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Third transplant patient cured of HIV marks important firsts
that has plagued the world for decades.
But while this case is certainly cause for celebration, experts involved in the effort say we are still a long way from a universal cure.
Researcher Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, told those attending the Conference on Retroviruses and Opportunistic Infections that this case is special. The patient was a woman living with HIV who is multiracial. The previous two patients were men: one white, one Latinx.
The woman in this case was given transplants of stem cells and umbilical cord blood to treat leukemia. The treatment not only sent her cancer into remission, but her HIV as well.
The success of this case suggests that cord stem cell transplants should be considered to produce remission and cure for those with HIV who also have cancers and other diseases, the researchers said.
While the news was met with excitement in the scientific community, the approach will not be available universally, since the transplants were all done to treat cancers in the three HIV-infected patients. Overall, Dr. Bryson estimates that about 50 people per year may benefit from this procedure.
Even so, other experts say the approach could provide insight into other ways to find cures. And Dr. Bryson says it opens up options for more diverse populations.
“A bone marrow transplant is not a viable large-scale strategy for curing HIV, but it does present a proof of concept that HIV can be cured,” said Sharon Lewin, MD, president-elect of the International AIDS Society. “It also further strengthens using gene therapy as a viable strategy for an HIV cure.”
The woman needed a stem cell transplant after being diagnosed with leukemia. The stem cell transplant technique used was also novel, Dr. Bryson said. The medical team used a combination of adult stem cells from a relative’s blood and umbilical cord blood from a cord-blood bank that had a rare mutation that makes the immune system resistant to HIV.
In the previous two cases of HIV cures after transplants, both patients were treated with stem cell transplants, with the same mutation, but from bone marrow transplants, a more difficult procedure. And no cord blood was used for those.
The combination of adult cells and cord-blood cells proved to be the ticket to success. Using the adult cells provides a kind of bridge that helps until the cord blood takes over, the researchers said. By day 100 after the transplant, Dr. Bryson said, the woman basically had a new immune system.
HIV remained undetectable in T cells and in bone marrow. And 37 months after the transplant, the woman stopped taking the antiretroviral treatment commonly given to treat HIV infection.
‘’She is currently clinically well,” Dr. Bryson said. Her cancer is in remission.
Case histories: Three patients
The woman, who is middle-aged, has requested privacy, asking that neither her age nor other details be released. But the researchers did provide some background on her medical history and her route back to health. She was diagnosed with HIV in 2013 and began treatment with antiretroviral therapy (ART). Four years after her HIV diagnosis, she developed high-risk acute myelogenous leukemia. The transplant was done to treat that.
Her recovery was much less bumpy than that of the previous two patients, the researchers said. She left the hospital 17 days after the transplant. She didn’t have serious complications like the first two, who developed a condition that occurs when donor bone marrow or stem cells attack the recipient.
“This case also suggests that it’s the transplant of HIV-resistant cells that was key to achieving a cure here,” said Dr. Lewin. The first patient who had HIV remission after a stem cell transplant, a White man, stayed in remission for 12 years and was termed cured. But he died of leukemia in September 2020. The other, a Latinx man, has been in remission for more than 30 months.
HIV statistics, ethnic/racial burdens
In the United States, about 1.2 million people have HIV, according to HIV.gov. Thirteen percent of those who have it do not know they have it. In 2019, 34,800 new infections were diagnosed.
Certain ethnic and racial groups are more affected by HIV than others, given their proportions in the U.S. population, federal statistics suggest. In 2019, for instance, African Americans were 13% of the U.S. population but 40% of those with HIV. Hispanics/Latinx represented 18.5% of the total population but 25% of those diagnosed with HIV.
Disparities also affect women unequally, with Black women disproportionately affected, compared to women of other ethnic and racial groups. Annual HIV infections remained stable overall among Black women from 2015 to 2019, but the rate of new HIV infections among Black women is 11 times that of White women and 4 times that of Latinx, according to federal statistics.
Expert perspective, reactions
Vincent Marconi, MD, professor of infectious diseases at Emory University, Atlanta, whose research focuses on disparities in HIV treatment responses, called the news “an exciting development for the cure agenda. This is the first woman to have been cured for at least 14 months, and they used cord blood, which could allow for potentially less toxic regimens and fewer adverse effects.”
Although the approach, meant to be used to treat the cancers, will not be widely available, he said that ‘’it does provide insight into somewhat related alternative models of cure involving gene therapy.”
Meanwhile, Dr. Marconi and other researchers are focusing on the concept of long-term HIV remission if a cure is not possible. Among the strategies under study are gene editing and immune-based treatments. HIV remission is generally defined as having an HIV viral load that is not detectable after stopping treatment.
A version of this article first appeared on WebMD.com.
that has plagued the world for decades.
But while this case is certainly cause for celebration, experts involved in the effort say we are still a long way from a universal cure.
Researcher Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, told those attending the Conference on Retroviruses and Opportunistic Infections that this case is special. The patient was a woman living with HIV who is multiracial. The previous two patients were men: one white, one Latinx.
The woman in this case was given transplants of stem cells and umbilical cord blood to treat leukemia. The treatment not only sent her cancer into remission, but her HIV as well.
The success of this case suggests that cord stem cell transplants should be considered to produce remission and cure for those with HIV who also have cancers and other diseases, the researchers said.
While the news was met with excitement in the scientific community, the approach will not be available universally, since the transplants were all done to treat cancers in the three HIV-infected patients. Overall, Dr. Bryson estimates that about 50 people per year may benefit from this procedure.
Even so, other experts say the approach could provide insight into other ways to find cures. And Dr. Bryson says it opens up options for more diverse populations.
“A bone marrow transplant is not a viable large-scale strategy for curing HIV, but it does present a proof of concept that HIV can be cured,” said Sharon Lewin, MD, president-elect of the International AIDS Society. “It also further strengthens using gene therapy as a viable strategy for an HIV cure.”
The woman needed a stem cell transplant after being diagnosed with leukemia. The stem cell transplant technique used was also novel, Dr. Bryson said. The medical team used a combination of adult stem cells from a relative’s blood and umbilical cord blood from a cord-blood bank that had a rare mutation that makes the immune system resistant to HIV.
In the previous two cases of HIV cures after transplants, both patients were treated with stem cell transplants, with the same mutation, but from bone marrow transplants, a more difficult procedure. And no cord blood was used for those.
The combination of adult cells and cord-blood cells proved to be the ticket to success. Using the adult cells provides a kind of bridge that helps until the cord blood takes over, the researchers said. By day 100 after the transplant, Dr. Bryson said, the woman basically had a new immune system.
HIV remained undetectable in T cells and in bone marrow. And 37 months after the transplant, the woman stopped taking the antiretroviral treatment commonly given to treat HIV infection.
‘’She is currently clinically well,” Dr. Bryson said. Her cancer is in remission.
Case histories: Three patients
The woman, who is middle-aged, has requested privacy, asking that neither her age nor other details be released. But the researchers did provide some background on her medical history and her route back to health. She was diagnosed with HIV in 2013 and began treatment with antiretroviral therapy (ART). Four years after her HIV diagnosis, she developed high-risk acute myelogenous leukemia. The transplant was done to treat that.
Her recovery was much less bumpy than that of the previous two patients, the researchers said. She left the hospital 17 days after the transplant. She didn’t have serious complications like the first two, who developed a condition that occurs when donor bone marrow or stem cells attack the recipient.
“This case also suggests that it’s the transplant of HIV-resistant cells that was key to achieving a cure here,” said Dr. Lewin. The first patient who had HIV remission after a stem cell transplant, a White man, stayed in remission for 12 years and was termed cured. But he died of leukemia in September 2020. The other, a Latinx man, has been in remission for more than 30 months.
HIV statistics, ethnic/racial burdens
In the United States, about 1.2 million people have HIV, according to HIV.gov. Thirteen percent of those who have it do not know they have it. In 2019, 34,800 new infections were diagnosed.
Certain ethnic and racial groups are more affected by HIV than others, given their proportions in the U.S. population, federal statistics suggest. In 2019, for instance, African Americans were 13% of the U.S. population but 40% of those with HIV. Hispanics/Latinx represented 18.5% of the total population but 25% of those diagnosed with HIV.
Disparities also affect women unequally, with Black women disproportionately affected, compared to women of other ethnic and racial groups. Annual HIV infections remained stable overall among Black women from 2015 to 2019, but the rate of new HIV infections among Black women is 11 times that of White women and 4 times that of Latinx, according to federal statistics.
Expert perspective, reactions
Vincent Marconi, MD, professor of infectious diseases at Emory University, Atlanta, whose research focuses on disparities in HIV treatment responses, called the news “an exciting development for the cure agenda. This is the first woman to have been cured for at least 14 months, and they used cord blood, which could allow for potentially less toxic regimens and fewer adverse effects.”
Although the approach, meant to be used to treat the cancers, will not be widely available, he said that ‘’it does provide insight into somewhat related alternative models of cure involving gene therapy.”
Meanwhile, Dr. Marconi and other researchers are focusing on the concept of long-term HIV remission if a cure is not possible. Among the strategies under study are gene editing and immune-based treatments. HIV remission is generally defined as having an HIV viral load that is not detectable after stopping treatment.
A version of this article first appeared on WebMD.com.
that has plagued the world for decades.
But while this case is certainly cause for celebration, experts involved in the effort say we are still a long way from a universal cure.
Researcher Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, told those attending the Conference on Retroviruses and Opportunistic Infections that this case is special. The patient was a woman living with HIV who is multiracial. The previous two patients were men: one white, one Latinx.
The woman in this case was given transplants of stem cells and umbilical cord blood to treat leukemia. The treatment not only sent her cancer into remission, but her HIV as well.
The success of this case suggests that cord stem cell transplants should be considered to produce remission and cure for those with HIV who also have cancers and other diseases, the researchers said.
While the news was met with excitement in the scientific community, the approach will not be available universally, since the transplants were all done to treat cancers in the three HIV-infected patients. Overall, Dr. Bryson estimates that about 50 people per year may benefit from this procedure.
Even so, other experts say the approach could provide insight into other ways to find cures. And Dr. Bryson says it opens up options for more diverse populations.
“A bone marrow transplant is not a viable large-scale strategy for curing HIV, but it does present a proof of concept that HIV can be cured,” said Sharon Lewin, MD, president-elect of the International AIDS Society. “It also further strengthens using gene therapy as a viable strategy for an HIV cure.”
The woman needed a stem cell transplant after being diagnosed with leukemia. The stem cell transplant technique used was also novel, Dr. Bryson said. The medical team used a combination of adult stem cells from a relative’s blood and umbilical cord blood from a cord-blood bank that had a rare mutation that makes the immune system resistant to HIV.
In the previous two cases of HIV cures after transplants, both patients were treated with stem cell transplants, with the same mutation, but from bone marrow transplants, a more difficult procedure. And no cord blood was used for those.
The combination of adult cells and cord-blood cells proved to be the ticket to success. Using the adult cells provides a kind of bridge that helps until the cord blood takes over, the researchers said. By day 100 after the transplant, Dr. Bryson said, the woman basically had a new immune system.
HIV remained undetectable in T cells and in bone marrow. And 37 months after the transplant, the woman stopped taking the antiretroviral treatment commonly given to treat HIV infection.
‘’She is currently clinically well,” Dr. Bryson said. Her cancer is in remission.
Case histories: Three patients
The woman, who is middle-aged, has requested privacy, asking that neither her age nor other details be released. But the researchers did provide some background on her medical history and her route back to health. She was diagnosed with HIV in 2013 and began treatment with antiretroviral therapy (ART). Four years after her HIV diagnosis, she developed high-risk acute myelogenous leukemia. The transplant was done to treat that.
Her recovery was much less bumpy than that of the previous two patients, the researchers said. She left the hospital 17 days after the transplant. She didn’t have serious complications like the first two, who developed a condition that occurs when donor bone marrow or stem cells attack the recipient.
“This case also suggests that it’s the transplant of HIV-resistant cells that was key to achieving a cure here,” said Dr. Lewin. The first patient who had HIV remission after a stem cell transplant, a White man, stayed in remission for 12 years and was termed cured. But he died of leukemia in September 2020. The other, a Latinx man, has been in remission for more than 30 months.
HIV statistics, ethnic/racial burdens
In the United States, about 1.2 million people have HIV, according to HIV.gov. Thirteen percent of those who have it do not know they have it. In 2019, 34,800 new infections were diagnosed.
Certain ethnic and racial groups are more affected by HIV than others, given their proportions in the U.S. population, federal statistics suggest. In 2019, for instance, African Americans were 13% of the U.S. population but 40% of those with HIV. Hispanics/Latinx represented 18.5% of the total population but 25% of those diagnosed with HIV.
Disparities also affect women unequally, with Black women disproportionately affected, compared to women of other ethnic and racial groups. Annual HIV infections remained stable overall among Black women from 2015 to 2019, but the rate of new HIV infections among Black women is 11 times that of White women and 4 times that of Latinx, according to federal statistics.
Expert perspective, reactions
Vincent Marconi, MD, professor of infectious diseases at Emory University, Atlanta, whose research focuses on disparities in HIV treatment responses, called the news “an exciting development for the cure agenda. This is the first woman to have been cured for at least 14 months, and they used cord blood, which could allow for potentially less toxic regimens and fewer adverse effects.”
Although the approach, meant to be used to treat the cancers, will not be widely available, he said that ‘’it does provide insight into somewhat related alternative models of cure involving gene therapy.”
Meanwhile, Dr. Marconi and other researchers are focusing on the concept of long-term HIV remission if a cure is not possible. Among the strategies under study are gene editing and immune-based treatments. HIV remission is generally defined as having an HIV viral load that is not detectable after stopping treatment.
A version of this article first appeared on WebMD.com.
FROM CROI 22
Infectious disease pop quiz: Clinical challenge #15 for the ObGyn
What is the most appropriate treatment for a pregnant woman who is moderately to severely ill with COVID-19 infection?
Continue to the answer...
Moderately to severely ill pregnant women with COVID-19 infection should be hospitalized and treated with supplementary oxygen, remdesivir, and dexamethasone. Other possible therapies include inhaled nitric oxide, baricitinib (a Janus kinase inhibitor), and tocilizumab (an anti-interleukin 6 receptor antibody). (RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med. 2021;384:693-704. Kalil AC, Patterson TF, Mehta AK, et al; ACTT-2 Study Group. Baricitinib plus remdesivir for hospitalized adults with COVID-19. N Engl J Med. 2021;384:795-807. Berlin DA, Gulick RM, Martinez FJ, et al. Severe COVID-19. N Engl J Med. 2020;383;2451-2460.)
- Duff P. Maternal and perinatal infections: bacterial. In: Landon MB, Galan HL, Jauniaux ERM, et al. Gabbe’s Obstetrics: Normal and Problem Pregnancies. 8th ed. Elsevier; 2021:1124-1146.
- Duff P. Maternal and fetal infections. In: Resnik R, Lockwood CJ, Moore TJ, et al. Creasy & Resnik’s Maternal-Fetal Medicine: Principles and Practice. 8th ed. Elsevier; 2019:862-919.
Dr. Edwards is a Resident in the Department of Medicine, University of Florida College of Medicine, Gainesville.
Dr. Duff is Professor of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.
The authors report no financial relationships relevant to this article.
Dr. Edwards is a Resident in the Department of Medicine, University of Florida College of Medicine, Gainesville.
Dr. Duff is Professor of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.
The authors report no financial relationships relevant to this article.
Dr. Edwards is a Resident in the Department of Medicine, University of Florida College of Medicine, Gainesville.
Dr. Duff is Professor of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.
The authors report no financial relationships relevant to this article.
What is the most appropriate treatment for a pregnant woman who is moderately to severely ill with COVID-19 infection?
Continue to the answer...
Moderately to severely ill pregnant women with COVID-19 infection should be hospitalized and treated with supplementary oxygen, remdesivir, and dexamethasone. Other possible therapies include inhaled nitric oxide, baricitinib (a Janus kinase inhibitor), and tocilizumab (an anti-interleukin 6 receptor antibody). (RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med. 2021;384:693-704. Kalil AC, Patterson TF, Mehta AK, et al; ACTT-2 Study Group. Baricitinib plus remdesivir for hospitalized adults with COVID-19. N Engl J Med. 2021;384:795-807. Berlin DA, Gulick RM, Martinez FJ, et al. Severe COVID-19. N Engl J Med. 2020;383;2451-2460.)
What is the most appropriate treatment for a pregnant woman who is moderately to severely ill with COVID-19 infection?
Continue to the answer...
Moderately to severely ill pregnant women with COVID-19 infection should be hospitalized and treated with supplementary oxygen, remdesivir, and dexamethasone. Other possible therapies include inhaled nitric oxide, baricitinib (a Janus kinase inhibitor), and tocilizumab (an anti-interleukin 6 receptor antibody). (RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med. 2021;384:693-704. Kalil AC, Patterson TF, Mehta AK, et al; ACTT-2 Study Group. Baricitinib plus remdesivir for hospitalized adults with COVID-19. N Engl J Med. 2021;384:795-807. Berlin DA, Gulick RM, Martinez FJ, et al. Severe COVID-19. N Engl J Med. 2020;383;2451-2460.)
- Duff P. Maternal and perinatal infections: bacterial. In: Landon MB, Galan HL, Jauniaux ERM, et al. Gabbe’s Obstetrics: Normal and Problem Pregnancies. 8th ed. Elsevier; 2021:1124-1146.
- Duff P. Maternal and fetal infections. In: Resnik R, Lockwood CJ, Moore TJ, et al. Creasy & Resnik’s Maternal-Fetal Medicine: Principles and Practice. 8th ed. Elsevier; 2019:862-919.
- Duff P. Maternal and perinatal infections: bacterial. In: Landon MB, Galan HL, Jauniaux ERM, et al. Gabbe’s Obstetrics: Normal and Problem Pregnancies. 8th ed. Elsevier; 2021:1124-1146.
- Duff P. Maternal and fetal infections. In: Resnik R, Lockwood CJ, Moore TJ, et al. Creasy & Resnik’s Maternal-Fetal Medicine: Principles and Practice. 8th ed. Elsevier; 2019:862-919.
