Don’t wait to give patients with first-episode psychosis long-acting injectable formulations of second-generation antipsychotics, according to Henry A. Nasrallah, MD.

Many clinicians wait to use long-acting injectables (LAIs) until the patient has experienced multiple relapses, but using them after the first discharge may help prevent future relapse, Dr. Nasrallah, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, said at the virtual Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education.

LAIs and clozapine are “vastly underutilized” after the first discharge, he noted. “I really encourage everybody to use them without hesitation as early as possible.”

In patients with first-episode psychosis, “the most important thing, in my opinion, is to start establishing a therapeutic alliance with the patient from day one,” Dr. Nasrallah said. “It’s always important in psychiatry, but it’s particularly important for first-episode psychosis.”

These patients respond to low doses of antipsychotics and should not be given first-generation antipsychotics because of a risk for acute extrapyramidal symptoms, tardive dyskinesia, and neurotoxicity.

“I usually select an antipsychotic that is extended release and also available as a long-acting injectable formulation,” Dr. Nasrallah said, noting that it helps when he gives a patient a long-acting injectable right after discharge. During hospitalization, Dr. Nasrallah said, he educates the patient and their family about psychosis, treatment, how psychosis affects the brain, and adherence to treatment.

“The primary goal, of course, is to achieve remission and very importantly, to prevent a second episode,” he said. “This is the golden opportunity for us psychiatrists to prevent the patient from relapsing again and again. That is the reason for disability and for brain damage, because every psychotic episode destroys brain tissue. That is why I am very eager to not only achieve a remission in the first episode but also to position the patient to be protected after discharge by giving them long-acting injectable.”

After a clinician performs a full workup to rule out substance use or a general medical condition inducing first-episode psychosis, Dr. Nasrallah recommends paliperidone extended-release (ER), given to patients in the morning because of its tolerability and the availability of an LAI version of the drug. “I start with 3 mg a day; that’s the lowest dose,” he said. “If the patient is very sick and agitated, I might go to 6 mg a day, which is actually a very good dose for first-episode patients, and it’s still quite well tolerated.”

Oral or injectable lorazepam taken as needed may be given to a patient with first-episode psychosis with agitation. For patients who manifest akathisia, twice or thrice daily propranolol at dose of 10-20 mg can be used off label, he said. Dr. Nasrallah also recommended twice-daily omega 3 at a dose of 1,000 mg or N-acetylcysteine at a dose of 600 mg per day as supplements.

“They’re not approved by the [Food and Drug Administration] for first-episode psychosis, but there are numerous publications in the literature by academic psychiatrists showing that they are quite beneficial, and they reduce the two destructive processes during psychosis, which are neuroinflammation and oxidative stress, or free radicals,” he said. “Those two supplements can help in the acute phase of the illness.”

Another option for clinicians is to begin a patient with first-episode psychosis on oral aripiprazole at a dose of 5 mg per day for 2 days, increasing the dose to 7.5 mg per day for 2 days, then increasing to 10 mg per day. “It is not extended-release, so you have to start with low doses to protect the patient from side effects,” Dr. Nasrallah explained. “Some patients may need 15 or 20 [mg], but most first-episode patients may do well on 10 [mg] without risking side effects.”
 

Planning for discharge

Patients who tolerate aripiprazole can start the long-acting aripiprazole lauroxil at discharge, and clinicians have two options to choose from. One formulation “requires 2 weeks of oral supplementation, which you can do in the hospital if you start the patient on oral aripiprazole, and then you can give that injection prior to discharge.” Another option involves giving the patient “any antipsychotic you like and then switch[ing] the patient to aripiprazole lauroxil. The full dose can be given without oral supplementation on the day of discharge.”

Dr. Nasrallah emphasized the use of LAIs in patients discharged for first-episode psychosis. In a study published in JAMA Psychiatry, researchers found use of LAI risperidone in patients with first-episode psychosis significantly reduced the risk of psychotic exacerbation and relapse compared with patients who were given oral risperidone (JAMA Psychiatry. 2015;72:822-9).

“This kind of well-done study shows you that you can do a great job protecting your patient from the very beginning by giving long-acting injectables,” Dr. Nasrallah explained. “That’s why you have to develop rapport with the patient. That’s why you have to convince the patient to take the injectable, and that’s why you have to educate the patient about the hazards of psychosis to the brain, and the fact that it’s very hard to remember to take the pills, because the illness itself can interfere with that due to cognitive impairment [and] negative symptoms.” Another reason for nonadherence is that the patients might not believe they are sick, he added.

After 2 or 3 weeks, if a patient with first-episode psychosis has a minimal response or does not response at all to an LAI, clozapine is an “aggressive” option that may help nonresponders. For patients with schizophrenia, “about 65%-70% would respond to a dopamine antagonist and the remaining 30% are going to need clozapine sooner or later,” Dr. Nasrallah said. “For clozapine after one or two failures [on LAIs] with an adequate dose and adequate duration, don’t wait. Give the patient clozapine, give them an opportunity to regain their life. I’ve seen some very gratifying results with clozapine in those who respond to it.

“The outcome of schizophrenia may be far less malignant than the perception out there if we actually ensure adherence very early and manage the first-episode aggressively, like cardiologists manage the first heart attack,” he said. “[Cardiologists] do everything in their power to protect the patient from a second heart attack, and I regard psychosis as a ‘brain attack.’ ”

Global Academy and this news organization are owned by the same parent company. Dr. Nasrallah reported that he has received research grants from Acadia; served as a consultant for Acadia, Alkermes, Allergan, Janssen, Otsuka, Indivior, Intracellular, Neurocrine, Sunovion, Teva, and Boehringer-Ingelheim; and is on the speakers bureau for Acadia, Alkermes, Allergan, Janssen, Otsuka, Indivior, Intracellular, Neurocrine, Noven, Sunovion, and Teva.

Don’t wait to give patients with first-episode psychosis long-acting injectable formulations of second-generation antipsychotics, according to Henry A. Nasrallah, MD.

Many clinicians wait to use long-acting injectables (LAIs) until the patient has experienced multiple relapses, but using them after the first discharge may help prevent future relapse, Dr. Nasrallah, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, said at the virtual Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education.

LAIs and clozapine are “vastly underutilized” after the first discharge, he noted. “I really encourage everybody to use them without hesitation as early as possible.”

In patients with first-episode psychosis, “the most important thing, in my opinion, is to start establishing a therapeutic alliance with the patient from day one,” Dr. Nasrallah said. “It’s always important in psychiatry, but it’s particularly important for first-episode psychosis.”

These patients respond to low doses of antipsychotics and should not be given first-generation antipsychotics because of a risk for acute extrapyramidal symptoms, tardive dyskinesia, and neurotoxicity.

“I usually select an antipsychotic that is extended release and also available as a long-acting injectable formulation,” Dr. Nasrallah said, noting that it helps when he gives a patient a long-acting injectable right after discharge. During hospitalization, Dr. Nasrallah said, he educates the patient and their family about psychosis, treatment, how psychosis affects the brain, and adherence to treatment.

“The primary goal, of course, is to achieve remission and very importantly, to prevent a second episode,” he said. “This is the golden opportunity for us psychiatrists to prevent the patient from relapsing again and again. That is the reason for disability and for brain damage, because every psychotic episode destroys brain tissue. That is why I am very eager to not only achieve a remission in the first episode but also to position the patient to be protected after discharge by giving them long-acting injectable.”

After a clinician performs a full workup to rule out substance use or a general medical condition inducing first-episode psychosis, Dr. Nasrallah recommends paliperidone extended-release (ER), given to patients in the morning because of its tolerability and the availability of an LAI version of the drug. “I start with 3 mg a day; that’s the lowest dose,” he said. “If the patient is very sick and agitated, I might go to 6 mg a day, which is actually a very good dose for first-episode patients, and it’s still quite well tolerated.”

Oral or injectable lorazepam taken as needed may be given to a patient with first-episode psychosis with agitation. For patients who manifest akathisia, twice or thrice daily propranolol at dose of 10-20 mg can be used off label, he said. Dr. Nasrallah also recommended twice-daily omega 3 at a dose of 1,000 mg or N-acetylcysteine at a dose of 600 mg per day as supplements.

“They’re not approved by the [Food and Drug Administration] for first-episode psychosis, but there are numerous publications in the literature by academic psychiatrists showing that they are quite beneficial, and they reduce the two destructive processes during psychosis, which are neuroinflammation and oxidative stress, or free radicals,” he said. “Those two supplements can help in the acute phase of the illness.”

Another option for clinicians is to begin a patient with first-episode psychosis on oral aripiprazole at a dose of 5 mg per day for 2 days, increasing the dose to 7.5 mg per day for 2 days, then increasing to 10 mg per day. “It is not extended-release, so you have to start with low doses to protect the patient from side effects,” Dr. Nasrallah explained. “Some patients may need 15 or 20 [mg], but most first-episode patients may do well on 10 [mg] without risking side effects.”
 

Planning for discharge

Patients who tolerate aripiprazole can start the long-acting aripiprazole lauroxil at discharge, and clinicians have two options to choose from. One formulation “requires 2 weeks of oral supplementation, which you can do in the hospital if you start the patient on oral aripiprazole, and then you can give that injection prior to discharge.” Another option involves giving the patient “any antipsychotic you like and then switch[ing] the patient to aripiprazole lauroxil. The full dose can be given without oral supplementation on the day of discharge.”

Dr. Nasrallah emphasized the use of LAIs in patients discharged for first-episode psychosis. In a study published in JAMA Psychiatry, researchers found use of LAI risperidone in patients with first-episode psychosis significantly reduced the risk of psychotic exacerbation and relapse compared with patients who were given oral risperidone (JAMA Psychiatry. 2015;72:822-9).

“This kind of well-done study shows you that you can do a great job protecting your patient from the very beginning by giving long-acting injectables,” Dr. Nasrallah explained. “That’s why you have to develop rapport with the patient. That’s why you have to convince the patient to take the injectable, and that’s why you have to educate the patient about the hazards of psychosis to the brain, and the fact that it’s very hard to remember to take the pills, because the illness itself can interfere with that due to cognitive impairment [and] negative symptoms.” Another reason for nonadherence is that the patients might not believe they are sick, he added.

After 2 or 3 weeks, if a patient with first-episode psychosis has a minimal response or does not response at all to an LAI, clozapine is an “aggressive” option that may help nonresponders. For patients with schizophrenia, “about 65%-70% would respond to a dopamine antagonist and the remaining 30% are going to need clozapine sooner or later,” Dr. Nasrallah said. “For clozapine after one or two failures [on LAIs] with an adequate dose and adequate duration, don’t wait. Give the patient clozapine, give them an opportunity to regain their life. I’ve seen some very gratifying results with clozapine in those who respond to it.

“The outcome of schizophrenia may be far less malignant than the perception out there if we actually ensure adherence very early and manage the first-episode aggressively, like cardiologists manage the first heart attack,” he said. “[Cardiologists] do everything in their power to protect the patient from a second heart attack, and I regard psychosis as a ‘brain attack.’ ”

Global Academy and this news organization are owned by the same parent company. Dr. Nasrallah reported that he has received research grants from Acadia; served as a consultant for Acadia, Alkermes, Allergan, Janssen, Otsuka, Indivior, Intracellular, Neurocrine, Sunovion, Teva, and Boehringer-Ingelheim; and is on the speakers bureau for Acadia, Alkermes, Allergan, Janssen, Otsuka, Indivior, Intracellular, Neurocrine, Noven, Sunovion, and Teva.

Don’t wait to give patients with first-episode psychosis long-acting injectable formulations of second-generation antipsychotics, according to Henry A. Nasrallah, MD.

Many clinicians wait to use long-acting injectables (LAIs) until the patient has experienced multiple relapses, but using them after the first discharge may help prevent future relapse, Dr. Nasrallah, professor of psychiatry, neurology, and neuroscience at the University of Cincinnati, said at the virtual Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education.

LAIs and clozapine are “vastly underutilized” after the first discharge, he noted. “I really encourage everybody to use them without hesitation as early as possible.”

In patients with first-episode psychosis, “the most important thing, in my opinion, is to start establishing a therapeutic alliance with the patient from day one,” Dr. Nasrallah said. “It’s always important in psychiatry, but it’s particularly important for first-episode psychosis.”

These patients respond to low doses of antipsychotics and should not be given first-generation antipsychotics because of a risk for acute extrapyramidal symptoms, tardive dyskinesia, and neurotoxicity.

“I usually select an antipsychotic that is extended release and also available as a long-acting injectable formulation,” Dr. Nasrallah said, noting that it helps when he gives a patient a long-acting injectable right after discharge. During hospitalization, Dr. Nasrallah said, he educates the patient and their family about psychosis, treatment, how psychosis affects the brain, and adherence to treatment.

“The primary goal, of course, is to achieve remission and very importantly, to prevent a second episode,” he said. “This is the golden opportunity for us psychiatrists to prevent the patient from relapsing again and again. That is the reason for disability and for brain damage, because every psychotic episode destroys brain tissue. That is why I am very eager to not only achieve a remission in the first episode but also to position the patient to be protected after discharge by giving them long-acting injectable.”

After a clinician performs a full workup to rule out substance use or a general medical condition inducing first-episode psychosis, Dr. Nasrallah recommends paliperidone extended-release (ER), given to patients in the morning because of its tolerability and the availability of an LAI version of the drug. “I start with 3 mg a day; that’s the lowest dose,” he said. “If the patient is very sick and agitated, I might go to 6 mg a day, which is actually a very good dose for first-episode patients, and it’s still quite well tolerated.”

Oral or injectable lorazepam taken as needed may be given to a patient with first-episode psychosis with agitation. For patients who manifest akathisia, twice or thrice daily propranolol at dose of 10-20 mg can be used off label, he said. Dr. Nasrallah also recommended twice-daily omega 3 at a dose of 1,000 mg or N-acetylcysteine at a dose of 600 mg per day as supplements.

“They’re not approved by the [Food and Drug Administration] for first-episode psychosis, but there are numerous publications in the literature by academic psychiatrists showing that they are quite beneficial, and they reduce the two destructive processes during psychosis, which are neuroinflammation and oxidative stress, or free radicals,” he said. “Those two supplements can help in the acute phase of the illness.”

Another option for clinicians is to begin a patient with first-episode psychosis on oral aripiprazole at a dose of 5 mg per day for 2 days, increasing the dose to 7.5 mg per day for 2 days, then increasing to 10 mg per day. “It is not extended-release, so you have to start with low doses to protect the patient from side effects,” Dr. Nasrallah explained. “Some patients may need 15 or 20 [mg], but most first-episode patients may do well on 10 [mg] without risking side effects.”
 

Planning for discharge

Patients who tolerate aripiprazole can start the long-acting aripiprazole lauroxil at discharge, and clinicians have two options to choose from. One formulation “requires 2 weeks of oral supplementation, which you can do in the hospital if you start the patient on oral aripiprazole, and then you can give that injection prior to discharge.” Another option involves giving the patient “any antipsychotic you like and then switch[ing] the patient to aripiprazole lauroxil. The full dose can be given without oral supplementation on the day of discharge.”

Dr. Nasrallah emphasized the use of LAIs in patients discharged for first-episode psychosis. In a study published in JAMA Psychiatry, researchers found use of LAI risperidone in patients with first-episode psychosis significantly reduced the risk of psychotic exacerbation and relapse compared with patients who were given oral risperidone (JAMA Psychiatry. 2015;72:822-9).

“This kind of well-done study shows you that you can do a great job protecting your patient from the very beginning by giving long-acting injectables,” Dr. Nasrallah explained. “That’s why you have to develop rapport with the patient. That’s why you have to convince the patient to take the injectable, and that’s why you have to educate the patient about the hazards of psychosis to the brain, and the fact that it’s very hard to remember to take the pills, because the illness itself can interfere with that due to cognitive impairment [and] negative symptoms.” Another reason for nonadherence is that the patients might not believe they are sick, he added.

After 2 or 3 weeks, if a patient with first-episode psychosis has a minimal response or does not response at all to an LAI, clozapine is an “aggressive” option that may help nonresponders. For patients with schizophrenia, “about 65%-70% would respond to a dopamine antagonist and the remaining 30% are going to need clozapine sooner or later,” Dr. Nasrallah said. “For clozapine after one or two failures [on LAIs] with an adequate dose and adequate duration, don’t wait. Give the patient clozapine, give them an opportunity to regain their life. I’ve seen some very gratifying results with clozapine in those who respond to it.

