Venous Thromboembolism

A diagnostic workup for pulmonary embolism (PE) should be performed in all patients with recent onset of exertional dyspnea, according to the authors of an article published in the Journal of Thrombosis and Haemostasis. That conclusion emerged from an analysis of PE prevalence in 417 patients with recent marked exertional dyspnea performing previously well-tolerated physical activities.

Exertional dyspnea is a frequently encountered complaint in clinical practice. Missteps in both diagnosis and early management, however, have been found to be prevalent in emergency department practices. PE diagnosis can be delayed or altogether missed through nonspecific clinical manifestations or the absence of typical signs and symptoms, with a complicated clinical course or mortality as a consequence, stated the researchers. Also, failure to diagnose PE is a common malpractice allegation.

Noting that the prevalence of PE among patients with dyspnea on exertion has not been reported, the authors hypothesized: “PE might be a frequent underlying condition in patients presenting for care complaining of marked dyspnea on exertion of recent onset.”

In a multicenter prospective, cross-sectional study among 14 university or hospital centers in Italy, patients who were referred for outpatient evaluation with recent (< 1 month) dyspnea on exertion with a severity of 3 or 4 on the modified Medical Research Council dyspnea scale were potentially eligible for the study. Prior deep-vein thrombosis (DVT), PE, and use of therapeutic anticoagulation were among exclusion criteria. All patients aged 75 years or younger with recent (< 1 month) marked exertional dyspnea had a systematic workup for PE, irrespective of concomitant signs or symptoms of venous thromboembolism and alternative explanations for dyspnea. The main study outcome was prevalence of PE in the entire cohort of patients with recent marked dyspnea on exertion.

When about 400 patients had been enrolled after an interim analysis in which the preestablished stopping rule (if the lower limit of the 95% confidence interval of the prevalence of PE exceeds 20%) was met, the study was prematurely terminated. PE was found, after exclusion of 134 patients based on low PE clinical probability and normal D-dimer, in 134 (47.3%) of the remaining 283 patients. The overall PE prevalence was 32.1% (95% confidence interval, 27.8-36.8).

PE was present in 40 of 204 (19.6%) patients without other findings suspicious for PE and in 94 of 213 patients (44.1%) with PE-suspicious findings. PE involved a main pulmonary artery in 37% and multiple lobes in 87% of the patients.

The researchers pointed out that, while the prevalence of PE was highest (44%) in patients who had concomitant signs or symptoms suspicious of PE or underlying DVT, PE was detected in almost 20% of patients without concomitant PE signs and symptoms. Also, the detected pulmonary emboli were deemed significant.

“Our findings suggest that, regardless of the diagnostic algorithm in use, physicians should rule in or out PE in patients who solely report recent onset of marked dyspnea on exertion,” they concluded.

Agreeing with the authors’ conclusions, Mary Jo S. Farmer, MD, PhD, of the department of medicine at University of Massachusetts, Worcester, stated in an interview, “The results of the current study support a diagnostic workup for pulmonary embolus in all patients with recent onset of exertional dyspnea.” She added, “Pulmonary emboli detected were significant as almost all were segmental or more proximal emboli involving multiple lobes. The observed overall prevalence of pulmonary embolus of 32% may seem high when compared with the low prevalence of 7%-13% reported in other studies of patients with suspected pulmonary embolus. However, the prevalence of pulmonary embolus among emergency department cohorts in European countries is generally higher, as is the diagnostic yield from [CT pulmonary angiogram] compared to North American countries. This could be explained by differences in applied thresholds for suspicion of pulmonary embolus. The incidence of COVID-19 and association with thrombosis was not reported.

“It has been reported that nonspecific clinical manifestations and absence of typical signs and symptoms can result in delay in diagnosis of pulmonary embolus or result in pulmonary embolus being missed, an unfortunate situation that could result in malpractice allegation.” Dr. Farmer concluded.

