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Infusion center directors shuffle treatment services in the era of COVID-19
It’s anything but business as usual for clinicians who oversee office-based infusion centers, as they scramble to maintain services for patients considered to be at heightened risk for severe illness should they become infected with COVID-19.
“For many reasons, the guidance for patients right now is that they stay on their medications,” Max I. Hamburger, MD, a managing partner at Rheumatology Associates of Long Island (N.Y.), said in an interview. “Some have decided to stop the drug, and then they call us up to tell us that they’re flaring. The beginning of a flare is tiredness and other things. Now they’re worried: Are they tired because of the disease, or are they tired because they have COVID-19?”
With five office locations located in a region considered to be the epicenter of the COVID-19 pandemic in the United States, Dr. Hamburger and his colleagues are hypervigilant about screening patients for symptoms of the virus before they visit one of the three practice locations that provide infusion services. This starts with an automated phone system that reminds patients of their appointment time. “Part of that robocall now has some questions like, ‘Do you have any symptoms of COVID-19?’ ‘Are you running a fever?’ ‘Do you have any reason to worry about yourself? If so, please call us.’ ” The infusion nurses are also calling the patients in advance of their appointment to check on their status. “When they get to the office location, we ask them again about their general health and check their temperature,” said Dr. Hamburger, who is also founder and executive chairman of United Rheumatology, which is a nationwide rheumatology care management services organization with 650 members in 39 states. “We’re doing everything we can to talk to them about their own state of health and to question them about what I call extended paranoia: like, ‘Who are you living with?’ ‘Who are you hanging out with?’ ‘What are all the six degrees of separation here?’ I want to know what the patient’s husband did last night. I want to know where their kids were over this past week, et cetera. We do everything we can to see if there’s anybody who might have had the slightest [contact with someone who has COVID-19]. Because if I lose my infusion nurse, then I’m up the creek.”
The infusion nurse wears scrubs, a face mask, and latex gloves. She and her staff are using hand sanitizer and cleaning infusion equipment with sanitizing wipes as one might do in a surgical setting. “Every surface is wiped down between patients, and the nurse is changing gloves between patients,” said Dr. Hamburger, who was founding president of the New York State Rheumatology Society before retiring from that post in 2017. “Getting masks has been tough. We’re doing the best we can there. We’re not gloving patients but we’re masking patients.”
As noted in guidance from the American College of Rheumatology and other medical organizations, following the CDC’s recommendation to stay at home during the pandemic has jump-started conversations between physicians and their patients about modifying the time interval between infusions. “If they have been doing well for the last 9 months, we’re having a conversation such as ‘Maybe instead of getting your Orencia every 4 weeks, maybe we’ll push it out to 5 weeks, or maybe we’ll push the Enbrel out to 10 days and the Humira out 3 weeks, et cetera,” Dr. Hamburger said. “One has to be very careful about when you do that, because you don’t want the patient to flare up because it’s hard to get them in, but it is a natural opportunity to look at this. We’re seeing how we can optimize the dose, but I don’t want to send the message that we’re doing this because it changes the patient’s outcome, because there’s zero evidence that it’s a good thing to do in terms of resistance.”
At the infusion centers operated by the Johns Hopkins division of gastroenterology and hepatology, Baltimore, clinicians are not increasing the time interval between infusions for patients at this time. “We’re keeping them as they are, to prevent any flare-ups. Our main goal is to keep patients in remission and out of the hospital,” said Alyssa M. Parian, MD, medical director of the infusion center and associate director of the university’s GI department. “With Remicade specifically, there’s also the risk of developing antibodies if you delay treatment, so we’re basically keeping everyone on track. We’re not recommending a switch from infusions to injectables, and we also are not speeding up infusions, either. Before this pandemic happened, we had already tried to decrease all Remicade infusions from 2 hours to 1 hour for patient satisfaction. The Entyvio is a pretty quick, 30-minute infusion.”
To accommodate patients during this era of physical distancing measures recommended by the Centers for Disease Control and Prevention, Dr. Parian and her infusion nurse manager Elisheva Weiser converted one of their two outpatient GI centers into an infusion-only suite with 12 individual clinic rooms. As soon as patients exit the second-floor elevator, they encounter a workstation prior to entering the office where they are screened for COVID-19 symptoms and their temperature is taken. “If any symptoms or temperature comes back positive, we’re asking them to postpone their treatment and consider COVID testing,” she said.
Instead of one nurse looking after four patients in one room during infusion therapy, now one nurse looks after two patients who are in rooms next to each other. All patients and all staff wear masks while in the center. “We always have physician oversight at our infusion centers,” Dr. Parian said. “We are trying to maintain a ‘COVID-free zone.’ Therefore, no physicians who have served in a hospital ward are allowed in the infusion suite because we don’t want any carriers of COVID-19. Same with the nurses. Additionally, we limit the staff within the suite to only those who are essential and don’t allow anyone to perform telemedicine or urgent clinic visits in this location. Our infusion center staff are on a strict protocol to not come in with any symptoms at all. They are asked to take their temperature before coming in to work.”
She and her colleagues drew from recommendations from the joint GI society message on COVID-19, the Crohn’s and Colitis Foundation, and the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) to inform their approach in serving patients during this unprecedented time. “We went as conservative as possible because these are immunosuppressed patients,” she said. One patient on her panel who receives an infusion every 8 weeks tested positive for COVID-19 between infusions, but was not hospitalized. Dr. Parian said that person will only be treated 14 days after the all symptoms disappear. “That person will wear a mask and will be infused in a separate room,” she said.
In Aventura, Fla., Norman B. Gaylis, MD, and his colleagues at Arthritis & Rheumatic Disease Specialties are looking into shutting down their infusion services during the time period that local public health officials consider to be the peak level of exposure to COVID-19. “We’ve tried to work around that, and bring people in a little early,” said Dr. Gaylis, medical director of rheumatology and infusion services at the practice. “We’ve done our best to mitigate the risk [of exposure] as much as possible.” This includes staggering their caseload by infusing 5 patients at a time, compared with the 15 patients at a time they could treat during prepandemic conditions. “Everyone is at least 20 feet apart,” said Dr. Gaylis, who is a member of the American College of Rheumatology Board of Directors. “While we don’t have the kind of protective garments you might see in an ICU, we still are gowning, gloving, and masking our staff, and trying to practice sterile techniques as much as we can.”
The pandemic has caused him to reflect more broadly on the way he and his colleagues deliver care for patients on infusion therapy. “We see patients who really want their treatment because they feel it’s helpful and beneficial,” he said. “There are also patients who may truly be in remission who could stop [infusion therapy]. We could possibly extend the duration of their therapy, try and push it back.”
Dr. Gaylis emphasized that any discussion about halting infusion therapy requires clinical, serological, and ideally even MRI evidence that the disease is in a dormant state. “You wouldn’t stop treatment in someone who is showing signs in their blood that their disease is still active,” he said. “You’re using all those parameters in that conversation.”
In his clinical opinion, now is not the time to switch patients to self-injectable agents as a perceived matter of convenience. “I don’t really think that’s a good idea because self-injectables are different,” Dr. Gaylis said. “You’re basically switching treatment patterns. The practicality of getting a specialty pharmacy to switch, the insurance companies to cover it, and determine copay for it, is a burden on patients. That’s why I’m against it, because you’re starting a whole new process and problem.”
One patient tested positive for COVID-19 about 3 weeks after an infusion at the facility. “That does lead to a point: Have my staff been tested? We have not had the tests available to us,” Dr. Gaylis said. “One provider had a contact with someone with COVID-19 and stayed home for 2 weeks. That person tested negative. Soon we are going to receive a kit that will allow us to measure IgM and IgG COVID-19 antibodies. Because we’re going to be closed for 2 weeks, measuring us now would be a great way to handle it.”
In rural Western Kentucky, Christopher R. Phillips, MD, and his colleagues at Paducah Rheumatology have arranged for “drive-by” injections for some of their higher-risk patients who require subcutaneous administration of biologic agents. “We have them call us when they’re in the parking lot, and we give them the treatment while they sit in their car,” said Dr. Phillips, who chairs the ACR Insurance Subcommittee and is a member of the ACR COVID-19 Practice and Advocacy Task Force.
For patients who require infusions, they’ve arranged three chairs in the clinic to be at least 6 feet apart, and moved the fourth chair into a separate room. “My infusion nurse knows these patients well; we’re a small community,” he said. “She checks in with them the day before to screen for any symptoms of infection and asks them to call when they get here. A lot of them wait in their car to be brought in. She’ll bring them in, screen for infection symptoms, and check their temperature. She and the receptionist are masked and gloved, and disinfect aggressively between patients. The other thing we are trying to be on top of is making sure that everyone’s insurance coverage is active when they come in, in light of the number of people who have been laid off or had changes in their employment.”
Dr. Phillips has considered increasing the infusion time interval for some patients, but not knowing when current physical distancing guidelines will ease up presents a conundrum. “If I have a patient coming in today, and their next treatment is due in a month, I don’t know how to say that, if we stretch the infusion to 2 months, that things are going to be better,” he said. “For some very well-controlled patients and/or high-risk patients, that is something we’ve done: stretch the interval or skip a treatment. For most patients, our default is to stick with the normal schedule. We feel that, for most patients who have moderate to severe underlying rheumatic disease, the risk of disease flare and subsequent need for steroids may be a larger risk than the treatment itself, though that is an individualized decision.”
To date, Dr. Phillips has not treated a patient who has recovered from COVID-19, but the thought of that scenario gives him pause. “There is some literature suggesting these patients may asymptomatically shed virus for some time after they’ve clinically recovered, but we don’t really know enough about that,” he said. “If I had one of those patients, I’d probably be delaying them for a longer period of time, and I’d be looking for some guidance from the literature on postsymptomatic viral shedding.”
In the meantime, the level of anxiety that many of his patients express during this pandemic is palpable. “They really are between a rock and a hard place,” Dr. Phillips said. “If they come off their effective treatment, they risk flare of a disease that can be life or limb threatening. And yet, because of their disease and their treatment, they’re potentially at increased risk for serious illness if they become infected with COVID-19. We look for ways to try to reassure patients and to comfort them, and work with them to make the best of the situation.”
It’s anything but business as usual for clinicians who oversee office-based infusion centers, as they scramble to maintain services for patients considered to be at heightened risk for severe illness should they become infected with COVID-19.
“For many reasons, the guidance for patients right now is that they stay on their medications,” Max I. Hamburger, MD, a managing partner at Rheumatology Associates of Long Island (N.Y.), said in an interview. “Some have decided to stop the drug, and then they call us up to tell us that they’re flaring. The beginning of a flare is tiredness and other things. Now they’re worried: Are they tired because of the disease, or are they tired because they have COVID-19?”
With five office locations located in a region considered to be the epicenter of the COVID-19 pandemic in the United States, Dr. Hamburger and his colleagues are hypervigilant about screening patients for symptoms of the virus before they visit one of the three practice locations that provide infusion services. This starts with an automated phone system that reminds patients of their appointment time. “Part of that robocall now has some questions like, ‘Do you have any symptoms of COVID-19?’ ‘Are you running a fever?’ ‘Do you have any reason to worry about yourself? If so, please call us.’ ” The infusion nurses are also calling the patients in advance of their appointment to check on their status. “When they get to the office location, we ask them again about their general health and check their temperature,” said Dr. Hamburger, who is also founder and executive chairman of United Rheumatology, which is a nationwide rheumatology care management services organization with 650 members in 39 states. “We’re doing everything we can to talk to them about their own state of health and to question them about what I call extended paranoia: like, ‘Who are you living with?’ ‘Who are you hanging out with?’ ‘What are all the six degrees of separation here?’ I want to know what the patient’s husband did last night. I want to know where their kids were over this past week, et cetera. We do everything we can to see if there’s anybody who might have had the slightest [contact with someone who has COVID-19]. Because if I lose my infusion nurse, then I’m up the creek.”
The infusion nurse wears scrubs, a face mask, and latex gloves. She and her staff are using hand sanitizer and cleaning infusion equipment with sanitizing wipes as one might do in a surgical setting. “Every surface is wiped down between patients, and the nurse is changing gloves between patients,” said Dr. Hamburger, who was founding president of the New York State Rheumatology Society before retiring from that post in 2017. “Getting masks has been tough. We’re doing the best we can there. We’re not gloving patients but we’re masking patients.”
As noted in guidance from the American College of Rheumatology and other medical organizations, following the CDC’s recommendation to stay at home during the pandemic has jump-started conversations between physicians and their patients about modifying the time interval between infusions. “If they have been doing well for the last 9 months, we’re having a conversation such as ‘Maybe instead of getting your Orencia every 4 weeks, maybe we’ll push it out to 5 weeks, or maybe we’ll push the Enbrel out to 10 days and the Humira out 3 weeks, et cetera,” Dr. Hamburger said. “One has to be very careful about when you do that, because you don’t want the patient to flare up because it’s hard to get them in, but it is a natural opportunity to look at this. We’re seeing how we can optimize the dose, but I don’t want to send the message that we’re doing this because it changes the patient’s outcome, because there’s zero evidence that it’s a good thing to do in terms of resistance.”
At the infusion centers operated by the Johns Hopkins division of gastroenterology and hepatology, Baltimore, clinicians are not increasing the time interval between infusions for patients at this time. “We’re keeping them as they are, to prevent any flare-ups. Our main goal is to keep patients in remission and out of the hospital,” said Alyssa M. Parian, MD, medical director of the infusion center and associate director of the university’s GI department. “With Remicade specifically, there’s also the risk of developing antibodies if you delay treatment, so we’re basically keeping everyone on track. We’re not recommending a switch from infusions to injectables, and we also are not speeding up infusions, either. Before this pandemic happened, we had already tried to decrease all Remicade infusions from 2 hours to 1 hour for patient satisfaction. The Entyvio is a pretty quick, 30-minute infusion.”
To accommodate patients during this era of physical distancing measures recommended by the Centers for Disease Control and Prevention, Dr. Parian and her infusion nurse manager Elisheva Weiser converted one of their two outpatient GI centers into an infusion-only suite with 12 individual clinic rooms. As soon as patients exit the second-floor elevator, they encounter a workstation prior to entering the office where they are screened for COVID-19 symptoms and their temperature is taken. “If any symptoms or temperature comes back positive, we’re asking them to postpone their treatment and consider COVID testing,” she said.
Instead of one nurse looking after four patients in one room during infusion therapy, now one nurse looks after two patients who are in rooms next to each other. All patients and all staff wear masks while in the center. “We always have physician oversight at our infusion centers,” Dr. Parian said. “We are trying to maintain a ‘COVID-free zone.’ Therefore, no physicians who have served in a hospital ward are allowed in the infusion suite because we don’t want any carriers of COVID-19. Same with the nurses. Additionally, we limit the staff within the suite to only those who are essential and don’t allow anyone to perform telemedicine or urgent clinic visits in this location. Our infusion center staff are on a strict protocol to not come in with any symptoms at all. They are asked to take their temperature before coming in to work.”
She and her colleagues drew from recommendations from the joint GI society message on COVID-19, the Crohn’s and Colitis Foundation, and the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) to inform their approach in serving patients during this unprecedented time. “We went as conservative as possible because these are immunosuppressed patients,” she said. One patient on her panel who receives an infusion every 8 weeks tested positive for COVID-19 between infusions, but was not hospitalized. Dr. Parian said that person will only be treated 14 days after the all symptoms disappear. “That person will wear a mask and will be infused in a separate room,” she said.
In Aventura, Fla., Norman B. Gaylis, MD, and his colleagues at Arthritis & Rheumatic Disease Specialties are looking into shutting down their infusion services during the time period that local public health officials consider to be the peak level of exposure to COVID-19. “We’ve tried to work around that, and bring people in a little early,” said Dr. Gaylis, medical director of rheumatology and infusion services at the practice. “We’ve done our best to mitigate the risk [of exposure] as much as possible.” This includes staggering their caseload by infusing 5 patients at a time, compared with the 15 patients at a time they could treat during prepandemic conditions. “Everyone is at least 20 feet apart,” said Dr. Gaylis, who is a member of the American College of Rheumatology Board of Directors. “While we don’t have the kind of protective garments you might see in an ICU, we still are gowning, gloving, and masking our staff, and trying to practice sterile techniques as much as we can.”
The pandemic has caused him to reflect more broadly on the way he and his colleagues deliver care for patients on infusion therapy. “We see patients who really want their treatment because they feel it’s helpful and beneficial,” he said. “There are also patients who may truly be in remission who could stop [infusion therapy]. We could possibly extend the duration of their therapy, try and push it back.”
Dr. Gaylis emphasized that any discussion about halting infusion therapy requires clinical, serological, and ideally even MRI evidence that the disease is in a dormant state. “You wouldn’t stop treatment in someone who is showing signs in their blood that their disease is still active,” he said. “You’re using all those parameters in that conversation.”
In his clinical opinion, now is not the time to switch patients to self-injectable agents as a perceived matter of convenience. “I don’t really think that’s a good idea because self-injectables are different,” Dr. Gaylis said. “You’re basically switching treatment patterns. The practicality of getting a specialty pharmacy to switch, the insurance companies to cover it, and determine copay for it, is a burden on patients. That’s why I’m against it, because you’re starting a whole new process and problem.”
One patient tested positive for COVID-19 about 3 weeks after an infusion at the facility. “That does lead to a point: Have my staff been tested? We have not had the tests available to us,” Dr. Gaylis said. “One provider had a contact with someone with COVID-19 and stayed home for 2 weeks. That person tested negative. Soon we are going to receive a kit that will allow us to measure IgM and IgG COVID-19 antibodies. Because we’re going to be closed for 2 weeks, measuring us now would be a great way to handle it.”
In rural Western Kentucky, Christopher R. Phillips, MD, and his colleagues at Paducah Rheumatology have arranged for “drive-by” injections for some of their higher-risk patients who require subcutaneous administration of biologic agents. “We have them call us when they’re in the parking lot, and we give them the treatment while they sit in their car,” said Dr. Phillips, who chairs the ACR Insurance Subcommittee and is a member of the ACR COVID-19 Practice and Advocacy Task Force.
For patients who require infusions, they’ve arranged three chairs in the clinic to be at least 6 feet apart, and moved the fourth chair into a separate room. “My infusion nurse knows these patients well; we’re a small community,” he said. “She checks in with them the day before to screen for any symptoms of infection and asks them to call when they get here. A lot of them wait in their car to be brought in. She’ll bring them in, screen for infection symptoms, and check their temperature. She and the receptionist are masked and gloved, and disinfect aggressively between patients. The other thing we are trying to be on top of is making sure that everyone’s insurance coverage is active when they come in, in light of the number of people who have been laid off or had changes in their employment.”
Dr. Phillips has considered increasing the infusion time interval for some patients, but not knowing when current physical distancing guidelines will ease up presents a conundrum. “If I have a patient coming in today, and their next treatment is due in a month, I don’t know how to say that, if we stretch the infusion to 2 months, that things are going to be better,” he said. “For some very well-controlled patients and/or high-risk patients, that is something we’ve done: stretch the interval or skip a treatment. For most patients, our default is to stick with the normal schedule. We feel that, for most patients who have moderate to severe underlying rheumatic disease, the risk of disease flare and subsequent need for steroids may be a larger risk than the treatment itself, though that is an individualized decision.”
To date, Dr. Phillips has not treated a patient who has recovered from COVID-19, but the thought of that scenario gives him pause. “There is some literature suggesting these patients may asymptomatically shed virus for some time after they’ve clinically recovered, but we don’t really know enough about that,” he said. “If I had one of those patients, I’d probably be delaying them for a longer period of time, and I’d be looking for some guidance from the literature on postsymptomatic viral shedding.”
In the meantime, the level of anxiety that many of his patients express during this pandemic is palpable. “They really are between a rock and a hard place,” Dr. Phillips said. “If they come off their effective treatment, they risk flare of a disease that can be life or limb threatening. And yet, because of their disease and their treatment, they’re potentially at increased risk for serious illness if they become infected with COVID-19. We look for ways to try to reassure patients and to comfort them, and work with them to make the best of the situation.”
It’s anything but business as usual for clinicians who oversee office-based infusion centers, as they scramble to maintain services for patients considered to be at heightened risk for severe illness should they become infected with COVID-19.
“For many reasons, the guidance for patients right now is that they stay on their medications,” Max I. Hamburger, MD, a managing partner at Rheumatology Associates of Long Island (N.Y.), said in an interview. “Some have decided to stop the drug, and then they call us up to tell us that they’re flaring. The beginning of a flare is tiredness and other things. Now they’re worried: Are they tired because of the disease, or are they tired because they have COVID-19?”
With five office locations located in a region considered to be the epicenter of the COVID-19 pandemic in the United States, Dr. Hamburger and his colleagues are hypervigilant about screening patients for symptoms of the virus before they visit one of the three practice locations that provide infusion services. This starts with an automated phone system that reminds patients of their appointment time. “Part of that robocall now has some questions like, ‘Do you have any symptoms of COVID-19?’ ‘Are you running a fever?’ ‘Do you have any reason to worry about yourself? If so, please call us.’ ” The infusion nurses are also calling the patients in advance of their appointment to check on their status. “When they get to the office location, we ask them again about their general health and check their temperature,” said Dr. Hamburger, who is also founder and executive chairman of United Rheumatology, which is a nationwide rheumatology care management services organization with 650 members in 39 states. “We’re doing everything we can to talk to them about their own state of health and to question them about what I call extended paranoia: like, ‘Who are you living with?’ ‘Who are you hanging out with?’ ‘What are all the six degrees of separation here?’ I want to know what the patient’s husband did last night. I want to know where their kids were over this past week, et cetera. We do everything we can to see if there’s anybody who might have had the slightest [contact with someone who has COVID-19]. Because if I lose my infusion nurse, then I’m up the creek.”