“The outcome of schizophrenia may be far less malignant than the perception out there if we actually ensure adherence very early and manage the first-episode aggressively, like cardiologists manage the first heart attack,” he said. “[Cardiologists] do everything in their power to protect the patient from a second heart attack, and I regard psychosis as a ‘brain attack.’ ”

Global Academy and this news organization are owned by the same parent company. Dr. Nasrallah reported that he has received research grants from Acadia; served as a consultant for Acadia, Alkermes, Allergan, Janssen, Otsuka, Indivior, Intracellular, Neurocrine, Sunovion, Teva, and Boehringer-Ingelheim; and is on the speakers bureau for Acadia, Alkermes, Allergan, Janssen, Otsuka, Indivior, Intracellular, Neurocrine, Noven, Sunovion, and Teva.

During the COVID-19 pandemic, nearly all primary care clinicians have been engaged in telemedicine. Telemedicine visits have certain ­advantages—especially convenience to patients. But there are dangers, as well. The ­following true story illustrates one of the important dangers.

The outcome might have been much different if there had been further delay.

“I had an interesting experience late last week that reminded me how important it is to be one’s own advocate in health care. I cut my foot going for an outdoor swim. It got infected so I had a telehealth visit with a physician assistant. She prescribed an antibiotic. The next day, Friday, the swelling and redness were rapidly moving up my foot. I called the office twice. I sent a picture of my foot. No call-back.

I texted my podiatrist the same photo with the question: Do I sit tight or go to the ED? A half hour later, he called me: Go to the hospital. I did. I got IV antibiotics and a tetanus shot. I was also told by the ED doc that my itchy palms were a reaction to the antibiotic I’d been prescribed, and that the physician assistant shouldn’t have prescribed a sulfa drug, given that my chart listed a past reaction to sulfa eye drops.”

The patient is a top-flight triathlete and the editor of JFP, Marya Ostrowski. She was gracious to share her story with us, and she did recover uneventfully, although the outcome might have been much different if there had been further delay.

Her story has 3 important teaching points:

1. We must ensure that our office phone system prioritizes calls from patients. If there is any hint that the problem is urgent, it must be handled immediately.^a
2. CAREFULLY check for allergies before prescribing medication. Perhaps the physician assistant did check the medication list and noted an allergy to eye drops but did not zero in on the fact that they were sulfa. Medication allergy lists can be misleading because they can be too specific. Had her medication allergy been listed as “sulfa medications,” rather than the specific eye drop, the physician assistant may have recognized the allergy correctly.
3. Finally, and most important in my estimation: Patients must act as their own health advocates. Patients are the final common barrier against medical ­errors and we must learn to listen to them carefully. We should encourage our patients to report problems and irregularities in care.

^a The physician assistant returned Marya’s calls at 4:30 that Friday afternoon—8 hours after her first outreach. Marya was already in an ED bed and the nursing staff was starting her IV.

During the COVID-19 pandemic, nearly all primary care clinicians have been engaged in telemedicine. Telemedicine visits have certain ­advantages—especially convenience to patients. But there are dangers, as well. The ­following true story illustrates one of the important dangers.

The outcome might have been much different if there had been further delay.

“I had an interesting experience late last week that reminded me how important it is to be one’s own advocate in health care. I cut my foot going for an outdoor swim. It got infected so I had a telehealth visit with a physician assistant. She prescribed an antibiotic. The next day, Friday, the swelling and redness were rapidly moving up my foot. I called the office twice. I sent a picture of my foot. No call-back.

I texted my podiatrist the same photo with the question: Do I sit tight or go to the ED? A half hour later, he called me: Go to the hospital. I did. I got IV antibiotics and a tetanus shot. I was also told by the ED doc that my itchy palms were a reaction to the antibiotic I’d been prescribed, and that the physician assistant shouldn’t have prescribed a sulfa drug, given that my chart listed a past reaction to sulfa eye drops.”

The patient is a top-flight triathlete and the editor of JFP, Marya Ostrowski. She was gracious to share her story with us, and she did recover uneventfully, although the outcome might have been much different if there had been further delay.

Her story has 3 important teaching points:

1. We must ensure that our office phone system prioritizes calls from patients. If there is any hint that the problem is urgent, it must be handled immediately.^a
2. CAREFULLY check for allergies before prescribing medication. Perhaps the physician assistant did check the medication list and noted an allergy to eye drops but did not zero in on the fact that they were sulfa. Medication allergy lists can be misleading because they can be too specific. Had her medication allergy been listed as “sulfa medications,” rather than the specific eye drop, the physician assistant may have recognized the allergy correctly.
3. Finally, and most important in my estimation: Patients must act as their own health advocates. Patients are the final common barrier against medical ­errors and we must learn to listen to them carefully. We should encourage our patients to report problems and irregularities in care.

^a The physician assistant returned Marya’s calls at 4:30 that Friday afternoon—8 hours after her first outreach. Marya was already in an ED bed and the nursing staff was starting her IV.

During the COVID-19 pandemic, nearly all primary care clinicians have been engaged in telemedicine. Telemedicine visits have certain ­advantages—especially convenience to patients. But there are dangers, as well. The ­following true story illustrates one of the important dangers.

The outcome might have been much different if there had been further delay.

“I had an interesting experience late last week that reminded me how important it is to be one’s own advocate in health care. I cut my foot going for an outdoor swim. It got infected so I had a telehealth visit with a physician assistant. She prescribed an antibiotic. The next day, Friday, the swelling and redness were rapidly moving up my foot. I called the office twice. I sent a picture of my foot. No call-back.

I texted my podiatrist the same photo with the question: Do I sit tight or go to the ED? A half hour later, he called me: Go to the hospital. I did. I got IV antibiotics and a tetanus shot. I was also told by the ED doc that my itchy palms were a reaction to the antibiotic I’d been prescribed, and that the physician assistant shouldn’t have prescribed a sulfa drug, given that my chart listed a past reaction to sulfa eye drops.”

The patient is a top-flight triathlete and the editor of JFP, Marya Ostrowski. She was gracious to share her story with us, and she did recover uneventfully, although the outcome might have been much different if there had been further delay.

Her story has 3 important teaching points:

1. We must ensure that our office phone system prioritizes calls from patients. If there is any hint that the problem is urgent, it must be handled immediately.^a
2. CAREFULLY check for allergies before prescribing medication. Perhaps the physician assistant did check the medication list and noted an allergy to eye drops but did not zero in on the fact that they were sulfa. Medication allergy lists can be misleading because they can be too specific. Had her medication allergy been listed as “sulfa medications,” rather than the specific eye drop, the physician assistant may have recognized the allergy correctly.
3. Finally, and most important in my estimation: Patients must act as their own health advocates. Patients are the final common barrier against medical ­errors and we must learn to listen to them carefully. We should encourage our patients to report problems and irregularities in care.

^a The physician assistant returned Marya’s calls at 4:30 that Friday afternoon—8 hours after her first outreach. Marya was already in an ED bed and the nursing staff was starting her IV.

A draft guideline for the management of patients with juvenile idiopathic arthritis reflects changes in therapy away from reliance on NSAIDs and glucocorticoids and toward earlier introduction of biologic disease-modifying antirheumatic drugs (DMARDs).

The guideline, described in an oral session during the virtual annual meeting of the American College of Rheumatology, contains weighted recommendations for the treatment of JIA, including therapeutic approaches for oligoarthritis, tempromandibular joint (TMJ) arthritis, and systemic JIA (sJIA). The recommendations were the result of expert consensus and literature review using GRADE methodology, with input from clinicians, as well as patients and parents.

“Although evidence remains very low and many recommendations are conditional, the inclusion of parents and patients in the decision-making process strengthens their validity,” said project principal investigator Karen Onel, MD, of the Hospital for Special Surgery and Weill Cornell Medicine, both in New York.

She added that “it’s important to remember that these guidelines are meant to be guidelines; clinical care remains in the hands of the provider and the patient, and we endorse the importance of shared decision-making in coming to these agreements.”

Dr. Onel outlined key recommendations for patients for whom a diagnosis of JIA has already been made and who have no contraindications to recommended therapies. The strength of the recommendations (strong or conditional) and evidence levels (high, moderate, low, very low) were also reported.
 

Oligoarthritis with fewer than five involved joints

For these patients, intra-articular glucocorticoids (IAGC) are recommended as a part of initial therapy (strong, very low evidence).

Triamcinolone acetonide is the preferred agent in this situation (strong, low evidence).

The guideline also has a conditional recommendation (very low evidence) for a trial of consistent NSAIDS as part of initial therapy and a conditional recommendation against oral glucocorticoids for initial therapy (very low evidence).

Patients with no or incomplete responses or intolerance to NSAIDS and/or IAGC may be tried on a nonbiologic DMARD (strong, very low evidence), with methotrexate as the preferred agent (conditional, low evidence).

If the patient has no response or an inadequate response to at least one nonbiologic DMARD, biologic DMARDs are recommended (strong, very low evidence), with no preferred agent.

The guideline also conditionally recommends (all with very low evidence) using risk factors and validated disease activity measures to guide treatment decisions, as well as imaging guidance of joints that are difficult to access or to localize the distribution of inflammation.
 

TMJ arthritis

For patients with temporomandibular joint arthritis, isolated or not, IAGCs are conditionally recommended as part of initial therapy (very low evidence) with no preferred agents. The guideline also conditionally recommends in favor of a trial of consistent NSAIDs, and against oral glucocorticoids in initial therapy (evidence for both very low).

Recommendations for patients with TMJ with no or an incomplete response to the initial therapy are the same as for patients with oligoarthritis, with no preferred agent.
 

sJIA without macrophage activation syndrome

For patients with sJIA without macrophage activation syndrome (MAS), NSAIDS are conditionally recommended as initial monotherapy (very low evidence). Biologic DMARDS (including interleukin-1 and IL-6 inhibitors) are also recommended, conditionally, as initial monotherapy, with no preferred agent.

If the patient has an inadequate response or intolerance to NSAIDS and at least one nonbiologic DMARD, a single biologic DMARD is recommended over a combination of nonbiologic therapies (strong, very low evidence).

“However, there have been reports of emergent, highly severe lung disease associated with the use of biologics in children with systemic JIA, especially in those who are young, with chronic macrophage activation syndrome, and those with trisomy 21. More information is needed to clarify the safety of these agents,” Dr. Onel said.

There is a conditional recommendation against oral glucocorticoids as initial monotherapy, and strong recommendation against nonbiologic DMARDs as initial monotherapy (both very low evidence).

sJIA with MAS

“Macrophage activation syndrome is a major cause of morbidity and mortality for children with sJIA. Cytokine storm and secondary hemophagocytic syndrome can be seen with any rheumatic disease, but are most commonly seen with sJIA,” she said.

The features of MAS include fever, high ferritin levels, cytopenias, elevated liver-function test results, and high triglyceride levels.

For these patients, glucocorticoids are recommended as initial monotherapy (conditional, very low evidence). Biologic DMARDs (IL-1 and IL-6 inhibitors) are recommended over calcineurin inhibitors for achieving inactive disease and resolution of MAS (conditional, very low evidence). There is no preferred agent.

For patients with residual arthritis and an incomplete response to IL-1 or IL-6 inhibitors, biologic and nonbiologic DMARDs are recommended over chronic glucocorticoids (strong, very low evidence). There is no preferred agent.

After an MAS inactive disease state has been attained, the guideline recommends tapering and discontinuing glucocorticoids (strong, very low evidence) and the same for biologic DMARDs (conditional, very low evidence).
 

All children with JIA

In addition to the recommendations on specific clinical situations, the guideline includes recommendations for all children with JIA on medication monitoring, laboratory testing, and infection screening, as well as immunization and nonpharmacologic management.

A rheumatologist who was not involved in development of the guidelines commented on the importance of optimal management of JIA.

“Children are not immune from devastating rheumatic diseases, and the largest group is juvenile idiopathic arthritis. In my clinic, I have patients in their 30s, 40s, and 50s who have adult persistence of their arthritis from JIA who have permanent joint damage and even ongoing hard-to-control disease, and it has to do with the lack of therapies in the 1990s,” said Donald Thomas, MD, from Arthritis and Pain Associates of Prince George’s County (Md.).

“Today when we get a young adult transitioned from the pediatric clinic they’re usually in remission or have low disease activity because these treatments have paralleled those of our adult RA patients. Yet they do [provide clinicians with] unique challenges, with stunting of growth, macrophage activiation syndrome, and having to work with family members of the patient,” he said at a press briefing he moderated following the presentation of RA and JIA guidelines.

Eyal Muscal, MD, associate professor of pediatrics and rheumatology at Baylor College of Medicine, Houston, said in an interview that the guidelines clarify recommendations about earlier use of targeted therapies, primarily biologics.

“This will not change care, but hopefully remind all to adopt such strategies. Yet earlier utilization of often expensive biologic agents is delayed by administrative and insurance hurdles in the U.S. and access to these medications globally. I hope the guidelines will enhance advocacy on a state, national, and global stage,” he said when asked for comment.

The guideline development process is supported by ACR. Dr. Onel, Dr. Thomas, and Dr. Muscal reported no relevant conflicts of interest.

SOURCE: Onel K et al. ACR 2020, Presented November 8.

A draft guideline for the management of patients with juvenile idiopathic arthritis reflects changes in therapy away from reliance on NSAIDs and glucocorticoids and toward earlier introduction of biologic disease-modifying antirheumatic drugs (DMARDs).

The guideline, described in an oral session during the virtual annual meeting of the American College of Rheumatology, contains weighted recommendations for the treatment of JIA, including therapeutic approaches for oligoarthritis, tempromandibular joint (TMJ) arthritis, and systemic JIA (sJIA). The recommendations were the result of expert consensus and literature review using GRADE methodology, with input from clinicians, as well as patients and parents.

“Although evidence remains very low and many recommendations are conditional, the inclusion of parents and patients in the decision-making process strengthens their validity,” said project principal investigator Karen Onel, MD, of the Hospital for Special Surgery and Weill Cornell Medicine, both in New York.

She added that “it’s important to remember that these guidelines are meant to be guidelines; clinical care remains in the hands of the provider and the patient, and we endorse the importance of shared decision-making in coming to these agreements.”

Dr. Onel outlined key recommendations for patients for whom a diagnosis of JIA has already been made and who have no contraindications to recommended therapies. The strength of the recommendations (strong or conditional) and evidence levels (high, moderate, low, very low) were also reported.
 

Oligoarthritis with fewer than five involved joints

For these patients, intra-articular glucocorticoids (IAGC) are recommended as a part of initial therapy (strong, very low evidence).

Triamcinolone acetonide is the preferred agent in this situation (strong, low evidence).

The guideline also has a conditional recommendation (very low evidence) for a trial of consistent NSAIDS as part of initial therapy and a conditional recommendation against oral glucocorticoids for initial therapy (very low evidence).

Patients with no or incomplete responses or intolerance to NSAIDS and/or IAGC may be tried on a nonbiologic DMARD (strong, very low evidence), with methotrexate as the preferred agent (conditional, low evidence).

If the patient has no response or an inadequate response to at least one nonbiologic DMARD, biologic DMARDs are recommended (strong, very low evidence), with no preferred agent.

The guideline also conditionally recommends (all with very low evidence) using risk factors and validated disease activity measures to guide treatment decisions, as well as imaging guidance of joints that are difficult to access or to localize the distribution of inflammation.
 

TMJ arthritis

For patients with temporomandibular joint arthritis, isolated or not, IAGCs are conditionally recommended as part of initial therapy (very low evidence) with no preferred agents. The guideline also conditionally recommends in favor of a trial of consistent NSAIDs, and against oral glucocorticoids in initial therapy (evidence for both very low).

Recommendations for patients with TMJ with no or an incomplete response to the initial therapy are the same as for patients with oligoarthritis, with no preferred agent.
 

sJIA without macrophage activation syndrome

For patients with sJIA without macrophage activation syndrome (MAS), NSAIDS are conditionally recommended as initial monotherapy (very low evidence). Biologic DMARDS (including interleukin-1 and IL-6 inhibitors) are also recommended, conditionally, as initial monotherapy, with no preferred agent.

If the patient has an inadequate response or intolerance to NSAIDS and at least one nonbiologic DMARD, a single biologic DMARD is recommended over a combination of nonbiologic therapies (strong, very low evidence).

“However, there have been reports of emergent, highly severe lung disease associated with the use of biologics in children with systemic JIA, especially in those who are young, with chronic macrophage activation syndrome, and those with trisomy 21. More information is needed to clarify the safety of these agents,” Dr. Onel said.

There is a conditional recommendation against oral glucocorticoids as initial monotherapy, and strong recommendation against nonbiologic DMARDs as initial monotherapy (both very low evidence).

sJIA with MAS

“Macrophage activation syndrome is a major cause of morbidity and mortality for children with sJIA. Cytokine storm and secondary hemophagocytic syndrome can be seen with any rheumatic disease, but are most commonly seen with sJIA,” she said.