Among limitations of the study, the authors noted that their results are not applicable to patients older than 75 years or patients with chronic (more than 1 month) symptoms of dyspnea or less severe dyspnea (modified Medical Research Council dyspnea score of 2 or lower). Also, no attempt to stratify the clinical relevance of PE was made.

The study was funded by the Arianna Foundation on Anticoagulation, Bologna, Italy. The authors reported that they had no potential conflicts. Dr. Farmer also declared she had no relevant conflicts.

A diagnostic workup for pulmonary embolism (PE) should be performed in all patients with recent onset of exertional dyspnea, according to the authors of an article published in the Journal of Thrombosis and Haemostasis. That conclusion emerged from an analysis of PE prevalence in 417 patients with recent marked exertional dyspnea performing previously well-tolerated physical activities.

Exertional dyspnea is a frequently encountered complaint in clinical practice. Missteps in both diagnosis and early management, however, have been found to be prevalent in emergency department practices. PE diagnosis can be delayed or altogether missed through nonspecific clinical manifestations or the absence of typical signs and symptoms, with a complicated clinical course or mortality as a consequence, stated the researchers. Also, failure to diagnose PE is a common malpractice allegation.

Noting that the prevalence of PE among patients with dyspnea on exertion has not been reported, the authors hypothesized: “PE might be a frequent underlying condition in patients presenting for care complaining of marked dyspnea on exertion of recent onset.”

In a multicenter prospective, cross-sectional study among 14 university or hospital centers in Italy, patients who were referred for outpatient evaluation with recent (< 1 month) dyspnea on exertion with a severity of 3 or 4 on the modified Medical Research Council dyspnea scale were potentially eligible for the study. Prior deep-vein thrombosis (DVT), PE, and use of therapeutic anticoagulation were among exclusion criteria. All patients aged 75 years or younger with recent (< 1 month) marked exertional dyspnea had a systematic workup for PE, irrespective of concomitant signs or symptoms of venous thromboembolism and alternative explanations for dyspnea. The main study outcome was prevalence of PE in the entire cohort of patients with recent marked dyspnea on exertion.

When about 400 patients had been enrolled after an interim analysis in which the preestablished stopping rule (if the lower limit of the 95% confidence interval of the prevalence of PE exceeds 20%) was met, the study was prematurely terminated. PE was found, after exclusion of 134 patients based on low PE clinical probability and normal D-dimer, in 134 (47.3%) of the remaining 283 patients. The overall PE prevalence was 32.1% (95% confidence interval, 27.8-36.8).

PE was present in 40 of 204 (19.6%) patients without other findings suspicious for PE and in 94 of 213 patients (44.1%) with PE-suspicious findings. PE involved a main pulmonary artery in 37% and multiple lobes in 87% of the patients.

The researchers pointed out that, while the prevalence of PE was highest (44%) in patients who had concomitant signs or symptoms suspicious of PE or underlying DVT, PE was detected in almost 20% of patients without concomitant PE signs and symptoms. Also, the detected pulmonary emboli were deemed significant.

“Our findings suggest that, regardless of the diagnostic algorithm in use, physicians should rule in or out PE in patients who solely report recent onset of marked dyspnea on exertion,” they concluded.

Agreeing with the authors’ conclusions, Mary Jo S. Farmer, MD, PhD, of the department of medicine at University of Massachusetts, Worcester, stated in an interview, “The results of the current study support a diagnostic workup for pulmonary embolus in all patients with recent onset of exertional dyspnea.” She added, “Pulmonary emboli detected were significant as almost all were segmental or more proximal emboli involving multiple lobes. The observed overall prevalence of pulmonary embolus of 32% may seem high when compared with the low prevalence of 7%-13% reported in other studies of patients with suspected pulmonary embolus. However, the prevalence of pulmonary embolus among emergency department cohorts in European countries is generally higher, as is the diagnostic yield from [CT pulmonary angiogram] compared to North American countries. This could be explained by differences in applied thresholds for suspicion of pulmonary embolus. The incidence of COVID-19 and association with thrombosis was not reported.

