency manifesting as memory impairment alongside a cognitive and behavioral decline, with no clear consensus on the sequence of appearance of symptoms. The typical relationship is thought to be a progression of WE to KS if untreated.
From a mental health perspective, WE presents with delirium and confusion whereas KS manifests with irreversible dementia and a cognitive deterioration. Though it is commonly taught that KS-induced memory loss is permanent due to neuronal damage (classically identified as damage to the mammillary bodies - though other structures have been implicated as well), more recent research suggest otherwise.2 A review published in 2018, for example, gathered several case reports and case series that suggest significant improvement in memory and cognition attributed to behavioral and pharmacologic interventions, indicating this as an area deserving of further study.3 About 20% of patients diagnosed with WE by autopsy exhibited none of the classical triad symptoms prior to death.4 Hence, these conditions are surmised to be significantly underdiagnosed and misdiagnosed.
Though consensus regarding the appropriate treatment regimen is lacking for WE, a common protocol consists of high-dose parenteral thiamine for 4 to 7 days.5 This is usually followed by daily oral thiamine repletion until the patient either achieves complete abstinence from alcohol (ideal) or decreases consumption. The goal is to allow thiamine stores to replete and maintain at minimum required body levels moving forward. In this case report, we highlight the utilization of a long-term, unconventional intramuscular (IM) thiamine repletion regimen to ensure maintenance of a patient’s mental status, highlighting discrepancies in our understanding of the mechanisms at play in WE and its treatment.
Case Presentation
A 65-year-old male patient with a more than 3-decade history of daily hard liquor intake, multiple psychiatric hospitalizations for WE, and a prior suicide attempt, presented to the emergency department (ED) with increased frequency of falls, poor oral intake, confabulation, and diminished verbal communication. A chart review revealed memory impairment alongside the diagnoses of schizoaffective disorder and WE, and confusion that was responsive to thiamine administration as well as a history of hypertension, hyperlipidemia, osteoarthritis, and urinary retention secondary to benign prostatic hyperplasia (BPH).
On examination the patient was found to be disoriented with a clouded sensorium. While the history of heavy daily alcohol use was clear in the chart and confirmed by other sources, it appeared unlikely that the patient had been using alcohol in the preceding month due to restricted access in his most recent living environment (a shared apartment with daily nursing assistance). He reported no lightheadedness, dizziness, palpitations, numbness, tingling, or any head trauma. He also negated the presence of active mood symptoms, auditory or visual hallucinations or suicidal ideation (SI)
The patient was admitted to the Internal Medicine Service and received a workup for the causes of delirium, including consideration of normal pressure hydrocephalus (NPH) and other neurologic conditions. Laboratory tests including a comprehensive metabolic panel, thyroid stimulating hormone, urinalysis, urine toxicology screen, and vitamin B12 and folate levels were in normal ranges. Although brain imaging revealed enlarged ventricles, NPH was considered unlikely because of the absence of ophthalmologic abnormalities, like gaze nystagmus, and urinary incontinence; conversely, there was some presence of urinary retention attributed to BPH and required an admission a few months prior. Moreover, magnetic resonance images showed that the ventricles were enlarged slightly out of proportion to the sulci, which can be seen with predominantly central volume loss compared with the pattern typically seen in NPH.
In light of concern for WE and the patient's history, treatment with IV thiamine and IV fluids was initiated and the Liaison Psychiatry Service was consulted for cognitive disability and treatment of his mood. Administration of IV thiamine rapidly restored his sensorium, but he became abruptly disorganized as the IV regimen graduated to an oral thiamine dose of 200 mg 3 times daily. Simultaneously, as medical stabilization was achieved, the patient was transferred to the inpatient psychiatry unit to address the nonresolving cognitive impairment and behavioral disorganization. This specifically involved newly emerging, impulsive, self-harming behaviors like throwing himself on the ground and banging his head on the floor. Such behaviors along with paucity of speech and decreased oral intake, ultimately warranted constant observation, which led to a decrease in self-harming activity. All this behavior was noted even though the patient was adherent to oral administration of thiamine. Throughout this time, the patient underwent several transfers back and forth between the Psychiatry and Internal Medicine services due to ongoing concern for the possibility of delirium or WE. However, the Neurology and Internal Medicine services did not feel that WE would explain the patient’s mental and behavioral status, in part due to his ongoing adherence with daily oral thiamine dosing that was not associated with improvement in mental status.
