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extacy
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A peer-reviewed clinical journal serving healthcare professionals working with the Department of Veterans Affairs, the Department of Defense, and the Public Health Service.
Americans avoided emergency departments early in the pandemic
compared with the corresponding period in 2019, according to a report from the Centers for Disease Control and Prevention.
“The striking decline in ED visits nationwide … suggests that the pandemic has altered the use of the ED by the public,” Kathleen P. Hartnett, PhD, and associates at the CDC said June 3 in the Mortality and Morbidity Weekly Report.
The weekly mean was just over 1.2 million ED visits for the 4 weeks from March 29 to April 25, 2020, compared with the nearly 2.2 million visits per week recorded from March 31 to April 27, 2019 – a drop of 42%, based on an analysis of data from the National Syndromic Surveillance Program.
Despite that drop, ED visits for infectious disease–related reasons, taken as a proportion of all 1.2 ED visits during the early pandemic period, were 3.8 times higher than the comparison period in 2019, the investigators reported.
ED visits also were higher in 2020 for specified and unspecified lower respiratory disease not including influenza, pneumonia, asthma, or bronchitis (prevalence ratio of 1.99, compared with 2019), cardiac arrest and ventricular fibrillation (PR, 1.98), and pneumonia not caused by tuberculosis (PR, 1.91), Dr. Hartnett and associates said.
Prevalence ratios for the early pandemic period were down for most other conditions, with some of the largest decreases seen for influenza (PR, 0.16), otitis media (PR, 0.35), and neoplasm-related encounters (PR, 0.40), they said.
Visits have increased each week since reaching their lowest point during April 12-18, but the number for the most recent full week, May 24-30, which was not included in the analysis, was still 26% lower than the corresponding week in 2019, the CDC team pointed out.
“Some persons could be delaying care for conditions that might result in additional mortality if left untreated,” the investigators noted, and those “who use the ED as a safety net because they lack access to primary care and telemedicine might be disproportionately affected if they avoid seeking care because of concerns about the infection risk in the ED.”
SOURCE: Hartnett KP et al. MMWR. 2020 Jun 3. 69:1-6.
compared with the corresponding period in 2019, according to a report from the Centers for Disease Control and Prevention.
“The striking decline in ED visits nationwide … suggests that the pandemic has altered the use of the ED by the public,” Kathleen P. Hartnett, PhD, and associates at the CDC said June 3 in the Mortality and Morbidity Weekly Report.
The weekly mean was just over 1.2 million ED visits for the 4 weeks from March 29 to April 25, 2020, compared with the nearly 2.2 million visits per week recorded from March 31 to April 27, 2019 – a drop of 42%, based on an analysis of data from the National Syndromic Surveillance Program.
Despite that drop, ED visits for infectious disease–related reasons, taken as a proportion of all 1.2 ED visits during the early pandemic period, were 3.8 times higher than the comparison period in 2019, the investigators reported.
ED visits also were higher in 2020 for specified and unspecified lower respiratory disease not including influenza, pneumonia, asthma, or bronchitis (prevalence ratio of 1.99, compared with 2019), cardiac arrest and ventricular fibrillation (PR, 1.98), and pneumonia not caused by tuberculosis (PR, 1.91), Dr. Hartnett and associates said.
Prevalence ratios for the early pandemic period were down for most other conditions, with some of the largest decreases seen for influenza (PR, 0.16), otitis media (PR, 0.35), and neoplasm-related encounters (PR, 0.40), they said.
Visits have increased each week since reaching their lowest point during April 12-18, but the number for the most recent full week, May 24-30, which was not included in the analysis, was still 26% lower than the corresponding week in 2019, the CDC team pointed out.
“Some persons could be delaying care for conditions that might result in additional mortality if left untreated,” the investigators noted, and those “who use the ED as a safety net because they lack access to primary care and telemedicine might be disproportionately affected if they avoid seeking care because of concerns about the infection risk in the ED.”
SOURCE: Hartnett KP et al. MMWR. 2020 Jun 3. 69:1-6.
compared with the corresponding period in 2019, according to a report from the Centers for Disease Control and Prevention.
“The striking decline in ED visits nationwide … suggests that the pandemic has altered the use of the ED by the public,” Kathleen P. Hartnett, PhD, and associates at the CDC said June 3 in the Mortality and Morbidity Weekly Report.
The weekly mean was just over 1.2 million ED visits for the 4 weeks from March 29 to April 25, 2020, compared with the nearly 2.2 million visits per week recorded from March 31 to April 27, 2019 – a drop of 42%, based on an analysis of data from the National Syndromic Surveillance Program.
Despite that drop, ED visits for infectious disease–related reasons, taken as a proportion of all 1.2 ED visits during the early pandemic period, were 3.8 times higher than the comparison period in 2019, the investigators reported.
ED visits also were higher in 2020 for specified and unspecified lower respiratory disease not including influenza, pneumonia, asthma, or bronchitis (prevalence ratio of 1.99, compared with 2019), cardiac arrest and ventricular fibrillation (PR, 1.98), and pneumonia not caused by tuberculosis (PR, 1.91), Dr. Hartnett and associates said.
Prevalence ratios for the early pandemic period were down for most other conditions, with some of the largest decreases seen for influenza (PR, 0.16), otitis media (PR, 0.35), and neoplasm-related encounters (PR, 0.40), they said.
Visits have increased each week since reaching their lowest point during April 12-18, but the number for the most recent full week, May 24-30, which was not included in the analysis, was still 26% lower than the corresponding week in 2019, the CDC team pointed out.
“Some persons could be delaying care for conditions that might result in additional mortality if left untreated,” the investigators noted, and those “who use the ED as a safety net because they lack access to primary care and telemedicine might be disproportionately affected if they avoid seeking care because of concerns about the infection risk in the ED.”
SOURCE: Hartnett KP et al. MMWR. 2020 Jun 3. 69:1-6.
FROM MMWR
Is cannabis gaining acceptance as a treatment for neuropathic pain?
, a recent debate on the topic suggests. During the debate, one expert argued for, and another against, there being sufficient evidence for the use of cannabis to treat neuropathic pain, but in the end, they agreed that some patients do benefit.
The discussion took place at the Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual online meeting because of the COVID-19 pandemic.
The cannabis plant has 460 constituents. The two main components are tetrahydrocannabinol (THC) and cannabidiol (CBD). It can be consumed by swallowing oil extracts, by the sublingual route, or by smoking or eating the plant. Cannabis medications already in use include oral THC (nabilone, dronabinol) and an oral mucosal spray, nabiximols (Sativex).
Arguing that therapeutic cannabis is helpful for neuropathic pain, Elon Eisenberg, MD, professor of neurology and pain medicine, Israel Institute of Technology, Haifa, cited a number of encouraging randomized, controlled trials and meta-analyses of studies on the subject.
Opioid substitute
Dr. Eisenberg discussed three relevant articles. One was a 2016 viewpoint article published in JAMA that concluded that “cannabis seems to be a substitute, a rather good one, for opioids,” said Dr. Eisenberg.
A “comprehensive” 440-page review, published by the National Academies Press in 2017, evaluated the evidence to that point and “came to the conclusion there is substantial evidence that cannabis is an effective treatment for chronic pain in adults,” said Dr. Eisenberg.
And a 2018 position paper from the European Pain Federation determined that “the quantity and quality of evidence is such that cannabis-based medicines may be reasonably considered for chronic neuropathic pain,” he said.
He noted that the most recent results from an Israeli prospective cohort registry study that is following more than 851 patients who are taking cannabis over 1 year are positive. Analyses show a steady reduction in pain intensity and improvements in catastrophizing and disability. Importantly, he said, participants are using fewer opioids. However, about 40% of patients in that registry study experienced some adverse event, although most were not serious, said Dr. Eisenberg.
Not convinced
Arguing on the other side – that therapeutic cannabis is not helpful for neuropathic pain – was Nadine Attal, MD, PhD, professor of therapeutics and pain at the University Versailles Saint Quentin, France. She questioned the quality of some of the research to date and stressed that studies should consider neuropathic pain as a primary outcome – not spasticity or pain in general. They should also be double-blind, randomized, and placebo controlled, she said.
In addition, she said these studies should enroll at least 10 patients per group and should continue for 3 weeks or longer.
Dr. Attal wondered which of the many plant derivatives (phytocannabinoids) are used in cannabis studies.
She discussed four meta-analyses or reviews on the topic, some of which she said are “heterogeneous” and don’t provide convincing evidence for cannabis use in neuropathic pain.
For example, one review examined only marijuana, and all studies in it were short term. One of the studies in this review was of spasticity. Another review included two studies of cancer pain, and the most positive study in NP used short-term inhaled THC.
“There is no evidence to date that cannabinoids, including nabiximols or oral THC, administered for at least 3 weeks are more effective than placebo in neuropathic pain,” she concluded.
Some responders
However, Dr. Attal acknowledged that cannabis might be effective for some patients. In her experience, which has been borne out by some observational studies, patients with paroxysmal pain, or sudden stabbing pain, seem to get more relief from cannabis. “It’s absolutely possible that there’s a subgroup of symptoms or a subgroup of patients with specific symptoms who are much better responders to cannabis than others,” she said.
Asked if patients experience increased pain after withdrawing from cannabis, Dr. Eisenberg said he has observed that many patients stop taking cannabis when they start feeling better, but he hasn’t seen severe withdrawal symptoms.
However, there are other concerns related to cannabis use, said Dr. Eisenberg. A major concern regards driving a vehicle. In Israel, getting behind the wheel is prohibited within 6 hours of using cannabis.
But Dr. Eisenberg pointed out that published data on the safety of cannabis and driving were based on recreational users. “We need to keep in mind that recreational users typically use other substances, so we’re not sure the data is accurate,” he said.
There are increasing reports of stroke, transient ischemic attack, and MI among cannabis users. This is especially concerning because many of these cases involve young male adults who have no risk factors, said Dr. Eisenberg.
One conference delegate asked whether legal issues make it difficult to properly investigate cannabis in large studies. Dr. Eisenberg noted that legal concerns may help explain why there have not been any new randomized, controlled trials for about 2 years. “In the U.S., you can’t do clinical trials; cannabis is still regarded as schedule I substance,” he said.
Some physicians “are reluctant to deal with cannabis unless they get better data,” he said. “Doing research on cannabis seems to be somehow out of the mainstream.” Moreover, the research is difficult to carry out, owing to the complexity of the cannabis plant, which has many constituents. Perhaps it’s a matter of identifying and adding particular components to better demonstrate reduced pain, said Dr. Eisenberg.
Another complicating factor is that bioavailability differs considerably from one patient to another, “sometimes even by 10-fold,” he said.
Dr. Attal’s group will be starting a study next January that will enroll a large sample of patients with neuropathic pain or spasticity. In that study, cannabis will be dispensed through pharmacies and primary care. The aim of the study is “to see how it works in a real-life setting,” she said
Those participating in the virtual session were asked to vote on which side they agreed with. About 57% voted in favor of cannabis use, 14% voted against, and 28% had no opinion.
Dr. Eisenberg has received research grants from Rafa Laboratories, Saga Medical Ltd., Israel Pain Association, and Teva Israel. Dr. Attal has received support from Merck Sharp & Dohme, Sanofi, Ipsen, Novartis, Aptinyx, Air Liquide, Lilly, and Grunenthal.
A version of this article originally appeared on Medscape.com.
, a recent debate on the topic suggests. During the debate, one expert argued for, and another against, there being sufficient evidence for the use of cannabis to treat neuropathic pain, but in the end, they agreed that some patients do benefit.
The discussion took place at the Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual online meeting because of the COVID-19 pandemic.
The cannabis plant has 460 constituents. The two main components are tetrahydrocannabinol (THC) and cannabidiol (CBD). It can be consumed by swallowing oil extracts, by the sublingual route, or by smoking or eating the plant. Cannabis medications already in use include oral THC (nabilone, dronabinol) and an oral mucosal spray, nabiximols (Sativex).
Arguing that therapeutic cannabis is helpful for neuropathic pain, Elon Eisenberg, MD, professor of neurology and pain medicine, Israel Institute of Technology, Haifa, cited a number of encouraging randomized, controlled trials and meta-analyses of studies on the subject.
Opioid substitute
Dr. Eisenberg discussed three relevant articles. One was a 2016 viewpoint article published in JAMA that concluded that “cannabis seems to be a substitute, a rather good one, for opioids,” said Dr. Eisenberg.
A “comprehensive” 440-page review, published by the National Academies Press in 2017, evaluated the evidence to that point and “came to the conclusion there is substantial evidence that cannabis is an effective treatment for chronic pain in adults,” said Dr. Eisenberg.
And a 2018 position paper from the European Pain Federation determined that “the quantity and quality of evidence is such that cannabis-based medicines may be reasonably considered for chronic neuropathic pain,” he said.
He noted that the most recent results from an Israeli prospective cohort registry study that is following more than 851 patients who are taking cannabis over 1 year are positive. Analyses show a steady reduction in pain intensity and improvements in catastrophizing and disability. Importantly, he said, participants are using fewer opioids. However, about 40% of patients in that registry study experienced some adverse event, although most were not serious, said Dr. Eisenberg.
Not convinced
Arguing on the other side – that therapeutic cannabis is not helpful for neuropathic pain – was Nadine Attal, MD, PhD, professor of therapeutics and pain at the University Versailles Saint Quentin, France. She questioned the quality of some of the research to date and stressed that studies should consider neuropathic pain as a primary outcome – not spasticity or pain in general. They should also be double-blind, randomized, and placebo controlled, she said.
In addition, she said these studies should enroll at least 10 patients per group and should continue for 3 weeks or longer.
Dr. Attal wondered which of the many plant derivatives (phytocannabinoids) are used in cannabis studies.
She discussed four meta-analyses or reviews on the topic, some of which she said are “heterogeneous” and don’t provide convincing evidence for cannabis use in neuropathic pain.
For example, one review examined only marijuana, and all studies in it were short term. One of the studies in this review was of spasticity. Another review included two studies of cancer pain, and the most positive study in NP used short-term inhaled THC.
“There is no evidence to date that cannabinoids, including nabiximols or oral THC, administered for at least 3 weeks are more effective than placebo in neuropathic pain,” she concluded.
Some responders
However, Dr. Attal acknowledged that cannabis might be effective for some patients. In her experience, which has been borne out by some observational studies, patients with paroxysmal pain, or sudden stabbing pain, seem to get more relief from cannabis. “It’s absolutely possible that there’s a subgroup of symptoms or a subgroup of patients with specific symptoms who are much better responders to cannabis than others,” she said.
Asked if patients experience increased pain after withdrawing from cannabis, Dr. Eisenberg said he has observed that many patients stop taking cannabis when they start feeling better, but he hasn’t seen severe withdrawal symptoms.
However, there are other concerns related to cannabis use, said Dr. Eisenberg. A major concern regards driving a vehicle. In Israel, getting behind the wheel is prohibited within 6 hours of using cannabis.
But Dr. Eisenberg pointed out that published data on the safety of cannabis and driving were based on recreational users. “We need to keep in mind that recreational users typically use other substances, so we’re not sure the data is accurate,” he said.
There are increasing reports of stroke, transient ischemic attack, and MI among cannabis users. This is especially concerning because many of these cases involve young male adults who have no risk factors, said Dr. Eisenberg.
One conference delegate asked whether legal issues make it difficult to properly investigate cannabis in large studies. Dr. Eisenberg noted that legal concerns may help explain why there have not been any new randomized, controlled trials for about 2 years. “In the U.S., you can’t do clinical trials; cannabis is still regarded as schedule I substance,” he said.
Some physicians “are reluctant to deal with cannabis unless they get better data,” he said. “Doing research on cannabis seems to be somehow out of the mainstream.” Moreover, the research is difficult to carry out, owing to the complexity of the cannabis plant, which has many constituents. Perhaps it’s a matter of identifying and adding particular components to better demonstrate reduced pain, said Dr. Eisenberg.