DOACs comparable to warfarin in CVT
and are less likely to result in major bleeding, a retrospective study suggests.
The ACTION CVT study was presented at the International Stroke Conference (ISC) 2022 by Ekaterina Bakradze, MD, assistant professor of neurology at the University of Alabama at Birmingham.
It was also simultaneously published online in Stroke.
“This real-world data supports use of direct oral anticoagulant drugs as a reasonable alternative to warfarin in patients with cerebral venous thrombosis,” Dr. Bakradze concluded.
But she added that because this study was based on retrospective observational data, the findings should be interpreted with caution and require confirmation by larger prospective studies.
Two such studies are now underway: the Direct Oral Anticoagulants in the Treatment of Cerebral Venous Thrombosis (DOAC-CVT) study and the randomized Study of Rivaroxaban for Cerebral Venous Thrombosis (SECRET) trial.
Dr. Bakradze explained that cerebral venous thrombosis is a less common cause of stroke and occurs more often in women and younger patients, with a median age of 37 years. Current recommended treatment consists of heparin followed by oral anticoagulation.
She noted that although randomized trials and current guidelines indicate that DOACs are a preferred alternative to warfarin for the treatment of patients with venous thromboembolism, there are limited data on their use in patients with CVT.
A small, randomized trial (RESPECT-CVT) showed no significant difference in efficacy and safety outcomes between dabigatran and warfarin in patients with cerebral venous thrombosis, but with only 120 patients, this trial was too small for definite answers to this question.
A better understanding of this issue is important, because the mechanisms underlying cerebral venous thrombosis and other thromboembolism and their subsequent risks may differ, Dr. Bakradze said.
As randomized trials in patients with cerebral venous thrombosis are difficult to perform because the condition has a low incidence and low event rates, the researchers decided to look at this question with a large retrospective multicenter study.
The ACTION-CVT study involved 845 consecutive patients with cerebral venous thrombosis over 6 years (from January 2015 and December 2020) from 27 centers in Italy, New Zealand, Switzerland, and the United States. Patients were identified from medical records with diagnostic codes and confirmed with imaging.
The primary predictor in the study was oral anticoagulant type (DOAC vs. warfarin). Study outcomes were abstracted by individual sites through review of all available medical records.
The primary outcome was recurrent venous thrombosis (venous thromboembolism or cerebral venous thrombosis) during follow-up. Imaging outcomes based on recanalization status on last venous imaging study abstracted from radiology reports were also reported.
The safety outcome was major hemorrhage, defined as new or worsening intracranial hemorrhage (ICH), or major extracranial hemorrhage. Results were adjusted for age, sex, and relevant medical conditions.
The mean age of the patients included was 44.8 years, 64.7% were women, 33% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times.
Results showed that during a median follow-up of 345 days, there were 5.68 recurrent venous thrombosis events, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years.
Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization.
When compared with warfarin, DOAC treatment was associated with similar risk for recurrent venous thrombosis (adjusted hazard ratio, 0.94; 95% confidence interval, 0.51-1.73; P = .84), death (aHR, 0.71, 95% CI, 0.24-2.08; P = .53), and rate of partial/complete recanalization (aHR, 0.92, 95% CI, 0.48-1.73; P = .79).
But patients who received a DOAC had a significantly lower rate of major hemorrhage (aHR, 0.35; 95% CI, 0.15-0.81; P = .02).
When examined separately, the occurrence of ICH per 100 patient-years was much lower among the patients prescribed DOACs than those who were prescribed warfarin (1.52 vs. 3.51), whereas the occurrence of major bleeding outside the brain was similar (0.91 vs. 1.15).
Similar efficacy, better safety
Commenting on the study at an ISC press conference, Mitchell Elkind, MD, immediate past president of the American Heart Association/American Stroke Association and professor of neurology at Columbia University, New York, said: “The community has been concerned about extending the use of these new direct-acting oral anticoagulant drugs to cerebral venous thrombosis, but this study suggests that these patients may benefit from these new agents too.”
Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, also commented: “This study confirms what we already know from other indications about these DOAC drugs: that they have similar efficacy to warfarin but a better safety profile. These results are really spot on with that. These drugs are also much easier and more convenient to use than warfarin.”
“This is a great step forward,” he added. “Only 30% of patients in this study received DOACs, reflecting the fact that clinicians may be a little reluctant to use them in this condition. But this study now has the potential to change practice.”
In an editorial accompanying the publication in Stroke, Johnathon Gorman, MD, and Thalia Field, MD, from the Vancouver Stroke Program at the University of British Columbia, say that despite its methodological limitations, the ACTION-CVT study “provides added value to the current state of knowledge by virtue of its size and ‘real world’ setting that is reflective of how DOACs are being used to manage CVT in current clinical practice.”
They point out that although baseline characteristics between the DOAC and warfarin groups were similar, the possibility of confounding cannot be excluded, and “other characteristics not easily captured in a retrospective study may sway anticoagulation strategy.”
They acknowledge, however, that an additional propensity score analysis “provides reassurance that the groups are reasonably balanced, adjusting for variables associated with recurrent cerebral venous thrombosis, recanalization, and hemorrhage.”
The editorialists conclude that ACTION-CVT gives additional reassurance for DOACs as an alternative approach to warfarin as a treatment for cerebral venous thrombosis and for the shifts in clinical practice that are already occurring at many centers.
The study was partially supported by the Italian Ministry of Health Ricerca Corrente–IRCCS MultiMedica. Dr. Bakradze reports no disclosures. Dr. Field is the principal investigator of the SECRET trial, which received in-kind study medication from Bayer Canada. She reports honoraria from HLS Therapeutics outside the submitted work and is on the board of Destine Health. The other editorialist reports no conflicts.
A version of this article first appeared on Medscape.com.
and are less likely to result in major bleeding, a retrospective study suggests.
The ACTION CVT study was presented at the International Stroke Conference (ISC) 2022 by Ekaterina Bakradze, MD, assistant professor of neurology at the University of Alabama at Birmingham.
It was also simultaneously published online in Stroke.
“This real-world data supports use of direct oral anticoagulant drugs as a reasonable alternative to warfarin in patients with cerebral venous thrombosis,” Dr. Bakradze concluded.
But she added that because this study was based on retrospective observational data, the findings should be interpreted with caution and require confirmation by larger prospective studies.
Two such studies are now underway: the Direct Oral Anticoagulants in the Treatment of Cerebral Venous Thrombosis (DOAC-CVT) study and the randomized Study of Rivaroxaban for Cerebral Venous Thrombosis (SECRET) trial.
Dr. Bakradze explained that cerebral venous thrombosis is a less common cause of stroke and occurs more often in women and younger patients, with a median age of 37 years. Current recommended treatment consists of heparin followed by oral anticoagulation.
She noted that although randomized trials and current guidelines indicate that DOACs are a preferred alternative to warfarin for the treatment of patients with venous thromboembolism, there are limited data on their use in patients with CVT.
A small, randomized trial (RESPECT-CVT) showed no significant difference in efficacy and safety outcomes between dabigatran and warfarin in patients with cerebral venous thrombosis, but with only 120 patients, this trial was too small for definite answers to this question.
A better understanding of this issue is important, because the mechanisms underlying cerebral venous thrombosis and other thromboembolism and their subsequent risks may differ, Dr. Bakradze said.
As randomized trials in patients with cerebral venous thrombosis are difficult to perform because the condition has a low incidence and low event rates, the researchers decided to look at this question with a large retrospective multicenter study.
The ACTION-CVT study involved 845 consecutive patients with cerebral venous thrombosis over 6 years (from January 2015 and December 2020) from 27 centers in Italy, New Zealand, Switzerland, and the United States. Patients were identified from medical records with diagnostic codes and confirmed with imaging.
The primary predictor in the study was oral anticoagulant type (DOAC vs. warfarin). Study outcomes were abstracted by individual sites through review of all available medical records.
The primary outcome was recurrent venous thrombosis (venous thromboembolism or cerebral venous thrombosis) during follow-up. Imaging outcomes based on recanalization status on last venous imaging study abstracted from radiology reports were also reported.
The safety outcome was major hemorrhage, defined as new or worsening intracranial hemorrhage (ICH), or major extracranial hemorrhage. Results were adjusted for age, sex, and relevant medical conditions.
The mean age of the patients included was 44.8 years, 64.7% were women, 33% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times.
Results showed that during a median follow-up of 345 days, there were 5.68 recurrent venous thrombosis events, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years.
Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization.
When compared with warfarin, DOAC treatment was associated with similar risk for recurrent venous thrombosis (adjusted hazard ratio, 0.94; 95% confidence interval, 0.51-1.73; P = .84), death (aHR, 0.71, 95% CI, 0.24-2.08; P = .53), and rate of partial/complete recanalization (aHR, 0.92, 95% CI, 0.48-1.73; P = .79).
But patients who received a DOAC had a significantly lower rate of major hemorrhage (aHR, 0.35; 95% CI, 0.15-0.81; P = .02).
When examined separately, the occurrence of ICH per 100 patient-years was much lower among the patients prescribed DOACs than those who were prescribed warfarin (1.52 vs. 3.51), whereas the occurrence of major bleeding outside the brain was similar (0.91 vs. 1.15).
Similar efficacy, better safety
Commenting on the study at an ISC press conference, Mitchell Elkind, MD, immediate past president of the American Heart Association/American Stroke Association and professor of neurology at Columbia University, New York, said: “The community has been concerned about extending the use of these new direct-acting oral anticoagulant drugs to cerebral venous thrombosis, but this study suggests that these patients may benefit from these new agents too.”
Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, also commented: “This study confirms what we already know from other indications about these DOAC drugs: that they have similar efficacy to warfarin but a better safety profile. These results are really spot on with that. These drugs are also much easier and more convenient to use than warfarin.”
“This is a great step forward,” he added. “Only 30% of patients in this study received DOACs, reflecting the fact that clinicians may be a little reluctant to use them in this condition. But this study now has the potential to change practice.”
In an editorial accompanying the publication in Stroke, Johnathon Gorman, MD, and Thalia Field, MD, from the Vancouver Stroke Program at the University of British Columbia, say that despite its methodological limitations, the ACTION-CVT study “provides added value to the current state of knowledge by virtue of its size and ‘real world’ setting that is reflective of how DOACs are being used to manage CVT in current clinical practice.”
They point out that although baseline characteristics between the DOAC and warfarin groups were similar, the possibility of confounding cannot be excluded, and “other characteristics not easily captured in a retrospective study may sway anticoagulation strategy.”
They acknowledge, however, that an additional propensity score analysis “provides reassurance that the groups are reasonably balanced, adjusting for variables associated with recurrent cerebral venous thrombosis, recanalization, and hemorrhage.”
The editorialists conclude that ACTION-CVT gives additional reassurance for DOACs as an alternative approach to warfarin as a treatment for cerebral venous thrombosis and for the shifts in clinical practice that are already occurring at many centers.
The study was partially supported by the Italian Ministry of Health Ricerca Corrente–IRCCS MultiMedica. Dr. Bakradze reports no disclosures. Dr. Field is the principal investigator of the SECRET trial, which received in-kind study medication from Bayer Canada. She reports honoraria from HLS Therapeutics outside the submitted work and is on the board of Destine Health. The other editorialist reports no conflicts.
A version of this article first appeared on Medscape.com.
and are less likely to result in major bleeding, a retrospective study suggests.
The ACTION CVT study was presented at the International Stroke Conference (ISC) 2022 by Ekaterina Bakradze, MD, assistant professor of neurology at the University of Alabama at Birmingham.
It was also simultaneously published online in Stroke.
“This real-world data supports use of direct oral anticoagulant drugs as a reasonable alternative to warfarin in patients with cerebral venous thrombosis,” Dr. Bakradze concluded.
But she added that because this study was based on retrospective observational data, the findings should be interpreted with caution and require confirmation by larger prospective studies.
Two such studies are now underway: the Direct Oral Anticoagulants in the Treatment of Cerebral Venous Thrombosis (DOAC-CVT) study and the randomized Study of Rivaroxaban for Cerebral Venous Thrombosis (SECRET) trial.
Dr. Bakradze explained that cerebral venous thrombosis is a less common cause of stroke and occurs more often in women and younger patients, with a median age of 37 years. Current recommended treatment consists of heparin followed by oral anticoagulation.
She noted that although randomized trials and current guidelines indicate that DOACs are a preferred alternative to warfarin for the treatment of patients with venous thromboembolism, there are limited data on their use in patients with CVT.
A small, randomized trial (RESPECT-CVT) showed no significant difference in efficacy and safety outcomes between dabigatran and warfarin in patients with cerebral venous thrombosis, but with only 120 patients, this trial was too small for definite answers to this question.
A better understanding of this issue is important, because the mechanisms underlying cerebral venous thrombosis and other thromboembolism and their subsequent risks may differ, Dr. Bakradze said.
As randomized trials in patients with cerebral venous thrombosis are difficult to perform because the condition has a low incidence and low event rates, the researchers decided to look at this question with a large retrospective multicenter study.
The ACTION-CVT study involved 845 consecutive patients with cerebral venous thrombosis over 6 years (from January 2015 and December 2020) from 27 centers in Italy, New Zealand, Switzerland, and the United States. Patients were identified from medical records with diagnostic codes and confirmed with imaging.
The primary predictor in the study was oral anticoagulant type (DOAC vs. warfarin). Study outcomes were abstracted by individual sites through review of all available medical records.
The primary outcome was recurrent venous thrombosis (venous thromboembolism or cerebral venous thrombosis) during follow-up. Imaging outcomes based on recanalization status on last venous imaging study abstracted from radiology reports were also reported.
The safety outcome was major hemorrhage, defined as new or worsening intracranial hemorrhage (ICH), or major extracranial hemorrhage. Results were adjusted for age, sex, and relevant medical conditions.
The mean age of the patients included was 44.8 years, 64.7% were women, 33% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times.
Results showed that during a median follow-up of 345 days, there were 5.68 recurrent venous thrombosis events, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years.
Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization.
When compared with warfarin, DOAC treatment was associated with similar risk for recurrent venous thrombosis (adjusted hazard ratio, 0.94; 95% confidence interval, 0.51-1.73; P = .84), death (aHR, 0.71, 95% CI, 0.24-2.08; P = .53), and rate of partial/complete recanalization (aHR, 0.92, 95% CI, 0.48-1.73; P = .79).
But patients who received a DOAC had a significantly lower rate of major hemorrhage (aHR, 0.35; 95% CI, 0.15-0.81; P = .02).
When examined separately, the occurrence of ICH per 100 patient-years was much lower among the patients prescribed DOACs than those who were prescribed warfarin (1.52 vs. 3.51), whereas the occurrence of major bleeding outside the brain was similar (0.91 vs. 1.15).
Similar efficacy, better safety
Commenting on the study at an ISC press conference, Mitchell Elkind, MD, immediate past president of the American Heart Association/American Stroke Association and professor of neurology at Columbia University, New York, said: “The community has been concerned about extending the use of these new direct-acting oral anticoagulant drugs to cerebral venous thrombosis, but this study suggests that these patients may benefit from these new agents too.”
Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, also commented: “This study confirms what we already know from other indications about these DOAC drugs: that they have similar efficacy to warfarin but a better safety profile. These results are really spot on with that. These drugs are also much easier and more convenient to use than warfarin.”
“This is a great step forward,” he added. “Only 30% of patients in this study received DOACs, reflecting the fact that clinicians may be a little reluctant to use them in this condition. But this study now has the potential to change practice.”
In an editorial accompanying the publication in Stroke, Johnathon Gorman, MD, and Thalia Field, MD, from the Vancouver Stroke Program at the University of British Columbia, say that despite its methodological limitations, the ACTION-CVT study “provides added value to the current state of knowledge by virtue of its size and ‘real world’ setting that is reflective of how DOACs are being used to manage CVT in current clinical practice.”
They point out that although baseline characteristics between the DOAC and warfarin groups were similar, the possibility of confounding cannot be excluded, and “other characteristics not easily captured in a retrospective study may sway anticoagulation strategy.”
They acknowledge, however, that an additional propensity score analysis “provides reassurance that the groups are reasonably balanced, adjusting for variables associated with recurrent cerebral venous thrombosis, recanalization, and hemorrhage.”
The editorialists conclude that ACTION-CVT gives additional reassurance for DOACs as an alternative approach to warfarin as a treatment for cerebral venous thrombosis and for the shifts in clinical practice that are already occurring at many centers.
The study was partially supported by the Italian Ministry of Health Ricerca Corrente–IRCCS MultiMedica. Dr. Bakradze reports no disclosures. Dr. Field is the principal investigator of the SECRET trial, which received in-kind study medication from Bayer Canada. She reports honoraria from HLS Therapeutics outside the submitted work and is on the board of Destine Health. The other editorialist reports no conflicts.
A version of this article first appeared on Medscape.com.
From ISC 2022
Full-press therapy rare in diabetes with ASCVD
A high percentage of people with type 2 diabetes also have atherosclerotic cardiovascular disease (ASCVD), but fewer than 1 in 20 get the triumvirate of evidence-based medications – drugs to lower cholesterol, blood pressure, and glucose levels – that can mitigate the dominant health risks they face, a large multicenter cohort study reported.
The cohort consisted of 324,706 patients with diabetes and ASCVD in the National Patient-Centered Clinical Research Network in 2018.
Senior study author Christopher B. Granger, MD, said in an interview that the findings represent “a shocking underuse of treatments proven to improve outcomes in this high-risk population.” For example, he noted that high-intensity statins are “inexpensive, well tolerated, and highly effective, but the fact that they’re only used in 26.8% of this population is really an indictment and embarrassment for our health-care system.”
The study analyzed prescriptions of high-intensity statins to lower cholesterol, ACE inhibitors or angiotensin-receptor blockers (ARBs) for blood pressure, and SGLT2 inhibitors or GLP-1 receptor agonists for hyperglycemia in a population with both diabetes and ASCVD.