Recollecting the patient’s improvement with the parenteral thiamine regimen (IV and IM), the psychiatry unit tried a thiamine regimen of 200 mg IM and 100 mg oral 2 times daily. After about 2 weeks on this regimen, the patient subsequently achieved remarkable improvement in his cognitive and behavioral status, with resolution of selfharming behaviors. The patient was noted to be calmer, more linear, and more oriented, though he remained incompletely oriented throughout his hospitalization. As improvement in sensorium was established and the patient’s hospital stay prolonged (Figure), his mood symptoms began manifesting as guilt, low energy, decreased appetite, withdrawal, and passive SI. This was followed by a trial of lithium that was discontinued due to elevated creatine levels. As the patient continued to report depression, a multidrug regimen of divalproex, fluoxetine, and quetiapine was administered, which lead to remarkable improvement.
At this time, it was concluded that the stores of thiamine in the patient’s body may have been replenished, the alcohol intake completely ceased and that he needed to be weaned off of thiamine. The next step taken was reduction of the twice daily 200 mg IM thiamine dose to a once daily regimen, and oral thiamine was put on hold. Over the next 48 hours, the patient became less verbal, more withdrawn, incontinent of urine, and delirious. The twice daily IM 200 mg thiamine was restarted, but this time the patient demonstrated very slow improvement. After 2 weeks, the IM thiamine 200 mg was increased to 3 times daily, and the patient showed marked improvement in recall, mood, and effect.
Several attempts were made to reduce the IM thiamine burden on the patient and/ or transition to an exclusively oral regimen. However, he rapidly decompensated within hours of each attempt to taper the IM dose and required immediate reinstation. On the IM thiamine regimen, he eventually appeared to reach a stable cognitive and affective baseline marked by incomplete orientation but pleasant affect, he reported no mood complaints, behavioral stability, and an ability to comply with care needs and have simple conversations. Some speech content remained disorganized particularly if engaged beyond simple exchanges.
The patient was discharged to a skilled nursing facility after a month of 3 times daily IM administration of thiamine. Within the next 24 hours, the patient returned to the ED with the originally reported symptoms of ataxia, agitation, and confusion. On inquiry, it was revealed that the ordered vials of IM thiamine for injection had not arrived with him at the nursing facility and he had missed 2 doses. The blood laboratory results, scans, and all other parameters were otherwise found to be normal and the patient was adherent to his prescribed antipsychotics and antidepressants. As anticipated, restoration of the IM thiamine regimen revived his baseline within hours. While confusion and delirium resolved completely with treatment, the memory impairments persisted. This patient has been administered a 3 times daily IM dose of 200 mg thiamine for more than 2 years with a stable cognitive clinical picture.
Discussion
According to data from the 2016 National Survey on Drug Use and Health, 16 million individuals in the US aged ≥ 12 years reported heavy alcohol use, which is defined as binge drinking on ≥ 5 days in the past month.6,7 Thiamine deficiency is an alcoholrelated disorder that is frequently encountered in hospital settings. This deficiency can also occur in the context of malabsorption, malnutrition, a prolonged course of vomiting, and bariatric surgery.8,9
The deficiency in thiamine, which is sometimes known as WE, manifests rarely with all 3 of the classic triad of gait disturbances, abnormal eye movements, and mental status changes, with only 16.5% of patients displaying all of the triad.4 Moreover, there may be additional symptoms not listed in this triad, such as memory impairment, bilateral sixth nerve palsy, ptosis, hypotension, and hypothermia.10.11 This inconsistent presentation makes the diagnosis challenging and therefore requires a higher threshold for suspicion. If undiagnosed and/or untreated, WE can lead to chronic thiamine deficiency causing permanent brain damage in the guise of KS. This further increases the importance of timely diagnosis and treatment.
Our case highlights the utilization of an unconventional thiamine regimen that appeared to be temporally associated with mental status improvement. The patient’s clouded sensorium and confusion could not be attributed to metabolic, encephalopathic, or infectious pathologies due to the absence of supportive laboratory evidence. He responded to IV and IM doses of thiamine, but repeated attempts to taper the IM doses with the objective of transitioning to oral thiamine supplementation were followed by immediate decompensations in mental status. This was atypical of WE as the patient seemed adequately replete with thiamine, and missing a few doses should not be enough to deplete his stores. Thus, reflecting a unique case of thiamine-dependent chronically set WE when even a single missed dose of thiamine adversely affected the patient’s cognitive baseline. Interesting to note is this patient’s memory issue, as evident by clinical examination and dating back at least 5 years as per chart review. This premature amnestic component of his presentation indicates a likely parallel running KS component of his presentation. Conversely, the patient’s long history of alcohol use disorder, prior episodes of WE, and ideal response achieved only on parenteral thiamine repletion further supported the diagnosis of WE and our impression of the scenario.