Another complicating factor is that bioavailability differs considerably from one patient to another, “sometimes even by 10-fold,” he said.
Dr. Attal’s group will be starting a study next January that will enroll a large sample of patients with neuropathic pain or spasticity. In that study, cannabis will be dispensed through pharmacies and primary care. The aim of the study is “to see how it works in a real-life setting,” she said
Those participating in the virtual session were asked to vote on which side they agreed with. About 57% voted in favor of cannabis use, 14% voted against, and 28% had no opinion.
Dr. Eisenberg has received research grants from Rafa Laboratories, Saga Medical Ltd., Israel Pain Association, and Teva Israel. Dr. Attal has received support from Merck Sharp & Dohme, Sanofi, Ipsen, Novartis, Aptinyx, Air Liquide, Lilly, and Grunenthal.
A version of this article originally appeared on Medscape.com.
, a recent debate on the topic suggests. During the debate, one expert argued for, and another against, there being sufficient evidence for the use of cannabis to treat neuropathic pain, but in the end, they agreed that some patients do benefit.
The discussion took place at the Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual online meeting because of the COVID-19 pandemic.
The cannabis plant has 460 constituents. The two main components are tetrahydrocannabinol (THC) and cannabidiol (CBD). It can be consumed by swallowing oil extracts, by the sublingual route, or by smoking or eating the plant. Cannabis medications already in use include oral THC (nabilone, dronabinol) and an oral mucosal spray, nabiximols (Sativex).
Arguing that therapeutic cannabis is helpful for neuropathic pain, Elon Eisenberg, MD, professor of neurology and pain medicine, Israel Institute of Technology, Haifa, cited a number of encouraging randomized, controlled trials and meta-analyses of studies on the subject.
Opioid substitute
Dr. Eisenberg discussed three relevant articles. One was a 2016 viewpoint article published in JAMA that concluded that “cannabis seems to be a substitute, a rather good one, for opioids,” said Dr. Eisenberg.
A “comprehensive” 440-page review, published by the National Academies Press in 2017, evaluated the evidence to that point and “came to the conclusion there is substantial evidence that cannabis is an effective treatment for chronic pain in adults,” said Dr. Eisenberg.
And a 2018 position paper from the European Pain Federation determined that “the quantity and quality of evidence is such that cannabis-based medicines may be reasonably considered for chronic neuropathic pain,” he said.
He noted that the most recent results from an Israeli prospective cohort registry study that is following more than 851 patients who are taking cannabis over 1 year are positive. Analyses show a steady reduction in pain intensity and improvements in catastrophizing and disability. Importantly, he said, participants are using fewer opioids. However, about 40% of patients in that registry study experienced some adverse event, although most were not serious, said Dr. Eisenberg.
Not convinced
Arguing on the other side – that therapeutic cannabis is not helpful for neuropathic pain – was Nadine Attal, MD, PhD, professor of therapeutics and pain at the University Versailles Saint Quentin, France. She questioned the quality of some of the research to date and stressed that studies should consider neuropathic pain as a primary outcome – not spasticity or pain in general. They should also be double-blind, randomized, and placebo controlled, she said.
In addition, she said these studies should enroll at least 10 patients per group and should continue for 3 weeks or longer.
Dr. Attal wondered which of the many plant derivatives (phytocannabinoids) are used in cannabis studies.
She discussed four meta-analyses or reviews on the topic, some of which she said are “heterogeneous” and don’t provide convincing evidence for cannabis use in neuropathic pain.
For example, one review examined only marijuana, and all studies in it were short term. One of the studies in this review was of spasticity. Another review included two studies of cancer pain, and the most positive study in NP used short-term inhaled THC.
“There is no evidence to date that cannabinoids, including nabiximols or oral THC, administered for at least 3 weeks are more effective than placebo in neuropathic pain,” she concluded.
Some responders
However, Dr. Attal acknowledged that cannabis might be effective for some patients. In her experience, which has been borne out by some observational studies, patients with paroxysmal pain, or sudden stabbing pain, seem to get more relief from cannabis. “It’s absolutely possible that there’s a subgroup of symptoms or a subgroup of patients with specific symptoms who are much better responders to cannabis than others,” she said.
Asked if patients experience increased pain after withdrawing from cannabis, Dr. Eisenberg said he has observed that many patients stop taking cannabis when they start feeling better, but he hasn’t seen severe withdrawal symptoms.
However, there are other concerns related to cannabis use, said Dr. Eisenberg. A major concern regards driving a vehicle. In Israel, getting behind the wheel is prohibited within 6 hours of using cannabis.
But Dr. Eisenberg pointed out that published data on the safety of cannabis and driving were based on recreational users. “We need to keep in mind that recreational users typically use other substances, so we’re not sure the data is accurate,” he said.
There are increasing reports of stroke, transient ischemic attack, and MI among cannabis users. This is especially concerning because many of these cases involve young male adults who have no risk factors, said Dr. Eisenberg.
One conference delegate asked whether legal issues make it difficult to properly investigate cannabis in large studies. Dr. Eisenberg noted that legal concerns may help explain why there have not been any new randomized, controlled trials for about 2 years. “In the U.S., you can’t do clinical trials; cannabis is still regarded as schedule I substance,” he said.
Some physicians “are reluctant to deal with cannabis unless they get better data,” he said. “Doing research on cannabis seems to be somehow out of the mainstream.” Moreover, the research is difficult to carry out, owing to the complexity of the cannabis plant, which has many constituents. Perhaps it’s a matter of identifying and adding particular components to better demonstrate reduced pain, said Dr. Eisenberg.
Another complicating factor is that bioavailability differs considerably from one patient to another, “sometimes even by 10-fold,” he said.
Dr. Attal’s group will be starting a study next January that will enroll a large sample of patients with neuropathic pain or spasticity. In that study, cannabis will be dispensed through pharmacies and primary care. The aim of the study is “to see how it works in a real-life setting,” she said
Those participating in the virtual session were asked to vote on which side they agreed with. About 57% voted in favor of cannabis use, 14% voted against, and 28% had no opinion.
Dr. Eisenberg has received research grants from Rafa Laboratories, Saga Medical Ltd., Israel Pain Association, and Teva Israel. Dr. Attal has received support from Merck Sharp & Dohme, Sanofi, Ipsen, Novartis, Aptinyx, Air Liquide, Lilly, and Grunenthal.
A version of this article originally appeared on Medscape.com.
FROM EAN 2020
Atopic dermatitis in adults, children linked to neuropsychiatric disorders
according to a study presented at the annual meeting of the Society for Investigative Dermatology, held virtually.
“The risk increase ranges from as low as 5% up to 59%, depending on the outcome, with generally greater effects observed among the adults,” Joy Wan, MD, a postdoctoral dermatology fellow at the University of Pennsylvania, Philadelphia, said in her presentation. The risk was independent of other atopic disease, gender, age, and socioeconomic status.
Dr. Wan and colleagues conducted a cohort study of patients with AD in the United Kingdom using data from the Health Improvement Network (THIN) electronic records database, matching AD patients in THIN with up to five patients without AD, similar in age and also registered to general practices. The researchers validated AD disease status using an algorithm that identified patients with a diagnostic code and two therapy codes related to AD. Outcomes of interest included anxiety, depression, bipolar disorder, obsessive-compulsive disorder, ADHD, schizophrenia, and autism. Patients entered into the cohort when they were diagnosed with AD, registered by a practice, or when data from a practice was reported to THIN. The researchers stopped following patients when they developed a neuropsychiatric outcome of interest, left a practice, died, or when the study ended.
“Previous studies have found associations between atopic dermatitis and anxiety, depression, and attention-deficit/hyperactivity disorder. However, many previous studies had been cross-sectional and they were unable to evaluate the directionality of association between atopic dermatitis and neuropsychiatric outcomes, while other previous studies have relied on the self-report of atopic dermatitis and outcomes as well,” Dr. Wan said. “Thus, longitudinal studies, using validated measures of atopic dermatitis, and those that include the entire age span, are really needed.”
Overall, 434,859 children and adolescents under aged 18 with AD in the THIN database were matched to 1,983,589 controls, and 644,802 adults with AD were matched to almost 2,900,000 adults without AD. In the pediatric group, demographics were mostly balanced between children with and without AD: the average age ranged between about 5 and almost 6 years. In pediatric patients with AD, there was a higher rate of allergic rhinitis (6.2% vs. 4%) and asthma (13.5% vs. 9.3%) than in the control group.
For adults, the average age was about 48 years in both groups. Compared with patients who did not have AD, adults with AD also had higher rates of allergic rhinitis (15.2% vs. 9.6%) and asthma (19.9% vs. 12.6%).
After adjusting for age, gender, socioeconomic status, asthma, and allergic rhinitis, Dr. Wan and colleagues found greater rates of bipolar disorder (hazard ratio, 1.34; 95% confidence interval, 1.09-1.65), obsessive-compulsive disorder (HR, 1.30; 95% CI, 1.21-1.41), anxiety (HR, 1.09; 95% CI, 1.07-1.11), and depression (HR, 1.06; 95% CI, 1.04-1.08) among children and adolescents with AD, compared with controls.
In the adult cohort, a diagnosis of AD was associated with an increased risk of autism (HR, 1.53; 95% CI, 1.30-1.80), obsessive-compulsive disorder (HR, 1.49; 95% CI, 1.40-1.59), ADHD (HR, 1.31; 95% CI, 1.13-1.53), anxiety (HR, 1.17; 95% CI, 1.15-1.18), depression (HR, 1.15; 95% CI, 1.14-1.16), and bipolar disorder (HR, 1.12; 95% CI, 1.04-1.21), after adjusting for age, gender, socioeconomic status, asthma, and allergic rhinitis.
One reason for the increased associations among the adults, even for ADHD and autism, which are more characteristically diagnosed in childhood, Dr. Wan said, is that, since they looked at incident outcomes, “many children may already have had these prevalent comorbidities at the time of the entry in the cohort.”
She noted that the study may have observation bias or unknown confounders, but she hopes these results raise awareness of the association between AD and neuropsychiatric disorders, although more research is needed to determine how AD severity affects neuropsychiatric outcomes. “Additional work is needed to really understand the mechanisms that drive these associations, whether it’s mediated through symptoms of atopic dermatitis such as itch and poor sleep, or potentially the stigma of having a chronic skin disease, or perhaps shared pathophysiology between atopic dermatitis and these neuropsychiatric diseases,” she said.
The study was funded by a grant from Pfizer. Dr. Wan reports receiving research funding from Pfizer paid to the University of Pennsylvania.
according to a study presented at the annual meeting of the Society for Investigative Dermatology, held virtually.
“The risk increase ranges from as low as 5% up to 59%, depending on the outcome, with generally greater effects observed among the adults,” Joy Wan, MD, a postdoctoral dermatology fellow at the University of Pennsylvania, Philadelphia, said in her presentation. The risk was independent of other atopic disease, gender, age, and socioeconomic status.
Dr. Wan and colleagues conducted a cohort study of patients with AD in the United Kingdom using data from the Health Improvement Network (THIN) electronic records database, matching AD patients in THIN with up to five patients without AD, similar in age and also registered to general practices. The researchers validated AD disease status using an algorithm that identified patients with a diagnostic code and two therapy codes related to AD. Outcomes of interest included anxiety, depression, bipolar disorder, obsessive-compulsive disorder, ADHD, schizophrenia, and autism. Patients entered into the cohort when they were diagnosed with AD, registered by a practice, or when data from a practice was reported to THIN. The researchers stopped following patients when they developed a neuropsychiatric outcome of interest, left a practice, died, or when the study ended.
“Previous studies have found associations between atopic dermatitis and anxiety, depression, and attention-deficit/hyperactivity disorder. However, many previous studies had been cross-sectional and they were unable to evaluate the directionality of association between atopic dermatitis and neuropsychiatric outcomes, while other previous studies have relied on the self-report of atopic dermatitis and outcomes as well,” Dr. Wan said. “Thus, longitudinal studies, using validated measures of atopic dermatitis, and those that include the entire age span, are really needed.”
Overall, 434,859 children and adolescents under aged 18 with AD in the THIN database were matched to 1,983,589 controls, and 644,802 adults with AD were matched to almost 2,900,000 adults without AD. In the pediatric group, demographics were mostly balanced between children with and without AD: the average age ranged between about 5 and almost 6 years. In pediatric patients with AD, there was a higher rate of allergic rhinitis (6.2% vs. 4%) and asthma (13.5% vs. 9.3%) than in the control group.
For adults, the average age was about 48 years in both groups. Compared with patients who did not have AD, adults with AD also had higher rates of allergic rhinitis (15.2% vs. 9.6%) and asthma (19.9% vs. 12.6%).
After adjusting for age, gender, socioeconomic status, asthma, and allergic rhinitis, Dr. Wan and colleagues found greater rates of bipolar disorder (hazard ratio, 1.34; 95% confidence interval, 1.09-1.65), obsessive-compulsive disorder (HR, 1.30; 95% CI, 1.21-1.41), anxiety (HR, 1.09; 95% CI, 1.07-1.11), and depression (HR, 1.06; 95% CI, 1.04-1.08) among children and adolescents with AD, compared with controls.
In the adult cohort, a diagnosis of AD was associated with an increased risk of autism (HR, 1.53; 95% CI, 1.30-1.80), obsessive-compulsive disorder (HR, 1.49; 95% CI, 1.40-1.59), ADHD (HR, 1.31; 95% CI, 1.13-1.53), anxiety (HR, 1.17; 95% CI, 1.15-1.18), depression (HR, 1.15; 95% CI, 1.14-1.16), and bipolar disorder (HR, 1.12; 95% CI, 1.04-1.21), after adjusting for age, gender, socioeconomic status, asthma, and allergic rhinitis.
One reason for the increased associations among the adults, even for ADHD and autism, which are more characteristically diagnosed in childhood, Dr. Wan said, is that, since they looked at incident outcomes, “many children may already have had these prevalent comorbidities at the time of the entry in the cohort.”
She noted that the study may have observation bias or unknown confounders, but she hopes these results raise awareness of the association between AD and neuropsychiatric disorders, although more research is needed to determine how AD severity affects neuropsychiatric outcomes. “Additional work is needed to really understand the mechanisms that drive these associations, whether it’s mediated through symptoms of atopic dermatitis such as itch and poor sleep, or potentially the stigma of having a chronic skin disease, or perhaps shared pathophysiology between atopic dermatitis and these neuropsychiatric diseases,” she said.
The study was funded by a grant from Pfizer. Dr. Wan reports receiving research funding from Pfizer paid to the University of Pennsylvania.
according to a study presented at the annual meeting of the Society for Investigative Dermatology, held virtually.
“The risk increase ranges from as low as 5% up to 59%, depending on the outcome, with generally greater effects observed among the adults,” Joy Wan, MD, a postdoctoral dermatology fellow at the University of Pennsylvania, Philadelphia, said in her presentation. The risk was independent of other atopic disease, gender, age, and socioeconomic status.
Dr. Wan and colleagues conducted a cohort study of patients with AD in the United Kingdom using data from the Health Improvement Network (THIN) electronic records database, matching AD patients in THIN with up to five patients without AD, similar in age and also registered to general practices. The researchers validated AD disease status using an algorithm that identified patients with a diagnostic code and two therapy codes related to AD. Outcomes of interest included anxiety, depression, bipolar disorder, obsessive-compulsive disorder, ADHD, schizophrenia, and autism. Patients entered into the cohort when they were diagnosed with AD, registered by a practice, or when data from a practice was reported to THIN. The researchers stopped following patients when they developed a neuropsychiatric outcome of interest, left a practice, died, or when the study ended.
“Previous studies have found associations between atopic dermatitis and anxiety, depression, and attention-deficit/hyperactivity disorder. However, many previous studies had been cross-sectional and they were unable to evaluate the directionality of association between atopic dermatitis and neuropsychiatric outcomes, while other previous studies have relied on the self-report of atopic dermatitis and outcomes as well,” Dr. Wan said. “Thus, longitudinal studies, using validated measures of atopic dermatitis, and those that include the entire age span, are really needed.”