The infusion nurse wears scrubs, a face mask, and latex gloves. She and her staff are using hand sanitizer and cleaning infusion equipment with sanitizing wipes as one might do in a surgical setting. “Every surface is wiped down between patients, and the nurse is changing gloves between patients,” said Dr. Hamburger, who was founding president of the New York State Rheumatology Society before retiring from that post in 2017. “Getting masks has been tough. We’re doing the best we can there. We’re not gloving patients but we’re masking patients.”
As noted in guidance from the American College of Rheumatology and other medical organizations, following the CDC’s recommendation to stay at home during the pandemic has jump-started conversations between physicians and their patients about modifying the time interval between infusions. “If they have been doing well for the last 9 months, we’re having a conversation such as ‘Maybe instead of getting your Orencia every 4 weeks, maybe we’ll push it out to 5 weeks, or maybe we’ll push the Enbrel out to 10 days and the Humira out 3 weeks, et cetera,” Dr. Hamburger said. “One has to be very careful about when you do that, because you don’t want the patient to flare up because it’s hard to get them in, but it is a natural opportunity to look at this. We’re seeing how we can optimize the dose, but I don’t want to send the message that we’re doing this because it changes the patient’s outcome, because there’s zero evidence that it’s a good thing to do in terms of resistance.”
At the infusion centers operated by the Johns Hopkins division of gastroenterology and hepatology, Baltimore, clinicians are not increasing the time interval between infusions for patients at this time. “We’re keeping them as they are, to prevent any flare-ups. Our main goal is to keep patients in remission and out of the hospital,” said Alyssa M. Parian, MD, medical director of the infusion center and associate director of the university’s GI department. “With Remicade specifically, there’s also the risk of developing antibodies if you delay treatment, so we’re basically keeping everyone on track. We’re not recommending a switch from infusions to injectables, and we also are not speeding up infusions, either. Before this pandemic happened, we had already tried to decrease all Remicade infusions from 2 hours to 1 hour for patient satisfaction. The Entyvio is a pretty quick, 30-minute infusion.”
To accommodate patients during this era of physical distancing measures recommended by the Centers for Disease Control and Prevention, Dr. Parian and her infusion nurse manager Elisheva Weiser converted one of their two outpatient GI centers into an infusion-only suite with 12 individual clinic rooms. As soon as patients exit the second-floor elevator, they encounter a workstation prior to entering the office where they are screened for COVID-19 symptoms and their temperature is taken. “If any symptoms or temperature comes back positive, we’re asking them to postpone their treatment and consider COVID testing,” she said.
Instead of one nurse looking after four patients in one room during infusion therapy, now one nurse looks after two patients who are in rooms next to each other. All patients and all staff wear masks while in the center. “We always have physician oversight at our infusion centers,” Dr. Parian said. “We are trying to maintain a ‘COVID-free zone.’ Therefore, no physicians who have served in a hospital ward are allowed in the infusion suite because we don’t want any carriers of COVID-19. Same with the nurses. Additionally, we limit the staff within the suite to only those who are essential and don’t allow anyone to perform telemedicine or urgent clinic visits in this location. Our infusion center staff are on a strict protocol to not come in with any symptoms at all. They are asked to take their temperature before coming in to work.”
She and her colleagues drew from recommendations from the joint GI society message on COVID-19, the Crohn’s and Colitis Foundation, and the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) to inform their approach in serving patients during this unprecedented time. “We went as conservative as possible because these are immunosuppressed patients,” she said. One patient on her panel who receives an infusion every 8 weeks tested positive for COVID-19 between infusions, but was not hospitalized. Dr. Parian said that person will only be treated 14 days after the all symptoms disappear. “That person will wear a mask and will be infused in a separate room,” she said.
In Aventura, Fla., Norman B. Gaylis, MD, and his colleagues at Arthritis & Rheumatic Disease Specialties are looking into shutting down their infusion services during the time period that local public health officials consider to be the peak level of exposure to COVID-19. “We’ve tried to work around that, and bring people in a little early,” said Dr. Gaylis, medical director of rheumatology and infusion services at the practice. “We’ve done our best to mitigate the risk [of exposure] as much as possible.” This includes staggering their caseload by infusing 5 patients at a time, compared with the 15 patients at a time they could treat during prepandemic conditions. “Everyone is at least 20 feet apart,” said Dr. Gaylis, who is a member of the American College of Rheumatology Board of Directors. “While we don’t have the kind of protective garments you might see in an ICU, we still are gowning, gloving, and masking our staff, and trying to practice sterile techniques as much as we can.”
The pandemic has caused him to reflect more broadly on the way he and his colleagues deliver care for patients on infusion therapy. “We see patients who really want their treatment because they feel it’s helpful and beneficial,” he said. “There are also patients who may truly be in remission who could stop [infusion therapy]. We could possibly extend the duration of their therapy, try and push it back.”
Dr. Gaylis emphasized that any discussion about halting infusion therapy requires clinical, serological, and ideally even MRI evidence that the disease is in a dormant state. “You wouldn’t stop treatment in someone who is showing signs in their blood that their disease is still active,” he said. “You’re using all those parameters in that conversation.”
In his clinical opinion, now is not the time to switch patients to self-injectable agents as a perceived matter of convenience. “I don’t really think that’s a good idea because self-injectables are different,” Dr. Gaylis said. “You’re basically switching treatment patterns. The practicality of getting a specialty pharmacy to switch, the insurance companies to cover it, and determine copay for it, is a burden on patients. That’s why I’m against it, because you’re starting a whole new process and problem.”
One patient tested positive for COVID-19 about 3 weeks after an infusion at the facility. “That does lead to a point: Have my staff been tested? We have not had the tests available to us,” Dr. Gaylis said. “One provider had a contact with someone with COVID-19 and stayed home for 2 weeks. That person tested negative. Soon we are going to receive a kit that will allow us to measure IgM and IgG COVID-19 antibodies. Because we’re going to be closed for 2 weeks, measuring us now would be a great way to handle it.”
In rural Western Kentucky, Christopher R. Phillips, MD, and his colleagues at Paducah Rheumatology have arranged for “drive-by” injections for some of their higher-risk patients who require subcutaneous administration of biologic agents. “We have them call us when they’re in the parking lot, and we give them the treatment while they sit in their car,” said Dr. Phillips, who chairs the ACR Insurance Subcommittee and is a member of the ACR COVID-19 Practice and Advocacy Task Force.
For patients who require infusions, they’ve arranged three chairs in the clinic to be at least 6 feet apart, and moved the fourth chair into a separate room. “My infusion nurse knows these patients well; we’re a small community,” he said. “She checks in with them the day before to screen for any symptoms of infection and asks them to call when they get here. A lot of them wait in their car to be brought in. She’ll bring them in, screen for infection symptoms, and check their temperature. She and the receptionist are masked and gloved, and disinfect aggressively between patients. The other thing we are trying to be on top of is making sure that everyone’s insurance coverage is active when they come in, in light of the number of people who have been laid off or had changes in their employment.”
Dr. Phillips has considered increasing the infusion time interval for some patients, but not knowing when current physical distancing guidelines will ease up presents a conundrum. “If I have a patient coming in today, and their next treatment is due in a month, I don’t know how to say that, if we stretch the infusion to 2 months, that things are going to be better,” he said. “For some very well-controlled patients and/or high-risk patients, that is something we’ve done: stretch the interval or skip a treatment. For most patients, our default is to stick with the normal schedule. We feel that, for most patients who have moderate to severe underlying rheumatic disease, the risk of disease flare and subsequent need for steroids may be a larger risk than the treatment itself, though that is an individualized decision.”
To date, Dr. Phillips has not treated a patient who has recovered from COVID-19, but the thought of that scenario gives him pause. “There is some literature suggesting these patients may asymptomatically shed virus for some time after they’ve clinically recovered, but we don’t really know enough about that,” he said. “If I had one of those patients, I’d probably be delaying them for a longer period of time, and I’d be looking for some guidance from the literature on postsymptomatic viral shedding.”
In the meantime, the level of anxiety that many of his patients express during this pandemic is palpable. “They really are between a rock and a hard place,” Dr. Phillips said. “If they come off their effective treatment, they risk flare of a disease that can be life or limb threatening. And yet, because of their disease and their treatment, they’re potentially at increased risk for serious illness if they become infected with COVID-19. We look for ways to try to reassure patients and to comfort them, and work with them to make the best of the situation.”
When to treat, delay, or omit breast cancer therapy in the face of COVID-19
Nothing is business as usual during the COVID-19 pandemic, and that includes breast cancer therapy. That’s why two groups have released guidance documents on treating breast cancer patients during the pandemic.
A guidance on surgery, drug therapy, and radiotherapy was created by the COVID-19 Pandemic Breast Cancer Consortium. This guidance is set to be published in Breast Cancer Research and Treatment and can be downloaded from the American College of Surgeons website.
A group from Memorial Sloan Kettering Cancer Center (MSKCC) created a guidance document on radiotherapy for breast cancer patients, and that guidance was recently published in Advances in Radiation Oncology.
Prioritizing certain patients and treatments
As hospital beds and clinics fill with coronavirus-infected patients, oncologists must balance the need for timely therapy for their patients with the imperative to protect vulnerable, immunosuppressed patients from exposure and keep clinical resources as free as possible.
“As we’re taking care of breast cancer patients during this unprecedented pandemic, what we’re all trying to do is balance the most effective treatments for our patients against the risk of additional exposures, either from other patients [or] from being outside, and considerations about the safety of our staff,” said Steven Isakoff, MD, PhD, of Massachusetts General Hospital Cancer Center in Boston, who is an author of the COVID-19 Pandemic Breast Cancer Consortium guidance.
The consortium’s guidance recommends prioritizing treatment according to patient needs and the disease type and stage. The three basic categories for considering when to treat are:
- Priority A: Patients who have immediately life-threatening conditions, are clinically unstable, or would experience a significant change in prognosis with even a short delay in treatment.
- Priority B: Deferring treatment for a short time (6-12 weeks) would not impact overall outcomes in these patients.
- Priority C: These patients are stable enough that treatment can be delayed for the duration of the COVID-19 pandemic.
“The consortium highly recommends multidisciplinary discussion regarding priority for elective surgery and adjuvant treatments for your breast cancer patients,” the guidance authors wrote. “The COVID-19 pandemic may vary in severity over time, and these recommendations are subject to change with changing COVID-19 pandemic severity.”
For example, depending on local circumstances, the guidance recommends limiting immediate outpatient visits to patients with potentially unstable conditions such as infection or hematoma. Established patients with new problems or patients with a new diagnosis of noninvasive cancer might be managed with telemedicine visits, and patients who are on follow-up with no new issues or who have benign lesions might have their visits safely postponed.
Surgery and drug recommendations
High-priority surgical procedures include operative drainage of a breast abscess in a septic patient and evacuation of expanding hematoma in a hemodynamically unstable patient, according to the consortium guidance.
Other surgical situations are more nuanced. For example, for patients with triple-negative breast cancer (TNBC) or HER2-positive disease, the guidance recommends neoadjuvant chemotherapy or HER2-targeted chemotherapy in some cases. In other cases, institutions may proceed with surgery before chemotherapy, but “these decisions will depend on institutional resources and patient factors,” according to the authors.
The guidance states that chemotherapy and other drug treatments should not be delayed in patients with oncologic emergencies, such as febrile neutropenia, hypercalcemia, intolerable pain, symptomatic pleural effusions, or brain metastases.
In addition, patients with inflammatory breast cancer, TNBC, or HER2-positive breast cancer should receive neoadjuvant/adjuvant chemotherapy. Patients with metastatic disease that is likely to benefit from therapy should start chemotherapy, endocrine therapy, or targeted therapy. And patients who have already started neoadjuvant/adjuvant chemotherapy or oral adjuvant endocrine therapy should continue on these treatments.
Radiation therapy recommendations
The consortium guidance recommends administering radiation to patients with bleeding or painful inoperable locoregional disease, those with symptomatic metastatic disease, and patients who progress on neoadjuvant chemotherapy.
In contrast, older patients (aged 65-70 years) with lower-risk, stage I, hormone receptor–positive, HER2-negative cancers who are on adjuvant endocrine therapy can safely defer or omit radiation without affecting their overall survival, according to the guidance. Patients with ductal carcinoma in situ, especially those with estrogen receptor–positive disease on endocrine therapy, can safely omit radiation.
“There are clearly conditions where radiation might reduce the risk of recurrence but not improve overall survival, where a delay in treatment really will have minimal or no impact,” Dr. Isakoff said.
The MSKCC guidance recommends omitting radiation for some patients with favorable-risk disease and truncating or accelerating regimens using hypofractionation for others who require whole-breast radiation or post-mastectomy treatment.
The MSKCC guidance also contains recommendations for prioritization of patients according to disease state and the urgency of care. It divides cases into high, intermediate, and low priority for breast radiotherapy, as follows:
- Tier 1 (high priority): Patients with inflammatory breast cancer, residual node-positive disease after neoadjuvant chemotherapy, four or more positive nodes (N2), recurrent disease, node-positive TNBC, or extensive lymphovascular invasion.
- Tier 2 (intermediate priority): Patients with estrogen receptor–positive disease with one to three positive nodes (N1a), pathologic stage N0 after neoadjuvant chemotherapy, lymphovascular invasion not otherwise specified, or node-negative TNBC.
- Tier 3 (low priority): Patients with early-stage estrogen receptor-positive breast cancer (especially patients of advanced age), patients with ductal carcinoma in situ, or those who otherwise do not meet the criteria for tiers 1 or 2.
The MSKCC guidance also contains recommended hypofractionated or accelerated radiotherapy regimens for partial and whole-breast irradiation, post-mastectomy treatment, and breast and regional node irradiation, including recommended techniques (for example, 3-D conformal or intensity modulated approaches).
The authors of the MSKCC guidance disclosed relationships with eContour, Volastra Therapeutics, Sanofi, the Prostate Cancer Foundation, and Cancer Research UK. The authors of the COVID-19 Pandemic Breast Cancer Consortium guidance did not disclose any conflicts and said there was no funding source for the guidance.
SOURCES: Braunstein LZ et al. Adv Radiat Oncol. 2020 Apr 1. doi:10.1016/j.adro.2020.03.013; Dietz JR et al. 2020 Apr. Recommendations for prioritization, treatment and triage of breast cancer patients during the COVID-19 pandemic. Accepted for publication in Breast Cancer Research and Treatment.
Nothing is business as usual during the COVID-19 pandemic, and that includes breast cancer therapy. That’s why two groups have released guidance documents on treating breast cancer patients during the pandemic.
A guidance on surgery, drug therapy, and radiotherapy was created by the COVID-19 Pandemic Breast Cancer Consortium. This guidance is set to be published in Breast Cancer Research and Treatment and can be downloaded from the American College of Surgeons website.
A group from Memorial Sloan Kettering Cancer Center (MSKCC) created a guidance document on radiotherapy for breast cancer patients, and that guidance was recently published in Advances in Radiation Oncology.
Prioritizing certain patients and treatments
As hospital beds and clinics fill with coronavirus-infected patients, oncologists must balance the need for timely therapy for their patients with the imperative to protect vulnerable, immunosuppressed patients from exposure and keep clinical resources as free as possible.
“As we’re taking care of breast cancer patients during this unprecedented pandemic, what we’re all trying to do is balance the most effective treatments for our patients against the risk of additional exposures, either from other patients [or] from being outside, and considerations about the safety of our staff,” said Steven Isakoff, MD, PhD, of Massachusetts General Hospital Cancer Center in Boston, who is an author of the COVID-19 Pandemic Breast Cancer Consortium guidance.
The consortium’s guidance recommends prioritizing treatment according to patient needs and the disease type and stage. The three basic categories for considering when to treat are:
- Priority A: Patients who have immediately life-threatening conditions, are clinically unstable, or would experience a significant change in prognosis with even a short delay in treatment.
- Priority B: Deferring treatment for a short time (6-12 weeks) would not impact overall outcomes in these patients.
- Priority C: These patients are stable enough that treatment can be delayed for the duration of the COVID-19 pandemic.
“The consortium highly recommends multidisciplinary discussion regarding priority for elective surgery and adjuvant treatments for your breast cancer patients,” the guidance authors wrote. “The COVID-19 pandemic may vary in severity over time, and these recommendations are subject to change with changing COVID-19 pandemic severity.”
For example, depending on local circumstances, the guidance recommends limiting immediate outpatient visits to patients with potentially unstable conditions such as infection or hematoma. Established patients with new problems or patients with a new diagnosis of noninvasive cancer might be managed with telemedicine visits, and patients who are on follow-up with no new issues or who have benign lesions might have their visits safely postponed.
Surgery and drug recommendations
High-priority surgical procedures include operative drainage of a breast abscess in a septic patient and evacuation of expanding hematoma in a hemodynamically unstable patient, according to the consortium guidance.
Other surgical situations are more nuanced. For example, for patients with triple-negative breast cancer (TNBC) or HER2-positive disease, the guidance recommends neoadjuvant chemotherapy or HER2-targeted chemotherapy in some cases. In other cases, institutions may proceed with surgery before chemotherapy, but “these decisions will depend on institutional resources and patient factors,” according to the authors.
The guidance states that chemotherapy and other drug treatments should not be delayed in patients with oncologic emergencies, such as febrile neutropenia, hypercalcemia, intolerable pain, symptomatic pleural effusions, or brain metastases.
In addition, patients with inflammatory breast cancer, TNBC, or HER2-positive breast cancer should receive neoadjuvant/adjuvant chemotherapy. Patients with metastatic disease that is likely to benefit from therapy should start chemotherapy, endocrine therapy, or targeted therapy. And patients who have already started neoadjuvant/adjuvant chemotherapy or oral adjuvant endocrine therapy should continue on these treatments.
Radiation therapy recommendations
The consortium guidance recommends administering radiation to patients with bleeding or painful inoperable locoregional disease, those with symptomatic metastatic disease, and patients who progress on neoadjuvant chemotherapy.
In contrast, older patients (aged 65-70 years) with lower-risk, stage I, hormone receptor–positive, HER2-negative cancers who are on adjuvant endocrine therapy can safely defer or omit radiation without affecting their overall survival, according to the guidance. Patients with ductal carcinoma in situ, especially those with estrogen receptor–positive disease on endocrine therapy, can safely omit radiation.
“There are clearly conditions where radiation might reduce the risk of recurrence but not improve overall survival, where a delay in treatment really will have minimal or no impact,” Dr. Isakoff said.
The MSKCC guidance recommends omitting radiation for some patients with favorable-risk disease and truncating or accelerating regimens using hypofractionation for others who require whole-breast radiation or post-mastectomy treatment.
The MSKCC guidance also contains recommendations for prioritization of patients according to disease state and the urgency of care. It divides cases into high, intermediate, and low priority for breast radiotherapy, as follows:
- Tier 1 (high priority): Patients with inflammatory breast cancer, residual node-positive disease after neoadjuvant chemotherapy, four or more positive nodes (N2), recurrent disease, node-positive TNBC, or extensive lymphovascular invasion.
- Tier 2 (intermediate priority): Patients with estrogen receptor–positive disease with one to three positive nodes (N1a), pathologic stage N0 after neoadjuvant chemotherapy, lymphovascular invasion not otherwise specified, or node-negative TNBC.
- Tier 3 (low priority): Patients with early-stage estrogen receptor-positive breast cancer (especially patients of advanced age), patients with ductal carcinoma in situ, or those who otherwise do not meet the criteria for tiers 1 or 2.
The MSKCC guidance also contains recommended hypofractionated or accelerated radiotherapy regimens for partial and whole-breast irradiation, post-mastectomy treatment, and breast and regional node irradiation, including recommended techniques (for example, 3-D conformal or intensity modulated approaches).
The authors of the MSKCC guidance disclosed relationships with eContour, Volastra Therapeutics, Sanofi, the Prostate Cancer Foundation, and Cancer Research UK. The authors of the COVID-19 Pandemic Breast Cancer Consortium guidance did not disclose any conflicts and said there was no funding source for the guidance.
SOURCES: Braunstein LZ et al. Adv Radiat Oncol. 2020 Apr 1. doi:10.1016/j.adro.2020.03.013; Dietz JR et al. 2020 Apr. Recommendations for prioritization, treatment and triage of breast cancer patients during the COVID-19 pandemic. Accepted for publication in Breast Cancer Research and Treatment.
Nothing is business as usual during the COVID-19 pandemic, and that includes breast cancer therapy. That’s why two groups have released guidance documents on treating breast cancer patients during the pandemic.
A guidance on surgery, drug therapy, and radiotherapy was created by the COVID-19 Pandemic Breast Cancer Consortium. This guidance is set to be published in Breast Cancer Research and Treatment and can be downloaded from the American College of Surgeons website.
A group from Memorial Sloan Kettering Cancer Center (MSKCC) created a guidance document on radiotherapy for breast cancer patients, and that guidance was recently published in Advances in Radiation Oncology.
Prioritizing certain patients and treatments
As hospital beds and clinics fill with coronavirus-infected patients, oncologists must balance the need for timely therapy for their patients with the imperative to protect vulnerable, immunosuppressed patients from exposure and keep clinical resources as free as possible.
“As we’re taking care of breast cancer patients during this unprecedented pandemic, what we’re all trying to do is balance the most effective treatments for our patients against the risk of additional exposures, either from other patients [or] from being outside, and considerations about the safety of our staff,” said Steven Isakoff, MD, PhD, of Massachusetts General Hospital Cancer Center in Boston, who is an author of the COVID-19 Pandemic Breast Cancer Consortium guidance.