Even though this patient had prior episodes of WE, there remained diagnostic uncertainty regarding his altered mental status for some time before the nonoral thiamine repletion treatment was implemented. Particularly in this admission, the patient’s mental status frequently waxed and waned and there was the additional confusion of whether a potential psychiatric etiology contributed to some of the elements of his presentation, such as his impulsive self-harm behaviors. This behavior led to recurrent transfers among the Psychiatry Service, Internal Medicine Service, and the ED.
The patient’s presentation did not reflect the classical triad of WE, and while this is consistent with the majority of clinical manifestations, various services were reluctant to attribute his symptoms to WE. Once the threshold of suspicion of thiamine deficiency was lowered and the deficit treated more aggressively, the patient seemed to improve tremendously. Presence of memory problems and confabulation, both of which this patient exhibited, are suggestive of KS and are not expected to recover with treatment, yet for this patient there did seem to be some improvement—though not complete resolution. This is consistent with newer evidence suggesting that some recovery from the deficits seen in KS is possible.3
Once diagnosed, the treatment objective is the replenishment of thiamine stores and optimization of the metabolic scenario of the body to prevent recurrence. For acute WE symptoms, many regimens call for 250 to 500 mg of IV thiamine supplementation 2 to 3 times daily for 3 to 5 days. High dose IV thiamine (≥ 500 mg daily) has been proposed to be efficacious and free of considerable adverse effects.12 A study conducted at the University of North Carolina described thiamine prescribing practices in a large academic hospital, analyzing data with the objective of assessing outcomes of ordering high-dose IV thiamine (HDIV, ≥ 200 mg IV twice daily) to patients with encephalopathy. 13 The researchers concluded that HDIV, even though rarely prescribed, was associated with decreased inpatient mortality in bivariable models. However, in multivariable analyses this decrease was found to be clinically insignificant. Our patient benefitted from both IV and IM delivery.
Ideally, after the initial IV thiamine dose, oral administration of thiamine 250 to 1,000 mg is continued until a reduction, if not abstinence, from alcohol use is achieved.5 Many patients are discharged on an oral maintenance dose of thiamine 100 mg. Oral thiamine is poorly absorbed and less effective in both prophylaxis and treatment of newly diagnosed WE; therefore, it is typically used only after IM or IV replenishment. It remains unclear why this patient required IM thiamine multiple times per day to maintain his mental status, and why he would present with selfinjurious behaviors after missing doses. The patient’s response can be attributed to late-onset defects in oral thiamine absorption at the carrier protein level of the brush border and basolateral membranes of his jejunum; however, an invasive procedure like a jejunal biopsy to establish the definitive etiology was neither necessary nor practical once treatment response was observed. 14 Other possible explanations include rapid thiamine metabolism, poor gastrointestinal absorption and a late-onset deficit in the thiamine diffusion mechanisms, and active transport systems (thiamine utilization depends on active transport in low availability states and passive transport when readily available). The nature of these mechanisms deserves further study. Less data have been reported on the administration and utility of IM thiamine for chronic WE; hence, our case report is one of the first illustrating the role of this method for sustained repletion.
Conclusions
This case presented a clinical dilemma because the conventional treatment regimen for WE didn’t yield the desired outcome until the mode and duration of thiamine administration were adjusted. It illustrates the utility of a sustained intensive thiamine regimen irrespective of sobriety status, as opposed to the traditional regimen of parenteral (primarily IV) thiamine for 3 to 7 days, followed by oral repletion until the patient achieves sustained abstinence. In this patient’s case, access to nursing care postdischarge facilitated his continued adherence to IM thiamine therapy.
The longitudinal time course of this case suggests a relationship between this route of administration and improvement in symptom burden and indicates that this patient may have a long-term need for IM thiamine to maintain his baseline mental status. Of great benefit in such patients would be the availability of a long-acting IM thiamine therapy. Risk of overdose is unlikely due to the water solubility of B group vitamins.