Overall, 434,859 children and adolescents under aged 18 with AD in the THIN database were matched to 1,983,589 controls, and 644,802 adults with AD were matched to almost 2,900,000 adults without AD. In the pediatric group, demographics were mostly balanced between children with and without AD: the average age ranged between about 5 and almost 6 years. In pediatric patients with AD, there was a higher rate of allergic rhinitis (6.2% vs. 4%) and asthma (13.5% vs. 9.3%) than in the control group.
For adults, the average age was about 48 years in both groups. Compared with patients who did not have AD, adults with AD also had higher rates of allergic rhinitis (15.2% vs. 9.6%) and asthma (19.9% vs. 12.6%).
After adjusting for age, gender, socioeconomic status, asthma, and allergic rhinitis, Dr. Wan and colleagues found greater rates of bipolar disorder (hazard ratio, 1.34; 95% confidence interval, 1.09-1.65), obsessive-compulsive disorder (HR, 1.30; 95% CI, 1.21-1.41), anxiety (HR, 1.09; 95% CI, 1.07-1.11), and depression (HR, 1.06; 95% CI, 1.04-1.08) among children and adolescents with AD, compared with controls.
In the adult cohort, a diagnosis of AD was associated with an increased risk of autism (HR, 1.53; 95% CI, 1.30-1.80), obsessive-compulsive disorder (HR, 1.49; 95% CI, 1.40-1.59), ADHD (HR, 1.31; 95% CI, 1.13-1.53), anxiety (HR, 1.17; 95% CI, 1.15-1.18), depression (HR, 1.15; 95% CI, 1.14-1.16), and bipolar disorder (HR, 1.12; 95% CI, 1.04-1.21), after adjusting for age, gender, socioeconomic status, asthma, and allergic rhinitis.
One reason for the increased associations among the adults, even for ADHD and autism, which are more characteristically diagnosed in childhood, Dr. Wan said, is that, since they looked at incident outcomes, “many children may already have had these prevalent comorbidities at the time of the entry in the cohort.”
She noted that the study may have observation bias or unknown confounders, but she hopes these results raise awareness of the association between AD and neuropsychiatric disorders, although more research is needed to determine how AD severity affects neuropsychiatric outcomes. “Additional work is needed to really understand the mechanisms that drive these associations, whether it’s mediated through symptoms of atopic dermatitis such as itch and poor sleep, or potentially the stigma of having a chronic skin disease, or perhaps shared pathophysiology between atopic dermatitis and these neuropsychiatric diseases,” she said.
The study was funded by a grant from Pfizer. Dr. Wan reports receiving research funding from Pfizer paid to the University of Pennsylvania.
FROM SID 2020
Acute lymphoblastic leukemia can be successfully treated in the frail elderly
A treatment schedule of very attenuated chemotherapy using standard drugs is feasible and effective in frail and elderly patients with acute lymphoblastic leukemia (ALL), according to a prospective study published in Clinical Lymphoma, Myeloma & Leukemia.
The study comprised 67 previously untreated patients with B- or T-lineage Philadelphia chromosome–negative ALL from 30 Spanish hospitals who were enrolled in the prospective, multicenter ALL-07FRAIL trial (NCT01358201) from the Spanish PETHEMA (Programa Español de Tratamientos en Hematologia) group from January 2008 to October 2019.
The median patient age in this analysis was 67 years and 51 patients (76%) were older than 70 years. The median Charlson Comorbidity Index was 5, with the main comorbidities being cardiovascular (47 patients), other neoplasia (24), diabetes (17), and very advanced age (>80 years; 12).
The attenuated treatment regimen consisted of a prephase with dexamethasone and intrathecal therapy with methotrexate was given for a maximum of 1 week. Then weekly induction therapy consisted of weekly vincristine (capped at 1 mg/week) and daily dexamethasone with a progressively decreasing dose along 4 weeks, as well as two additional doses of intrathecal methotrexate.
Those patients who achieved complete remission received maintenance therapy with mercaptopurine and methotrexate to complete 2 years of treatment. In addition, reinduction pulses with vincristine and dexamethasone were given every 3 months during the first year, according to Josep-Maria Ribera, MD, of the Universitat Autònoma de Barcelona, Badalona, Spain and colleagues on behalf of the PETHEMA group of the Spanish Society of Hematology.
The complete remission rate was 54% (36/67 patients). The median disease-free survival and overall survival were 6.9 months and 7.6 months, respectively.
Of the 32 patients who initiated maintenance therapy, 5 patients died of infection (2), hemorrhage (2), and acute cognitive impairment (1), and 23 relapsed, with a cumulative incidence of relapse of 74% and a median time to relapse of 12.3 months.
The most frequent toxic events reported were hematologic (neutropenia 77% and thrombocytopenia 54%, of grade III-IV in all cases) followed by infections, metabolic (mainly hyperglycemia), and neurologic, according to the researchers.
“The lack of similar trials specifically directed to this frail population is one of the major strengths of this study, and we consider that this minimal chemotherapy approach could be used as a backbone for addition of immuno/targeted therapy in this subset of infirm patients,” the researchers concluded.
The study was supported by the CERCA Program/Generalitat de Catalunya and the Josep Carreras Leukemia Research Institute. The authors reported having no disclosures.
SOURCE: Ribera J-M et al. Clin Lymphoma Myeloma Leuk. 2020 Apr 5. doi: 10.1016/j.clml.2020.03.011.
A treatment schedule of very attenuated chemotherapy using standard drugs is feasible and effective in frail and elderly patients with acute lymphoblastic leukemia (ALL), according to a prospective study published in Clinical Lymphoma, Myeloma & Leukemia.
The study comprised 67 previously untreated patients with B- or T-lineage Philadelphia chromosome–negative ALL from 30 Spanish hospitals who were enrolled in the prospective, multicenter ALL-07FRAIL trial (NCT01358201) from the Spanish PETHEMA (Programa Español de Tratamientos en Hematologia) group from January 2008 to October 2019.
The median patient age in this analysis was 67 years and 51 patients (76%) were older than 70 years. The median Charlson Comorbidity Index was 5, with the main comorbidities being cardiovascular (47 patients), other neoplasia (24), diabetes (17), and very advanced age (>80 years; 12).
The attenuated treatment regimen consisted of a prephase with dexamethasone and intrathecal therapy with methotrexate was given for a maximum of 1 week. Then weekly induction therapy consisted of weekly vincristine (capped at 1 mg/week) and daily dexamethasone with a progressively decreasing dose along 4 weeks, as well as two additional doses of intrathecal methotrexate.
Those patients who achieved complete remission received maintenance therapy with mercaptopurine and methotrexate to complete 2 years of treatment. In addition, reinduction pulses with vincristine and dexamethasone were given every 3 months during the first year, according to Josep-Maria Ribera, MD, of the Universitat Autònoma de Barcelona, Badalona, Spain and colleagues on behalf of the PETHEMA group of the Spanish Society of Hematology.
The complete remission rate was 54% (36/67 patients). The median disease-free survival and overall survival were 6.9 months and 7.6 months, respectively.
Of the 32 patients who initiated maintenance therapy, 5 patients died of infection (2), hemorrhage (2), and acute cognitive impairment (1), and 23 relapsed, with a cumulative incidence of relapse of 74% and a median time to relapse of 12.3 months.
The most frequent toxic events reported were hematologic (neutropenia 77% and thrombocytopenia 54%, of grade III-IV in all cases) followed by infections, metabolic (mainly hyperglycemia), and neurologic, according to the researchers.
“The lack of similar trials specifically directed to this frail population is one of the major strengths of this study, and we consider that this minimal chemotherapy approach could be used as a backbone for addition of immuno/targeted therapy in this subset of infirm patients,” the researchers concluded.
The study was supported by the CERCA Program/Generalitat de Catalunya and the Josep Carreras Leukemia Research Institute. The authors reported having no disclosures.
SOURCE: Ribera J-M et al. Clin Lymphoma Myeloma Leuk. 2020 Apr 5. doi: 10.1016/j.clml.2020.03.011.
A treatment schedule of very attenuated chemotherapy using standard drugs is feasible and effective in frail and elderly patients with acute lymphoblastic leukemia (ALL), according to a prospective study published in Clinical Lymphoma, Myeloma & Leukemia.
The study comprised 67 previously untreated patients with B- or T-lineage Philadelphia chromosome–negative ALL from 30 Spanish hospitals who were enrolled in the prospective, multicenter ALL-07FRAIL trial (NCT01358201) from the Spanish PETHEMA (Programa Español de Tratamientos en Hematologia) group from January 2008 to October 2019.
The median patient age in this analysis was 67 years and 51 patients (76%) were older than 70 years. The median Charlson Comorbidity Index was 5, with the main comorbidities being cardiovascular (47 patients), other neoplasia (24), diabetes (17), and very advanced age (>80 years; 12).
The attenuated treatment regimen consisted of a prephase with dexamethasone and intrathecal therapy with methotrexate was given for a maximum of 1 week. Then weekly induction therapy consisted of weekly vincristine (capped at 1 mg/week) and daily dexamethasone with a progressively decreasing dose along 4 weeks, as well as two additional doses of intrathecal methotrexate.
Those patients who achieved complete remission received maintenance therapy with mercaptopurine and methotrexate to complete 2 years of treatment. In addition, reinduction pulses with vincristine and dexamethasone were given every 3 months during the first year, according to Josep-Maria Ribera, MD, of the Universitat Autònoma de Barcelona, Badalona, Spain and colleagues on behalf of the PETHEMA group of the Spanish Society of Hematology.
The complete remission rate was 54% (36/67 patients). The median disease-free survival and overall survival were 6.9 months and 7.6 months, respectively.
Of the 32 patients who initiated maintenance therapy, 5 patients died of infection (2), hemorrhage (2), and acute cognitive impairment (1), and 23 relapsed, with a cumulative incidence of relapse of 74% and a median time to relapse of 12.3 months.
The most frequent toxic events reported were hematologic (neutropenia 77% and thrombocytopenia 54%, of grade III-IV in all cases) followed by infections, metabolic (mainly hyperglycemia), and neurologic, according to the researchers.
“The lack of similar trials specifically directed to this frail population is one of the major strengths of this study, and we consider that this minimal chemotherapy approach could be used as a backbone for addition of immuno/targeted therapy in this subset of infirm patients,” the researchers concluded.
The study was supported by the CERCA Program/Generalitat de Catalunya and the Josep Carreras Leukemia Research Institute. The authors reported having no disclosures.
SOURCE: Ribera J-M et al. Clin Lymphoma Myeloma Leuk. 2020 Apr 5. doi: 10.1016/j.clml.2020.03.011.
FROM CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA
Germline testing in advanced cancer can lead to targeted treatment
The study involved 11,974 patients with various tumor types. All the patients underwent germline genetic testing from 2015 to 2019 at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York, using the next-generation sequencing panel MSK-IMPACT.
This testing showed that 17.1% of patients had variants in cancer predisposition genes, and 7.1%-8.6% had variants that could potentially be targeted.
“Of course, these numbers are not static,” commented lead author Zsofia K. Stadler, MD, a medical oncologist at MSKCC. “And with the emergence of novel targeted treatments with new FDA indications, the therapeutic actionability of germline variants is likely to increase over time.
“Our study demonstrates the first comprehensive assessment of the clinical utility of germline alterations for therapeutic actionability in a population of patients with advanced cancer,” she added.
Dr. Stadler presented the study results during a virtual scientific program of the American Society of Clinical Oncology 2020.
Testing for somatic mutations is evolving as the standard of care in many cancer types, and somatic genomic testing is rapidly becoming an integral part of the regimen for patients with advanced disease. Some studies suggest that 9%-11% of patients harbor actionable genetic alterations, as determined on the basis of tumor profiling.
“The take-home message from this is that now, more than ever before, germline testing is indicated for the selection of cancer treatment,” said Erin Wysong Hofstatter, MD, from Yale University, New Haven, Conn., in a Highlights of the Day session.
An emerging indication for germline testing is the selection of treatment in the advanced setting, she noted. “And it is important to know your test. Remember that tumor sequencing is not a substitute for comprehensive germline testing.”
Implications in cancer treatment
For their study, Dr. Stadler and colleagues reviewed the medical records of patients with likely pathogenic/pathogenic germline (LP/P) alterations in genes that had known therapeutic targets so as to identify germline-targeted treatment either in a clinical or research setting.
“Since 2015, patients undergoing MSK-IMPACT may also choose to provide additional consent for secondary germline genetic analysis, wherein up to 88 genes known to be associated with cancer predisposition are analyzed,” she said. “Likely pathogenic and pathogenic germline alterations identified are disclosed to the patient and treating physician via the Clinical Genetic Service.”
A total of 2043 (17.1%) patients who harbored LP/P variants in a cancer predisposition gene were identified. Of these, 11% of patients harbored pathogenic alterations in high or moderate penetrance cancer predisposition genes. When the analysis was limited to genes with targeted therapeutic actionability, or what the authors defined as tier 1 and tier 2 genes, 7.1% of patients (n = 849) harbored a targetable pathogenic germline alteration.
BRCA alterations accounted for half (52%) of the findings, and 20% were associated with Lynch syndrome.
The tier 2 genes, which included PALB2, ATM, RAD51C, and RAD51D, accounted for about a quarter of the findings. Dr. Hofstatter noted that, using strict criteria, 7.1% of patients (n = 849) were found to harbor a pathogenic alteration and a targetable gene. Using less stringent criteria, additional tier 3 genes and additional genes associated with DNA homologous recombination repair brought the number up to 8.6% (n = 1,003).
Therapeutic action
For determining therapeutic actionability, the strict criteria were used; 593 patients (4.95%) with recurrent or metastatic disease were identified. For these patients, consideration of a targeted therapy, either as part of standard care or as part of an investigation or research protocol, was important.
Of this group, 44% received therapy targeting the germline alteration. Regarding specific genes, 50% of BRCA1/2 carriers and 58% of Lynch syndrome patients received targeted treatment. With respect to tier 2 genes, 40% of patients with PALB2, 19% with ATM, and 37% with RAD51C or 51D received a poly (ADP-ribose) polymerase (PARP) inhibitor.
Among patients with a BRCA1/2 mutation who received a PARP inhibitor, 55.1% had breast or ovarian cancer, and 44.8% had other tumor types, including pancreas, prostate, bile duct, gastric cancers. These patients received the drug in a research setting.
For patients with PALB2 alterations who received PARP inhibitors, 53.3% had breast or pancreas cancer, and 46.7% had cancer of the prostate, ovary, or an unknown primary.
Looking ahead
The discussant for the paper, Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center, Houston, pointed out that most of the BRCA-positive patients had cancers traditionally associated with the mutation. “There were no patients with PTEN mutations treated, and interestingly, no patients with NF1 were treated,” she said. “But actionability is evolving, as the MEK inhibitor selumitinib was recently approved for NF1.”
Some questions remain unanswered, she noted, such as: “What percentage of patients undergoing tumor-normal testing signed a germline protocol?” and “Does the population introduce a bias – such as younger patients, family history, and so on?”
It is also unknown what percentage of germline alterations were known in comparison with those identified through tumor/normal testing. Also of importance is the fact that in this study, the results of germline testing were delivered in an academic setting, she emphasized. “What if they were delivered elsewhere? What would be the impact of identifying these alterations in an environment with less access to trials?
“But to be fair, it is not easy to seek the germline mutations,” Dr. Meric-Bernstam continued. “These studies were done under institutional review board protocols, and it is important to note that most profiling is done as standard of care without consenting and soliciting patient preference on the return of germline results.”
An infrastructure is needed to return/counsel/offer cascade testing, and “analyses need to be facilitated to ensure that findings can be acted upon in a timely fashion,” she added.
