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Aspirin shows little benefit for primary prevention of vascular disease in diabetes
Background: Multiple large, randomized, controlled trials and meta-analyses that used aspirin as primary prevention for vascular events showed decreased vascular events, but a significant counterbalanced risk of bleeding. Since diabetes carries a higher risk of vascular events, this study examines aspirin for primary prevention of vascular events in diabetic patients.
Study design: Large, randomized, controlled trial.
Setting: British registry-based study.
Synopsis: This is a 9-year randomized, controlled trial that included 15,480 British patients with diabetes without known vascular disease who were randomized to receive a 100-mg aspirin daily or placebo. Participants in each group were closely matched patients with diabetes who were recruited using registry data and were aged 40 years and older with no alternative strong indication for aspirin.
Overall, aspirin provided no difference in mortality but showed an absolute 1.3% decrease in first vascular events or revascularization procedures with an absolute 1.1% increase in first occurrence of major bleeding event. Approximately 60% of the bleeding events were gastrointestinal or “other” urinary/nose bleeding, and there was no statistically significant increase in intracranial hemorrhage, hemorrhagic stroke, or vision-threatening eye bleeding. Vascular events were defined as transient ischemic attack (TIA), nonfatal MI, nonfatal ischemic stroke, or vascular death excluding intracranial hemorrhage. The major limitation of this study is that it had a composite of endpoints of different clinical significance. Furthermore, TIA as a major vascular event was added after the study began to increase statistical power, and when it is excluded, the difference for vascular events is not statistically significant.
Bottom line: Aspirin when used in primary prevention of vascular events in diabetes provides no improvement in mortality, and the benefit of prevention of vascular events must be weighed against the risks of bleeding.
Citation: The ASCEND Study Collaborative Group. Effects of aspirin for primary prevention in diabetes. N Eng J Med. 2018 Oct 18;379(16):1529-39.
Dr. Scott is an assistant professor in the division of hospital medicine, University of New Mexico.
Background: Multiple large, randomized, controlled trials and meta-analyses that used aspirin as primary prevention for vascular events showed decreased vascular events, but a significant counterbalanced risk of bleeding. Since diabetes carries a higher risk of vascular events, this study examines aspirin for primary prevention of vascular events in diabetic patients.
Study design: Large, randomized, controlled trial.
Setting: British registry-based study.
Synopsis: This is a 9-year randomized, controlled trial that included 15,480 British patients with diabetes without known vascular disease who were randomized to receive a 100-mg aspirin daily or placebo. Participants in each group were closely matched patients with diabetes who were recruited using registry data and were aged 40 years and older with no alternative strong indication for aspirin.
Overall, aspirin provided no difference in mortality but showed an absolute 1.3% decrease in first vascular events or revascularization procedures with an absolute 1.1% increase in first occurrence of major bleeding event. Approximately 60% of the bleeding events were gastrointestinal or “other” urinary/nose bleeding, and there was no statistically significant increase in intracranial hemorrhage, hemorrhagic stroke, or vision-threatening eye bleeding. Vascular events were defined as transient ischemic attack (TIA), nonfatal MI, nonfatal ischemic stroke, or vascular death excluding intracranial hemorrhage. The major limitation of this study is that it had a composite of endpoints of different clinical significance. Furthermore, TIA as a major vascular event was added after the study began to increase statistical power, and when it is excluded, the difference for vascular events is not statistically significant.
Bottom line: Aspirin when used in primary prevention of vascular events in diabetes provides no improvement in mortality, and the benefit of prevention of vascular events must be weighed against the risks of bleeding.
Citation: The ASCEND Study Collaborative Group. Effects of aspirin for primary prevention in diabetes. N Eng J Med. 2018 Oct 18;379(16):1529-39.
Dr. Scott is an assistant professor in the division of hospital medicine, University of New Mexico.
Background: Multiple large, randomized, controlled trials and meta-analyses that used aspirin as primary prevention for vascular events showed decreased vascular events, but a significant counterbalanced risk of bleeding. Since diabetes carries a higher risk of vascular events, this study examines aspirin for primary prevention of vascular events in diabetic patients.
Study design: Large, randomized, controlled trial.
Setting: British registry-based study.
Synopsis: This is a 9-year randomized, controlled trial that included 15,480 British patients with diabetes without known vascular disease who were randomized to receive a 100-mg aspirin daily or placebo. Participants in each group were closely matched patients with diabetes who were recruited using registry data and were aged 40 years and older with no alternative strong indication for aspirin.
Overall, aspirin provided no difference in mortality but showed an absolute 1.3% decrease in first vascular events or revascularization procedures with an absolute 1.1% increase in first occurrence of major bleeding event. Approximately 60% of the bleeding events were gastrointestinal or “other” urinary/nose bleeding, and there was no statistically significant increase in intracranial hemorrhage, hemorrhagic stroke, or vision-threatening eye bleeding. Vascular events were defined as transient ischemic attack (TIA), nonfatal MI, nonfatal ischemic stroke, or vascular death excluding intracranial hemorrhage. The major limitation of this study is that it had a composite of endpoints of different clinical significance. Furthermore, TIA as a major vascular event was added after the study began to increase statistical power, and when it is excluded, the difference for vascular events is not statistically significant.
Bottom line: Aspirin when used in primary prevention of vascular events in diabetes provides no improvement in mortality, and the benefit of prevention of vascular events must be weighed against the risks of bleeding.
Citation: The ASCEND Study Collaborative Group. Effects of aspirin for primary prevention in diabetes. N Eng J Med. 2018 Oct 18;379(16):1529-39.
Dr. Scott is an assistant professor in the division of hospital medicine, University of New Mexico.
Whatever “my last doctor” did, I don’t take the bait
In car repair, there’s a mysterious bogeyman known as “the last guy.”
“The last guy put it in wrong.”
“The last guy didn’t use the right part.”
“I have no idea what the last guy was thinking.”
In medicine, there’s “my last doctor.”
“My last doctor ordered the wrong test.”
“The medication, from my last doctor, almost killed me.”
“My last doctor didn’t know what he was doing.”
I don’t say anything, I just listen. Most of the time I’m not convinced the other doctor did anything wrong, and even if I were, I’d stay silent. Every doctor makes mistakes. It’s inevitable in any job.
Sometimes the patients mention this in passing, at other times they seem to be hoping for a response from me. I don’t give them one. Bashing other doctors is common enough as it is, and I’m not going to join in. My job is to do my best to help them, which is what the last doctor was trying to do, too.
The fact is that you can’t make everyone happy. Outside competency and human errors, there are too many variables in human relationships – the chemistry between people – to know what went wrong. Some patients have legitimate grievances, others may just be nitpicking and looking for trouble. It’s not my role to address it. If the patients came here for that, they’re at the wrong place. Most of the time, I happen to know their previous physicians, and think they’re decent neurologists.
The problem with these types of things is that it propagates. Even if I do everything right, and try my best, there’s a good chance that, in a few months, I’ll be “my last doctor.” I can only hope the next doctor feels the same way about me as I do about the last one.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
In car repair, there’s a mysterious bogeyman known as “the last guy.”
“The last guy put it in wrong.”
“The last guy didn’t use the right part.”
“I have no idea what the last guy was thinking.”
In medicine, there’s “my last doctor.”
“My last doctor ordered the wrong test.”
“The medication, from my last doctor, almost killed me.”
“My last doctor didn’t know what he was doing.”
I don’t say anything, I just listen. Most of the time I’m not convinced the other doctor did anything wrong, and even if I were, I’d stay silent. Every doctor makes mistakes. It’s inevitable in any job.
Sometimes the patients mention this in passing, at other times they seem to be hoping for a response from me. I don’t give them one. Bashing other doctors is common enough as it is, and I’m not going to join in. My job is to do my best to help them, which is what the last doctor was trying to do, too.
The fact is that you can’t make everyone happy. Outside competency and human errors, there are too many variables in human relationships – the chemistry between people – to know what went wrong. Some patients have legitimate grievances, others may just be nitpicking and looking for trouble. It’s not my role to address it. If the patients came here for that, they’re at the wrong place. Most of the time, I happen to know their previous physicians, and think they’re decent neurologists.
The problem with these types of things is that it propagates. Even if I do everything right, and try my best, there’s a good chance that, in a few months, I’ll be “my last doctor.” I can only hope the next doctor feels the same way about me as I do about the last one.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
In car repair, there’s a mysterious bogeyman known as “the last guy.”
“The last guy put it in wrong.”
“The last guy didn’t use the right part.”
“I have no idea what the last guy was thinking.”
In medicine, there’s “my last doctor.”
“My last doctor ordered the wrong test.”
“The medication, from my last doctor, almost killed me.”
“My last doctor didn’t know what he was doing.”
I don’t say anything, I just listen. Most of the time I’m not convinced the other doctor did anything wrong, and even if I were, I’d stay silent. Every doctor makes mistakes. It’s inevitable in any job.
Sometimes the patients mention this in passing, at other times they seem to be hoping for a response from me. I don’t give them one. Bashing other doctors is common enough as it is, and I’m not going to join in. My job is to do my best to help them, which is what the last doctor was trying to do, too.
The fact is that you can’t make everyone happy. Outside competency and human errors, there are too many variables in human relationships – the chemistry between people – to know what went wrong. Some patients have legitimate grievances, others may just be nitpicking and looking for trouble. It’s not my role to address it. If the patients came here for that, they’re at the wrong place. Most of the time, I happen to know their previous physicians, and think they’re decent neurologists.
The problem with these types of things is that it propagates. Even if I do everything right, and try my best, there’s a good chance that, in a few months, I’ll be “my last doctor.” I can only hope the next doctor feels the same way about me as I do about the last one.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Maternal immunization protects against serious RSV infection in infancy
LJUBLJANA, SLOVENIA – Passive protection of infants from severe respiratory syncytial virus lower respiratory tract infection during the first 6 months of life has convincingly been achieved through maternal immunization using a novel nanoparticle vaccine in the landmark PREPARE trial.
“I think it’s important for everyone, especially people like myself who’ve been working on maternal immunization for about 20 years, to realize that this is a historic study,” Flor M. Munoz, MD, declared in reporting the study results at the annual meeting of the European Society for Paediatric Infectious Diseases.
“We have here for the first time a phase-3, global, randomized, placebo-controlled, observer-blinded clinical trial looking at an experimental vaccine in pregnant women for the protection of infants from a disease for which we really don’t have other potential solutions quite yet, and in a period of high vulnerability,” said Dr. Munoz, a pediatric infectious disease specialist at Baylor College of Medicine, Houston.
Indeed, respiratory syncytial virus (RSV) is the No. 2 cause of mortality worldwide during the first year of life. Moreover, most cases of severe RSV lower respiratory tract infection occur in otherwise healthy infants aged less than 5 months, when active immunization presents daunting challenges.