“It has been reported that nonspecific clinical manifestations and absence of typical signs and symptoms can result in delay in diagnosis of pulmonary embolus or result in pulmonary embolus being missed, an unfortunate situation that could result in malpractice allegation.” Dr. Farmer concluded.

Among limitations of the study, the authors noted that their results are not applicable to patients older than 75 years or patients with chronic (more than 1 month) symptoms of dyspnea or less severe dyspnea (modified Medical Research Council dyspnea score of 2 or lower). Also, no attempt to stratify the clinical relevance of PE was made.

The study was funded by the Arianna Foundation on Anticoagulation, Bologna, Italy. The authors reported that they had no potential conflicts. Dr. Farmer also declared she had no relevant conflicts.

A diagnostic workup for pulmonary embolism (PE) should be performed in all patients with recent onset of exertional dyspnea, according to the authors of an article published in the Journal of Thrombosis and Haemostasis. That conclusion emerged from an analysis of PE prevalence in 417 patients with recent marked exertional dyspnea performing previously well-tolerated physical activities.

Exertional dyspnea is a frequently encountered complaint in clinical practice. Missteps in both diagnosis and early management, however, have been found to be prevalent in emergency department practices. PE diagnosis can be delayed or altogether missed through nonspecific clinical manifestations or the absence of typical signs and symptoms, with a complicated clinical course or mortality as a consequence, stated the researchers. Also, failure to diagnose PE is a common malpractice allegation.

Noting that the prevalence of PE among patients with dyspnea on exertion has not been reported, the authors hypothesized: “PE might be a frequent underlying condition in patients presenting for care complaining of marked dyspnea on exertion of recent onset.”

In a multicenter prospective, cross-sectional study among 14 university or hospital centers in Italy, patients who were referred for outpatient evaluation with recent (< 1 month) dyspnea on exertion with a severity of 3 or 4 on the modified Medical Research Council dyspnea scale were potentially eligible for the study. Prior deep-vein thrombosis (DVT), PE, and use of therapeutic anticoagulation were among exclusion criteria. All patients aged 75 years or younger with recent (< 1 month) marked exertional dyspnea had a systematic workup for PE, irrespective of concomitant signs or symptoms of venous thromboembolism and alternative explanations for dyspnea. The main study outcome was prevalence of PE in the entire cohort of patients with recent marked dyspnea on exertion.

When about 400 patients had been enrolled after an interim analysis in which the preestablished stopping rule (if the lower limit of the 95% confidence interval of the prevalence of PE exceeds 20%) was met, the study was prematurely terminated. PE was found, after exclusion of 134 patients based on low PE clinical probability and normal D-dimer, in 134 (47.3%) of the remaining 283 patients. The overall PE prevalence was 32.1% (95% confidence interval, 27.8-36.8).

PE was present in 40 of 204 (19.6%) patients without other findings suspicious for PE and in 94 of 213 patients (44.1%) with PE-suspicious findings. PE involved a main pulmonary artery in 37% and multiple lobes in 87% of the patients.

The researchers pointed out that, while the prevalence of PE was highest (44%) in patients who had concomitant signs or symptoms suspicious of PE or underlying DVT, PE was detected in almost 20% of patients without concomitant PE signs and symptoms. Also, the detected pulmonary emboli were deemed significant.

“Our findings suggest that, regardless of the diagnostic algorithm in use, physicians should rule in or out PE in patients who solely report recent onset of marked dyspnea on exertion,” they concluded.