This study amplifies the perceived treatment gap in cardiovascular risk reduction in persons with diabetes,” Paul S. Jellinger, MD, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., said in an interview. “The unfortunate treatment deficiency documented among 325,000 patients in 12 health systems is carefully quantitated and the message is loud, clear, and simple: There is gross underutilization of agents – ACE inhibitors and ARBs, SGLT-2 inhibitors, GLP-1 receptor agonists, and high-intensity statins – with definitively proven ASCVD benefit.”
In the cohort population, 44% were women and 56% were men; 18.2% were black and 12.8% were Latinx. In terms of care patterns for the 205,885 patients who had specialized visit data from the year before the study, the most (74.8%) saw a primary care physician, while only 8.7% visited an endocrinologist and 26.4% saw a cardiologist.
In terms of the prescriptions they received, 58.6% were on a statin, with less than half on a high-intensity statin; 45.5% were on either an ACE inhibitor or ARB, 3.9% received a GLP-1 receptor agonist, and 2.8% were taking a SGLT2 inhibitor.
The investigators pointed out that figure of 58.6% for patients who got a statin was significantly lower than the 74.6% reported in a study of a database of commercially insured patients, but was more in line with findings a 2018 study of patients with diabetes and ASCVD.
Only 4.8% of patients got all three types of therapies, and a high percentage (42.6%) didn’t get any prescription for the three major risk factors.
Overcoming barriers to prescriptions
The study noted that more work needs to be done to overcome the barriers to more widespread use of these therapies in patients with both diabetes and ASCVD.
Specifically with SGLT2 inhibitors and GLP-1 receptor agonists, cost was more likely to be a barrier than with the other drug groups, but that didn’t explain the low levels of high-intensity statin prescriptions, said Dr. Granger of Duke University, Durham, N.C.
The first barrier he mentioned is what he called “clinical inertia.” He said: “I’m a cardiologist who cares for these patients in my clinic each week, and there are so many different things that we need to be trying to achieve with the brief time we have with each patient in our clinic setting that people tend to miss the opportunity.”
The cost barrier, especially with the glucose-lowering therapies, can be overcome with clinic and health care system programs that aid patients in getting discounted drugs, he noted.
Other barriers Dr. Granger pointed out are lack of education – “So many people think that people with previous muscle aches can’t take a high-intensity statin, and we know that’s not true” – and misinformation, which he called “the more nefarious issue.”
He said, “Part of the problem is that misinformation travels much faster than accurate information. There’s so much out there about statins being toxic, which is just not true.”
Fragmentation of the U.S. health care system and the lack of feedback on quality measures, and physicians deferring decisions on glucose-lowering therapy to endocrinologists also pose barriers to more widespread use of evidence-based therapies in patients with diabetes and ASCVD, Dr. Granger said.
“This is a call to action,” Dr. Granger said. “By clearly describing these gaps, we hope that people will see this as an important opportunity to improve care not only at the level of individual providers, but even more importantly at the level of health systems.”
Dr. Jellinger said the “dismal results” of the study serve as a “wake-up call,” adding that “my own perception among my colleagues, along with the data referred to in this article, point to definitely higher usage among commercially insured patients. However, even in more enriched populations the message is not having its full impact. We have remarkable agents for our patients with diabetes that can make a real impact in diabetes-related morbidity and mortality. Our twofold goal should be to aggressively educate a broad slate of health care professionals and, of course, make patient access easy and affordable without ‘prior authorization.’ ”
The study noted the need to bring the prescribing patterns for patients with both diabetes and ASCVD more in line with evidence-based guidelines. To that end, said Dr. Granger, the researchers are moving ahead on a randomized study of a quality improvement project involving about 45 U.S. cardiology clinics using a feedback loop to apply more consistent prescribing patterns for the three therapy groups. “Hopefully a year from now we’ll have a lot more information about this problem,” Dr. Granger added.
Boehringer Ingelheim and Lilly funded the study. Dr. Granger reported financial relationships with Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Pfizer, Medtronic, Akros Pharma, Apple, AstraZeneca, Daichi-Sankyo, Novartis, AbbVie, Bayer, Boston Scientific, CeleCor, Correvio, Espero, Merck, Novo Nordisk, Rhoshan Pharmaceuticals, and Roche Diagnostics. Dr. Jellinger is on speaker’s bureaus for Esperion and Amgen.
A high percentage of people with type 2 diabetes also have atherosclerotic cardiovascular disease (ASCVD), but fewer than 1 in 20 get the triumvirate of evidence-based medications – drugs to lower cholesterol, blood pressure, and glucose levels – that can mitigate the dominant health risks they face, a large multicenter cohort study reported.
The cohort consisted of 324,706 patients with diabetes and ASCVD in the National Patient-Centered Clinical Research Network in 2018.
Senior study author Christopher B. Granger, MD, said in an interview that the findings represent “a shocking underuse of treatments proven to improve outcomes in this high-risk population.” For example, he noted that high-intensity statins are “inexpensive, well tolerated, and highly effective, but the fact that they’re only used in 26.8% of this population is really an indictment and embarrassment for our health-care system.”
The study analyzed prescriptions of high-intensity statins to lower cholesterol, ACE inhibitors or angiotensin-receptor blockers (ARBs) for blood pressure, and SGLT2 inhibitors or GLP-1 receptor agonists for hyperglycemia in a population with both diabetes and ASCVD.
This study amplifies the perceived treatment gap in cardiovascular risk reduction in persons with diabetes,” Paul S. Jellinger, MD, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., said in an interview. “The unfortunate treatment deficiency documented among 325,000 patients in 12 health systems is carefully quantitated and the message is loud, clear, and simple: There is gross underutilization of agents – ACE inhibitors and ARBs, SGLT-2 inhibitors, GLP-1 receptor agonists, and high-intensity statins – with definitively proven ASCVD benefit.”
In the cohort population, 44% were women and 56% were men; 18.2% were black and 12.8% were Latinx. In terms of care patterns for the 205,885 patients who had specialized visit data from the year before the study, the most (74.8%) saw a primary care physician, while only 8.7% visited an endocrinologist and 26.4% saw a cardiologist.
In terms of the prescriptions they received, 58.6% were on a statin, with less than half on a high-intensity statin; 45.5% were on either an ACE inhibitor or ARB, 3.9% received a GLP-1 receptor agonist, and 2.8% were taking a SGLT2 inhibitor.
The investigators pointed out that figure of 58.6% for patients who got a statin was significantly lower than the 74.6% reported in a study of a database of commercially insured patients, but was more in line with findings a 2018 study of patients with diabetes and ASCVD.
Only 4.8% of patients got all three types of therapies, and a high percentage (42.6%) didn’t get any prescription for the three major risk factors.
Overcoming barriers to prescriptions
The study noted that more work needs to be done to overcome the barriers to more widespread use of these therapies in patients with both diabetes and ASCVD.
Specifically with SGLT2 inhibitors and GLP-1 receptor agonists, cost was more likely to be a barrier than with the other drug groups, but that didn’t explain the low levels of high-intensity statin prescriptions, said Dr. Granger of Duke University, Durham, N.C.
The first barrier he mentioned is what he called “clinical inertia.” He said: “I’m a cardiologist who cares for these patients in my clinic each week, and there are so many different things that we need to be trying to achieve with the brief time we have with each patient in our clinic setting that people tend to miss the opportunity.”
The cost barrier, especially with the glucose-lowering therapies, can be overcome with clinic and health care system programs that aid patients in getting discounted drugs, he noted.
Other barriers Dr. Granger pointed out are lack of education – “So many people think that people with previous muscle aches can’t take a high-intensity statin, and we know that’s not true” – and misinformation, which he called “the more nefarious issue.”
He said, “Part of the problem is that misinformation travels much faster than accurate information. There’s so much out there about statins being toxic, which is just not true.”
Fragmentation of the U.S. health care system and the lack of feedback on quality measures, and physicians deferring decisions on glucose-lowering therapy to endocrinologists also pose barriers to more widespread use of evidence-based therapies in patients with diabetes and ASCVD, Dr. Granger said.
“This is a call to action,” Dr. Granger said. “By clearly describing these gaps, we hope that people will see this as an important opportunity to improve care not only at the level of individual providers, but even more importantly at the level of health systems.”
Dr. Jellinger said the “dismal results” of the study serve as a “wake-up call,” adding that “my own perception among my colleagues, along with the data referred to in this article, point to definitely higher usage among commercially insured patients. However, even in more enriched populations the message is not having its full impact. We have remarkable agents for our patients with diabetes that can make a real impact in diabetes-related morbidity and mortality. Our twofold goal should be to aggressively educate a broad slate of health care professionals and, of course, make patient access easy and affordable without ‘prior authorization.’ ”
The study noted the need to bring the prescribing patterns for patients with both diabetes and ASCVD more in line with evidence-based guidelines. To that end, said Dr. Granger, the researchers are moving ahead on a randomized study of a quality improvement project involving about 45 U.S. cardiology clinics using a feedback loop to apply more consistent prescribing patterns for the three therapy groups. “Hopefully a year from now we’ll have a lot more information about this problem,” Dr. Granger added.
Boehringer Ingelheim and Lilly funded the study. Dr. Granger reported financial relationships with Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Pfizer, Medtronic, Akros Pharma, Apple, AstraZeneca, Daichi-Sankyo, Novartis, AbbVie, Bayer, Boston Scientific, CeleCor, Correvio, Espero, Merck, Novo Nordisk, Rhoshan Pharmaceuticals, and Roche Diagnostics. Dr. Jellinger is on speaker’s bureaus for Esperion and Amgen.
A high percentage of people with type 2 diabetes also have atherosclerotic cardiovascular disease (ASCVD), but fewer than 1 in 20 get the triumvirate of evidence-based medications – drugs to lower cholesterol, blood pressure, and glucose levels – that can mitigate the dominant health risks they face, a large multicenter cohort study reported.
The cohort consisted of 324,706 patients with diabetes and ASCVD in the National Patient-Centered Clinical Research Network in 2018.
Senior study author Christopher B. Granger, MD, said in an interview that the findings represent “a shocking underuse of treatments proven to improve outcomes in this high-risk population.” For example, he noted that high-intensity statins are “inexpensive, well tolerated, and highly effective, but the fact that they’re only used in 26.8% of this population is really an indictment and embarrassment for our health-care system.”
The study analyzed prescriptions of high-intensity statins to lower cholesterol, ACE inhibitors or angiotensin-receptor blockers (ARBs) for blood pressure, and SGLT2 inhibitors or GLP-1 receptor agonists for hyperglycemia in a population with both diabetes and ASCVD.
This study amplifies the perceived treatment gap in cardiovascular risk reduction in persons with diabetes,” Paul S. Jellinger, MD, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., said in an interview. “The unfortunate treatment deficiency documented among 325,000 patients in 12 health systems is carefully quantitated and the message is loud, clear, and simple: There is gross underutilization of agents – ACE inhibitors and ARBs, SGLT-2 inhibitors, GLP-1 receptor agonists, and high-intensity statins – with definitively proven ASCVD benefit.”
In the cohort population, 44% were women and 56% were men; 18.2% were black and 12.8% were Latinx. In terms of care patterns for the 205,885 patients who had specialized visit data from the year before the study, the most (74.8%) saw a primary care physician, while only 8.7% visited an endocrinologist and 26.4% saw a cardiologist.
In terms of the prescriptions they received, 58.6% were on a statin, with less than half on a high-intensity statin; 45.5% were on either an ACE inhibitor or ARB, 3.9% received a GLP-1 receptor agonist, and 2.8% were taking a SGLT2 inhibitor.
The investigators pointed out that figure of 58.6% for patients who got a statin was significantly lower than the 74.6% reported in a study of a database of commercially insured patients, but was more in line with findings a 2018 study of patients with diabetes and ASCVD.
Only 4.8% of patients got all three types of therapies, and a high percentage (42.6%) didn’t get any prescription for the three major risk factors.
Overcoming barriers to prescriptions
The study noted that more work needs to be done to overcome the barriers to more widespread use of these therapies in patients with both diabetes and ASCVD.
Specifically with SGLT2 inhibitors and GLP-1 receptor agonists, cost was more likely to be a barrier than with the other drug groups, but that didn’t explain the low levels of high-intensity statin prescriptions, said Dr. Granger of Duke University, Durham, N.C.
The first barrier he mentioned is what he called “clinical inertia.” He said: “I’m a cardiologist who cares for these patients in my clinic each week, and there are so many different things that we need to be trying to achieve with the brief time we have with each patient in our clinic setting that people tend to miss the opportunity.”
The cost barrier, especially with the glucose-lowering therapies, can be overcome with clinic and health care system programs that aid patients in getting discounted drugs, he noted.
Other barriers Dr. Granger pointed out are lack of education – “So many people think that people with previous muscle aches can’t take a high-intensity statin, and we know that’s not true” – and misinformation, which he called “the more nefarious issue.”
He said, “Part of the problem is that misinformation travels much faster than accurate information. There’s so much out there about statins being toxic, which is just not true.”
Fragmentation of the U.S. health care system and the lack of feedback on quality measures, and physicians deferring decisions on glucose-lowering therapy to endocrinologists also pose barriers to more widespread use of evidence-based therapies in patients with diabetes and ASCVD, Dr. Granger said.
“This is a call to action,” Dr. Granger said. “By clearly describing these gaps, we hope that people will see this as an important opportunity to improve care not only at the level of individual providers, but even more importantly at the level of health systems.”
Dr. Jellinger said the “dismal results” of the study serve as a “wake-up call,” adding that “my own perception among my colleagues, along with the data referred to in this article, point to definitely higher usage among commercially insured patients. However, even in more enriched populations the message is not having its full impact. We have remarkable agents for our patients with diabetes that can make a real impact in diabetes-related morbidity and mortality. Our twofold goal should be to aggressively educate a broad slate of health care professionals and, of course, make patient access easy and affordable without ‘prior authorization.’ ”
The study noted the need to bring the prescribing patterns for patients with both diabetes and ASCVD more in line with evidence-based guidelines. To that end, said Dr. Granger, the researchers are moving ahead on a randomized study of a quality improvement project involving about 45 U.S. cardiology clinics using a feedback loop to apply more consistent prescribing patterns for the three therapy groups. “Hopefully a year from now we’ll have a lot more information about this problem,” Dr. Granger added.
Boehringer Ingelheim and Lilly funded the study. Dr. Granger reported financial relationships with Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Pfizer, Medtronic, Akros Pharma, Apple, AstraZeneca, Daichi-Sankyo, Novartis, AbbVie, Bayer, Boston Scientific, CeleCor, Correvio, Espero, Merck, Novo Nordisk, Rhoshan Pharmaceuticals, and Roche Diagnostics. Dr. Jellinger is on speaker’s bureaus for Esperion and Amgen.
FROM JAMA OPEN NETWORK
Long COVID is real and consists of these conditions – or does it?
Loss of smell. Fatigue. Mental health challenges. Difficulty breathing and other lower respiratory diseases. Fluid and electrolyte disorders. Cardiac dysrhythmia and other nonspecific chest pains. Trouble with urination. Diabetes?
Statistically, . The data, presented at the Conference on Retroviruses and Opportunistic Infections, can be used to guide diagnoses of long COVID, and may be the guide soon at Kaiser Permanente offices, Michael Horberg, MD, executive director of research, community benefit, and Medicaid strategy at the Mid-Atlantic Permanente Research Institute, said in an interview.
“There are some real conditions you could ask about” if you were evaluating a patient who believes they have PASC, Dr. Horberg said. “And there are real conditions that are symptoms patients have but they don’t fit the PASC diagnosis.”
That list is likely to evolve as specific symptoms emerge with new variants, he said. And there’s also the nationwide Researching COVID to Enhance Recovery (RECOVER) trial being conducted by the National Institutes of Health (NIH). Dr. Horberg is withholding judgment on diabetes, though, until more data come in.
During the global pandemic, Dr. Horberg, an HIV physician by training, found himself writing policies and guidelines for Kaiser’s Mid-Atlantic States (KPMAS) COVID response. Not long after that, the reports of symptoms that have come to be called long COVID started to come in. But they were “a mishmash of things” – everything from binge eating to the skin condition vitiligo to cranial nerve impairment, along with the more common complaints like fever, insomnia, and shortness of breath.
So Dr. Horberg looked back through KPMAS patient charts and found 28,118 members who had received a positive SARS-CoV-2 PCR test result in 2020. Then he matched them 3:1 with 70,293 members who didn’t have a positive PCR. The majority were women, nearly half were younger than 50, more than 40% were Black, and 24.5% were Latinx. The majority met clinical definitions of overweight or obese and many had other chronic illnesses, including diabetes (18.7% in the COVID-positive group), chronic kidney disease (3%) and cancer (2.6%). Rates of chronic illnesses were similar between arms.
Then they went back to 4 years before each positive PCR test and looked for all the illnesses before COVID, all those that emerged within 30 days of COVID diagnosis and those illnesses that emerged between 1 and 3 months after diagnosis.
From that search, they found 15 symptoms that were more common among people who’d had COVID. In addition to the symptoms listed above, those included abdominal pain, other nervous system disorders, dizziness or vertigo, and nausea and vomiting. Then they looked at whether each patient had experienced those symptoms in the 4 years before COVID to see if they were, in fact, new diagnoses.
More than 1 in 10
About one in four people who’d had COVID reported symptoms they thought might be long COVID, but through the analysis, they found that only 13% actually developed new conditions that could be categorized as long COVID.
“When you start controlling for all those chronic conditions, a lot of symptoms fall out,” Dr. Horberg told this news organization. “Plus, when you start comparing to the COVID-negative population, especially in the first 30 days of your positive diagnosis, actually, the COVID-negative patients have essentially almost the same amount, sometimes more.”
For instance, in the first month after diagnosis, though people with COVID reported anxiety symptoms after their diagnoses, people who’d never had COVID were coming in even more often with that symptom. And although gastrointestinal disorders were common in people who’d had COVID, they were just as likely in people who had not. Nausea and vomiting were actually 19% more common in people without COVID than in those with it. And people without COVID were nearly twice as likely to develop nutritional and endocrine disorders.
In the longer run, people who’d had COVID were 25% more likely to develop dysrhythmias, 20% more likely to develop diabetes, 60% more likely to develop fatigue, 21% more likely to develop genitourinary conditions, 39% more likely to develop chest pains, and a full 3.88 times more likely to develop trouble with olfaction.