“While certainly mortality is uncommon in high-income countries, we do see significant hospitalization there due to severe RSV lower respiratory tract infection in the first year of life, sometimes more than other common diseases, like influenza,” she noted.
PREPARE included 4,636 women with low-risk pregnancies who were randomized 2:1 to a single intramuscular injection of the investigational RSV vaccine or placebo during gestational weeks 28-36, with efficacy assessed through the first 180 days of life. The study took place at 87 sites in 11 countries during 4 years worth of RSV seasons. Roughly half of participants were South African, one-quarter were in the United States, and the rest were drawn from nine other low-, middle-, or high-income countries in the Northern and Southern Hemispheres. The median gestational age at vaccination was 32 weeks.
The primary efficacy endpoint specified by the Food and Drug Administration – but not other regulatory agencies – was the placebo-subtracted rate of RSV lower respiratory tract infection as defined by RSV detected by reverse transcription polymerase chain reaction, along with at least one clinical manifestation of lower respiratory tract infection, oxygen saturation below 95%, and/or tachypnea. The risk of this outcome was reduced by 39% during the first 90 days of life and by 27% through 180 days in infants in the maternal immunization group, a difference which didn’t achieve statistical significance.
However, prespecified major secondary endpoints arguably of greater clinical relevance were consistently positive. Notably, when levels of transplacentally transferred neutralizing antibodies against RSV A and B were highest, with events occurring in 57 of 2,765 evaluable infants in the active treatment arm and in 53 of 1,430 controls. Similarly, there was a 40% reduction through day 180. Moreover, rates of another key secondary endpoint – RSV lower respiratory tract infection plus severe hypoxemia with an oxygen saturation below 92% – were reduced by 48% and 42% through days 90 and 180, respectively. Thus, the vaccine’s protective effect was greatest against the most severe outcomes of RSV infection in infancy, according to Dr. Munoz.
No safety signals related to this immunization strategy were seen during 1 year of follow-up of infants and 6 months for the mothers. Side effects were essentially limited to mild, self-limited injection site reactions, with zero impact on pregnancy and delivery.
An intriguing finding in an exploratory analysis was that the vaccine appeared to have ancillary benefits beyond prevention of medically significant RSV disease in the young infants. For example, the rate of all lower respiratory tract infections with severe hypoxemia – with no requirement for demonstration of RSV infection – was reduced by 46% during the first 90 days of life in the immunized group. Similarly, the rate of all-cause lower respiratory tract infection resulting in hospitalization was reduced by 28%.
“This is actually quite interesting, because these are unexpected benefits in terms of all-cause effects,” the pediatrician commented, adding that she and her coinvestigators are delving into this phenomenon in order to gain better understanding.
Additional analyses of the recently completed PREPARE study are ongoing but already have yielded some important findings. For example, women immunized before 33 weeks’ gestation had significantly greater transplacental antibody transfer than those immunized later in pregnancy, with resultant markedly greater vaccine efficacy in their offspring as well: A placebo-subtracted 70% reduction in RSV lower respiratory tract infection with severe hypoxemia through 90 days, compared with a 44% reduction associated with immunization at gestational week 33 or later. And when the interval between immunization and delivery was at least 30 days, the risk of this endpoint was reduced by 65%; in contrast, there was no significant difference between vaccine and placebo groups when time from immunization to delivery was less than 30 days.
Also noteworthy was that maternal immunization afforded no infant protection in the United States. This unanticipated finding is still under investigation, although suspicion centers around the fact that RSV seasons were generally milder there, and American women were vaccinated at a later gestational age, with a corresponding shorter interval to delivery.
The novel recombinant nanoparticle vaccine tested in PREPARE contains a nearly full-length RSV fusion protein produced in insect cells. The nanoparticles express both prefusion epitopes and epitopes common to pre- and postfusion conformations. Aluminum phosphate is employed as the adjuvant.
Novavax’s stock price has been kicked to the curb since the company earlier reported that a large phase 3 trial of the vaccine failed to meet its primary endpoint for prevention of RSV lower respiratory tract infection in older adults. Now the vaccine’s failure to meet its prespecified FDA-mandated primary endpoint in the maternal immunization study will doubtless spawn further financially dismissive headlines in the business press as well.
But pediatricians are famously advocates for children, and PREPARE received a warm welcome from the pediatric infectious disease community, regardless of investor response. Indeed, PREPARE was the only clinical trial deemed of sufficient import to be featured in the opening plenary session of ESPID 2019.
Ulrich Heininger, MD, professor of pediatrics at the University of Basel (Switzerland), who cochaired the session, jointly sponsored by ESPID and the Pediatric Infectious Diseases Society, declared, “These findings, I think, are a great step forward.”
Dr. Munoz reported receiving research grants from Janssen, the National Institutes of Health, the Centers for Disease Control and Prevention, and Novavax, which sponsored the PREPARE trial, assisted by an $89 million grant from the Bill and Melinda Gates Foundation.
LJUBLJANA, SLOVENIA – Passive protection of infants from severe respiratory syncytial virus lower respiratory tract infection during the first 6 months of life has convincingly been achieved through maternal immunization using a novel nanoparticle vaccine in the landmark PREPARE trial.
“I think it’s important for everyone, especially people like myself who’ve been working on maternal immunization for about 20 years, to realize that this is a historic study,” Flor M. Munoz, MD, declared in reporting the study results at the annual meeting of the European Society for Paediatric Infectious Diseases.
“We have here for the first time a phase-3, global, randomized, placebo-controlled, observer-blinded clinical trial looking at an experimental vaccine in pregnant women for the protection of infants from a disease for which we really don’t have other potential solutions quite yet, and in a period of high vulnerability,” said Dr. Munoz, a pediatric infectious disease specialist at Baylor College of Medicine, Houston.
Indeed, respiratory syncytial virus (RSV) is the No. 2 cause of mortality worldwide during the first year of life. Moreover, most cases of severe RSV lower respiratory tract infection occur in otherwise healthy infants aged less than 5 months, when active immunization presents daunting challenges.
“While certainly mortality is uncommon in high-income countries, we do see significant hospitalization there due to severe RSV lower respiratory tract infection in the first year of life, sometimes more than other common diseases, like influenza,” she noted.
PREPARE included 4,636 women with low-risk pregnancies who were randomized 2:1 to a single intramuscular injection of the investigational RSV vaccine or placebo during gestational weeks 28-36, with efficacy assessed through the first 180 days of life. The study took place at 87 sites in 11 countries during 4 years worth of RSV seasons. Roughly half of participants were South African, one-quarter were in the United States, and the rest were drawn from nine other low-, middle-, or high-income countries in the Northern and Southern Hemispheres. The median gestational age at vaccination was 32 weeks.
The primary efficacy endpoint specified by the Food and Drug Administration – but not other regulatory agencies – was the placebo-subtracted rate of RSV lower respiratory tract infection as defined by RSV detected by reverse transcription polymerase chain reaction, along with at least one clinical manifestation of lower respiratory tract infection, oxygen saturation below 95%, and/or tachypnea. The risk of this outcome was reduced by 39% during the first 90 days of life and by 27% through 180 days in infants in the maternal immunization group, a difference which didn’t achieve statistical significance.
However, prespecified major secondary endpoints arguably of greater clinical relevance were consistently positive. Notably, when levels of transplacentally transferred neutralizing antibodies against RSV A and B were highest, with events occurring in 57 of 2,765 evaluable infants in the active treatment arm and in 53 of 1,430 controls. Similarly, there was a 40% reduction through day 180. Moreover, rates of another key secondary endpoint – RSV lower respiratory tract infection plus severe hypoxemia with an oxygen saturation below 92% – were reduced by 48% and 42% through days 90 and 180, respectively. Thus, the vaccine’s protective effect was greatest against the most severe outcomes of RSV infection in infancy, according to Dr. Munoz.
No safety signals related to this immunization strategy were seen during 1 year of follow-up of infants and 6 months for the mothers. Side effects were essentially limited to mild, self-limited injection site reactions, with zero impact on pregnancy and delivery.
An intriguing finding in an exploratory analysis was that the vaccine appeared to have ancillary benefits beyond prevention of medically significant RSV disease in the young infants. For example, the rate of all lower respiratory tract infections with severe hypoxemia – with no requirement for demonstration of RSV infection – was reduced by 46% during the first 90 days of life in the immunized group. Similarly, the rate of all-cause lower respiratory tract infection resulting in hospitalization was reduced by 28%.
“This is actually quite interesting, because these are unexpected benefits in terms of all-cause effects,” the pediatrician commented, adding that she and her coinvestigators are delving into this phenomenon in order to gain better understanding.
Additional analyses of the recently completed PREPARE study are ongoing but already have yielded some important findings. For example, women immunized before 33 weeks’ gestation had significantly greater transplacental antibody transfer than those immunized later in pregnancy, with resultant markedly greater vaccine efficacy in their offspring as well: A placebo-subtracted 70% reduction in RSV lower respiratory tract infection with severe hypoxemia through 90 days, compared with a 44% reduction associated with immunization at gestational week 33 or later. And when the interval between immunization and delivery was at least 30 days, the risk of this endpoint was reduced by 65%; in contrast, there was no significant difference between vaccine and placebo groups when time from immunization to delivery was less than 30 days.
Also noteworthy was that maternal immunization afforded no infant protection in the United States. This unanticipated finding is still under investigation, although suspicion centers around the fact that RSV seasons were generally milder there, and American women were vaccinated at a later gestational age, with a corresponding shorter interval to delivery.
The novel recombinant nanoparticle vaccine tested in PREPARE contains a nearly full-length RSV fusion protein produced in insect cells. The nanoparticles express both prefusion epitopes and epitopes common to pre- and postfusion conformations. Aluminum phosphate is employed as the adjuvant.
Novavax’s stock price has been kicked to the curb since the company earlier reported that a large phase 3 trial of the vaccine failed to meet its primary endpoint for prevention of RSV lower respiratory tract infection in older adults. Now the vaccine’s failure to meet its prespecified FDA-mandated primary endpoint in the maternal immunization study will doubtless spawn further financially dismissive headlines in the business press as well.
But pediatricians are famously advocates for children, and PREPARE received a warm welcome from the pediatric infectious disease community, regardless of investor response. Indeed, PREPARE was the only clinical trial deemed of sufficient import to be featured in the opening plenary session of ESPID 2019.
Ulrich Heininger, MD, professor of pediatrics at the University of Basel (Switzerland), who cochaired the session, jointly sponsored by ESPID and the Pediatric Infectious Diseases Society, declared, “These findings, I think, are a great step forward.”
Dr. Munoz reported receiving research grants from Janssen, the National Institutes of Health, the Centers for Disease Control and Prevention, and Novavax, which sponsored the PREPARE trial, assisted by an $89 million grant from the Bill and Melinda Gates Foundation.