Agreeing with the authors’ conclusions, Mary Jo S. Farmer, MD, PhD, of the department of medicine at University of Massachusetts, Worcester, stated in an interview, “The results of the current study support a diagnostic workup for pulmonary embolus in all patients with recent onset of exertional dyspnea.” She added, “Pulmonary emboli detected were significant as almost all were segmental or more proximal emboli involving multiple lobes. The observed overall prevalence of pulmonary embolus of 32% may seem high when compared with the low prevalence of 7%-13% reported in other studies of patients with suspected pulmonary embolus. However, the prevalence of pulmonary embolus among emergency department cohorts in European countries is generally higher, as is the diagnostic yield from [CT pulmonary angiogram] compared to North American countries. This could be explained by differences in applied thresholds for suspicion of pulmonary embolus. The incidence of COVID-19 and association with thrombosis was not reported.

“It has been reported that nonspecific clinical manifestations and absence of typical signs and symptoms can result in delay in diagnosis of pulmonary embolus or result in pulmonary embolus being missed, an unfortunate situation that could result in malpractice allegation.” Dr. Farmer concluded.

Among limitations of the study, the authors noted that their results are not applicable to patients older than 75 years or patients with chronic (more than 1 month) symptoms of dyspnea or less severe dyspnea (modified Medical Research Council dyspnea score of 2 or lower). Also, no attempt to stratify the clinical relevance of PE was made.

The study was funded by the Arianna Foundation on Anticoagulation, Bologna, Italy. The authors reported that they had no potential conflicts. Dr. Farmer also declared she had no relevant conflicts.

Butylphthalide, a medication derived from celery seed, may improve outcomes after an acute ischemic stroke when given in addition to thrombolysis or endovascular treatment, a new report suggests.

Patients treated with butylphthalide had fewer severe neurologic symptoms and better function 90 days after the stroke, compared with those receiving placebo.

Butylphthalide is approved and available for use in China, where the study was conducted. However, the medication hasn’t been approved for use by the U.S. Food and Drug Administration.

“Patients who received butylphthalide had less severe neurological symptoms and a better living status at 90 days post stroke, compared to those who received the placebo,” said coauthor Baixue Jia, MD, an attending physician in interventional neuroradiology at the Beijing Tiantan Hospital of Capital Medical University and a faculty member at the China National Clinical Research Center for Neurological Diseases in Beijing. “If the results are confirmed in other trials, this may lead to more options to treat strokes caused by clots.”

The study was presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Studying stroke outcomes

The researchers described butylphthalide as a cerebroprotective drug that was originally extracted from seeds of Apium graveolens. In China, previous studies have shown that the drug has cerebroprotective effects in animal models of ischemia-reperfusion, they noted.

In this randomized, double-blind, placebo-controlled trial, Dr. Jia and colleagues evaluated whether treatment with butylphthalide could improve 90-day outcomes for adults with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (tPA), endovascular treatment, or both.

The participants were treated at one of 59 medical centers in China between July 2018 and February 2022. Those who had minimal stroke symptoms on their initial exam, defined as a score of 0-3 on the National Institutes of Health Stroke Scale, or had severe stroke symptoms, defined as having a score of 26 or higher on the NIHSS, were excluded from the study.

Along with an initial revascularization intervention chosen by their physician, participants were randomly selected to receive either butylphthalide or a placebo daily for 90 days. The drug was administered through daily intravenous injections for the first 14 days, after which patients received oral capsules for 76 days.

The research team defined the outcomes as “favorable” if a patient fell into one of the following categories 90 days after the stroke: an initially mild to moderate stroke (NIHSS, 4-7) and no symptoms after treatment, defined as a score of 0 on the Modified Rankin Scale (mRS), which measures disability and dependence; an initially moderate to serious stroke (NIHSS, 8-14) and no residual symptoms or mild symptoms that don’t impair the ability to perform routine activities of daily living without assistance (mRS, 0-1); or an initially serious to severe stroke (NIHSS, 15-25) and no remaining symptoms or a slight disability that impairs some activities but allows one to conduct daily living without assistance (mRS, 0-2).

Secondary outcomes included symptomatic intracranial hemorrhage, recurrent stroke, and mortality.