And although people who’d had COVID were numerically 5% more likely to develop both abdominal pain and vertigo, 4% more likely to develop nervous system disorders, and 1% more likely to develop anxiety disorders longer term, none of those reached statistical significance.
The only diagnosis that doesn’t make sense to Dr. Horberg is diabetes.
“At this point I don’t think it’s been fully explained,” Dr. Horberg said. “I don’t think COVID is affecting the pancreas. But I do think that these are people who probably sought medical care, who hadn’t been seeking medical care and that the findings of diabetes were incidental diagnoses.”
Still, Dr. Horberg isn’t saying never on that. “As they say, more research is needed,” he added.
Ready to define long COVID?
As an intensive care unit physician and pulmonologist, Michael Risbano, MD, assistant professor of medicine at the University of Pittsburgh, has seen a lot of COVID. As the co-manager of the medical system’s post-COVID clinic, he’s also seen a lot of people coming in for help with what could be long COVID. When he saw the data from Dr. Horberg’s presentation, at first it seemed to confirm what he’d already known. But then he looked further.
“Well, this is actually making sense,” Dr. Risbano thought. At his clinic, it’s been an ongoing challenge to tease out what symptoms existed before COVID. Unlike Kaiser, the University of Pittsburgh Medical Center is not a closed system.
“We know some people who tend to get sick [with COVID] have some underlying medical issues already,” Dr. Risbano said in an interview. “But we don’t always have a good baseline as to what they were like beforehand, so we don’t always know what’s changed.”
He said the study design here, though retrospective and based on chart review rather than prospective observation, starts to put symptoms into the larger context of a patient’s life. And the diabetes association really stood out to him. He recalled one patient who, when she was admitted to the ICU, had a hemoglobin A1c that was totally normal. But when that patient returned a few months later, her blood sugar had skyrocketed.
“It was sky-high, like 13, and she was in diabetic ketoacidosis,” he said. “I know that’s an N of 1, but my wife is a dietitian and a case manager, and she’s having a lot of people coming in with a new diagnosis of diabetes.”
Still, he said he’s not sure that the conditions the study identified should be the basis for a definition of long COVID.
“I don’t know if you can come up with a definition out of this,” he said. “But I think this is at least helpful in telling us what disease states are different pre- and post-COVID, and what sorts of diagnoses clinicians should look for when a patient comes in after having a COVID diagnosis.”
Dr. Horberg and Dr. Risbano have disclosed no relevant financial relationships. The study was funded by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.
A version of this article first appeared on Medscape.com.
Loss of smell. Fatigue. Mental health challenges. Difficulty breathing and other lower respiratory diseases. Fluid and electrolyte disorders. Cardiac dysrhythmia and other nonspecific chest pains. Trouble with urination. Diabetes?
Statistically, . The data, presented at the Conference on Retroviruses and Opportunistic Infections, can be used to guide diagnoses of long COVID, and may be the guide soon at Kaiser Permanente offices, Michael Horberg, MD, executive director of research, community benefit, and Medicaid strategy at the Mid-Atlantic Permanente Research Institute, said in an interview.
“There are some real conditions you could ask about” if you were evaluating a patient who believes they have PASC, Dr. Horberg said. “And there are real conditions that are symptoms patients have but they don’t fit the PASC diagnosis.”
That list is likely to evolve as specific symptoms emerge with new variants, he said. And there’s also the nationwide Researching COVID to Enhance Recovery (RECOVER) trial being conducted by the National Institutes of Health (NIH). Dr. Horberg is withholding judgment on diabetes, though, until more data come in.
During the global pandemic, Dr. Horberg, an HIV physician by training, found himself writing policies and guidelines for Kaiser’s Mid-Atlantic States (KPMAS) COVID response. Not long after that, the reports of symptoms that have come to be called long COVID started to come in. But they were “a mishmash of things” – everything from binge eating to the skin condition vitiligo to cranial nerve impairment, along with the more common complaints like fever, insomnia, and shortness of breath.
So Dr. Horberg looked back through KPMAS patient charts and found 28,118 members who had received a positive SARS-CoV-2 PCR test result in 2020. Then he matched them 3:1 with 70,293 members who didn’t have a positive PCR. The majority were women, nearly half were younger than 50, more than 40% were Black, and 24.5% were Latinx. The majority met clinical definitions of overweight or obese and many had other chronic illnesses, including diabetes (18.7% in the COVID-positive group), chronic kidney disease (3%) and cancer (2.6%). Rates of chronic illnesses were similar between arms.
Then they went back to 4 years before each positive PCR test and looked for all the illnesses before COVID, all those that emerged within 30 days of COVID diagnosis and those illnesses that emerged between 1 and 3 months after diagnosis.
From that search, they found 15 symptoms that were more common among people who’d had COVID. In addition to the symptoms listed above, those included abdominal pain, other nervous system disorders, dizziness or vertigo, and nausea and vomiting. Then they looked at whether each patient had experienced those symptoms in the 4 years before COVID to see if they were, in fact, new diagnoses.
More than 1 in 10
About one in four people who’d had COVID reported symptoms they thought might be long COVID, but through the analysis, they found that only 13% actually developed new conditions that could be categorized as long COVID.
“When you start controlling for all those chronic conditions, a lot of symptoms fall out,” Dr. Horberg told this news organization. “Plus, when you start comparing to the COVID-negative population, especially in the first 30 days of your positive diagnosis, actually, the COVID-negative patients have essentially almost the same amount, sometimes more.”
For instance, in the first month after diagnosis, though people with COVID reported anxiety symptoms after their diagnoses, people who’d never had COVID were coming in even more often with that symptom. And although gastrointestinal disorders were common in people who’d had COVID, they were just as likely in people who had not. Nausea and vomiting were actually 19% more common in people without COVID than in those with it. And people without COVID were nearly twice as likely to develop nutritional and endocrine disorders.
In the longer run, people who’d had COVID were 25% more likely to develop dysrhythmias, 20% more likely to develop diabetes, 60% more likely to develop fatigue, 21% more likely to develop genitourinary conditions, 39% more likely to develop chest pains, and a full 3.88 times more likely to develop trouble with olfaction.
And although people who’d had COVID were numerically 5% more likely to develop both abdominal pain and vertigo, 4% more likely to develop nervous system disorders, and 1% more likely to develop anxiety disorders longer term, none of those reached statistical significance.
The only diagnosis that doesn’t make sense to Dr. Horberg is diabetes.
“At this point I don’t think it’s been fully explained,” Dr. Horberg said. “I don’t think COVID is affecting the pancreas. But I do think that these are people who probably sought medical care, who hadn’t been seeking medical care and that the findings of diabetes were incidental diagnoses.”
Still, Dr. Horberg isn’t saying never on that. “As they say, more research is needed,” he added.
Ready to define long COVID?
As an intensive care unit physician and pulmonologist, Michael Risbano, MD, assistant professor of medicine at the University of Pittsburgh, has seen a lot of COVID. As the co-manager of the medical system’s post-COVID clinic, he’s also seen a lot of people coming in for help with what could be long COVID. When he saw the data from Dr. Horberg’s presentation, at first it seemed to confirm what he’d already known. But then he looked further.
“Well, this is actually making sense,” Dr. Risbano thought. At his clinic, it’s been an ongoing challenge to tease out what symptoms existed before COVID. Unlike Kaiser, the University of Pittsburgh Medical Center is not a closed system.
“We know some people who tend to get sick [with COVID] have some underlying medical issues already,” Dr. Risbano said in an interview. “But we don’t always have a good baseline as to what they were like beforehand, so we don’t always know what’s changed.”
He said the study design here, though retrospective and based on chart review rather than prospective observation, starts to put symptoms into the larger context of a patient’s life. And the diabetes association really stood out to him. He recalled one patient who, when she was admitted to the ICU, had a hemoglobin A1c that was totally normal. But when that patient returned a few months later, her blood sugar had skyrocketed.
“It was sky-high, like 13, and she was in diabetic ketoacidosis,” he said. “I know that’s an N of 1, but my wife is a dietitian and a case manager, and she’s having a lot of people coming in with a new diagnosis of diabetes.”
Still, he said he’s not sure that the conditions the study identified should be the basis for a definition of long COVID.
“I don’t know if you can come up with a definition out of this,” he said. “But I think this is at least helpful in telling us what disease states are different pre- and post-COVID, and what sorts of diagnoses clinicians should look for when a patient comes in after having a COVID diagnosis.”
Dr. Horberg and Dr. Risbano have disclosed no relevant financial relationships. The study was funded by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.
A version of this article first appeared on Medscape.com.
Loss of smell. Fatigue. Mental health challenges. Difficulty breathing and other lower respiratory diseases. Fluid and electrolyte disorders. Cardiac dysrhythmia and other nonspecific chest pains. Trouble with urination. Diabetes?
Statistically, . The data, presented at the Conference on Retroviruses and Opportunistic Infections, can be used to guide diagnoses of long COVID, and may be the guide soon at Kaiser Permanente offices, Michael Horberg, MD, executive director of research, community benefit, and Medicaid strategy at the Mid-Atlantic Permanente Research Institute, said in an interview.
“There are some real conditions you could ask about” if you were evaluating a patient who believes they have PASC, Dr. Horberg said. “And there are real conditions that are symptoms patients have but they don’t fit the PASC diagnosis.”
That list is likely to evolve as specific symptoms emerge with new variants, he said. And there’s also the nationwide Researching COVID to Enhance Recovery (RECOVER) trial being conducted by the National Institutes of Health (NIH). Dr. Horberg is withholding judgment on diabetes, though, until more data come in.
During the global pandemic, Dr. Horberg, an HIV physician by training, found himself writing policies and guidelines for Kaiser’s Mid-Atlantic States (KPMAS) COVID response. Not long after that, the reports of symptoms that have come to be called long COVID started to come in. But they were “a mishmash of things” – everything from binge eating to the skin condition vitiligo to cranial nerve impairment, along with the more common complaints like fever, insomnia, and shortness of breath.
So Dr. Horberg looked back through KPMAS patient charts and found 28,118 members who had received a positive SARS-CoV-2 PCR test result in 2020. Then he matched them 3:1 with 70,293 members who didn’t have a positive PCR. The majority were women, nearly half were younger than 50, more than 40% were Black, and 24.5% were Latinx. The majority met clinical definitions of overweight or obese and many had other chronic illnesses, including diabetes (18.7% in the COVID-positive group), chronic kidney disease (3%) and cancer (2.6%). Rates of chronic illnesses were similar between arms.
Then they went back to 4 years before each positive PCR test and looked for all the illnesses before COVID, all those that emerged within 30 days of COVID diagnosis and those illnesses that emerged between 1 and 3 months after diagnosis.
From that search, they found 15 symptoms that were more common among people who’d had COVID. In addition to the symptoms listed above, those included abdominal pain, other nervous system disorders, dizziness or vertigo, and nausea and vomiting. Then they looked at whether each patient had experienced those symptoms in the 4 years before COVID to see if they were, in fact, new diagnoses.
More than 1 in 10
About one in four people who’d had COVID reported symptoms they thought might be long COVID, but through the analysis, they found that only 13% actually developed new conditions that could be categorized as long COVID.
“When you start controlling for all those chronic conditions, a lot of symptoms fall out,” Dr. Horberg told this news organization. “Plus, when you start comparing to the COVID-negative population, especially in the first 30 days of your positive diagnosis, actually, the COVID-negative patients have essentially almost the same amount, sometimes more.”
For instance, in the first month after diagnosis, though people with COVID reported anxiety symptoms after their diagnoses, people who’d never had COVID were coming in even more often with that symptom. And although gastrointestinal disorders were common in people who’d had COVID, they were just as likely in people who had not. Nausea and vomiting were actually 19% more common in people without COVID than in those with it. And people without COVID were nearly twice as likely to develop nutritional and endocrine disorders.
In the longer run, people who’d had COVID were 25% more likely to develop dysrhythmias, 20% more likely to develop diabetes, 60% more likely to develop fatigue, 21% more likely to develop genitourinary conditions, 39% more likely to develop chest pains, and a full 3.88 times more likely to develop trouble with olfaction.
And although people who’d had COVID were numerically 5% more likely to develop both abdominal pain and vertigo, 4% more likely to develop nervous system disorders, and 1% more likely to develop anxiety disorders longer term, none of those reached statistical significance.
The only diagnosis that doesn’t make sense to Dr. Horberg is diabetes.
“At this point I don’t think it’s been fully explained,” Dr. Horberg said. “I don’t think COVID is affecting the pancreas. But I do think that these are people who probably sought medical care, who hadn’t been seeking medical care and that the findings of diabetes were incidental diagnoses.”
Still, Dr. Horberg isn’t saying never on that. “As they say, more research is needed,” he added.
Ready to define long COVID?
As an intensive care unit physician and pulmonologist, Michael Risbano, MD, assistant professor of medicine at the University of Pittsburgh, has seen a lot of COVID. As the co-manager of the medical system’s post-COVID clinic, he’s also seen a lot of people coming in for help with what could be long COVID. When he saw the data from Dr. Horberg’s presentation, at first it seemed to confirm what he’d already known. But then he looked further.
“Well, this is actually making sense,” Dr. Risbano thought. At his clinic, it’s been an ongoing challenge to tease out what symptoms existed before COVID. Unlike Kaiser, the University of Pittsburgh Medical Center is not a closed system.
“We know some people who tend to get sick [with COVID] have some underlying medical issues already,” Dr. Risbano said in an interview. “But we don’t always have a good baseline as to what they were like beforehand, so we don’t always know what’s changed.”
He said the study design here, though retrospective and based on chart review rather than prospective observation, starts to put symptoms into the larger context of a patient’s life. And the diabetes association really stood out to him. He recalled one patient who, when she was admitted to the ICU, had a hemoglobin A1c that was totally normal. But when that patient returned a few months later, her blood sugar had skyrocketed.
“It was sky-high, like 13, and she was in diabetic ketoacidosis,” he said. “I know that’s an N of 1, but my wife is a dietitian and a case manager, and she’s having a lot of people coming in with a new diagnosis of diabetes.”
Still, he said he’s not sure that the conditions the study identified should be the basis for a definition of long COVID.
“I don’t know if you can come up with a definition out of this,” he said. “But I think this is at least helpful in telling us what disease states are different pre- and post-COVID, and what sorts of diagnoses clinicians should look for when a patient comes in after having a COVID diagnosis.”
Dr. Horberg and Dr. Risbano have disclosed no relevant financial relationships. The study was funded by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.
A version of this article first appeared on Medscape.com.
FROM CROI 2022
Obstetrical care for gender diverse patients: A summary from the SMFM annual meeting
The purpose of this commentary is to provide a brief summary of discussions centering around reproductive health experiences and obstetrical care for gender-diverse patients from the recent Society of Maternal & Fetal Medicine meeting. Two presentations featured patient perspectives combined with physician lectures to provide a comprehensive outlook on unique reproductive care needs for this growing population.
One of the speakers, Trystan Reese, is a transgender activist, educator, and transgender male who chose to carry his own pregnancy and subsequently delivered his son in 2017. During the summit, he described many barriers that he faced during his pregnancy and offered providers suggestions on how to improve the care for members of the gender-diverse community seeking to start a family.
We often think of conception and pregnancy as experiences unique to one gender. This is simply not the case. In discussing preconceptual care and pregnancy, it is paramount for providers to make the distinction between gender identity and natal sex. Gender identity is an internal sense of self in relation to natal sex. Depending on this intrinsic feeling, people may identify as cisgender, transgender, or as a gender outside of the standard binary. Natal sex describes biologic characteristics such as chromosomal makeup, reproductive anatomy, and secondary sexual changes. In keeping these distinctions in mind, pregnancy is therefore exclusive to a person’s natal sex, not gender identity. One of the biggest challenges in caring for transgender patients who desire pregnancy, is the psychological distress related to the gendered notions surrounding this experience.1
There are many ways in which patients encounter unintentional marginalization within the medical system. For example, many electronic medical record systems don’t allow for pronouns or give error messages if the patient’s gender identity is different from their sex assigned at birth. Patients who attend prenatal appointments or birth classes are given documents that center around cisgender women and heterosexual relationships. The labor and delivery wards themselves typically include language such as “maternity,” and birth certificates have distinct “mother” and “father” denotations.1 Insurance coverage for prenatal care and delivery can be problematic if a patient who is assigned female at birth has changed their gender marker to “male” on their insurance card.
Many of these roadblocks can be ameliorated by utilizing more inclusive terminology. Terms such as “maternal” can be replaced with “pregnant patients, parent, or patients giving birth.” Names of maternity wards can be altered to perinatal units, which is more inclusive and more descriptive of the wide variety of patients that may experience childbirth and parenthood.1 Introducing “you-centered” language can also be helpful. Instead of saying “women may find ...” providers can try saying “patients may find ...” or “individuals may find.”1
Most of the medical and obstetrical care of gender-diverse patients is routine. Prenatal labs, aneuploidy screening, ultrasounds, and fetal surveillance do not differ between transgender and cisgender patients. However, the experience of pregnancy itself can significantly heighten feelings of dysphoria as it inherently leads to patients confronting aspects of their biological sex.2 Because of the teratogenic nature of testosterone, patients are required to stop taking testosterone prior to conception and for the duration of pregnancy. This can also heighten dysphoria and lead to increased rates of anxiety and depression.3
Many transgender patients can safely achieve a normal vaginal birth.4 A small survey of 41 people demonstrated that more transgender men who had taken testosterone were delivered by cesarean section (36% vs. 19%).3 Staff training is an important aspect of caring for a transgender patient in labor to ensure that all members of the labor unit are cognizant of appropriate name and pronoun usage. Another interesting, although unsurprising, fact is that many transgender gestational parents chose a community-based (out-of-hospital) birth according to a 2014 study.1 This is predominantly because of the discrimination patients face when delivering within a hospital setting.