The study was supported by MSKCC internal funding. Dr. Stadler reported relationships (institutional) with Adverum, Alimera Sciences, Allergan, Biomarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Meric-Bernstram reported relationships with numerous pharmaceutical companies.
This article first appeared on Medscape.com.
The study involved 11,974 patients with various tumor types. All the patients underwent germline genetic testing from 2015 to 2019 at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York, using the next-generation sequencing panel MSK-IMPACT.
This testing showed that 17.1% of patients had variants in cancer predisposition genes, and 7.1%-8.6% had variants that could potentially be targeted.
“Of course, these numbers are not static,” commented lead author Zsofia K. Stadler, MD, a medical oncologist at MSKCC. “And with the emergence of novel targeted treatments with new FDA indications, the therapeutic actionability of germline variants is likely to increase over time.
“Our study demonstrates the first comprehensive assessment of the clinical utility of germline alterations for therapeutic actionability in a population of patients with advanced cancer,” she added.
Dr. Stadler presented the study results during a virtual scientific program of the American Society of Clinical Oncology 2020.
Testing for somatic mutations is evolving as the standard of care in many cancer types, and somatic genomic testing is rapidly becoming an integral part of the regimen for patients with advanced disease. Some studies suggest that 9%-11% of patients harbor actionable genetic alterations, as determined on the basis of tumor profiling.
“The take-home message from this is that now, more than ever before, germline testing is indicated for the selection of cancer treatment,” said Erin Wysong Hofstatter, MD, from Yale University, New Haven, Conn., in a Highlights of the Day session.
An emerging indication for germline testing is the selection of treatment in the advanced setting, she noted. “And it is important to know your test. Remember that tumor sequencing is not a substitute for comprehensive germline testing.”
Implications in cancer treatment
For their study, Dr. Stadler and colleagues reviewed the medical records of patients with likely pathogenic/pathogenic germline (LP/P) alterations in genes that had known therapeutic targets so as to identify germline-targeted treatment either in a clinical or research setting.
“Since 2015, patients undergoing MSK-IMPACT may also choose to provide additional consent for secondary germline genetic analysis, wherein up to 88 genes known to be associated with cancer predisposition are analyzed,” she said. “Likely pathogenic and pathogenic germline alterations identified are disclosed to the patient and treating physician via the Clinical Genetic Service.”
A total of 2043 (17.1%) patients who harbored LP/P variants in a cancer predisposition gene were identified. Of these, 11% of patients harbored pathogenic alterations in high or moderate penetrance cancer predisposition genes. When the analysis was limited to genes with targeted therapeutic actionability, or what the authors defined as tier 1 and tier 2 genes, 7.1% of patients (n = 849) harbored a targetable pathogenic germline alteration.
BRCA alterations accounted for half (52%) of the findings, and 20% were associated with Lynch syndrome.
The tier 2 genes, which included PALB2, ATM, RAD51C, and RAD51D, accounted for about a quarter of the findings. Dr. Hofstatter noted that, using strict criteria, 7.1% of patients (n = 849) were found to harbor a pathogenic alteration and a targetable gene. Using less stringent criteria, additional tier 3 genes and additional genes associated with DNA homologous recombination repair brought the number up to 8.6% (n = 1,003).
Therapeutic action
For determining therapeutic actionability, the strict criteria were used; 593 patients (4.95%) with recurrent or metastatic disease were identified. For these patients, consideration of a targeted therapy, either as part of standard care or as part of an investigation or research protocol, was important.
Of this group, 44% received therapy targeting the germline alteration. Regarding specific genes, 50% of BRCA1/2 carriers and 58% of Lynch syndrome patients received targeted treatment. With respect to tier 2 genes, 40% of patients with PALB2, 19% with ATM, and 37% with RAD51C or 51D received a poly (ADP-ribose) polymerase (PARP) inhibitor.
Among patients with a BRCA1/2 mutation who received a PARP inhibitor, 55.1% had breast or ovarian cancer, and 44.8% had other tumor types, including pancreas, prostate, bile duct, gastric cancers. These patients received the drug in a research setting.
For patients with PALB2 alterations who received PARP inhibitors, 53.3% had breast or pancreas cancer, and 46.7% had cancer of the prostate, ovary, or an unknown primary.
Looking ahead
The discussant for the paper, Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center, Houston, pointed out that most of the BRCA-positive patients had cancers traditionally associated with the mutation. “There were no patients with PTEN mutations treated, and interestingly, no patients with NF1 were treated,” she said. “But actionability is evolving, as the MEK inhibitor selumitinib was recently approved for NF1.”
Some questions remain unanswered, she noted, such as: “What percentage of patients undergoing tumor-normal testing signed a germline protocol?” and “Does the population introduce a bias – such as younger patients, family history, and so on?”
It is also unknown what percentage of germline alterations were known in comparison with those identified through tumor/normal testing. Also of importance is the fact that in this study, the results of germline testing were delivered in an academic setting, she emphasized. “What if they were delivered elsewhere? What would be the impact of identifying these alterations in an environment with less access to trials?
“But to be fair, it is not easy to seek the germline mutations,” Dr. Meric-Bernstam continued. “These studies were done under institutional review board protocols, and it is important to note that most profiling is done as standard of care without consenting and soliciting patient preference on the return of germline results.”
An infrastructure is needed to return/counsel/offer cascade testing, and “analyses need to be facilitated to ensure that findings can be acted upon in a timely fashion,” she added.
The study was supported by MSKCC internal funding. Dr. Stadler reported relationships (institutional) with Adverum, Alimera Sciences, Allergan, Biomarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Meric-Bernstram reported relationships with numerous pharmaceutical companies.
This article first appeared on Medscape.com.
The study involved 11,974 patients with various tumor types. All the patients underwent germline genetic testing from 2015 to 2019 at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York, using the next-generation sequencing panel MSK-IMPACT.
This testing showed that 17.1% of patients had variants in cancer predisposition genes, and 7.1%-8.6% had variants that could potentially be targeted.
“Of course, these numbers are not static,” commented lead author Zsofia K. Stadler, MD, a medical oncologist at MSKCC. “And with the emergence of novel targeted treatments with new FDA indications, the therapeutic actionability of germline variants is likely to increase over time.
“Our study demonstrates the first comprehensive assessment of the clinical utility of germline alterations for therapeutic actionability in a population of patients with advanced cancer,” she added.
Dr. Stadler presented the study results during a virtual scientific program of the American Society of Clinical Oncology 2020.
Testing for somatic mutations is evolving as the standard of care in many cancer types, and somatic genomic testing is rapidly becoming an integral part of the regimen for patients with advanced disease. Some studies suggest that 9%-11% of patients harbor actionable genetic alterations, as determined on the basis of tumor profiling.
“The take-home message from this is that now, more than ever before, germline testing is indicated for the selection of cancer treatment,” said Erin Wysong Hofstatter, MD, from Yale University, New Haven, Conn., in a Highlights of the Day session.
An emerging indication for germline testing is the selection of treatment in the advanced setting, she noted. “And it is important to know your test. Remember that tumor sequencing is not a substitute for comprehensive germline testing.”
Implications in cancer treatment
For their study, Dr. Stadler and colleagues reviewed the medical records of patients with likely pathogenic/pathogenic germline (LP/P) alterations in genes that had known therapeutic targets so as to identify germline-targeted treatment either in a clinical or research setting.
“Since 2015, patients undergoing MSK-IMPACT may also choose to provide additional consent for secondary germline genetic analysis, wherein up to 88 genes known to be associated with cancer predisposition are analyzed,” she said. “Likely pathogenic and pathogenic germline alterations identified are disclosed to the patient and treating physician via the Clinical Genetic Service.”
A total of 2043 (17.1%) patients who harbored LP/P variants in a cancer predisposition gene were identified. Of these, 11% of patients harbored pathogenic alterations in high or moderate penetrance cancer predisposition genes. When the analysis was limited to genes with targeted therapeutic actionability, or what the authors defined as tier 1 and tier 2 genes, 7.1% of patients (n = 849) harbored a targetable pathogenic germline alteration.
BRCA alterations accounted for half (52%) of the findings, and 20% were associated with Lynch syndrome.
The tier 2 genes, which included PALB2, ATM, RAD51C, and RAD51D, accounted for about a quarter of the findings. Dr. Hofstatter noted that, using strict criteria, 7.1% of patients (n = 849) were found to harbor a pathogenic alteration and a targetable gene. Using less stringent criteria, additional tier 3 genes and additional genes associated with DNA homologous recombination repair brought the number up to 8.6% (n = 1,003).
Therapeutic action
For determining therapeutic actionability, the strict criteria were used; 593 patients (4.95%) with recurrent or metastatic disease were identified. For these patients, consideration of a targeted therapy, either as part of standard care or as part of an investigation or research protocol, was important.
Of this group, 44% received therapy targeting the germline alteration. Regarding specific genes, 50% of BRCA1/2 carriers and 58% of Lynch syndrome patients received targeted treatment. With respect to tier 2 genes, 40% of patients with PALB2, 19% with ATM, and 37% with RAD51C or 51D received a poly (ADP-ribose) polymerase (PARP) inhibitor.
Among patients with a BRCA1/2 mutation who received a PARP inhibitor, 55.1% had breast or ovarian cancer, and 44.8% had other tumor types, including pancreas, prostate, bile duct, gastric cancers. These patients received the drug in a research setting.
For patients with PALB2 alterations who received PARP inhibitors, 53.3% had breast or pancreas cancer, and 46.7% had cancer of the prostate, ovary, or an unknown primary.
Looking ahead
The discussant for the paper, Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center, Houston, pointed out that most of the BRCA-positive patients had cancers traditionally associated with the mutation. “There were no patients with PTEN mutations treated, and interestingly, no patients with NF1 were treated,” she said. “But actionability is evolving, as the MEK inhibitor selumitinib was recently approved for NF1.”
Some questions remain unanswered, she noted, such as: “What percentage of patients undergoing tumor-normal testing signed a germline protocol?” and “Does the population introduce a bias – such as younger patients, family history, and so on?”
It is also unknown what percentage of germline alterations were known in comparison with those identified through tumor/normal testing. Also of importance is the fact that in this study, the results of germline testing were delivered in an academic setting, she emphasized. “What if they were delivered elsewhere? What would be the impact of identifying these alterations in an environment with less access to trials?
“But to be fair, it is not easy to seek the germline mutations,” Dr. Meric-Bernstam continued. “These studies were done under institutional review board protocols, and it is important to note that most profiling is done as standard of care without consenting and soliciting patient preference on the return of germline results.”
An infrastructure is needed to return/counsel/offer cascade testing, and “analyses need to be facilitated to ensure that findings can be acted upon in a timely fashion,” she added.
The study was supported by MSKCC internal funding. Dr. Stadler reported relationships (institutional) with Adverum, Alimera Sciences, Allergan, Biomarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Meric-Bernstram reported relationships with numerous pharmaceutical companies.
This article first appeared on Medscape.com.
FROM ASCO 2020
June 2020 Public Pathogens
Click here to access June 2020 Public Pathogens
Table of Contents
- COVID-19 Data & Trends
- Open Clinical Trials for Patients With COVID-19
- Lessons From the COVID-19 Pandemic: It’s Time to Invest in Public Health
- Gap Analysis for the Conversion to Area Under the Curve Vancomycin Monitoring in a Small Rural Hospital
- Outcomes Comparison of the Veterans’ Choice Program Withthe Veterans Affairs Health Care System for Hepatitis C Treatment
Click here to access June 2020 Public Pathogens
Table of Contents
- COVID-19 Data & Trends
- Open Clinical Trials for Patients With COVID-19
- Lessons From the COVID-19 Pandemic: It’s Time to Invest in Public Health
- Gap Analysis for the Conversion to Area Under the Curve Vancomycin Monitoring in a Small Rural Hospital
- Outcomes Comparison of the Veterans’ Choice Program Withthe Veterans Affairs Health Care System for Hepatitis C Treatment
Click here to access June 2020 Public Pathogens
Table of Contents
- COVID-19 Data & Trends
- Open Clinical Trials for Patients With COVID-19
- Lessons From the COVID-19 Pandemic: It’s Time to Invest in Public Health
- Gap Analysis for the Conversion to Area Under the Curve Vancomycin Monitoring in a Small Rural Hospital
- Outcomes Comparison of the Veterans’ Choice Program Withthe Veterans Affairs Health Care System for Hepatitis C Treatment
COVID-19: Problematic gambling could worsen
The confluence of isolation, excess available time, and anxiety about illness or finances as a result of the COVID-19 pandemic have the potential to increase problem gambling behaviors during this public health emergency, so it’s essential to gather data and supply guidance on this issue, according to a call to action published May 18 in the Journal of Addiction Medicine.
“When facing an unforeseen situation with confinement, fear of disease, and financial uncertainty for the future, problem gambling may be an important health hazard to monitor and prevent during and following the COVID-19 crisis, especially given current online gambling availability,” wrote Anders Håkansson, PhD, of Lund University in Sweden and coauthors.
Both stress and trauma have been linked to gambling problems, and both are occurring during the pandemic, said coauthor Marc N. Potenza, MD, PhD, of Yale University, New Haven, Conn., in an interview.
“People are likely to be experiencing stress at levels they haven’t experienced previously,” Dr. Potenza said. While multiple factors can contribute to addictive behaviors, “with respect to the pandemic, one concern is that so-called negative reinforcement motivations – engaging in an addictive behavior to escape from depressed or negative mood states – may be a driving motivation for a significant number of people during this time,” he said.
David Hodgins, PhD, CPsych, a professor of psychology at the University of Calgary in Alberta, who was not involved with the commentary, noted that gambling relapse is triggered by “negative emotional states, interpersonal stress, and financial stress” – all three of which the pandemic contributes to.
Financial stress can especially “inflame erroneous gambling-related cognitions,” he said in an interview, including “beliefs such as the idea that gambling can solve financial problems, even when this is statistically almost impossible as debt increases, and that debt has been caused by gambling.”
Increased social isolation also is particularly problematic, pointed out Shane W. Kraus, PhD, from the University of Nevada, Las Vegas. Dr. Kraus also was not involved with the paper.
“If someone is already struggling with already negative emotions, negative feelings, thoughts, and depression, and you’re now isolating them quite a bit, that’s not going to be a recipe for success,” Dr. Kraus said in an interview.
Dr. Potenza said.
“We should be mindful of ways in which people develop addictions in these settings,” he said. “One of the aspects of the pandemic is that many people are at home for longer periods of time, and they use digital technologies more frequently.”
The use of digital technologies can include interaction on social media platforms and on meeting applications such as Zoom, but such use also offers opportunities for problematic gambling, gaming, and pornography use. The World Health Organization recognizes addiction disorders for gambling and for gaming, and online gaming platforms and pornography sites have reported substantial increases in their traffic during the pandemic, Dr. Potenza said.
The increase in frequency is unsurprising and not necessarily a concern by itself, Dr. Kraus said.
“It’s all about loss of control or difficulty engaging or disengaging,” Dr. Kraus said. “When you can’t stop doing something even if you like it or love it, when it interferes with your day-to-day activities and relationships, that’s when it’s a problem.”
Gambling online: Easy, available
The authors note that past research has identified increased gambling problems during economic crises in other countries.
“While currently speculative, financial hardships may promote gambling as individuals may be motivated to gamble to try to win money,” the authors suggested. “Although presently limited, existing data suggest that COVID-19–related financial concerns may increase gambling-related harms, and this possibility merits systematic research.”
But trends and characteristics of the gambling market, including direct effects from the pandemic, can potentially influence behaviors, too. Most casinos have closed during the pandemic, and most of the sports that people bet on have been canceled or postponed.
“Fewer people are gambling on sports, but they turn then to other areas,” Dr. Potenza said. “If they can’t bet on major league type sports, they might gamble on more local sporting events, or they may bet on other activities going on in society during the pandemic.”
But online gambling poses greater risk.