Among the 1,216 participants, 607 were assigned to the treatment group, and 609 were assigned to the placebo group. The average age was 66 years, and 68% were men.

Overall, participants in the butylphthalide group were 70% more likely to have a favorable 90-day outcome, compared with the placebo group. Favorable outcomes occurred in 344 patients (56.7%) in the butylphthalide group, compared with 268 patients (44%) in the placebo group (odds ratio, 1.70; 95% confidence interval, 1.35-2.14; P < .001).

In addition, butylphthalide improved function equally well for the patients who initially received tPA, those who received endovascular treatment, and those who received both tPA and endovascular treatment.

Secondary events, such as recurrent stroke and intracranial hemorrhage, weren’t significantly different between the butylphthalide and placebo groups.
 

Ongoing questions

Dr. Jia and colleagues noted the need to understand how butylphthalide works in the brain. Animal studies have suggested several possible mechanisms, but it remains unclear.

“The next step should be investigating the exact mechanisms of butylphthalide in humans,” Dr. Jia said.

Additional research should assess the medication in other populations, the authors noted, particularly because the study involved participants who received initial treatment with tPA, endovascular treatment, or both. The results may not be generalizable to stroke patients who receive other treatments or to populations outside of China.

“While these are interesting results, this is only one relatively small study on a fairly select population in China. Butylphthalide, a medication initially compounded from celery seed, is not ready for use in standard stroke treatment,” said Daniel Lackland, DrPH, professor of neurology and director of the division of translational neurosciences and population studies at the Medical University of South Carolina, Charleston.

Dr. Lackland, who wasn’t involved with the study, is a member of the American Stroke Association’s Stroke Council. Although butylphthalide was originally extracted from seeds, he noted, it’s not what patients would find commercially available.

“The medication used in this study is not the same as celery seed or celery seed extract supplements,” he said. “Stroke survivors should always consult with their neurologist or healthcare professional regarding diet after a stroke.”

The study was funded by the National Key Technology Research and Development Program of the Ministry of Science and Technology of the People’s Republic of China and Shijiazhuang Pharmaceutical Group dl-3-butylphthalide Pharmaceutical. Several authors are employed with Beijing Tiantan Hospital and the Beijing Institute of Brain Disorders. Dr. Lackland reported no relevant financial relationships.

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

Butylphthalide, a medication derived from celery seed, may improve outcomes after an acute ischemic stroke when given in addition to thrombolysis or endovascular treatment, a new report suggests.

Patients treated with butylphthalide had fewer severe neurologic symptoms and better function 90 days after the stroke, compared with those receiving placebo.

Butylphthalide is approved and available for use in China, where the study was conducted. However, the medication hasn’t been approved for use by the U.S. Food and Drug Administration.

“Patients who received butylphthalide had less severe neurological symptoms and a better living status at 90 days post stroke, compared to those who received the placebo,” said coauthor Baixue Jia, MD, an attending physician in interventional neuroradiology at the Beijing Tiantan Hospital of Capital Medical University and a faculty member at the China National Clinical Research Center for Neurological Diseases in Beijing. “If the results are confirmed in other trials, this may lead to more options to treat strokes caused by clots.”

The study was presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Studying stroke outcomes

The researchers described butylphthalide as a cerebroprotective drug that was originally extracted from seeds of Apium graveolens. In China, previous studies have shown that the drug has cerebroprotective effects in animal models of ischemia-reperfusion, they noted.

In this randomized, double-blind, placebo-controlled trial, Dr. Jia and colleagues evaluated whether treatment with butylphthalide could improve 90-day outcomes for adults with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (tPA), endovascular treatment, or both.

The participants were treated at one of 59 medical centers in China between July 2018 and February 2022. Those who had minimal stroke symptoms on their initial exam, defined as a score of 0-3 on the National Institutes of Health Stroke Scale, or had severe stroke symptoms, defined as having a score of 26 or higher on the NIHSS, were excluded from the study.