This case report highlights the importance of setting a high clinical suspicion for WE due to its ever-increasing incidence in these times. We also wish to direct researchers to consider other out-of-the-box treatment options in case of failure of the conventional regime. In documenting this patient report, we invite more medical providers to investigate and explore other therapeutic options for WE treatment with the aim of decreasing both morbidity and mortality secondary to the condition.
Wernicke-Korsakoff syndrome is a cluster of symptoms attributed to a disorder of vitamin B1 (thiamine) deficiency, manifesting as a combined presentation of alcohol-induced Wernicke encephalopathy (WE) and Korsakoff syndrome (KS).1 While there is consensus on the characteristic presentation and symptoms of WE, there is a lack of agreement on the exact definition of KS. The classic triad describing WE consists of ataxia, ophthalmoplegia, and confusion; however, reports now suggest that a majority of patients exhibit only 1 or 2 of the elements of the triad. KS is often seen as a condition of chronic thiamine deficiency manifesting as memory impairment alongside a cognitive and behavioral decline, with no clear consensus on the sequence of appearance of symptoms. The typical relationship is thought to be a progression of WE to KS if untreated.
From a mental health perspective, WE presents with delirium and confusion whereas KS manifests with irreversible dementia and a cognitive deterioration. Though it is commonly taught that KS-induced memory loss is permanent due to neuronal damage (classically identified as damage to the mammillary bodies - though other structures have been implicated as well), more recent research suggest otherwise.2 A review published in 2018, for example, gathered several case reports and case series that suggest significant improvement in memory and cognition attributed to behavioral and pharmacologic interventions, indicating this as an area deserving of further study.3 About 20% of patients diagnosed with WE by autopsy exhibited none of the classical triad symptoms prior to death.4 Hence, these conditions are surmised to be significantly underdiagnosed and misdiagnosed.
Though consensus regarding the appropriate treatment regimen is lacking for WE, a common protocol consists of high-dose parenteral thiamine for 4 to 7 days.5 This is usually followed by daily oral thiamine repletion until the patient either achieves complete abstinence from alcohol (ideal) or decreases consumption. The goal is to allow thiamine stores to replete and maintain at minimum required body levels moving forward. In this case report, we highlight the utilization of a long-term, unconventional intramuscular (IM) thiamine repletion regimen to ensure maintenance of a patient’s mental status, highlighting discrepancies in our understanding of the mechanisms at play in WE and its treatment.
Case Presentation
A 65-year-old male patient with a more than 3-decade history of daily hard liquor intake, multiple psychiatric hospitalizations for WE, and a prior suicide attempt, presented to the emergency department (ED) with increased frequency of falls, poor oral intake, confabulation, and diminished verbal communication. A chart review revealed memory impairment alongside the diagnoses of schizoaffective disorder and WE, and confusion that was responsive to thiamine administration as well as a history of hypertension, hyperlipidemia, osteoarthritis, and urinary retention secondary to benign prostatic hyperplasia (BPH).
On examination the patient was found to be disoriented with a clouded sensorium. While the history of heavy daily alcohol use was clear in the chart and confirmed by other sources, it appeared unlikely that the patient had been using alcohol in the preceding month due to restricted access in his most recent living environment (a shared apartment with daily nursing assistance). He reported no lightheadedness, dizziness, palpitations, numbness, tingling, or any head trauma. He also negated the presence of active mood symptoms, auditory or visual hallucinations or suicidal ideation (SI)
The patient was admitted to the Internal Medicine Service and received a workup for the causes of delirium, including consideration of normal pressure hydrocephalus (NPH) and other neurologic conditions. Laboratory tests including a comprehensive metabolic panel, thyroid stimulating hormone, urinalysis, urine toxicology screen, and vitamin B12 and folate levels were in normal ranges. Although brain imaging revealed enlarged ventricles, NPH was considered unlikely because of the absence of ophthalmologic abnormalities, like gaze nystagmus, and urinary incontinence; conversely, there was some presence of urinary retention attributed to BPH and required an admission a few months prior. Moreover, magnetic resonance images showed that the ventricles were enlarged slightly out of proportion to the sulci, which can be seen with predominantly central volume loss compared with the pattern typically seen in NPH.