The consortium’s guidance recommends prioritizing treatment according to patient needs and the disease type and stage. The three basic categories for considering when to treat are:
- Priority A: Patients who have immediately life-threatening conditions, are clinically unstable, or would experience a significant change in prognosis with even a short delay in treatment.
- Priority B: Deferring treatment for a short time (6-12 weeks) would not impact overall outcomes in these patients.
- Priority C: These patients are stable enough that treatment can be delayed for the duration of the COVID-19 pandemic.
“The consortium highly recommends multidisciplinary discussion regarding priority for elective surgery and adjuvant treatments for your breast cancer patients,” the guidance authors wrote. “The COVID-19 pandemic may vary in severity over time, and these recommendations are subject to change with changing COVID-19 pandemic severity.”
For example, depending on local circumstances, the guidance recommends limiting immediate outpatient visits to patients with potentially unstable conditions such as infection or hematoma. Established patients with new problems or patients with a new diagnosis of noninvasive cancer might be managed with telemedicine visits, and patients who are on follow-up with no new issues or who have benign lesions might have their visits safely postponed.
Surgery and drug recommendations
High-priority surgical procedures include operative drainage of a breast abscess in a septic patient and evacuation of expanding hematoma in a hemodynamically unstable patient, according to the consortium guidance.
Other surgical situations are more nuanced. For example, for patients with triple-negative breast cancer (TNBC) or HER2-positive disease, the guidance recommends neoadjuvant chemotherapy or HER2-targeted chemotherapy in some cases. In other cases, institutions may proceed with surgery before chemotherapy, but “these decisions will depend on institutional resources and patient factors,” according to the authors.
The guidance states that chemotherapy and other drug treatments should not be delayed in patients with oncologic emergencies, such as febrile neutropenia, hypercalcemia, intolerable pain, symptomatic pleural effusions, or brain metastases.
In addition, patients with inflammatory breast cancer, TNBC, or HER2-positive breast cancer should receive neoadjuvant/adjuvant chemotherapy. Patients with metastatic disease that is likely to benefit from therapy should start chemotherapy, endocrine therapy, or targeted therapy. And patients who have already started neoadjuvant/adjuvant chemotherapy or oral adjuvant endocrine therapy should continue on these treatments.
Radiation therapy recommendations
The consortium guidance recommends administering radiation to patients with bleeding or painful inoperable locoregional disease, those with symptomatic metastatic disease, and patients who progress on neoadjuvant chemotherapy.
In contrast, older patients (aged 65-70 years) with lower-risk, stage I, hormone receptor–positive, HER2-negative cancers who are on adjuvant endocrine therapy can safely defer or omit radiation without affecting their overall survival, according to the guidance. Patients with ductal carcinoma in situ, especially those with estrogen receptor–positive disease on endocrine therapy, can safely omit radiation.
“There are clearly conditions where radiation might reduce the risk of recurrence but not improve overall survival, where a delay in treatment really will have minimal or no impact,” Dr. Isakoff said.
The MSKCC guidance recommends omitting radiation for some patients with favorable-risk disease and truncating or accelerating regimens using hypofractionation for others who require whole-breast radiation or post-mastectomy treatment.
The MSKCC guidance also contains recommendations for prioritization of patients according to disease state and the urgency of care. It divides cases into high, intermediate, and low priority for breast radiotherapy, as follows:
- Tier 1 (high priority): Patients with inflammatory breast cancer, residual node-positive disease after neoadjuvant chemotherapy, four or more positive nodes (N2), recurrent disease, node-positive TNBC, or extensive lymphovascular invasion.
- Tier 2 (intermediate priority): Patients with estrogen receptor–positive disease with one to three positive nodes (N1a), pathologic stage N0 after neoadjuvant chemotherapy, lymphovascular invasion not otherwise specified, or node-negative TNBC.
- Tier 3 (low priority): Patients with early-stage estrogen receptor-positive breast cancer (especially patients of advanced age), patients with ductal carcinoma in situ, or those who otherwise do not meet the criteria for tiers 1 or 2.
The MSKCC guidance also contains recommended hypofractionated or accelerated radiotherapy regimens for partial and whole-breast irradiation, post-mastectomy treatment, and breast and regional node irradiation, including recommended techniques (for example, 3-D conformal or intensity modulated approaches).
The authors of the MSKCC guidance disclosed relationships with eContour, Volastra Therapeutics, Sanofi, the Prostate Cancer Foundation, and Cancer Research UK. The authors of the COVID-19 Pandemic Breast Cancer Consortium guidance did not disclose any conflicts and said there was no funding source for the guidance.
SOURCES: Braunstein LZ et al. Adv Radiat Oncol. 2020 Apr 1. doi:10.1016/j.adro.2020.03.013; Dietz JR et al. 2020 Apr. Recommendations for prioritization, treatment and triage of breast cancer patients during the COVID-19 pandemic. Accepted for publication in Breast Cancer Research and Treatment.
Biotin may benefit patients with IBD
Patients with inflammatory bowel disease (IBD) may benefit from biotin supplementation, according to a preclinical study.
In mice, biotin supplementation delayed onset of colitis, minimized pathology, and accelerated healing, reported lead author Jonathan Skupsky, MD, of the University of California, Irvine, and colleagues.
“Biotin deficiency often is overlooked in the setting of IBD and there have been several reports of biotin deficiency in patients with IBD,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.
In addition to these clinical reports, Dr. Skupsky and colleagues were motivated by their previous research, which showed that, in mice, knockout of the sodium-dependent multivitamin transporter (SMVT) for intestinal biotin uptake led to intestinal inflammation and dysplasia, thereby adding evidence that IBD and biotin could be linked.
In the present study, the investigators first compared mice fed a biotin-deficient diet with those fed a biotin-rich diet. Mice lacking biotin developed alopecia and weight loss within 7 weeks, and over time, stool that was soft and bloody. At week 14, mice fed the biotin-deficient diet had intestinal inflammation, based on elevated fecal calprotectin levels. In contrast, mice fed a biotin-rich diet had no gastrointestinal pathology.
“Although no mouse model entirely recapitulates patients with IBD, this model reproduces many of the findings including weight loss, bloody diarrhea, increased fecal calprotectin, altered crypt architecture, and infiltration of neutrophils and lymphocytes to the mucosa and submucosa,” the investigators wrote.
After this experiment, another group of mice were given drinking water with 3% dextran sodium sulfate (DSS), which induced severe colitis within 7 days. The distal colons of these mice had reduced expression of SMVT, the biotin transporter. This finding was also observed in biopsy samples from patients with ulcerative colitis, suggesting a shared pathway.
“This raises the possibility that [the biotin transport pathway] could be a target for therapy,” the investigators wrote.
Next the investigators tested the effect of prophylactic biotin supplementation in mice receiving 1.5% DSS in drinking water. Compared with mice that went without biotin, those that received a week of supplementation before DSS challenge had delayed, milder colitis, with histologic findings and fecal calprotectin levels that approximated those of healthy controls.
In a similar experiment, two groups of mice were given DSS for 7 days, then water or water plus biotin. Those in the biotin group recovered faster and more completely, again with clinical and histologic findings that was close to controls.
According to the investigators, these findings suggest that biotin may be able to protect against development of colitis and speed healing during early remission.
Further experiments dove deeper into cellular processes and molecular mechanisms, ultimately revealing that biotin supplementation reduced activation of NF-kappaB, which led to decreased intestinal permeability and inflammatory cytokines.
“The specific mechanism(s) linking biotin and NF-kappaB is unclear but could be mediated via the different cellular pathways that are affected by biotin availability,” the investigators wrote.
They noted that IBD is a complex condition, which can make it difficult to accurately model the disease; however, they also suggested that the findings are compelling enough to prompt further investigation in human patients because biotin could be a convenient therapeutic add-on.
“We are optimistic that the data presented here will serve as the foundation for future clinical studies to determine if biotin supplementation should be used as adjunct therapy in IBD,” the investigators wrote. “Biotin is available over the counter, is affordable, and it has minimal side effects, making it an ideal therapeutic if clinical trials can show similar efficacy to what we have seen in this preclinical model.
The study was funded by the Veteran’s Administration and the National Institutes of Health. The investigators reported no conflicts of interest.
SOURCE: Skupsky J et al. Cell Mol Gastroenterol Hepatol. 2019 Nov 28. doi: 10.1016/j.jcmgh.2019.11.011.
Nutrient deficiency is commonly observed in patients with inflammatory bowel disease (IBD). In fact, over half of IBD patients show deficiency in micronutrients (essential vitamins and minerals). Similarly, there are also reports of the potential negative effect of nutrient deprivation on intestinal epithelium, which could ultimately contribute to IBD. However, to date there is limited evidence supporting the notion of nutrient deficiency as a cause or an effect of IBD.
This study by Skupsky et al. highlights the role of this essential vitamin biotin in IBD pathogenesis and its potential use as a therapeutic modality in colitis. Specifically, the authors first described how biotin deficiency could lead to a colitis-like phenotype in mice and then demonstrated that deficiency of biotin was observed in a mouse model of colitis. Further, it was also shown that biotin supplementation during colitis in mice was capable of alleviating inflammation. The authors also alluded to the potential loss of the biotin transporter, a sodium-dependent multivitamin transporter (SMVT), (which was found to be down-regulated in mice with colitis, as well as in IBD patients) as one of the causative factors for biotin deficiency in IBD. However, to date, biotin deficiency has not been conclusively established in IBD patients and further systematic and well-powered studies are needed.
Since micronutrients have emerged as safe and relatively less explored agents for beneficial effects in IBD, it may be worthwhile to initiate clinical studies to examine the potential beneficial role of biotin supplementation in IBD patients.
Pradeep K. Dudeja, PhD, is professor of physiology and director, divisional scholarly activities, division of gastroenterology and hepatology, department of medicine, University of Illinois at Chicago, as well as senior research career scientist, Jesse Brown VA Medical Center, Chicago.
Nutrient deficiency is commonly observed in patients with inflammatory bowel disease (IBD). In fact, over half of IBD patients show deficiency in micronutrients (essential vitamins and minerals). Similarly, there are also reports of the potential negative effect of nutrient deprivation on intestinal epithelium, which could ultimately contribute to IBD. However, to date there is limited evidence supporting the notion of nutrient deficiency as a cause or an effect of IBD.
This study by Skupsky et al. highlights the role of this essential vitamin biotin in IBD pathogenesis and its potential use as a therapeutic modality in colitis. Specifically, the authors first described how biotin deficiency could lead to a colitis-like phenotype in mice and then demonstrated that deficiency of biotin was observed in a mouse model of colitis. Further, it was also shown that biotin supplementation during colitis in mice was capable of alleviating inflammation. The authors also alluded to the potential loss of the biotin transporter, a sodium-dependent multivitamin transporter (SMVT), (which was found to be down-regulated in mice with colitis, as well as in IBD patients) as one of the causative factors for biotin deficiency in IBD. However, to date, biotin deficiency has not been conclusively established in IBD patients and further systematic and well-powered studies are needed.
Since micronutrients have emerged as safe and relatively less explored agents for beneficial effects in IBD, it may be worthwhile to initiate clinical studies to examine the potential beneficial role of biotin supplementation in IBD patients.
Pradeep K. Dudeja, PhD, is professor of physiology and director, divisional scholarly activities, division of gastroenterology and hepatology, department of medicine, University of Illinois at Chicago, as well as senior research career scientist, Jesse Brown VA Medical Center, Chicago.
Nutrient deficiency is commonly observed in patients with inflammatory bowel disease (IBD). In fact, over half of IBD patients show deficiency in micronutrients (essential vitamins and minerals). Similarly, there are also reports of the potential negative effect of nutrient deprivation on intestinal epithelium, which could ultimately contribute to IBD. However, to date there is limited evidence supporting the notion of nutrient deficiency as a cause or an effect of IBD.
This study by Skupsky et al. highlights the role of this essential vitamin biotin in IBD pathogenesis and its potential use as a therapeutic modality in colitis. Specifically, the authors first described how biotin deficiency could lead to a colitis-like phenotype in mice and then demonstrated that deficiency of biotin was observed in a mouse model of colitis. Further, it was also shown that biotin supplementation during colitis in mice was capable of alleviating inflammation. The authors also alluded to the potential loss of the biotin transporter, a sodium-dependent multivitamin transporter (SMVT), (which was found to be down-regulated in mice with colitis, as well as in IBD patients) as one of the causative factors for biotin deficiency in IBD. However, to date, biotin deficiency has not been conclusively established in IBD patients and further systematic and well-powered studies are needed.
Since micronutrients have emerged as safe and relatively less explored agents for beneficial effects in IBD, it may be worthwhile to initiate clinical studies to examine the potential beneficial role of biotin supplementation in IBD patients.
Pradeep K. Dudeja, PhD, is professor of physiology and director, divisional scholarly activities, division of gastroenterology and hepatology, department of medicine, University of Illinois at Chicago, as well as senior research career scientist, Jesse Brown VA Medical Center, Chicago.
Patients with inflammatory bowel disease (IBD) may benefit from biotin supplementation, according to a preclinical study.
In mice, biotin supplementation delayed onset of colitis, minimized pathology, and accelerated healing, reported lead author Jonathan Skupsky, MD, of the University of California, Irvine, and colleagues.
“Biotin deficiency often is overlooked in the setting of IBD and there have been several reports of biotin deficiency in patients with IBD,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.
In addition to these clinical reports, Dr. Skupsky and colleagues were motivated by their previous research, which showed that, in mice, knockout of the sodium-dependent multivitamin transporter (SMVT) for intestinal biotin uptake led to intestinal inflammation and dysplasia, thereby adding evidence that IBD and biotin could be linked.
In the present study, the investigators first compared mice fed a biotin-deficient diet with those fed a biotin-rich diet. Mice lacking biotin developed alopecia and weight loss within 7 weeks, and over time, stool that was soft and bloody. At week 14, mice fed the biotin-deficient diet had intestinal inflammation, based on elevated fecal calprotectin levels. In contrast, mice fed a biotin-rich diet had no gastrointestinal pathology.
“Although no mouse model entirely recapitulates patients with IBD, this model reproduces many of the findings including weight loss, bloody diarrhea, increased fecal calprotectin, altered crypt architecture, and infiltration of neutrophils and lymphocytes to the mucosa and submucosa,” the investigators wrote.
After this experiment, another group of mice were given drinking water with 3% dextran sodium sulfate (DSS), which induced severe colitis within 7 days. The distal colons of these mice had reduced expression of SMVT, the biotin transporter. This finding was also observed in biopsy samples from patients with ulcerative colitis, suggesting a shared pathway.
“This raises the possibility that [the biotin transport pathway] could be a target for therapy,” the investigators wrote.
Next the investigators tested the effect of prophylactic biotin supplementation in mice receiving 1.5% DSS in drinking water. Compared with mice that went without biotin, those that received a week of supplementation before DSS challenge had delayed, milder colitis, with histologic findings and fecal calprotectin levels that approximated those of healthy controls.
In a similar experiment, two groups of mice were given DSS for 7 days, then water or water plus biotin. Those in the biotin group recovered faster and more completely, again with clinical and histologic findings that was close to controls.
According to the investigators, these findings suggest that biotin may be able to protect against development of colitis and speed healing during early remission.
Further experiments dove deeper into cellular processes and molecular mechanisms, ultimately revealing that biotin supplementation reduced activation of NF-kappaB, which led to decreased intestinal permeability and inflammatory cytokines.
“The specific mechanism(s) linking biotin and NF-kappaB is unclear but could be mediated via the different cellular pathways that are affected by biotin availability,” the investigators wrote.
They noted that IBD is a complex condition, which can make it difficult to accurately model the disease; however, they also suggested that the findings are compelling enough to prompt further investigation in human patients because biotin could be a convenient therapeutic add-on.
“We are optimistic that the data presented here will serve as the foundation for future clinical studies to determine if biotin supplementation should be used as adjunct therapy in IBD,” the investigators wrote. “Biotin is available over the counter, is affordable, and it has minimal side effects, making it an ideal therapeutic if clinical trials can show similar efficacy to what we have seen in this preclinical model.
The study was funded by the Veteran’s Administration and the National Institutes of Health. The investigators reported no conflicts of interest.
SOURCE: Skupsky J et al. Cell Mol Gastroenterol Hepatol. 2019 Nov 28. doi: 10.1016/j.jcmgh.2019.11.011.
Patients with inflammatory bowel disease (IBD) may benefit from biotin supplementation, according to a preclinical study.
In mice, biotin supplementation delayed onset of colitis, minimized pathology, and accelerated healing, reported lead author Jonathan Skupsky, MD, of the University of California, Irvine, and colleagues.
“Biotin deficiency often is overlooked in the setting of IBD and there have been several reports of biotin deficiency in patients with IBD,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.
In addition to these clinical reports, Dr. Skupsky and colleagues were motivated by their previous research, which showed that, in mice, knockout of the sodium-dependent multivitamin transporter (SMVT) for intestinal biotin uptake led to intestinal inflammation and dysplasia, thereby adding evidence that IBD and biotin could be linked.
In the present study, the investigators first compared mice fed a biotin-deficient diet with those fed a biotin-rich diet. Mice lacking biotin developed alopecia and weight loss within 7 weeks, and over time, stool that was soft and bloody. At week 14, mice fed the biotin-deficient diet had intestinal inflammation, based on elevated fecal calprotectin levels. In contrast, mice fed a biotin-rich diet had no gastrointestinal pathology.
“Although no mouse model entirely recapitulates patients with IBD, this model reproduces many of the findings including weight loss, bloody diarrhea, increased fecal calprotectin, altered crypt architecture, and infiltration of neutrophils and lymphocytes to the mucosa and submucosa,” the investigators wrote.
After this experiment, another group of mice were given drinking water with 3% dextran sodium sulfate (DSS), which induced severe colitis within 7 days. The distal colons of these mice had reduced expression of SMVT, the biotin transporter. This finding was also observed in biopsy samples from patients with ulcerative colitis, suggesting a shared pathway.
“This raises the possibility that [the biotin transport pathway] could be a target for therapy,” the investigators wrote.
Next the investigators tested the effect of prophylactic biotin supplementation in mice receiving 1.5% DSS in drinking water. Compared with mice that went without biotin, those that received a week of supplementation before DSS challenge had delayed, milder colitis, with histologic findings and fecal calprotectin levels that approximated those of healthy controls.
In a similar experiment, two groups of mice were given DSS for 7 days, then water or water plus biotin. Those in the biotin group recovered faster and more completely, again with clinical and histologic findings that was close to controls.
According to the investigators, these findings suggest that biotin may be able to protect against development of colitis and speed healing during early remission.
Further experiments dove deeper into cellular processes and molecular mechanisms, ultimately revealing that biotin supplementation reduced activation of NF-kappaB, which led to decreased intestinal permeability and inflammatory cytokines.
“The specific mechanism(s) linking biotin and NF-kappaB is unclear but could be mediated via the different cellular pathways that are affected by biotin availability,” the investigators wrote.
They noted that IBD is a complex condition, which can make it difficult to accurately model the disease; however, they also suggested that the findings are compelling enough to prompt further investigation in human patients because biotin could be a convenient therapeutic add-on.
“We are optimistic that the data presented here will serve as the foundation for future clinical studies to determine if biotin supplementation should be used as adjunct therapy in IBD,” the investigators wrote. “Biotin is available over the counter, is affordable, and it has minimal side effects, making it an ideal therapeutic if clinical trials can show similar efficacy to what we have seen in this preclinical model.
The study was funded by the Veteran’s Administration and the National Institutes of Health. The investigators reported no conflicts of interest.
SOURCE: Skupsky J et al. Cell Mol Gastroenterol Hepatol. 2019 Nov 28. doi: 10.1016/j.jcmgh.2019.11.011.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
CDC issues new return-to-work guidelines
The Centers for Disease Control and Prevention is releasing new guidance on return-to-work rules for critical workers exposed to a COVID-19 case, or a suspected case, replacing previous guidance to stay home for 14 days.
“One of the most important things we can do is keep our critical workforce working,” CDC Director Robert Redfield said at a White House briefing on April 8. “In certain circumstances they can go back to work,” he said.
Neither Redfield nor the other governmental officials specified what counts as an essential worker, although it has generally referred to food-service and health care workers.
They must take their temperature before work, wear a facial mask at all times and practice social distancing when at work, the new guidance says. They cannot share headsets or other objects used near the face.
Employers must take the worker’s temperature and assess each one for symptoms before work starts, sending a worker home if he or she is sick. Employers must increase the cleaning of frequently used surfaces, increase air exchange in the building and test the use of face masks to be sure they do not interfere with workflow.
Pressed on whether he would reopen the country at the end of the 30-day Stop the Spread effort on April 30 — since one model has revised the U.S. death toll down from 100,000-240,000 to 61,000 — President Donald Trump said meetings will take place soon to discuss the decision and that he will ‘’rely very heavily” on health experts.
“We know now for sure that the mitigation we have been doing is having a positive effect,” said Anthony Fauci, MD, a coronavirus task force member and director of the National Institute of Allergy and Infectious Diseases.
This article first appeared on WebMD.
The Centers for Disease Control and Prevention is releasing new guidance on return-to-work rules for critical workers exposed to a COVID-19 case, or a suspected case, replacing previous guidance to stay home for 14 days.
“One of the most important things we can do is keep our critical workforce working,” CDC Director Robert Redfield said at a White House briefing on April 8. “In certain circumstances they can go back to work,” he said.
Neither Redfield nor the other governmental officials specified what counts as an essential worker, although it has generally referred to food-service and health care workers.
They must take their temperature before work, wear a facial mask at all times and practice social distancing when at work, the new guidance says. They cannot share headsets or other objects used near the face.