Postpartum depression screening should be conducted prior to patients leaving the hospital and individualized during postpartum appointments. Reinitiation of testosterone can occur 4-6 weeks after delivery.1
While pregnancy can pose some unique challenges to gender-diverse individuals, these intricacies are not insurmountable. The result of pregnancy, regardless of one’s gender identity, is the same – parenthood. One patient’s description of his experience was particularly poignant: “Pregnancy and childbirth were very male experiences for me. When I birthed my children, I was born into fatherhood.”1 It is up to all providers to modify clinical settings, as well as our patient interactions and use of language, if we are to provide inclusion in obstetrics.1,5
Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.
References
1. Brandt JS et al. “Understanding intersections: Care for transgender and gender diverse patient populations.” SMFM 2022 annual meeting. 2022 Feb 2.
2. Hoffkling A et al. BMC Pregnancy Childbirth. 2017 Nov 8;17(Suppl 2):332.
3. Light AD et al. Obstet Gynecol. 2014;124:1120-7.
4. Moseson H et al. Int J Transgend Health. 2021 Nov 17;22(1-2):30-41.
5. Brandt JS et al. Obstetrical care for trans*person, in “Trans*gynecology: Managing transgender patients in obstetrics and gynecology practice.” (Cambridge, England: Cambridge University Press, 2022).
The purpose of this commentary is to provide a brief summary of discussions centering around reproductive health experiences and obstetrical care for gender-diverse patients from the recent Society of Maternal & Fetal Medicine meeting. Two presentations featured patient perspectives combined with physician lectures to provide a comprehensive outlook on unique reproductive care needs for this growing population.
One of the speakers, Trystan Reese, is a transgender activist, educator, and transgender male who chose to carry his own pregnancy and subsequently delivered his son in 2017. During the summit, he described many barriers that he faced during his pregnancy and offered providers suggestions on how to improve the care for members of the gender-diverse community seeking to start a family.
We often think of conception and pregnancy as experiences unique to one gender. This is simply not the case. In discussing preconceptual care and pregnancy, it is paramount for providers to make the distinction between gender identity and natal sex. Gender identity is an internal sense of self in relation to natal sex. Depending on this intrinsic feeling, people may identify as cisgender, transgender, or as a gender outside of the standard binary. Natal sex describes biologic characteristics such as chromosomal makeup, reproductive anatomy, and secondary sexual changes. In keeping these distinctions in mind, pregnancy is therefore exclusive to a person’s natal sex, not gender identity. One of the biggest challenges in caring for transgender patients who desire pregnancy, is the psychological distress related to the gendered notions surrounding this experience.1
There are many ways in which patients encounter unintentional marginalization within the medical system. For example, many electronic medical record systems don’t allow for pronouns or give error messages if the patient’s gender identity is different from their sex assigned at birth. Patients who attend prenatal appointments or birth classes are given documents that center around cisgender women and heterosexual relationships. The labor and delivery wards themselves typically include language such as “maternity,” and birth certificates have distinct “mother” and “father” denotations.1 Insurance coverage for prenatal care and delivery can be problematic if a patient who is assigned female at birth has changed their gender marker to “male” on their insurance card.
Many of these roadblocks can be ameliorated by utilizing more inclusive terminology. Terms such as “maternal” can be replaced with “pregnant patients, parent, or patients giving birth.” Names of maternity wards can be altered to perinatal units, which is more inclusive and more descriptive of the wide variety of patients that may experience childbirth and parenthood.1 Introducing “you-centered” language can also be helpful. Instead of saying “women may find ...” providers can try saying “patients may find ...” or “individuals may find.”1
Most of the medical and obstetrical care of gender-diverse patients is routine. Prenatal labs, aneuploidy screening, ultrasounds, and fetal surveillance do not differ between transgender and cisgender patients. However, the experience of pregnancy itself can significantly heighten feelings of dysphoria as it inherently leads to patients confronting aspects of their biological sex.2 Because of the teratogenic nature of testosterone, patients are required to stop taking testosterone prior to conception and for the duration of pregnancy. This can also heighten dysphoria and lead to increased rates of anxiety and depression.3
Many transgender patients can safely achieve a normal vaginal birth.4 A small survey of 41 people demonstrated that more transgender men who had taken testosterone were delivered by cesarean section (36% vs. 19%).3 Staff training is an important aspect of caring for a transgender patient in labor to ensure that all members of the labor unit are cognizant of appropriate name and pronoun usage. Another interesting, although unsurprising, fact is that many transgender gestational parents chose a community-based (out-of-hospital) birth according to a 2014 study.1 This is predominantly because of the discrimination patients face when delivering within a hospital setting.
Postpartum depression screening should be conducted prior to patients leaving the hospital and individualized during postpartum appointments. Reinitiation of testosterone can occur 4-6 weeks after delivery.1
While pregnancy can pose some unique challenges to gender-diverse individuals, these intricacies are not insurmountable. The result of pregnancy, regardless of one’s gender identity, is the same – parenthood. One patient’s description of his experience was particularly poignant: “Pregnancy and childbirth were very male experiences for me. When I birthed my children, I was born into fatherhood.”1 It is up to all providers to modify clinical settings, as well as our patient interactions and use of language, if we are to provide inclusion in obstetrics.1,5
Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.
References
1. Brandt JS et al. “Understanding intersections: Care for transgender and gender diverse patient populations.” SMFM 2022 annual meeting. 2022 Feb 2.
2. Hoffkling A et al. BMC Pregnancy Childbirth. 2017 Nov 8;17(Suppl 2):332.
3. Light AD et al. Obstet Gynecol. 2014;124:1120-7.
4. Moseson H et al. Int J Transgend Health. 2021 Nov 17;22(1-2):30-41.
5. Brandt JS et al. Obstetrical care for trans*person, in “Trans*gynecology: Managing transgender patients in obstetrics and gynecology practice.” (Cambridge, England: Cambridge University Press, 2022).
The purpose of this commentary is to provide a brief summary of discussions centering around reproductive health experiences and obstetrical care for gender-diverse patients from the recent Society of Maternal & Fetal Medicine meeting. Two presentations featured patient perspectives combined with physician lectures to provide a comprehensive outlook on unique reproductive care needs for this growing population.
One of the speakers, Trystan Reese, is a transgender activist, educator, and transgender male who chose to carry his own pregnancy and subsequently delivered his son in 2017. During the summit, he described many barriers that he faced during his pregnancy and offered providers suggestions on how to improve the care for members of the gender-diverse community seeking to start a family.
We often think of conception and pregnancy as experiences unique to one gender. This is simply not the case. In discussing preconceptual care and pregnancy, it is paramount for providers to make the distinction between gender identity and natal sex. Gender identity is an internal sense of self in relation to natal sex. Depending on this intrinsic feeling, people may identify as cisgender, transgender, or as a gender outside of the standard binary. Natal sex describes biologic characteristics such as chromosomal makeup, reproductive anatomy, and secondary sexual changes. In keeping these distinctions in mind, pregnancy is therefore exclusive to a person’s natal sex, not gender identity. One of the biggest challenges in caring for transgender patients who desire pregnancy, is the psychological distress related to the gendered notions surrounding this experience.1
There are many ways in which patients encounter unintentional marginalization within the medical system. For example, many electronic medical record systems don’t allow for pronouns or give error messages if the patient’s gender identity is different from their sex assigned at birth. Patients who attend prenatal appointments or birth classes are given documents that center around cisgender women and heterosexual relationships. The labor and delivery wards themselves typically include language such as “maternity,” and birth certificates have distinct “mother” and “father” denotations.1 Insurance coverage for prenatal care and delivery can be problematic if a patient who is assigned female at birth has changed their gender marker to “male” on their insurance card.
Many of these roadblocks can be ameliorated by utilizing more inclusive terminology. Terms such as “maternal” can be replaced with “pregnant patients, parent, or patients giving birth.” Names of maternity wards can be altered to perinatal units, which is more inclusive and more descriptive of the wide variety of patients that may experience childbirth and parenthood.1 Introducing “you-centered” language can also be helpful. Instead of saying “women may find ...” providers can try saying “patients may find ...” or “individuals may find.”1
Most of the medical and obstetrical care of gender-diverse patients is routine. Prenatal labs, aneuploidy screening, ultrasounds, and fetal surveillance do not differ between transgender and cisgender patients. However, the experience of pregnancy itself can significantly heighten feelings of dysphoria as it inherently leads to patients confronting aspects of their biological sex.2 Because of the teratogenic nature of testosterone, patients are required to stop taking testosterone prior to conception and for the duration of pregnancy. This can also heighten dysphoria and lead to increased rates of anxiety and depression.3
Many transgender patients can safely achieve a normal vaginal birth.4 A small survey of 41 people demonstrated that more transgender men who had taken testosterone were delivered by cesarean section (36% vs. 19%).3 Staff training is an important aspect of caring for a transgender patient in labor to ensure that all members of the labor unit are cognizant of appropriate name and pronoun usage. Another interesting, although unsurprising, fact is that many transgender gestational parents chose a community-based (out-of-hospital) birth according to a 2014 study.1 This is predominantly because of the discrimination patients face when delivering within a hospital setting.
Postpartum depression screening should be conducted prior to patients leaving the hospital and individualized during postpartum appointments. Reinitiation of testosterone can occur 4-6 weeks after delivery.1
While pregnancy can pose some unique challenges to gender-diverse individuals, these intricacies are not insurmountable. The result of pregnancy, regardless of one’s gender identity, is the same – parenthood. One patient’s description of his experience was particularly poignant: “Pregnancy and childbirth were very male experiences for me. When I birthed my children, I was born into fatherhood.”1 It is up to all providers to modify clinical settings, as well as our patient interactions and use of language, if we are to provide inclusion in obstetrics.1,5
Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.
References
1. Brandt JS et al. “Understanding intersections: Care for transgender and gender diverse patient populations.” SMFM 2022 annual meeting. 2022 Feb 2.
2. Hoffkling A et al. BMC Pregnancy Childbirth. 2017 Nov 8;17(Suppl 2):332.
3. Light AD et al. Obstet Gynecol. 2014;124:1120-7.
4. Moseson H et al. Int J Transgend Health. 2021 Nov 17;22(1-2):30-41.
5. Brandt JS et al. Obstetrical care for trans*person, in “Trans*gynecology: Managing transgender patients in obstetrics and gynecology practice.” (Cambridge, England: Cambridge University Press, 2022).
IBD or something else? Key characteristics offer clues
Immune-mediated inflammatory diseases (IMIDs) of the gastrointestinal (GI) tract, with features that often mimic each other, commonly present clinical challenges. But key characteristics can help distinguish the most common – inflammatory bowel disease (IBD) – from other IMIDs, allowing for proper diagnosis and treatment, according to a new review.
“Although these disorders share a common pathophysiology, the defects can occur anywhere in the complex network of cytokines, inflammatory mediators, and innate and adaptive systems, leading to unregulated inflammation,” the authors of the review reported in JGH Open.
“Precise knowledge about them will help determine the possible targeted therapy. Thus, it is essential to distinguish these disorders from IBD,” underscored the authors, who were affiliated with the department of gastroenterology at All India Institute of Medical Sciences, New Delhi, India.
IBD, with its two major phenotypes of Crohn’s disease and ulcerative colitis, represents the most common IMIDs of the GI tract.
However, alternative diagnoses with overlapping features that can often be confused with IBD are plentiful, including celiac disease, GI vasculitis, eosinophilic gastroenteritis, some monogenic disorders, sarcoidosis, immune checkpoint inhibitor-induced colitis (ICI colitis), and microscopic colitis, explained the authors.
They recommended that, when evaluating patients with the common features that the disorders share, “one should think with an open mind and look for other possibilities, especially in patients not responding to conventional therapies.”
Monogenic disorders that mimic IBD
To determine monogenic disorders that mimic IBD, a key starting point can be the utilization of next-generation sequencing methods, which have become more available and less costly, the authors explained.
Most monogenic IBD variants present in the first decade of life and can be classified into different groups based on the pathways involved, they noted. These include disorders of epithelial barrier integrity, immune dysregulation, immunodeficiency, autoinflammatory disorders, and innate immune defects, including phagocyte killing.
Though monogenic IBD phenotypes are rare, measures to identify them are important, and can include taking peripheral blood counts, immunoglobulin profiles, and lymphocyte assays to identify common immunodeficiency disorders such as CVID and lymphocyte disorders.
While treatment can be difficult, “targeting the underlying defective immune pathway might be beneficial,” the authors noted, adding that some monogenic disorders, such as mutations of IL-10, can be effectively cured by hematopoietic stem cell transplantation (HSCT), while IL-1b receptor antagonists may be helpful in those with excesses in IL-1b.
Celiac disease
Celiac disease, previously believed to be a childhood disease, can occur at any age and, unlike IBD, has known environmental and genetic causes, with genetically predisposed individuals experiencing symptoms triggered by the ingestion of gluten proteins.
The disease can be diagnosed by the presence of serological markers including IgA tTG, anti-endomysial antibody, and anti-deamidated gliadin peptide antibodies, the authors noted.
In addition, they may have evidence of villous atrophy of the duodenal epithelium “with the exception in children, where more than 10 times elevation of IgA tTG is sufficient to make a diagnosis.”
Management includes avoidance of gluten-containing food products and nutritional supplementation of deficient nutrients and vitamins, and fewer than 5% of patients do not respond if they adhere to a gluten-free diet.
Other considerations besides IBD
Additional non-IBD phenotype disorders mimicking IBD to consider include the following:
Vasculitis-related enteropathy, characterized by inflammation of blood vessels and with clinical manifestations varying from abdominal pain and diarrhea to acute intestinal perforation. Symptoms can vary according to the type of vasculitis, ranging from mild abdominal pain and diarrhea to acute intestinal perforation.
Eosinophilic gastroenteritis, a rare eosinophil-mediated inflammatory disorder that can be difficult to diagnose and mimics IBD and other GI disorders.
“Mucosal disease is the most common clinical presentation, occurring in approximately 50% of cases and presents with abdominal pain, malabsorption, and protein-losing enteropathy,” the authors explained. “Whereas muscular disease presents as intestinal obstruction and serosal disease presents with eosinophilic ascites and pleural effusion.”
Microscopic colitis, an inflammatory disease of the large intestine, is often missed or confused with diarrhea-predominant irritable bowel syndrome (IBS), and the symptoms can result in severe impairment in the quality of life.
Unlike some other disorders, its incidence tends to increase with age, with a peak incidence in the sixth and seventh decades of life, the authors noted.
Immune checkpoint inhibitor–induced colitis, a major immune-mediated adverse event associated with checkpoint inhibitor drugs. Immune-mediated colitis (IMC) has clinical, radiological, and histopathological manifestations that mimic those of IBD, and may require urgent therapy depending on the grade of severity.
Major risk factors include the dose, type of agent, use of NSAIDs, preexisting IBD, as well as the type of tumor, the authors wrote.
“Management is more or less similar to that of IBD, and it depends on the severity of IMC,” they added.
Gastrointestinal sarcoidosis occurs in fewer than 1% of cases of sarcoidosis, a systemic granulomatous disease of unknown etiology, characterized by the formation of nonnecrotizing granulomas.
Diagnosis can be made by demonstrating nonnecrotizing granulomas on histopathology, with pulmonary and thoracic involvement suggesting sarcoidosis, and corticosteroid treatment.
Key indicators that it’s not IBD
Overall, key red flags that should raise suspicion of non-IBD disorder should include the presence of atypical features such as very young age of onset, being refractory to biologics, and involvement of other organ systems, the authors noted.
“Immunoglobulin assays, lymphocyte profiling, and neutrophilic functional assays should be carried out in patients with suspected underlying immunodeficiency disorder,” they added. “Whole-exome/genome sequencing and targeted gene analysis should be reserved for cases with a strong suspicion of monogenic disorders with IBD-like phenotype.”
Joseph A. Murray, MD, professor of medicine at the Mayo Clinic in Rochester, Minn., noted in an interview that the review offers some important insights.
“This is a very good review for people who are seeing patients and considering whether they have inflammatory bowel disease, and is comprehensive in the area of monogenic causes of inflammation,” he said.
In addition to the disorders described in the review, Dr. Murray noted that “other types of diseases that I often see include drug-induced enteropathy, tropical sprue [a chronic diarrheal disease], autoimmune enteropathy, and lymphoproliferative diseases.”
Other drug-induced enteropathies include those associated with angiotensin receptor blockers and azathioprine enteritis, he noted.
Dr. Murray and colleagues previously reported on further nonceliac enteropathies in a separate review, titled “Not All That Flattens Villi Is Celiac Disease: A Review of Enteropathies” in the Mayo Clinic Proceedings.
Further commenting, Tauseef Ali, MD, executive medical director, Saints Digestive Health Institute, SSM Health, Oklahoma City, noted that “the publication is one of the first and most comprehensive reviews summarizing the gastrointestinal tract’s different immune-mediated inflammatory diseases.
“The review gives us an excellent glimpse of the complex interplay of shared genetic and immune pathways involved in many inflammatory bowel conditions,” he added, noting that it also provides “an excellent platform for developing future clinical research methodologies and designs.”
The review authors had no disclosures to report. Dr. Murray has received grant support from the NIH, Alvine Pharmaceuticals and Alba Therapeutics, and receives ongoing support from Oberkotter Foundation and Broad Medical Research Program at CCFA. He serves on the advisory board of Celimmune and ImmunoGenx, was a consultant to BioLineRx, GlaxoSmithKline, Genentech and Glenmark Pharmaceuticals, and currently serves as a consultant to ImmunosanT, Institute for Protein Design (PvP Biologics), Takeda Pharmaceuticals, Innovate Biopharmaceuticals, and Intrexon. Dr. Ali has received honoraria for speaking, teaching, and consultation from AbbVie, Janssen, Pfizer, RedHill Biopharma, and Takeda.
Immune-mediated inflammatory diseases (IMIDs) of the gastrointestinal (GI) tract, with features that often mimic each other, commonly present clinical challenges. But key characteristics can help distinguish the most common – inflammatory bowel disease (IBD) – from other IMIDs, allowing for proper diagnosis and treatment, according to a new review.
“Although these disorders share a common pathophysiology, the defects can occur anywhere in the complex network of cytokines, inflammatory mediators, and innate and adaptive systems, leading to unregulated inflammation,” the authors of the review reported in JGH Open.