LJUBLJANA, SLOVENIA – Passive protection of infants from severe respiratory syncytial virus lower respiratory tract infection during the first 6 months of life has convincingly been achieved through maternal immunization using a novel nanoparticle vaccine in the landmark PREPARE trial.
“I think it’s important for everyone, especially people like myself who’ve been working on maternal immunization for about 20 years, to realize that this is a historic study,” Flor M. Munoz, MD, declared in reporting the study results at the annual meeting of the European Society for Paediatric Infectious Diseases.
“We have here for the first time a phase-3, global, randomized, placebo-controlled, observer-blinded clinical trial looking at an experimental vaccine in pregnant women for the protection of infants from a disease for which we really don’t have other potential solutions quite yet, and in a period of high vulnerability,” said Dr. Munoz, a pediatric infectious disease specialist at Baylor College of Medicine, Houston.
Indeed, respiratory syncytial virus (RSV) is the No. 2 cause of mortality worldwide during the first year of life. Moreover, most cases of severe RSV lower respiratory tract infection occur in otherwise healthy infants aged less than 5 months, when active immunization presents daunting challenges.
“While certainly mortality is uncommon in high-income countries, we do see significant hospitalization there due to severe RSV lower respiratory tract infection in the first year of life, sometimes more than other common diseases, like influenza,” she noted.
PREPARE included 4,636 women with low-risk pregnancies who were randomized 2:1 to a single intramuscular injection of the investigational RSV vaccine or placebo during gestational weeks 28-36, with efficacy assessed through the first 180 days of life. The study took place at 87 sites in 11 countries during 4 years worth of RSV seasons. Roughly half of participants were South African, one-quarter were in the United States, and the rest were drawn from nine other low-, middle-, or high-income countries in the Northern and Southern Hemispheres. The median gestational age at vaccination was 32 weeks.
The primary efficacy endpoint specified by the Food and Drug Administration – but not other regulatory agencies – was the placebo-subtracted rate of RSV lower respiratory tract infection as defined by RSV detected by reverse transcription polymerase chain reaction, along with at least one clinical manifestation of lower respiratory tract infection, oxygen saturation below 95%, and/or tachypnea. The risk of this outcome was reduced by 39% during the first 90 days of life and by 27% through 180 days in infants in the maternal immunization group, a difference which didn’t achieve statistical significance.
However, prespecified major secondary endpoints arguably of greater clinical relevance were consistently positive. Notably, when levels of transplacentally transferred neutralizing antibodies against RSV A and B were highest, with events occurring in 57 of 2,765 evaluable infants in the active treatment arm and in 53 of 1,430 controls. Similarly, there was a 40% reduction through day 180. Moreover, rates of another key secondary endpoint – RSV lower respiratory tract infection plus severe hypoxemia with an oxygen saturation below 92% – were reduced by 48% and 42% through days 90 and 180, respectively. Thus, the vaccine’s protective effect was greatest against the most severe outcomes of RSV infection in infancy, according to Dr. Munoz.
No safety signals related to this immunization strategy were seen during 1 year of follow-up of infants and 6 months for the mothers. Side effects were essentially limited to mild, self-limited injection site reactions, with zero impact on pregnancy and delivery.
An intriguing finding in an exploratory analysis was that the vaccine appeared to have ancillary benefits beyond prevention of medically significant RSV disease in the young infants. For example, the rate of all lower respiratory tract infections with severe hypoxemia – with no requirement for demonstration of RSV infection – was reduced by 46% during the first 90 days of life in the immunized group. Similarly, the rate of all-cause lower respiratory tract infection resulting in hospitalization was reduced by 28%.
“This is actually quite interesting, because these are unexpected benefits in terms of all-cause effects,” the pediatrician commented, adding that she and her coinvestigators are delving into this phenomenon in order to gain better understanding.
Additional analyses of the recently completed PREPARE study are ongoing but already have yielded some important findings. For example, women immunized before 33 weeks’ gestation had significantly greater transplacental antibody transfer than those immunized later in pregnancy, with resultant markedly greater vaccine efficacy in their offspring as well: A placebo-subtracted 70% reduction in RSV lower respiratory tract infection with severe hypoxemia through 90 days, compared with a 44% reduction associated with immunization at gestational week 33 or later. And when the interval between immunization and delivery was at least 30 days, the risk of this endpoint was reduced by 65%; in contrast, there was no significant difference between vaccine and placebo groups when time from immunization to delivery was less than 30 days.
Also noteworthy was that maternal immunization afforded no infant protection in the United States. This unanticipated finding is still under investigation, although suspicion centers around the fact that RSV seasons were generally milder there, and American women were vaccinated at a later gestational age, with a corresponding shorter interval to delivery.
The novel recombinant nanoparticle vaccine tested in PREPARE contains a nearly full-length RSV fusion protein produced in insect cells. The nanoparticles express both prefusion epitopes and epitopes common to pre- and postfusion conformations. Aluminum phosphate is employed as the adjuvant.
Novavax’s stock price has been kicked to the curb since the company earlier reported that a large phase 3 trial of the vaccine failed to meet its primary endpoint for prevention of RSV lower respiratory tract infection in older adults. Now the vaccine’s failure to meet its prespecified FDA-mandated primary endpoint in the maternal immunization study will doubtless spawn further financially dismissive headlines in the business press as well.
But pediatricians are famously advocates for children, and PREPARE received a warm welcome from the pediatric infectious disease community, regardless of investor response. Indeed, PREPARE was the only clinical trial deemed of sufficient import to be featured in the opening plenary session of ESPID 2019.
Ulrich Heininger, MD, professor of pediatrics at the University of Basel (Switzerland), who cochaired the session, jointly sponsored by ESPID and the Pediatric Infectious Diseases Society, declared, “These findings, I think, are a great step forward.”
Dr. Munoz reported receiving research grants from Janssen, the National Institutes of Health, the Centers for Disease Control and Prevention, and Novavax, which sponsored the PREPARE trial, assisted by an $89 million grant from the Bill and Melinda Gates Foundation.
REPORTING FROM ESPID 2019
Is it measles? – Diagnosis and management for the pediatric provider
The mother of an 8-month-old calls your office and is hysterical. Her daughter has had cough for a few days with high fevers and now has developed a full body rash. She is worried about measles and is on her way to your office.
We are in the middle of a measles epidemic, there’s no denying it. Measles was declared eliminated in 2000, but reported cases in the United States have been on the rise, and are now at the highest number since 2014. Five months into 2019, there have been 839 reported cases as of May 13). Measles outbreaks (defined by the Centers for Disease Control and Prevention as three or more cases) have been reported in California, Georgia, Maryland, Michigan, New Jersey, New York, and Pennsylvania. When vaccination rates fall, it is easy for measles to spread. The virus is highly contagious in nonimmune people, because of its airborne spread and its persistence in the environment for hours.
First – is it really measles?
It can be difficult to distinguish the maculopapular rash of measles from similar rashes that occur with more benign viral illnesses. Adding to the challenge, the last major measles outbreak in the United States was over 2 decades ago, and many practicing pediatricians have never seen a single case. So, what clinical features can help distinguish measles from other febrile illnesses?
The prodromal phase of measles lasts approximately 2-4 days and children have high fevers (103°-105° F), anorexia, and malaise. Conjunctivitis, coryza, and cough develop during this phase, and precede any rash. Koplik spots appear during the prodromal phase, but are not seen in all cases. These spots are 1- to 3-mm blue-white lesions on an erythematous base on the buccal mucosa, classically opposite the first molar. The spots often slough once the rash appears. The rash appears 2-4 days after the onset of fever, and is initially maculopapular and blanching. The first lesions appear on the face and neck, and the rash spreads cranial to caudal, typically sparing palms and soles. After days 3-4, the rash will no longer blanch. High fevers persist for 2-4 more days with rash, ongoing respiratory symptoms, conjunctivitis, and pharyngitis. Note that the fever will persist even with development of the rash, unlike in roseola.
It is not only important to diagnosis measles from a public health standpoint, but also because measles can have severe complications, especially in infants and children under 5 years. During the 1989-1991 outbreak, the mortality rate was 2.2 deaths per 1,000 cases (J Infect Dis. 2004 May 1. doi: 10.1086/377694).
Six percent of patients develop pneumonia, which in infants and toddlers can lead to respiratory distress or failure requiring hospitalization. Pneumonia is responsible for 60% of measles deaths, according to the CDC “Pink Book,” Epidemiology and Prevention of Vaccine-Preventable Diseases, chapter 13 on measles, 13th Ed., 2015. Ocular complications include keratitis and corneal ulceration. Measles also can cause serious neurologic complications. Encephalitis, seen in 1 per 1,000 cases, usually arises several days after the rash and may present with seizure or encephalopathy. Acute disseminated encephalomyelitis (ADEM), an inflammatory demyelinating disease of the central nervous system, occurs in approximately 1 per 1,000 cases, typically presents during the recovery phase (1-2 weeks after rash), and can have long-term sequelae. Subacute sclerosing panencephalitis (SSPE) is a progressive and fatal neurodegenerative disorder, and presents 7-10 years after measles infection.
Should you transfer the patient to a hospital?
Unless there is a medical need for the child to be admitted, sending a patient with potential measles to the hospital is not necessary, and can cause exposure to a large group of medical personnel, and patients who cannot be vaccinated (such as infants, immunocompromised patients, and pregnant women). However, if there is concern for complications such as seizures, encephalitis, or pneumonia, then transfer is indicated. Call the accepting hospital in advance so the staff can prepare for the patient. During transfer, place a standard face mask on the patient and instruct the patient not to remove it.
For hospitals accepting a suspected measles case, meet the patient outside of the facility and ensure that the patient is wearing a standard face mask. All staff interacting with the patient should practice contact and airborne precautions (N95 respirator mask). Take the patient directly to an isolation room with negative airflow. Caution pregnant staff that they should not have contact with the patient.
Which diagnostic tests should you use?
Diagnosis can be made based on serum antibody tests (measles IgM and IgG), throat or urine viral cultures, and nasopharyngeal and throat specimen polymerase chain reaction (PCR) testing. The CDC recommends obtaining a serum sample for measles IgM testing and a throat swab for PCR in all suspected cases, but local health departments vary in their specific testing recommendations. Familiarize yourself with the tests recommended by your local department of health, and where they prefer testing on outpatients to be done. Confirmed measles should be reported to your department of health.
What are considerations for community pediatric offices?
Update families in emails to call ahead if they suspect measles. This way the office can prepare a room for the family, and have the family immediately brought back without exposing staff and other families in the waiting area. It may be more prudent to examine these children at the end of the clinic day as the virus can persist for up to 2 hours on fomites and in the air. Therefore, all waiting areas and shared air spaces (including those with shared air ducts) should be cleared for 2 hours after the patient leaves.