The features of MAS include fever, high ferritin levels, cytopenias, elevated liver-function test results, and high triglyceride levels.

For these patients, glucocorticoids are recommended as initial monotherapy (conditional, very low evidence). Biologic DMARDs (IL-1 and IL-6 inhibitors) are recommended over calcineurin inhibitors for achieving inactive disease and resolution of MAS (conditional, very low evidence). There is no preferred agent.

For patients with residual arthritis and an incomplete response to IL-1 or IL-6 inhibitors, biologic and nonbiologic DMARDs are recommended over chronic glucocorticoids (strong, very low evidence). There is no preferred agent.

After an MAS inactive disease state has been attained, the guideline recommends tapering and discontinuing glucocorticoids (strong, very low evidence) and the same for biologic DMARDs (conditional, very low evidence).
 

All children with JIA

In addition to the recommendations on specific clinical situations, the guideline includes recommendations for all children with JIA on medication monitoring, laboratory testing, and infection screening, as well as immunization and nonpharmacologic management.

A rheumatologist who was not involved in development of the guidelines commented on the importance of optimal management of JIA.

“Children are not immune from devastating rheumatic diseases, and the largest group is juvenile idiopathic arthritis. In my clinic, I have patients in their 30s, 40s, and 50s who have adult persistence of their arthritis from JIA who have permanent joint damage and even ongoing hard-to-control disease, and it has to do with the lack of therapies in the 1990s,” said Donald Thomas, MD, from Arthritis and Pain Associates of Prince George’s County (Md.).

“Today when we get a young adult transitioned from the pediatric clinic they’re usually in remission or have low disease activity because these treatments have paralleled those of our adult RA patients. Yet they do [provide clinicians with] unique challenges, with stunting of growth, macrophage activiation syndrome, and having to work with family members of the patient,” he said at a press briefing he moderated following the presentation of RA and JIA guidelines.

Eyal Muscal, MD, associate professor of pediatrics and rheumatology at Baylor College of Medicine, Houston, said in an interview that the guidelines clarify recommendations about earlier use of targeted therapies, primarily biologics.

“This will not change care, but hopefully remind all to adopt such strategies. Yet earlier utilization of often expensive biologic agents is delayed by administrative and insurance hurdles in the U.S. and access to these medications globally. I hope the guidelines will enhance advocacy on a state, national, and global stage,” he said when asked for comment.

The guideline development process is supported by ACR. Dr. Onel, Dr. Thomas, and Dr. Muscal reported no relevant conflicts of interest.

SOURCE: Onel K et al. ACR 2020, Presented November 8.

A draft guideline for the management of patients with juvenile idiopathic arthritis reflects changes in therapy away from reliance on NSAIDs and glucocorticoids and toward earlier introduction of biologic disease-modifying antirheumatic drugs (DMARDs).

The guideline, described in an oral session during the virtual annual meeting of the American College of Rheumatology, contains weighted recommendations for the treatment of JIA, including therapeutic approaches for oligoarthritis, tempromandibular joint (TMJ) arthritis, and systemic JIA (sJIA). The recommendations were the result of expert consensus and literature review using GRADE methodology, with input from clinicians, as well as patients and parents.

“Although evidence remains very low and many recommendations are conditional, the inclusion of parents and patients in the decision-making process strengthens their validity,” said project principal investigator Karen Onel, MD, of the Hospital for Special Surgery and Weill Cornell Medicine, both in New York.

She added that “it’s important to remember that these guidelines are meant to be guidelines; clinical care remains in the hands of the provider and the patient, and we endorse the importance of shared decision-making in coming to these agreements.”

Dr. Onel outlined key recommendations for patients for whom a diagnosis of JIA has already been made and who have no contraindications to recommended therapies. The strength of the recommendations (strong or conditional) and evidence levels (high, moderate, low, very low) were also reported.
 

Oligoarthritis with fewer than five involved joints

For these patients, intra-articular glucocorticoids (IAGC) are recommended as a part of initial therapy (strong, very low evidence).

Triamcinolone acetonide is the preferred agent in this situation (strong, low evidence).

The guideline also has a conditional recommendation (very low evidence) for a trial of consistent NSAIDS as part of initial therapy and a conditional recommendation against oral glucocorticoids for initial therapy (very low evidence).

Patients with no or incomplete responses or intolerance to NSAIDS and/or IAGC may be tried on a nonbiologic DMARD (strong, very low evidence), with methotrexate as the preferred agent (conditional, low evidence).

If the patient has no response or an inadequate response to at least one nonbiologic DMARD, biologic DMARDs are recommended (strong, very low evidence), with no preferred agent.

The guideline also conditionally recommends (all with very low evidence) using risk factors and validated disease activity measures to guide treatment decisions, as well as imaging guidance of joints that are difficult to access or to localize the distribution of inflammation.
 

TMJ arthritis

For patients with temporomandibular joint arthritis, isolated or not, IAGCs are conditionally recommended as part of initial therapy (very low evidence) with no preferred agents. The guideline also conditionally recommends in favor of a trial of consistent NSAIDs, and against oral glucocorticoids in initial therapy (evidence for both very low).

Recommendations for patients with TMJ with no or an incomplete response to the initial therapy are the same as for patients with oligoarthritis, with no preferred agent.
 

sJIA without macrophage activation syndrome

For patients with sJIA without macrophage activation syndrome (MAS), NSAIDS are conditionally recommended as initial monotherapy (very low evidence). Biologic DMARDS (including interleukin-1 and IL-6 inhibitors) are also recommended, conditionally, as initial monotherapy, with no preferred agent.

If the patient has an inadequate response or intolerance to NSAIDS and at least one nonbiologic DMARD, a single biologic DMARD is recommended over a combination of nonbiologic therapies (strong, very low evidence).

“However, there have been reports of emergent, highly severe lung disease associated with the use of biologics in children with systemic JIA, especially in those who are young, with chronic macrophage activation syndrome, and those with trisomy 21. More information is needed to clarify the safety of these agents,” Dr. Onel said.

There is a conditional recommendation against oral glucocorticoids as initial monotherapy, and strong recommendation against nonbiologic DMARDs as initial monotherapy (both very low evidence).

sJIA with MAS

“Macrophage activation syndrome is a major cause of morbidity and mortality for children with sJIA. Cytokine storm and secondary hemophagocytic syndrome can be seen with any rheumatic disease, but are most commonly seen with sJIA,” she said.

The features of MAS include fever, high ferritin levels, cytopenias, elevated liver-function test results, and high triglyceride levels.

For these patients, glucocorticoids are recommended as initial monotherapy (conditional, very low evidence). Biologic DMARDs (IL-1 and IL-6 inhibitors) are recommended over calcineurin inhibitors for achieving inactive disease and resolution of MAS (conditional, very low evidence). There is no preferred agent.

For patients with residual arthritis and an incomplete response to IL-1 or IL-6 inhibitors, biologic and nonbiologic DMARDs are recommended over chronic glucocorticoids (strong, very low evidence). There is no preferred agent.

After an MAS inactive disease state has been attained, the guideline recommends tapering and discontinuing glucocorticoids (strong, very low evidence) and the same for biologic DMARDs (conditional, very low evidence).
 

All children with JIA

In addition to the recommendations on specific clinical situations, the guideline includes recommendations for all children with JIA on medication monitoring, laboratory testing, and infection screening, as well as immunization and nonpharmacologic management.

A rheumatologist who was not involved in development of the guidelines commented on the importance of optimal management of JIA.

“Children are not immune from devastating rheumatic diseases, and the largest group is juvenile idiopathic arthritis. In my clinic, I have patients in their 30s, 40s, and 50s who have adult persistence of their arthritis from JIA who have permanent joint damage and even ongoing hard-to-control disease, and it has to do with the lack of therapies in the 1990s,” said Donald Thomas, MD, from Arthritis and Pain Associates of Prince George’s County (Md.).

“Today when we get a young adult transitioned from the pediatric clinic they’re usually in remission or have low disease activity because these treatments have paralleled those of our adult RA patients. Yet they do [provide clinicians with] unique challenges, with stunting of growth, macrophage activiation syndrome, and having to work with family members of the patient,” he said at a press briefing he moderated following the presentation of RA and JIA guidelines.

Eyal Muscal, MD, associate professor of pediatrics and rheumatology at Baylor College of Medicine, Houston, said in an interview that the guidelines clarify recommendations about earlier use of targeted therapies, primarily biologics.

“This will not change care, but hopefully remind all to adopt such strategies. Yet earlier utilization of often expensive biologic agents is delayed by administrative and insurance hurdles in the U.S. and access to these medications globally. I hope the guidelines will enhance advocacy on a state, national, and global stage,” he said when asked for comment.

The guideline development process is supported by ACR. Dr. Onel, Dr. Thomas, and Dr. Muscal reported no relevant conflicts of interest.

SOURCE: Onel K et al. ACR 2020, Presented November 8.

ILLUSTRATIVE CASE

A 55-year-old man with well-controlled diabetes, hypertension, and sleep apnea arrives at your office for a routine annual physical. In reviewing his medications, you note that he takes a low-dose aspirin daily for “heart health.” He has no known cardiovascular disease (CVD). His calculated 10-year risk of a major cardiovascular event is 11%.

Should this patient continue taking a daily aspirin for primary prevention of CVD?

Many patients in the United States take aspirin for primary prevention of CVD as recommended by the US Preventive Services Task Force (USPSTF).² This recommendation was based on older studies of populations in which smoking rates were higher and statin use was less common, leading to an overall higher risk of CVD.³ (The USPSTF is currently in the process of updating its recommendation.) More recent RCTs have been done in patients with a lower baseline risk of CVD, and these outcomes are more generalizable to today’s population. This new meta-analysis includes recent RCTs that evaluated whether there is value in using aspirin for the primary prevention of CVD.

STUDY SUMMARY

No reduction in risk, increased chance of bleeding

Mahmoud and colleagues conducted a meta-analysis of 11 randomized controlled trials that included 157,248 patients and assessed the efficacy and safety of aspirin for primary prevention of cardiovascular events.¹ The mean age of the total population was 61.3 years; 52% were women and 14% were smokers. The doses of aspirin used in most of the studies were ≤ 100 mg/d, although 2 of the studies examined doses that were higher. Patients were followed for a mean of 6.6 years. The primary efficacy outcome was all-cause mortality, and the primary safety outcome was major bleeding (as defined by each study). The secondary outcomes included cardiovascular mortality, fatal and nonfatal myocardial infarction (MI), and fatal and ­nonfatal ischemic stroke.

Aspirin did not lower all-cause mortality (risk ratio [RR] = 0.98; 95% confidence ­interval [CI], 0.93-1.02) and was associated with an increased risk of major bleeding (RR = 1.47; 95% CI, 1.31-1.65; number needed to harm = 250) and intracranial hemorrhage (RR = 1.33; 95% CI, 1.13-1.58). Aspirin also had no effect on all-cause mortality in subgroup analyses of patients with diabetes mellitus or high cardiovascular risk (10-year risk > 7.5%). There was (again) an increased risk of major bleeding.

Review of current guidelines and studies regarding the use of aspirin for primary prevention of CVD shows that the tide has been turning against this practice.

Aspirin had no effect on the secondary outcomes—with the exception of the incidence of MI (RR = 0.82; 95% CI, 0.71-0.94; number needed to treat = 333). However, this outcome was associated with considerable heterogeneity (I² = 67%), and the reduction was no longer evident after limiting the analysis to the more recent trials.

WHAT’S NEW?

Study is emblematic of a shift away from daily aspirin

Review of current guidelines and studies regarding the use of aspirin for primary prevention of CVD shows that the tide has been turning against this practice, but the change has been gradual. Newer studies—large RCTs such as ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events) and ASCEND (A Study of Cardiovascular Events iN Diabetes)—found no mortality benefit (all-cause or cardiovascular) from using aspirin in this context.

Continue to: The USPSTF guidelines...

The USPSTF guidelines in 2016 recommended prescribing daily aspirin for adults ages 50 to 59 who have a > 10% 10-year CVD risk and discussing with adults ages 60 to 69 the risks and benefits of daily aspirin.²

The 2019 American College of ­Cardiology/American Heart Association guidelines state that aspirin should no longer be used routinely for primary prevention, given the lack of net benefit. Patients ages 40 to 70 who are not at increased risk of bleeding with a higher risk of CVD may be considered for daily low-dose aspirin. The guidelines also state that adults > 70 years or those with increased risk of ­bleeding should not be started on a daily aspirin.⁴

CAVEATS

Jury is still out regarding very high-risk patients

While the meta-analysis by Mahmoud and colleagues makes a good case for discontinuing aspirin for primary prevention in most patients, the data do not examine in detail whether there is a benefit in patients with very high risk (> 20%) for atherosclerotic CVD. More studies are needed before making recommendations for that specific subgroup.

CHALLENGES TO IMPLEMENTATION

Patients may not be eager to give up an accepted practice

Physicians have been recommending aspirin for primary prevention of CVD for decades and many patients, who purchase aspirin themselves, are vested in the notion that aspirin protects them. It will take time for this change in practice to be accepted. Some patients may continue taking aspirin despite recommendation to stop. Primary care physicians will need to educate patients and clearly explain the rationale for stopping daily aspirin.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 55-year-old man with well-controlled diabetes, hypertension, and sleep apnea arrives at your office for a routine annual physical. In reviewing his medications, you note that he takes a low-dose aspirin daily for “heart health.” He has no known cardiovascular disease (CVD). His calculated 10-year risk of a major cardiovascular event is 11%.

Should this patient continue taking a daily aspirin for primary prevention of CVD?

Many patients in the United States take aspirin for primary prevention of CVD as recommended by the US Preventive Services Task Force (USPSTF).² This recommendation was based on older studies of populations in which smoking rates were higher and statin use was less common, leading to an overall higher risk of CVD.³ (The USPSTF is currently in the process of updating its recommendation.) More recent RCTs have been done in patients with a lower baseline risk of CVD, and these outcomes are more generalizable to today’s population. This new meta-analysis includes recent RCTs that evaluated whether there is value in using aspirin for the primary prevention of CVD.

STUDY SUMMARY

No reduction in risk, increased chance of bleeding

Mahmoud and colleagues conducted a meta-analysis of 11 randomized controlled trials that included 157,248 patients and assessed the efficacy and safety of aspirin for primary prevention of cardiovascular events.¹ The mean age of the total population was 61.3 years; 52% were women and 14% were smokers. The doses of aspirin used in most of the studies were ≤ 100 mg/d, although 2 of the studies examined doses that were higher. Patients were followed for a mean of 6.6 years. The primary efficacy outcome was all-cause mortality, and the primary safety outcome was major bleeding (as defined by each study). The secondary outcomes included cardiovascular mortality, fatal and nonfatal myocardial infarction (MI), and fatal and ­nonfatal ischemic stroke.

Aspirin did not lower all-cause mortality (risk ratio [RR] = 0.98; 95% confidence ­interval [CI], 0.93-1.02) and was associated with an increased risk of major bleeding (RR = 1.47; 95% CI, 1.31-1.65; number needed to harm = 250) and intracranial hemorrhage (RR = 1.33; 95% CI, 1.13-1.58). Aspirin also had no effect on all-cause mortality in subgroup analyses of patients with diabetes mellitus or high cardiovascular risk (10-year risk > 7.5%). There was (again) an increased risk of major bleeding.

Review of current guidelines and studies regarding the use of aspirin for primary prevention of CVD shows that the tide has been turning against this practice.

Aspirin had no effect on the secondary outcomes—with the exception of the incidence of MI (RR = 0.82; 95% CI, 0.71-0.94; number needed to treat = 333). However, this outcome was associated with considerable heterogeneity (I² = 67%), and the reduction was no longer evident after limiting the analysis to the more recent trials.

WHAT’S NEW?

Study is emblematic of a shift away from daily aspirin

Review of current guidelines and studies regarding the use of aspirin for primary prevention of CVD shows that the tide has been turning against this practice, but the change has been gradual. Newer studies—large RCTs such as ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events) and ASCEND (A Study of Cardiovascular Events iN Diabetes)—found no mortality benefit (all-cause or cardiovascular) from using aspirin in this context.

Continue to: The USPSTF guidelines...

The USPSTF guidelines in 2016 recommended prescribing daily aspirin for adults ages 50 to 59 who have a > 10% 10-year CVD risk and discussing with adults ages 60 to 69 the risks and benefits of daily aspirin.²

The 2019 American College of ­Cardiology/American Heart Association guidelines state that aspirin should no longer be used routinely for primary prevention, given the lack of net benefit. Patients ages 40 to 70 who are not at increased risk of bleeding with a higher risk of CVD may be considered for daily low-dose aspirin. The guidelines also state that adults > 70 years or those with increased risk of ­bleeding should not be started on a daily aspirin.⁴

CAVEATS

Jury is still out regarding very high-risk patients

While the meta-analysis by Mahmoud and colleagues makes a good case for discontinuing aspirin for primary prevention in most patients, the data do not examine in detail whether there is a benefit in patients with very high risk (> 20%) for atherosclerotic CVD. More studies are needed before making recommendations for that specific subgroup.