Employers must take the worker’s temperature and assess each one for symptoms before work starts, sending a worker home if he or she is sick. Employers must increase the cleaning of frequently used surfaces, increase air exchange in the building and test the use of face masks to be sure they do not interfere with workflow.
Pressed on whether he would reopen the country at the end of the 30-day Stop the Spread effort on April 30 — since one model has revised the U.S. death toll down from 100,000-240,000 to 61,000 — President Donald Trump said meetings will take place soon to discuss the decision and that he will ‘’rely very heavily” on health experts.
“We know now for sure that the mitigation we have been doing is having a positive effect,” said Anthony Fauci, MD, a coronavirus task force member and director of the National Institute of Allergy and Infectious Diseases.
This article first appeared on WebMD.
The Centers for Disease Control and Prevention is releasing new guidance on return-to-work rules for critical workers exposed to a COVID-19 case, or a suspected case, replacing previous guidance to stay home for 14 days.
“One of the most important things we can do is keep our critical workforce working,” CDC Director Robert Redfield said at a White House briefing on April 8. “In certain circumstances they can go back to work,” he said.
Neither Redfield nor the other governmental officials specified what counts as an essential worker, although it has generally referred to food-service and health care workers.
They must take their temperature before work, wear a facial mask at all times and practice social distancing when at work, the new guidance says. They cannot share headsets or other objects used near the face.
Employers must take the worker’s temperature and assess each one for symptoms before work starts, sending a worker home if he or she is sick. Employers must increase the cleaning of frequently used surfaces, increase air exchange in the building and test the use of face masks to be sure they do not interfere with workflow.
Pressed on whether he would reopen the country at the end of the 30-day Stop the Spread effort on April 30 — since one model has revised the U.S. death toll down from 100,000-240,000 to 61,000 — President Donald Trump said meetings will take place soon to discuss the decision and that he will ‘’rely very heavily” on health experts.
“We know now for sure that the mitigation we have been doing is having a positive effect,” said Anthony Fauci, MD, a coronavirus task force member and director of the National Institute of Allergy and Infectious Diseases.
This article first appeared on WebMD.
May 2020 – ICYMI
Gastroenterology
February 2020
Gastric electrical stimulation reduces refractory vomiting in a randomized crossover trial. Philippe Ducrotte et al. 2020 Feb;158(3):506-14.e2. doi: 10.1053/j.gastro.2019.10.018
Efficacy and safety of vedolizumab subcutaneous formulation in a randomized trial of patients with ulcerative colitis. William J. Sandborn et al. 2020 Feb;158(3)562-72.e12. doi: 10.1053/j.gastro.2019.08.027
AGA Clinical Practice Guidelines on management of gastric intestinal metaplasia. Samir Gupta et al. 2020 Feb;158(3):693-702. doi: 10.1053/j.gastro.2019.12.003
March 2020
Approaches and challenges to management of pediatric and adult patients with eosinophilic esophagitis. Ikuo Hirano, Glenn T. Furuta. 2020 Mar;158(4):840-51. doi: 10.1053/j.gastro.2019.09.052
Uptake of colorectal cancer screening by physicians is associated with greater uptake by their patients. Owen Litwin et al. 2020 Mar;158(4):905-14. doi: 10.1053/j.gastro.2019.10.027
Recommendations for follow-up after colonoscopy and polypectomy: A consensus update by the US Multi-Society Task Force on Colorectal Cancer. Samir Gupta et al. 2020 Mar;158(4):1131-53.e5. doi: 10.1053/j.gastro.2019.10.026
Differences in fecal microbiomes and metabolomes of people with vs without irritable bowel syndrome and bile acid malabsorption. Ian B. Jeffery et al. 2020 Mar;158(4):1016-28.e8. doi: 10.1053/j.gastro.2019.11.301
April 2020
How to set up a successful motility lab. Rena Yadlapati et al. 2020 April;158(5):1202-10. doi: 10.1053/j.gastro.2020.01.030
Mechanisms, evaluation, and management of chronic constipation. Adil E. Bharucha, Brian E. Lacy. 2020 April;158(5):1232-49.e3. doi: 10.1053/j.gastro.2019.12.034.
Incidence of venous thromboembolism in patients with newly diagnosed pancreatic cancer and factors associated with outcomes. Corinne Frere et al. 2020 April;158(5):1346-58.e4. doi: 10.1053/j.gastro.2019.12.009
Clinical Gastroenterology and Hepatology
February 2020
Increased incidence and mortality of gastric cancer in immigrant populations from high to low regions of incidence: A systematic review and meta-analysis. Baldeep S. Pabla et al. 2020 Feb;18(2):347-59.e5. doi: 10.1016/j.cgh.2019.05.032
Risk of gastrointestinal bleeding increases with combinations of antithrombotic agents and patient age. Neena S. Abraham et al. 2020 Feb;18(2):337-46.e19. doi: 10.1016/j.cgh.2019.05.017
Alcohol rehabilitation within 30 days of hospital discharge is associated with reduced readmission, relapse, and death in patients with alcoholic hepatitis. Thoetchai (Bee) Peeraphatdit et al. 2020 Feb;18(2):477-85.e5. doi: 10.1016/j.cgh.2019.04.048
March 2020
Telemedicine in gastroenterology: A value-added service for patients. Theresa Lee, Lawrence Kim. 2020 Mar;18(3):530-3. doi: 10.1016/j.cgh.2019.12.005
Best practices in teaching endoscopy based on a Delphi survey of gastroenterology program directors and experts in endoscopy education. Navin L. Kumar et al. 2020 Mar;18(3):574-9.e1. doi: 10.1016/j.cgh.2019.05.023
Consumption of fish and long-chain n-3 polyunsaturated fatty acids is associated with reduced risk of colorectal cancer in a large European cohort. Elom K. Aglago et al. 2020 Mar;18(3):654-66.e6. doi: 10.1016/j.cgh.2019.06.031
April 2020
Low incidence of aerodigestive cancers in patients with negative results from colonoscopies, regardless of findings from multitarget stool DNA tests. Barry M. Berger et al. 2020 April;18(4):864-71. doi: 10.1016/j.cgh.2019.07.057
Lifetime economic burden of Crohn’s disease and ulcerative colitis by age at diagnosis. Gary R. Lichtenstein et al. 2020 April;18(4):889-97.e10. doi: 10.1016/j.cgh.2019.07.022
Clinical and Molecular Gastroenterology and Hepatology
Etiopathogenetic mechanisms in diverticular disease of the colon. Michael Camilleri et al. 2020;9(1):15-32. doi: 10.1016/j.jcmgh.2019.07.007
Gastroenterology
February 2020
Gastric electrical stimulation reduces refractory vomiting in a randomized crossover trial. Philippe Ducrotte et al. 2020 Feb;158(3):506-14.e2. doi: 10.1053/j.gastro.2019.10.018
Efficacy and safety of vedolizumab subcutaneous formulation in a randomized trial of patients with ulcerative colitis. William J. Sandborn et al. 2020 Feb;158(3)562-72.e12. doi: 10.1053/j.gastro.2019.08.027
AGA Clinical Practice Guidelines on management of gastric intestinal metaplasia. Samir Gupta et al. 2020 Feb;158(3):693-702. doi: 10.1053/j.gastro.2019.12.003
March 2020
Approaches and challenges to management of pediatric and adult patients with eosinophilic esophagitis. Ikuo Hirano, Glenn T. Furuta. 2020 Mar;158(4):840-51. doi: 10.1053/j.gastro.2019.09.052
Uptake of colorectal cancer screening by physicians is associated with greater uptake by their patients. Owen Litwin et al. 2020 Mar;158(4):905-14. doi: 10.1053/j.gastro.2019.10.027
Recommendations for follow-up after colonoscopy and polypectomy: A consensus update by the US Multi-Society Task Force on Colorectal Cancer. Samir Gupta et al. 2020 Mar;158(4):1131-53.e5. doi: 10.1053/j.gastro.2019.10.026
Differences in fecal microbiomes and metabolomes of people with vs without irritable bowel syndrome and bile acid malabsorption. Ian B. Jeffery et al. 2020 Mar;158(4):1016-28.e8. doi: 10.1053/j.gastro.2019.11.301
April 2020
How to set up a successful motility lab. Rena Yadlapati et al. 2020 April;158(5):1202-10. doi: 10.1053/j.gastro.2020.01.030
Mechanisms, evaluation, and management of chronic constipation. Adil E. Bharucha, Brian E. Lacy. 2020 April;158(5):1232-49.e3. doi: 10.1053/j.gastro.2019.12.034.
Incidence of venous thromboembolism in patients with newly diagnosed pancreatic cancer and factors associated with outcomes. Corinne Frere et al. 2020 April;158(5):1346-58.e4. doi: 10.1053/j.gastro.2019.12.009
Clinical Gastroenterology and Hepatology
February 2020
Increased incidence and mortality of gastric cancer in immigrant populations from high to low regions of incidence: A systematic review and meta-analysis. Baldeep S. Pabla et al. 2020 Feb;18(2):347-59.e5. doi: 10.1016/j.cgh.2019.05.032
Risk of gastrointestinal bleeding increases with combinations of antithrombotic agents and patient age. Neena S. Abraham et al. 2020 Feb;18(2):337-46.e19. doi: 10.1016/j.cgh.2019.05.017
Alcohol rehabilitation within 30 days of hospital discharge is associated with reduced readmission, relapse, and death in patients with alcoholic hepatitis. Thoetchai (Bee) Peeraphatdit et al. 2020 Feb;18(2):477-85.e5. doi: 10.1016/j.cgh.2019.04.048
March 2020
Telemedicine in gastroenterology: A value-added service for patients. Theresa Lee, Lawrence Kim. 2020 Mar;18(3):530-3. doi: 10.1016/j.cgh.2019.12.005
Best practices in teaching endoscopy based on a Delphi survey of gastroenterology program directors and experts in endoscopy education. Navin L. Kumar et al. 2020 Mar;18(3):574-9.e1. doi: 10.1016/j.cgh.2019.05.023
Consumption of fish and long-chain n-3 polyunsaturated fatty acids is associated with reduced risk of colorectal cancer in a large European cohort. Elom K. Aglago et al. 2020 Mar;18(3):654-66.e6. doi: 10.1016/j.cgh.2019.06.031
April 2020
Low incidence of aerodigestive cancers in patients with negative results from colonoscopies, regardless of findings from multitarget stool DNA tests. Barry M. Berger et al. 2020 April;18(4):864-71. doi: 10.1016/j.cgh.2019.07.057
Lifetime economic burden of Crohn’s disease and ulcerative colitis by age at diagnosis. Gary R. Lichtenstein et al. 2020 April;18(4):889-97.e10. doi: 10.1016/j.cgh.2019.07.022
Clinical and Molecular Gastroenterology and Hepatology
Etiopathogenetic mechanisms in diverticular disease of the colon. Michael Camilleri et al. 2020;9(1):15-32. doi: 10.1016/j.jcmgh.2019.07.007
Gastroenterology
February 2020
Gastric electrical stimulation reduces refractory vomiting in a randomized crossover trial. Philippe Ducrotte et al. 2020 Feb;158(3):506-14.e2. doi: 10.1053/j.gastro.2019.10.018
Efficacy and safety of vedolizumab subcutaneous formulation in a randomized trial of patients with ulcerative colitis. William J. Sandborn et al. 2020 Feb;158(3)562-72.e12. doi: 10.1053/j.gastro.2019.08.027
AGA Clinical Practice Guidelines on management of gastric intestinal metaplasia. Samir Gupta et al. 2020 Feb;158(3):693-702. doi: 10.1053/j.gastro.2019.12.003
March 2020
Approaches and challenges to management of pediatric and adult patients with eosinophilic esophagitis. Ikuo Hirano, Glenn T. Furuta. 2020 Mar;158(4):840-51. doi: 10.1053/j.gastro.2019.09.052
Uptake of colorectal cancer screening by physicians is associated with greater uptake by their patients. Owen Litwin et al. 2020 Mar;158(4):905-14. doi: 10.1053/j.gastro.2019.10.027
Recommendations for follow-up after colonoscopy and polypectomy: A consensus update by the US Multi-Society Task Force on Colorectal Cancer. Samir Gupta et al. 2020 Mar;158(4):1131-53.e5. doi: 10.1053/j.gastro.2019.10.026
Differences in fecal microbiomes and metabolomes of people with vs without irritable bowel syndrome and bile acid malabsorption. Ian B. Jeffery et al. 2020 Mar;158(4):1016-28.e8. doi: 10.1053/j.gastro.2019.11.301
April 2020
How to set up a successful motility lab. Rena Yadlapati et al. 2020 April;158(5):1202-10. doi: 10.1053/j.gastro.2020.01.030
Mechanisms, evaluation, and management of chronic constipation. Adil E. Bharucha, Brian E. Lacy. 2020 April;158(5):1232-49.e3. doi: 10.1053/j.gastro.2019.12.034.
Incidence of venous thromboembolism in patients with newly diagnosed pancreatic cancer and factors associated with outcomes. Corinne Frere et al. 2020 April;158(5):1346-58.e4. doi: 10.1053/j.gastro.2019.12.009
Clinical Gastroenterology and Hepatology
February 2020
Increased incidence and mortality of gastric cancer in immigrant populations from high to low regions of incidence: A systematic review and meta-analysis. Baldeep S. Pabla et al. 2020 Feb;18(2):347-59.e5. doi: 10.1016/j.cgh.2019.05.032
Risk of gastrointestinal bleeding increases with combinations of antithrombotic agents and patient age. Neena S. Abraham et al. 2020 Feb;18(2):337-46.e19. doi: 10.1016/j.cgh.2019.05.017
Alcohol rehabilitation within 30 days of hospital discharge is associated with reduced readmission, relapse, and death in patients with alcoholic hepatitis. Thoetchai (Bee) Peeraphatdit et al. 2020 Feb;18(2):477-85.e5. doi: 10.1016/j.cgh.2019.04.048
March 2020
Telemedicine in gastroenterology: A value-added service for patients. Theresa Lee, Lawrence Kim. 2020 Mar;18(3):530-3. doi: 10.1016/j.cgh.2019.12.005
Best practices in teaching endoscopy based on a Delphi survey of gastroenterology program directors and experts in endoscopy education. Navin L. Kumar et al. 2020 Mar;18(3):574-9.e1. doi: 10.1016/j.cgh.2019.05.023
Consumption of fish and long-chain n-3 polyunsaturated fatty acids is associated with reduced risk of colorectal cancer in a large European cohort. Elom K. Aglago et al. 2020 Mar;18(3):654-66.e6. doi: 10.1016/j.cgh.2019.06.031
April 2020
Low incidence of aerodigestive cancers in patients with negative results from colonoscopies, regardless of findings from multitarget stool DNA tests. Barry M. Berger et al. 2020 April;18(4):864-71. doi: 10.1016/j.cgh.2019.07.057
Lifetime economic burden of Crohn’s disease and ulcerative colitis by age at diagnosis. Gary R. Lichtenstein et al. 2020 April;18(4):889-97.e10. doi: 10.1016/j.cgh.2019.07.022
Clinical and Molecular Gastroenterology and Hepatology
Etiopathogenetic mechanisms in diverticular disease of the colon. Michael Camilleri et al. 2020;9(1):15-32. doi: 10.1016/j.jcmgh.2019.07.007
With mild or stable lupus, few patients flare during, after pregnancy
Approximately 26% of women with inactive or mild lupus at conception experienced flares at some point during pregnancy, based on data from 384 patients.
Active systemic lupus erythematosus (SLE) is a known predictor of poor pregnancy outcomes, including preterm birth, growth restriction, and fetal loss, but predictors of flares during and after pregnancy in women with SLE have not been well studied, wrote Julia Davis-Porada, MD, of the Hospital for Special Surgery, New York, and her colleagues.
In a study published in Arthritis Research & Therapy, the investigators reviewed data from the PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study, a prospective study of pregnant women aged 18-45 years. The women were enrolled at less than 12 weeks’ gestation, and participants had a baseline hematocrit greater than 26%. Participants met criteria for inactive or mild/stable disease at the time of conception.
Overall, 20.8% of patients experienced at least one mild or moderate flare and 6.25% had one or more severe flares during pregnancy. Mild to moderate flares and severe flares occurred postpartum (2-6 months after the end of pregnancy) in 22.7% and 1.7% of patients, respectively.
Patients who were younger and those who had lower C4 at baseline and higher Physician Global Assessment scores at baseline were significantly more likely to have at least one flare during pregnancy (P = .003, P = .024, P = .0005, respectively).
In the analysis of postpartum flares, the incidence rates for mild to moderate and severe flares were 0.8 and 0.06 per person-year, respectively. “In contrast to the findings observed for flares that occurred during pregnancy, baseline patient characteristics were not correlated with postpartum flares,” the researchers wrote.
No medications were associated with flares during or after pregnancy.
The study findings were limited by several factors, including the exclusion of SLE patients with current nephritis and those who needed high-dose prednisone; the potential for missed flares; and the lack of postpartum data for approximately 10% of patients, the researchers noted. Also, “since many patients presented to this study only after conception, we have no data to review disease activity prior to pregnancy to determine whether pregnancy per se increased the risk for flare,” they said.
However, the results were strengthened by the large, multiethnic population and prospective study design, and support physicians in reassuring patients with SLE that pregnancy and postpartum flares are unlikely if they plan pregnancy during a time of mild or inactive disease, they concluded.
The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The researchers had no financial conflicts to disclose.
SOURCE: Davis-Porada J et al. Arthritis Res Ther. 2020 Mar 19. doi: 10.1186/s13075-020-2139-9.
Approximately 26% of women with inactive or mild lupus at conception experienced flares at some point during pregnancy, based on data from 384 patients.
Active systemic lupus erythematosus (SLE) is a known predictor of poor pregnancy outcomes, including preterm birth, growth restriction, and fetal loss, but predictors of flares during and after pregnancy in women with SLE have not been well studied, wrote Julia Davis-Porada, MD, of the Hospital for Special Surgery, New York, and her colleagues.
In a study published in Arthritis Research & Therapy, the investigators reviewed data from the PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study, a prospective study of pregnant women aged 18-45 years. The women were enrolled at less than 12 weeks’ gestation, and participants had a baseline hematocrit greater than 26%. Participants met criteria for inactive or mild/stable disease at the time of conception.
Overall, 20.8% of patients experienced at least one mild or moderate flare and 6.25% had one or more severe flares during pregnancy. Mild to moderate flares and severe flares occurred postpartum (2-6 months after the end of pregnancy) in 22.7% and 1.7% of patients, respectively.
Patients who were younger and those who had lower C4 at baseline and higher Physician Global Assessment scores at baseline were significantly more likely to have at least one flare during pregnancy (P = .003, P = .024, P = .0005, respectively).
In the analysis of postpartum flares, the incidence rates for mild to moderate and severe flares were 0.8 and 0.06 per person-year, respectively. “In contrast to the findings observed for flares that occurred during pregnancy, baseline patient characteristics were not correlated with postpartum flares,” the researchers wrote.
No medications were associated with flares during or after pregnancy.
The study findings were limited by several factors, including the exclusion of SLE patients with current nephritis and those who needed high-dose prednisone; the potential for missed flares; and the lack of postpartum data for approximately 10% of patients, the researchers noted. Also, “since many patients presented to this study only after conception, we have no data to review disease activity prior to pregnancy to determine whether pregnancy per se increased the risk for flare,” they said.
However, the results were strengthened by the large, multiethnic population and prospective study design, and support physicians in reassuring patients with SLE that pregnancy and postpartum flares are unlikely if they plan pregnancy during a time of mild or inactive disease, they concluded.
The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The researchers had no financial conflicts to disclose.
SOURCE: Davis-Porada J et al. Arthritis Res Ther. 2020 Mar 19. doi: 10.1186/s13075-020-2139-9.
Approximately 26% of women with inactive or mild lupus at conception experienced flares at some point during pregnancy, based on data from 384 patients.
Active systemic lupus erythematosus (SLE) is a known predictor of poor pregnancy outcomes, including preterm birth, growth restriction, and fetal loss, but predictors of flares during and after pregnancy in women with SLE have not been well studied, wrote Julia Davis-Porada, MD, of the Hospital for Special Surgery, New York, and her colleagues.
In a study published in Arthritis Research & Therapy, the investigators reviewed data from the PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study, a prospective study of pregnant women aged 18-45 years. The women were enrolled at less than 12 weeks’ gestation, and participants had a baseline hematocrit greater than 26%. Participants met criteria for inactive or mild/stable disease at the time of conception.
Overall, 20.8% of patients experienced at least one mild or moderate flare and 6.25% had one or more severe flares during pregnancy. Mild to moderate flares and severe flares occurred postpartum (2-6 months after the end of pregnancy) in 22.7% and 1.7% of patients, respectively.
Patients who were younger and those who had lower C4 at baseline and higher Physician Global Assessment scores at baseline were significantly more likely to have at least one flare during pregnancy (P = .003, P = .024, P = .0005, respectively).
In the analysis of postpartum flares, the incidence rates for mild to moderate and severe flares were 0.8 and 0.06 per person-year, respectively. “In contrast to the findings observed for flares that occurred during pregnancy, baseline patient characteristics were not correlated with postpartum flares,” the researchers wrote.
No medications were associated with flares during or after pregnancy.
The study findings were limited by several factors, including the exclusion of SLE patients with current nephritis and those who needed high-dose prednisone; the potential for missed flares; and the lack of postpartum data for approximately 10% of patients, the researchers noted. Also, “since many patients presented to this study only after conception, we have no data to review disease activity prior to pregnancy to determine whether pregnancy per se increased the risk for flare,” they said.