When should you provide prophylaxis after exposure?
A patient with suspected measles does not require immediate vaccination. If it is measles, it is already too late to vaccinate. If measles is ruled out, the child should follow the standard measles vaccination guidelines.
Individuals are contagious from 4 days before to 4 days after the rash appears.
If measles is confirmed, all people who are unvaccinated or undervaccinated and were exposed to the confirmed case during the contagious period should be vaccinated within 72 hours of exposure. Infants 6 months or older may safely receive the MMR vaccine. However, infants vaccinated with MMR before their first birthday must be vaccinated again at age 12-15 months (greater than 28 days after prior vaccine) and at 4-6 years. Immunoglobulin prophylaxis should be given intramuscularly in exposed infants ages birth to less than 6 months, and in those ages 6-12 months who present beyond the 72-hour window. Unvaccinated or undervaccinated, exposed individuals at high risk for complications from measles (immunocompromised, pregnant) also should receive immunoglobulin.
What should you tell traveling families?
Several countries have large, ongoing measles outbreaks, including Israel, Ukraine, and the Philippines. Before international travel, infants 6-11 months should receive one dose of MMR vaccine, and children 12 months and older need two doses separated by at least 28 days. For unvaccinated or undervaccinated children, consider advising families to hold off travel to high-risk countries, or understand the indications to vaccinate a child upon return.
Dr. Angelica DesPain is a pediatric emergency medicine fellow at Children’s National Medical Center in Washington. She said she has no relevant financial disclosures. Dr. Emily Willner is a pediatric emergency medicine attending at Children’s National Medical Center, and an assistant professor of pediatrics and emergency medicine at George Washington University, Washington. She has no relevant financial disclosures.
The mother of an 8-month-old calls your office and is hysterical. Her daughter has had cough for a few days with high fevers and now has developed a full body rash. She is worried about measles and is on her way to your office.
We are in the middle of a measles epidemic, there’s no denying it. Measles was declared eliminated in 2000, but reported cases in the United States have been on the rise, and are now at the highest number since 2014. Five months into 2019, there have been 839 reported cases as of May 13). Measles outbreaks (defined by the Centers for Disease Control and Prevention as three or more cases) have been reported in California, Georgia, Maryland, Michigan, New Jersey, New York, and Pennsylvania. When vaccination rates fall, it is easy for measles to spread. The virus is highly contagious in nonimmune people, because of its airborne spread and its persistence in the environment for hours.
First – is it really measles?
It can be difficult to distinguish the maculopapular rash of measles from similar rashes that occur with more benign viral illnesses. Adding to the challenge, the last major measles outbreak in the United States was over 2 decades ago, and many practicing pediatricians have never seen a single case. So, what clinical features can help distinguish measles from other febrile illnesses?
The prodromal phase of measles lasts approximately 2-4 days and children have high fevers (103°-105° F), anorexia, and malaise. Conjunctivitis, coryza, and cough develop during this phase, and precede any rash. Koplik spots appear during the prodromal phase, but are not seen in all cases. These spots are 1- to 3-mm blue-white lesions on an erythematous base on the buccal mucosa, classically opposite the first molar. The spots often slough once the rash appears. The rash appears 2-4 days after the onset of fever, and is initially maculopapular and blanching. The first lesions appear on the face and neck, and the rash spreads cranial to caudal, typically sparing palms and soles. After days 3-4, the rash will no longer blanch. High fevers persist for 2-4 more days with rash, ongoing respiratory symptoms, conjunctivitis, and pharyngitis. Note that the fever will persist even with development of the rash, unlike in roseola.
It is not only important to diagnosis measles from a public health standpoint, but also because measles can have severe complications, especially in infants and children under 5 years. During the 1989-1991 outbreak, the mortality rate was 2.2 deaths per 1,000 cases (J Infect Dis. 2004 May 1. doi: 10.1086/377694).
Six percent of patients develop pneumonia, which in infants and toddlers can lead to respiratory distress or failure requiring hospitalization. Pneumonia is responsible for 60% of measles deaths, according to the CDC “Pink Book,” Epidemiology and Prevention of Vaccine-Preventable Diseases, chapter 13 on measles, 13th Ed., 2015. Ocular complications include keratitis and corneal ulceration. Measles also can cause serious neurologic complications. Encephalitis, seen in 1 per 1,000 cases, usually arises several days after the rash and may present with seizure or encephalopathy. Acute disseminated encephalomyelitis (ADEM), an inflammatory demyelinating disease of the central nervous system, occurs in approximately 1 per 1,000 cases, typically presents during the recovery phase (1-2 weeks after rash), and can have long-term sequelae. Subacute sclerosing panencephalitis (SSPE) is a progressive and fatal neurodegenerative disorder, and presents 7-10 years after measles infection.
Should you transfer the patient to a hospital?
Unless there is a medical need for the child to be admitted, sending a patient with potential measles to the hospital is not necessary, and can cause exposure to a large group of medical personnel, and patients who cannot be vaccinated (such as infants, immunocompromised patients, and pregnant women). However, if there is concern for complications such as seizures, encephalitis, or pneumonia, then transfer is indicated. Call the accepting hospital in advance so the staff can prepare for the patient. During transfer, place a standard face mask on the patient and instruct the patient not to remove it.
For hospitals accepting a suspected measles case, meet the patient outside of the facility and ensure that the patient is wearing a standard face mask. All staff interacting with the patient should practice contact and airborne precautions (N95 respirator mask). Take the patient directly to an isolation room with negative airflow. Caution pregnant staff that they should not have contact with the patient.
Which diagnostic tests should you use?
Diagnosis can be made based on serum antibody tests (measles IgM and IgG), throat or urine viral cultures, and nasopharyngeal and throat specimen polymerase chain reaction (PCR) testing. The CDC recommends obtaining a serum sample for measles IgM testing and a throat swab for PCR in all suspected cases, but local health departments vary in their specific testing recommendations. Familiarize yourself with the tests recommended by your local department of health, and where they prefer testing on outpatients to be done. Confirmed measles should be reported to your department of health.
What are considerations for community pediatric offices?
Update families in emails to call ahead if they suspect measles. This way the office can prepare a room for the family, and have the family immediately brought back without exposing staff and other families in the waiting area. It may be more prudent to examine these children at the end of the clinic day as the virus can persist for up to 2 hours on fomites and in the air. Therefore, all waiting areas and shared air spaces (including those with shared air ducts) should be cleared for 2 hours after the patient leaves.
When should you provide prophylaxis after exposure?
A patient with suspected measles does not require immediate vaccination. If it is measles, it is already too late to vaccinate. If measles is ruled out, the child should follow the standard measles vaccination guidelines.
Individuals are contagious from 4 days before to 4 days after the rash appears.
If measles is confirmed, all people who are unvaccinated or undervaccinated and were exposed to the confirmed case during the contagious period should be vaccinated within 72 hours of exposure. Infants 6 months or older may safely receive the MMR vaccine. However, infants vaccinated with MMR before their first birthday must be vaccinated again at age 12-15 months (greater than 28 days after prior vaccine) and at 4-6 years. Immunoglobulin prophylaxis should be given intramuscularly in exposed infants ages birth to less than 6 months, and in those ages 6-12 months who present beyond the 72-hour window. Unvaccinated or undervaccinated, exposed individuals at high risk for complications from measles (immunocompromised, pregnant) also should receive immunoglobulin.
What should you tell traveling families?
Several countries have large, ongoing measles outbreaks, including Israel, Ukraine, and the Philippines. Before international travel, infants 6-11 months should receive one dose of MMR vaccine, and children 12 months and older need two doses separated by at least 28 days. For unvaccinated or undervaccinated children, consider advising families to hold off travel to high-risk countries, or understand the indications to vaccinate a child upon return.
Dr. Angelica DesPain is a pediatric emergency medicine fellow at Children’s National Medical Center in Washington. She said she has no relevant financial disclosures. Dr. Emily Willner is a pediatric emergency medicine attending at Children’s National Medical Center, and an assistant professor of pediatrics and emergency medicine at George Washington University, Washington. She has no relevant financial disclosures.
The mother of an 8-month-old calls your office and is hysterical. Her daughter has had cough for a few days with high fevers and now has developed a full body rash. She is worried about measles and is on her way to your office.
We are in the middle of a measles epidemic, there’s no denying it. Measles was declared eliminated in 2000, but reported cases in the United States have been on the rise, and are now at the highest number since 2014. Five months into 2019, there have been 839 reported cases as of May 13). Measles outbreaks (defined by the Centers for Disease Control and Prevention as three or more cases) have been reported in California, Georgia, Maryland, Michigan, New Jersey, New York, and Pennsylvania. When vaccination rates fall, it is easy for measles to spread. The virus is highly contagious in nonimmune people, because of its airborne spread and its persistence in the environment for hours.
First – is it really measles?
It can be difficult to distinguish the maculopapular rash of measles from similar rashes that occur with more benign viral illnesses. Adding to the challenge, the last major measles outbreak in the United States was over 2 decades ago, and many practicing pediatricians have never seen a single case. So, what clinical features can help distinguish measles from other febrile illnesses?
The prodromal phase of measles lasts approximately 2-4 days and children have high fevers (103°-105° F), anorexia, and malaise. Conjunctivitis, coryza, and cough develop during this phase, and precede any rash. Koplik spots appear during the prodromal phase, but are not seen in all cases. These spots are 1- to 3-mm blue-white lesions on an erythematous base on the buccal mucosa, classically opposite the first molar. The spots often slough once the rash appears. The rash appears 2-4 days after the onset of fever, and is initially maculopapular and blanching. The first lesions appear on the face and neck, and the rash spreads cranial to caudal, typically sparing palms and soles. After days 3-4, the rash will no longer blanch. High fevers persist for 2-4 more days with rash, ongoing respiratory symptoms, conjunctivitis, and pharyngitis. Note that the fever will persist even with development of the rash, unlike in roseola.
It is not only important to diagnosis measles from a public health standpoint, but also because measles can have severe complications, especially in infants and children under 5 years. During the 1989-1991 outbreak, the mortality rate was 2.2 deaths per 1,000 cases (J Infect Dis. 2004 May 1. doi: 10.1086/377694).
Six percent of patients develop pneumonia, which in infants and toddlers can lead to respiratory distress or failure requiring hospitalization. Pneumonia is responsible for 60% of measles deaths, according to the CDC “Pink Book,” Epidemiology and Prevention of Vaccine-Preventable Diseases, chapter 13 on measles, 13th Ed., 2015. Ocular complications include keratitis and corneal ulceration. Measles also can cause serious neurologic complications. Encephalitis, seen in 1 per 1,000 cases, usually arises several days after the rash and may present with seizure or encephalopathy. Acute disseminated encephalomyelitis (ADEM), an inflammatory demyelinating disease of the central nervous system, occurs in approximately 1 per 1,000 cases, typically presents during the recovery phase (1-2 weeks after rash), and can have long-term sequelae. Subacute sclerosing panencephalitis (SSPE) is a progressive and fatal neurodegenerative disorder, and presents 7-10 years after measles infection.