CHALLENGES TO IMPLEMENTATION

Patients may not be eager to give up an accepted practice

Physicians have been recommending aspirin for primary prevention of CVD for decades and many patients, who purchase aspirin themselves, are vested in the notion that aspirin protects them. It will take time for this change in practice to be accepted. Some patients may continue taking aspirin despite recommendation to stop. Primary care physicians will need to educate patients and clearly explain the rationale for stopping daily aspirin.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 55-year-old man with well-controlled diabetes, hypertension, and sleep apnea arrives at your office for a routine annual physical. In reviewing his medications, you note that he takes a low-dose aspirin daily for “heart health.” He has no known cardiovascular disease (CVD). His calculated 10-year risk of a major cardiovascular event is 11%.

Should this patient continue taking a daily aspirin for primary prevention of CVD?

Many patients in the United States take aspirin for primary prevention of CVD as recommended by the US Preventive Services Task Force (USPSTF).² This recommendation was based on older studies of populations in which smoking rates were higher and statin use was less common, leading to an overall higher risk of CVD.³ (The USPSTF is currently in the process of updating its recommendation.) More recent RCTs have been done in patients with a lower baseline risk of CVD, and these outcomes are more generalizable to today’s population. This new meta-analysis includes recent RCTs that evaluated whether there is value in using aspirin for the primary prevention of CVD.

STUDY SUMMARY

No reduction in risk, increased chance of bleeding

Mahmoud and colleagues conducted a meta-analysis of 11 randomized controlled trials that included 157,248 patients and assessed the efficacy and safety of aspirin for primary prevention of cardiovascular events.¹ The mean age of the total population was 61.3 years; 52% were women and 14% were smokers. The doses of aspirin used in most of the studies were ≤ 100 mg/d, although 2 of the studies examined doses that were higher. Patients were followed for a mean of 6.6 years. The primary efficacy outcome was all-cause mortality, and the primary safety outcome was major bleeding (as defined by each study). The secondary outcomes included cardiovascular mortality, fatal and nonfatal myocardial infarction (MI), and fatal and ­nonfatal ischemic stroke.

Aspirin did not lower all-cause mortality (risk ratio [RR] = 0.98; 95% confidence ­interval [CI], 0.93-1.02) and was associated with an increased risk of major bleeding (RR = 1.47; 95% CI, 1.31-1.65; number needed to harm = 250) and intracranial hemorrhage (RR = 1.33; 95% CI, 1.13-1.58). Aspirin also had no effect on all-cause mortality in subgroup analyses of patients with diabetes mellitus or high cardiovascular risk (10-year risk > 7.5%). There was (again) an increased risk of major bleeding.

Review of current guidelines and studies regarding the use of aspirin for primary prevention of CVD shows that the tide has been turning against this practice.

Aspirin had no effect on the secondary outcomes—with the exception of the incidence of MI (RR = 0.82; 95% CI, 0.71-0.94; number needed to treat = 333). However, this outcome was associated with considerable heterogeneity (I² = 67%), and the reduction was no longer evident after limiting the analysis to the more recent trials.

WHAT’S NEW?

Study is emblematic of a shift away from daily aspirin

Review of current guidelines and studies regarding the use of aspirin for primary prevention of CVD shows that the tide has been turning against this practice, but the change has been gradual. Newer studies—large RCTs such as ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events) and ASCEND (A Study of Cardiovascular Events iN Diabetes)—found no mortality benefit (all-cause or cardiovascular) from using aspirin in this context.

Continue to: The USPSTF guidelines...

The USPSTF guidelines in 2016 recommended prescribing daily aspirin for adults ages 50 to 59 who have a > 10% 10-year CVD risk and discussing with adults ages 60 to 69 the risks and benefits of daily aspirin.²

The 2019 American College of ­Cardiology/American Heart Association guidelines state that aspirin should no longer be used routinely for primary prevention, given the lack of net benefit. Patients ages 40 to 70 who are not at increased risk of bleeding with a higher risk of CVD may be considered for daily low-dose aspirin. The guidelines also state that adults > 70 years or those with increased risk of ­bleeding should not be started on a daily aspirin.⁴

CAVEATS

Jury is still out regarding very high-risk patients

While the meta-analysis by Mahmoud and colleagues makes a good case for discontinuing aspirin for primary prevention in most patients, the data do not examine in detail whether there is a benefit in patients with very high risk (> 20%) for atherosclerotic CVD. More studies are needed before making recommendations for that specific subgroup.

CHALLENGES TO IMPLEMENTATION

Patients may not be eager to give up an accepted practice

Physicians have been recommending aspirin for primary prevention of CVD for decades and many patients, who purchase aspirin themselves, are vested in the notion that aspirin protects them. It will take time for this change in practice to be accepted. Some patients may continue taking aspirin despite recommendation to stop. Primary care physicians will need to educate patients and clearly explain the rationale for stopping daily aspirin.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

As President Donald J. Trump starts firing officials of his administration – even if it appears that they would only have a few months left in the job – some health officials may find their positions on the line.

Others may soon depart voluntarily. Politico reported in late October that more than two dozen political appointees had already left the U.S. Department Health and Human Services (HHS) since the start of the COVID-19 pandemic in February and that potentially dozens of the more than 100 in the department would leave if Trump was not reelected.

Trump hasn’t conceded, he is challenging the election results, and he has already fired his Defense Secretary, Mark Esper.

Among those possibly in Trump’s sights: HHS Secretary Alex Azar, US Food and Drug Administration (FDA) Commissioner Stephen Hahn, MD, Centers for Disease Control and Prevention (CDC) Director Robert Redfield, MD, and White House Coronavirus Task Force member Anthony Fauci, MD, who is also the director of the National Institutes of Allergy and Infectious Diseases.

Seema Verma, the administrator of the Centers for Medicare & Medicaid Services (CMS), is likely safe. According to Politico, Verma is expected to leave on her own terms.

Azar has had a long run as a Trump appointee. He took office in January 2018 and has been a staunch loyalist. But he’s frequently been the butt of grousing by Trump for not doing enough to help lower drug prices and for his handling of the coronavirus pandemic. Azar was initially in charge of the Trump virus effort but was quickly replaced by Vice President Mike Pence.

It was widely reported in late April that Trump was considering firing Azar, but the president called that “fake news” in a tweet.

Azar has complained about Hahn, who was confirmed in December 2019. According to Politico, Azar was looking into how to remove Hahn as commissioner because of the FDA’s battle with the White House over standards for emergency use authorization of a coronavirus vaccine.

In addition, Trump was infuriated by the agency’s insistence that it stick to the highest bar for an emergency approval. “The deep state, or whoever, over at the FDA is making it very difficult for drug companies to get people in order to test the vaccines and therapeutics. Obviously, they are hoping to delay the answer until after November 3rd,” Trump tweeted at Hahn.
 

Fauci on the firing line?

Most of the president’s ire has been directed at Fauci. As far back as April, Trump retweeted a call for Fauci’s firing. Twitter removed the original tweet but kept Trump’s comments on the original tweet.

The president has frequently questioned Fauci’s advice, sidelined him from task force meetings, and infrequently met with him. Trump called Fauci a “disaster” during a call with supporters in October, and then, at a campaign rally in November, intimated that he would fire the scientist after the election, according to The Washington Post.

But such a firing cannot be easily done. Some have speculated that Trump could pressure Fauci’s boss, Francis Collins, MD, PhD — the director of the National Institutes of Health (NIH), who is a political appointee — to get rid of him. But Collins would have to come up with a reason to fire Fauci. Because he is not a political appointee, Fauci is afforded a raft of protections given to civil service employees of the federal government.

To demote or fire Fauci, Collins would have to give him 30 days’ notice unless there’s a belief that he committed a crime. Fauci would have at least a week to offer evidence and affidavits in support of his service.

He’d also be entitled to legal representation, a written decision, and the specific reasons for the action being taken quickly. He could also request a hearing, and he’d be able to appeal any action to the Merit Systems Protection Board. The process could take months, if not years.

In late October, Trump issued an executive order that would reclassify certain federal employees so that they wouldn’t have such protections. But agencies have until mid-January to come up with lists of such workers, according to Government Executive.

Collins has been with NIH since 1993, when he headed the Human Genome Project and the National Human Genome Research Institute. Politico has speculated that Collins, 70, might retire if Trump was reelected. It’s unclear what he’ll do now.

Redfield, who has taken heat for his leadership from many in public health — and was asked in October to stand up to Trump by former CDC Director William H. Foege, MD — has been openly contradicted by the president on more than one occasion, according to The New York Times.

In September, The Hill reported that Trump told reporters that he’d chastised Redfield by phone soon after Redfield had told a Senate committee that a coronavirus vaccine would not be available until mid-2021.

This article first appeared on Medscape.com.

As President Donald J. Trump starts firing officials of his administration – even if it appears that they would only have a few months left in the job – some health officials may find their positions on the line.

Others may soon depart voluntarily. Politico reported in late October that more than two dozen political appointees had already left the U.S. Department Health and Human Services (HHS) since the start of the COVID-19 pandemic in February and that potentially dozens of the more than 100 in the department would leave if Trump was not reelected.

Trump hasn’t conceded, he is challenging the election results, and he has already fired his Defense Secretary, Mark Esper.

Among those possibly in Trump’s sights: HHS Secretary Alex Azar, US Food and Drug Administration (FDA) Commissioner Stephen Hahn, MD, Centers for Disease Control and Prevention (CDC) Director Robert Redfield, MD, and White House Coronavirus Task Force member Anthony Fauci, MD, who is also the director of the National Institutes of Allergy and Infectious Diseases.

Seema Verma, the administrator of the Centers for Medicare & Medicaid Services (CMS), is likely safe. According to Politico, Verma is expected to leave on her own terms.

Azar has had a long run as a Trump appointee. He took office in January 2018 and has been a staunch loyalist. But he’s frequently been the butt of grousing by Trump for not doing enough to help lower drug prices and for his handling of the coronavirus pandemic. Azar was initially in charge of the Trump virus effort but was quickly replaced by Vice President Mike Pence.

It was widely reported in late April that Trump was considering firing Azar, but the president called that “fake news” in a tweet.

Azar has complained about Hahn, who was confirmed in December 2019. According to Politico, Azar was looking into how to remove Hahn as commissioner because of the FDA’s battle with the White House over standards for emergency use authorization of a coronavirus vaccine.

In addition, Trump was infuriated by the agency’s insistence that it stick to the highest bar for an emergency approval. “The deep state, or whoever, over at the FDA is making it very difficult for drug companies to get people in order to test the vaccines and therapeutics. Obviously, they are hoping to delay the answer until after November 3rd,” Trump tweeted at Hahn.
 

Fauci on the firing line?

Most of the president’s ire has been directed at Fauci. As far back as April, Trump retweeted a call for Fauci’s firing. Twitter removed the original tweet but kept Trump’s comments on the original tweet.

The president has frequently questioned Fauci’s advice, sidelined him from task force meetings, and infrequently met with him. Trump called Fauci a “disaster” during a call with supporters in October, and then, at a campaign rally in November, intimated that he would fire the scientist after the election, according to The Washington Post.

But such a firing cannot be easily done. Some have speculated that Trump could pressure Fauci’s boss, Francis Collins, MD, PhD — the director of the National Institutes of Health (NIH), who is a political appointee — to get rid of him. But Collins would have to come up with a reason to fire Fauci. Because he is not a political appointee, Fauci is afforded a raft of protections given to civil service employees of the federal government.

To demote or fire Fauci, Collins would have to give him 30 days’ notice unless there’s a belief that he committed a crime. Fauci would have at least a week to offer evidence and affidavits in support of his service.

He’d also be entitled to legal representation, a written decision, and the specific reasons for the action being taken quickly. He could also request a hearing, and he’d be able to appeal any action to the Merit Systems Protection Board. The process could take months, if not years.

In late October, Trump issued an executive order that would reclassify certain federal employees so that they wouldn’t have such protections. But agencies have until mid-January to come up with lists of such workers, according to Government Executive.

Collins has been with NIH since 1993, when he headed the Human Genome Project and the National Human Genome Research Institute. Politico has speculated that Collins, 70, might retire if Trump was reelected. It’s unclear what he’ll do now.

Redfield, who has taken heat for his leadership from many in public health — and was asked in October to stand up to Trump by former CDC Director William H. Foege, MD — has been openly contradicted by the president on more than one occasion, according to The New York Times.

In September, The Hill reported that Trump told reporters that he’d chastised Redfield by phone soon after Redfield had told a Senate committee that a coronavirus vaccine would not be available until mid-2021.

This article first appeared on Medscape.com.

As President Donald J. Trump starts firing officials of his administration – even if it appears that they would only have a few months left in the job – some health officials may find their positions on the line.

Others may soon depart voluntarily. Politico reported in late October that more than two dozen political appointees had already left the U.S. Department Health and Human Services (HHS) since the start of the COVID-19 pandemic in February and that potentially dozens of the more than 100 in the department would leave if Trump was not reelected.

Trump hasn’t conceded, he is challenging the election results, and he has already fired his Defense Secretary, Mark Esper.

Among those possibly in Trump’s sights: HHS Secretary Alex Azar, US Food and Drug Administration (FDA) Commissioner Stephen Hahn, MD, Centers for Disease Control and Prevention (CDC) Director Robert Redfield, MD, and White House Coronavirus Task Force member Anthony Fauci, MD, who is also the director of the National Institutes of Allergy and Infectious Diseases.

Seema Verma, the administrator of the Centers for Medicare & Medicaid Services (CMS), is likely safe. According to Politico, Verma is expected to leave on her own terms.

Azar has had a long run as a Trump appointee. He took office in January 2018 and has been a staunch loyalist. But he’s frequently been the butt of grousing by Trump for not doing enough to help lower drug prices and for his handling of the coronavirus pandemic. Azar was initially in charge of the Trump virus effort but was quickly replaced by Vice President Mike Pence.

It was widely reported in late April that Trump was considering firing Azar, but the president called that “fake news” in a tweet.

Azar has complained about Hahn, who was confirmed in December 2019. According to Politico, Azar was looking into how to remove Hahn as commissioner because of the FDA’s battle with the White House over standards for emergency use authorization of a coronavirus vaccine.

In addition, Trump was infuriated by the agency’s insistence that it stick to the highest bar for an emergency approval. “The deep state, or whoever, over at the FDA is making it very difficult for drug companies to get people in order to test the vaccines and therapeutics. Obviously, they are hoping to delay the answer until after November 3rd,” Trump tweeted at Hahn.
 

Fauci on the firing line?

Most of the president’s ire has been directed at Fauci. As far back as April, Trump retweeted a call for Fauci’s firing. Twitter removed the original tweet but kept Trump’s comments on the original tweet.

The president has frequently questioned Fauci’s advice, sidelined him from task force meetings, and infrequently met with him. Trump called Fauci a “disaster” during a call with supporters in October, and then, at a campaign rally in November, intimated that he would fire the scientist after the election, according to The Washington Post.

But such a firing cannot be easily done. Some have speculated that Trump could pressure Fauci’s boss, Francis Collins, MD, PhD — the director of the National Institutes of Health (NIH), who is a political appointee — to get rid of him. But Collins would have to come up with a reason to fire Fauci. Because he is not a political appointee, Fauci is afforded a raft of protections given to civil service employees of the federal government.

To demote or fire Fauci, Collins would have to give him 30 days’ notice unless there’s a belief that he committed a crime. Fauci would have at least a week to offer evidence and affidavits in support of his service.

He’d also be entitled to legal representation, a written decision, and the specific reasons for the action being taken quickly. He could also request a hearing, and he’d be able to appeal any action to the Merit Systems Protection Board. The process could take months, if not years.

In late October, Trump issued an executive order that would reclassify certain federal employees so that they wouldn’t have such protections. But agencies have until mid-January to come up with lists of such workers, according to Government Executive.

Collins has been with NIH since 1993, when he headed the Human Genome Project and the National Human Genome Research Institute. Politico has speculated that Collins, 70, might retire if Trump was reelected. It’s unclear what he’ll do now.

Redfield, who has taken heat for his leadership from many in public health — and was asked in October to stand up to Trump by former CDC Director William H. Foege, MD — has been openly contradicted by the president on more than one occasion, according to The New York Times.

In September, The Hill reported that Trump told reporters that he’d chastised Redfield by phone soon after Redfield had told a Senate committee that a coronavirus vaccine would not be available until mid-2021.