“Precise knowledge about them will help determine the possible targeted therapy. Thus, it is essential to distinguish these disorders from IBD,” underscored the authors, who were affiliated with the department of gastroenterology at All India Institute of Medical Sciences, New Delhi, India.
IBD, with its two major phenotypes of Crohn’s disease and ulcerative colitis, represents the most common IMIDs of the GI tract.
However, alternative diagnoses with overlapping features that can often be confused with IBD are plentiful, including celiac disease, GI vasculitis, eosinophilic gastroenteritis, some monogenic disorders, sarcoidosis, immune checkpoint inhibitor-induced colitis (ICI colitis), and microscopic colitis, explained the authors.
They recommended that, when evaluating patients with the common features that the disorders share, “one should think with an open mind and look for other possibilities, especially in patients not responding to conventional therapies.”
Monogenic disorders that mimic IBD
To determine monogenic disorders that mimic IBD, a key starting point can be the utilization of next-generation sequencing methods, which have become more available and less costly, the authors explained.
Most monogenic IBD variants present in the first decade of life and can be classified into different groups based on the pathways involved, they noted. These include disorders of epithelial barrier integrity, immune dysregulation, immunodeficiency, autoinflammatory disorders, and innate immune defects, including phagocyte killing.
Though monogenic IBD phenotypes are rare, measures to identify them are important, and can include taking peripheral blood counts, immunoglobulin profiles, and lymphocyte assays to identify common immunodeficiency disorders such as CVID and lymphocyte disorders.
While treatment can be difficult, “targeting the underlying defective immune pathway might be beneficial,” the authors noted, adding that some monogenic disorders, such as mutations of IL-10, can be effectively cured by hematopoietic stem cell transplantation (HSCT), while IL-1b receptor antagonists may be helpful in those with excesses in IL-1b.
Celiac disease
Celiac disease, previously believed to be a childhood disease, can occur at any age and, unlike IBD, has known environmental and genetic causes, with genetically predisposed individuals experiencing symptoms triggered by the ingestion of gluten proteins.
The disease can be diagnosed by the presence of serological markers including IgA tTG, anti-endomysial antibody, and anti-deamidated gliadin peptide antibodies, the authors noted.
In addition, they may have evidence of villous atrophy of the duodenal epithelium “with the exception in children, where more than 10 times elevation of IgA tTG is sufficient to make a diagnosis.”
Management includes avoidance of gluten-containing food products and nutritional supplementation of deficient nutrients and vitamins, and fewer than 5% of patients do not respond if they adhere to a gluten-free diet.
Other considerations besides IBD
Additional non-IBD phenotype disorders mimicking IBD to consider include the following:
Vasculitis-related enteropathy, characterized by inflammation of blood vessels and with clinical manifestations varying from abdominal pain and diarrhea to acute intestinal perforation. Symptoms can vary according to the type of vasculitis, ranging from mild abdominal pain and diarrhea to acute intestinal perforation.
Eosinophilic gastroenteritis, a rare eosinophil-mediated inflammatory disorder that can be difficult to diagnose and mimics IBD and other GI disorders.
“Mucosal disease is the most common clinical presentation, occurring in approximately 50% of cases and presents with abdominal pain, malabsorption, and protein-losing enteropathy,” the authors explained. “Whereas muscular disease presents as intestinal obstruction and serosal disease presents with eosinophilic ascites and pleural effusion.”
Microscopic colitis, an inflammatory disease of the large intestine, is often missed or confused with diarrhea-predominant irritable bowel syndrome (IBS), and the symptoms can result in severe impairment in the quality of life.
Unlike some other disorders, its incidence tends to increase with age, with a peak incidence in the sixth and seventh decades of life, the authors noted.
Immune checkpoint inhibitor–induced colitis, a major immune-mediated adverse event associated with checkpoint inhibitor drugs. Immune-mediated colitis (IMC) has clinical, radiological, and histopathological manifestations that mimic those of IBD, and may require urgent therapy depending on the grade of severity.
Major risk factors include the dose, type of agent, use of NSAIDs, preexisting IBD, as well as the type of tumor, the authors wrote.
“Management is more or less similar to that of IBD, and it depends on the severity of IMC,” they added.
Gastrointestinal sarcoidosis occurs in fewer than 1% of cases of sarcoidosis, a systemic granulomatous disease of unknown etiology, characterized by the formation of nonnecrotizing granulomas.
Diagnosis can be made by demonstrating nonnecrotizing granulomas on histopathology, with pulmonary and thoracic involvement suggesting sarcoidosis, and corticosteroid treatment.
Key indicators that it’s not IBD
Overall, key red flags that should raise suspicion of non-IBD disorder should include the presence of atypical features such as very young age of onset, being refractory to biologics, and involvement of other organ systems, the authors noted.
“Immunoglobulin assays, lymphocyte profiling, and neutrophilic functional assays should be carried out in patients with suspected underlying immunodeficiency disorder,” they added. “Whole-exome/genome sequencing and targeted gene analysis should be reserved for cases with a strong suspicion of monogenic disorders with IBD-like phenotype.”
Joseph A. Murray, MD, professor of medicine at the Mayo Clinic in Rochester, Minn., noted in an interview that the review offers some important insights.
“This is a very good review for people who are seeing patients and considering whether they have inflammatory bowel disease, and is comprehensive in the area of monogenic causes of inflammation,” he said.
In addition to the disorders described in the review, Dr. Murray noted that “other types of diseases that I often see include drug-induced enteropathy, tropical sprue [a chronic diarrheal disease], autoimmune enteropathy, and lymphoproliferative diseases.”
Other drug-induced enteropathies include those associated with angiotensin receptor blockers and azathioprine enteritis, he noted.
Dr. Murray and colleagues previously reported on further nonceliac enteropathies in a separate review, titled “Not All That Flattens Villi Is Celiac Disease: A Review of Enteropathies” in the Mayo Clinic Proceedings.
Further commenting, Tauseef Ali, MD, executive medical director, Saints Digestive Health Institute, SSM Health, Oklahoma City, noted that “the publication is one of the first and most comprehensive reviews summarizing the gastrointestinal tract’s different immune-mediated inflammatory diseases.
“The review gives us an excellent glimpse of the complex interplay of shared genetic and immune pathways involved in many inflammatory bowel conditions,” he added, noting that it also provides “an excellent platform for developing future clinical research methodologies and designs.”
The review authors had no disclosures to report. Dr. Murray has received grant support from the NIH, Alvine Pharmaceuticals and Alba Therapeutics, and receives ongoing support from Oberkotter Foundation and Broad Medical Research Program at CCFA. He serves on the advisory board of Celimmune and ImmunoGenx, was a consultant to BioLineRx, GlaxoSmithKline, Genentech and Glenmark Pharmaceuticals, and currently serves as a consultant to ImmunosanT, Institute for Protein Design (PvP Biologics), Takeda Pharmaceuticals, Innovate Biopharmaceuticals, and Intrexon. Dr. Ali has received honoraria for speaking, teaching, and consultation from AbbVie, Janssen, Pfizer, RedHill Biopharma, and Takeda.
Immune-mediated inflammatory diseases (IMIDs) of the gastrointestinal (GI) tract, with features that often mimic each other, commonly present clinical challenges. But key characteristics can help distinguish the most common – inflammatory bowel disease (IBD) – from other IMIDs, allowing for proper diagnosis and treatment, according to a new review.
“Although these disorders share a common pathophysiology, the defects can occur anywhere in the complex network of cytokines, inflammatory mediators, and innate and adaptive systems, leading to unregulated inflammation,” the authors of the review reported in JGH Open.
“Precise knowledge about them will help determine the possible targeted therapy. Thus, it is essential to distinguish these disorders from IBD,” underscored the authors, who were affiliated with the department of gastroenterology at All India Institute of Medical Sciences, New Delhi, India.
IBD, with its two major phenotypes of Crohn’s disease and ulcerative colitis, represents the most common IMIDs of the GI tract.
However, alternative diagnoses with overlapping features that can often be confused with IBD are plentiful, including celiac disease, GI vasculitis, eosinophilic gastroenteritis, some monogenic disorders, sarcoidosis, immune checkpoint inhibitor-induced colitis (ICI colitis), and microscopic colitis, explained the authors.
They recommended that, when evaluating patients with the common features that the disorders share, “one should think with an open mind and look for other possibilities, especially in patients not responding to conventional therapies.”
Monogenic disorders that mimic IBD
To determine monogenic disorders that mimic IBD, a key starting point can be the utilization of next-generation sequencing methods, which have become more available and less costly, the authors explained.
Most monogenic IBD variants present in the first decade of life and can be classified into different groups based on the pathways involved, they noted. These include disorders of epithelial barrier integrity, immune dysregulation, immunodeficiency, autoinflammatory disorders, and innate immune defects, including phagocyte killing.
Though monogenic IBD phenotypes are rare, measures to identify them are important, and can include taking peripheral blood counts, immunoglobulin profiles, and lymphocyte assays to identify common immunodeficiency disorders such as CVID and lymphocyte disorders.
While treatment can be difficult, “targeting the underlying defective immune pathway might be beneficial,” the authors noted, adding that some monogenic disorders, such as mutations of IL-10, can be effectively cured by hematopoietic stem cell transplantation (HSCT), while IL-1b receptor antagonists may be helpful in those with excesses in IL-1b.
Celiac disease
Celiac disease, previously believed to be a childhood disease, can occur at any age and, unlike IBD, has known environmental and genetic causes, with genetically predisposed individuals experiencing symptoms triggered by the ingestion of gluten proteins.
The disease can be diagnosed by the presence of serological markers including IgA tTG, anti-endomysial antibody, and anti-deamidated gliadin peptide antibodies, the authors noted.
In addition, they may have evidence of villous atrophy of the duodenal epithelium “with the exception in children, where more than 10 times elevation of IgA tTG is sufficient to make a diagnosis.”
Management includes avoidance of gluten-containing food products and nutritional supplementation of deficient nutrients and vitamins, and fewer than 5% of patients do not respond if they adhere to a gluten-free diet.
Other considerations besides IBD
Additional non-IBD phenotype disorders mimicking IBD to consider include the following:
Vasculitis-related enteropathy, characterized by inflammation of blood vessels and with clinical manifestations varying from abdominal pain and diarrhea to acute intestinal perforation. Symptoms can vary according to the type of vasculitis, ranging from mild abdominal pain and diarrhea to acute intestinal perforation.
Eosinophilic gastroenteritis, a rare eosinophil-mediated inflammatory disorder that can be difficult to diagnose and mimics IBD and other GI disorders.
“Mucosal disease is the most common clinical presentation, occurring in approximately 50% of cases and presents with abdominal pain, malabsorption, and protein-losing enteropathy,” the authors explained. “Whereas muscular disease presents as intestinal obstruction and serosal disease presents with eosinophilic ascites and pleural effusion.”
Microscopic colitis, an inflammatory disease of the large intestine, is often missed or confused with diarrhea-predominant irritable bowel syndrome (IBS), and the symptoms can result in severe impairment in the quality of life.
Unlike some other disorders, its incidence tends to increase with age, with a peak incidence in the sixth and seventh decades of life, the authors noted.
Immune checkpoint inhibitor–induced colitis, a major immune-mediated adverse event associated with checkpoint inhibitor drugs. Immune-mediated colitis (IMC) has clinical, radiological, and histopathological manifestations that mimic those of IBD, and may require urgent therapy depending on the grade of severity.
Major risk factors include the dose, type of agent, use of NSAIDs, preexisting IBD, as well as the type of tumor, the authors wrote.
“Management is more or less similar to that of IBD, and it depends on the severity of IMC,” they added.
Gastrointestinal sarcoidosis occurs in fewer than 1% of cases of sarcoidosis, a systemic granulomatous disease of unknown etiology, characterized by the formation of nonnecrotizing granulomas.
Diagnosis can be made by demonstrating nonnecrotizing granulomas on histopathology, with pulmonary and thoracic involvement suggesting sarcoidosis, and corticosteroid treatment.
Key indicators that it’s not IBD
Overall, key red flags that should raise suspicion of non-IBD disorder should include the presence of atypical features such as very young age of onset, being refractory to biologics, and involvement of other organ systems, the authors noted.
“Immunoglobulin assays, lymphocyte profiling, and neutrophilic functional assays should be carried out in patients with suspected underlying immunodeficiency disorder,” they added. “Whole-exome/genome sequencing and targeted gene analysis should be reserved for cases with a strong suspicion of monogenic disorders with IBD-like phenotype.”
Joseph A. Murray, MD, professor of medicine at the Mayo Clinic in Rochester, Minn., noted in an interview that the review offers some important insights.
“This is a very good review for people who are seeing patients and considering whether they have inflammatory bowel disease, and is comprehensive in the area of monogenic causes of inflammation,” he said.
In addition to the disorders described in the review, Dr. Murray noted that “other types of diseases that I often see include drug-induced enteropathy, tropical sprue [a chronic diarrheal disease], autoimmune enteropathy, and lymphoproliferative diseases.”
Other drug-induced enteropathies include those associated with angiotensin receptor blockers and azathioprine enteritis, he noted.
Dr. Murray and colleagues previously reported on further nonceliac enteropathies in a separate review, titled “Not All That Flattens Villi Is Celiac Disease: A Review of Enteropathies” in the Mayo Clinic Proceedings.
Further commenting, Tauseef Ali, MD, executive medical director, Saints Digestive Health Institute, SSM Health, Oklahoma City, noted that “the publication is one of the first and most comprehensive reviews summarizing the gastrointestinal tract’s different immune-mediated inflammatory diseases.
“The review gives us an excellent glimpse of the complex interplay of shared genetic and immune pathways involved in many inflammatory bowel conditions,” he added, noting that it also provides “an excellent platform for developing future clinical research methodologies and designs.”
The review authors had no disclosures to report. Dr. Murray has received grant support from the NIH, Alvine Pharmaceuticals and Alba Therapeutics, and receives ongoing support from Oberkotter Foundation and Broad Medical Research Program at CCFA. He serves on the advisory board of Celimmune and ImmunoGenx, was a consultant to BioLineRx, GlaxoSmithKline, Genentech and Glenmark Pharmaceuticals, and currently serves as a consultant to ImmunosanT, Institute for Protein Design (PvP Biologics), Takeda Pharmaceuticals, Innovate Biopharmaceuticals, and Intrexon. Dr. Ali has received honoraria for speaking, teaching, and consultation from AbbVie, Janssen, Pfizer, RedHill Biopharma, and Takeda.
FROM JGH OPEN
Most Americans unaware alcohol can cause cancer
The majority of Americans are not aware that alcohol consumption causes a variety of cancers and especially do not consider wine and beer to have a link with cancer, suggest the results from a national survey.
write lead author Andrew Seidenberg, PhD, MPH, National Cancer Institute, Rockville, Md., and colleagues.
“Increasing awareness of the alcohol-cancer link, such as through multimedia campaigns and patient-provider communication, may be an important new strategy for health advocates working to implement preventive alcohol policies,” they add.
The findings were published in the February issue of the American Journal of Preventive Medicine.
“This is the first study to examine the relationship between alcohol control policy support and awareness of the alcohol-cancer link among a national U.S. sample,” the authors write.
The results show that there is some public support for the idea of adding written warnings about the alcohol-cancer risk to alcoholic beverages, which is something that a number of cancer organizations have been petitioning for.
A petition filed by the American Society of Clinical Oncology, the American Institute for Cancer Research, and Breast Cancer Prevention Partners, all in collaboration with several public health organizations, proposes labeling that would read: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”
Such labeling has “the potential to save lives by ensuring that consumers have a more accurate understanding of the link between alcohol and cancer, which will empower them to better protect their health,” the groups said in the petition.
Public support
The findings come from an analysis of the 2020 Health Information National Trends Survey 5 Cycle 4. A total of 3,865 adults participated in the survey, approximately half of whom were nondrinkers.
As well as investigating how aware people were of the alcohol-cancer link, the investigators looked at how prevalent public support might be for the following three communication-focused alcohol policies:
- Banning outdoor alcohol-related advertising
- Requiring health warnings on alcohol beverage containers
- Requiring recommended drinking guidelines on alcoholic beverage containers
“Awareness of the alcohol-cancer link was measured separately for wine, beer, and liquor by asking: In your opinion, how much does drinking the following types of alcohol affect the risk of getting cancer?” the authors explain.
“Awareness of the alcohol-cancer link was low,” the investigators comment; only about one-third (31.8%) of participants were aware that alcohol increases the risk of cancer. The figures were even lower for individual beverage type, at 20.3% for wine, 24.9% for beer, and 31.2% for liquor. Furthermore, approximately half of participants responded with “don’t know” to the three awareness items, investigators noted.
On the other hand, more than half of the Americans surveyed supported adding both health warning labels (65.1%) and information on recommended drinking guidelines (63.9%) to alcoholic beverage containers. Support was lower (34.4% of respondents) for banning outdoor alcohol advertising.
Among Americans who were aware that alcohol increased cancer risk, support was also higher for all three policies.
For example, about 75% of respondents who were aware that alcohol increases cancer risk supported adding health warnings and drinking guidelines to beverage containers, compared with about half of Americans who felt that alcohol consumption had either no effect on or decreased cancer risk.
Even among those who were aware of the alcohol-cancer link, public support for outdoor advertising was not high (37.8%), but it was even lower (23.6%) among respondents who felt alcohol had no effect on or decreased the risk of cancer.
“Policy support was highest among nondrinkers, followed by drinkers, and was lowest among heavier drinkers,” the authors report.
For example, almost 43% of nondrinkers supported restrictions on outdoor alcohol advertising, compared with only about 28.6% of drinkers and 22% of heavier drinkers. More respondents supported adding health warning labels on alcoholic beverages – 70% of nondrinkers, 65% of drinkers, and 57% of heavier drinkers, investigators observe.
The study had no specific funding. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The majority of Americans are not aware that alcohol consumption causes a variety of cancers and especially do not consider wine and beer to have a link with cancer, suggest the results from a national survey.
write lead author Andrew Seidenberg, PhD, MPH, National Cancer Institute, Rockville, Md., and colleagues.