“Properties of online gambling may constitute a particular health hazard when many people are confined to their homes and have had rapid changes in working conditions, psychosocial stress, anxiety, and depression, as has been described in China,” the paper’s authors wrote. “Online gambling may be particularly concerning due to its availability and velocity” and association with higher debt levels.
In addition to online gaming’s ease and availability, past research has found patients report boredom and escapism as reasons they turned to it.
Again, boredom on its own is not necessarily a problem, but for those who already struggle with addictive behaviors, it can be a trigger, Dr. Kraus said.
“Boredom is very tough for them because it’s often associated with negative emotions,” such as dwelling on things not going well in their lives, he said. “In a pandemic, people are by themselves quite a bit, socially isolated, so for those who are struggling already with some depression or anxiety, it’s only going to be increased.”
Online gaming trends may vary with demographics, however. Dr. Kraus noted that his former clinic at the Veterans Administration has been seeing lower gambling in patients with addictive disorders, but those patients are also older and primarily frequented casinos.
“It’s going to depend on age and familiarity with technology,” he said, but even if older problem gamblers are not going to the Internet now, “let’s wait and see what happens in the next 2 or 3 months.”
The authors noted results from a small survey of patients in treatment for gambling addiction at the Bellvitge University Hospital in Barcelona, Spain, where two of the coauthors work. They conducted telephone surveys with 26 patients about the first 4 weeks of sheltering in place because of the coronavirus. All but four of the patients were male, and their average age was 45 years.
“Most presented worries about increased uncertainties, such as the negative impact on their work, risk of COVID-19 infection of themselves or their loved ones and their treatment,” the authors reported.
Although 19% were completely abstinent, an additional 12% (n = 3) reported worsened gambling. In addition, almost half (46%) reported anxiety symptoms and more than a quarter (27%) had depressive symptoms.
Appropriate care
A particularly complicating factor of the pandemic is how it has disrupted traditional ways of seeking health care, particularly with how much mental health and other medical care has shifted to telehealth and online delivery, Dr. Potenza pointed out.
“This is a change for many people, and it’s important for both caretakers and people in treatment to be mindful of this and to try to ensure that appropriate services are maintained for people during this time,” he said.
For example, 12-step programs traditionally meet in person, which is largely impossible during the pandemic. Some have moved meetings online, and other programs have turned to apps, such as the Addiction Policy Forum’s app Connections, an empirically validated digital therapy platform that lets patients and clinicians remain connected with remote check-ins.
The move to more telehealth may actually increase access, suggested Dr. Hodgins.
“There is no evidence that this is less effective, and in fact, its convenience might be an advantage in reaching more people,” he said. “More challenging is offering group therapies remotely, but this is also feasible.”
The treatment with the strongest evidence remains cognitive-behavioral therapy (CBT), Dr. Hodgins said.
“This therapy, in part, helps people become aware of their erroneous cognitions and to challenge them, but also helps people restructure their activities to change their habits,” he said. He also noted the rise of online therapy, whether supported by a therapist or entirely self-directed, such as Gambling Self-help.
“These programs typically provide cognitive behavior content but also content that comes from studying how people recover from gambling problems,” he said. “The challenge of completely self-directed approaches is follow-through. Like most online content, people tend to flit around more than they might in therapy.” Still, he added, research has shown good outcomes from these programs.
Dr. Potenza also noted that several organizations, including the International Society of Addiction Medicine and Children and Screens, have been hosting webinars related to COVID-19 coping and/or addiction that clinicians and patients might find helpful.
Identification of problematic behaviors
One challenge in watching for problematic gambling behaviors during the pandemic is the set of unusual living circumstances for most people right now. At almost no other time in history have people been primarily confined to their homes, many unable to go to work or working from home, with extra leisure time and nowhere to go.
“With the COVID-19 pandemic, a lot of daily life has changed,” Dr. Potenza said. “It’s unclear whether certain behaviors that have become habitual during the pandemic, such as gaming or online gambling, will then interfere with daily life when the pandemic subsides.”
“The problem is, a small proportion of people who are very vulnerable will develop a disorder and might maintain it,” Dr. Kraus said. Those who already struggle with mental health and may be out of work have greater potential for problematic behaviors.
Dr. Potenza collaborated with other psychiatrists in drafting consensus guidelines on maintaining healthy use of the Internet specifically during the pandemic (Compr Psychiatry. 2020 Jul. doi: 10.10161/comppsych.2020.152180).
“It’s important to think about where one draws the line between normative everyday behaviors – behaviors that are not interfering with life functioning – and those that do interfere with life functioning,” Dr. Potenza said. “If someone is having difficulty making work or family or school obligations, these are important signs that the behavior may be problematic.”
He offered suggestions for things people can do to promote their health during the pandemic, such as having regular routines that include getting physical exercise and social interaction, dining with family if isolating together, and making time for self-care. He also recommended setting limits on the use of digital devices and aiming for a healthy balance in keeping up with the news. The idea is to stay aware of what’s happening without getting burned out or traumatized by news coverage.
Guidance for clinicians
An urgent need for research and guidelines related to gambling and the pandemic exists, the authors argued.
In the meantime, aside from various validated screeners available, Dr. Kraus offered some practical advice for clinicians checking in with their patients: “Ask your patients what they have been doing to cope with this difficult time.”
Some might mention their faith, family, or friends, and others might not have an answer or mention drinking, gaming, or engaging in other activities. “We all do things to cope. Sometimes you use healthy coping and sometimes you use unhealthy coping,” Dr. Kraus said. “I would have a dialogue with my patients around, ‘How are you getting through? What’s helping you? What are some things you’ve tried that are tripping you up?’ ”
If gambling in particular is a possible concern, he encouraged clinicians to ask their patients whether they have tried to quit or what would happen if they stopped gambling.
“What we’d expect is the problem gamblers will have more irritability, crankiness, difficulty with quitting,” he said.
Dr. Hodgins agreed that checking in on how patients’ lives and activities have changed, and their emotion reactions to those changes, is prudent.
“The change in activities might be healthy or might include increased addictive behaviors, including increased use of substances, gaming, pornography, food, and gambling,” he said.
In addition, the paper authors list several examples of guidelines that might be considered in drafting guidance for clinicians, including the following:
- Limiting the extent of gambling
- Not gambling to regulate negative emotions
- Not gambling in order to try to solve financial problems or financial concerns
- Not gambling under the influence of alcohol or drugs
- Carefully monitoring gambling-related time and financial expenditures
- Maintaining and establishing daily routines involving activities other than gambling
- Minding gambling-related attitudes and behaviors in the presence of minors
- Not starting to gamble because of stressors
The research did not receive external funding. Dr. Håkansson has received research funding from the Swedish Sport Foundation, the Swedish alcohol monopoly Systembolaget, and the Swedish state-owned gambling operator AB Svenska Spel. He is working with the company Kontigo Care on devices for gambling addiction follow-up care. Dr. Potenza has received consulting or advisory compensation from several entities, including the Addiction Policy Forum, AXA Gaming, Idorsia, Opiant, and RiverMend Health. Dr. Potenza has received research funding from Mohegan Sun casino and the National Center for Responsible Gaming. No other authors or outside sources had industry-related disclosures.
SOURCE: Håkansson A et al. J Addict Med. 2020 May 18. doi: 10.1097/ADM.0000000000000690.
The confluence of isolation, excess available time, and anxiety about illness or finances as a result of the COVID-19 pandemic have the potential to increase problem gambling behaviors during this public health emergency, so it’s essential to gather data and supply guidance on this issue, according to a call to action published May 18 in the Journal of Addiction Medicine.
“When facing an unforeseen situation with confinement, fear of disease, and financial uncertainty for the future, problem gambling may be an important health hazard to monitor and prevent during and following the COVID-19 crisis, especially given current online gambling availability,” wrote Anders Håkansson, PhD, of Lund University in Sweden and coauthors.
Both stress and trauma have been linked to gambling problems, and both are occurring during the pandemic, said coauthor Marc N. Potenza, MD, PhD, of Yale University, New Haven, Conn., in an interview.
“People are likely to be experiencing stress at levels they haven’t experienced previously,” Dr. Potenza said. While multiple factors can contribute to addictive behaviors, “with respect to the pandemic, one concern is that so-called negative reinforcement motivations – engaging in an addictive behavior to escape from depressed or negative mood states – may be a driving motivation for a significant number of people during this time,” he said.
David Hodgins, PhD, CPsych, a professor of psychology at the University of Calgary in Alberta, who was not involved with the commentary, noted that gambling relapse is triggered by “negative emotional states, interpersonal stress, and financial stress” – all three of which the pandemic contributes to.
Financial stress can especially “inflame erroneous gambling-related cognitions,” he said in an interview, including “beliefs such as the idea that gambling can solve financial problems, even when this is statistically almost impossible as debt increases, and that debt has been caused by gambling.”
Increased social isolation also is particularly problematic, pointed out Shane W. Kraus, PhD, from the University of Nevada, Las Vegas. Dr. Kraus also was not involved with the paper.
“If someone is already struggling with already negative emotions, negative feelings, thoughts, and depression, and you’re now isolating them quite a bit, that’s not going to be a recipe for success,” Dr. Kraus said in an interview.
Dr. Potenza said.
“We should be mindful of ways in which people develop addictions in these settings,” he said. “One of the aspects of the pandemic is that many people are at home for longer periods of time, and they use digital technologies more frequently.”
The use of digital technologies can include interaction on social media platforms and on meeting applications such as Zoom, but such use also offers opportunities for problematic gambling, gaming, and pornography use. The World Health Organization recognizes addiction disorders for gambling and for gaming, and online gaming platforms and pornography sites have reported substantial increases in their traffic during the pandemic, Dr. Potenza said.
The increase in frequency is unsurprising and not necessarily a concern by itself, Dr. Kraus said.
“It’s all about loss of control or difficulty engaging or disengaging,” Dr. Kraus said. “When you can’t stop doing something even if you like it or love it, when it interferes with your day-to-day activities and relationships, that’s when it’s a problem.”
Gambling online: Easy, available
The authors note that past research has identified increased gambling problems during economic crises in other countries.
“While currently speculative, financial hardships may promote gambling as individuals may be motivated to gamble to try to win money,” the authors suggested. “Although presently limited, existing data suggest that COVID-19–related financial concerns may increase gambling-related harms, and this possibility merits systematic research.”
But trends and characteristics of the gambling market, including direct effects from the pandemic, can potentially influence behaviors, too. Most casinos have closed during the pandemic, and most of the sports that people bet on have been canceled or postponed.
“Fewer people are gambling on sports, but they turn then to other areas,” Dr. Potenza said. “If they can’t bet on major league type sports, they might gamble on more local sporting events, or they may bet on other activities going on in society during the pandemic.”
But online gambling poses greater risk.
“Properties of online gambling may constitute a particular health hazard when many people are confined to their homes and have had rapid changes in working conditions, psychosocial stress, anxiety, and depression, as has been described in China,” the paper’s authors wrote. “Online gambling may be particularly concerning due to its availability and velocity” and association with higher debt levels.
In addition to online gaming’s ease and availability, past research has found patients report boredom and escapism as reasons they turned to it.
Again, boredom on its own is not necessarily a problem, but for those who already struggle with addictive behaviors, it can be a trigger, Dr. Kraus said.
“Boredom is very tough for them because it’s often associated with negative emotions,” such as dwelling on things not going well in their lives, he said. “In a pandemic, people are by themselves quite a bit, socially isolated, so for those who are struggling already with some depression or anxiety, it’s only going to be increased.”
Online gaming trends may vary with demographics, however. Dr. Kraus noted that his former clinic at the Veterans Administration has been seeing lower gambling in patients with addictive disorders, but those patients are also older and primarily frequented casinos.
“It’s going to depend on age and familiarity with technology,” he said, but even if older problem gamblers are not going to the Internet now, “let’s wait and see what happens in the next 2 or 3 months.”
The authors noted results from a small survey of patients in treatment for gambling addiction at the Bellvitge University Hospital in Barcelona, Spain, where two of the coauthors work. They conducted telephone surveys with 26 patients about the first 4 weeks of sheltering in place because of the coronavirus. All but four of the patients were male, and their average age was 45 years.
“Most presented worries about increased uncertainties, such as the negative impact on their work, risk of COVID-19 infection of themselves or their loved ones and their treatment,” the authors reported.
Although 19% were completely abstinent, an additional 12% (n = 3) reported worsened gambling. In addition, almost half (46%) reported anxiety symptoms and more than a quarter (27%) had depressive symptoms.
Appropriate care
A particularly complicating factor of the pandemic is how it has disrupted traditional ways of seeking health care, particularly with how much mental health and other medical care has shifted to telehealth and online delivery, Dr. Potenza pointed out.
“This is a change for many people, and it’s important for both caretakers and people in treatment to be mindful of this and to try to ensure that appropriate services are maintained for people during this time,” he said.
For example, 12-step programs traditionally meet in person, which is largely impossible during the pandemic. Some have moved meetings online, and other programs have turned to apps, such as the Addiction Policy Forum’s app Connections, an empirically validated digital therapy platform that lets patients and clinicians remain connected with remote check-ins.
The move to more telehealth may actually increase access, suggested Dr. Hodgins.
“There is no evidence that this is less effective, and in fact, its convenience might be an advantage in reaching more people,” he said. “More challenging is offering group therapies remotely, but this is also feasible.”
The treatment with the strongest evidence remains cognitive-behavioral therapy (CBT), Dr. Hodgins said.
“This therapy, in part, helps people become aware of their erroneous cognitions and to challenge them, but also helps people restructure their activities to change their habits,” he said. He also noted the rise of online therapy, whether supported by a therapist or entirely self-directed, such as Gambling Self-help.
“These programs typically provide cognitive behavior content but also content that comes from studying how people recover from gambling problems,” he said. “The challenge of completely self-directed approaches is follow-through. Like most online content, people tend to flit around more than they might in therapy.” Still, he added, research has shown good outcomes from these programs.
Dr. Potenza also noted that several organizations, including the International Society of Addiction Medicine and Children and Screens, have been hosting webinars related to COVID-19 coping and/or addiction that clinicians and patients might find helpful.
Identification of problematic behaviors
One challenge in watching for problematic gambling behaviors during the pandemic is the set of unusual living circumstances for most people right now. At almost no other time in history have people been primarily confined to their homes, many unable to go to work or working from home, with extra leisure time and nowhere to go.
“With the COVID-19 pandemic, a lot of daily life has changed,” Dr. Potenza said. “It’s unclear whether certain behaviors that have become habitual during the pandemic, such as gaming or online gambling, will then interfere with daily life when the pandemic subsides.”
“The problem is, a small proportion of people who are very vulnerable will develop a disorder and might maintain it,” Dr. Kraus said. Those who already struggle with mental health and may be out of work have greater potential for problematic behaviors.
Dr. Potenza collaborated with other psychiatrists in drafting consensus guidelines on maintaining healthy use of the Internet specifically during the pandemic (Compr Psychiatry. 2020 Jul. doi: 10.10161/comppsych.2020.152180).
“It’s important to think about where one draws the line between normative everyday behaviors – behaviors that are not interfering with life functioning – and those that do interfere with life functioning,” Dr. Potenza said. “If someone is having difficulty making work or family or school obligations, these are important signs that the behavior may be problematic.”
He offered suggestions for things people can do to promote their health during the pandemic, such as having regular routines that include getting physical exercise and social interaction, dining with family if isolating together, and making time for self-care. He also recommended setting limits on the use of digital devices and aiming for a healthy balance in keeping up with the news. The idea is to stay aware of what’s happening without getting burned out or traumatized by news coverage.
Guidance for clinicians
An urgent need for research and guidelines related to gambling and the pandemic exists, the authors argued.
In the meantime, aside from various validated screeners available, Dr. Kraus offered some practical advice for clinicians checking in with their patients: “Ask your patients what they have been doing to cope with this difficult time.”