This article first appeared on Medscape.com.

Among patients with ulcerative colitis who were treated in routine practice, a point-based clinical scoring tool predicted nonresponse to vedolizumab therapy, according to study findings published online in Clinical Gastroenterology and Hepatology.

A cutoff of 26 points or less was 93% sensitive (95% confidence interval, 79%-98%) for identifying patients who did not reach corticosteroid-free remission during 26 weeks of treatment and was 88% sensitive (95% CI, 83%-92%) for identifying patients who required colectomy, reported Parambir S. Dulai, MBBS, of the University of California, San Diego, and his associates. The tool was less reliable for predicting response to tumor necrosis factor (TNF) antagonists, indicating that it is treatment specific, they noted.

Vedolizumab, an alpha-4-beta-7 anti-integrin that restricts the migration of proinflammatory lymphocytes to the gut, can induce corticosteroid-free remissions and mucosal healing in patients with ulcerative colitis. In clinical practice, 22-week rates of clinical response and remission were approximately 51% and 30%, respectively, in a recent study. Noting the lack of real-world data on predictors of response, the researchers modeled data from 620 patients who received induction and maintenance vedolizumab during the blinded phase 3 GEMINI 1 trial. They used this model to create the clinical scoring tool, which they validated in a cohort of 322 patients with ulcerative colitis who had received vedolizumab (199 patients) or TNF antagonists (123 patients) in routine practice during the Vedolizumab for Health Outcomes in Inflammatory Bowel Diseases (VICTORY) study.

In the final multivariable model, predictors of steroid-free remission were TNF antagonist naivety, at least a 2-year history of ulcerative colitis, moderate rather than severe endoscopy activity, and baseline albumin concentration. The resulting clinical scoring tool included these four variables and multiplied them by factors ranging from 0.0647 (for baseline albumin concentration) to 0.2820 (for no prior TNF antagonist exposure). In the validation cohort, patients were categorized as “high probability” (of response) if they scored 33 points or more on the tool and “low probability” if they scored 26 points or fewer. Rates of corticosteroid-free remissions were substantially different at 32% and 12%, respectively. The tool also predicted responses to vedolizumab more accurately than it did predicted responses to TNF antagonists, indicating that it was drug specific.

In the validation cohort, 46% (10 of 22) of low- or intermediate-probability patients showed least a 50% decrease in symptom activity after their vedolizumab infusion interval was shortened to address an insufficient initial response. “However, none of the high-probability patients showed a clinical response to interval shortening,” probably because they had higher vedolizumab trough concentrations to begin with, the researchers said. They called for prospective validation of this finding, “ideally in a randomized, controlled trial setting.”

The derivation and validation cohorts differed in several important ways. The validation cohort included significantly more females, smokers, patients with moderate endoscopic disease, and patients who had failed prior TNF antagonist therapy. These patients also had a significantly higher median albumin level and a longer history of disease. “The lower bound of the confidence interval for the [model’s] performance reached 0.5, suggesting that model discrimination may not be ideal,” the researchers said. “Further validation will therefore be needed to understand external validity on additional cohorts.”

An American Gastroenterological Association Research Scholar Award supported the work. Dr. Dulai reported holding a provisional patent for the prediction model and consulting relationships and other ties to Takeda, Janssen, Pfizer, and AbbVie. His coinvestigators reported ties to numerous pharmaceutical companies.

SOURCE: Dulai PS et al. Clin Gastroenterol Hepatol. 2020 Feb 13. doi: 10.1016/j.cgh.2020.02.010.

Among patients with ulcerative colitis who were treated in routine practice, a point-based clinical scoring tool predicted nonresponse to vedolizumab therapy, according to study findings published online in Clinical Gastroenterology and Hepatology.

A cutoff of 26 points or less was 93% sensitive (95% confidence interval, 79%-98%) for identifying patients who did not reach corticosteroid-free remission during 26 weeks of treatment and was 88% sensitive (95% CI, 83%-92%) for identifying patients who required colectomy, reported Parambir S. Dulai, MBBS, of the University of California, San Diego, and his associates. The tool was less reliable for predicting response to tumor necrosis factor (TNF) antagonists, indicating that it is treatment specific, they noted.

Vedolizumab, an alpha-4-beta-7 anti-integrin that restricts the migration of proinflammatory lymphocytes to the gut, can induce corticosteroid-free remissions and mucosal healing in patients with ulcerative colitis. In clinical practice, 22-week rates of clinical response and remission were approximately 51% and 30%, respectively, in a recent study. Noting the lack of real-world data on predictors of response, the researchers modeled data from 620 patients who received induction and maintenance vedolizumab during the blinded phase 3 GEMINI 1 trial. They used this model to create the clinical scoring tool, which they validated in a cohort of 322 patients with ulcerative colitis who had received vedolizumab (199 patients) or TNF antagonists (123 patients) in routine practice during the Vedolizumab for Health Outcomes in Inflammatory Bowel Diseases (VICTORY) study.

In the final multivariable model, predictors of steroid-free remission were TNF antagonist naivety, at least a 2-year history of ulcerative colitis, moderate rather than severe endoscopy activity, and baseline albumin concentration. The resulting clinical scoring tool included these four variables and multiplied them by factors ranging from 0.0647 (for baseline albumin concentration) to 0.2820 (for no prior TNF antagonist exposure). In the validation cohort, patients were categorized as “high probability” (of response) if they scored 33 points or more on the tool and “low probability” if they scored 26 points or fewer. Rates of corticosteroid-free remissions were substantially different at 32% and 12%, respectively. The tool also predicted responses to vedolizumab more accurately than it did predicted responses to TNF antagonists, indicating that it was drug specific.

In the validation cohort, 46% (10 of 22) of low- or intermediate-probability patients showed least a 50% decrease in symptom activity after their vedolizumab infusion interval was shortened to address an insufficient initial response. “However, none of the high-probability patients showed a clinical response to interval shortening,” probably because they had higher vedolizumab trough concentrations to begin with, the researchers said. They called for prospective validation of this finding, “ideally in a randomized, controlled trial setting.”

The derivation and validation cohorts differed in several important ways. The validation cohort included significantly more females, smokers, patients with moderate endoscopic disease, and patients who had failed prior TNF antagonist therapy. These patients also had a significantly higher median albumin level and a longer history of disease. “The lower bound of the confidence interval for the [model’s] performance reached 0.5, suggesting that model discrimination may not be ideal,” the researchers said. “Further validation will therefore be needed to understand external validity on additional cohorts.”

An American Gastroenterological Association Research Scholar Award supported the work. Dr. Dulai reported holding a provisional patent for the prediction model and consulting relationships and other ties to Takeda, Janssen, Pfizer, and AbbVie. His coinvestigators reported ties to numerous pharmaceutical companies.

SOURCE: Dulai PS et al. Clin Gastroenterol Hepatol. 2020 Feb 13. doi: 10.1016/j.cgh.2020.02.010.

Among patients with ulcerative colitis who were treated in routine practice, a point-based clinical scoring tool predicted nonresponse to vedolizumab therapy, according to study findings published online in Clinical Gastroenterology and Hepatology.

A cutoff of 26 points or less was 93% sensitive (95% confidence interval, 79%-98%) for identifying patients who did not reach corticosteroid-free remission during 26 weeks of treatment and was 88% sensitive (95% CI, 83%-92%) for identifying patients who required colectomy, reported Parambir S. Dulai, MBBS, of the University of California, San Diego, and his associates. The tool was less reliable for predicting response to tumor necrosis factor (TNF) antagonists, indicating that it is treatment specific, they noted.

Vedolizumab, an alpha-4-beta-7 anti-integrin that restricts the migration of proinflammatory lymphocytes to the gut, can induce corticosteroid-free remissions and mucosal healing in patients with ulcerative colitis. In clinical practice, 22-week rates of clinical response and remission were approximately 51% and 30%, respectively, in a recent study. Noting the lack of real-world data on predictors of response, the researchers modeled data from 620 patients who received induction and maintenance vedolizumab during the blinded phase 3 GEMINI 1 trial. They used this model to create the clinical scoring tool, which they validated in a cohort of 322 patients with ulcerative colitis who had received vedolizumab (199 patients) or TNF antagonists (123 patients) in routine practice during the Vedolizumab for Health Outcomes in Inflammatory Bowel Diseases (VICTORY) study.

In the final multivariable model, predictors of steroid-free remission were TNF antagonist naivety, at least a 2-year history of ulcerative colitis, moderate rather than severe endoscopy activity, and baseline albumin concentration. The resulting clinical scoring tool included these four variables and multiplied them by factors ranging from 0.0647 (for baseline albumin concentration) to 0.2820 (for no prior TNF antagonist exposure). In the validation cohort, patients were categorized as “high probability” (of response) if they scored 33 points or more on the tool and “low probability” if they scored 26 points or fewer. Rates of corticosteroid-free remissions were substantially different at 32% and 12%, respectively. The tool also predicted responses to vedolizumab more accurately than it did predicted responses to TNF antagonists, indicating that it was drug specific.

In the validation cohort, 46% (10 of 22) of low- or intermediate-probability patients showed least a 50% decrease in symptom activity after their vedolizumab infusion interval was shortened to address an insufficient initial response. “However, none of the high-probability patients showed a clinical response to interval shortening,” probably because they had higher vedolizumab trough concentrations to begin with, the researchers said. They called for prospective validation of this finding, “ideally in a randomized, controlled trial setting.”

The derivation and validation cohorts differed in several important ways. The validation cohort included significantly more females, smokers, patients with moderate endoscopic disease, and patients who had failed prior TNF antagonist therapy. These patients also had a significantly higher median albumin level and a longer history of disease. “The lower bound of the confidence interval for the [model’s] performance reached 0.5, suggesting that model discrimination may not be ideal,” the researchers said. “Further validation will therefore be needed to understand external validity on additional cohorts.”

An American Gastroenterological Association Research Scholar Award supported the work. Dr. Dulai reported holding a provisional patent for the prediction model and consulting relationships and other ties to Takeda, Janssen, Pfizer, and AbbVie. His coinvestigators reported ties to numerous pharmaceutical companies.

SOURCE: Dulai PS et al. Clin Gastroenterol Hepatol. 2020 Feb 13. doi: 10.1016/j.cgh.2020.02.010.

Life expectancy increased for adults with inflammatory bowel disease (IBD) over recent decades, but still remained lower than life expectancy for individuals without IBD, according to data from a retrospective cohort study using Canadian health databases.

“Management of IBD has improved through increased access to specialist care, biologic therapies, and a treat-to-target approach,” wrote M. Ellen Kuenzig, PhD, of the Children’s Hospital of Eastern Ontario and colleagues. However, “Most studies evaluating mortality were conducted before the biologic era, and none evaluated life expectancy or health-adjusted life expectancy,” they said.

In a study published in the Canadian Medical Association Journal, the researchers used Canadian databases to identify a study population of 32,818 people with IBD matched to 163,284 people without IBD in 1996 that increased to 83,672 people with IBD matched to 418,360 people without IBD in 2011.

Life expectancy increases, but with caveats

Overall, life expectancy for IBD patients increased from 75.5 years to 78.4 years for women and from 72.2 years to 75.5 years for men between 1996 and 2011.

However, health-adjusted life expectancy, defined as the number of years a person is expected to live in full health, decreased by 3.9 years for men with IBD between 1996 and 2008, but did not change significantly for women with IBD, although the gap in health-adjusted life expectancy increased between women with IBD and women without IBD.

Both life expectancy and health-adjusted life expectancy remained consistently lower for individuals with IBD compared to those without IBD. Differences in life expectancy for women with and without IBD ranged from 6.6 to 8.1 years and from 5.0 to 6.1 years for men with and without IBD, depending on the year.

Differences in health-adjusted life expectancy ranged from 9.5 to 13.5 years in women with and without IBD, and from 2.6 years to 6.7 years in men with and without IBD depending on the year, the researchers said.

In addition, the researchers used the pain-attributed utility of the Health Utility Index (HUI) to calculate health-adjusted life expectancy with the effect of pain on health status. The health-adjusted life expectancy using HUI for pain was stable in women with IBD, but increased over time for women without IBD. This pattern was similar for individuals with Crohn’s disease but stable for women with and without ulcerative colitis. In men, health-adjusted life expectancy using the pain-attributed utility of the HUI was stable for those with IBD, decreased in those with Crohn’s disease, and increased among those with ulcerative colitis.

The study findings were limited by several factors including potential confounding by disease phenotype and severity, as well as lack of data on medication use for individuals younger than 65 years and limited data on confounders including smoking, ethnicity, and environmental factors, the researchers said.

In addition, “mortality may increase with disease duration, which would violate the assumption that age- and sex-specific mortality rates remain constant over a person’s lifetime that is required when using lifetables,” they said.
 

Future research should pursue effect of pain

The results support the persistence of a gap in life expectancy between individuals with and without IBD and suggest the need for improving pain management in IBD patients, given the contribution of pain to reduced health-adjusted life expectancy, they concluded. Additional research is needed to determine the effect of comorbid conditions and medication use on the difference in life expectancy for those with and without IBD, they added.

The study was supported by the Institute for Clinical Evaluative Services (Canada). Lead author Dr. Kuenzig received a Post-Doctoral Fellowship Award from the Canadian Institutes of Health Research, Canadian Association of Gastroenterology, and Crohn’s and Colitis Canada. The researchers had no financial conflicts to disclose.

SOURCE: Kuenzig ME et al. CMAJ. 2020 Nov 9. doi: 10.1503/cmaj.190976.

Life expectancy increased for adults with inflammatory bowel disease (IBD) over recent decades, but still remained lower than life expectancy for individuals without IBD, according to data from a retrospective cohort study using Canadian health databases.

“Management of IBD has improved through increased access to specialist care, biologic therapies, and a treat-to-target approach,” wrote M. Ellen Kuenzig, PhD, of the Children’s Hospital of Eastern Ontario and colleagues. However, “Most studies evaluating mortality were conducted before the biologic era, and none evaluated life expectancy or health-adjusted life expectancy,” they said.

In a study published in the Canadian Medical Association Journal, the researchers used Canadian databases to identify a study population of 32,818 people with IBD matched to 163,284 people without IBD in 1996 that increased to 83,672 people with IBD matched to 418,360 people without IBD in 2011.

Life expectancy increases, but with caveats

Overall, life expectancy for IBD patients increased from 75.5 years to 78.4 years for women and from 72.2 years to 75.5 years for men between 1996 and 2011.

However, health-adjusted life expectancy, defined as the number of years a person is expected to live in full health, decreased by 3.9 years for men with IBD between 1996 and 2008, but did not change significantly for women with IBD, although the gap in health-adjusted life expectancy increased between women with IBD and women without IBD.

Both life expectancy and health-adjusted life expectancy remained consistently lower for individuals with IBD compared to those without IBD. Differences in life expectancy for women with and without IBD ranged from 6.6 to 8.1 years and from 5.0 to 6.1 years for men with and without IBD, depending on the year.

Differences in health-adjusted life expectancy ranged from 9.5 to 13.5 years in women with and without IBD, and from 2.6 years to 6.7 years in men with and without IBD depending on the year, the researchers said.

In addition, the researchers used the pain-attributed utility of the Health Utility Index (HUI) to calculate health-adjusted life expectancy with the effect of pain on health status. The health-adjusted life expectancy using HUI for pain was stable in women with IBD, but increased over time for women without IBD. This pattern was similar for individuals with Crohn’s disease but stable for women with and without ulcerative colitis. In men, health-adjusted life expectancy using the pain-attributed utility of the HUI was stable for those with IBD, decreased in those with Crohn’s disease, and increased among those with ulcerative colitis.

The study findings were limited by several factors including potential confounding by disease phenotype and severity, as well as lack of data on medication use for individuals younger than 65 years and limited data on confounders including smoking, ethnicity, and environmental factors, the researchers said.

In addition, “mortality may increase with disease duration, which would violate the assumption that age- and sex-specific mortality rates remain constant over a person’s lifetime that is required when using lifetables,” they said.
 

Future research should pursue effect of pain

The results support the persistence of a gap in life expectancy between individuals with and without IBD and suggest the need for improving pain management in IBD patients, given the contribution of pain to reduced health-adjusted life expectancy, they concluded. Additional research is needed to determine the effect of comorbid conditions and medication use on the difference in life expectancy for those with and without IBD, they added.

The study was supported by the Institute for Clinical Evaluative Services (Canada). Lead author Dr. Kuenzig received a Post-Doctoral Fellowship Award from the Canadian Institutes of Health Research, Canadian Association of Gastroenterology, and Crohn’s and Colitis Canada. The researchers had no financial conflicts to disclose.