However, the results were strengthened by the large, multiethnic population and prospective study design, and support physicians in reassuring patients with SLE that pregnancy and postpartum flares are unlikely if they plan pregnancy during a time of mild or inactive disease, they concluded.
The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The researchers had no financial conflicts to disclose.
SOURCE: Davis-Porada J et al. Arthritis Res Ther. 2020 Mar 19. doi: 10.1186/s13075-020-2139-9.
FROM ARTHRITIS RESEARCH & THERAPY
Low-risk TAVR loses ground at 2 years in PARTNER 3
Transcatheter aortic valve replacement (TAVR) continued to show superiority over surgical replacement in terms of the primary composite endpoint in low-surgical-risk patients at 2 years of follow-up in the landmark randomized PARTNER 3 trial, but the between-group differences favoring the transcatheter procedure in some key outcomes have narrowed considerably, Michael J. Mack, MD, reported in a video presentation of his research during the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.
“On the basis of 1-year data, many physicians were counseling patients that TAVR outcomes were better than surgery. Now we see that the outcomes are roughly the same at 2 years,” said Dr. Mack, who is medical director of cardiothoracic surgery and chairman of the Baylor Scott & White The Heart Hospital – Plano (Tex.) Research Center.
PARTNER 3 randomized 1,000 patients with severe symptomatic aortic stenosis with a tricuspid valve and a very low mean Society of Thoracic Surgeons risk score of 1.9% to TAVR with the Sapien 3 valve or surgical aortic valve replacement (SAVR). The 1-year results presented at ACC 2019 caused a huge stir, with the primary composite outcome of death, stroke, or cardiovascular rehospitalization occurring in 8.5% of TAVR patients and 15.6% of the SAVR group, representing a 48% relative risk reduction and a resounding win for TAVR (N Engl J Med. 2019 May 2;380:1695-705). At 2 years, the difference in the composite outcome remained statistically significant, but the gap had closed: 11.5% with TAVR and 17.4% with SAVR for a 37% relative risk reduction.
Moreover, the between-group difference in stroke, which at 1 year was significantly in favor of TAVR at 1.2% versus 3.3%, was no longer significant at 2 years, with rates of 2.4% versus 3.6%. Nor was the difference in mortality significant: 2.4% with TAVR, 3.2% with SAVR.
What was a statistically significant between-group difference at 2 years – and an eye-catching one at that – involved the cumulative incidence of valve thrombosis confirmed by CT or echocardiography: 2.6% in the TAVR arm, compared with 0.7% with SAVR, with most of these unwanted events coming in year 2.
The good news was there was no echocardiographic evidence of deterioration in valve structure or function in either study arm at 2 years. The mean gradients and aortic valve areas remained unchanged in both arms between 1 and 2 years, as did the frequency of mild or moderate paravalvular leak. Prospective follow-up will continue annually out to 10 years.
“I think it’s way too early to expect to see a signal, but I think it’s somewhat comforting at this point that there’s no signal of early structural valve deterioration,” Dr. Mack said.
Discussant Howard C. Hermann, MD, commented: “I guess the biggest concern in looking at the data is the increase in stroke and valve thrombosis, both numerically and relative to SAVR, between years 1 and 2.”
Dr. Mack offered a note of reassurance regarding the valve thrombosis findings: The rates he presented were based upon the now-outdated second Valve Academic Research Consortium (VARC-2) definition, per study protocol. When he and his coinvestigators recalculated the valve thrombosis rates using the contemporary VARC-3 definition of valve deterioration and bioprosthetic valve failure, the incidence was very low and not significantly different in the two study arms, at roughly 1%.
Dr. Hermann, professor of medicine and director of the cardiac catheterization laboratories at the University of Pennsylvania, Philadelphia, had a question: As a clinician taking care of TAVR patients, what clinical or hemodynamic findings should prompt an imaging study looking for valve thrombus or deterioration that might prompt initiating oral anticoagulation?
“If there’s a change in hemodynamics, an increasing valve gradient, if there’s increasing paravalvular leak, or if there’s a change in symptoms, that should prompt an imaging study. Only with confirmation of valve thrombosis on an imaging study should anticoagulation be considered. Oral anticoagulation is not benign: Of the six clinical events associated with valve thrombosis in the study, two were related to anticoagulation,” Dr. Mack replied.
“Regarding whether patients should receive warfarin or a novel anticoagulant, I don’t think we have evidence that there’s benefit to anything other than warfarin at the current time,” he added.
Dr. Mack reported receiving research support from Edwards Lifesciences, the sponsor of PARTNER 3, as well as from Abbott, Gore, and Medtronic.
Transcatheter aortic valve replacement (TAVR) continued to show superiority over surgical replacement in terms of the primary composite endpoint in low-surgical-risk patients at 2 years of follow-up in the landmark randomized PARTNER 3 trial, but the between-group differences favoring the transcatheter procedure in some key outcomes have narrowed considerably, Michael J. Mack, MD, reported in a video presentation of his research during the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.
“On the basis of 1-year data, many physicians were counseling patients that TAVR outcomes were better than surgery. Now we see that the outcomes are roughly the same at 2 years,” said Dr. Mack, who is medical director of cardiothoracic surgery and chairman of the Baylor Scott & White The Heart Hospital – Plano (Tex.) Research Center.
PARTNER 3 randomized 1,000 patients with severe symptomatic aortic stenosis with a tricuspid valve and a very low mean Society of Thoracic Surgeons risk score of 1.9% to TAVR with the Sapien 3 valve or surgical aortic valve replacement (SAVR). The 1-year results presented at ACC 2019 caused a huge stir, with the primary composite outcome of death, stroke, or cardiovascular rehospitalization occurring in 8.5% of TAVR patients and 15.6% of the SAVR group, representing a 48% relative risk reduction and a resounding win for TAVR (N Engl J Med. 2019 May 2;380:1695-705). At 2 years, the difference in the composite outcome remained statistically significant, but the gap had closed: 11.5% with TAVR and 17.4% with SAVR for a 37% relative risk reduction.
Moreover, the between-group difference in stroke, which at 1 year was significantly in favor of TAVR at 1.2% versus 3.3%, was no longer significant at 2 years, with rates of 2.4% versus 3.6%. Nor was the difference in mortality significant: 2.4% with TAVR, 3.2% with SAVR.
What was a statistically significant between-group difference at 2 years – and an eye-catching one at that – involved the cumulative incidence of valve thrombosis confirmed by CT or echocardiography: 2.6% in the TAVR arm, compared with 0.7% with SAVR, with most of these unwanted events coming in year 2.
The good news was there was no echocardiographic evidence of deterioration in valve structure or function in either study arm at 2 years. The mean gradients and aortic valve areas remained unchanged in both arms between 1 and 2 years, as did the frequency of mild or moderate paravalvular leak. Prospective follow-up will continue annually out to 10 years.
“I think it’s way too early to expect to see a signal, but I think it’s somewhat comforting at this point that there’s no signal of early structural valve deterioration,” Dr. Mack said.
Discussant Howard C. Hermann, MD, commented: “I guess the biggest concern in looking at the data is the increase in stroke and valve thrombosis, both numerically and relative to SAVR, between years 1 and 2.”
Dr. Mack offered a note of reassurance regarding the valve thrombosis findings: The rates he presented were based upon the now-outdated second Valve Academic Research Consortium (VARC-2) definition, per study protocol. When he and his coinvestigators recalculated the valve thrombosis rates using the contemporary VARC-3 definition of valve deterioration and bioprosthetic valve failure, the incidence was very low and not significantly different in the two study arms, at roughly 1%.
Dr. Hermann, professor of medicine and director of the cardiac catheterization laboratories at the University of Pennsylvania, Philadelphia, had a question: As a clinician taking care of TAVR patients, what clinical or hemodynamic findings should prompt an imaging study looking for valve thrombus or deterioration that might prompt initiating oral anticoagulation?
“If there’s a change in hemodynamics, an increasing valve gradient, if there’s increasing paravalvular leak, or if there’s a change in symptoms, that should prompt an imaging study. Only with confirmation of valve thrombosis on an imaging study should anticoagulation be considered. Oral anticoagulation is not benign: Of the six clinical events associated with valve thrombosis in the study, two were related to anticoagulation,” Dr. Mack replied.
“Regarding whether patients should receive warfarin or a novel anticoagulant, I don’t think we have evidence that there’s benefit to anything other than warfarin at the current time,” he added.
Dr. Mack reported receiving research support from Edwards Lifesciences, the sponsor of PARTNER 3, as well as from Abbott, Gore, and Medtronic.
Transcatheter aortic valve replacement (TAVR) continued to show superiority over surgical replacement in terms of the primary composite endpoint in low-surgical-risk patients at 2 years of follow-up in the landmark randomized PARTNER 3 trial, but the between-group differences favoring the transcatheter procedure in some key outcomes have narrowed considerably, Michael J. Mack, MD, reported in a video presentation of his research during the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.
“On the basis of 1-year data, many physicians were counseling patients that TAVR outcomes were better than surgery. Now we see that the outcomes are roughly the same at 2 years,” said Dr. Mack, who is medical director of cardiothoracic surgery and chairman of the Baylor Scott & White The Heart Hospital – Plano (Tex.) Research Center.
PARTNER 3 randomized 1,000 patients with severe symptomatic aortic stenosis with a tricuspid valve and a very low mean Society of Thoracic Surgeons risk score of 1.9% to TAVR with the Sapien 3 valve or surgical aortic valve replacement (SAVR). The 1-year results presented at ACC 2019 caused a huge stir, with the primary composite outcome of death, stroke, or cardiovascular rehospitalization occurring in 8.5% of TAVR patients and 15.6% of the SAVR group, representing a 48% relative risk reduction and a resounding win for TAVR (N Engl J Med. 2019 May 2;380:1695-705). At 2 years, the difference in the composite outcome remained statistically significant, but the gap had closed: 11.5% with TAVR and 17.4% with SAVR for a 37% relative risk reduction.
Moreover, the between-group difference in stroke, which at 1 year was significantly in favor of TAVR at 1.2% versus 3.3%, was no longer significant at 2 years, with rates of 2.4% versus 3.6%. Nor was the difference in mortality significant: 2.4% with TAVR, 3.2% with SAVR.
What was a statistically significant between-group difference at 2 years – and an eye-catching one at that – involved the cumulative incidence of valve thrombosis confirmed by CT or echocardiography: 2.6% in the TAVR arm, compared with 0.7% with SAVR, with most of these unwanted events coming in year 2.
The good news was there was no echocardiographic evidence of deterioration in valve structure or function in either study arm at 2 years. The mean gradients and aortic valve areas remained unchanged in both arms between 1 and 2 years, as did the frequency of mild or moderate paravalvular leak. Prospective follow-up will continue annually out to 10 years.
“I think it’s way too early to expect to see a signal, but I think it’s somewhat comforting at this point that there’s no signal of early structural valve deterioration,” Dr. Mack said.
Discussant Howard C. Hermann, MD, commented: “I guess the biggest concern in looking at the data is the increase in stroke and valve thrombosis, both numerically and relative to SAVR, between years 1 and 2.”
Dr. Mack offered a note of reassurance regarding the valve thrombosis findings: The rates he presented were based upon the now-outdated second Valve Academic Research Consortium (VARC-2) definition, per study protocol. When he and his coinvestigators recalculated the valve thrombosis rates using the contemporary VARC-3 definition of valve deterioration and bioprosthetic valve failure, the incidence was very low and not significantly different in the two study arms, at roughly 1%.
Dr. Hermann, professor of medicine and director of the cardiac catheterization laboratories at the University of Pennsylvania, Philadelphia, had a question: As a clinician taking care of TAVR patients, what clinical or hemodynamic findings should prompt an imaging study looking for valve thrombus or deterioration that might prompt initiating oral anticoagulation?
“If there’s a change in hemodynamics, an increasing valve gradient, if there’s increasing paravalvular leak, or if there’s a change in symptoms, that should prompt an imaging study. Only with confirmation of valve thrombosis on an imaging study should anticoagulation be considered. Oral anticoagulation is not benign: Of the six clinical events associated with valve thrombosis in the study, two were related to anticoagulation,” Dr. Mack replied.
“Regarding whether patients should receive warfarin or a novel anticoagulant, I don’t think we have evidence that there’s benefit to anything other than warfarin at the current time,” he added.
Dr. Mack reported receiving research support from Edwards Lifesciences, the sponsor of PARTNER 3, as well as from Abbott, Gore, and Medtronic.
FROM ACC 2020
Fellowship Burnout: What can we do to identify those at risk and minimize the impact?
Jeff is a high-performing first-year gastroenterology fellow who started with eagerness and enthusiasm. He seemed to enjoy talking to patients, wrote thorough notes, and often participated during case discussions at morning report. He initiated a quality improvement project and joined a hospital committee. Over the past few months, he has interacted less with his peers in the fellow’s office and stayed late to complete his patient encounters. He now frequently arrives late to work, is unprepared for rounds, and forgets to place important orders. One day, you notice him shuffling through several papers when the attending asks him a question about his patient. Later that day, he snapped at a nurse who paged to ask a question about a patient who just had a colonoscopy. When you ask him how he is doing, he becomes tearful and reports that he is under a lot of stress between work and home and does not feel the work he is doing is meaningful.
Introduction
The above scenario is all too familiar. Gastroenterology training can be a stressful period in an individual’s life. Long hours, steep learning curves for new cognitive and mechanical skill sets, as well as managing personal relationships and responsibilities at home all contribute to the stress of training and finding appropriate work-life balance. These stressors can result in burnout. The last decade has brought about a renewed emphasis on mitigating the impact of occupational burnout and improving trainee lifestyle through interventions such as work-hour restrictions, resiliency training, instruction on the importance of sleep, and team-building activities.
The problem
The World Health Organization (WHO) defines occupational burnout as chronic work-related stress, which may be characterized by feelings of energy depletion, mental distance from one’s job or feelings of negativity toward it, and reduced professional efficacy. Occupational burnout has been identified as an increasing problem both in practicing providers and trainees. Surveys in gastroenterologists show rates of burnout ranging between 37% and 50%,1 with trainees and early-career physicians disproportionately affected.1,2Physicians along the entire training spectrum are more likely to report high emotional exhaustion, high depersonalization, and burnout than a population control sample.2
Several individual factors identified for those at increased risk for burnout include younger age, not being married, and being male.2 Individuals spending less than 20% of their time working on activities they find meaningful and productive were more likely to show evidence of burnout.1
Symptoms of burnout can have a profound impact on trainees’ work performance, personal interactions, and the learning environment as a whole. The Accreditation Council for Graduate Medical Education (ACGME) annual survey of trainees asks them how strongly they agree or disagree on various components of burnout such as how meaningful they find their work, if they have enough time to think and reflect, if they feel emotionally drained at work, and if they feel worn out and weary after work. The intent of these questions is to provide anonymous feedback to training programs to help identify year to year trends and intervene early to prevent occupational burnout from becoming an increasing issue.
The solution
Considerations for any intervention should take several factors into account: the impact it may have on training and the development of a competent physician in their individualized specialty, the sustainability of the intervention, and whether it is something that will be accepted by the invested parties.
One method proposed for preventing burnout during fellowship has been designated as the three R’s: relaxation, reflection, and regrouping.3
- Relax. In order to relax, trainees need ways to decompress. Activities such as exercise and social events can be helpful. Within our own program the fellows have started their own group exercise program, playing wallyball weekly before clinical duties. We also encourage use of vacation days and build comradery by organizing potluck dinners for major holidays, graduation parties at the program director’s house, and an end-of-the-year golf outing in which trainees play against staff followed by a discussion regarding the state of the program. More recently we have added one half-day per a quarter for morale and team building. During this first year, the activities in which trainees have collectively decided to participate include an escape room, a rock-climbing facility, and laser tag. The addition of more team-building days has been well received by our program’s trainees and the simple addition of these team-building days has resulted in the trainees interacting more together outside of work, particularly in the form of group dinners.
Walter Reed National Military Medical Center fellows gathering for wallyball. - Reflect. They describe reflection as a necessary checkpoint which typically occurs every 6 months.3 These “checkpoints” provide an opportunity to provide feedback to the fellow as well as check in on their well-being and receive feedback about the program. We give frequent feedback to fellows in the form of spot, rotational, and mid-/end-of-year feedback. Additionally, we have developed a unique feedback system in which the trainees meet at the end of the year to discuss collective feedback for the staff and the program. This feedback is collated by the chief fellow and given to the program director as anonymous feedback, which is then passed to the individual staff.
- Regroup. Finally, regrouping to form new strategies.3 This regrouping provides an opportunity to improve on areas in which the trainee may have a deficiency and build on their strengths. To facilitate regrouping, we identify a mentor within the department and occasionally in other departments to meet regularly with the trainee. A successful mentor ensures effective regrouping and can help the trainee avoid pitfalls that they may have experienced in similar situations.
Moving forward
Occupational burnout is a systemic problem within the medical field, with trainees disproportionately affected. It is imperative that training programs continue to work toward creating a culture that prevents development of burnout. Along with the ideas presented here, the ACGME has launched AWARE, which is a suite of resources directed specifically at the GME community, with a goal of mitigating stress and preventing burnout. No one approach will be universally applicable but continued awareness and efforts to address this on an individual and programmatic level should be encouraged.
Dr. Ordway is a chief fellow, Dr. Tritsch and Dr. Singla are associate program directors, and Dr. Torres the program director, division of gastroenterology and hepatology, Walter Reed National Military Medical Center, Bethesda, Md.
References
1. Barnes EL et al. Dig Dis Sci. 2019;64(2):302-6.
2. Dyrbye LN et al. Acad Med. 2014;89(3):443-51.
3. Waldo OA. J Am Coll Cardiol. 2015;66(11):1303-6.
Jeff is a high-performing first-year gastroenterology fellow who started with eagerness and enthusiasm. He seemed to enjoy talking to patients, wrote thorough notes, and often participated during case discussions at morning report. He initiated a quality improvement project and joined a hospital committee. Over the past few months, he has interacted less with his peers in the fellow’s office and stayed late to complete his patient encounters. He now frequently arrives late to work, is unprepared for rounds, and forgets to place important orders. One day, you notice him shuffling through several papers when the attending asks him a question about his patient. Later that day, he snapped at a nurse who paged to ask a question about a patient who just had a colonoscopy. When you ask him how he is doing, he becomes tearful and reports that he is under a lot of stress between work and home and does not feel the work he is doing is meaningful.
Introduction
The above scenario is all too familiar. Gastroenterology training can be a stressful period in an individual’s life. Long hours, steep learning curves for new cognitive and mechanical skill sets, as well as managing personal relationships and responsibilities at home all contribute to the stress of training and finding appropriate work-life balance. These stressors can result in burnout. The last decade has brought about a renewed emphasis on mitigating the impact of occupational burnout and improving trainee lifestyle through interventions such as work-hour restrictions, resiliency training, instruction on the importance of sleep, and team-building activities.
The problem
The World Health Organization (WHO) defines occupational burnout as chronic work-related stress, which may be characterized by feelings of energy depletion, mental distance from one’s job or feelings of negativity toward it, and reduced professional efficacy. Occupational burnout has been identified as an increasing problem both in practicing providers and trainees. Surveys in gastroenterologists show rates of burnout ranging between 37% and 50%,1 with trainees and early-career physicians disproportionately affected.1,2Physicians along the entire training spectrum are more likely to report high emotional exhaustion, high depersonalization, and burnout than a population control sample.2
Several individual factors identified for those at increased risk for burnout include younger age, not being married, and being male.2 Individuals spending less than 20% of their time working on activities they find meaningful and productive were more likely to show evidence of burnout.1
Symptoms of burnout can have a profound impact on trainees’ work performance, personal interactions, and the learning environment as a whole. The Accreditation Council for Graduate Medical Education (ACGME) annual survey of trainees asks them how strongly they agree or disagree on various components of burnout such as how meaningful they find their work, if they have enough time to think and reflect, if they feel emotionally drained at work, and if they feel worn out and weary after work. The intent of these questions is to provide anonymous feedback to training programs to help identify year to year trends and intervene early to prevent occupational burnout from becoming an increasing issue.
The solution
Considerations for any intervention should take several factors into account: the impact it may have on training and the development of a competent physician in their individualized specialty, the sustainability of the intervention, and whether it is something that will be accepted by the invested parties.
One method proposed for preventing burnout during fellowship has been designated as the three R’s: relaxation, reflection, and regrouping.3
- Relax. In order to relax, trainees need ways to decompress. Activities such as exercise and social events can be helpful. Within our own program the fellows have started their own group exercise program, playing wallyball weekly before clinical duties. We also encourage use of vacation days and build comradery by organizing potluck dinners for major holidays, graduation parties at the program director’s house, and an end-of-the-year golf outing in which trainees play against staff followed by a discussion regarding the state of the program. More recently we have added one half-day per a quarter for morale and team building. During this first year, the activities in which trainees have collectively decided to participate include an escape room, a rock-climbing facility, and laser tag. The addition of more team-building days has been well received by our program’s trainees and the simple addition of these team-building days has resulted in the trainees interacting more together outside of work, particularly in the form of group dinners.
Walter Reed National Military Medical Center fellows gathering for wallyball. - Reflect. They describe reflection as a necessary checkpoint which typically occurs every 6 months.3 These “checkpoints” provide an opportunity to provide feedback to the fellow as well as check in on their well-being and receive feedback about the program. We give frequent feedback to fellows in the form of spot, rotational, and mid-/end-of-year feedback. Additionally, we have developed a unique feedback system in which the trainees meet at the end of the year to discuss collective feedback for the staff and the program. This feedback is collated by the chief fellow and given to the program director as anonymous feedback, which is then passed to the individual staff.