Some might mention their faith, family, or friends, and others might not have an answer or mention drinking, gaming, or engaging in other activities. “We all do things to cope. Sometimes you use healthy coping and sometimes you use unhealthy coping,” Dr. Kraus said. “I would have a dialogue with my patients around, ‘How are you getting through? What’s helping you? What are some things you’ve tried that are tripping you up?’ ”
If gambling in particular is a possible concern, he encouraged clinicians to ask their patients whether they have tried to quit or what would happen if they stopped gambling.
“What we’d expect is the problem gamblers will have more irritability, crankiness, difficulty with quitting,” he said.
Dr. Hodgins agreed that checking in on how patients’ lives and activities have changed, and their emotion reactions to those changes, is prudent.
“The change in activities might be healthy or might include increased addictive behaviors, including increased use of substances, gaming, pornography, food, and gambling,” he said.
In addition, the paper authors list several examples of guidelines that might be considered in drafting guidance for clinicians, including the following:
- Limiting the extent of gambling
- Not gambling to regulate negative emotions
- Not gambling in order to try to solve financial problems or financial concerns
- Not gambling under the influence of alcohol or drugs
- Carefully monitoring gambling-related time and financial expenditures
- Maintaining and establishing daily routines involving activities other than gambling
- Minding gambling-related attitudes and behaviors in the presence of minors
- Not starting to gamble because of stressors
The research did not receive external funding. Dr. Håkansson has received research funding from the Swedish Sport Foundation, the Swedish alcohol monopoly Systembolaget, and the Swedish state-owned gambling operator AB Svenska Spel. He is working with the company Kontigo Care on devices for gambling addiction follow-up care. Dr. Potenza has received consulting or advisory compensation from several entities, including the Addiction Policy Forum, AXA Gaming, Idorsia, Opiant, and RiverMend Health. Dr. Potenza has received research funding from Mohegan Sun casino and the National Center for Responsible Gaming. No other authors or outside sources had industry-related disclosures.
SOURCE: Håkansson A et al. J Addict Med. 2020 May 18. doi: 10.1097/ADM.0000000000000690.
The confluence of isolation, excess available time, and anxiety about illness or finances as a result of the COVID-19 pandemic have the potential to increase problem gambling behaviors during this public health emergency, so it’s essential to gather data and supply guidance on this issue, according to a call to action published May 18 in the Journal of Addiction Medicine.
“When facing an unforeseen situation with confinement, fear of disease, and financial uncertainty for the future, problem gambling may be an important health hazard to monitor and prevent during and following the COVID-19 crisis, especially given current online gambling availability,” wrote Anders Håkansson, PhD, of Lund University in Sweden and coauthors.
Both stress and trauma have been linked to gambling problems, and both are occurring during the pandemic, said coauthor Marc N. Potenza, MD, PhD, of Yale University, New Haven, Conn., in an interview.
“People are likely to be experiencing stress at levels they haven’t experienced previously,” Dr. Potenza said. While multiple factors can contribute to addictive behaviors, “with respect to the pandemic, one concern is that so-called negative reinforcement motivations – engaging in an addictive behavior to escape from depressed or negative mood states – may be a driving motivation for a significant number of people during this time,” he said.
David Hodgins, PhD, CPsych, a professor of psychology at the University of Calgary in Alberta, who was not involved with the commentary, noted that gambling relapse is triggered by “negative emotional states, interpersonal stress, and financial stress” – all three of which the pandemic contributes to.
Financial stress can especially “inflame erroneous gambling-related cognitions,” he said in an interview, including “beliefs such as the idea that gambling can solve financial problems, even when this is statistically almost impossible as debt increases, and that debt has been caused by gambling.”
Increased social isolation also is particularly problematic, pointed out Shane W. Kraus, PhD, from the University of Nevada, Las Vegas. Dr. Kraus also was not involved with the paper.
“If someone is already struggling with already negative emotions, negative feelings, thoughts, and depression, and you’re now isolating them quite a bit, that’s not going to be a recipe for success,” Dr. Kraus said in an interview.
Dr. Potenza said.
“We should be mindful of ways in which people develop addictions in these settings,” he said. “One of the aspects of the pandemic is that many people are at home for longer periods of time, and they use digital technologies more frequently.”
The use of digital technologies can include interaction on social media platforms and on meeting applications such as Zoom, but such use also offers opportunities for problematic gambling, gaming, and pornography use. The World Health Organization recognizes addiction disorders for gambling and for gaming, and online gaming platforms and pornography sites have reported substantial increases in their traffic during the pandemic, Dr. Potenza said.
The increase in frequency is unsurprising and not necessarily a concern by itself, Dr. Kraus said.
“It’s all about loss of control or difficulty engaging or disengaging,” Dr. Kraus said. “When you can’t stop doing something even if you like it or love it, when it interferes with your day-to-day activities and relationships, that’s when it’s a problem.”
Gambling online: Easy, available
The authors note that past research has identified increased gambling problems during economic crises in other countries.
“While currently speculative, financial hardships may promote gambling as individuals may be motivated to gamble to try to win money,” the authors suggested. “Although presently limited, existing data suggest that COVID-19–related financial concerns may increase gambling-related harms, and this possibility merits systematic research.”
But trends and characteristics of the gambling market, including direct effects from the pandemic, can potentially influence behaviors, too. Most casinos have closed during the pandemic, and most of the sports that people bet on have been canceled or postponed.
“Fewer people are gambling on sports, but they turn then to other areas,” Dr. Potenza said. “If they can’t bet on major league type sports, they might gamble on more local sporting events, or they may bet on other activities going on in society during the pandemic.”
But online gambling poses greater risk.
“Properties of online gambling may constitute a particular health hazard when many people are confined to their homes and have had rapid changes in working conditions, psychosocial stress, anxiety, and depression, as has been described in China,” the paper’s authors wrote. “Online gambling may be particularly concerning due to its availability and velocity” and association with higher debt levels.
In addition to online gaming’s ease and availability, past research has found patients report boredom and escapism as reasons they turned to it.
Again, boredom on its own is not necessarily a problem, but for those who already struggle with addictive behaviors, it can be a trigger, Dr. Kraus said.
“Boredom is very tough for them because it’s often associated with negative emotions,” such as dwelling on things not going well in their lives, he said. “In a pandemic, people are by themselves quite a bit, socially isolated, so for those who are struggling already with some depression or anxiety, it’s only going to be increased.”
Online gaming trends may vary with demographics, however. Dr. Kraus noted that his former clinic at the Veterans Administration has been seeing lower gambling in patients with addictive disorders, but those patients are also older and primarily frequented casinos.
“It’s going to depend on age and familiarity with technology,” he said, but even if older problem gamblers are not going to the Internet now, “let’s wait and see what happens in the next 2 or 3 months.”
The authors noted results from a small survey of patients in treatment for gambling addiction at the Bellvitge University Hospital in Barcelona, Spain, where two of the coauthors work. They conducted telephone surveys with 26 patients about the first 4 weeks of sheltering in place because of the coronavirus. All but four of the patients were male, and their average age was 45 years.
“Most presented worries about increased uncertainties, such as the negative impact on their work, risk of COVID-19 infection of themselves or their loved ones and their treatment,” the authors reported.
Although 19% were completely abstinent, an additional 12% (n = 3) reported worsened gambling. In addition, almost half (46%) reported anxiety symptoms and more than a quarter (27%) had depressive symptoms.
Appropriate care
A particularly complicating factor of the pandemic is how it has disrupted traditional ways of seeking health care, particularly with how much mental health and other medical care has shifted to telehealth and online delivery, Dr. Potenza pointed out.
“This is a change for many people, and it’s important for both caretakers and people in treatment to be mindful of this and to try to ensure that appropriate services are maintained for people during this time,” he said.
For example, 12-step programs traditionally meet in person, which is largely impossible during the pandemic. Some have moved meetings online, and other programs have turned to apps, such as the Addiction Policy Forum’s app Connections, an empirically validated digital therapy platform that lets patients and clinicians remain connected with remote check-ins.
The move to more telehealth may actually increase access, suggested Dr. Hodgins.
“There is no evidence that this is less effective, and in fact, its convenience might be an advantage in reaching more people,” he said. “More challenging is offering group therapies remotely, but this is also feasible.”
The treatment with the strongest evidence remains cognitive-behavioral therapy (CBT), Dr. Hodgins said.
“This therapy, in part, helps people become aware of their erroneous cognitions and to challenge them, but also helps people restructure their activities to change their habits,” he said. He also noted the rise of online therapy, whether supported by a therapist or entirely self-directed, such as Gambling Self-help.
“These programs typically provide cognitive behavior content but also content that comes from studying how people recover from gambling problems,” he said. “The challenge of completely self-directed approaches is follow-through. Like most online content, people tend to flit around more than they might in therapy.” Still, he added, research has shown good outcomes from these programs.
Dr. Potenza also noted that several organizations, including the International Society of Addiction Medicine and Children and Screens, have been hosting webinars related to COVID-19 coping and/or addiction that clinicians and patients might find helpful.
Identification of problematic behaviors
One challenge in watching for problematic gambling behaviors during the pandemic is the set of unusual living circumstances for most people right now. At almost no other time in history have people been primarily confined to their homes, many unable to go to work or working from home, with extra leisure time and nowhere to go.
“With the COVID-19 pandemic, a lot of daily life has changed,” Dr. Potenza said. “It’s unclear whether certain behaviors that have become habitual during the pandemic, such as gaming or online gambling, will then interfere with daily life when the pandemic subsides.”
“The problem is, a small proportion of people who are very vulnerable will develop a disorder and might maintain it,” Dr. Kraus said. Those who already struggle with mental health and may be out of work have greater potential for problematic behaviors.
Dr. Potenza collaborated with other psychiatrists in drafting consensus guidelines on maintaining healthy use of the Internet specifically during the pandemic (Compr Psychiatry. 2020 Jul. doi: 10.10161/comppsych.2020.152180).
“It’s important to think about where one draws the line between normative everyday behaviors – behaviors that are not interfering with life functioning – and those that do interfere with life functioning,” Dr. Potenza said. “If someone is having difficulty making work or family or school obligations, these are important signs that the behavior may be problematic.”
He offered suggestions for things people can do to promote their health during the pandemic, such as having regular routines that include getting physical exercise and social interaction, dining with family if isolating together, and making time for self-care. He also recommended setting limits on the use of digital devices and aiming for a healthy balance in keeping up with the news. The idea is to stay aware of what’s happening without getting burned out or traumatized by news coverage.
Guidance for clinicians
An urgent need for research and guidelines related to gambling and the pandemic exists, the authors argued.
In the meantime, aside from various validated screeners available, Dr. Kraus offered some practical advice for clinicians checking in with their patients: “Ask your patients what they have been doing to cope with this difficult time.”
Some might mention their faith, family, or friends, and others might not have an answer or mention drinking, gaming, or engaging in other activities. “We all do things to cope. Sometimes you use healthy coping and sometimes you use unhealthy coping,” Dr. Kraus said. “I would have a dialogue with my patients around, ‘How are you getting through? What’s helping you? What are some things you’ve tried that are tripping you up?’ ”
If gambling in particular is a possible concern, he encouraged clinicians to ask their patients whether they have tried to quit or what would happen if they stopped gambling.
“What we’d expect is the problem gamblers will have more irritability, crankiness, difficulty with quitting,” he said.
Dr. Hodgins agreed that checking in on how patients’ lives and activities have changed, and their emotion reactions to those changes, is prudent.
“The change in activities might be healthy or might include increased addictive behaviors, including increased use of substances, gaming, pornography, food, and gambling,” he said.
In addition, the paper authors list several examples of guidelines that might be considered in drafting guidance for clinicians, including the following:
- Limiting the extent of gambling
- Not gambling to regulate negative emotions
- Not gambling in order to try to solve financial problems or financial concerns
- Not gambling under the influence of alcohol or drugs
- Carefully monitoring gambling-related time and financial expenditures
- Maintaining and establishing daily routines involving activities other than gambling
- Minding gambling-related attitudes and behaviors in the presence of minors
- Not starting to gamble because of stressors
The research did not receive external funding. Dr. Håkansson has received research funding from the Swedish Sport Foundation, the Swedish alcohol monopoly Systembolaget, and the Swedish state-owned gambling operator AB Svenska Spel. He is working with the company Kontigo Care on devices for gambling addiction follow-up care. Dr. Potenza has received consulting or advisory compensation from several entities, including the Addiction Policy Forum, AXA Gaming, Idorsia, Opiant, and RiverMend Health. Dr. Potenza has received research funding from Mohegan Sun casino and the National Center for Responsible Gaming. No other authors or outside sources had industry-related disclosures.
SOURCE: Håkansson A et al. J Addict Med. 2020 May 18. doi: 10.1097/ADM.0000000000000690.
FROM THE JOURNAL OF ADDICTION MEDICINE
Today’s top news highlights: Addressing racism in maternity care, group forms to protect health professionals from retaliation
Here are the stories our MDedge editors across specialties think you need to know about today:
Addressing racism in the maternal mortality crisis
The emerging racial disparities in COVID-19 incidence and outcomes in the United States are on a collision course with long-standing racial disparities in U.S. maternal care and mortality. “The saying is that ‘the virus doesn’t discriminate,’ but it understands our biases, right? So, the virus takes advantage of the weaknesses in our system,” said Joia A. Crear-Perry, MD, an ob.gyn. and founder and president of the National Birth Equity Collaborative, a New Orleans–based research, training, and advocacy organization working to optimize black maternal and infant health. This article is part of an ongoing feature series on the crisis in maternal mortality in the United States. Here we explore potential solutions for addressing the inequities as proposed by thought leaders and key stakeholders. Read more.
A ‘Beacon’ for physicians, nurses facing retaliation
Sejal Hathi, MD, and two colleagues had long kicked around the idea of starting a nonprofit group that would center on civic and legal advocacy. Once the COVID-19 pandemic hit, the three friends – who have a mix of legal, medical, and advocacy backgrounds – began chatting by email and through Zoom video meetings about how to make the plan a reality. The new organization – named Beacon – quickly mobilized, assembled their team, and launched a website. Beacon’s first project now aims to highlight and protect the legal rights of medical professionals who speak out about personal protection equipment supply and other matters of public concern related to coronavirus. “There are a flurry of reports coming our way about physicians and nurses, as well as other health care workers, who are for whatever reason being disciplined or retaliated against for simply seeking appropriate safety policies at their workplaces,” Dr. Hathi said. “What we’ve found is that many of them don’t even know what their options look like. Doctors, nurses, health care workers are not the typical type to engage politically, to speak out, [or to] advocate for themselves.” Read more.
COVID-19 ravages the Navajo Nation
The Navajo Nation has the most cases of the COVID-19 virus of any tribe in the United States, and numbers as of May 31, 2020, are 5,348, with 246 confirmed deaths. These devastating numbers, which might be leveling off, are associated with Navajo people having higher-than-average rates of diabetes, heart disease, and cancer. This is compounded with 30%-40% of homes having no electricity or running water, and a poverty rate of about 38%. “We endured and learned from each Naayee, hunger, and death to name a few adversities. The COVID-19 pandemic, or “Big Cough” (Dikos Nitsaa’igii -19 in Navajo language), is a monster confronting the Navajo today. It has had significant impact on our nation and people,” Mary Hasbah Roessel, MD, a Navajo board-certified psychiatrist practicing in Santa Fe, N.M., wrote in a commentary on MDedge. Read more.
Heart pump system authorized for COVID-19 patients
The Food and Drug Administration issued an emergency use authorization (EUA) for use of the Impella RP heart pump system in COVID-19 patients with right heart failure or decompensation. The EUA indication for the Impella RP system is to provide temporary right ventricular support for up to 14 days in critical care patients with a body surface area of at least 1.5 m2 for the treatment of acute right heart failure or decompensation caused by complications related to COVID-19, including pulmonary embolism. Read more.