SOURCE: Kuenzig ME et al. CMAJ. 2020 Nov 9. doi: 10.1503/cmaj.190976.

Life expectancy increased for adults with inflammatory bowel disease (IBD) over recent decades, but still remained lower than life expectancy for individuals without IBD, according to data from a retrospective cohort study using Canadian health databases.

“Management of IBD has improved through increased access to specialist care, biologic therapies, and a treat-to-target approach,” wrote M. Ellen Kuenzig, PhD, of the Children’s Hospital of Eastern Ontario and colleagues. However, “Most studies evaluating mortality were conducted before the biologic era, and none evaluated life expectancy or health-adjusted life expectancy,” they said.

In a study published in the Canadian Medical Association Journal, the researchers used Canadian databases to identify a study population of 32,818 people with IBD matched to 163,284 people without IBD in 1996 that increased to 83,672 people with IBD matched to 418,360 people without IBD in 2011.

Life expectancy increases, but with caveats

Overall, life expectancy for IBD patients increased from 75.5 years to 78.4 years for women and from 72.2 years to 75.5 years for men between 1996 and 2011.

However, health-adjusted life expectancy, defined as the number of years a person is expected to live in full health, decreased by 3.9 years for men with IBD between 1996 and 2008, but did not change significantly for women with IBD, although the gap in health-adjusted life expectancy increased between women with IBD and women without IBD.

Both life expectancy and health-adjusted life expectancy remained consistently lower for individuals with IBD compared to those without IBD. Differences in life expectancy for women with and without IBD ranged from 6.6 to 8.1 years and from 5.0 to 6.1 years for men with and without IBD, depending on the year.

Differences in health-adjusted life expectancy ranged from 9.5 to 13.5 years in women with and without IBD, and from 2.6 years to 6.7 years in men with and without IBD depending on the year, the researchers said.

In addition, the researchers used the pain-attributed utility of the Health Utility Index (HUI) to calculate health-adjusted life expectancy with the effect of pain on health status. The health-adjusted life expectancy using HUI for pain was stable in women with IBD, but increased over time for women without IBD. This pattern was similar for individuals with Crohn’s disease but stable for women with and without ulcerative colitis. In men, health-adjusted life expectancy using the pain-attributed utility of the HUI was stable for those with IBD, decreased in those with Crohn’s disease, and increased among those with ulcerative colitis.

The study findings were limited by several factors including potential confounding by disease phenotype and severity, as well as lack of data on medication use for individuals younger than 65 years and limited data on confounders including smoking, ethnicity, and environmental factors, the researchers said.

In addition, “mortality may increase with disease duration, which would violate the assumption that age- and sex-specific mortality rates remain constant over a person’s lifetime that is required when using lifetables,” they said.
 

Future research should pursue effect of pain

The results support the persistence of a gap in life expectancy between individuals with and without IBD and suggest the need for improving pain management in IBD patients, given the contribution of pain to reduced health-adjusted life expectancy, they concluded. Additional research is needed to determine the effect of comorbid conditions and medication use on the difference in life expectancy for those with and without IBD, they added.

The study was supported by the Institute for Clinical Evaluative Services (Canada). Lead author Dr. Kuenzig received a Post-Doctoral Fellowship Award from the Canadian Institutes of Health Research, Canadian Association of Gastroenterology, and Crohn’s and Colitis Canada. The researchers had no financial conflicts to disclose.

SOURCE: Kuenzig ME et al. CMAJ. 2020 Nov 9. doi: 10.1503/cmaj.190976.

Cervical cancer screening is a routine procedure, but in rare instances, there can be medical complications. A new study finds that, compared with women who have normal results, women who are diagnosed with an invasive malignancy have an increased risk for iatrogenic injuries.

Researchers in Sweden analyzed data on more than 3 million women who had undergone cervical cancer screening. The team found that 42 iatrogenic injuries that required at least 2 days of hospitalization occurred during the diagnostic work-up of women who had an abnormal screening test.

“Although cervical cancer screening is one of the most successful cancer prevention programs ... our research indicates that women with invasive cervical cancer experienced medical complications and psychological stress during their diagnostic work-up, although at a very low level,” commented corresponding author Qing Shen, PhD, from the department of medical epidemiology and biostatistics at the Karolinska Institute in Stockholm, Sweden.

The study was published in Cancer Epidemiology, Biomarkers & Prevention.

“Injuries can occur with diagnostic evaluation for cervical cancer,” commented Kecia Gaither, MD, MPH, FACOG, director of perinatal services at Lincoln Medical and Mental Health Center, New York City Health and Hospitals System, who was not involved in the study.

“Given the fact that neovascularization occurs with cancers, a large biopsy in such a circumstance could lead to a hematoma or excessive blood loss. It rarely occurs but most certainly is possible,” said Dr. Gaither.

Also weighing in with comments, Cathy Popadiuk, MD, FRCS, an associate professor of medicine in the department of obstetrics and gynecology at Memorial University of Newfoundland, St. John’s, said the findings are reflective of the real-world and North American experience.

“There are indeed rare bad things that can happen during diagnostic work-up of abnormal pap smears, and usually this is with associated other disease, such as actual cancer or fibroids that can also bleed and may be in the cervix, etc.,” she told this news organization. “And definitely, when there is undetected cancer, this can bleed, requiring transfusion and hospital admission.”

Dr. Popadiuk pointed out that Sweden may be more liberal in admitting patients to hospital, whereas in North America, “we are trying to move away from inpatient care.” She added, “When you are getting these relatively minor procedures, you don’t expect something bad to happen in the clinic.”

Women may become anxious, and admission is the easiest way to arrange for care such as transfusions or observation for more bleeding, she noted. In addition, vaginal packing may be needed to control hemorrhage, and “with vaginal packing, women are unable to void and need a Foley catheter, and that, again, cannot be managed at home easily,” she explained. “After bleeding settles, the vaginal pack is removed, often the next day.” This may be why some women are admitted to hospital.
 

Increased risk of injury

In a previous study, Dr. Shen and colleagues found there was an increased risk for injuries during the period before and after a diagnosis of any cancer (BMJ. 2016;354:i4218). Those findings suggested the interval between first suspicion of cancer and diagnosis or initiation of treatment might be a high-risk time for injuries in cancer care.

In this latest study, they assessed whether there was a similar increase in injury risk among patients screened for cervical cancer. Using the Swedish Total Population Register, they identified 3,016,307 women who had undergone cervical screening during the period 2001-2012.

The final analysis included 1,853,510 women whose pap smear results were normal; 22,435 women who were diagnosed with cervical intraepithelial neoplasia (CIN); 20,692 women with CIN2; 36,542 women with CIN3 or adenocarcinoma in situ (AIS); and 5,189 women with invasive cervical cancer.

The team found that, among women who had an abnormal screening test, 42 iatrogenic injuries occurred that required at least 2 days of hospital admission. The highest risk was among women diagnosed with invasive cancer. The risk was also increased among women diagnosed with CIN3/AIS, but not among women with lower grades of CIN.

The most common types of iatrogenic injuries were hemorrhage or hematoma and infections. Among all groups of women, the incidence rate of injuries that were caused by medical procedures and care was greater than that of injuries caused by drugs or biological substances.

A total of 91 noniatrogenic injuries that required at least 1 day of hospitalization were identified. The risk was increased among women with invasive cervical cancer but not for women with other cervical abnormalities. The most common type of noniatrogenic injury was unintentional injuries.

The study was sponsored by the Swedish Cancer Society and the Swedish Research Council for Health, Working Life and Welfare. One author received a Karolinska Institute Senior Researcher Award and a Strategic Research Area in Epidemiology Award, and one author received a grant from the China Scholarship Council. Dr. Shen has disclosed no relevant financial relationships. Dr. Popadiuk has received personal fees and nonfinancial support as a member of the OncoSim Initiative from the Canadian Partnership Against Cancer.
 

A version of this article originally appeared on Medscape.com.

Cervical cancer screening is a routine procedure, but in rare instances, there can be medical complications. A new study finds that, compared with women who have normal results, women who are diagnosed with an invasive malignancy have an increased risk for iatrogenic injuries.

Researchers in Sweden analyzed data on more than 3 million women who had undergone cervical cancer screening. The team found that 42 iatrogenic injuries that required at least 2 days of hospitalization occurred during the diagnostic work-up of women who had an abnormal screening test.

“Although cervical cancer screening is one of the most successful cancer prevention programs ... our research indicates that women with invasive cervical cancer experienced medical complications and psychological stress during their diagnostic work-up, although at a very low level,” commented corresponding author Qing Shen, PhD, from the department of medical epidemiology and biostatistics at the Karolinska Institute in Stockholm, Sweden.

The study was published in Cancer Epidemiology, Biomarkers & Prevention.

“Injuries can occur with diagnostic evaluation for cervical cancer,” commented Kecia Gaither, MD, MPH, FACOG, director of perinatal services at Lincoln Medical and Mental Health Center, New York City Health and Hospitals System, who was not involved in the study.

“Given the fact that neovascularization occurs with cancers, a large biopsy in such a circumstance could lead to a hematoma or excessive blood loss. It rarely occurs but most certainly is possible,” said Dr. Gaither.

Also weighing in with comments, Cathy Popadiuk, MD, FRCS, an associate professor of medicine in the department of obstetrics and gynecology at Memorial University of Newfoundland, St. John’s, said the findings are reflective of the real-world and North American experience.

“There are indeed rare bad things that can happen during diagnostic work-up of abnormal pap smears, and usually this is with associated other disease, such as actual cancer or fibroids that can also bleed and may be in the cervix, etc.,” she told this news organization. “And definitely, when there is undetected cancer, this can bleed, requiring transfusion and hospital admission.”

Dr. Popadiuk pointed out that Sweden may be more liberal in admitting patients to hospital, whereas in North America, “we are trying to move away from inpatient care.” She added, “When you are getting these relatively minor procedures, you don’t expect something bad to happen in the clinic.”

Women may become anxious, and admission is the easiest way to arrange for care such as transfusions or observation for more bleeding, she noted. In addition, vaginal packing may be needed to control hemorrhage, and “with vaginal packing, women are unable to void and need a Foley catheter, and that, again, cannot be managed at home easily,” she explained. “After bleeding settles, the vaginal pack is removed, often the next day.” This may be why some women are admitted to hospital.
 

Increased risk of injury

In a previous study, Dr. Shen and colleagues found there was an increased risk for injuries during the period before and after a diagnosis of any cancer (BMJ. 2016;354:i4218). Those findings suggested the interval between first suspicion of cancer and diagnosis or initiation of treatment might be a high-risk time for injuries in cancer care.

In this latest study, they assessed whether there was a similar increase in injury risk among patients screened for cervical cancer. Using the Swedish Total Population Register, they identified 3,016,307 women who had undergone cervical screening during the period 2001-2012.

The final analysis included 1,853,510 women whose pap smear results were normal; 22,435 women who were diagnosed with cervical intraepithelial neoplasia (CIN); 20,692 women with CIN2; 36,542 women with CIN3 or adenocarcinoma in situ (AIS); and 5,189 women with invasive cervical cancer.

The team found that, among women who had an abnormal screening test, 42 iatrogenic injuries occurred that required at least 2 days of hospital admission. The highest risk was among women diagnosed with invasive cancer. The risk was also increased among women diagnosed with CIN3/AIS, but not among women with lower grades of CIN.

The most common types of iatrogenic injuries were hemorrhage or hematoma and infections. Among all groups of women, the incidence rate of injuries that were caused by medical procedures and care was greater than that of injuries caused by drugs or biological substances.

A total of 91 noniatrogenic injuries that required at least 1 day of hospitalization were identified. The risk was increased among women with invasive cervical cancer but not for women with other cervical abnormalities. The most common type of noniatrogenic injury was unintentional injuries.

The study was sponsored by the Swedish Cancer Society and the Swedish Research Council for Health, Working Life and Welfare. One author received a Karolinska Institute Senior Researcher Award and a Strategic Research Area in Epidemiology Award, and one author received a grant from the China Scholarship Council. Dr. Shen has disclosed no relevant financial relationships. Dr. Popadiuk has received personal fees and nonfinancial support as a member of the OncoSim Initiative from the Canadian Partnership Against Cancer.
 

A version of this article originally appeared on Medscape.com.

Cervical cancer screening is a routine procedure, but in rare instances, there can be medical complications. A new study finds that, compared with women who have normal results, women who are diagnosed with an invasive malignancy have an increased risk for iatrogenic injuries.

Researchers in Sweden analyzed data on more than 3 million women who had undergone cervical cancer screening. The team found that 42 iatrogenic injuries that required at least 2 days of hospitalization occurred during the diagnostic work-up of women who had an abnormal screening test.

“Although cervical cancer screening is one of the most successful cancer prevention programs ... our research indicates that women with invasive cervical cancer experienced medical complications and psychological stress during their diagnostic work-up, although at a very low level,” commented corresponding author Qing Shen, PhD, from the department of medical epidemiology and biostatistics at the Karolinska Institute in Stockholm, Sweden.

The study was published in Cancer Epidemiology, Biomarkers & Prevention.

“Injuries can occur with diagnostic evaluation for cervical cancer,” commented Kecia Gaither, MD, MPH, FACOG, director of perinatal services at Lincoln Medical and Mental Health Center, New York City Health and Hospitals System, who was not involved in the study.

“Given the fact that neovascularization occurs with cancers, a large biopsy in such a circumstance could lead to a hematoma or excessive blood loss. It rarely occurs but most certainly is possible,” said Dr. Gaither.

Also weighing in with comments, Cathy Popadiuk, MD, FRCS, an associate professor of medicine in the department of obstetrics and gynecology at Memorial University of Newfoundland, St. John’s, said the findings are reflective of the real-world and North American experience.

“There are indeed rare bad things that can happen during diagnostic work-up of abnormal pap smears, and usually this is with associated other disease, such as actual cancer or fibroids that can also bleed and may be in the cervix, etc.,” she told this news organization. “And definitely, when there is undetected cancer, this can bleed, requiring transfusion and hospital admission.”

Dr. Popadiuk pointed out that Sweden may be more liberal in admitting patients to hospital, whereas in North America, “we are trying to move away from inpatient care.” She added, “When you are getting these relatively minor procedures, you don’t expect something bad to happen in the clinic.”

Women may become anxious, and admission is the easiest way to arrange for care such as transfusions or observation for more bleeding, she noted. In addition, vaginal packing may be needed to control hemorrhage, and “with vaginal packing, women are unable to void and need a Foley catheter, and that, again, cannot be managed at home easily,” she explained. “After bleeding settles, the vaginal pack is removed, often the next day.” This may be why some women are admitted to hospital.
 

Increased risk of injury

In a previous study, Dr. Shen and colleagues found there was an increased risk for injuries during the period before and after a diagnosis of any cancer (BMJ. 2016;354:i4218). Those findings suggested the interval between first suspicion of cancer and diagnosis or initiation of treatment might be a high-risk time for injuries in cancer care.

In this latest study, they assessed whether there was a similar increase in injury risk among patients screened for cervical cancer. Using the Swedish Total Population Register, they identified 3,016,307 women who had undergone cervical screening during the period 2001-2012.

The final analysis included 1,853,510 women whose pap smear results were normal; 22,435 women who were diagnosed with cervical intraepithelial neoplasia (CIN); 20,692 women with CIN2; 36,542 women with CIN3 or adenocarcinoma in situ (AIS); and 5,189 women with invasive cervical cancer.

The team found that, among women who had an abnormal screening test, 42 iatrogenic injuries occurred that required at least 2 days of hospital admission. The highest risk was among women diagnosed with invasive cancer. The risk was also increased among women diagnosed with CIN3/AIS, but not among women with lower grades of CIN.

The most common types of iatrogenic injuries were hemorrhage or hematoma and infections. Among all groups of women, the incidence rate of injuries that were caused by medical procedures and care was greater than that of injuries caused by drugs or biological substances.

A total of 91 noniatrogenic injuries that required at least 1 day of hospitalization were identified. The risk was increased among women with invasive cervical cancer but not for women with other cervical abnormalities. The most common type of noniatrogenic injury was unintentional injuries.

The study was sponsored by the Swedish Cancer Society and the Swedish Research Council for Health, Working Life and Welfare. One author received a Karolinska Institute Senior Researcher Award and a Strategic Research Area in Epidemiology Award, and one author received a grant from the China Scholarship Council. Dr. Shen has disclosed no relevant financial relationships. Dr. Popadiuk has received personal fees and nonfinancial support as a member of the OncoSim Initiative from the Canadian Partnership Against Cancer.
 

A version of this article originally appeared on Medscape.com.

From the beginning, SHM has consciously and consistently taken a unique approach to its advocacy efforts with the federal government. The advocacy priorities of SHM most often concern issues that we feel have an impact on our patients and the broader delivery system, as opposed to a focus on issues that have direct financial benefit to our members.