Should you transfer the patient to a hospital?
Unless there is a medical need for the child to be admitted, sending a patient with potential measles to the hospital is not necessary, and can cause exposure to a large group of medical personnel, and patients who cannot be vaccinated (such as infants, immunocompromised patients, and pregnant women). However, if there is concern for complications such as seizures, encephalitis, or pneumonia, then transfer is indicated. Call the accepting hospital in advance so the staff can prepare for the patient. During transfer, place a standard face mask on the patient and instruct the patient not to remove it.
For hospitals accepting a suspected measles case, meet the patient outside of the facility and ensure that the patient is wearing a standard face mask. All staff interacting with the patient should practice contact and airborne precautions (N95 respirator mask). Take the patient directly to an isolation room with negative airflow. Caution pregnant staff that they should not have contact with the patient.
Which diagnostic tests should you use?
Diagnosis can be made based on serum antibody tests (measles IgM and IgG), throat or urine viral cultures, and nasopharyngeal and throat specimen polymerase chain reaction (PCR) testing. The CDC recommends obtaining a serum sample for measles IgM testing and a throat swab for PCR in all suspected cases, but local health departments vary in their specific testing recommendations. Familiarize yourself with the tests recommended by your local department of health, and where they prefer testing on outpatients to be done. Confirmed measles should be reported to your department of health.
What are considerations for community pediatric offices?
Update families in emails to call ahead if they suspect measles. This way the office can prepare a room for the family, and have the family immediately brought back without exposing staff and other families in the waiting area. It may be more prudent to examine these children at the end of the clinic day as the virus can persist for up to 2 hours on fomites and in the air. Therefore, all waiting areas and shared air spaces (including those with shared air ducts) should be cleared for 2 hours after the patient leaves.
When should you provide prophylaxis after exposure?
A patient with suspected measles does not require immediate vaccination. If it is measles, it is already too late to vaccinate. If measles is ruled out, the child should follow the standard measles vaccination guidelines.
Individuals are contagious from 4 days before to 4 days after the rash appears.
If measles is confirmed, all people who are unvaccinated or undervaccinated and were exposed to the confirmed case during the contagious period should be vaccinated within 72 hours of exposure. Infants 6 months or older may safely receive the MMR vaccine. However, infants vaccinated with MMR before their first birthday must be vaccinated again at age 12-15 months (greater than 28 days after prior vaccine) and at 4-6 years. Immunoglobulin prophylaxis should be given intramuscularly in exposed infants ages birth to less than 6 months, and in those ages 6-12 months who present beyond the 72-hour window. Unvaccinated or undervaccinated, exposed individuals at high risk for complications from measles (immunocompromised, pregnant) also should receive immunoglobulin.
What should you tell traveling families?
Several countries have large, ongoing measles outbreaks, including Israel, Ukraine, and the Philippines. Before international travel, infants 6-11 months should receive one dose of MMR vaccine, and children 12 months and older need two doses separated by at least 28 days. For unvaccinated or undervaccinated children, consider advising families to hold off travel to high-risk countries, or understand the indications to vaccinate a child upon return.
Dr. Angelica DesPain is a pediatric emergency medicine fellow at Children’s National Medical Center in Washington. She said she has no relevant financial disclosures. Dr. Emily Willner is a pediatric emergency medicine attending at Children’s National Medical Center, and an assistant professor of pediatrics and emergency medicine at George Washington University, Washington. She has no relevant financial disclosures.
Younger patients with NSCLC tend to live longer
Younger patients with non–small cell lung cancer (NSCLC) may have better survival, despite higher rates of brain metastasis and driver mutations, according to results from a retrospective analysis.
“We carried out a comprehensive analysis of patient clinicopathologic features and clinical outcomes in both young (age ≤ 50 years) and older (age > 60 years) patients with NSCLC,” wrote Anna May Suidan of Tel Aviv University, and colleagues. The findings were published in the Journal of Global Oncology.
The researchers reviewed medical records of patients who were diagnosed with lung cancer at a large cancer treatment facility in Israel from 2010 to 2015. Patients were categorized into two groups according to age at cancer diagnosis, which was established based on tumor pathology.
Various clinical data were collected, including demographic information, history of malignancy, smoking history, histologic subtype, and survival data.
In all, 62 patients were included in the younger cohort (median age, 44.5 years) and 124 patients in the older cohort (median age, 68.0 years).
After analysis, the researchers found that younger patients had a higher incidence of brain metastasis (39% vs. 25%, respectively; P = .04), and increased rates of EGFR mutations (23% vs. 18%, respectively; P = .4) and ALK translocations (13% vs. 2%, respectively; P = .002) versus older patients.
“Our cohort, which was [composed] of white patients, demonstrated that younger patients harbored more targetable driver mutations compared with older patients (34% vs. 18%; P = .01),” the researchers wrote.
In addition, among those with a driver mutation, younger patients showed a trend toward better survival (median survival, 33 vs. 25 months, respectively; P = .4).
Two key limitations of the study were the small sample size and retrospective design.
“[These results] highlight the importance of genetic background assessments and considering lung cancer as a possible diagnosis in young symptomatic patients in clinical settings,” the researchers concluded.
No funding sources were reported. The authors reported financial affiliations with Astra Zeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Novartis, Roche, Teva Pharmaceuticals, and several others.
SOURCE: Suidan AM et al. J Glob Oncol. 2019 May 8. doi: 10.1200/JGO.18.00216.
Younger patients with non–small cell lung cancer (NSCLC) may have better survival, despite higher rates of brain metastasis and driver mutations, according to results from a retrospective analysis.
“We carried out a comprehensive analysis of patient clinicopathologic features and clinical outcomes in both young (age ≤ 50 years) and older (age > 60 years) patients with NSCLC,” wrote Anna May Suidan of Tel Aviv University, and colleagues. The findings were published in the Journal of Global Oncology.
The researchers reviewed medical records of patients who were diagnosed with lung cancer at a large cancer treatment facility in Israel from 2010 to 2015. Patients were categorized into two groups according to age at cancer diagnosis, which was established based on tumor pathology.
Various clinical data were collected, including demographic information, history of malignancy, smoking history, histologic subtype, and survival data.
In all, 62 patients were included in the younger cohort (median age, 44.5 years) and 124 patients in the older cohort (median age, 68.0 years).
After analysis, the researchers found that younger patients had a higher incidence of brain metastasis (39% vs. 25%, respectively; P = .04), and increased rates of EGFR mutations (23% vs. 18%, respectively; P = .4) and ALK translocations (13% vs. 2%, respectively; P = .002) versus older patients.
“Our cohort, which was [composed] of white patients, demonstrated that younger patients harbored more targetable driver mutations compared with older patients (34% vs. 18%; P = .01),” the researchers wrote.
In addition, among those with a driver mutation, younger patients showed a trend toward better survival (median survival, 33 vs. 25 months, respectively; P = .4).
Two key limitations of the study were the small sample size and retrospective design.
“[These results] highlight the importance of genetic background assessments and considering lung cancer as a possible diagnosis in young symptomatic patients in clinical settings,” the researchers concluded.
No funding sources were reported. The authors reported financial affiliations with Astra Zeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Novartis, Roche, Teva Pharmaceuticals, and several others.
SOURCE: Suidan AM et al. J Glob Oncol. 2019 May 8. doi: 10.1200/JGO.18.00216.
Younger patients with non–small cell lung cancer (NSCLC) may have better survival, despite higher rates of brain metastasis and driver mutations, according to results from a retrospective analysis.
“We carried out a comprehensive analysis of patient clinicopathologic features and clinical outcomes in both young (age ≤ 50 years) and older (age > 60 years) patients with NSCLC,” wrote Anna May Suidan of Tel Aviv University, and colleagues. The findings were published in the Journal of Global Oncology.
The researchers reviewed medical records of patients who were diagnosed with lung cancer at a large cancer treatment facility in Israel from 2010 to 2015. Patients were categorized into two groups according to age at cancer diagnosis, which was established based on tumor pathology.
Various clinical data were collected, including demographic information, history of malignancy, smoking history, histologic subtype, and survival data.
In all, 62 patients were included in the younger cohort (median age, 44.5 years) and 124 patients in the older cohort (median age, 68.0 years).
After analysis, the researchers found that younger patients had a higher incidence of brain metastasis (39% vs. 25%, respectively; P = .04), and increased rates of EGFR mutations (23% vs. 18%, respectively; P = .4) and ALK translocations (13% vs. 2%, respectively; P = .002) versus older patients.
“Our cohort, which was [composed] of white patients, demonstrated that younger patients harbored more targetable driver mutations compared with older patients (34% vs. 18%; P = .01),” the researchers wrote.
In addition, among those with a driver mutation, younger patients showed a trend toward better survival (median survival, 33 vs. 25 months, respectively; P = .4).
Two key limitations of the study were the small sample size and retrospective design.
“[These results] highlight the importance of genetic background assessments and considering lung cancer as a possible diagnosis in young symptomatic patients in clinical settings,” the researchers concluded.
No funding sources were reported. The authors reported financial affiliations with Astra Zeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Novartis, Roche, Teva Pharmaceuticals, and several others.
SOURCE: Suidan AM et al. J Glob Oncol. 2019 May 8. doi: 10.1200/JGO.18.00216.
FROM THE JOURNAL OF GLOBAL ONCOLOGY
Infections within first year of life predicted IBD
according to the findings of a large population-based study.
It remains unclear whether the risk reflects infections in themselves or the use of antibiotic therapy, wrote Charles N. Bernstein, MD, of the University of Manitoba, Winnipeg, and associates. Infections did not appear to be a proxy for immunodeficiency disorders, which were similarly infrequent among cases and controls, they noted. Limiting antibiotic usage, while desirable, would be difficult to do for infections as serious as many in the study. Hence, they suggested research to determine “exactly what antibiotic intake does to infant gut microflora or intestinal or systemic immune responses,” and whether giving probiotics or prebiotics after antibiotic therapy helps attenuate the risk of inflammatory bowel disease (IBD) and other autoimmune disorders. The findings were published in Gastroenterology.
IBD is probably multifactorial, but specific causal factors remain unclear. Based on mounting evidence for the role of gut dysbiosis, the researchers explored whether IBD is associated with higher rates of infections and other critical events during the neonatal period and the first year of life by comparing 825 patients with IBD and 5,999 controls matched by age, sex, and area of residence. The data source was the University of Manitoba IBD Epidemiology Database, which includes all Manitobans diagnosed with IBD from 1984 to 2010. The researchers also compared patients with 1,740 unaffected siblings.