- Regroup. Finally, regrouping to form new strategies.3 This regrouping provides an opportunity to improve on areas in which the trainee may have a deficiency and build on their strengths. To facilitate regrouping, we identify a mentor within the department and occasionally in other departments to meet regularly with the trainee. A successful mentor ensures effective regrouping and can help the trainee avoid pitfalls that they may have experienced in similar situations.
Moving forward
Occupational burnout is a systemic problem within the medical field, with trainees disproportionately affected. It is imperative that training programs continue to work toward creating a culture that prevents development of burnout. Along with the ideas presented here, the ACGME has launched AWARE, which is a suite of resources directed specifically at the GME community, with a goal of mitigating stress and preventing burnout. No one approach will be universally applicable but continued awareness and efforts to address this on an individual and programmatic level should be encouraged.
Dr. Ordway is a chief fellow, Dr. Tritsch and Dr. Singla are associate program directors, and Dr. Torres the program director, division of gastroenterology and hepatology, Walter Reed National Military Medical Center, Bethesda, Md.
References
1. Barnes EL et al. Dig Dis Sci. 2019;64(2):302-6.
2. Dyrbye LN et al. Acad Med. 2014;89(3):443-51.
3. Waldo OA. J Am Coll Cardiol. 2015;66(11):1303-6.
Jeff is a high-performing first-year gastroenterology fellow who started with eagerness and enthusiasm. He seemed to enjoy talking to patients, wrote thorough notes, and often participated during case discussions at morning report. He initiated a quality improvement project and joined a hospital committee. Over the past few months, he has interacted less with his peers in the fellow’s office and stayed late to complete his patient encounters. He now frequently arrives late to work, is unprepared for rounds, and forgets to place important orders. One day, you notice him shuffling through several papers when the attending asks him a question about his patient. Later that day, he snapped at a nurse who paged to ask a question about a patient who just had a colonoscopy. When you ask him how he is doing, he becomes tearful and reports that he is under a lot of stress between work and home and does not feel the work he is doing is meaningful.
Introduction
The above scenario is all too familiar. Gastroenterology training can be a stressful period in an individual’s life. Long hours, steep learning curves for new cognitive and mechanical skill sets, as well as managing personal relationships and responsibilities at home all contribute to the stress of training and finding appropriate work-life balance. These stressors can result in burnout. The last decade has brought about a renewed emphasis on mitigating the impact of occupational burnout and improving trainee lifestyle through interventions such as work-hour restrictions, resiliency training, instruction on the importance of sleep, and team-building activities.
The problem
The World Health Organization (WHO) defines occupational burnout as chronic work-related stress, which may be characterized by feelings of energy depletion, mental distance from one’s job or feelings of negativity toward it, and reduced professional efficacy. Occupational burnout has been identified as an increasing problem both in practicing providers and trainees. Surveys in gastroenterologists show rates of burnout ranging between 37% and 50%,1 with trainees and early-career physicians disproportionately affected.1,2Physicians along the entire training spectrum are more likely to report high emotional exhaustion, high depersonalization, and burnout than a population control sample.2
Several individual factors identified for those at increased risk for burnout include younger age, not being married, and being male.2 Individuals spending less than 20% of their time working on activities they find meaningful and productive were more likely to show evidence of burnout.1
Symptoms of burnout can have a profound impact on trainees’ work performance, personal interactions, and the learning environment as a whole. The Accreditation Council for Graduate Medical Education (ACGME) annual survey of trainees asks them how strongly they agree or disagree on various components of burnout such as how meaningful they find their work, if they have enough time to think and reflect, if they feel emotionally drained at work, and if they feel worn out and weary after work. The intent of these questions is to provide anonymous feedback to training programs to help identify year to year trends and intervene early to prevent occupational burnout from becoming an increasing issue.
The solution
Considerations for any intervention should take several factors into account: the impact it may have on training and the development of a competent physician in their individualized specialty, the sustainability of the intervention, and whether it is something that will be accepted by the invested parties.
One method proposed for preventing burnout during fellowship has been designated as the three R’s: relaxation, reflection, and regrouping.3
- Relax. In order to relax, trainees need ways to decompress. Activities such as exercise and social events can be helpful. Within our own program the fellows have started their own group exercise program, playing wallyball weekly before clinical duties. We also encourage use of vacation days and build comradery by organizing potluck dinners for major holidays, graduation parties at the program director’s house, and an end-of-the-year golf outing in which trainees play against staff followed by a discussion regarding the state of the program. More recently we have added one half-day per a quarter for morale and team building. During this first year, the activities in which trainees have collectively decided to participate include an escape room, a rock-climbing facility, and laser tag. The addition of more team-building days has been well received by our program’s trainees and the simple addition of these team-building days has resulted in the trainees interacting more together outside of work, particularly in the form of group dinners.
Walter Reed National Military Medical Center fellows gathering for wallyball. - Reflect. They describe reflection as a necessary checkpoint which typically occurs every 6 months.3 These “checkpoints” provide an opportunity to provide feedback to the fellow as well as check in on their well-being and receive feedback about the program. We give frequent feedback to fellows in the form of spot, rotational, and mid-/end-of-year feedback. Additionally, we have developed a unique feedback system in which the trainees meet at the end of the year to discuss collective feedback for the staff and the program. This feedback is collated by the chief fellow and given to the program director as anonymous feedback, which is then passed to the individual staff.
- Regroup. Finally, regrouping to form new strategies.3 This regrouping provides an opportunity to improve on areas in which the trainee may have a deficiency and build on their strengths. To facilitate regrouping, we identify a mentor within the department and occasionally in other departments to meet regularly with the trainee. A successful mentor ensures effective regrouping and can help the trainee avoid pitfalls that they may have experienced in similar situations.
Moving forward
Occupational burnout is a systemic problem within the medical field, with trainees disproportionately affected. It is imperative that training programs continue to work toward creating a culture that prevents development of burnout. Along with the ideas presented here, the ACGME has launched AWARE, which is a suite of resources directed specifically at the GME community, with a goal of mitigating stress and preventing burnout. No one approach will be universally applicable but continued awareness and efforts to address this on an individual and programmatic level should be encouraged.
Dr. Ordway is a chief fellow, Dr. Tritsch and Dr. Singla are associate program directors, and Dr. Torres the program director, division of gastroenterology and hepatology, Walter Reed National Military Medical Center, Bethesda, Md.
References
1. Barnes EL et al. Dig Dis Sci. 2019;64(2):302-6.
2. Dyrbye LN et al. Acad Med. 2014;89(3):443-51.
3. Waldo OA. J Am Coll Cardiol. 2015;66(11):1303-6.
Can drinking more water prevent urinary tract infections?
ILLUSTRATIVE CASE
A 23-year-old nonpregnant woman, whom you treated 3 times in the past year for cystitis, comes to you for follow-up. She wants to know what she can do to prevent another urinary tract infection other than taking prophylactic antibiotics. Should you recommend that this patient increase her daily water intake to prevent recurrent cystitis?
Urinary tract infection (UTI) is the most common bacterial infection encountered in the ambulatory setting. Half of all women report having had at least 1 UTI by the time they are 32 years old.2 Recurrence is also common, with 27% of women having 1 recurrence within 6 months of their first episode.2
Because of growing antimicrobial resistance, the World Health Organization has urged using novel antimicrobial-sparing approaches to infectious diseases.3 Physicians have long recommended behavioral, nonantimicrobial strategies for prevention of recurrent uncomplicated cystitis. Such behavioral recommendations include drinking fluids liberally, urinating after intercourse, not delaying urination, wiping front to back, and avoiding tight-fitting underwear. However, these behavior modification strategies have been studied largely in case-control trials that have yet to find an association between behavior modification and reduced risk of UTI.2 Although unproven as a prevention strategy, increasing daily fluid intake has long been a recommendation because of the belief that it helps to dilute and clear bactiuria.4 This study is the first non–case-control trial to examine the association between increased fluid intake and decreased UTIs.1
STUDY SUMMARY
RCT looks at whether more water leads to fewer UTIs
Hooton and colleagues1 conducted an open-label, randomized controlled trial (RCT) of premenopausal women with recurrent UTIs and low baseline fluid intake and compared increased fluid intake (an additional 1.5 L/d) with no additional fluids. Participants were provided three 500-mL bottles of water per day and were followed for 1 year. Screened women were included if they had 3 or more symptomatic UTIs in the previous year, 1 culture-confirmed UTI, self-reported fluid intake < 1.5 L /d, and were otherwise in good health. Fluid intake was verified by 24-hour urine collection, requiring a volume < 1.2 L and urine osmolality of ≥ 500 mOsm/kg. Exclusion criteria included a history of pyelonephritis within the past year, interstitial cystitis, pregnancy, or current symptoms of UTI.
The primary outcome was frequency of UTI during the study period, defined as 1 urinary symptom and at least 103 CFU/mL uropathogens in a urine culture. Secondary outcomes included the number of antimicrobial agents used, time to first UTI, mean time interval between cystitis episodes, and adverse events.1
A total of 140 participants were randomized with 70 in the water group and 70 in the control group. The mean age of the participants was 35.7 years, and the mean number of reported cystitis episodes was 3.3 in the 12 months prior to the study. By the end of the 12-month study period, mean daily fluid intake had increased by 1.7 L above baseline in the water group. During the 12-month study period, the mean (SD) number of cystitis episodes was 1.7 (95% confidence interval [CI], 1.5-1.8) in the water group compared with 3.2 (95% CI, 3-3.4) in the control group, with a difference in means of 1.5 (95% CI, 1.2-1.8; P < .001).
The mean number of antimicrobial agents used for UTI was 1.9 (95% CI, 1.7-2.2) in the water group and 3.6 (95% CI, 3.3-4) in the control group. The median time to first UTI episode was 148 days in the water group compared with 93.5 days in the control group (hazard ratio [HR] = 0.51; 95% CI, 0.36-0.74; P < .001) and the difference in means for the time interval between UTI episodes was 58.4 days (95% CI, 39.4-77.4; P < .001). No serious adverse events were reported.1
Continue to: WHAT'S NEW
WHAT’S NEW
Proof that increased fluid intake reduces the risk of recurrent UTI
Increasing daily fluid intake is a long-held but previously unproven recommendation. This is the first RCT to show increased daily water intake can reduce the risk of recurrent cystitis in premenopausal patients at high risk for UTI and with low fluid intake. No additional risk of adverse events was found.
CAVEATS
Is there a risk of overhydration?
The study did not address the effect of increasing water intake in women who do not have low-volume fluid intake. Case reports of overhydration emphasize the need to be cautious when making recommendations to hydrate.5 It is not known if physicians should screen for fluid intake at baseline to identify those (with low intake) who would be eligible for this intervention.
CHALLENGES TO IMPLEMENTATION
It’s unclear whether the strategy will work without monitoring
The intervention is both low-risk and low-cost to the patient. However, the intervention was supported by home delivery of water and monthly monitoring interventions that are not typical in normal care. Although the clinical intervention of drinking more fluids (primarily water) appears sound, it is not known whether a physician’s recommendation would result in the same adherence and risk reduction as water delivery and monitoring.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. Hooton TM, Vecchio M, Iroz A, et al. Effect of increased daily water intake in premenopausal women with recurrent urinary tract infections: a randomized clinical trial. JAMA Intern Med. 2018;178:1509-1515.
2. Hooton TM. Clinical practice. Uncomplicated urinary tract infection. N Engl J Med. 2012;366:1028-1037.
3. WHO. Antimicrobial resistance: global report on surveillance. April 2014. www.who.int/drugresistance/documents/surveillancereport/en/. Accessed March 23, 2020.
4. Fasugba O, Mitchell BG, McInnes E, et al. Increased fluid intake for the prevention of urinary tract infection in adults and children in all settings: a systematic review. J Hosp Infect. 2020;104:68-77.
5. Lee LC, Noronha M. When plenty is too much: water intoxication in a patient with a simple urinary tract infection. BMJ Case Rep. 2016. doi:10.1136/bcr-2016-216882.
ILLUSTRATIVE CASE
A 23-year-old nonpregnant woman, whom you treated 3 times in the past year for cystitis, comes to you for follow-up. She wants to know what she can do to prevent another urinary tract infection other than taking prophylactic antibiotics. Should you recommend that this patient increase her daily water intake to prevent recurrent cystitis?
Urinary tract infection (UTI) is the most common bacterial infection encountered in the ambulatory setting. Half of all women report having had at least 1 UTI by the time they are 32 years old.2 Recurrence is also common, with 27% of women having 1 recurrence within 6 months of their first episode.2
Because of growing antimicrobial resistance, the World Health Organization has urged using novel antimicrobial-sparing approaches to infectious diseases.3 Physicians have long recommended behavioral, nonantimicrobial strategies for prevention of recurrent uncomplicated cystitis. Such behavioral recommendations include drinking fluids liberally, urinating after intercourse, not delaying urination, wiping front to back, and avoiding tight-fitting underwear. However, these behavior modification strategies have been studied largely in case-control trials that have yet to find an association between behavior modification and reduced risk of UTI.2 Although unproven as a prevention strategy, increasing daily fluid intake has long been a recommendation because of the belief that it helps to dilute and clear bactiuria.4 This study is the first non–case-control trial to examine the association between increased fluid intake and decreased UTIs.1
STUDY SUMMARY
RCT looks at whether more water leads to fewer UTIs
Hooton and colleagues1 conducted an open-label, randomized controlled trial (RCT) of premenopausal women with recurrent UTIs and low baseline fluid intake and compared increased fluid intake (an additional 1.5 L/d) with no additional fluids. Participants were provided three 500-mL bottles of water per day and were followed for 1 year. Screened women were included if they had 3 or more symptomatic UTIs in the previous year, 1 culture-confirmed UTI, self-reported fluid intake < 1.5 L /d, and were otherwise in good health. Fluid intake was verified by 24-hour urine collection, requiring a volume < 1.2 L and urine osmolality of ≥ 500 mOsm/kg. Exclusion criteria included a history of pyelonephritis within the past year, interstitial cystitis, pregnancy, or current symptoms of UTI.
The primary outcome was frequency of UTI during the study period, defined as 1 urinary symptom and at least 103 CFU/mL uropathogens in a urine culture. Secondary outcomes included the number of antimicrobial agents used, time to first UTI, mean time interval between cystitis episodes, and adverse events.1
A total of 140 participants were randomized with 70 in the water group and 70 in the control group. The mean age of the participants was 35.7 years, and the mean number of reported cystitis episodes was 3.3 in the 12 months prior to the study. By the end of the 12-month study period, mean daily fluid intake had increased by 1.7 L above baseline in the water group. During the 12-month study period, the mean (SD) number of cystitis episodes was 1.7 (95% confidence interval [CI], 1.5-1.8) in the water group compared with 3.2 (95% CI, 3-3.4) in the control group, with a difference in means of 1.5 (95% CI, 1.2-1.8; P < .001).
The mean number of antimicrobial agents used for UTI was 1.9 (95% CI, 1.7-2.2) in the water group and 3.6 (95% CI, 3.3-4) in the control group. The median time to first UTI episode was 148 days in the water group compared with 93.5 days in the control group (hazard ratio [HR] = 0.51; 95% CI, 0.36-0.74; P < .001) and the difference in means for the time interval between UTI episodes was 58.4 days (95% CI, 39.4-77.4; P < .001). No serious adverse events were reported.1
Continue to: WHAT'S NEW
WHAT’S NEW
Proof that increased fluid intake reduces the risk of recurrent UTI
Increasing daily fluid intake is a long-held but previously unproven recommendation. This is the first RCT to show increased daily water intake can reduce the risk of recurrent cystitis in premenopausal patients at high risk for UTI and with low fluid intake. No additional risk of adverse events was found.
CAVEATS
Is there a risk of overhydration?
The study did not address the effect of increasing water intake in women who do not have low-volume fluid intake. Case reports of overhydration emphasize the need to be cautious when making recommendations to hydrate.5 It is not known if physicians should screen for fluid intake at baseline to identify those (with low intake) who would be eligible for this intervention.
CHALLENGES TO IMPLEMENTATION
It’s unclear whether the strategy will work without monitoring
The intervention is both low-risk and low-cost to the patient. However, the intervention was supported by home delivery of water and monthly monitoring interventions that are not typical in normal care. Although the clinical intervention of drinking more fluids (primarily water) appears sound, it is not known whether a physician’s recommendation would result in the same adherence and risk reduction as water delivery and monitoring.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
ILLUSTRATIVE CASE
A 23-year-old nonpregnant woman, whom you treated 3 times in the past year for cystitis, comes to you for follow-up. She wants to know what she can do to prevent another urinary tract infection other than taking prophylactic antibiotics. Should you recommend that this patient increase her daily water intake to prevent recurrent cystitis?
Urinary tract infection (UTI) is the most common bacterial infection encountered in the ambulatory setting. Half of all women report having had at least 1 UTI by the time they are 32 years old.2 Recurrence is also common, with 27% of women having 1 recurrence within 6 months of their first episode.2
Because of growing antimicrobial resistance, the World Health Organization has urged using novel antimicrobial-sparing approaches to infectious diseases.3 Physicians have long recommended behavioral, nonantimicrobial strategies for prevention of recurrent uncomplicated cystitis. Such behavioral recommendations include drinking fluids liberally, urinating after intercourse, not delaying urination, wiping front to back, and avoiding tight-fitting underwear. However, these behavior modification strategies have been studied largely in case-control trials that have yet to find an association between behavior modification and reduced risk of UTI.2 Although unproven as a prevention strategy, increasing daily fluid intake has long been a recommendation because of the belief that it helps to dilute and clear bactiuria.4 This study is the first non–case-control trial to examine the association between increased fluid intake and decreased UTIs.1
STUDY SUMMARY
RCT looks at whether more water leads to fewer UTIs
Hooton and colleagues1 conducted an open-label, randomized controlled trial (RCT) of premenopausal women with recurrent UTIs and low baseline fluid intake and compared increased fluid intake (an additional 1.5 L/d) with no additional fluids. Participants were provided three 500-mL bottles of water per day and were followed for 1 year. Screened women were included if they had 3 or more symptomatic UTIs in the previous year, 1 culture-confirmed UTI, self-reported fluid intake < 1.5 L /d, and were otherwise in good health. Fluid intake was verified by 24-hour urine collection, requiring a volume < 1.2 L and urine osmolality of ≥ 500 mOsm/kg. Exclusion criteria included a history of pyelonephritis within the past year, interstitial cystitis, pregnancy, or current symptoms of UTI.
The primary outcome was frequency of UTI during the study period, defined as 1 urinary symptom and at least 103 CFU/mL uropathogens in a urine culture. Secondary outcomes included the number of antimicrobial agents used, time to first UTI, mean time interval between cystitis episodes, and adverse events.1
A total of 140 participants were randomized with 70 in the water group and 70 in the control group. The mean age of the participants was 35.7 years, and the mean number of reported cystitis episodes was 3.3 in the 12 months prior to the study. By the end of the 12-month study period, mean daily fluid intake had increased by 1.7 L above baseline in the water group. During the 12-month study period, the mean (SD) number of cystitis episodes was 1.7 (95% confidence interval [CI], 1.5-1.8) in the water group compared with 3.2 (95% CI, 3-3.4) in the control group, with a difference in means of 1.5 (95% CI, 1.2-1.8; P < .001).
The mean number of antimicrobial agents used for UTI was 1.9 (95% CI, 1.7-2.2) in the water group and 3.6 (95% CI, 3.3-4) in the control group. The median time to first UTI episode was 148 days in the water group compared with 93.5 days in the control group (hazard ratio [HR] = 0.51; 95% CI, 0.36-0.74; P < .001) and the difference in means for the time interval between UTI episodes was 58.4 days (95% CI, 39.4-77.4; P < .001). No serious adverse events were reported.1
Continue to: WHAT'S NEW
WHAT’S NEW
Proof that increased fluid intake reduces the risk of recurrent UTI
Increasing daily fluid intake is a long-held but previously unproven recommendation. This is the first RCT to show increased daily water intake can reduce the risk of recurrent cystitis in premenopausal patients at high risk for UTI and with low fluid intake. No additional risk of adverse events was found.
CAVEATS
Is there a risk of overhydration?
The study did not address the effect of increasing water intake in women who do not have low-volume fluid intake. Case reports of overhydration emphasize the need to be cautious when making recommendations to hydrate.5 It is not known if physicians should screen for fluid intake at baseline to identify those (with low intake) who would be eligible for this intervention.
CHALLENGES TO IMPLEMENTATION
It’s unclear whether the strategy will work without monitoring
The intervention is both low-risk and low-cost to the patient. However, the intervention was supported by home delivery of water and monthly monitoring interventions that are not typical in normal care. Although the clinical intervention of drinking more fluids (primarily water) appears sound, it is not known whether a physician’s recommendation would result in the same adherence and risk reduction as water delivery and monitoring.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. Hooton TM, Vecchio M, Iroz A, et al. Effect of increased daily water intake in premenopausal women with recurrent urinary tract infections: a randomized clinical trial. JAMA Intern Med. 2018;178:1509-1515.
2. Hooton TM. Clinical practice. Uncomplicated urinary tract infection. N Engl J Med. 2012;366:1028-1037.
3. WHO. Antimicrobial resistance: global report on surveillance. April 2014. www.who.int/drugresistance/documents/surveillancereport/en/. Accessed March 23, 2020.
4. Fasugba O, Mitchell BG, McInnes E, et al. Increased fluid intake for the prevention of urinary tract infection in adults and children in all settings: a systematic review. J Hosp Infect. 2020;104:68-77.
5. Lee LC, Noronha M. When plenty is too much: water intoxication in a patient with a simple urinary tract infection. BMJ Case Rep. 2016. doi:10.1136/bcr-2016-216882.