Deprescribing hypertension meds looks safe for older adults
Some patients aged 80 years or older can potentially cut back on their number of antihypertensive meds, under physician guidance, without an important loss of blood pressure control, researchers concluded based on findings from a randomized multicenter trial. The study, called Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTIMISE), entered “patients in whom the benefits of taking blood pressure-lowering treatments might start to be outweighed by the potential harms,” said James P. Sheppard, PhD, of University of Oxford (England). The report was published in JAMA. Read more.
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Here are the stories our MDedge editors across specialties think you need to know about today:
Addressing racism in the maternal mortality crisis
The emerging racial disparities in COVID-19 incidence and outcomes in the United States are on a collision course with long-standing racial disparities in U.S. maternal care and mortality. “The saying is that ‘the virus doesn’t discriminate,’ but it understands our biases, right? So, the virus takes advantage of the weaknesses in our system,” said Joia A. Crear-Perry, MD, an ob.gyn. and founder and president of the National Birth Equity Collaborative, a New Orleans–based research, training, and advocacy organization working to optimize black maternal and infant health. This article is part of an ongoing feature series on the crisis in maternal mortality in the United States. Here we explore potential solutions for addressing the inequities as proposed by thought leaders and key stakeholders. Read more.
A ‘Beacon’ for physicians, nurses facing retaliation
Sejal Hathi, MD, and two colleagues had long kicked around the idea of starting a nonprofit group that would center on civic and legal advocacy. Once the COVID-19 pandemic hit, the three friends – who have a mix of legal, medical, and advocacy backgrounds – began chatting by email and through Zoom video meetings about how to make the plan a reality. The new organization – named Beacon – quickly mobilized, assembled their team, and launched a website. Beacon’s first project now aims to highlight and protect the legal rights of medical professionals who speak out about personal protection equipment supply and other matters of public concern related to coronavirus. “There are a flurry of reports coming our way about physicians and nurses, as well as other health care workers, who are for whatever reason being disciplined or retaliated against for simply seeking appropriate safety policies at their workplaces,” Dr. Hathi said. “What we’ve found is that many of them don’t even know what their options look like. Doctors, nurses, health care workers are not the typical type to engage politically, to speak out, [or to] advocate for themselves.” Read more.
COVID-19 ravages the Navajo Nation
The Navajo Nation has the most cases of the COVID-19 virus of any tribe in the United States, and numbers as of May 31, 2020, are 5,348, with 246 confirmed deaths. These devastating numbers, which might be leveling off, are associated with Navajo people having higher-than-average rates of diabetes, heart disease, and cancer. This is compounded with 30%-40% of homes having no electricity or running water, and a poverty rate of about 38%. “We endured and learned from each Naayee, hunger, and death to name a few adversities. The COVID-19 pandemic, or “Big Cough” (Dikos Nitsaa’igii -19 in Navajo language), is a monster confronting the Navajo today. It has had significant impact on our nation and people,” Mary Hasbah Roessel, MD, a Navajo board-certified psychiatrist practicing in Santa Fe, N.M., wrote in a commentary on MDedge. Read more.
Heart pump system authorized for COVID-19 patients
The Food and Drug Administration issued an emergency use authorization (EUA) for use of the Impella RP heart pump system in COVID-19 patients with right heart failure or decompensation. The EUA indication for the Impella RP system is to provide temporary right ventricular support for up to 14 days in critical care patients with a body surface area of at least 1.5 m2 for the treatment of acute right heart failure or decompensation caused by complications related to COVID-19, including pulmonary embolism. Read more.
Deprescribing hypertension meds looks safe for older adults
Some patients aged 80 years or older can potentially cut back on their number of antihypertensive meds, under physician guidance, without an important loss of blood pressure control, researchers concluded based on findings from a randomized multicenter trial. The study, called Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTIMISE), entered “patients in whom the benefits of taking blood pressure-lowering treatments might start to be outweighed by the potential harms,” said James P. Sheppard, PhD, of University of Oxford (England). The report was published in JAMA. Read more.
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Here are the stories our MDedge editors across specialties think you need to know about today:
Addressing racism in the maternal mortality crisis
The emerging racial disparities in COVID-19 incidence and outcomes in the United States are on a collision course with long-standing racial disparities in U.S. maternal care and mortality. “The saying is that ‘the virus doesn’t discriminate,’ but it understands our biases, right? So, the virus takes advantage of the weaknesses in our system,” said Joia A. Crear-Perry, MD, an ob.gyn. and founder and president of the National Birth Equity Collaborative, a New Orleans–based research, training, and advocacy organization working to optimize black maternal and infant health. This article is part of an ongoing feature series on the crisis in maternal mortality in the United States. Here we explore potential solutions for addressing the inequities as proposed by thought leaders and key stakeholders. Read more.
A ‘Beacon’ for physicians, nurses facing retaliation
Sejal Hathi, MD, and two colleagues had long kicked around the idea of starting a nonprofit group that would center on civic and legal advocacy. Once the COVID-19 pandemic hit, the three friends – who have a mix of legal, medical, and advocacy backgrounds – began chatting by email and through Zoom video meetings about how to make the plan a reality. The new organization – named Beacon – quickly mobilized, assembled their team, and launched a website. Beacon’s first project now aims to highlight and protect the legal rights of medical professionals who speak out about personal protection equipment supply and other matters of public concern related to coronavirus. “There are a flurry of reports coming our way about physicians and nurses, as well as other health care workers, who are for whatever reason being disciplined or retaliated against for simply seeking appropriate safety policies at their workplaces,” Dr. Hathi said. “What we’ve found is that many of them don’t even know what their options look like. Doctors, nurses, health care workers are not the typical type to engage politically, to speak out, [or to] advocate for themselves.” Read more.
COVID-19 ravages the Navajo Nation
The Navajo Nation has the most cases of the COVID-19 virus of any tribe in the United States, and numbers as of May 31, 2020, are 5,348, with 246 confirmed deaths. These devastating numbers, which might be leveling off, are associated with Navajo people having higher-than-average rates of diabetes, heart disease, and cancer. This is compounded with 30%-40% of homes having no electricity or running water, and a poverty rate of about 38%. “We endured and learned from each Naayee, hunger, and death to name a few adversities. The COVID-19 pandemic, or “Big Cough” (Dikos Nitsaa’igii -19 in Navajo language), is a monster confronting the Navajo today. It has had significant impact on our nation and people,” Mary Hasbah Roessel, MD, a Navajo board-certified psychiatrist practicing in Santa Fe, N.M., wrote in a commentary on MDedge. Read more.
Heart pump system authorized for COVID-19 patients
The Food and Drug Administration issued an emergency use authorization (EUA) for use of the Impella RP heart pump system in COVID-19 patients with right heart failure or decompensation. The EUA indication for the Impella RP system is to provide temporary right ventricular support for up to 14 days in critical care patients with a body surface area of at least 1.5 m2 for the treatment of acute right heart failure or decompensation caused by complications related to COVID-19, including pulmonary embolism. Read more.
Deprescribing hypertension meds looks safe for older adults
Some patients aged 80 years or older can potentially cut back on their number of antihypertensive meds, under physician guidance, without an important loss of blood pressure control, researchers concluded based on findings from a randomized multicenter trial. The study, called Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTIMISE), entered “patients in whom the benefits of taking blood pressure-lowering treatments might start to be outweighed by the potential harms,” said James P. Sheppard, PhD, of University of Oxford (England). The report was published in JAMA. Read more.
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Low IgG levels in COPD patients linked to increased risk of hospitalization
Among patients with COPD, the presence of hypogammaglobulinemia confers a nearly 30% increased risk of hospitalization, results from a pooled analysis of four studies showed.
“Mechanistic studies are still warranted to better elucidate how IgG and other immunoglobulins, in particular IgA, may contribute to the local airway host defense,” researchers led by Fernando Sergio Leitao Filho, MD, PhD, wrote in a study published in Chest (2020 May 18. doi: 10.1016/j.chest.2020.04.058). “Nevertheless, our results raise the possibility that, in select COPD patients, IgG replacement therapy may be effective in reducing the risk of COPD hospitalizations. Given the growing rate of COPD hospitalization in the U.S. and elsewhere, there is a pressing need for a large well-designed trial to test this hypothesis.”
In an effort to evaluate the effect of IgG levels on the cumulative incidence of COPD hospitalizations, Dr. Leitao Filho, of the University of British Columbia, Vancouver, and colleagues drew from 2,259 patients who participated in four different trials: Azithromycin for Prevention of Exacerbations of COPD (MACRO), Simvastatin for the Prevention of Exacerbations in Moderate and Severe COPD (STATCOPE), the Long-Term Oxygen Treatment Trial (LOTT), and COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE). The mean baseline age of study participants was 66 years, and 641 (28.4%) had hypogammaglobulinemia, which was defined as having a serum IgG levels of less than 7.0 g/L, while the remainder had normal IgG levels.
The pooled meta-analysis, which is believed to be the largest of its kind, revealed that the presence of hypogammaglobulinemia was associated with an incidence of COPD hospitalizations that was 1.29-fold higher than that observed among participants who had normal IgG levels (P = .01). The incidence was even higher among patients with prior COPD admissions (pooled subdistribution hazard ratio, 1.58; P < .01), yet the risk of COPD admissions was similar between IgG groups in patients with no prior hospitalizations (pooled SHR, 1.15; P = .34). Patients with hypogammaglobulinemia also showed significantly higher rates of COPD hospitalizations per person-year, compared with their counterparts who had normal IgG levels (0.48 vs. 0.29, respectively; P < .001.)
The authors acknowledged certain limitations of the study, including the fact that they measured serum IgG levels only at baseline “when participants were clinically stable; thus, the variability of IgG levels in a given individual over time and during the course of an AECOPD [severe acute exacerbation of COPD] is uncertain. Secondly, clinical data on corticosteroid use (formulations, dose, and length of use) were not readily available. However, systemic steroid use (one or more courses due to AECOPD prior to study entry) was accounted for in our analyses.”
The MACRO, STATCOPE, LOTT trials, and the CASCADE cohort were supported by the National Heart, Lung, and Blood Institute; National Institutes of Health; and Department of Health & Human Services. The current study was funded by the Canadian Institutes of Health Research and BC Lung Association. The authors reported having no relevant disclosures.
SOURCE: Leitao Filho SF et al. Chest. 2020 May 18. doi: 10.1016/j.chest.2020.04.058.
Among patients with COPD, the presence of hypogammaglobulinemia confers a nearly 30% increased risk of hospitalization, results from a pooled analysis of four studies showed.
“Mechanistic studies are still warranted to better elucidate how IgG and other immunoglobulins, in particular IgA, may contribute to the local airway host defense,” researchers led by Fernando Sergio Leitao Filho, MD, PhD, wrote in a study published in Chest (2020 May 18. doi: 10.1016/j.chest.2020.04.058). “Nevertheless, our results raise the possibility that, in select COPD patients, IgG replacement therapy may be effective in reducing the risk of COPD hospitalizations. Given the growing rate of COPD hospitalization in the U.S. and elsewhere, there is a pressing need for a large well-designed trial to test this hypothesis.”
In an effort to evaluate the effect of IgG levels on the cumulative incidence of COPD hospitalizations, Dr. Leitao Filho, of the University of British Columbia, Vancouver, and colleagues drew from 2,259 patients who participated in four different trials: Azithromycin for Prevention of Exacerbations of COPD (MACRO), Simvastatin for the Prevention of Exacerbations in Moderate and Severe COPD (STATCOPE), the Long-Term Oxygen Treatment Trial (LOTT), and COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE). The mean baseline age of study participants was 66 years, and 641 (28.4%) had hypogammaglobulinemia, which was defined as having a serum IgG levels of less than 7.0 g/L, while the remainder had normal IgG levels.
The pooled meta-analysis, which is believed to be the largest of its kind, revealed that the presence of hypogammaglobulinemia was associated with an incidence of COPD hospitalizations that was 1.29-fold higher than that observed among participants who had normal IgG levels (P = .01). The incidence was even higher among patients with prior COPD admissions (pooled subdistribution hazard ratio, 1.58; P < .01), yet the risk of COPD admissions was similar between IgG groups in patients with no prior hospitalizations (pooled SHR, 1.15; P = .34). Patients with hypogammaglobulinemia also showed significantly higher rates of COPD hospitalizations per person-year, compared with their counterparts who had normal IgG levels (0.48 vs. 0.29, respectively; P < .001.)
The authors acknowledged certain limitations of the study, including the fact that they measured serum IgG levels only at baseline “when participants were clinically stable; thus, the variability of IgG levels in a given individual over time and during the course of an AECOPD [severe acute exacerbation of COPD] is uncertain. Secondly, clinical data on corticosteroid use (formulations, dose, and length of use) were not readily available. However, systemic steroid use (one or more courses due to AECOPD prior to study entry) was accounted for in our analyses.”
The MACRO, STATCOPE, LOTT trials, and the CASCADE cohort were supported by the National Heart, Lung, and Blood Institute; National Institutes of Health; and Department of Health & Human Services. The current study was funded by the Canadian Institutes of Health Research and BC Lung Association. The authors reported having no relevant disclosures.
SOURCE: Leitao Filho SF et al. Chest. 2020 May 18. doi: 10.1016/j.chest.2020.04.058.
Among patients with COPD, the presence of hypogammaglobulinemia confers a nearly 30% increased risk of hospitalization, results from a pooled analysis of four studies showed.
“Mechanistic studies are still warranted to better elucidate how IgG and other immunoglobulins, in particular IgA, may contribute to the local airway host defense,” researchers led by Fernando Sergio Leitao Filho, MD, PhD, wrote in a study published in Chest (2020 May 18. doi: 10.1016/j.chest.2020.04.058). “Nevertheless, our results raise the possibility that, in select COPD patients, IgG replacement therapy may be effective in reducing the risk of COPD hospitalizations. Given the growing rate of COPD hospitalization in the U.S. and elsewhere, there is a pressing need for a large well-designed trial to test this hypothesis.”
In an effort to evaluate the effect of IgG levels on the cumulative incidence of COPD hospitalizations, Dr. Leitao Filho, of the University of British Columbia, Vancouver, and colleagues drew from 2,259 patients who participated in four different trials: Azithromycin for Prevention of Exacerbations of COPD (MACRO), Simvastatin for the Prevention of Exacerbations in Moderate and Severe COPD (STATCOPE), the Long-Term Oxygen Treatment Trial (LOTT), and COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE). The mean baseline age of study participants was 66 years, and 641 (28.4%) had hypogammaglobulinemia, which was defined as having a serum IgG levels of less than 7.0 g/L, while the remainder had normal IgG levels.
The pooled meta-analysis, which is believed to be the largest of its kind, revealed that the presence of hypogammaglobulinemia was associated with an incidence of COPD hospitalizations that was 1.29-fold higher than that observed among participants who had normal IgG levels (P = .01). The incidence was even higher among patients with prior COPD admissions (pooled subdistribution hazard ratio, 1.58; P < .01), yet the risk of COPD admissions was similar between IgG groups in patients with no prior hospitalizations (pooled SHR, 1.15; P = .34). Patients with hypogammaglobulinemia also showed significantly higher rates of COPD hospitalizations per person-year, compared with their counterparts who had normal IgG levels (0.48 vs. 0.29, respectively; P < .001.)
The authors acknowledged certain limitations of the study, including the fact that they measured serum IgG levels only at baseline “when participants were clinically stable; thus, the variability of IgG levels in a given individual over time and during the course of an AECOPD [severe acute exacerbation of COPD] is uncertain. Secondly, clinical data on corticosteroid use (formulations, dose, and length of use) were not readily available. However, systemic steroid use (one or more courses due to AECOPD prior to study entry) was accounted for in our analyses.”
The MACRO, STATCOPE, LOTT trials, and the CASCADE cohort were supported by the National Heart, Lung, and Blood Institute; National Institutes of Health; and Department of Health & Human Services. The current study was funded by the Canadian Institutes of Health Research and BC Lung Association. The authors reported having no relevant disclosures.