Gastrointestinal infections, gastrointestinal disease, and abdominal pain during the first year of life did not predict subsequent IBD. Maternal IBD was the strongest risk factor (odds ratio, 4.5; 95% confidence interval, 3.1-6.7). Among neonatal events, the only significant risk factor was being in the highest versus the lowest socioeconomic quintile (OR, 1.35; 95% CI, 1.01-1.79). This association persisted during the first year of life.
Infections during the first year of life were a significant risk factor for IBD before age 10 (OR, 3.1; 95% CI, 1.1-8.8) and age 20 years (OR, 1.6; 95% CI, 1.2-2.2) in the population-based analysis. In contrast, patients and their unaffected siblings had similar rates of infection during early life. The study may have missed differences in exposures between these groups, or perhaps patients lack certain protective genes possessed by healthy siblings, the researchers wrote.
Numbers of antibiotic prescriptions during the first year and the first decade of life did not significantly differ between 33 cases and 270 controls with available data. However, there was a trend toward more antibiotics prescribed to patients versus controls.
“Together with our past reports that neither cesarean section birth nor antenatal or perinatal maternal use of antibiotics predict ultimate development of IBD, it seems that neonatal changes to the microbiome are subsumed by those occurring in the first year of life,” the investigators concluded. They recommended studying the infant gut microbiome before and for several months after infections and antibiotic exposure to determine which shifts in microbiota predict IBD onset.
The Manitoba Centre for Health Policy provided access to the Population Health Research Data Repository. Dr. Bernstein is supported by the Bingham Chair in Gastroenterology. He reported ties to AbbVie Canada, Ferring Canada, Janssen Canada, Shire Canada, Takeda Canada, Pfizer Canada, Napo Pharmaceuticals, 4D Pharma, and Mylan.
SOURCE: Bernstein CN et al. Gastroenterology. 2019 Feb 14. doi: 10.1053/j.gastro.2019.02.004.
Understanding and exploring factors that could impact inflammatory bowel disease (IBD) development is imperative. This study by Bernstein et al. evaluated whether environmental factors in the first year of life may impact subsequent diagnosis of IBD using population-based cohort data with robust and detailed health information. Maternal history of IBD was the most predictive factor in development of IBD, further evidence of a genetic component to disease pathogenesis. However, environmental factors such as high socioeconomic status within the first year of life were predictive of diagnosis of IBD later in life, possibly lending further support to the “hygiene hypothesis.”
Also, significant infections identified in the clinical setting or requiring hospitalization were predictive of subsequent IBD diagnosis. This is particularly interesting as gut microbiome perturbations increasingly take the stage as a possible pathway of significance in IBD. Could infection within the first year of life or the subsequent antibiotic use required affect the gut microbiome so significantly and perhaps permanently to affect development of later childhood or adult IBD?
Sara Horst, MD, MPH, is an associate professor of medicine in the department of gastroenterology, hepatology, and medicine at Vanderbilt University, Nashville, Tenn. She has consulted for Janssen, UCB, and Boehringer Ingelheim.
Understanding and exploring factors that could impact inflammatory bowel disease (IBD) development is imperative. This study by Bernstein et al. evaluated whether environmental factors in the first year of life may impact subsequent diagnosis of IBD using population-based cohort data with robust and detailed health information. Maternal history of IBD was the most predictive factor in development of IBD, further evidence of a genetic component to disease pathogenesis. However, environmental factors such as high socioeconomic status within the first year of life were predictive of diagnosis of IBD later in life, possibly lending further support to the “hygiene hypothesis.”
Also, significant infections identified in the clinical setting or requiring hospitalization were predictive of subsequent IBD diagnosis. This is particularly interesting as gut microbiome perturbations increasingly take the stage as a possible pathway of significance in IBD. Could infection within the first year of life or the subsequent antibiotic use required affect the gut microbiome so significantly and perhaps permanently to affect development of later childhood or adult IBD?
Sara Horst, MD, MPH, is an associate professor of medicine in the department of gastroenterology, hepatology, and medicine at Vanderbilt University, Nashville, Tenn. She has consulted for Janssen, UCB, and Boehringer Ingelheim.
Understanding and exploring factors that could impact inflammatory bowel disease (IBD) development is imperative. This study by Bernstein et al. evaluated whether environmental factors in the first year of life may impact subsequent diagnosis of IBD using population-based cohort data with robust and detailed health information. Maternal history of IBD was the most predictive factor in development of IBD, further evidence of a genetic component to disease pathogenesis. However, environmental factors such as high socioeconomic status within the first year of life were predictive of diagnosis of IBD later in life, possibly lending further support to the “hygiene hypothesis.”
Also, significant infections identified in the clinical setting or requiring hospitalization were predictive of subsequent IBD diagnosis. This is particularly interesting as gut microbiome perturbations increasingly take the stage as a possible pathway of significance in IBD. Could infection within the first year of life or the subsequent antibiotic use required affect the gut microbiome so significantly and perhaps permanently to affect development of later childhood or adult IBD?
Sara Horst, MD, MPH, is an associate professor of medicine in the department of gastroenterology, hepatology, and medicine at Vanderbilt University, Nashville, Tenn. She has consulted for Janssen, UCB, and Boehringer Ingelheim.
according to the findings of a large population-based study.
It remains unclear whether the risk reflects infections in themselves or the use of antibiotic therapy, wrote Charles N. Bernstein, MD, of the University of Manitoba, Winnipeg, and associates. Infections did not appear to be a proxy for immunodeficiency disorders, which were similarly infrequent among cases and controls, they noted. Limiting antibiotic usage, while desirable, would be difficult to do for infections as serious as many in the study. Hence, they suggested research to determine “exactly what antibiotic intake does to infant gut microflora or intestinal or systemic immune responses,” and whether giving probiotics or prebiotics after antibiotic therapy helps attenuate the risk of inflammatory bowel disease (IBD) and other autoimmune disorders. The findings were published in Gastroenterology.
IBD is probably multifactorial, but specific causal factors remain unclear. Based on mounting evidence for the role of gut dysbiosis, the researchers explored whether IBD is associated with higher rates of infections and other critical events during the neonatal period and the first year of life by comparing 825 patients with IBD and 5,999 controls matched by age, sex, and area of residence. The data source was the University of Manitoba IBD Epidemiology Database, which includes all Manitobans diagnosed with IBD from 1984 to 2010. The researchers also compared patients with 1,740 unaffected siblings.
Gastrointestinal infections, gastrointestinal disease, and abdominal pain during the first year of life did not predict subsequent IBD. Maternal IBD was the strongest risk factor (odds ratio, 4.5; 95% confidence interval, 3.1-6.7). Among neonatal events, the only significant risk factor was being in the highest versus the lowest socioeconomic quintile (OR, 1.35; 95% CI, 1.01-1.79). This association persisted during the first year of life.
Infections during the first year of life were a significant risk factor for IBD before age 10 (OR, 3.1; 95% CI, 1.1-8.8) and age 20 years (OR, 1.6; 95% CI, 1.2-2.2) in the population-based analysis. In contrast, patients and their unaffected siblings had similar rates of infection during early life. The study may have missed differences in exposures between these groups, or perhaps patients lack certain protective genes possessed by healthy siblings, the researchers wrote.
Numbers of antibiotic prescriptions during the first year and the first decade of life did not significantly differ between 33 cases and 270 controls with available data. However, there was a trend toward more antibiotics prescribed to patients versus controls.
“Together with our past reports that neither cesarean section birth nor antenatal or perinatal maternal use of antibiotics predict ultimate development of IBD, it seems that neonatal changes to the microbiome are subsumed by those occurring in the first year of life,” the investigators concluded. They recommended studying the infant gut microbiome before and for several months after infections and antibiotic exposure to determine which shifts in microbiota predict IBD onset.
The Manitoba Centre for Health Policy provided access to the Population Health Research Data Repository. Dr. Bernstein is supported by the Bingham Chair in Gastroenterology. He reported ties to AbbVie Canada, Ferring Canada, Janssen Canada, Shire Canada, Takeda Canada, Pfizer Canada, Napo Pharmaceuticals, 4D Pharma, and Mylan.
SOURCE: Bernstein CN et al. Gastroenterology. 2019 Feb 14. doi: 10.1053/j.gastro.2019.02.004.
according to the findings of a large population-based study.
It remains unclear whether the risk reflects infections in themselves or the use of antibiotic therapy, wrote Charles N. Bernstein, MD, of the University of Manitoba, Winnipeg, and associates. Infections did not appear to be a proxy for immunodeficiency disorders, which were similarly infrequent among cases and controls, they noted. Limiting antibiotic usage, while desirable, would be difficult to do for infections as serious as many in the study. Hence, they suggested research to determine “exactly what antibiotic intake does to infant gut microflora or intestinal or systemic immune responses,” and whether giving probiotics or prebiotics after antibiotic therapy helps attenuate the risk of inflammatory bowel disease (IBD) and other autoimmune disorders. The findings were published in Gastroenterology.
IBD is probably multifactorial, but specific causal factors remain unclear. Based on mounting evidence for the role of gut dysbiosis, the researchers explored whether IBD is associated with higher rates of infections and other critical events during the neonatal period and the first year of life by comparing 825 patients with IBD and 5,999 controls matched by age, sex, and area of residence. The data source was the University of Manitoba IBD Epidemiology Database, which includes all Manitobans diagnosed with IBD from 1984 to 2010. The researchers also compared patients with 1,740 unaffected siblings.
Gastrointestinal infections, gastrointestinal disease, and abdominal pain during the first year of life did not predict subsequent IBD. Maternal IBD was the strongest risk factor (odds ratio, 4.5; 95% confidence interval, 3.1-6.7). Among neonatal events, the only significant risk factor was being in the highest versus the lowest socioeconomic quintile (OR, 1.35; 95% CI, 1.01-1.79). This association persisted during the first year of life.
Infections during the first year of life were a significant risk factor for IBD before age 10 (OR, 3.1; 95% CI, 1.1-8.8) and age 20 years (OR, 1.6; 95% CI, 1.2-2.2) in the population-based analysis. In contrast, patients and their unaffected siblings had similar rates of infection during early life. The study may have missed differences in exposures between these groups, or perhaps patients lack certain protective genes possessed by healthy siblings, the researchers wrote.
Numbers of antibiotic prescriptions during the first year and the first decade of life did not significantly differ between 33 cases and 270 controls with available data. However, there was a trend toward more antibiotics prescribed to patients versus controls.
“Together with our past reports that neither cesarean section birth nor antenatal or perinatal maternal use of antibiotics predict ultimate development of IBD, it seems that neonatal changes to the microbiome are subsumed by those occurring in the first year of life,” the investigators concluded. They recommended studying the infant gut microbiome before and for several months after infections and antibiotic exposure to determine which shifts in microbiota predict IBD onset.