1. Hooton TM, Vecchio M, Iroz A, et al. Effect of increased daily water intake in premenopausal women with recurrent urinary tract infections: a randomized clinical trial. JAMA Intern Med. 2018;178:1509-1515.
2. Hooton TM. Clinical practice. Uncomplicated urinary tract infection. N Engl J Med. 2012;366:1028-1037.
3. WHO. Antimicrobial resistance: global report on surveillance. April 2014. www.who.int/drugresistance/documents/surveillancereport/en/. Accessed March 23, 2020.
4. Fasugba O, Mitchell BG, McInnes E, et al. Increased fluid intake for the prevention of urinary tract infection in adults and children in all settings: a systematic review. J Hosp Infect. 2020;104:68-77.
5. Lee LC, Noronha M. When plenty is too much: water intoxication in a patient with a simple urinary tract infection. BMJ Case Rep. 2016. doi:10.1136/bcr-2016-216882.
PRACTICE CHANGER
Advise premenopausal women with recurrent urinary tract infections (UTIs) and low-volume fluid intake to increase their water intake by at least 1.5 liters daily to reduce the frequency of UTIs.1
STRENGTH OF RECOMMENDATION
A: Based on a single, high-quality randomized controlled trial.
Hooton TM, Vecchio M, Iroz A, et al. Effect of increased daily water intake in premenopausal women with recurrent urinary tract infections: a randomized clinical trial. JAMA Intern Med. 2018;178:1509-1515.
Paranoid delusions • ideas of reference • sleep problems • Dx?
THE CASE
A 58-year-old married Asian woman with no apparent psychiatric history presented to the emergency department (ED) in an acute state with ideas of reference, paranoid delusions, and multiple, vague somatic symptoms.
Based on information in the patient’s medical record, there had been suspicion of an underlying psychiatric disorder 6 years earlier. At that time, the patient had presented to her primary care provider (PCP) with vague somatic complaints, including diffuse body pain, dry cough, chills, weakness, facial numbness, and concerns about infections. A physical examination and work-up did not reveal the source of her complaints. Unfortunately, the patient’s complaints increased in number and severity over time.
Her medical records also indicated that she had been assessed for depression severity using the Patient Health Questionnaire-9 (PHQ-9), with scores of 0 (4 years earlier) and 3 (3 years earlier). The scores suggested that she was not suffering from depression.
During this time, the patient also saw a psychiatrist; however, it was unclear whether her symptoms met the criteria for delusional disorder or schizophrenia because she did not exhibit negative symptoms or sensory hallucinations. In addition, the patient was extremely high-functioning in the community—she participated in dance classes and other social events—and had the equivalent of a medical degree from another country. Based on chart review, when she went to the psychiatrist 3 years prior to her current presentation, there were no antipsychotics prescribed.
In the weeks leading up to her current presentation, the patient reported that she was struggling with sleep, sometimes spending days in bed and other times needing unspecified medication obtained overseas to help her sleep. Her husband reported that she had become increasingly withdrawn and stopped attending her dance classes and social events.
The patient believed the government was trying to poison her via radiation and that unknown people were trying to harm her via an online messaging application. Immediately prior to her arrival in the ED, the police were called to pull her away from oncoming traffic because she ran into the road to find the assassins that were stalking her.
During this recent visit to the ED, the patient presented with labile affect, rapid speech, and anxious and angry mood. She complained about darkened spots on her arm (inflicted through radiation by the media), vaginal bleeding, paralysis below the waist (although she was pacing around), and unspecific pain around her belly. Physical examination revealed no obvious signs of head trauma, intact extraocular movements, no coughing or wheezing, regular heart rate and rhythm, a nontender abdomen to palpation, and normal bowel sounds. No focal neurological deficits were appreciated. She had no rashes, bruises, or skin abrasions on her abdomen or upper extremities.
Continue to: The patient tried to...
The patient tried to leave the ED, saying that her third eye could see the radiation. She required medication and 4-point restraints.
Her initial laboratory work-up for heavy metals, Lyme disease, human immunodeficiency virus (HIV), syphilis, delirium, and drug use were all negative. She also underwent head imaging studies that were also found to be negative. Her mental status exam was notable for a tangential thought process, preservation of delusions with loose associations, labile mood, and dysphoric affect. The patient demonstrated limited insight and judgment, although she was fully oriented to person, place, and time, which suggested against delirium at the time of evaluation.
THE DIAGNOSIS
Based on the patient’s current presentation and in light of her medical history, the health care team arrived at a
DISCUSSION
Schizophrenia is a severe, lifelong mental disorder characterized by at least 2 symptoms of delusions, hallucinations, disorganized speech, disorganized or catatonic behavior, or negative symptoms for at least 6 months, with significant social, occupational, and functional deterioration. Current models attribute the neurodevelopmental deregulation of the brain in patients with schizophrenia to dopaminergic hyperactivity and hypofunction of the glutamatergic neurotransmitter system, explaining why its onset is usually in adolescence or young adulthood.1,2 However, 23% of patients present with symptoms after age 40, with 7% of patients being diagnosed between the ages of 51 and 60.3
Late-onset vs early-onset schizophrenia. LOS is often a missed diagnosis because the clinical presentation is different from early-onset schizophrenia (EOS). Although the prodromal symptoms of EOS and LOS are similar and include marked isolation that subsequently progresses to suspiciousness and ideas of reference,4 patients with EOS often also have prodromal negative symptoms. These prodromal negative symptoms associated with EOS may include loss of motivation, social passivity, and disorganized behavior. These symptoms are hypothesized to be caused by dopaminergic dysregulation in the anterior cingulate cortex. EOS is characterized by the patient experiencing more negative symptoms than LOS, which is characterized by the patient experiencing more positive symptoms.
Continue to: Patients with late-onset schizophrenia...
Patients with LOS typically do not exhibit negative symptoms because remodeling and myelination of neuronal circuitry matures by late adulthood, and thus becomes more resistant to impairment of motivational processes in the anterior cingulate gyrus.4,5,6
LOS is characterized by paranoid personality with predominantly positive symptoms, likely due to disruptions in
Other features of LOS include a high female:male ratio and symptomatic improvement with antipsychotics.7,10 Studies show that the LOS ratio of women:men can range from 2.2:1 to 22.5:1, which could be explained by the effect of dopaminergic-modulating estrogen from different sex-specific aging brain patterns.8,11,12 Finally, patients with LOS are less likely to seek care for sensory deficits than their age-equivalent counterparts.8,10 Fortunately, many of the characteristics of LOS predict good prognosis: Patients are usually female, display positive symptoms, have acute onset of symptoms, and are married with social support.10
Diagnosing LOS
LOS can be challenging to diagnose because of its atypical presentation compared with EOS, relative rarity in the population, and its propensity to be confused with progressive Alzheimer disease/dementia, delusional disorder, and major depressive disorder with psychotic features.3,6 Patients with no prior psychiatric history often do not have ready access to psychiatrists and depend on PCPs and other clinicians to identify mental health issues. A careful history, including familial involvement, utilization of the Montreal Cognitive Assessment (MoCA) test, and evaluation of environmental factors, are crucial to arriving at the proper diagnosis.
Continue to: Differential diagnosis
Differential diagnosis. When psychosis appears later in life, it is important to consider a broad differential (TABLE13-18), which includes the following:
Alzheimer disease. LOS can be easily differentiated from psychosis associated with Alzheimer disease or dementia through findings from neuropsychologic assessments and brain imaging. The initial first-line assessment for Alzheimer disease includes determining time course of daily living impairment and memory with follow-up brain imaging. Magnetic resonance imaging of patients with Alzheimer disease shows clear atrophy of the medial temporal lobes and general brain atrophy.19 Other than hypoperfusion in the frontal and temporal area, brain imaging of patients with LOS will not reveal any pathology.1
Delusional disorder and LOS are often more challenging to differentiate because symptoms can overlap, and many of the negative symptoms that would otherwise help clinicians diagnose schizophrenia in a younger population are absent in LOS. The milder symptoms of LOS may also lead clinicians to favor a diagnosis of delusional disorder. However, the following differences can help physicians differentiate between LOS and delusional disorder. Delusional disorder20-22:
- often will include paranoid beliefs, but these beliefs will not be bizarre, and the patient’s daily functioning will not be impaired, whereas patients with schizophrenia would have an increase in isolation and impairment in functioning that tends to be distinct from baseline.
- is more rare than schizophrenia. Delusional disorder has a prevalence of 0.05% to 0.1% compared to 1% for schizophrenia.
Major depressive disorder (MDD) with psychotic features. Major depressive disorder with psychotic features is an important differential to consider in this setting because the treatment intervention can be considerably different. Among patients who have MDD with psychotic features, a significant mood component is present, and treatment typically focuses on optimizing a selective serotonin reuptake inhibitor (SSRI); depending on severity, electroconvulsive therapy (ECT) also may be warranted.19
Continue to: For patients with LOS...
For patients with LOS, optimizing an antipsychotic medication is the typical course of treatment, and ECT would likely have less of an impact than it does with MDD with psychotic features.
Other. Finally, in an acute setting, other differential diagnoses for mental status changes (depending on clinical findings) might include:
- drug/medication use
- delirium
- nutrient deficiencies
- acute head trauma
- chronic subdural hematoma
- syphilis
- Lyme disease
- HIV encephalitis
- heavy metal toxicity.
Treatment involves antipsychotics—especially certain ones
Antipsychotic medications are utilized for the treatment of patients with LOS. A Cochrane review concluded that there are no trial-based evidence guidelines for the treatment of patients with LOS, and that physicians should continue with their current practice and use clinical judgment and prescribing patterns to guide their selection of antipsychotic medications.22,23 Pearlson et al24 found that 76% of patients with schizophrenia achieved at least partial remission and 48% achieved full remission with antipsychotic treatment.
The preferred treatment for patients with schizophrenia is low doses of newer antipsychotics (atypical or second-generation antipsychotics [SGAs]) because they are less likely to cause extrapyramidal symptoms/adverse effects than first-generation antipsychotics. Examples of SGAs include aripiprazole, risperidone, olanzapine, quetiapine, and ziprasidone.
Effective treatment for LOS includes antipsychotics at a quarter to one-half of the usual therapeutic doses. In patients with very late-onset schizophrenia, doses should be started at a tenth of therapeutic dose.1,23 Physicians should titrate up carefully, as needed.
Continue to: As with any significant mental illness...
As with any significant mental illness, to improve clinical outcomes, family support may help patients’ medication adherence and ensure they attend scheduled medical appointments.
Our patient was eventually stabilized on long-acting injectable risperidone, 25 mg, with improvement in symptoms. Unfortunately, she was not convinced that her symptoms were psychiatric in nature and did not continue with her medications as an outpatient.
The patient’s nonadherence to her medication regimen led to 2 more hospitalizations with similar presentations over the following 2 years. On her most recent discharge, she was stabilized on oral olanzapine, 10 mg every night at bedtime, with close outpatient follow-up and family education.
THE TAKEAWAY
The prodromal phase of patients with LOS is similar to patients with EOS and includes withdrawal and isolation from others, making it difficult for physicians to evaluate and treat patients. Patients with LOS predominantly experience positive symptoms that may include delusions and hallucinations. Brain imaging studies can help rule out progressive dementia diseases. A neuropsychological evaluation can assess the patient’s functional level and types of delusions, which helps to differentiate LOS from other late-age psychoses. Treatment with SGAs make for a good prognosis; however, this requires patients to be adherent to treatment.
CORRESPONDENCE
Sandy Chan, MD, Department of Internal Medicine, UMass Memorial Medical Center, 55N Lake Avenue, Worcester, MA 01605; Sandy.Chan@umassmemorial.org
1. Howard R, Rabins P, Seeman M, et al. Late-onset schizophrenia and very-late-onset schizophrenia-like psychosis: an international crisis. Am J Psychiatry 2000;157:172-178.
2. Pickard B. Progress in defining the biological causes of schizophrenia. Expert Rev Mol Med. 2011;13:e25.
3. Jeste D, Symonds L, Harris M, et al. Nondementia nonpraecox dementia praecox? Am J Geriatr Psychiatry. 1997;5:302-317.
4. Gourzis P, Katrivanou A, Beratis S. Symptomatology of the initial prodromal phase of schizophrenia. Schizophr Bull. 2002;28:415-429.
5. Dolan R, Fletcher P, Frith C, et al. Dopaminergic modulation of impaired cognitive activation in the anterior cingulate cortex in schizophrenia. Nature. 1995;378:180-182.
6. Skokou M, Katrivanou A, Andriopoulos I, et al. Active and prodromal phase symptomatology of young-onset and late-onset paranoid schizophrenia. Rev Psiquiatr Salud Ment. 2012;5:150-159.
7. Riecher-Rossler A, Loffler W, Munk-Jorgensen P. What do we really know about late-onset schizophrenia? Eur Arch Psychiatry Clin Neurosci. 1997;247:195-208.
8. Lubman D, Castle D. Late-onset schizophrenia: make the right diagnosis when psychosis emerges after age 60. Current Psychiatry. 2002;1:35-44.
9. Howard R, Castle D, Wessely S, et al. A comparative study of 470 cases of early-onset and late-onset schizophrenia. British Journal of Psychiatry. 1993;163:352-357.
10. Harris M, Jeste D. Late-onset schizophrenia: an overview. Schizophr Bull. 1988;14:39-55.
11. Castle D, Murray R. The epidemiology of late-onset schizophrenia. Schizophr Bull. 1993;19:691-700.
12. Lindamer L, Lohr J, Harris M, Jeste D. Gender, estrogen, and schizophrenia. Psychopharmacol Bull. 1997;33:221-228.
13. Gaudiano BA, Dalrymple KL, Zimmerman M. Prevalence and clinical characteristics of psychotic versus non-psychotic major depression in a general psychiatric outpatient clinic. Depress Anxiety. 2009;26:54-64.
14. Saha S, Chant D, Welham J, et al. A systematic review of the prevalence of schizophrenia. PLoS Med. 2005;2:e141.
15. Gao S, Hendrie H, Hall K. The relationships between age, sex, and the incidence of dementia and Alzheimer Disease. JAMA Psychiatry. 1998;55:809-815.
16. Reitz C, Brayne C, Mayeux R. Epidemiology of Alzheimer Disease. Nature Reviews Neurology. 2011;7:137-152
17. Winokur G. Delusional Disorder (Paranoia). Comprehensive Psychiatry. 1977;18:511-521.
18. Scheltens P, Leys D, Huglo D, et al. Atrophy of medial temporal lobes on MRI in “probable” Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol, Neurosurg Psychiatry. 1992;55:967-972.
19. Copeland J, Dewey M, Scott A, et al. Schizophrenia and delusional disorder in older age: community prevalence, incidence, comorbidity, and outcome. Schizophr Bull. 1998;24:153-161.
20. Kendler K. Demography of paranoid psychosis (delusional disorder): a review and comparison with schizophrenia and affective illness. Arch Gen Psychiatry 1982;39:890-902.
21. McGrath J, Saha S, Chant D, et al. Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiol Rev. 2008;30:67.
22. Essali A, Ali G. Antipsychotic drug treatment for elderly people with late-onset schizophrenia. Cochrane Database Syst Rev. 2012;(2):CD004162.
23. Sweet R, Pollock B. New atypical antipsychotics- experience and utility in the elderly. Drugs Aging. 1998;12:115-127.
24. Pearlson G, Kreger L, Rabins P, et al. A chart review study of late-onset and early-onset schizophrenia. Am J Psychiatry.1989;146:1568-1574.
THE CASE
A 58-year-old married Asian woman with no apparent psychiatric history presented to the emergency department (ED) in an acute state with ideas of reference, paranoid delusions, and multiple, vague somatic symptoms.
Based on information in the patient’s medical record, there had been suspicion of an underlying psychiatric disorder 6 years earlier. At that time, the patient had presented to her primary care provider (PCP) with vague somatic complaints, including diffuse body pain, dry cough, chills, weakness, facial numbness, and concerns about infections. A physical examination and work-up did not reveal the source of her complaints. Unfortunately, the patient’s complaints increased in number and severity over time.
Her medical records also indicated that she had been assessed for depression severity using the Patient Health Questionnaire-9 (PHQ-9), with scores of 0 (4 years earlier) and 3 (3 years earlier). The scores suggested that she was not suffering from depression.
During this time, the patient also saw a psychiatrist; however, it was unclear whether her symptoms met the criteria for delusional disorder or schizophrenia because she did not exhibit negative symptoms or sensory hallucinations. In addition, the patient was extremely high-functioning in the community—she participated in dance classes and other social events—and had the equivalent of a medical degree from another country. Based on chart review, when she went to the psychiatrist 3 years prior to her current presentation, there were no antipsychotics prescribed.
In the weeks leading up to her current presentation, the patient reported that she was struggling with sleep, sometimes spending days in bed and other times needing unspecified medication obtained overseas to help her sleep. Her husband reported that she had become increasingly withdrawn and stopped attending her dance classes and social events.
The patient believed the government was trying to poison her via radiation and that unknown people were trying to harm her via an online messaging application. Immediately prior to her arrival in the ED, the police were called to pull her away from oncoming traffic because she ran into the road to find the assassins that were stalking her.
During this recent visit to the ED, the patient presented with labile affect, rapid speech, and anxious and angry mood. She complained about darkened spots on her arm (inflicted through radiation by the media), vaginal bleeding, paralysis below the waist (although she was pacing around), and unspecific pain around her belly. Physical examination revealed no obvious signs of head trauma, intact extraocular movements, no coughing or wheezing, regular heart rate and rhythm, a nontender abdomen to palpation, and normal bowel sounds. No focal neurological deficits were appreciated. She had no rashes, bruises, or skin abrasions on her abdomen or upper extremities.
Continue to: The patient tried to...
The patient tried to leave the ED, saying that her third eye could see the radiation. She required medication and 4-point restraints.
Her initial laboratory work-up for heavy metals, Lyme disease, human immunodeficiency virus (HIV), syphilis, delirium, and drug use were all negative. She also underwent head imaging studies that were also found to be negative. Her mental status exam was notable for a tangential thought process, preservation of delusions with loose associations, labile mood, and dysphoric affect. The patient demonstrated limited insight and judgment, although she was fully oriented to person, place, and time, which suggested against delirium at the time of evaluation.
THE DIAGNOSIS
Based on the patient’s current presentation and in light of her medical history, the health care team arrived at a
DISCUSSION
Schizophrenia is a severe, lifelong mental disorder characterized by at least 2 symptoms of delusions, hallucinations, disorganized speech, disorganized or catatonic behavior, or negative symptoms for at least 6 months, with significant social, occupational, and functional deterioration. Current models attribute the neurodevelopmental deregulation of the brain in patients with schizophrenia to dopaminergic hyperactivity and hypofunction of the glutamatergic neurotransmitter system, explaining why its onset is usually in adolescence or young adulthood.1,2 However, 23% of patients present with symptoms after age 40, with 7% of patients being diagnosed between the ages of 51 and 60.3
Late-onset vs early-onset schizophrenia. LOS is often a missed diagnosis because the clinical presentation is different from early-onset schizophrenia (EOS). Although the prodromal symptoms of EOS and LOS are similar and include marked isolation that subsequently progresses to suspiciousness and ideas of reference,4 patients with EOS often also have prodromal negative symptoms. These prodromal negative symptoms associated with EOS may include loss of motivation, social passivity, and disorganized behavior. These symptoms are hypothesized to be caused by dopaminergic dysregulation in the anterior cingulate cortex. EOS is characterized by the patient experiencing more negative symptoms than LOS, which is characterized by the patient experiencing more positive symptoms.
Continue to: Patients with late-onset schizophrenia...
Patients with LOS typically do not exhibit negative symptoms because remodeling and myelination of neuronal circuitry matures by late adulthood, and thus becomes more resistant to impairment of motivational processes in the anterior cingulate gyrus.4,5,6
LOS is characterized by paranoid personality with predominantly positive symptoms, likely due to disruptions in
Other features of LOS include a high female:male ratio and symptomatic improvement with antipsychotics.7,10 Studies show that the LOS ratio of women:men can range from 2.2:1 to 22.5:1, which could be explained by the effect of dopaminergic-modulating estrogen from different sex-specific aging brain patterns.8,11,12 Finally, patients with LOS are less likely to seek care for sensory deficits than their age-equivalent counterparts.8,10 Fortunately, many of the characteristics of LOS predict good prognosis: Patients are usually female, display positive symptoms, have acute onset of symptoms, and are married with social support.10
Diagnosing LOS
LOS can be challenging to diagnose because of its atypical presentation compared with EOS, relative rarity in the population, and its propensity to be confused with progressive Alzheimer disease/dementia, delusional disorder, and major depressive disorder with psychotic features.3,6 Patients with no prior psychiatric history often do not have ready access to psychiatrists and depend on PCPs and other clinicians to identify mental health issues. A careful history, including familial involvement, utilization of the Montreal Cognitive Assessment (MoCA) test, and evaluation of environmental factors, are crucial to arriving at the proper diagnosis.
Continue to: Differential diagnosis
Differential diagnosis. When psychosis appears later in life, it is important to consider a broad differential (TABLE13-18), which includes the following:
Alzheimer disease. LOS can be easily differentiated from psychosis associated with Alzheimer disease or dementia through findings from neuropsychologic assessments and brain imaging. The initial first-line assessment for Alzheimer disease includes determining time course of daily living impairment and memory with follow-up brain imaging. Magnetic resonance imaging of patients with Alzheimer disease shows clear atrophy of the medial temporal lobes and general brain atrophy.19 Other than hypoperfusion in the frontal and temporal area, brain imaging of patients with LOS will not reveal any pathology.1
Delusional disorder and LOS are often more challenging to differentiate because symptoms can overlap, and many of the negative symptoms that would otherwise help clinicians diagnose schizophrenia in a younger population are absent in LOS. The milder symptoms of LOS may also lead clinicians to favor a diagnosis of delusional disorder. However, the following differences can help physicians differentiate between LOS and delusional disorder. Delusional disorder20-22:
- often will include paranoid beliefs, but these beliefs will not be bizarre, and the patient’s daily functioning will not be impaired, whereas patients with schizophrenia would have an increase in isolation and impairment in functioning that tends to be distinct from baseline.