In light of concern for WE and the patient's history, treatment with IV thiamine and IV fluids was initiated and the Liaison Psychiatry Service was consulted for cognitive disability and treatment of his mood. Administration of IV thiamine rapidly restored his sensorium, but he became abruptly disorganized as the IV regimen graduated to an oral thiamine dose of 200 mg 3 times daily. Simultaneously, as medical stabilization was achieved, the patient was transferred to the inpatient psychiatry unit to address the nonresolving cognitive impairment and behavioral disorganization. This specifically involved newly emerging, impulsive, self-harming behaviors like throwing himself on the ground and banging his head on the floor. Such behaviors along with paucity of speech and decreased oral intake, ultimately warranted constant observation, which led to a decrease in self-harming activity. All this behavior was noted even though the patient was adherent to oral administration of thiamine. Throughout this time, the patient underwent several transfers back and forth between the Psychiatry and Internal Medicine services due to ongoing concern for the possibility of delirium or WE. However, the Neurology and Internal Medicine services did not feel that WE would explain the patient’s mental and behavioral status, in part due to his ongoing adherence with daily oral thiamine dosing that was not associated with improvement in mental status.
Recollecting the patient’s improvement with the parenteral thiamine regimen (IV and IM), the psychiatry unit tried a thiamine regimen of 200 mg IM and 100 mg oral 2 times daily. After about 2 weeks on this regimen, the patient subsequently achieved remarkable improvement in his cognitive and behavioral status, with resolution of selfharming behaviors. The patient was noted to be calmer, more linear, and more oriented, though he remained incompletely oriented throughout his hospitalization. As improvement in sensorium was established and the patient’s hospital stay prolonged (Figure), his mood symptoms began manifesting as guilt, low energy, decreased appetite, withdrawal, and passive SI. This was followed by a trial of lithium that was discontinued due to elevated creatine levels. As the patient continued to report depression, a multidrug regimen of divalproex, fluoxetine, and quetiapine was administered, which lead to remarkable improvement.
At this time, it was concluded that the stores of thiamine in the patient’s body may have been replenished, the alcohol intake completely ceased and that he needed to be weaned off of thiamine. The next step taken was reduction of the twice daily 200 mg IM thiamine dose to a once daily regimen, and oral thiamine was put on hold. Over the next 48 hours, the patient became less verbal, more withdrawn, incontinent of urine, and delirious. The twice daily IM 200 mg thiamine was restarted, but this time the patient demonstrated very slow improvement. After 2 weeks, the IM thiamine 200 mg was increased to 3 times daily, and the patient showed marked improvement in recall, mood, and effect.
Several attempts were made to reduce the IM thiamine burden on the patient and/ or transition to an exclusively oral regimen. However, he rapidly decompensated within hours of each attempt to taper the IM dose and required immediate reinstation. On the IM thiamine regimen, he eventually appeared to reach a stable cognitive and affective baseline marked by incomplete orientation but pleasant affect, he reported no mood complaints, behavioral stability, and an ability to comply with care needs and have simple conversations. Some speech content remained disorganized particularly if engaged beyond simple exchanges.
The patient was discharged to a skilled nursing facility after a month of 3 times daily IM administration of thiamine. Within the next 24 hours, the patient returned to the ED with the originally reported symptoms of ataxia, agitation, and confusion. On inquiry, it was revealed that the ordered vials of IM thiamine for injection had not arrived with him at the nursing facility and he had missed 2 doses. The blood laboratory results, scans, and all other parameters were otherwise found to be normal and the patient was adherent to his prescribed antipsychotics and antidepressants. As anticipated, restoration of the IM thiamine regimen revived his baseline within hours. While confusion and delirium resolved completely with treatment, the memory impairments persisted. This patient has been administered a 3 times daily IM dose of 200 mg thiamine for more than 2 years with a stable cognitive clinical picture.
Discussion
According to data from the 2016 National Survey on Drug Use and Health, 16 million individuals in the US aged ≥ 12 years reported heavy alcohol use, which is defined as binge drinking on ≥ 5 days in the past month.6,7 Thiamine deficiency is an alcoholrelated disorder that is frequently encountered in hospital settings. This deficiency can also occur in the context of malabsorption, malnutrition, a prolonged course of vomiting, and bariatric surgery.8,9
The deficiency in thiamine, which is sometimes known as WE, manifests rarely with all 3 of the classic triad of gait disturbances, abnormal eye movements, and mental status changes, with only 16.5% of patients displaying all of the triad.4 Moreover, there may be additional symptoms not listed in this triad, such as memory impairment, bilateral sixth nerve palsy, ptosis, hypotension, and hypothermia.10.11 This inconsistent presentation makes the diagnosis challenging and therefore requires a higher threshold for suspicion. If undiagnosed and/or untreated, WE can lead to chronic thiamine deficiency causing permanent brain damage in the guise of KS. This further increases the importance of timely diagnosis and treatment.