The Manitoba Centre for Health Policy provided access to the Population Health Research Data Repository. Dr. Bernstein is supported by the Bingham Chair in Gastroenterology. He reported ties to AbbVie Canada, Ferring Canada, Janssen Canada, Shire Canada, Takeda Canada, Pfizer Canada, Napo Pharmaceuticals, 4D Pharma, and Mylan.
SOURCE: Bernstein CN et al. Gastroenterology. 2019 Feb 14. doi: 10.1053/j.gastro.2019.02.004.
FROM GASTROENTEROLOGY
Suicide Attempts Among Persons with Migraine
Persons with migraine had a much higher prevalence of ever attempting suicide than those without migraine, a recent study found. The study, a nationally representative analysis of the 2012 Canadian Community Health Survey – Mental Health, identified the gender-specific prevalence of suicide attempts among those with migraine and examined the factors associated with suicide attempts among migraineurs. Among the details:
- Of 21,744 respondents, 2223 had migraine.
- Those with migraine had a much higher prevalence of ever attempting suicide vs those without migraine (men: 7.5% vs 1.9%; women: 9.3% vs 2.7%).
- Among migraineurs, the odds of suicide attempts were higher among poorer respondents, those in chronic pain and those with a history of childhood adversities, substance dependence and/or mental illness.
Fuller-Thomson E, Hodgins GA. Suicide attempts among those with migraine: Finding from a nationally representative Canadian study. [Published online ahead of print April 4, 2019]. Arch Suicide Res. doi: 10.1080/13811118.2019.1578710.
Persons with migraine had a much higher prevalence of ever attempting suicide than those without migraine, a recent study found. The study, a nationally representative analysis of the 2012 Canadian Community Health Survey – Mental Health, identified the gender-specific prevalence of suicide attempts among those with migraine and examined the factors associated with suicide attempts among migraineurs. Among the details:
- Of 21,744 respondents, 2223 had migraine.
- Those with migraine had a much higher prevalence of ever attempting suicide vs those without migraine (men: 7.5% vs 1.9%; women: 9.3% vs 2.7%).
- Among migraineurs, the odds of suicide attempts were higher among poorer respondents, those in chronic pain and those with a history of childhood adversities, substance dependence and/or mental illness.
Fuller-Thomson E, Hodgins GA. Suicide attempts among those with migraine: Finding from a nationally representative Canadian study. [Published online ahead of print April 4, 2019]. Arch Suicide Res. doi: 10.1080/13811118.2019.1578710.
Persons with migraine had a much higher prevalence of ever attempting suicide than those without migraine, a recent study found. The study, a nationally representative analysis of the 2012 Canadian Community Health Survey – Mental Health, identified the gender-specific prevalence of suicide attempts among those with migraine and examined the factors associated with suicide attempts among migraineurs. Among the details:
- Of 21,744 respondents, 2223 had migraine.
- Those with migraine had a much higher prevalence of ever attempting suicide vs those without migraine (men: 7.5% vs 1.9%; women: 9.3% vs 2.7%).
- Among migraineurs, the odds of suicide attempts were higher among poorer respondents, those in chronic pain and those with a history of childhood adversities, substance dependence and/or mental illness.
Fuller-Thomson E, Hodgins GA. Suicide attempts among those with migraine: Finding from a nationally representative Canadian study. [Published online ahead of print April 4, 2019]. Arch Suicide Res. doi: 10.1080/13811118.2019.1578710.
Treatment Response Using Pharmacy Register in Migraine
Pharmacy databases are a valid source for identification of treatment response in migraine, a recent study found. In a clinical cohort, 1913 migraineurs were interviewed using a semi-structured interview to retrieve treatment response data for acute and prophylactic migraine drugs. Researchers assessed whether number or purchases at different thresholds could predict the specificity and sensitivity of treatment response. The found:
- Purchase of drugs was significantly associated with treatment response.
- Specifically, for migraine drugs, it was concluded that 10 purchases of triptans, or 4 purchases of prophylactic drugs, are sufficient to predict a positive treatment response.
- In the Danish pharmacy database, 73% of migraine patients had purchased 10 or more triptans, while 55% to 63% had purchased 1 or more of the 4 prophylactic drugs.
Hansen TF, Chalmer MA, Haspang TM, Kogelman L, Olesen J. Predicting treatment response using pharmacy register in migraine. J Headache Pain. 2019;20(1):31. doi:10.1186/s10194-019-0987-y.
Pharmacy databases are a valid source for identification of treatment response in migraine, a recent study found. In a clinical cohort, 1913 migraineurs were interviewed using a semi-structured interview to retrieve treatment response data for acute and prophylactic migraine drugs. Researchers assessed whether number or purchases at different thresholds could predict the specificity and sensitivity of treatment response. The found:
- Purchase of drugs was significantly associated with treatment response.
- Specifically, for migraine drugs, it was concluded that 10 purchases of triptans, or 4 purchases of prophylactic drugs, are sufficient to predict a positive treatment response.
- In the Danish pharmacy database, 73% of migraine patients had purchased 10 or more triptans, while 55% to 63% had purchased 1 or more of the 4 prophylactic drugs.
Hansen TF, Chalmer MA, Haspang TM, Kogelman L, Olesen J. Predicting treatment response using pharmacy register in migraine. J Headache Pain. 2019;20(1):31. doi:10.1186/s10194-019-0987-y.
Pharmacy databases are a valid source for identification of treatment response in migraine, a recent study found. In a clinical cohort, 1913 migraineurs were interviewed using a semi-structured interview to retrieve treatment response data for acute and prophylactic migraine drugs. Researchers assessed whether number or purchases at different thresholds could predict the specificity and sensitivity of treatment response. The found:
- Purchase of drugs was significantly associated with treatment response.
- Specifically, for migraine drugs, it was concluded that 10 purchases of triptans, or 4 purchases of prophylactic drugs, are sufficient to predict a positive treatment response.
- In the Danish pharmacy database, 73% of migraine patients had purchased 10 or more triptans, while 55% to 63% had purchased 1 or more of the 4 prophylactic drugs.
Hansen TF, Chalmer MA, Haspang TM, Kogelman L, Olesen J. Predicting treatment response using pharmacy register in migraine. J Headache Pain. 2019;20(1):31. doi:10.1186/s10194-019-0987-y.
Sleep Disturbances and Headaches in US Adolescents
Adolescents with migraine headaches have shorter sleep duration and wake up earlier compared to those without migraine, a new study found. The study sample included 10,123 adolescents in the National Comorbidity Survey – Adolescent Supplement, a face-to-face survey of adolescents aged 13 to 18 years in the continental United States. The cross-sectional study examined the associations of sleep patterns, symptoms, and disorders with specific headache subtypes in this population. Researchers found:
- No significant difference in bedtime between youth with and without headache was reported.
- Those with any headache, particularly migraine, had significantly more sleep disturbances than those without headache.
- Youth with migraine and aura were more likely to report difficultly maintaining sleep, early morning awakening, daytime fatigue, and persistent insomnia symptoms vs those with migraine without aura.
Lateef T, Witonsky K, He J, Merikangas KR. Headaches and sleep duration problems in US adolescents: Findings from the National Comorbidity Survey – Adolescent Supplement (NCS-A). [Published online ahead of print April 13, 2019]. Cephalalgia. doi:10.1177/0333102419835466.
Adolescents with migraine headaches have shorter sleep duration and wake up earlier compared to those without migraine, a new study found. The study sample included 10,123 adolescents in the National Comorbidity Survey – Adolescent Supplement, a face-to-face survey of adolescents aged 13 to 18 years in the continental United States. The cross-sectional study examined the associations of sleep patterns, symptoms, and disorders with specific headache subtypes in this population. Researchers found:
- No significant difference in bedtime between youth with and without headache was reported.
- Those with any headache, particularly migraine, had significantly more sleep disturbances than those without headache.
- Youth with migraine and aura were more likely to report difficultly maintaining sleep, early morning awakening, daytime fatigue, and persistent insomnia symptoms vs those with migraine without aura.
Lateef T, Witonsky K, He J, Merikangas KR. Headaches and sleep duration problems in US adolescents: Findings from the National Comorbidity Survey – Adolescent Supplement (NCS-A). [Published online ahead of print April 13, 2019]. Cephalalgia. doi:10.1177/0333102419835466.
Adolescents with migraine headaches have shorter sleep duration and wake up earlier compared to those without migraine, a new study found. The study sample included 10,123 adolescents in the National Comorbidity Survey – Adolescent Supplement, a face-to-face survey of adolescents aged 13 to 18 years in the continental United States. The cross-sectional study examined the associations of sleep patterns, symptoms, and disorders with specific headache subtypes in this population. Researchers found:
- No significant difference in bedtime between youth with and without headache was reported.
- Those with any headache, particularly migraine, had significantly more sleep disturbances than those without headache.
- Youth with migraine and aura were more likely to report difficultly maintaining sleep, early morning awakening, daytime fatigue, and persistent insomnia symptoms vs those with migraine without aura.
Lateef T, Witonsky K, He J, Merikangas KR. Headaches and sleep duration problems in US adolescents: Findings from the National Comorbidity Survey – Adolescent Supplement (NCS-A). [Published online ahead of print April 13, 2019]. Cephalalgia. doi:10.1177/0333102419835466.
Walk-in ultrasound helps to avoid unnecessary steroids for giant cell arteritis
BIRMINGHAM, England – More than half of all patients referred to a fast-track giant cell arteritis (GCA) clinic that offers a walk-in ultrasonography service avoided use of glucocorticoids, according to a report given at the annual conference of the British Society for Rheumatology.
The clinic, an initiative run by the University Hospital Coventry and Warwickshire (UHCW) NHS Trust for the past 6 years, provides same-day diagnosis and treatment for suspected GCA.
“Walk-in ultrasound helps to avoid steroids completely in a significant proportion of patients,” said study author and presenter Shirish Dubey, MBBS, a consultant rheumatologist at the UHCW NHS Trust. Of 652 patients seen at the UHCW GCA fast-track clinic between 2014 and 2017, 143 (22%) were diagnosed with GCA. Over 400 had not been exposed to glucocorticoids and 369 (57%) were able to avoid unnecessary glucocorticoid use in the cohort, Dr. Dubey reported.
The old NHS paradigm for managing patients with suspected GCA was that when they presented to their primary care physicians, they would be started on immediate glucocorticoid therapy while waiting for an urgent specialist referral. However, that referral could take anywhere from a couple of days to a couple of weeks to happen, Dr. Dubey explained. Patients would then undergo possible temporal artery biopsy (TAB) and only then, following confirmation of a GCA diagnosis, would a management plan be agreed upon.