“Increasing awareness of the alcohol-cancer link, such as through multimedia campaigns and patient-provider communication, may be an important new strategy for health advocates working to implement preventive alcohol policies,” they add.
The findings were published in the February issue of the American Journal of Preventive Medicine.
“This is the first study to examine the relationship between alcohol control policy support and awareness of the alcohol-cancer link among a national U.S. sample,” the authors write.
The results show that there is some public support for the idea of adding written warnings about the alcohol-cancer risk to alcoholic beverages, which is something that a number of cancer organizations have been petitioning for.
A petition filed by the American Society of Clinical Oncology, the American Institute for Cancer Research, and Breast Cancer Prevention Partners, all in collaboration with several public health organizations, proposes labeling that would read: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”
Such labeling has “the potential to save lives by ensuring that consumers have a more accurate understanding of the link between alcohol and cancer, which will empower them to better protect their health,” the groups said in the petition.
Public support
The findings come from an analysis of the 2020 Health Information National Trends Survey 5 Cycle 4. A total of 3,865 adults participated in the survey, approximately half of whom were nondrinkers.
As well as investigating how aware people were of the alcohol-cancer link, the investigators looked at how prevalent public support might be for the following three communication-focused alcohol policies:
- Banning outdoor alcohol-related advertising
- Requiring health warnings on alcohol beverage containers
- Requiring recommended drinking guidelines on alcoholic beverage containers
“Awareness of the alcohol-cancer link was measured separately for wine, beer, and liquor by asking: In your opinion, how much does drinking the following types of alcohol affect the risk of getting cancer?” the authors explain.
“Awareness of the alcohol-cancer link was low,” the investigators comment; only about one-third (31.8%) of participants were aware that alcohol increases the risk of cancer. The figures were even lower for individual beverage type, at 20.3% for wine, 24.9% for beer, and 31.2% for liquor. Furthermore, approximately half of participants responded with “don’t know” to the three awareness items, investigators noted.
On the other hand, more than half of the Americans surveyed supported adding both health warning labels (65.1%) and information on recommended drinking guidelines (63.9%) to alcoholic beverage containers. Support was lower (34.4% of respondents) for banning outdoor alcohol advertising.
Among Americans who were aware that alcohol increased cancer risk, support was also higher for all three policies.
For example, about 75% of respondents who were aware that alcohol increases cancer risk supported adding health warnings and drinking guidelines to beverage containers, compared with about half of Americans who felt that alcohol consumption had either no effect on or decreased cancer risk.
Even among those who were aware of the alcohol-cancer link, public support for outdoor advertising was not high (37.8%), but it was even lower (23.6%) among respondents who felt alcohol had no effect on or decreased the risk of cancer.
“Policy support was highest among nondrinkers, followed by drinkers, and was lowest among heavier drinkers,” the authors report.
For example, almost 43% of nondrinkers supported restrictions on outdoor alcohol advertising, compared with only about 28.6% of drinkers and 22% of heavier drinkers. More respondents supported adding health warning labels on alcoholic beverages – 70% of nondrinkers, 65% of drinkers, and 57% of heavier drinkers, investigators observe.
The study had no specific funding. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The majority of Americans are not aware that alcohol consumption causes a variety of cancers and especially do not consider wine and beer to have a link with cancer, suggest the results from a national survey.
write lead author Andrew Seidenberg, PhD, MPH, National Cancer Institute, Rockville, Md., and colleagues.
“Increasing awareness of the alcohol-cancer link, such as through multimedia campaigns and patient-provider communication, may be an important new strategy for health advocates working to implement preventive alcohol policies,” they add.
The findings were published in the February issue of the American Journal of Preventive Medicine.
“This is the first study to examine the relationship between alcohol control policy support and awareness of the alcohol-cancer link among a national U.S. sample,” the authors write.
The results show that there is some public support for the idea of adding written warnings about the alcohol-cancer risk to alcoholic beverages, which is something that a number of cancer organizations have been petitioning for.
A petition filed by the American Society of Clinical Oncology, the American Institute for Cancer Research, and Breast Cancer Prevention Partners, all in collaboration with several public health organizations, proposes labeling that would read: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”
Such labeling has “the potential to save lives by ensuring that consumers have a more accurate understanding of the link between alcohol and cancer, which will empower them to better protect their health,” the groups said in the petition.
Public support
The findings come from an analysis of the 2020 Health Information National Trends Survey 5 Cycle 4. A total of 3,865 adults participated in the survey, approximately half of whom were nondrinkers.
As well as investigating how aware people were of the alcohol-cancer link, the investigators looked at how prevalent public support might be for the following three communication-focused alcohol policies:
- Banning outdoor alcohol-related advertising
- Requiring health warnings on alcohol beverage containers
- Requiring recommended drinking guidelines on alcoholic beverage containers
“Awareness of the alcohol-cancer link was measured separately for wine, beer, and liquor by asking: In your opinion, how much does drinking the following types of alcohol affect the risk of getting cancer?” the authors explain.
“Awareness of the alcohol-cancer link was low,” the investigators comment; only about one-third (31.8%) of participants were aware that alcohol increases the risk of cancer. The figures were even lower for individual beverage type, at 20.3% for wine, 24.9% for beer, and 31.2% for liquor. Furthermore, approximately half of participants responded with “don’t know” to the three awareness items, investigators noted.
On the other hand, more than half of the Americans surveyed supported adding both health warning labels (65.1%) and information on recommended drinking guidelines (63.9%) to alcoholic beverage containers. Support was lower (34.4% of respondents) for banning outdoor alcohol advertising.
Among Americans who were aware that alcohol increased cancer risk, support was also higher for all three policies.
For example, about 75% of respondents who were aware that alcohol increases cancer risk supported adding health warnings and drinking guidelines to beverage containers, compared with about half of Americans who felt that alcohol consumption had either no effect on or decreased cancer risk.
Even among those who were aware of the alcohol-cancer link, public support for outdoor advertising was not high (37.8%), but it was even lower (23.6%) among respondents who felt alcohol had no effect on or decreased the risk of cancer.
“Policy support was highest among nondrinkers, followed by drinkers, and was lowest among heavier drinkers,” the authors report.
For example, almost 43% of nondrinkers supported restrictions on outdoor alcohol advertising, compared with only about 28.6% of drinkers and 22% of heavier drinkers. More respondents supported adding health warning labels on alcoholic beverages – 70% of nondrinkers, 65% of drinkers, and 57% of heavier drinkers, investigators observe.
The study had no specific funding. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF PREVENTIVE MEDICINE
Early flu treatment of hospital CAP patients improves outcomes
Early initiation of the antiviral oseltamivir (Tamiflu) reduces the risk for death in patients hospitalized with community-acquired pneumonia (CAP) but patients have to be tested for influenza first and that is not happening often enough, a large observational cohort of adult patients indicates.
“Early testing allows for early treatment, and we found that early treatment was associated with reduced mortality so testing patients during the flu season is crucial,” senior author Michael Rothberg, MD, MPH, of the Cleveland Clinic said in an interview.
“Even during the flu season, most patients with CAP in our study went untested for influenza [even though] those who received early oseltamivir exhibited lower 14-day in-hospital case fatality ... suggesting more widespread testing might improve patient outcomes,” the authors added.
The study was published online Feb. 5, 2022, in the journal CHEST.
Premier database
Data from the Premier Database – a hospital discharge database with information from over 600 hospitals in the United States – were analyzed between July 2010 and June 2015. Microbiological laboratory data was provided by 179 hospitals. “For each year, we evaluated the total percentage of patients tested for influenza A/B within 3 days of hospitalization,” lead author Abhishek Deshpande, MD, PhD, Cleveland Clinic, and colleagues explained.
A total of 166,268 patients with CAP were included in the study, among which only about one-quarter were tested for influenza. Some 11.5% tested positive for the flu, the authors noted. Testing did increase from 15.4% in 2010 to 35.6% in 2015 and it was higher at close to 29% during the influenza season, compared with only about 8% during the summer months.
Patients who were tested for influenza were younger at age 66.6 years, compared with untested patients, who were 70 years of age (P < .001). Tested patients were also less likely to have been admitted from a nursing facility (P < .001), were less likely to have been hospitalized in the preceding 6 months (P < .001) and have fewer comorbidities than those who were not tested (P < .001).
“Both groups had similar illness severities on admission,” the authors observed, “but patients who were tested were less likely to die in the hospital within 14 days,” the authors reported – at 6.7% versus 10.9% for untested patients (P < .001).
More than 80% of patients who tested positive for influenza received an antibacterial on day 1 of their admission, compared with virtually all those who were either not tested or who tested negative, the investigators added (P < .001). The mean duration of antibacterial therapy among patients with a bacterial coinfection was not influenced by influenza test results.
However, among those who tested positive for influenza, almost 60% received oseltamivir on day 1 whereas roughly 30% received treatment on day 2 or later. In fact, almost all patients who received early oseltamivir were tested for influenza on day 1, the investigators pointed out. Patients who received early oseltamivir had a 25% lower risk of death within the first 14 days in hospital at an adjusted odds ratio of 0.75 (95% confidence interval, 0.59-0.96).
Early initiation of the antiviral also reduced the risk of requiring subsequent ICU care by 36% at an aOR of 0.64; invasive mechanical ventilation by 46% at an aOR of 0.54, and the need for vasopressor therapy by 47% at an aOR of 0.53. All results were within the 95% confidence levels.
Early use of antiviral therapy also reduced both the length of hospital stay and the cost of that stay by 12%.
ATS-IDSA guidelines
As Dr. Deshpande noted, the American Thoracic Society and the Infectious Diseases Society of America guidelines recommend testing and empiric treatment of influenza in patients hospitalized with CAP. “Testing more inpatients especially during the flu season can reduce other diagnostic testing and improve antimicrobial stewardship,” Deshpande noted.
Thus, while the rate of testing for influenza did increase over the 5-year study interval, “there is substantial room for improvement,” he added, as a positive test clearly does trigger the need for intervention. As Dr. Deshpande also noted, the past two influenza seasons have been mild, but influenza activity has again picked up lately again in many parts of the United States.
With the COVID-19 pandemic overwhelming influenza over the past few years, “differentiating between the two based on symptoms alone can be challenging,” he acknowledged, “and clinicians will need to test and treat accordingly.” This is particularly important given that this study clearly indicates that early treatment with an antiviral can lower the risk of short-term mortality in hospitalized CAP patients.
One limitation of the study was the lack of data on time of symptom onset, which may be an important confounder of the effect of oseltamivir on outcomes, the authors point out. Asked to comment on the findings, Barbara Jones, MD, University of Utah Health, Salt Lake City, noted that timely antivirals for patients with influenza are highly effective at mitigating severe disease and are thus strongly recommended by practice guidelines.
“However, it is hard for clinicians to keep influenza on the radar and change testing and treatment approaches according to the season and prevalence [of influenza infections],” she said in an interview. “This is an important study that highlights this challenge.
“We need a better understanding of the solutions that have been effective at improving influenza recognition and treatment, possibly by studying facilities that perform well at this process,” she said.
Dr. Deshpande reported receiving research funding to his institution from the Clorox Company and consultant fees from Merck.
A version of this article first appeared on Medscape.com.
Early initiation of the antiviral oseltamivir (Tamiflu) reduces the risk for death in patients hospitalized with community-acquired pneumonia (CAP) but patients have to be tested for influenza first and that is not happening often enough, a large observational cohort of adult patients indicates.
“Early testing allows for early treatment, and we found that early treatment was associated with reduced mortality so testing patients during the flu season is crucial,” senior author Michael Rothberg, MD, MPH, of the Cleveland Clinic said in an interview.
“Even during the flu season, most patients with CAP in our study went untested for influenza [even though] those who received early oseltamivir exhibited lower 14-day in-hospital case fatality ... suggesting more widespread testing might improve patient outcomes,” the authors added.
The study was published online Feb. 5, 2022, in the journal CHEST.
Premier database
Data from the Premier Database – a hospital discharge database with information from over 600 hospitals in the United States – were analyzed between July 2010 and June 2015. Microbiological laboratory data was provided by 179 hospitals. “For each year, we evaluated the total percentage of patients tested for influenza A/B within 3 days of hospitalization,” lead author Abhishek Deshpande, MD, PhD, Cleveland Clinic, and colleagues explained.
A total of 166,268 patients with CAP were included in the study, among which only about one-quarter were tested for influenza. Some 11.5% tested positive for the flu, the authors noted. Testing did increase from 15.4% in 2010 to 35.6% in 2015 and it was higher at close to 29% during the influenza season, compared with only about 8% during the summer months.
Patients who were tested for influenza were younger at age 66.6 years, compared with untested patients, who were 70 years of age (P < .001). Tested patients were also less likely to have been admitted from a nursing facility (P < .001), were less likely to have been hospitalized in the preceding 6 months (P < .001) and have fewer comorbidities than those who were not tested (P < .001).
“Both groups had similar illness severities on admission,” the authors observed, “but patients who were tested were less likely to die in the hospital within 14 days,” the authors reported – at 6.7% versus 10.9% for untested patients (P < .001).
More than 80% of patients who tested positive for influenza received an antibacterial on day 1 of their admission, compared with virtually all those who were either not tested or who tested negative, the investigators added (P < .001). The mean duration of antibacterial therapy among patients with a bacterial coinfection was not influenced by influenza test results.
However, among those who tested positive for influenza, almost 60% received oseltamivir on day 1 whereas roughly 30% received treatment on day 2 or later. In fact, almost all patients who received early oseltamivir were tested for influenza on day 1, the investigators pointed out. Patients who received early oseltamivir had a 25% lower risk of death within the first 14 days in hospital at an adjusted odds ratio of 0.75 (95% confidence interval, 0.59-0.96).
Early initiation of the antiviral also reduced the risk of requiring subsequent ICU care by 36% at an aOR of 0.64; invasive mechanical ventilation by 46% at an aOR of 0.54, and the need for vasopressor therapy by 47% at an aOR of 0.53. All results were within the 95% confidence levels.
Early use of antiviral therapy also reduced both the length of hospital stay and the cost of that stay by 12%.
ATS-IDSA guidelines
As Dr. Deshpande noted, the American Thoracic Society and the Infectious Diseases Society of America guidelines recommend testing and empiric treatment of influenza in patients hospitalized with CAP. “Testing more inpatients especially during the flu season can reduce other diagnostic testing and improve antimicrobial stewardship,” Deshpande noted.
Thus, while the rate of testing for influenza did increase over the 5-year study interval, “there is substantial room for improvement,” he added, as a positive test clearly does trigger the need for intervention. As Dr. Deshpande also noted, the past two influenza seasons have been mild, but influenza activity has again picked up lately again in many parts of the United States.
With the COVID-19 pandemic overwhelming influenza over the past few years, “differentiating between the two based on symptoms alone can be challenging,” he acknowledged, “and clinicians will need to test and treat accordingly.” This is particularly important given that this study clearly indicates that early treatment with an antiviral can lower the risk of short-term mortality in hospitalized CAP patients.
One limitation of the study was the lack of data on time of symptom onset, which may be an important confounder of the effect of oseltamivir on outcomes, the authors point out. Asked to comment on the findings, Barbara Jones, MD, University of Utah Health, Salt Lake City, noted that timely antivirals for patients with influenza are highly effective at mitigating severe disease and are thus strongly recommended by practice guidelines.
“However, it is hard for clinicians to keep influenza on the radar and change testing and treatment approaches according to the season and prevalence [of influenza infections],” she said in an interview. “This is an important study that highlights this challenge.
“We need a better understanding of the solutions that have been effective at improving influenza recognition and treatment, possibly by studying facilities that perform well at this process,” she said.
Dr. Deshpande reported receiving research funding to his institution from the Clorox Company and consultant fees from Merck.
A version of this article first appeared on Medscape.com.
Early initiation of the antiviral oseltamivir (Tamiflu) reduces the risk for death in patients hospitalized with community-acquired pneumonia (CAP) but patients have to be tested for influenza first and that is not happening often enough, a large observational cohort of adult patients indicates.
“Early testing allows for early treatment, and we found that early treatment was associated with reduced mortality so testing patients during the flu season is crucial,” senior author Michael Rothberg, MD, MPH, of the Cleveland Clinic said in an interview.
“Even during the flu season, most patients with CAP in our study went untested for influenza [even though] those who received early oseltamivir exhibited lower 14-day in-hospital case fatality ... suggesting more widespread testing might improve patient outcomes,” the authors added.
The study was published online Feb. 5, 2022, in the journal CHEST.
Premier database
Data from the Premier Database – a hospital discharge database with information from over 600 hospitals in the United States – were analyzed between July 2010 and June 2015. Microbiological laboratory data was provided by 179 hospitals. “For each year, we evaluated the total percentage of patients tested for influenza A/B within 3 days of hospitalization,” lead author Abhishek Deshpande, MD, PhD, Cleveland Clinic, and colleagues explained.
A total of 166,268 patients with CAP were included in the study, among which only about one-quarter were tested for influenza. Some 11.5% tested positive for the flu, the authors noted. Testing did increase from 15.4% in 2010 to 35.6% in 2015 and it was higher at close to 29% during the influenza season, compared with only about 8% during the summer months.
Patients who were tested for influenza were younger at age 66.6 years, compared with untested patients, who were 70 years of age (P < .001). Tested patients were also less likely to have been admitted from a nursing facility (P < .001), were less likely to have been hospitalized in the preceding 6 months (P < .001) and have fewer comorbidities than those who were not tested (P < .001).
“Both groups had similar illness severities on admission,” the authors observed, “but patients who were tested were less likely to die in the hospital within 14 days,” the authors reported – at 6.7% versus 10.9% for untested patients (P < .001).
More than 80% of patients who tested positive for influenza received an antibacterial on day 1 of their admission, compared with virtually all those who were either not tested or who tested negative, the investigators added (P < .001). The mean duration of antibacterial therapy among patients with a bacterial coinfection was not influenced by influenza test results.
However, among those who tested positive for influenza, almost 60% received oseltamivir on day 1 whereas roughly 30% received treatment on day 2 or later. In fact, almost all patients who received early oseltamivir were tested for influenza on day 1, the investigators pointed out. Patients who received early oseltamivir had a 25% lower risk of death within the first 14 days in hospital at an adjusted odds ratio of 0.75 (95% confidence interval, 0.59-0.96).