This strategy has served SHM well. It has earned respect among policymakers and we have seen significant success for a young and relatively small medical society. The issues where we spend the bulk of our time and effort include advocating for issues like alternative payment models (APMs), which reward care quality as opposed to volume, as well as issues related to data integrity that APMs require. We have advocated strongly for changes to dysfunctional observation status rules, for workforce adequacy and sustainability, and for recognition of the importance of hospital medicine’s contribution to the redesign of our nations delivery system. And SHM will continue to advocate for many other issues identified as being important to hospital medicine and our patients.

This year, for the first time in the two decades that I have served on the SHM Public Policy Committee, Medicare has proposed changes that would create unprecedented financial hardship for hospital medicine groups. Each year, as a part of its advocacy agenda, SHM reviews and comments on proposed changes to the Medicare Physician Fee Schedule (PFS). Among other things, the PFS adjusts payment rates to physicians for specific services. Changes under the PFS are required to be budget neutral. In effect, budget neutrality means that whenever certain services receive an increased payment rate, CMS is required to offset these changes by making cuts to other services. This year, in an effort to correct the long-standing underfunding of primary care services, CMS has increased payment for many Evaluation and Management (E&M) codes associated with outpatient primary care services. However, due to budget neutrality requirements, many inpatient E&M care services will be receiving significant cuts.

The goal of increasing payment rates for primary care services is laudable, as many of these cognitive services have been long underfunded. However, the proposed payment increases will only apply to outpatient E&M codes and not their corresponding inpatient codes. While our outpatient Internal Medicine and Family Practice colleagues will benefit from these changes, inpatient providers, including hospitalists, stand to lose a significant amount revenue. SHM and the hospitalists we represent estimate that the proposed budget neutrality adjustment will lead to an approximate 8 percent decrease in Medicare Fee for Services (FFS) revenue. Hospitalists are among the specialties that will be most impacted from these proposed changes. If put into effect, these proposals will leave hospital medicine behind.

These changes have been proposed at a time when hospitalists, along with their colleagues in critical care and emergency medicine, have been caring for patients on the frontlines of the COVID-19 pandemic at great risk to themselves at their families. While hospitalists are working tirelessly to provide lifesaving care to COVID-positive patients throughout the country, hospitalist groups have struggled financially as a result of the pandemic. Inpatient volumes, and therefore care reimbursement, has dropped significantly. Many hospitalists have already reported pay reductions of 20% or more. Others have seen their shifts reduced, resulting in understaffing, which may compromise the quality of care. For many groups, a Medicare reimbursement cut of this magnitude add fuel to an already strained revenue stream and will not be financially sustainable.

SHM is, of course, fighting back. We are not asking CMS to completely abandon the increases in reimbursement for primary care outpatient codes, and we support properly valuing outpatient care services. However, we are asking CMS to find a solution that does not come at the expense of hospital medicine and the other specialties that care for acutely ill hospitalized patients, including patients with COVID-19. If a better solution requires holding off on the proposal for another year, CMS should do so. Furthermore, SHM is asking Congress to abandon the statutory requirement for budget neutrality in these extraordinary times as CMS and Congress work to find towards a solution that properly values both inpatient and outpatient care services.

To send a message to your representatives urging them to stop these payment cuts, please visit SHM’s Legislative Action Center at www.votervoice.net/SHM/campaigns/77226/respond. You can read our full comments on the Medicare Physician Fee Schedule Proposed Rule at www.hospitalmedicine.org/policy--advocacy/letters/2021-physician-fee-schedule-proposed-rule/.

From the beginning, SHM has consciously and consistently taken a unique approach to its advocacy efforts with the federal government. The advocacy priorities of SHM most often concern issues that we feel have an impact on our patients and the broader delivery system, as opposed to a focus on issues that have direct financial benefit to our members.

This strategy has served SHM well. It has earned respect among policymakers and we have seen significant success for a young and relatively small medical society. The issues where we spend the bulk of our time and effort include advocating for issues like alternative payment models (APMs), which reward care quality as opposed to volume, as well as issues related to data integrity that APMs require. We have advocated strongly for changes to dysfunctional observation status rules, for workforce adequacy and sustainability, and for recognition of the importance of hospital medicine’s contribution to the redesign of our nations delivery system. And SHM will continue to advocate for many other issues identified as being important to hospital medicine and our patients.

This year, for the first time in the two decades that I have served on the SHM Public Policy Committee, Medicare has proposed changes that would create unprecedented financial hardship for hospital medicine groups. Each year, as a part of its advocacy agenda, SHM reviews and comments on proposed changes to the Medicare Physician Fee Schedule (PFS). Among other things, the PFS adjusts payment rates to physicians for specific services. Changes under the PFS are required to be budget neutral. In effect, budget neutrality means that whenever certain services receive an increased payment rate, CMS is required to offset these changes by making cuts to other services. This year, in an effort to correct the long-standing underfunding of primary care services, CMS has increased payment for many Evaluation and Management (E&M) codes associated with outpatient primary care services. However, due to budget neutrality requirements, many inpatient E&M care services will be receiving significant cuts.

The goal of increasing payment rates for primary care services is laudable, as many of these cognitive services have been long underfunded. However, the proposed payment increases will only apply to outpatient E&M codes and not their corresponding inpatient codes. While our outpatient Internal Medicine and Family Practice colleagues will benefit from these changes, inpatient providers, including hospitalists, stand to lose a significant amount revenue. SHM and the hospitalists we represent estimate that the proposed budget neutrality adjustment will lead to an approximate 8 percent decrease in Medicare Fee for Services (FFS) revenue. Hospitalists are among the specialties that will be most impacted from these proposed changes. If put into effect, these proposals will leave hospital medicine behind.

These changes have been proposed at a time when hospitalists, along with their colleagues in critical care and emergency medicine, have been caring for patients on the frontlines of the COVID-19 pandemic at great risk to themselves at their families. While hospitalists are working tirelessly to provide lifesaving care to COVID-positive patients throughout the country, hospitalist groups have struggled financially as a result of the pandemic. Inpatient volumes, and therefore care reimbursement, has dropped significantly. Many hospitalists have already reported pay reductions of 20% or more. Others have seen their shifts reduced, resulting in understaffing, which may compromise the quality of care. For many groups, a Medicare reimbursement cut of this magnitude add fuel to an already strained revenue stream and will not be financially sustainable.

SHM is, of course, fighting back. We are not asking CMS to completely abandon the increases in reimbursement for primary care outpatient codes, and we support properly valuing outpatient care services. However, we are asking CMS to find a solution that does not come at the expense of hospital medicine and the other specialties that care for acutely ill hospitalized patients, including patients with COVID-19. If a better solution requires holding off on the proposal for another year, CMS should do so. Furthermore, SHM is asking Congress to abandon the statutory requirement for budget neutrality in these extraordinary times as CMS and Congress work to find towards a solution that properly values both inpatient and outpatient care services.

To send a message to your representatives urging them to stop these payment cuts, please visit SHM’s Legislative Action Center at www.votervoice.net/SHM/campaigns/77226/respond. You can read our full comments on the Medicare Physician Fee Schedule Proposed Rule at www.hospitalmedicine.org/policy--advocacy/letters/2021-physician-fee-schedule-proposed-rule/.

From the beginning, SHM has consciously and consistently taken a unique approach to its advocacy efforts with the federal government. The advocacy priorities of SHM most often concern issues that we feel have an impact on our patients and the broader delivery system, as opposed to a focus on issues that have direct financial benefit to our members.

This strategy has served SHM well. It has earned respect among policymakers and we have seen significant success for a young and relatively small medical society. The issues where we spend the bulk of our time and effort include advocating for issues like alternative payment models (APMs), which reward care quality as opposed to volume, as well as issues related to data integrity that APMs require. We have advocated strongly for changes to dysfunctional observation status rules, for workforce adequacy and sustainability, and for recognition of the importance of hospital medicine’s contribution to the redesign of our nations delivery system. And SHM will continue to advocate for many other issues identified as being important to hospital medicine and our patients.

This year, for the first time in the two decades that I have served on the SHM Public Policy Committee, Medicare has proposed changes that would create unprecedented financial hardship for hospital medicine groups. Each year, as a part of its advocacy agenda, SHM reviews and comments on proposed changes to the Medicare Physician Fee Schedule (PFS). Among other things, the PFS adjusts payment rates to physicians for specific services. Changes under the PFS are required to be budget neutral. In effect, budget neutrality means that whenever certain services receive an increased payment rate, CMS is required to offset these changes by making cuts to other services. This year, in an effort to correct the long-standing underfunding of primary care services, CMS has increased payment for many Evaluation and Management (E&M) codes associated with outpatient primary care services. However, due to budget neutrality requirements, many inpatient E&M care services will be receiving significant cuts.

The goal of increasing payment rates for primary care services is laudable, as many of these cognitive services have been long underfunded. However, the proposed payment increases will only apply to outpatient E&M codes and not their corresponding inpatient codes. While our outpatient Internal Medicine and Family Practice colleagues will benefit from these changes, inpatient providers, including hospitalists, stand to lose a significant amount revenue. SHM and the hospitalists we represent estimate that the proposed budget neutrality adjustment will lead to an approximate 8 percent decrease in Medicare Fee for Services (FFS) revenue. Hospitalists are among the specialties that will be most impacted from these proposed changes. If put into effect, these proposals will leave hospital medicine behind.

These changes have been proposed at a time when hospitalists, along with their colleagues in critical care and emergency medicine, have been caring for patients on the frontlines of the COVID-19 pandemic at great risk to themselves at their families. While hospitalists are working tirelessly to provide lifesaving care to COVID-positive patients throughout the country, hospitalist groups have struggled financially as a result of the pandemic. Inpatient volumes, and therefore care reimbursement, has dropped significantly. Many hospitalists have already reported pay reductions of 20% or more. Others have seen their shifts reduced, resulting in understaffing, which may compromise the quality of care. For many groups, a Medicare reimbursement cut of this magnitude add fuel to an already strained revenue stream and will not be financially sustainable.

SHM is, of course, fighting back. We are not asking CMS to completely abandon the increases in reimbursement for primary care outpatient codes, and we support properly valuing outpatient care services. However, we are asking CMS to find a solution that does not come at the expense of hospital medicine and the other specialties that care for acutely ill hospitalized patients, including patients with COVID-19. If a better solution requires holding off on the proposal for another year, CMS should do so. Furthermore, SHM is asking Congress to abandon the statutory requirement for budget neutrality in these extraordinary times as CMS and Congress work to find towards a solution that properly values both inpatient and outpatient care services.

To send a message to your representatives urging them to stop these payment cuts, please visit SHM’s Legislative Action Center at www.votervoice.net/SHM/campaigns/77226/respond. You can read our full comments on the Medicare Physician Fee Schedule Proposed Rule at www.hospitalmedicine.org/policy--advocacy/letters/2021-physician-fee-schedule-proposed-rule/.

Many of the US Supreme Court Justices seem disinclined to throw out the Affordable Care Act (ACA) – at least that was the takeaway from the questions they asked during oral arguments on whether the law is unconstitutional.

The Justices conducted arguments by telephone in the case, California v Texas (previously California v US), which was brought by 18 Republican state officials and two individual plaintiffs. The Trump administration joined the plaintiffs in June, arguing that the entire law should be overturned. The ACA is being defended by Democratic state officials from 16 states and Washington, D.C.

The Republican plaintiffs have essentially argued that the ACA cannot stand without the individual mandate requirement – that it is not possible to “sever” it from the rest of the Act. In 2017, Congress set the tax penalty to $0 if an individual did not buy insurance. The mandate to buy insurance was left in place, but there were no longer any consequences. The plaintiffs said that congressional act was equivalent to severing the mandate.

But many Justices appeared to take a dim view of that argument.

“It’s a very straightforward case for severability under our precedents,” said Justice Brett Kavanaugh. “Meaning that we would excise the mandate and leave the rest of the Act in play. Congress knows how to write an inseverability clause and that is not the language that they chose here,” he said.

Justice Elena Kagan also questioned how it would jibe with legal precedent to allow the severing of one part of a law when there was no clear instruction from Congress on the issue. She also raised the concern that it would open the door to all sorts of challenges.

“It would seem a big deal to say that, if you can point to injury with respect to one provision and you can concoct some kind of inseverability argument, that allows you to challenge anything else in the statute,” she said.

“Isn’t that something that really cuts against all of our doctrine?” asked Kagan.

“I think it’s hard for you to argue that Congress intended the entire Act to fall if the mandate was struck down when the same Congress that lowered the penalty to zero did not even try to repeal the rest of the act,” said Chief Justice John Roberts.

“I think, frankly, that they wanted the Court to do that but that’s not our job,” he added.
 

Proof of harm?

To have the standing to sue, the plaintiffs have to prove they have been harmed by the ACA. Texas Solicitor General Kyle Hawkins said that individuals feel compelled to buy insurance – even without a penalty hanging over their heads.

Justice Stephen Breyer argued that many laws include what he called “precatory” language – that is, they seek to compel citizens to do something. But most don’t penalize those who fail to act – just like the ACA currently.

If, as the Texas plaintiffs argued, it’s still unconstitutional to make such a request, “I think there will be an awful lot of language in an awful lot of statutes that will suddenly be the subject of court constitutional challenge,” he said.

Hawkins disagreed. He said the ACA’s mandate “is not some suggestion, not some hortatory statement. It is the law of the United States of America today that you have to purchase health insurance and not just any health insurance, but health insurance that the federal government has decided would be best for you.”

Hawkins said that, if just one additional person signed up for Medicaid, the state of Texas and the other plaintiff states would be harmed. He said people were continuing to enroll in the program because they believed the law required them to get health insurance.

Justice Sonia Sotomayor said that defied common sense. “The problem is that your theory assumes people that people are going to pay a tax and break the law by not buying insurance, but they wouldn’t do it when the tax is zero.”
 

What’s at stake

It’s unlikely the justices will issue a decision immediately. They have until the end of the term in June to rule.

Katie Keith, JD, MPH, a principal at Keith Policy Solutions, LLC, outlined the potential outcomes in Health Affairs .

“The most likely scenario is that the Court maintains the status quo,” she wrote. They could get there by deciding Texas et al. did not have standing to bring the case. Or they could decide that either the mandate is constitutional or that it is unconstitutional but can be severed from the rest of the ACA.

The Court could alternatively find that some or all of the law’s insurance provisions – such as protections for people with pre-existing conditions – can’t be severed from the mandate. Or the justices could strike down all of the insurance consumer protections, the health insurance marketplaces, premium tax credits, and other provisions, which would force states to come up with the money to help people buy insurance. And states are unlikely to be able to do so, especially with the pandemic stretching their budgets.

Finally, the Court could find that the mandate can’t be separated, which would essentially overturn the law.

If that happens, some 15 million people could lose Medicaid coverage, 11 million who buy on health insurance exchanges could lose coverage, and 2.3 million young adults would no longer be able to stay on parents’ policies, according to the Kaiser Family Foundation. Kaiser also estimates that 54 million people under age 65 who have pre-existing conditions would no longer be guaranteed coverage.

The Urban Institute estimates that 21 million people could lose insurance – 15 million through Medicaid and the Children’s Health Insurance Program (CHIP) and 7.6 million through private nongroup coverage.
 

Medical societies weigh in

Multiple physicians’ groups, patient advocates, and hospital organizations have filed briefs with the Court in favor of keeping the law intact.

Twenty patient groups representing millions with pre-existing conditions – including the American Cancer Society, American Diabetes Association, American Heart Association, National Alliance on Mental Illness, National Organization for Rare Disorders, and the Kennedy Forum – filed a court brief in May arguing that the law has expanded access to insurance and improved patient outcomes.

“The coronavirus pandemic has only served to underscore the necessity of meaningful coverage – especially for those who are at high risk of being severely affected by the virus – including countless Americans who have pre-existing, acute or chronic conditions like heart disease, cancer, diabetes, lung diseases and multiple sclerosis,” they said in a statement.

Jacqueline W. Fincher, MD, MACP, president of the American College of Physicians, which joined a court brief in support of the law with 19 other medical organizations, said the law has worked.

“The coverage, protections and benefits provided by the ACA are critical to the well-being of millions of Americans,” she said in a statement.

“If the ACA were to be thrown out at the same time that we face the pandemic, it would cause chaos for physicians and our patients, and for the entire health care system,” said Fincher, adding that millions of Americans who have been infected could lose insurance if protections for pre-existing conditions disappeared.

“The ACA has revolutionized access to care for tens of millions of women by helping them obtain meaningful health coverage, ensuring that essential care is covered by insurers, and protecting patients from unfair insurance practices,” said Maureen G. Phipps, MD, MPH, CEO of the American College of Obstetricians and Gynecologists (ACOG), in a statement.