Along with an initial revascularization intervention chosen by their physician, participants were randomly selected to receive either butylphthalide or a placebo daily for 90 days. The drug was administered through daily intravenous injections for the first 14 days, after which patients received oral capsules for 76 days.

The research team defined the outcomes as “favorable” if a patient fell into one of the following categories 90 days after the stroke: an initially mild to moderate stroke (NIHSS, 4-7) and no symptoms after treatment, defined as a score of 0 on the Modified Rankin Scale (mRS), which measures disability and dependence; an initially moderate to serious stroke (NIHSS, 8-14) and no residual symptoms or mild symptoms that don’t impair the ability to perform routine activities of daily living without assistance (mRS, 0-1); or an initially serious to severe stroke (NIHSS, 15-25) and no remaining symptoms or a slight disability that impairs some activities but allows one to conduct daily living without assistance (mRS, 0-2).

Secondary outcomes included symptomatic intracranial hemorrhage, recurrent stroke, and mortality.

Among the 1,216 participants, 607 were assigned to the treatment group, and 609 were assigned to the placebo group. The average age was 66 years, and 68% were men.

Overall, participants in the butylphthalide group were 70% more likely to have a favorable 90-day outcome, compared with the placebo group. Favorable outcomes occurred in 344 patients (56.7%) in the butylphthalide group, compared with 268 patients (44%) in the placebo group (odds ratio, 1.70; 95% confidence interval, 1.35-2.14; P < .001).

In addition, butylphthalide improved function equally well for the patients who initially received tPA, those who received endovascular treatment, and those who received both tPA and endovascular treatment.

Secondary events, such as recurrent stroke and intracranial hemorrhage, weren’t significantly different between the butylphthalide and placebo groups.
 

Ongoing questions

Dr. Jia and colleagues noted the need to understand how butylphthalide works in the brain. Animal studies have suggested several possible mechanisms, but it remains unclear.

“The next step should be investigating the exact mechanisms of butylphthalide in humans,” Dr. Jia said.

Additional research should assess the medication in other populations, the authors noted, particularly because the study involved participants who received initial treatment with tPA, endovascular treatment, or both. The results may not be generalizable to stroke patients who receive other treatments or to populations outside of China.

“While these are interesting results, this is only one relatively small study on a fairly select population in China. Butylphthalide, a medication initially compounded from celery seed, is not ready for use in standard stroke treatment,” said Daniel Lackland, DrPH, professor of neurology and director of the division of translational neurosciences and population studies at the Medical University of South Carolina, Charleston.

Dr. Lackland, who wasn’t involved with the study, is a member of the American Stroke Association’s Stroke Council. Although butylphthalide was originally extracted from seeds, he noted, it’s not what patients would find commercially available.

“The medication used in this study is not the same as celery seed or celery seed extract supplements,” he said. “Stroke survivors should always consult with their neurologist or healthcare professional regarding diet after a stroke.”

The study was funded by the National Key Technology Research and Development Program of the Ministry of Science and Technology of the People’s Republic of China and Shijiazhuang Pharmaceutical Group dl-3-butylphthalide Pharmaceutical. Several authors are employed with Beijing Tiantan Hospital and the Beijing Institute of Brain Disorders. Dr. Lackland reported no relevant financial relationships.

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

Butylphthalide, a medication derived from celery seed, may improve outcomes after an acute ischemic stroke when given in addition to thrombolysis or endovascular treatment, a new report suggests.

Patients treated with butylphthalide had fewer severe neurologic symptoms and better function 90 days after the stroke, compared with those receiving placebo.

Butylphthalide is approved and available for use in China, where the study was conducted. However, the medication hasn’t been approved for use by the U.S. Food and Drug Administration.