Our case highlights the utilization of an unconventional thiamine regimen that appeared to be temporally associated with mental status improvement. The patient’s clouded sensorium and confusion could not be attributed to metabolic, encephalopathic, or infectious pathologies due to the absence of supportive laboratory evidence. He responded to IV and IM doses of thiamine, but repeated attempts to taper the IM doses with the objective of transitioning to oral thiamine supplementation were followed by immediate decompensations in mental status. This was atypical of WE as the patient seemed adequately replete with thiamine, and missing a few doses should not be enough to deplete his stores. Thus, reflecting a unique case of thiamine-dependent chronically set WE when even a single missed dose of thiamine adversely affected the patient’s cognitive baseline. Interesting to note is this patient’s memory issue, as evident by clinical examination and dating back at least 5 years as per chart review. This premature amnestic component of his presentation indicates a likely parallel running KS component of his presentation. Conversely, the patient’s long history of alcohol use disorder, prior episodes of WE, and ideal response achieved only on parenteral thiamine repletion further supported the diagnosis of WE and our impression of the scenario.
Even though this patient had prior episodes of WE, there remained diagnostic uncertainty regarding his altered mental status for some time before the nonoral thiamine repletion treatment was implemented. Particularly in this admission, the patient’s mental status frequently waxed and waned and there was the additional confusion of whether a potential psychiatric etiology contributed to some of the elements of his presentation, such as his impulsive self-harm behaviors. This behavior led to recurrent transfers among the Psychiatry Service, Internal Medicine Service, and the ED.
The patient’s presentation did not reflect the classical triad of WE, and while this is consistent with the majority of clinical manifestations, various services were reluctant to attribute his symptoms to WE. Once the threshold of suspicion of thiamine deficiency was lowered and the deficit treated more aggressively, the patient seemed to improve tremendously. Presence of memory problems and confabulation, both of which this patient exhibited, are suggestive of KS and are not expected to recover with treatment, yet for this patient there did seem to be some improvement—though not complete resolution. This is consistent with newer evidence suggesting that some recovery from the deficits seen in KS is possible.3
Once diagnosed, the treatment objective is the replenishment of thiamine stores and optimization of the metabolic scenario of the body to prevent recurrence. For acute WE symptoms, many regimens call for 250 to 500 mg of IV thiamine supplementation 2 to 3 times daily for 3 to 5 days. High dose IV thiamine (≥ 500 mg daily) has been proposed to be efficacious and free of considerable adverse effects.12 A study conducted at the University of North Carolina described thiamine prescribing practices in a large academic hospital, analyzing data with the objective of assessing outcomes of ordering high-dose IV thiamine (HDIV, ≥ 200 mg IV twice daily) to patients with encephalopathy. 13 The researchers concluded that HDIV, even though rarely prescribed, was associated with decreased inpatient mortality in bivariable models. However, in multivariable analyses this decrease was found to be clinically insignificant. Our patient benefitted from both IV and IM delivery.
Ideally, after the initial IV thiamine dose, oral administration of thiamine 250 to 1,000 mg is continued until a reduction, if not abstinence, from alcohol use is achieved.5 Many patients are discharged on an oral maintenance dose of thiamine 100 mg. Oral thiamine is poorly absorbed and less effective in both prophylaxis and treatment of newly diagnosed WE; therefore, it is typically used only after IM or IV replenishment. It remains unclear why this patient required IM thiamine multiple times per day to maintain his mental status, and why he would present with selfinjurious behaviors after missing doses. The patient’s response can be attributed to late-onset defects in oral thiamine absorption at the carrier protein level of the brush border and basolateral membranes of his jejunum; however, an invasive procedure like a jejunal biopsy to establish the definitive etiology was neither necessary nor practical once treatment response was observed. 14 Other possible explanations include rapid thiamine metabolism, poor gastrointestinal absorption and a late-onset deficit in the thiamine diffusion mechanisms, and active transport systems (thiamine utilization depends on active transport in low availability states and passive transport when readily available). The nature of these mechanisms deserves further study. Less data have been reported on the administration and utility of IM thiamine for chronic WE; hence, our case report is one of the first illustrating the role of this method for sustained repletion.