Early initiation of the antiviral also reduced the risk of requiring subsequent ICU care by 36% at an aOR of 0.64; invasive mechanical ventilation by 46% at an aOR of 0.54, and the need for vasopressor therapy by 47% at an aOR of 0.53. All results were within the 95% confidence levels.
Early use of antiviral therapy also reduced both the length of hospital stay and the cost of that stay by 12%.
ATS-IDSA guidelines
As Dr. Deshpande noted, the American Thoracic Society and the Infectious Diseases Society of America guidelines recommend testing and empiric treatment of influenza in patients hospitalized with CAP. “Testing more inpatients especially during the flu season can reduce other diagnostic testing and improve antimicrobial stewardship,” Deshpande noted.
Thus, while the rate of testing for influenza did increase over the 5-year study interval, “there is substantial room for improvement,” he added, as a positive test clearly does trigger the need for intervention. As Dr. Deshpande also noted, the past two influenza seasons have been mild, but influenza activity has again picked up lately again in many parts of the United States.
With the COVID-19 pandemic overwhelming influenza over the past few years, “differentiating between the two based on symptoms alone can be challenging,” he acknowledged, “and clinicians will need to test and treat accordingly.” This is particularly important given that this study clearly indicates that early treatment with an antiviral can lower the risk of short-term mortality in hospitalized CAP patients.
One limitation of the study was the lack of data on time of symptom onset, which may be an important confounder of the effect of oseltamivir on outcomes, the authors point out. Asked to comment on the findings, Barbara Jones, MD, University of Utah Health, Salt Lake City, noted that timely antivirals for patients with influenza are highly effective at mitigating severe disease and are thus strongly recommended by practice guidelines.
“However, it is hard for clinicians to keep influenza on the radar and change testing and treatment approaches according to the season and prevalence [of influenza infections],” she said in an interview. “This is an important study that highlights this challenge.
“We need a better understanding of the solutions that have been effective at improving influenza recognition and treatment, possibly by studying facilities that perform well at this process,” she said.
Dr. Deshpande reported receiving research funding to his institution from the Clorox Company and consultant fees from Merck.
A version of this article first appeared on Medscape.com.
FROM CHEST
Group prenatal care had mixed effect on preterm birth disparities
Group prenatal care did not reduce preterm birth among low-income patients compared to patients receiving individual prenatal care, but the different care models did shrink racial disparities in low-birth-weight and preterm births, according to a study presented Feb. 3 at the annual meeting sponsored by the Society for Maternal-Fetal Medicine. Patients who attended more group prenatal care visits also had better outcomes, reported Amy Crockett, MD, professor of ob.gyn. and director of the Maternal-Fetal Medicine Fellowship Program at the University of South Carolina in Greenville.
Though the results did not show group prenatal care to be the “silver bullet” they might have hoped for in reducing preterm birth and low birth weight among Black women, the study did show group prenatal care to have some clinical effect, Dr. Crockett suggested.
Ilina Pluym, MD, assistant professor of maternal-fetal medicine at the University of California Los Angeles, said that preterm birth and low birth weight are complex problems that cannot be solved by a single fix.
“In terms of the racial disparities, it is difficult to prove that 9 months of good access to prenatal care will undo the years of limited health care and life stressors that, as a whole, possibly contribute more to the overall risk profile of the patient,” Dr. Pluym said. “But as providers, we want to intervene and help in the portion that we can, and optimizing prenatal care is one tangible thing we can try.”
The racial disparities that exist in preterm birth, low birth weight, and infant and maternal mortality are not caused by biologic or genetic factors, Dr. Crockett told attendees.
”Rather, they are the result of long-standing systemic racism and discrimination deeply embedded in the culture of the United States,” she said. “To achieve racial equity, we need reform at the societal level.” But she noted that it might be possible for individual practices to play a role as well, which led her to design a study comparing outcomes from group versus individual prenatal care.
The group care model used for the study is called Centering Pregnancy, in which 8-10 pregnant patients who are due in the same month attend 10 two-hour prenatal care sessions together. Dr. Crockett noted that other research has identified potential reductions in preterm birth with group care models, but some are underpowered while others are observational and limited by confounding, selection bias, or small sample sizes.
The researchers aimed to recruit 3,160 patients to ensure an adequately powered study after estimated losses to follow-up, but they were able to recruit only 2,350 patients, resulting in potentially underpowered results. All the patients were receiving care at a single obstetric practice for a medically low-risk singleton pregnancy of 20 or fewer weeks gestation. A total of 1,176 patients were randomly assigned to attend group prenatal care appointments, and 1,174 patients were assigned to individual prenatal care.
The patients in both groups were an average age of 25 with a prepregnancy body mass index of 29. A similar proportion in both the group and individual care were married (24%) patients and had a government payer (96%-97%). Approximately 41%were Black patients, 37% were White patients, and 21% were Hispanic patients in both groups. Rates of chronic hypertension, smoking, vaginal infection in pregnancy, parity, cervix length, and use of cerclage were similar in both groups.
Gestational age outcomes were available for 1,099 group care patients (94%) and 1,120 individual care patients (95%), and birth weight outcomes were available for 1,028 group care patients (87%) and 1,044 individual care patients (89%).
In the individual care group, 8.7% of the patients had a preterm birth, compared to 10.4% who attended group prenatal care, but the findings did not reach significance (odds ratio [OR], 1.22; 95% confidence interval [CI]: 0.92-1.63). The difference between the 9.6% of group care patients and 8.9% of individual care patients who had babies with low birth weights were not significantly different.
While no significant difference in preterm birth occurred between the groups, the secondary outcome looking at racial disparities yielded one statistically significant result. Black women receiving individual prenatal care were twice as likely as were White women to have an infant with a low birth weight (OR, 2.1; 95% CI: 1.29-3.5). Among those receiving group care, however, the 12.5% of Black women and 8.9% of White women whose infants had a low birth weight were not significantly different.
There was a trend toward narrower disparities in preterm birth in the group versus individual care groups. Among those receiving group care, 11.4% of Black women and 10.8% of White women had a preterm birth, compared to 10.2% of Black women and 7.7% of White women in the individual care group.
Then the researchers compared the groups with regard to compliance while adjusting for baseline differences. “We saw decreasing rates of preterm birth for Black patients relative to White patients, particularly after attending five or more sessions in the group care arm with the rates of preterm birth narrowing and the disparity becoming nonsignificant with more exposure to group care,” Dr. Crockett said. “In individual care, the rate of preterm birth remained the highest for Black women regardless of the number of visits attended.”
The idea of trying group prenatal care is appealing, Dr. Pluym said in an interview, though both models have their advantages.
”The strength of individual care is the focus on the patient exam and individual patient questions,” Dr. Pluym said. “The strengths of group prenatal care are the consolidation of the patient education aspect of prenatal care that is uniform for all patients, the sense of community patients feel, and the opportunity to hear other patients questions that you may not have thought of. It sounds like, anecdotally, patients and providers really found the group sessions valuable and they helped dampen implicit bias and build relationships.”
One potential limitation of this randomized controlled trial is that the providers were the same for both group and individual care, potentially causing some confounding, Dr. Pluym noted. But the study does have one clear clinical message, she said.
“My take away is more prenatal care is better – individual or group,” Dr. Pluym said. “Every clinic should evaluate their own structure and see if group care would be feasible for their patient population. There may be a benefit globally, but is it is not the ‘silver bullet,’ as they said, for lowering preterm birth or growth restriction.”
The research was funded by the Institute of Child Health and Development. The study researchers and Dr. Pluym reported no disclosures.
Group prenatal care did not reduce preterm birth among low-income patients compared to patients receiving individual prenatal care, but the different care models did shrink racial disparities in low-birth-weight and preterm births, according to a study presented Feb. 3 at the annual meeting sponsored by the Society for Maternal-Fetal Medicine. Patients who attended more group prenatal care visits also had better outcomes, reported Amy Crockett, MD, professor of ob.gyn. and director of the Maternal-Fetal Medicine Fellowship Program at the University of South Carolina in Greenville.
Though the results did not show group prenatal care to be the “silver bullet” they might have hoped for in reducing preterm birth and low birth weight among Black women, the study did show group prenatal care to have some clinical effect, Dr. Crockett suggested.
Ilina Pluym, MD, assistant professor of maternal-fetal medicine at the University of California Los Angeles, said that preterm birth and low birth weight are complex problems that cannot be solved by a single fix.
“In terms of the racial disparities, it is difficult to prove that 9 months of good access to prenatal care will undo the years of limited health care and life stressors that, as a whole, possibly contribute more to the overall risk profile of the patient,” Dr. Pluym said. “But as providers, we want to intervene and help in the portion that we can, and optimizing prenatal care is one tangible thing we can try.”
The racial disparities that exist in preterm birth, low birth weight, and infant and maternal mortality are not caused by biologic or genetic factors, Dr. Crockett told attendees.
”Rather, they are the result of long-standing systemic racism and discrimination deeply embedded in the culture of the United States,” she said. “To achieve racial equity, we need reform at the societal level.” But she noted that it might be possible for individual practices to play a role as well, which led her to design a study comparing outcomes from group versus individual prenatal care.
The group care model used for the study is called Centering Pregnancy, in which 8-10 pregnant patients who are due in the same month attend 10 two-hour prenatal care sessions together. Dr. Crockett noted that other research has identified potential reductions in preterm birth with group care models, but some are underpowered while others are observational and limited by confounding, selection bias, or small sample sizes.
The researchers aimed to recruit 3,160 patients to ensure an adequately powered study after estimated losses to follow-up, but they were able to recruit only 2,350 patients, resulting in potentially underpowered results. All the patients were receiving care at a single obstetric practice for a medically low-risk singleton pregnancy of 20 or fewer weeks gestation. A total of 1,176 patients were randomly assigned to attend group prenatal care appointments, and 1,174 patients were assigned to individual prenatal care.
The patients in both groups were an average age of 25 with a prepregnancy body mass index of 29. A similar proportion in both the group and individual care were married (24%) patients and had a government payer (96%-97%). Approximately 41%were Black patients, 37% were White patients, and 21% were Hispanic patients in both groups. Rates of chronic hypertension, smoking, vaginal infection in pregnancy, parity, cervix length, and use of cerclage were similar in both groups.
Gestational age outcomes were available for 1,099 group care patients (94%) and 1,120 individual care patients (95%), and birth weight outcomes were available for 1,028 group care patients (87%) and 1,044 individual care patients (89%).
In the individual care group, 8.7% of the patients had a preterm birth, compared to 10.4% who attended group prenatal care, but the findings did not reach significance (odds ratio [OR], 1.22; 95% confidence interval [CI]: 0.92-1.63). The difference between the 9.6% of group care patients and 8.9% of individual care patients who had babies with low birth weights were not significantly different.
While no significant difference in preterm birth occurred between the groups, the secondary outcome looking at racial disparities yielded one statistically significant result. Black women receiving individual prenatal care were twice as likely as were White women to have an infant with a low birth weight (OR, 2.1; 95% CI: 1.29-3.5). Among those receiving group care, however, the 12.5% of Black women and 8.9% of White women whose infants had a low birth weight were not significantly different.
There was a trend toward narrower disparities in preterm birth in the group versus individual care groups. Among those receiving group care, 11.4% of Black women and 10.8% of White women had a preterm birth, compared to 10.2% of Black women and 7.7% of White women in the individual care group.
Then the researchers compared the groups with regard to compliance while adjusting for baseline differences. “We saw decreasing rates of preterm birth for Black patients relative to White patients, particularly after attending five or more sessions in the group care arm with the rates of preterm birth narrowing and the disparity becoming nonsignificant with more exposure to group care,” Dr. Crockett said. “In individual care, the rate of preterm birth remained the highest for Black women regardless of the number of visits attended.”
The idea of trying group prenatal care is appealing, Dr. Pluym said in an interview, though both models have their advantages.
”The strength of individual care is the focus on the patient exam and individual patient questions,” Dr. Pluym said. “The strengths of group prenatal care are the consolidation of the patient education aspect of prenatal care that is uniform for all patients, the sense of community patients feel, and the opportunity to hear other patients questions that you may not have thought of. It sounds like, anecdotally, patients and providers really found the group sessions valuable and they helped dampen implicit bias and build relationships.”
One potential limitation of this randomized controlled trial is that the providers were the same for both group and individual care, potentially causing some confounding, Dr. Pluym noted. But the study does have one clear clinical message, she said.
“My take away is more prenatal care is better – individual or group,” Dr. Pluym said. “Every clinic should evaluate their own structure and see if group care would be feasible for their patient population. There may be a benefit globally, but is it is not the ‘silver bullet,’ as they said, for lowering preterm birth or growth restriction.”
The research was funded by the Institute of Child Health and Development. The study researchers and Dr. Pluym reported no disclosures.
Group prenatal care did not reduce preterm birth among low-income patients compared to patients receiving individual prenatal care, but the different care models did shrink racial disparities in low-birth-weight and preterm births, according to a study presented Feb. 3 at the annual meeting sponsored by the Society for Maternal-Fetal Medicine. Patients who attended more group prenatal care visits also had better outcomes, reported Amy Crockett, MD, professor of ob.gyn. and director of the Maternal-Fetal Medicine Fellowship Program at the University of South Carolina in Greenville.
Though the results did not show group prenatal care to be the “silver bullet” they might have hoped for in reducing preterm birth and low birth weight among Black women, the study did show group prenatal care to have some clinical effect, Dr. Crockett suggested.
Ilina Pluym, MD, assistant professor of maternal-fetal medicine at the University of California Los Angeles, said that preterm birth and low birth weight are complex problems that cannot be solved by a single fix.
“In terms of the racial disparities, it is difficult to prove that 9 months of good access to prenatal care will undo the years of limited health care and life stressors that, as a whole, possibly contribute more to the overall risk profile of the patient,” Dr. Pluym said. “But as providers, we want to intervene and help in the portion that we can, and optimizing prenatal care is one tangible thing we can try.”
The racial disparities that exist in preterm birth, low birth weight, and infant and maternal mortality are not caused by biologic or genetic factors, Dr. Crockett told attendees.
”Rather, they are the result of long-standing systemic racism and discrimination deeply embedded in the culture of the United States,” she said. “To achieve racial equity, we need reform at the societal level.” But she noted that it might be possible for individual practices to play a role as well, which led her to design a study comparing outcomes from group versus individual prenatal care.
The group care model used for the study is called Centering Pregnancy, in which 8-10 pregnant patients who are due in the same month attend 10 two-hour prenatal care sessions together. Dr. Crockett noted that other research has identified potential reductions in preterm birth with group care models, but some are underpowered while others are observational and limited by confounding, selection bias, or small sample sizes.
The researchers aimed to recruit 3,160 patients to ensure an adequately powered study after estimated losses to follow-up, but they were able to recruit only 2,350 patients, resulting in potentially underpowered results. All the patients were receiving care at a single obstetric practice for a medically low-risk singleton pregnancy of 20 or fewer weeks gestation. A total of 1,176 patients were randomly assigned to attend group prenatal care appointments, and 1,174 patients were assigned to individual prenatal care.
The patients in both groups were an average age of 25 with a prepregnancy body mass index of 29. A similar proportion in both the group and individual care were married (24%) patients and had a government payer (96%-97%). Approximately 41%were Black patients, 37% were White patients, and 21% were Hispanic patients in both groups. Rates of chronic hypertension, smoking, vaginal infection in pregnancy, parity, cervix length, and use of cerclage were similar in both groups.
Gestational age outcomes were available for 1,099 group care patients (94%) and 1,120 individual care patients (95%), and birth weight outcomes were available for 1,028 group care patients (87%) and 1,044 individual care patients (89%).
In the individual care group, 8.7% of the patients had a preterm birth, compared to 10.4% who attended group prenatal care, but the findings did not reach significance (odds ratio [OR], 1.22; 95% confidence interval [CI]: 0.92-1.63). The difference between the 9.6% of group care patients and 8.9% of individual care patients who had babies with low birth weights were not significantly different.
While no significant difference in preterm birth occurred between the groups, the secondary outcome looking at racial disparities yielded one statistically significant result. Black women receiving individual prenatal care were twice as likely as were White women to have an infant with a low birth weight (OR, 2.1; 95% CI: 1.29-3.5). Among those receiving group care, however, the 12.5% of Black women and 8.9% of White women whose infants had a low birth weight were not significantly different.
There was a trend toward narrower disparities in preterm birth in the group versus individual care groups. Among those receiving group care, 11.4% of Black women and 10.8% of White women had a preterm birth, compared to 10.2% of Black women and 7.7% of White women in the individual care group.
Then the researchers compared the groups with regard to compliance while adjusting for baseline differences. “We saw decreasing rates of preterm birth for Black patients relative to White patients, particularly after attending five or more sessions in the group care arm with the rates of preterm birth narrowing and the disparity becoming nonsignificant with more exposure to group care,” Dr. Crockett said. “In individual care, the rate of preterm birth remained the highest for Black women regardless of the number of visits attended.”
The idea of trying group prenatal care is appealing, Dr. Pluym said in an interview, though both models have their advantages.
”The strength of individual care is the focus on the patient exam and individual patient questions,” Dr. Pluym said. “The strengths of group prenatal care are the consolidation of the patient education aspect of prenatal care that is uniform for all patients, the sense of community patients feel, and the opportunity to hear other patients questions that you may not have thought of. It sounds like, anecdotally, patients and providers really found the group sessions valuable and they helped dampen implicit bias and build relationships.”
One potential limitation of this randomized controlled trial is that the providers were the same for both group and individual care, potentially causing some confounding, Dr. Pluym noted. But the study does have one clear clinical message, she said.
“My take away is more prenatal care is better – individual or group,” Dr. Pluym said. “Every clinic should evaluate their own structure and see if group care would be feasible for their patient population. There may be a benefit globally, but is it is not the ‘silver bullet,’ as they said, for lowering preterm birth or growth restriction.”
The research was funded by the Institute of Child Health and Development. The study researchers and Dr. Pluym reported no disclosures.
FROM THE PREGNANCY MEETING