Overturning the ACA “would be one of the most singularly disruptive acts to be committed during this public health crisis,” she said.

American Psychiatric Association President Jeffrey Geller, MD, MPH, also warned of disruptions to care, especially for those with mental health and substance use disorders. “We urge the Supreme Court to preserve the entire Act, including the individual mandate,” he said, in a statement.

“In the midst of COVID is no time to let down the millions who we serve as our patients,” said Chip Kahn, Federation of American Health Systems president and CEO, in a statement.

“As caregivers, the goal of hospitals for our patients is to see increased access to affordable coverage for all Americans – not new obstacles,” he said, adding that the ACA “can accomplish this goal. We hope the Supreme Court will see its way clear to allow it to go forward.”
 

For the defense

Many legal analysts on social media who listened in to today’s hearing agreed that the tenor of the proceedings seemed to lean toward survival of the ACA.

“At this point I would say it is *extremely* likely that the ACA will be upheld, but the mandate struck down and severed out,” tweeted Raffi Melkonian, an appellate lawyer in Houston, Texas. “A decision on standing (throwing out the case entirely) is also possible. The chance that the ACA is struck down v. low.”

“Both Kavanaugh and Roberts have suggested this morning that they may view the individual mandate as severable from the rest of the law. If those two justices join the court’s three liberals in finding that the mandate is severable, that would be five votes to save the ACA,” tweeted the analysts at SCOTUS Blog.

Sean Marotta, a lawyer with Hogan Lovells’ Supreme Court group, agreed. “Oral argument is always an imperfect measure, but the Act’s defenders should feel good today,” he tweeted.
 

This article first appeared on Medscape.com.

Many of the US Supreme Court Justices seem disinclined to throw out the Affordable Care Act (ACA) – at least that was the takeaway from the questions they asked during oral arguments on whether the law is unconstitutional.

The Justices conducted arguments by telephone in the case, California v Texas (previously California v US), which was brought by 18 Republican state officials and two individual plaintiffs. The Trump administration joined the plaintiffs in June, arguing that the entire law should be overturned. The ACA is being defended by Democratic state officials from 16 states and Washington, D.C.

The Republican plaintiffs have essentially argued that the ACA cannot stand without the individual mandate requirement – that it is not possible to “sever” it from the rest of the Act. In 2017, Congress set the tax penalty to $0 if an individual did not buy insurance. The mandate to buy insurance was left in place, but there were no longer any consequences. The plaintiffs said that congressional act was equivalent to severing the mandate.

But many Justices appeared to take a dim view of that argument.

“It’s a very straightforward case for severability under our precedents,” said Justice Brett Kavanaugh. “Meaning that we would excise the mandate and leave the rest of the Act in play. Congress knows how to write an inseverability clause and that is not the language that they chose here,” he said.

Justice Elena Kagan also questioned how it would jibe with legal precedent to allow the severing of one part of a law when there was no clear instruction from Congress on the issue. She also raised the concern that it would open the door to all sorts of challenges.

“It would seem a big deal to say that, if you can point to injury with respect to one provision and you can concoct some kind of inseverability argument, that allows you to challenge anything else in the statute,” she said.

“Isn’t that something that really cuts against all of our doctrine?” asked Kagan.

“I think it’s hard for you to argue that Congress intended the entire Act to fall if the mandate was struck down when the same Congress that lowered the penalty to zero did not even try to repeal the rest of the act,” said Chief Justice John Roberts.

“I think, frankly, that they wanted the Court to do that but that’s not our job,” he added.
 

Proof of harm?

To have the standing to sue, the plaintiffs have to prove they have been harmed by the ACA. Texas Solicitor General Kyle Hawkins said that individuals feel compelled to buy insurance – even without a penalty hanging over their heads.

Justice Stephen Breyer argued that many laws include what he called “precatory” language – that is, they seek to compel citizens to do something. But most don’t penalize those who fail to act – just like the ACA currently.

If, as the Texas plaintiffs argued, it’s still unconstitutional to make such a request, “I think there will be an awful lot of language in an awful lot of statutes that will suddenly be the subject of court constitutional challenge,” he said.

Hawkins disagreed. He said the ACA’s mandate “is not some suggestion, not some hortatory statement. It is the law of the United States of America today that you have to purchase health insurance and not just any health insurance, but health insurance that the federal government has decided would be best for you.”

Hawkins said that, if just one additional person signed up for Medicaid, the state of Texas and the other plaintiff states would be harmed. He said people were continuing to enroll in the program because they believed the law required them to get health insurance.

Justice Sonia Sotomayor said that defied common sense. “The problem is that your theory assumes people that people are going to pay a tax and break the law by not buying insurance, but they wouldn’t do it when the tax is zero.”
 

What’s at stake

It’s unlikely the justices will issue a decision immediately. They have until the end of the term in June to rule.

Katie Keith, JD, MPH, a principal at Keith Policy Solutions, LLC, outlined the potential outcomes in Health Affairs .

“The most likely scenario is that the Court maintains the status quo,” she wrote. They could get there by deciding Texas et al. did not have standing to bring the case. Or they could decide that either the mandate is constitutional or that it is unconstitutional but can be severed from the rest of the ACA.

The Court could alternatively find that some or all of the law’s insurance provisions – such as protections for people with pre-existing conditions – can’t be severed from the mandate. Or the justices could strike down all of the insurance consumer protections, the health insurance marketplaces, premium tax credits, and other provisions, which would force states to come up with the money to help people buy insurance. And states are unlikely to be able to do so, especially with the pandemic stretching their budgets.

Finally, the Court could find that the mandate can’t be separated, which would essentially overturn the law.

If that happens, some 15 million people could lose Medicaid coverage, 11 million who buy on health insurance exchanges could lose coverage, and 2.3 million young adults would no longer be able to stay on parents’ policies, according to the Kaiser Family Foundation. Kaiser also estimates that 54 million people under age 65 who have pre-existing conditions would no longer be guaranteed coverage.

The Urban Institute estimates that 21 million people could lose insurance – 15 million through Medicaid and the Children’s Health Insurance Program (CHIP) and 7.6 million through private nongroup coverage.
 

Medical societies weigh in

Multiple physicians’ groups, patient advocates, and hospital organizations have filed briefs with the Court in favor of keeping the law intact.

Twenty patient groups representing millions with pre-existing conditions – including the American Cancer Society, American Diabetes Association, American Heart Association, National Alliance on Mental Illness, National Organization for Rare Disorders, and the Kennedy Forum – filed a court brief in May arguing that the law has expanded access to insurance and improved patient outcomes.

“The coronavirus pandemic has only served to underscore the necessity of meaningful coverage – especially for those who are at high risk of being severely affected by the virus – including countless Americans who have pre-existing, acute or chronic conditions like heart disease, cancer, diabetes, lung diseases and multiple sclerosis,” they said in a statement.

Jacqueline W. Fincher, MD, MACP, president of the American College of Physicians, which joined a court brief in support of the law with 19 other medical organizations, said the law has worked.

“The coverage, protections and benefits provided by the ACA are critical to the well-being of millions of Americans,” she said in a statement.

“If the ACA were to be thrown out at the same time that we face the pandemic, it would cause chaos for physicians and our patients, and for the entire health care system,” said Fincher, adding that millions of Americans who have been infected could lose insurance if protections for pre-existing conditions disappeared.

“The ACA has revolutionized access to care for tens of millions of women by helping them obtain meaningful health coverage, ensuring that essential care is covered by insurers, and protecting patients from unfair insurance practices,” said Maureen G. Phipps, MD, MPH, CEO of the American College of Obstetricians and Gynecologists (ACOG), in a statement.

Overturning the ACA “would be one of the most singularly disruptive acts to be committed during this public health crisis,” she said.

American Psychiatric Association President Jeffrey Geller, MD, MPH, also warned of disruptions to care, especially for those with mental health and substance use disorders. “We urge the Supreme Court to preserve the entire Act, including the individual mandate,” he said, in a statement.

“In the midst of COVID is no time to let down the millions who we serve as our patients,” said Chip Kahn, Federation of American Health Systems president and CEO, in a statement.

“As caregivers, the goal of hospitals for our patients is to see increased access to affordable coverage for all Americans – not new obstacles,” he said, adding that the ACA “can accomplish this goal. We hope the Supreme Court will see its way clear to allow it to go forward.”
 

For the defense

Many legal analysts on social media who listened in to today’s hearing agreed that the tenor of the proceedings seemed to lean toward survival of the ACA.

“At this point I would say it is *extremely* likely that the ACA will be upheld, but the mandate struck down and severed out,” tweeted Raffi Melkonian, an appellate lawyer in Houston, Texas. “A decision on standing (throwing out the case entirely) is also possible. The chance that the ACA is struck down v. low.”

“Both Kavanaugh and Roberts have suggested this morning that they may view the individual mandate as severable from the rest of the law. If those two justices join the court’s three liberals in finding that the mandate is severable, that would be five votes to save the ACA,” tweeted the analysts at SCOTUS Blog.

Sean Marotta, a lawyer with Hogan Lovells’ Supreme Court group, agreed. “Oral argument is always an imperfect measure, but the Act’s defenders should feel good today,” he tweeted.
 

This article first appeared on Medscape.com.

Many of the US Supreme Court Justices seem disinclined to throw out the Affordable Care Act (ACA) – at least that was the takeaway from the questions they asked during oral arguments on whether the law is unconstitutional.

The Justices conducted arguments by telephone in the case, California v Texas (previously California v US), which was brought by 18 Republican state officials and two individual plaintiffs. The Trump administration joined the plaintiffs in June, arguing that the entire law should be overturned. The ACA is being defended by Democratic state officials from 16 states and Washington, D.C.

The Republican plaintiffs have essentially argued that the ACA cannot stand without the individual mandate requirement – that it is not possible to “sever” it from the rest of the Act. In 2017, Congress set the tax penalty to $0 if an individual did not buy insurance. The mandate to buy insurance was left in place, but there were no longer any consequences. The plaintiffs said that congressional act was equivalent to severing the mandate.

But many Justices appeared to take a dim view of that argument.

“It’s a very straightforward case for severability under our precedents,” said Justice Brett Kavanaugh. “Meaning that we would excise the mandate and leave the rest of the Act in play. Congress knows how to write an inseverability clause and that is not the language that they chose here,” he said.

Justice Elena Kagan also questioned how it would jibe with legal precedent to allow the severing of one part of a law when there was no clear instruction from Congress on the issue. She also raised the concern that it would open the door to all sorts of challenges.

“It would seem a big deal to say that, if you can point to injury with respect to one provision and you can concoct some kind of inseverability argument, that allows you to challenge anything else in the statute,” she said.

“Isn’t that something that really cuts against all of our doctrine?” asked Kagan.

“I think it’s hard for you to argue that Congress intended the entire Act to fall if the mandate was struck down when the same Congress that lowered the penalty to zero did not even try to repeal the rest of the act,” said Chief Justice John Roberts.

“I think, frankly, that they wanted the Court to do that but that’s not our job,” he added.
 

Proof of harm?

To have the standing to sue, the plaintiffs have to prove they have been harmed by the ACA. Texas Solicitor General Kyle Hawkins said that individuals feel compelled to buy insurance – even without a penalty hanging over their heads.

Justice Stephen Breyer argued that many laws include what he called “precatory” language – that is, they seek to compel citizens to do something. But most don’t penalize those who fail to act – just like the ACA currently.

If, as the Texas plaintiffs argued, it’s still unconstitutional to make such a request, “I think there will be an awful lot of language in an awful lot of statutes that will suddenly be the subject of court constitutional challenge,” he said.

Hawkins disagreed. He said the ACA’s mandate “is not some suggestion, not some hortatory statement. It is the law of the United States of America today that you have to purchase health insurance and not just any health insurance, but health insurance that the federal government has decided would be best for you.”

Hawkins said that, if just one additional person signed up for Medicaid, the state of Texas and the other plaintiff states would be harmed. He said people were continuing to enroll in the program because they believed the law required them to get health insurance.

Justice Sonia Sotomayor said that defied common sense. “The problem is that your theory assumes people that people are going to pay a tax and break the law by not buying insurance, but they wouldn’t do it when the tax is zero.”
 

What’s at stake

It’s unlikely the justices will issue a decision immediately. They have until the end of the term in June to rule.

Katie Keith, JD, MPH, a principal at Keith Policy Solutions, LLC, outlined the potential outcomes in Health Affairs .

“The most likely scenario is that the Court maintains the status quo,” she wrote. They could get there by deciding Texas et al. did not have standing to bring the case. Or they could decide that either the mandate is constitutional or that it is unconstitutional but can be severed from the rest of the ACA.

The Court could alternatively find that some or all of the law’s insurance provisions – such as protections for people with pre-existing conditions – can’t be severed from the mandate. Or the justices could strike down all of the insurance consumer protections, the health insurance marketplaces, premium tax credits, and other provisions, which would force states to come up with the money to help people buy insurance. And states are unlikely to be able to do so, especially with the pandemic stretching their budgets.

Finally, the Court could find that the mandate can’t be separated, which would essentially overturn the law.

If that happens, some 15 million people could lose Medicaid coverage, 11 million who buy on health insurance exchanges could lose coverage, and 2.3 million young adults would no longer be able to stay on parents’ policies, according to the Kaiser Family Foundation. Kaiser also estimates that 54 million people under age 65 who have pre-existing conditions would no longer be guaranteed coverage.

The Urban Institute estimates that 21 million people could lose insurance – 15 million through Medicaid and the Children’s Health Insurance Program (CHIP) and 7.6 million through private nongroup coverage.
 

Medical societies weigh in

Multiple physicians’ groups, patient advocates, and hospital organizations have filed briefs with the Court in favor of keeping the law intact.

Twenty patient groups representing millions with pre-existing conditions – including the American Cancer Society, American Diabetes Association, American Heart Association, National Alliance on Mental Illness, National Organization for Rare Disorders, and the Kennedy Forum – filed a court brief in May arguing that the law has expanded access to insurance and improved patient outcomes.

“The coronavirus pandemic has only served to underscore the necessity of meaningful coverage – especially for those who are at high risk of being severely affected by the virus – including countless Americans who have pre-existing, acute or chronic conditions like heart disease, cancer, diabetes, lung diseases and multiple sclerosis,” they said in a statement.

Jacqueline W. Fincher, MD, MACP, president of the American College of Physicians, which joined a court brief in support of the law with 19 other medical organizations, said the law has worked.

“The coverage, protections and benefits provided by the ACA are critical to the well-being of millions of Americans,” she said in a statement.

“If the ACA were to be thrown out at the same time that we face the pandemic, it would cause chaos for physicians and our patients, and for the entire health care system,” said Fincher, adding that millions of Americans who have been infected could lose insurance if protections for pre-existing conditions disappeared.

“The ACA has revolutionized access to care for tens of millions of women by helping them obtain meaningful health coverage, ensuring that essential care is covered by insurers, and protecting patients from unfair insurance practices,” said Maureen G. Phipps, MD, MPH, CEO of the American College of Obstetricians and Gynecologists (ACOG), in a statement.

Overturning the ACA “would be one of the most singularly disruptive acts to be committed during this public health crisis,” she said.

American Psychiatric Association President Jeffrey Geller, MD, MPH, also warned of disruptions to care, especially for those with mental health and substance use disorders. “We urge the Supreme Court to preserve the entire Act, including the individual mandate,” he said, in a statement.

“In the midst of COVID is no time to let down the millions who we serve as our patients,” said Chip Kahn, Federation of American Health Systems president and CEO, in a statement.

“As caregivers, the goal of hospitals for our patients is to see increased access to affordable coverage for all Americans – not new obstacles,” he said, adding that the ACA “can accomplish this goal. We hope the Supreme Court will see its way clear to allow it to go forward.”
 

For the defense

Many legal analysts on social media who listened in to today’s hearing agreed that the tenor of the proceedings seemed to lean toward survival of the ACA.

“At this point I would say it is *extremely* likely that the ACA will be upheld, but the mandate struck down and severed out,” tweeted Raffi Melkonian, an appellate lawyer in Houston, Texas. “A decision on standing (throwing out the case entirely) is also possible. The chance that the ACA is struck down v. low.”

“Both Kavanaugh and Roberts have suggested this morning that they may view the individual mandate as severable from the rest of the law. If those two justices join the court’s three liberals in finding that the mandate is severable, that would be five votes to save the ACA,” tweeted the analysts at SCOTUS Blog.

Sean Marotta, a lawyer with Hogan Lovells’ Supreme Court group, agreed. “Oral argument is always an imperfect measure, but the Act’s defenders should feel good today,” he tweeted.
 

This article first appeared on Medscape.com.