Conclusions
This case presented a clinical dilemma because the conventional treatment regimen for WE didn’t yield the desired outcome until the mode and duration of thiamine administration were adjusted. It illustrates the utility of a sustained intensive thiamine regimen irrespective of sobriety status, as opposed to the traditional regimen of parenteral (primarily IV) thiamine for 3 to 7 days, followed by oral repletion until the patient achieves sustained abstinence. In this patient’s case, access to nursing care postdischarge facilitated his continued adherence to IM thiamine therapy.
The longitudinal time course of this case suggests a relationship between this route of administration and improvement in symptom burden and indicates that this patient may have a long-term need for IM thiamine to maintain his baseline mental status. Of great benefit in such patients would be the availability of a long-acting IM thiamine therapy. Risk of overdose is unlikely due to the water solubility of B group vitamins.
This case report highlights the importance of setting a high clinical suspicion for WE due to its ever-increasing incidence in these times. We also wish to direct researchers to consider other out-of-the-box treatment options in case of failure of the conventional regime. In documenting this patient report, we invite more medical providers to investigate and explore other therapeutic options for WE treatment with the aim of decreasing both morbidity and mortality secondary to the condition.
1. Lough ME. Wernicke’s encephalopathy: expanding the diagnostic toolbox. Neuropsychol Rev. 2012;22(2):181-194. doi:10.1007/s11065-012-9200-7
2. Arts NJ, Walvoort SJ, Kessels RP. Korsakoff’s syndrome: a critical review. Neuropsychiatr Dis Treat. 2017;13:2875- 2890. Published 2017 Nov 27. doi:10.2147/NDT.S130078
3. Johnson JM, Fox V. Beyond thiamine: treatment for cognitive impairment in Korsakoff’s syndrome. Psychosomatics. 2018;59(4):311-317. doi:10.1016/j.psym.2018.03.011
4. Harper CG, Giles M, Finlay-Jones R. Clinical signs in the Wernicke-Korsakoff complex: a retrospective analysis of 131 cases diagnosed at necropsy. J Neurol Neurosurg Psychiatry. 1986;49(4):341-345. doi:10.1136/ jnnp.49.4.341
5. Xiong GL, Kenedl, CA. Wernicke-Korsakoff syndrome. https://emedicine.medscape.com/article/288379-overview. Updated May 16, 2018, Accessed July 24, 2020.
6. Ahrnsbrak R, Bose J, Hedden SL, Lipari RN, Park-Lee E. Results from the 2016 National Survey on Drug Use and Health. https://www.samhsa.gov/data/sites/default/files /NSDUH-FFR1-2016/NSDUH-FFR1-2016.htm. Accessed July 22, 2020.
7. National Institute on Alcohol Abuse and Alcoholism. Drinking Levels Defined. https://www.niaaa.nih.gov /alcohol-health/overview-alcohol-consumption/moderate -binge-drinking Accessed July 24, 2020.
8. Heye N, Terstegge K, Sirtl C, McMonagle U, Schreiber K, Meyer-Gessner M. Wernicke’s encephalopathy--causes to consider. Intensive Care Med. 1994;20(4):282-286. doi:10.1007/BF01708966
9. Aasheim ET. Wernicke encephalopathy after bariatric surgery: a systematic review. Ann Surg. 2008;248(5):714-720. doi:10.1097/SLA.0b013e3181884308
10. Victor M, Adams RD, Collins GH. The Wernicke-Korsakoff Syndrome and Related Neurologic Disorders Due to Alcoholism and Malnutrition. Philadelphia, PA: FA Davis; 1989.