- is more rare than schizophrenia. Delusional disorder has a prevalence of 0.05% to 0.1% compared to 1% for schizophrenia.
Major depressive disorder (MDD) with psychotic features. Major depressive disorder with psychotic features is an important differential to consider in this setting because the treatment intervention can be considerably different. Among patients who have MDD with psychotic features, a significant mood component is present, and treatment typically focuses on optimizing a selective serotonin reuptake inhibitor (SSRI); depending on severity, electroconvulsive therapy (ECT) also may be warranted.19
Continue to: For patients with LOS...
For patients with LOS, optimizing an antipsychotic medication is the typical course of treatment, and ECT would likely have less of an impact than it does with MDD with psychotic features.
Other. Finally, in an acute setting, other differential diagnoses for mental status changes (depending on clinical findings) might include:
- drug/medication use
- delirium
- nutrient deficiencies
- acute head trauma
- chronic subdural hematoma
- syphilis
- Lyme disease
- HIV encephalitis
- heavy metal toxicity.
Treatment involves antipsychotics—especially certain ones
Antipsychotic medications are utilized for the treatment of patients with LOS. A Cochrane review concluded that there are no trial-based evidence guidelines for the treatment of patients with LOS, and that physicians should continue with their current practice and use clinical judgment and prescribing patterns to guide their selection of antipsychotic medications.22,23 Pearlson et al24 found that 76% of patients with schizophrenia achieved at least partial remission and 48% achieved full remission with antipsychotic treatment.
The preferred treatment for patients with schizophrenia is low doses of newer antipsychotics (atypical or second-generation antipsychotics [SGAs]) because they are less likely to cause extrapyramidal symptoms/adverse effects than first-generation antipsychotics. Examples of SGAs include aripiprazole, risperidone, olanzapine, quetiapine, and ziprasidone.
Effective treatment for LOS includes antipsychotics at a quarter to one-half of the usual therapeutic doses. In patients with very late-onset schizophrenia, doses should be started at a tenth of therapeutic dose.1,23 Physicians should titrate up carefully, as needed.
Continue to: As with any significant mental illness...
As with any significant mental illness, to improve clinical outcomes, family support may help patients’ medication adherence and ensure they attend scheduled medical appointments.
Our patient was eventually stabilized on long-acting injectable risperidone, 25 mg, with improvement in symptoms. Unfortunately, she was not convinced that her symptoms were psychiatric in nature and did not continue with her medications as an outpatient.
The patient’s nonadherence to her medication regimen led to 2 more hospitalizations with similar presentations over the following 2 years. On her most recent discharge, she was stabilized on oral olanzapine, 10 mg every night at bedtime, with close outpatient follow-up and family education.
THE TAKEAWAY
The prodromal phase of patients with LOS is similar to patients with EOS and includes withdrawal and isolation from others, making it difficult for physicians to evaluate and treat patients. Patients with LOS predominantly experience positive symptoms that may include delusions and hallucinations. Brain imaging studies can help rule out progressive dementia diseases. A neuropsychological evaluation can assess the patient’s functional level and types of delusions, which helps to differentiate LOS from other late-age psychoses. Treatment with SGAs make for a good prognosis; however, this requires patients to be adherent to treatment.
CORRESPONDENCE
Sandy Chan, MD, Department of Internal Medicine, UMass Memorial Medical Center, 55N Lake Avenue, Worcester, MA 01605; Sandy.Chan@umassmemorial.org
THE CASE
A 58-year-old married Asian woman with no apparent psychiatric history presented to the emergency department (ED) in an acute state with ideas of reference, paranoid delusions, and multiple, vague somatic symptoms.
Based on information in the patient’s medical record, there had been suspicion of an underlying psychiatric disorder 6 years earlier. At that time, the patient had presented to her primary care provider (PCP) with vague somatic complaints, including diffuse body pain, dry cough, chills, weakness, facial numbness, and concerns about infections. A physical examination and work-up did not reveal the source of her complaints. Unfortunately, the patient’s complaints increased in number and severity over time.
Her medical records also indicated that she had been assessed for depression severity using the Patient Health Questionnaire-9 (PHQ-9), with scores of 0 (4 years earlier) and 3 (3 years earlier). The scores suggested that she was not suffering from depression.
During this time, the patient also saw a psychiatrist; however, it was unclear whether her symptoms met the criteria for delusional disorder or schizophrenia because she did not exhibit negative symptoms or sensory hallucinations. In addition, the patient was extremely high-functioning in the community—she participated in dance classes and other social events—and had the equivalent of a medical degree from another country. Based on chart review, when she went to the psychiatrist 3 years prior to her current presentation, there were no antipsychotics prescribed.
In the weeks leading up to her current presentation, the patient reported that she was struggling with sleep, sometimes spending days in bed and other times needing unspecified medication obtained overseas to help her sleep. Her husband reported that she had become increasingly withdrawn and stopped attending her dance classes and social events.
The patient believed the government was trying to poison her via radiation and that unknown people were trying to harm her via an online messaging application. Immediately prior to her arrival in the ED, the police were called to pull her away from oncoming traffic because she ran into the road to find the assassins that were stalking her.
During this recent visit to the ED, the patient presented with labile affect, rapid speech, and anxious and angry mood. She complained about darkened spots on her arm (inflicted through radiation by the media), vaginal bleeding, paralysis below the waist (although she was pacing around), and unspecific pain around her belly. Physical examination revealed no obvious signs of head trauma, intact extraocular movements, no coughing or wheezing, regular heart rate and rhythm, a nontender abdomen to palpation, and normal bowel sounds. No focal neurological deficits were appreciated. She had no rashes, bruises, or skin abrasions on her abdomen or upper extremities.
Continue to: The patient tried to...
The patient tried to leave the ED, saying that her third eye could see the radiation. She required medication and 4-point restraints.
Her initial laboratory work-up for heavy metals, Lyme disease, human immunodeficiency virus (HIV), syphilis, delirium, and drug use were all negative. She also underwent head imaging studies that were also found to be negative. Her mental status exam was notable for a tangential thought process, preservation of delusions with loose associations, labile mood, and dysphoric affect. The patient demonstrated limited insight and judgment, although she was fully oriented to person, place, and time, which suggested against delirium at the time of evaluation.
THE DIAGNOSIS
Based on the patient’s current presentation and in light of her medical history, the health care team arrived at a
DISCUSSION
Schizophrenia is a severe, lifelong mental disorder characterized by at least 2 symptoms of delusions, hallucinations, disorganized speech, disorganized or catatonic behavior, or negative symptoms for at least 6 months, with significant social, occupational, and functional deterioration. Current models attribute the neurodevelopmental deregulation of the brain in patients with schizophrenia to dopaminergic hyperactivity and hypofunction of the glutamatergic neurotransmitter system, explaining why its onset is usually in adolescence or young adulthood.1,2 However, 23% of patients present with symptoms after age 40, with 7% of patients being diagnosed between the ages of 51 and 60.3
Late-onset vs early-onset schizophrenia. LOS is often a missed diagnosis because the clinical presentation is different from early-onset schizophrenia (EOS). Although the prodromal symptoms of EOS and LOS are similar and include marked isolation that subsequently progresses to suspiciousness and ideas of reference,4 patients with EOS often also have prodromal negative symptoms. These prodromal negative symptoms associated with EOS may include loss of motivation, social passivity, and disorganized behavior. These symptoms are hypothesized to be caused by dopaminergic dysregulation in the anterior cingulate cortex. EOS is characterized by the patient experiencing more negative symptoms than LOS, which is characterized by the patient experiencing more positive symptoms.
Continue to: Patients with late-onset schizophrenia...
Patients with LOS typically do not exhibit negative symptoms because remodeling and myelination of neuronal circuitry matures by late adulthood, and thus becomes more resistant to impairment of motivational processes in the anterior cingulate gyrus.4,5,6
LOS is characterized by paranoid personality with predominantly positive symptoms, likely due to disruptions in
Other features of LOS include a high female:male ratio and symptomatic improvement with antipsychotics.7,10 Studies show that the LOS ratio of women:men can range from 2.2:1 to 22.5:1, which could be explained by the effect of dopaminergic-modulating estrogen from different sex-specific aging brain patterns.8,11,12 Finally, patients with LOS are less likely to seek care for sensory deficits than their age-equivalent counterparts.8,10 Fortunately, many of the characteristics of LOS predict good prognosis: Patients are usually female, display positive symptoms, have acute onset of symptoms, and are married with social support.10
Diagnosing LOS
LOS can be challenging to diagnose because of its atypical presentation compared with EOS, relative rarity in the population, and its propensity to be confused with progressive Alzheimer disease/dementia, delusional disorder, and major depressive disorder with psychotic features.3,6 Patients with no prior psychiatric history often do not have ready access to psychiatrists and depend on PCPs and other clinicians to identify mental health issues. A careful history, including familial involvement, utilization of the Montreal Cognitive Assessment (MoCA) test, and evaluation of environmental factors, are crucial to arriving at the proper diagnosis.
Continue to: Differential diagnosis
Differential diagnosis. When psychosis appears later in life, it is important to consider a broad differential (TABLE13-18), which includes the following:
Alzheimer disease. LOS can be easily differentiated from psychosis associated with Alzheimer disease or dementia through findings from neuropsychologic assessments and brain imaging. The initial first-line assessment for Alzheimer disease includes determining time course of daily living impairment and memory with follow-up brain imaging. Magnetic resonance imaging of patients with Alzheimer disease shows clear atrophy of the medial temporal lobes and general brain atrophy.19 Other than hypoperfusion in the frontal and temporal area, brain imaging of patients with LOS will not reveal any pathology.1
Delusional disorder and LOS are often more challenging to differentiate because symptoms can overlap, and many of the negative symptoms that would otherwise help clinicians diagnose schizophrenia in a younger population are absent in LOS. The milder symptoms of LOS may also lead clinicians to favor a diagnosis of delusional disorder. However, the following differences can help physicians differentiate between LOS and delusional disorder. Delusional disorder20-22:
- often will include paranoid beliefs, but these beliefs will not be bizarre, and the patient’s daily functioning will not be impaired, whereas patients with schizophrenia would have an increase in isolation and impairment in functioning that tends to be distinct from baseline.
- is more rare than schizophrenia. Delusional disorder has a prevalence of 0.05% to 0.1% compared to 1% for schizophrenia.
Major depressive disorder (MDD) with psychotic features. Major depressive disorder with psychotic features is an important differential to consider in this setting because the treatment intervention can be considerably different. Among patients who have MDD with psychotic features, a significant mood component is present, and treatment typically focuses on optimizing a selective serotonin reuptake inhibitor (SSRI); depending on severity, electroconvulsive therapy (ECT) also may be warranted.19
Continue to: For patients with LOS...
For patients with LOS, optimizing an antipsychotic medication is the typical course of treatment, and ECT would likely have less of an impact than it does with MDD with psychotic features.
Other. Finally, in an acute setting, other differential diagnoses for mental status changes (depending on clinical findings) might include:
- drug/medication use
- delirium
- nutrient deficiencies
- acute head trauma
- chronic subdural hematoma
- syphilis
- Lyme disease
- HIV encephalitis
- heavy metal toxicity.
Treatment involves antipsychotics—especially certain ones
Antipsychotic medications are utilized for the treatment of patients with LOS. A Cochrane review concluded that there are no trial-based evidence guidelines for the treatment of patients with LOS, and that physicians should continue with their current practice and use clinical judgment and prescribing patterns to guide their selection of antipsychotic medications.22,23 Pearlson et al24 found that 76% of patients with schizophrenia achieved at least partial remission and 48% achieved full remission with antipsychotic treatment.
The preferred treatment for patients with schizophrenia is low doses of newer antipsychotics (atypical or second-generation antipsychotics [SGAs]) because they are less likely to cause extrapyramidal symptoms/adverse effects than first-generation antipsychotics. Examples of SGAs include aripiprazole, risperidone, olanzapine, quetiapine, and ziprasidone.
Effective treatment for LOS includes antipsychotics at a quarter to one-half of the usual therapeutic doses. In patients with very late-onset schizophrenia, doses should be started at a tenth of therapeutic dose.1,23 Physicians should titrate up carefully, as needed.
Continue to: As with any significant mental illness...
As with any significant mental illness, to improve clinical outcomes, family support may help patients’ medication adherence and ensure they attend scheduled medical appointments.
Our patient was eventually stabilized on long-acting injectable risperidone, 25 mg, with improvement in symptoms. Unfortunately, she was not convinced that her symptoms were psychiatric in nature and did not continue with her medications as an outpatient.
The patient’s nonadherence to her medication regimen led to 2 more hospitalizations with similar presentations over the following 2 years. On her most recent discharge, she was stabilized on oral olanzapine, 10 mg every night at bedtime, with close outpatient follow-up and family education.
THE TAKEAWAY
The prodromal phase of patients with LOS is similar to patients with EOS and includes withdrawal and isolation from others, making it difficult for physicians to evaluate and treat patients. Patients with LOS predominantly experience positive symptoms that may include delusions and hallucinations. Brain imaging studies can help rule out progressive dementia diseases. A neuropsychological evaluation can assess the patient’s functional level and types of delusions, which helps to differentiate LOS from other late-age psychoses. Treatment with SGAs make for a good prognosis; however, this requires patients to be adherent to treatment.
CORRESPONDENCE
Sandy Chan, MD, Department of Internal Medicine, UMass Memorial Medical Center, 55N Lake Avenue, Worcester, MA 01605; Sandy.Chan@umassmemorial.org
1. Howard R, Rabins P, Seeman M, et al. Late-onset schizophrenia and very-late-onset schizophrenia-like psychosis: an international crisis. Am J Psychiatry 2000;157:172-178.
2. Pickard B. Progress in defining the biological causes of schizophrenia. Expert Rev Mol Med. 2011;13:e25.
3. Jeste D, Symonds L, Harris M, et al. Nondementia nonpraecox dementia praecox? Am J Geriatr Psychiatry. 1997;5:302-317.
4. Gourzis P, Katrivanou A, Beratis S. Symptomatology of the initial prodromal phase of schizophrenia. Schizophr Bull. 2002;28:415-429.
5. Dolan R, Fletcher P, Frith C, et al. Dopaminergic modulation of impaired cognitive activation in the anterior cingulate cortex in schizophrenia. Nature. 1995;378:180-182.
6. Skokou M, Katrivanou A, Andriopoulos I, et al. Active and prodromal phase symptomatology of young-onset and late-onset paranoid schizophrenia. Rev Psiquiatr Salud Ment. 2012;5:150-159.
7. Riecher-Rossler A, Loffler W, Munk-Jorgensen P. What do we really know about late-onset schizophrenia? Eur Arch Psychiatry Clin Neurosci. 1997;247:195-208.
8. Lubman D, Castle D. Late-onset schizophrenia: make the right diagnosis when psychosis emerges after age 60. Current Psychiatry. 2002;1:35-44.
9. Howard R, Castle D, Wessely S, et al. A comparative study of 470 cases of early-onset and late-onset schizophrenia. British Journal of Psychiatry. 1993;163:352-357.
10. Harris M, Jeste D. Late-onset schizophrenia: an overview. Schizophr Bull. 1988;14:39-55.
11. Castle D, Murray R. The epidemiology of late-onset schizophrenia. Schizophr Bull. 1993;19:691-700.
12. Lindamer L, Lohr J, Harris M, Jeste D. Gender, estrogen, and schizophrenia. Psychopharmacol Bull. 1997;33:221-228.
13. Gaudiano BA, Dalrymple KL, Zimmerman M. Prevalence and clinical characteristics of psychotic versus non-psychotic major depression in a general psychiatric outpatient clinic. Depress Anxiety. 2009;26:54-64.
14. Saha S, Chant D, Welham J, et al. A systematic review of the prevalence of schizophrenia. PLoS Med. 2005;2:e141.
15. Gao S, Hendrie H, Hall K. The relationships between age, sex, and the incidence of dementia and Alzheimer Disease. JAMA Psychiatry. 1998;55:809-815.
16. Reitz C, Brayne C, Mayeux R. Epidemiology of Alzheimer Disease. Nature Reviews Neurology. 2011;7:137-152
17. Winokur G. Delusional Disorder (Paranoia). Comprehensive Psychiatry. 1977;18:511-521.
18. Scheltens P, Leys D, Huglo D, et al. Atrophy of medial temporal lobes on MRI in “probable” Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol, Neurosurg Psychiatry. 1992;55:967-972.
19. Copeland J, Dewey M, Scott A, et al. Schizophrenia and delusional disorder in older age: community prevalence, incidence, comorbidity, and outcome. Schizophr Bull. 1998;24:153-161.
20. Kendler K. Demography of paranoid psychosis (delusional disorder): a review and comparison with schizophrenia and affective illness. Arch Gen Psychiatry 1982;39:890-902.
21. McGrath J, Saha S, Chant D, et al. Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiol Rev. 2008;30:67.
22. Essali A, Ali G. Antipsychotic drug treatment for elderly people with late-onset schizophrenia. Cochrane Database Syst Rev. 2012;(2):CD004162.
23. Sweet R, Pollock B. New atypical antipsychotics- experience and utility in the elderly. Drugs Aging. 1998;12:115-127.
24. Pearlson G, Kreger L, Rabins P, et al. A chart review study of late-onset and early-onset schizophrenia. Am J Psychiatry.1989;146:1568-1574.
1. Howard R, Rabins P, Seeman M, et al. Late-onset schizophrenia and very-late-onset schizophrenia-like psychosis: an international crisis. Am J Psychiatry 2000;157:172-178.
2. Pickard B. Progress in defining the biological causes of schizophrenia. Expert Rev Mol Med. 2011;13:e25.
3. Jeste D, Symonds L, Harris M, et al. Nondementia nonpraecox dementia praecox? Am J Geriatr Psychiatry. 1997;5:302-317.
4. Gourzis P, Katrivanou A, Beratis S. Symptomatology of the initial prodromal phase of schizophrenia. Schizophr Bull. 2002;28:415-429.
5. Dolan R, Fletcher P, Frith C, et al. Dopaminergic modulation of impaired cognitive activation in the anterior cingulate cortex in schizophrenia. Nature. 1995;378:180-182.
6. Skokou M, Katrivanou A, Andriopoulos I, et al. Active and prodromal phase symptomatology of young-onset and late-onset paranoid schizophrenia. Rev Psiquiatr Salud Ment. 2012;5:150-159.
7. Riecher-Rossler A, Loffler W, Munk-Jorgensen P. What do we really know about late-onset schizophrenia? Eur Arch Psychiatry Clin Neurosci. 1997;247:195-208.
8. Lubman D, Castle D. Late-onset schizophrenia: make the right diagnosis when psychosis emerges after age 60. Current Psychiatry. 2002;1:35-44.
9. Howard R, Castle D, Wessely S, et al. A comparative study of 470 cases of early-onset and late-onset schizophrenia. British Journal of Psychiatry. 1993;163:352-357.
10. Harris M, Jeste D. Late-onset schizophrenia: an overview. Schizophr Bull. 1988;14:39-55.
11. Castle D, Murray R. The epidemiology of late-onset schizophrenia. Schizophr Bull. 1993;19:691-700.
12. Lindamer L, Lohr J, Harris M, Jeste D. Gender, estrogen, and schizophrenia. Psychopharmacol Bull. 1997;33:221-228.
13. Gaudiano BA, Dalrymple KL, Zimmerman M. Prevalence and clinical characteristics of psychotic versus non-psychotic major depression in a general psychiatric outpatient clinic. Depress Anxiety. 2009;26:54-64.
14. Saha S, Chant D, Welham J, et al. A systematic review of the prevalence of schizophrenia. PLoS Med. 2005;2:e141.
15. Gao S, Hendrie H, Hall K. The relationships between age, sex, and the incidence of dementia and Alzheimer Disease. JAMA Psychiatry. 1998;55:809-815.
16. Reitz C, Brayne C, Mayeux R. Epidemiology of Alzheimer Disease. Nature Reviews Neurology. 2011;7:137-152
17. Winokur G. Delusional Disorder (Paranoia). Comprehensive Psychiatry. 1977;18:511-521.
18. Scheltens P, Leys D, Huglo D, et al. Atrophy of medial temporal lobes on MRI in “probable” Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol, Neurosurg Psychiatry. 1992;55:967-972.
19. Copeland J, Dewey M, Scott A, et al. Schizophrenia and delusional disorder in older age: community prevalence, incidence, comorbidity, and outcome. Schizophr Bull. 1998;24:153-161.
20. Kendler K. Demography of paranoid psychosis (delusional disorder): a review and comparison with schizophrenia and affective illness. Arch Gen Psychiatry 1982;39:890-902.
21. McGrath J, Saha S, Chant D, et al. Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiol Rev. 2008;30:67.
22. Essali A, Ali G. Antipsychotic drug treatment for elderly people with late-onset schizophrenia. Cochrane Database Syst Rev. 2012;(2):CD004162.
23. Sweet R, Pollock B. New atypical antipsychotics- experience and utility in the elderly. Drugs Aging. 1998;12:115-127.
24. Pearlson G, Kreger L, Rabins P, et al. A chart review study of late-onset and early-onset schizophrenia. Am J Psychiatry.1989;146:1568-1574.