SOURCE: Leitao Filho SF et al. Chest. 2020 May 18. doi: 10.1016/j.chest.2020.04.058.
FROM CHEST
Deprescribing hypertension meds can be safe in older patients
Some patients aged 80 years or older can potentially cut back on their number of antihypertensive meds, under physician guidance, without an important loss of blood pressure (BP) control, researchers concluded based on their randomized multicenter trial.
Deprescription of one of at least two antihypertensive meds in such patients was found noninferior to usual care in keeping systolic BP below 150 mm Hg at 12 weeks, in the study that randomly assigned only patients who were considered appropriate for BP-med reduction by their primary care physicians.
Major trials that have shaped some contemporary hypertension guidelines, notably SPRINT, in general have not included such older patients with hypertension along with other chronic conditions, such as diabetes or a history of stroke. So “it’s difficult to know whether their data are relevant for frail, multimorbid patients. In fact, the guidelines say you should use some clinical judgment when applying the results of SPRINT to the kind of patients seen in clinical practice,” James P. Sheppard, PhD, of University of Oxford (England) said in an interview.
The current study, called Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTIMISE), entered “patients in whom the benefits of taking blood pressure-lowering treatments might start to be outweighed by the potential harms,” Dr. Sheppard said.
The trial is meant to provide something of an otherwise-scant evidence base for how to deprescribe antihypertensive medications, said Dr. Sheppard, who is lead author on the report published May 25 in JAMA.
Of the trial’s 282 patients randomly assigned to the drug-reduction group, 86.4% reached the primary endpoint goal of systolic BP less than 150 mm Hg, compared with 87.7% of the 287 patients on usual care, a difference which in adjusted analysis met the predetermined standard for noninferiority.
The intervention group reduced its number of antihypertensive agents by a mean of 0.6 per patient, which the authors described as “a modest reduction.” However, they noted, drugs that were taken away could be reintroduced as judged necessary by the physicians, yet most of the group sustained their reductions until the end of the 12 weeks.
Had the primary endpoint instead specified a threshold of 130 mm Hg for BP control, which is more consistent with SPRINT and some guidelines in the United States, “the deprescribing strategy would have failed to be considered noninferior to usual care” as calculated by the OPTIMISE authors themselves, observed an accompanying editorial.
The 150 mm Hg threshold chosen by the trialists for the primary endpoint, therefore, “was somewhat of a low bar,” wrote Eric D. Peterson, MD, MPH, of Duke University, Durham, N.C., and Michael W. Rich, MD, of Washington University School of Medicine, St. Louis, Mo.
“Here in the UK it wouldn’t be considered a low bar,” Dr. Sheppard said in an interview. The National Institute for Health and Care Excellence guidelines in Britain “recommends that you treat people over the age of 18 regardless of whether they have any other conditions and to 150 mm Hg systolic.”
The study’s general practitioners, he said, “did what we told them to do, and as a result, two-thirds of the patients were able to reduce their medications. If we had a lower threshold for treatment, it’s possible that more patients might have had medications reintroduced. I think you still could have potentially ended up with a noninferior result.”
Participating physicians were instructed to enroll only “patients who, in their opinion, might potentially benefit from medication reduction due to one or more of the following existing characteristics: polypharmacy, comorbidity, nonadherence or dislike of medicines, or frailty,” the report notes.
They chose which antihypertensives would be dropped for each patient and “were given a medication reduction algorithm to assist with this decision.” Physicians also followed a guide for monitoring for safety issues and were told to reintroduce medications if systolic BP exceeded 150 mm Hg or diastolic BP rose above 90 mm Hg for more than 1 week or in the event of adverse events or signs of accelerated hypertension, the group wrote.
In the deprescription group, the mean systolic BP rose 4.3 points from baseline to 12 weeks, from 129.4 to 133.7 mm Hg. For those given usual care, mean systolic BP went from 130.5 to 130.8 mm Hg. Adjusted, the mean change in systolic BP was 3.4 mm Hg greater (P = .005) in the intervention group. The corresponding adjusted mean change in diastolic BP was a 2.2 mm Hg increase in the intervention group (P = .001).
Although the difference seems minimal, wrote Dr. Peterson and Dr. Rich, “such differences in BP can potentially lead to long-term differences in outcomes at the population level.”
Also, they pointed out, only about 10% of patients screened for enrollment actually entered the study, which brings into question the study’s generalizability, and “patients in the trial had relatively well-controlled BP at baseline.”
Dr. Sheppard said patients in the original screened population, taken from a national database, were directly invited to participate en masse by conventional mail, based on broad inclusion criteria. Far more than the number needed were invited, and nearly all of those excluded from the study had simply not responded to the invitation.
As for greater increases in systolic and diastolic pressures in the deprescribing group, the OPTIMISE authors acknowledged that “caution should be exercised when adopting this approach in routine clinical practice.”
His own view, Dr. Sheppard said, “is that there are some patients who will definitely benefit from intensive blood pressure lowering like you saw in the SPRINT trial. And there’s other patients who will benefit from deprescribing and having a slightly higher target. Those sorts of things very much need to be individualized at the patient level.”
And ideally, he added, clinicians in practice should probably be even more selective in choosing patients for a deprescribing strategy, “and focus on people who are at the highest risk of adverse events.”
Dr. Sheppard has disclosed no relevant financial relationships; disclosures for the other authors are in the report. Dr. Peterson disclosed receiving personal fees from Cerner and Livongo and grants and personal fees from AstraZeneca, Janssen, and Amgen; Dr. Rick has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Some patients aged 80 years or older can potentially cut back on their number of antihypertensive meds, under physician guidance, without an important loss of blood pressure (BP) control, researchers concluded based on their randomized multicenter trial.
Deprescription of one of at least two antihypertensive meds in such patients was found noninferior to usual care in keeping systolic BP below 150 mm Hg at 12 weeks, in the study that randomly assigned only patients who were considered appropriate for BP-med reduction by their primary care physicians.
Major trials that have shaped some contemporary hypertension guidelines, notably SPRINT, in general have not included such older patients with hypertension along with other chronic conditions, such as diabetes or a history of stroke. So “it’s difficult to know whether their data are relevant for frail, multimorbid patients. In fact, the guidelines say you should use some clinical judgment when applying the results of SPRINT to the kind of patients seen in clinical practice,” James P. Sheppard, PhD, of University of Oxford (England) said in an interview.
The current study, called Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTIMISE), entered “patients in whom the benefits of taking blood pressure-lowering treatments might start to be outweighed by the potential harms,” Dr. Sheppard said.
The trial is meant to provide something of an otherwise-scant evidence base for how to deprescribe antihypertensive medications, said Dr. Sheppard, who is lead author on the report published May 25 in JAMA.
Of the trial’s 282 patients randomly assigned to the drug-reduction group, 86.4% reached the primary endpoint goal of systolic BP less than 150 mm Hg, compared with 87.7% of the 287 patients on usual care, a difference which in adjusted analysis met the predetermined standard for noninferiority.
The intervention group reduced its number of antihypertensive agents by a mean of 0.6 per patient, which the authors described as “a modest reduction.” However, they noted, drugs that were taken away could be reintroduced as judged necessary by the physicians, yet most of the group sustained their reductions until the end of the 12 weeks.
Had the primary endpoint instead specified a threshold of 130 mm Hg for BP control, which is more consistent with SPRINT and some guidelines in the United States, “the deprescribing strategy would have failed to be considered noninferior to usual care” as calculated by the OPTIMISE authors themselves, observed an accompanying editorial.
The 150 mm Hg threshold chosen by the trialists for the primary endpoint, therefore, “was somewhat of a low bar,” wrote Eric D. Peterson, MD, MPH, of Duke University, Durham, N.C., and Michael W. Rich, MD, of Washington University School of Medicine, St. Louis, Mo.
“Here in the UK it wouldn’t be considered a low bar,” Dr. Sheppard said in an interview. The National Institute for Health and Care Excellence guidelines in Britain “recommends that you treat people over the age of 18 regardless of whether they have any other conditions and to 150 mm Hg systolic.”
The study’s general practitioners, he said, “did what we told them to do, and as a result, two-thirds of the patients were able to reduce their medications. If we had a lower threshold for treatment, it’s possible that more patients might have had medications reintroduced. I think you still could have potentially ended up with a noninferior result.”
Participating physicians were instructed to enroll only “patients who, in their opinion, might potentially benefit from medication reduction due to one or more of the following existing characteristics: polypharmacy, comorbidity, nonadherence or dislike of medicines, or frailty,” the report notes.
They chose which antihypertensives would be dropped for each patient and “were given a medication reduction algorithm to assist with this decision.” Physicians also followed a guide for monitoring for safety issues and were told to reintroduce medications if systolic BP exceeded 150 mm Hg or diastolic BP rose above 90 mm Hg for more than 1 week or in the event of adverse events or signs of accelerated hypertension, the group wrote.
In the deprescription group, the mean systolic BP rose 4.3 points from baseline to 12 weeks, from 129.4 to 133.7 mm Hg. For those given usual care, mean systolic BP went from 130.5 to 130.8 mm Hg. Adjusted, the mean change in systolic BP was 3.4 mm Hg greater (P = .005) in the intervention group. The corresponding adjusted mean change in diastolic BP was a 2.2 mm Hg increase in the intervention group (P = .001).
Although the difference seems minimal, wrote Dr. Peterson and Dr. Rich, “such differences in BP can potentially lead to long-term differences in outcomes at the population level.”
Also, they pointed out, only about 10% of patients screened for enrollment actually entered the study, which brings into question the study’s generalizability, and “patients in the trial had relatively well-controlled BP at baseline.”
Dr. Sheppard said patients in the original screened population, taken from a national database, were directly invited to participate en masse by conventional mail, based on broad inclusion criteria. Far more than the number needed were invited, and nearly all of those excluded from the study had simply not responded to the invitation.
As for greater increases in systolic and diastolic pressures in the deprescribing group, the OPTIMISE authors acknowledged that “caution should be exercised when adopting this approach in routine clinical practice.”
His own view, Dr. Sheppard said, “is that there are some patients who will definitely benefit from intensive blood pressure lowering like you saw in the SPRINT trial. And there’s other patients who will benefit from deprescribing and having a slightly higher target. Those sorts of things very much need to be individualized at the patient level.”
And ideally, he added, clinicians in practice should probably be even more selective in choosing patients for a deprescribing strategy, “and focus on people who are at the highest risk of adverse events.”
Dr. Sheppard has disclosed no relevant financial relationships; disclosures for the other authors are in the report. Dr. Peterson disclosed receiving personal fees from Cerner and Livongo and grants and personal fees from AstraZeneca, Janssen, and Amgen; Dr. Rick has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Some patients aged 80 years or older can potentially cut back on their number of antihypertensive meds, under physician guidance, without an important loss of blood pressure (BP) control, researchers concluded based on their randomized multicenter trial.
Deprescription of one of at least two antihypertensive meds in such patients was found noninferior to usual care in keeping systolic BP below 150 mm Hg at 12 weeks, in the study that randomly assigned only patients who were considered appropriate for BP-med reduction by their primary care physicians.
Major trials that have shaped some contemporary hypertension guidelines, notably SPRINT, in general have not included such older patients with hypertension along with other chronic conditions, such as diabetes or a history of stroke. So “it’s difficult to know whether their data are relevant for frail, multimorbid patients. In fact, the guidelines say you should use some clinical judgment when applying the results of SPRINT to the kind of patients seen in clinical practice,” James P. Sheppard, PhD, of University of Oxford (England) said in an interview.
The current study, called Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTIMISE), entered “patients in whom the benefits of taking blood pressure-lowering treatments might start to be outweighed by the potential harms,” Dr. Sheppard said.
The trial is meant to provide something of an otherwise-scant evidence base for how to deprescribe antihypertensive medications, said Dr. Sheppard, who is lead author on the report published May 25 in JAMA.
Of the trial’s 282 patients randomly assigned to the drug-reduction group, 86.4% reached the primary endpoint goal of systolic BP less than 150 mm Hg, compared with 87.7% of the 287 patients on usual care, a difference which in adjusted analysis met the predetermined standard for noninferiority.
The intervention group reduced its number of antihypertensive agents by a mean of 0.6 per patient, which the authors described as “a modest reduction.” However, they noted, drugs that were taken away could be reintroduced as judged necessary by the physicians, yet most of the group sustained their reductions until the end of the 12 weeks.
Had the primary endpoint instead specified a threshold of 130 mm Hg for BP control, which is more consistent with SPRINT and some guidelines in the United States, “the deprescribing strategy would have failed to be considered noninferior to usual care” as calculated by the OPTIMISE authors themselves, observed an accompanying editorial.
The 150 mm Hg threshold chosen by the trialists for the primary endpoint, therefore, “was somewhat of a low bar,” wrote Eric D. Peterson, MD, MPH, of Duke University, Durham, N.C., and Michael W. Rich, MD, of Washington University School of Medicine, St. Louis, Mo.
“Here in the UK it wouldn’t be considered a low bar,” Dr. Sheppard said in an interview. The National Institute for Health and Care Excellence guidelines in Britain “recommends that you treat people over the age of 18 regardless of whether they have any other conditions and to 150 mm Hg systolic.”
The study’s general practitioners, he said, “did what we told them to do, and as a result, two-thirds of the patients were able to reduce their medications. If we had a lower threshold for treatment, it’s possible that more patients might have had medications reintroduced. I think you still could have potentially ended up with a noninferior result.”
Participating physicians were instructed to enroll only “patients who, in their opinion, might potentially benefit from medication reduction due to one or more of the following existing characteristics: polypharmacy, comorbidity, nonadherence or dislike of medicines, or frailty,” the report notes.
They chose which antihypertensives would be dropped for each patient and “were given a medication reduction algorithm to assist with this decision.” Physicians also followed a guide for monitoring for safety issues and were told to reintroduce medications if systolic BP exceeded 150 mm Hg or diastolic BP rose above 90 mm Hg for more than 1 week or in the event of adverse events or signs of accelerated hypertension, the group wrote.
In the deprescription group, the mean systolic BP rose 4.3 points from baseline to 12 weeks, from 129.4 to 133.7 mm Hg. For those given usual care, mean systolic BP went from 130.5 to 130.8 mm Hg. Adjusted, the mean change in systolic BP was 3.4 mm Hg greater (P = .005) in the intervention group. The corresponding adjusted mean change in diastolic BP was a 2.2 mm Hg increase in the intervention group (P = .001).
Although the difference seems minimal, wrote Dr. Peterson and Dr. Rich, “such differences in BP can potentially lead to long-term differences in outcomes at the population level.”
Also, they pointed out, only about 10% of patients screened for enrollment actually entered the study, which brings into question the study’s generalizability, and “patients in the trial had relatively well-controlled BP at baseline.”
Dr. Sheppard said patients in the original screened population, taken from a national database, were directly invited to participate en masse by conventional mail, based on broad inclusion criteria. Far more than the number needed were invited, and nearly all of those excluded from the study had simply not responded to the invitation.
As for greater increases in systolic and diastolic pressures in the deprescribing group, the OPTIMISE authors acknowledged that “caution should be exercised when adopting this approach in routine clinical practice.”
His own view, Dr. Sheppard said, “is that there are some patients who will definitely benefit from intensive blood pressure lowering like you saw in the SPRINT trial. And there’s other patients who will benefit from deprescribing and having a slightly higher target. Those sorts of things very much need to be individualized at the patient level.”
And ideally, he added, clinicians in practice should probably be even more selective in choosing patients for a deprescribing strategy, “and focus on people who are at the highest risk of adverse events.”
Dr. Sheppard has disclosed no relevant financial relationships; disclosures for the other authors are in the report. Dr. Peterson disclosed receiving personal fees from Cerner and Livongo and grants and personal fees from AstraZeneca, Janssen, and Amgen; Dr. Rick has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.