11. Thomson AD, Cook CC, Touquet R, Henry JA; Royal College of Physicians, London. The Royal College of Physicians report on alcohol: guidelines for managing Wernicke’s encephalopathy in the accident and Emergency Department [published correction appears in Alcohol Alcohol. 2003 May-Jun;38(3):291]. Alcohol Alcohol. 2002;37(6):513-521. doi:10.1093/alcalc/37.6.513
12. Nishimoto A, Usery J, Winton JC, Twilla J. High-dose parenteral thiamine in treatment of Wernicke’s encephalopathy: case series and review of the literature. In Vivo. 2017;31(1):121-124. doi:10.21873/invivo.11034
13. Nakamura ZM, Tatreau JR, Rosenstein DL, Park EM. Clinical characteristics and outcomes associated with highdose intravenous thiamine administration in patients with encephalopathy. Psychosomatics. 2018;59(4):379-387. doi:10.1016/j.psym.2018.01.004
14. Subramanya SB, Subramanian VS, Said HM. Chronic alcohol consumption and intestinal thiamin absorption: effects on physiological and molecular parameters of the uptake process. Am J Physiol Gastrointest Liver Physiol. 2010;299(1):G23-G31. doi:10.1152/ajpgi.00132.2010
1. Lough ME. Wernicke’s encephalopathy: expanding the diagnostic toolbox. Neuropsychol Rev. 2012;22(2):181-194. doi:10.1007/s11065-012-9200-7
2. Arts NJ, Walvoort SJ, Kessels RP. Korsakoff’s syndrome: a critical review. Neuropsychiatr Dis Treat. 2017;13:2875- 2890. Published 2017 Nov 27. doi:10.2147/NDT.S130078
3. Johnson JM, Fox V. Beyond thiamine: treatment for cognitive impairment in Korsakoff’s syndrome. Psychosomatics. 2018;59(4):311-317. doi:10.1016/j.psym.2018.03.011
4. Harper CG, Giles M, Finlay-Jones R. Clinical signs in the Wernicke-Korsakoff complex: a retrospective analysis of 131 cases diagnosed at necropsy. J Neurol Neurosurg Psychiatry. 1986;49(4):341-345. doi:10.1136/ jnnp.49.4.341
5. Xiong GL, Kenedl, CA. Wernicke-Korsakoff syndrome. https://emedicine.medscape.com/article/288379-overview. Updated May 16, 2018, Accessed July 24, 2020.
6. Ahrnsbrak R, Bose J, Hedden SL, Lipari RN, Park-Lee E. Results from the 2016 National Survey on Drug Use and Health. https://www.samhsa.gov/data/sites/default/files /NSDUH-FFR1-2016/NSDUH-FFR1-2016.htm. Accessed July 22, 2020.
7. National Institute on Alcohol Abuse and Alcoholism. Drinking Levels Defined. https://www.niaaa.nih.gov /alcohol-health/overview-alcohol-consumption/moderate -binge-drinking Accessed July 24, 2020.
8. Heye N, Terstegge K, Sirtl C, McMonagle U, Schreiber K, Meyer-Gessner M. Wernicke’s encephalopathy--causes to consider. Intensive Care Med. 1994;20(4):282-286. doi:10.1007/BF01708966
9. Aasheim ET. Wernicke encephalopathy after bariatric surgery: a systematic review. Ann Surg. 2008;248(5):714-720. doi:10.1097/SLA.0b013e3181884308
10. Victor M, Adams RD, Collins GH. The Wernicke-Korsakoff Syndrome and Related Neurologic Disorders Due to Alcoholism and Malnutrition. Philadelphia, PA: FA Davis; 1989.
11. Thomson AD, Cook CC, Touquet R, Henry JA; Royal College of Physicians, London. The Royal College of Physicians report on alcohol: guidelines for managing Wernicke’s encephalopathy in the accident and Emergency Department [published correction appears in Alcohol Alcohol. 2003 May-Jun;38(3):291]. Alcohol Alcohol. 2002;37(6):513-521. doi:10.1093/alcalc/37.6.513
12. Nishimoto A, Usery J, Winton JC, Twilla J. High-dose parenteral thiamine in treatment of Wernicke’s encephalopathy: case series and review of the literature. In Vivo. 2017;31(1):121-124. doi:10.21873/invivo.11034
13. Nakamura ZM, Tatreau JR, Rosenstein DL, Park EM. Clinical characteristics and outcomes associated with highdose intravenous thiamine administration in patients with encephalopathy. Psychosomatics. 2018;59(4):379-387. doi:10.1016/j.psym.2018.01.004
14. Subramanya SB, Subramanian VS, Said HM. Chronic alcohol consumption and intestinal thiamin absorption: effects on physiological and molecular parameters of the uptake process. Am J Physiol Gastrointest Liver Physiol. 2010;299(1):G23-G31. doi:10.1152/ajpgi.00132.2010