UCHW introduced its fast-track pathway for the diagnosis of GCA in mid-2013. The pathway called for patients with suspected GCA aged 50 years or older who had two or more features present, such as an abrupt, new-onset headache or facial pain, scalp pain and tenderness, jaw claudication, or visual symptoms. Primary care physicians could make urgent referrals to the service via an on-call rheumatology trainee or ophthalmology senior house officer.
“Patients are normally steroid-naive and seen on the same day,” Dr. Dubey said. Doppler ultrasound of the temporal artery results in around 80% of diagnoses, with TAB still needed in some cases.
One of the downsides of the fast-track process perhaps is the increasing number of referrals. “One thing we find is that we have become a glorified headache service,” Dr. Dubey said. However, many patients do not have GCA and, when there is a low clinical probability and the ultrasound is negative, the patient is usually reassured and discharged with no need for glucocorticoids. Although the number of referrals have increased – 98 patients in 2014, 154 in 2015, 123 in 2016, and 277 in 2017 – the number of those diagnosed with GCA has remained around the same.
To see how ultrasound was faring in real-life practice, the UHCW NHS Trust team compared Doppler ultrasound findings against the final clinical diagnosis for the period 2014 to 2017. A sensitivity of just under 48% and specificity of 98% was recorded. The positive and negative predictive values were 87% and 88%, respectively.
The specificity of ultrasound was lower than that reported previously in the literature, the UHCW NHS Trust team pointed out in its abstract, but it does compare similarly with other real-world studies. The use of glucocorticoids affected the ultrasound results, with better sensitivity (55%) when these drugs were not used prior to the scan.
The use of TAB versus a clinical diagnosis in 100 patients seen over the same time period showed it had a sensitivity of 37% and a specificity of 100%, with positive and negative predictive values of 100% and 62%. The sensitivity of TAB is again low, Dr. Dubey said, but that could be because TAB is performed only when the diagnosis is uncertain.
This was an unselected cohort of patients, but overall there were good positive and negative predictive values. The UHCW NHS Trust team suggested that ultrasound can assist and reassure clinicians trying to diagnose or exclude GCA in their patients.
Regular multidisciplinary team meetings including rheumatology, ophthalmology, and vascular Doppler physiologists are key to the fast-track service, Dr. Dubey pointed out.
Despite the shortcomings of the retrospective study, Dr. Dubey stressed that the team was confident that none of the patients who had been ruled out as having GCA were subsequently diagnosed as having GCA.
Importantly, he said, the use of ultrasound had made a big difference in cost; the group plans to formally evaluate costs of ultrasound versus TAB.
The study received no commercial funding. Dr. Dubey had no conflicts of interest to disclose.
SOURCE: Pinnell J et al. Rheumatology. 2019;58(suppl 3):Abstract 038.
BIRMINGHAM, England – More than half of all patients referred to a fast-track giant cell arteritis (GCA) clinic that offers a walk-in ultrasonography service avoided use of glucocorticoids, according to a report given at the annual conference of the British Society for Rheumatology.
The clinic, an initiative run by the University Hospital Coventry and Warwickshire (UHCW) NHS Trust for the past 6 years, provides same-day diagnosis and treatment for suspected GCA.
“Walk-in ultrasound helps to avoid steroids completely in a significant proportion of patients,” said study author and presenter Shirish Dubey, MBBS, a consultant rheumatologist at the UHCW NHS Trust. Of 652 patients seen at the UHCW GCA fast-track clinic between 2014 and 2017, 143 (22%) were diagnosed with GCA. Over 400 had not been exposed to glucocorticoids and 369 (57%) were able to avoid unnecessary glucocorticoid use in the cohort, Dr. Dubey reported.
The old NHS paradigm for managing patients with suspected GCA was that when they presented to their primary care physicians, they would be started on immediate glucocorticoid therapy while waiting for an urgent specialist referral. However, that referral could take anywhere from a couple of days to a couple of weeks to happen, Dr. Dubey explained. Patients would then undergo possible temporal artery biopsy (TAB) and only then, following confirmation of a GCA diagnosis, would a management plan be agreed upon.
UCHW introduced its fast-track pathway for the diagnosis of GCA in mid-2013. The pathway called for patients with suspected GCA aged 50 years or older who had two or more features present, such as an abrupt, new-onset headache or facial pain, scalp pain and tenderness, jaw claudication, or visual symptoms. Primary care physicians could make urgent referrals to the service via an on-call rheumatology trainee or ophthalmology senior house officer.
“Patients are normally steroid-naive and seen on the same day,” Dr. Dubey said. Doppler ultrasound of the temporal artery results in around 80% of diagnoses, with TAB still needed in some cases.
One of the downsides of the fast-track process perhaps is the increasing number of referrals. “One thing we find is that we have become a glorified headache service,” Dr. Dubey said. However, many patients do not have GCA and, when there is a low clinical probability and the ultrasound is negative, the patient is usually reassured and discharged with no need for glucocorticoids. Although the number of referrals have increased – 98 patients in 2014, 154 in 2015, 123 in 2016, and 277 in 2017 – the number of those diagnosed with GCA has remained around the same.
To see how ultrasound was faring in real-life practice, the UHCW NHS Trust team compared Doppler ultrasound findings against the final clinical diagnosis for the period 2014 to 2017. A sensitivity of just under 48% and specificity of 98% was recorded. The positive and negative predictive values were 87% and 88%, respectively.
The specificity of ultrasound was lower than that reported previously in the literature, the UHCW NHS Trust team pointed out in its abstract, but it does compare similarly with other real-world studies. The use of glucocorticoids affected the ultrasound results, with better sensitivity (55%) when these drugs were not used prior to the scan.
The use of TAB versus a clinical diagnosis in 100 patients seen over the same time period showed it had a sensitivity of 37% and a specificity of 100%, with positive and negative predictive values of 100% and 62%. The sensitivity of TAB is again low, Dr. Dubey said, but that could be because TAB is performed only when the diagnosis is uncertain.
This was an unselected cohort of patients, but overall there were good positive and negative predictive values. The UHCW NHS Trust team suggested that ultrasound can assist and reassure clinicians trying to diagnose or exclude GCA in their patients.
Regular multidisciplinary team meetings including rheumatology, ophthalmology, and vascular Doppler physiologists are key to the fast-track service, Dr. Dubey pointed out.
Despite the shortcomings of the retrospective study, Dr. Dubey stressed that the team was confident that none of the patients who had been ruled out as having GCA were subsequently diagnosed as having GCA.
Importantly, he said, the use of ultrasound had made a big difference in cost; the group plans to formally evaluate costs of ultrasound versus TAB.
The study received no commercial funding. Dr. Dubey had no conflicts of interest to disclose.
SOURCE: Pinnell J et al. Rheumatology. 2019;58(suppl 3):Abstract 038.
BIRMINGHAM, England – More than half of all patients referred to a fast-track giant cell arteritis (GCA) clinic that offers a walk-in ultrasonography service avoided use of glucocorticoids, according to a report given at the annual conference of the British Society for Rheumatology.
The clinic, an initiative run by the University Hospital Coventry and Warwickshire (UHCW) NHS Trust for the past 6 years, provides same-day diagnosis and treatment for suspected GCA.
“Walk-in ultrasound helps to avoid steroids completely in a significant proportion of patients,” said study author and presenter Shirish Dubey, MBBS, a consultant rheumatologist at the UHCW NHS Trust. Of 652 patients seen at the UHCW GCA fast-track clinic between 2014 and 2017, 143 (22%) were diagnosed with GCA. Over 400 had not been exposed to glucocorticoids and 369 (57%) were able to avoid unnecessary glucocorticoid use in the cohort, Dr. Dubey reported.
The old NHS paradigm for managing patients with suspected GCA was that when they presented to their primary care physicians, they would be started on immediate glucocorticoid therapy while waiting for an urgent specialist referral. However, that referral could take anywhere from a couple of days to a couple of weeks to happen, Dr. Dubey explained. Patients would then undergo possible temporal artery biopsy (TAB) and only then, following confirmation of a GCA diagnosis, would a management plan be agreed upon.
UCHW introduced its fast-track pathway for the diagnosis of GCA in mid-2013. The pathway called for patients with suspected GCA aged 50 years or older who had two or more features present, such as an abrupt, new-onset headache or facial pain, scalp pain and tenderness, jaw claudication, or visual symptoms. Primary care physicians could make urgent referrals to the service via an on-call rheumatology trainee or ophthalmology senior house officer.
“Patients are normally steroid-naive and seen on the same day,” Dr. Dubey said. Doppler ultrasound of the temporal artery results in around 80% of diagnoses, with TAB still needed in some cases.
One of the downsides of the fast-track process perhaps is the increasing number of referrals. “One thing we find is that we have become a glorified headache service,” Dr. Dubey said. However, many patients do not have GCA and, when there is a low clinical probability and the ultrasound is negative, the patient is usually reassured and discharged with no need for glucocorticoids. Although the number of referrals have increased – 98 patients in 2014, 154 in 2015, 123 in 2016, and 277 in 2017 – the number of those diagnosed with GCA has remained around the same.
To see how ultrasound was faring in real-life practice, the UHCW NHS Trust team compared Doppler ultrasound findings against the final clinical diagnosis for the period 2014 to 2017. A sensitivity of just under 48% and specificity of 98% was recorded. The positive and negative predictive values were 87% and 88%, respectively.
The specificity of ultrasound was lower than that reported previously in the literature, the UHCW NHS Trust team pointed out in its abstract, but it does compare similarly with other real-world studies. The use of glucocorticoids affected the ultrasound results, with better sensitivity (55%) when these drugs were not used prior to the scan.
The use of TAB versus a clinical diagnosis in 100 patients seen over the same time period showed it had a sensitivity of 37% and a specificity of 100%, with positive and negative predictive values of 100% and 62%. The sensitivity of TAB is again low, Dr. Dubey said, but that could be because TAB is performed only when the diagnosis is uncertain.
This was an unselected cohort of patients, but overall there were good positive and negative predictive values. The UHCW NHS Trust team suggested that ultrasound can assist and reassure clinicians trying to diagnose or exclude GCA in their patients.
Regular multidisciplinary team meetings including rheumatology, ophthalmology, and vascular Doppler physiologists are key to the fast-track service, Dr. Dubey pointed out.
Despite the shortcomings of the retrospective study, Dr. Dubey stressed that the team was confident that none of the patients who had been ruled out as having GCA were subsequently diagnosed as having GCA.
Importantly, he said, the use of ultrasound had made a big difference in cost; the group plans to formally evaluate costs of ultrasound versus TAB.
The study received no commercial funding. Dr. Dubey had no conflicts of interest to disclose.
SOURCE: Pinnell J et al. Rheumatology. 2019;58(suppl 3):Abstract 038.
REPORTING FROM BSR 2019