“Patients who received butylphthalide had less severe neurological symptoms and a better living status at 90 days post stroke, compared to those who received the placebo,” said coauthor Baixue Jia, MD, an attending physician in interventional neuroradiology at the Beijing Tiantan Hospital of Capital Medical University and a faculty member at the China National Clinical Research Center for Neurological Diseases in Beijing. “If the results are confirmed in other trials, this may lead to more options to treat strokes caused by clots.”

The study was presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Studying stroke outcomes

The researchers described butylphthalide as a cerebroprotective drug that was originally extracted from seeds of Apium graveolens. In China, previous studies have shown that the drug has cerebroprotective effects in animal models of ischemia-reperfusion, they noted.

In this randomized, double-blind, placebo-controlled trial, Dr. Jia and colleagues evaluated whether treatment with butylphthalide could improve 90-day outcomes for adults with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (tPA), endovascular treatment, or both.

The participants were treated at one of 59 medical centers in China between July 2018 and February 2022. Those who had minimal stroke symptoms on their initial exam, defined as a score of 0-3 on the National Institutes of Health Stroke Scale, or had severe stroke symptoms, defined as having a score of 26 or higher on the NIHSS, were excluded from the study.

Along with an initial revascularization intervention chosen by their physician, participants were randomly selected to receive either butylphthalide or a placebo daily for 90 days. The drug was administered through daily intravenous injections for the first 14 days, after which patients received oral capsules for 76 days.

The research team defined the outcomes as “favorable” if a patient fell into one of the following categories 90 days after the stroke: an initially mild to moderate stroke (NIHSS, 4-7) and no symptoms after treatment, defined as a score of 0 on the Modified Rankin Scale (mRS), which measures disability and dependence; an initially moderate to serious stroke (NIHSS, 8-14) and no residual symptoms or mild symptoms that don’t impair the ability to perform routine activities of daily living without assistance (mRS, 0-1); or an initially serious to severe stroke (NIHSS, 15-25) and no remaining symptoms or a slight disability that impairs some activities but allows one to conduct daily living without assistance (mRS, 0-2).

Secondary outcomes included symptomatic intracranial hemorrhage, recurrent stroke, and mortality.

Among the 1,216 participants, 607 were assigned to the treatment group, and 609 were assigned to the placebo group. The average age was 66 years, and 68% were men.

Overall, participants in the butylphthalide group were 70% more likely to have a favorable 90-day outcome, compared with the placebo group. Favorable outcomes occurred in 344 patients (56.7%) in the butylphthalide group, compared with 268 patients (44%) in the placebo group (odds ratio, 1.70; 95% confidence interval, 1.35-2.14; P < .001).

In addition, butylphthalide improved function equally well for the patients who initially received tPA, those who received endovascular treatment, and those who received both tPA and endovascular treatment.

Secondary events, such as recurrent stroke and intracranial hemorrhage, weren’t significantly different between the butylphthalide and placebo groups.
 

Ongoing questions

Dr. Jia and colleagues noted the need to understand how butylphthalide works in the brain. Animal studies have suggested several possible mechanisms, but it remains unclear.

“The next step should be investigating the exact mechanisms of butylphthalide in humans,” Dr. Jia said.

Additional research should assess the medication in other populations, the authors noted, particularly because the study involved participants who received initial treatment with tPA, endovascular treatment, or both. The results may not be generalizable to stroke patients who receive other treatments or to populations outside of China.

“While these are interesting results, this is only one relatively small study on a fairly select population in China. Butylphthalide, a medication initially compounded from celery seed, is not ready for use in standard stroke treatment,” said Daniel Lackland, DrPH, professor of neurology and director of the division of translational neurosciences and population studies at the Medical University of South Carolina, Charleston.

Dr. Lackland, who wasn’t involved with the study, is a member of the American Stroke Association’s Stroke Council. Although butylphthalide was originally extracted from seeds, he noted, it’s not what patients would find commercially available.

“The medication used in this study is not the same as celery seed or celery seed extract supplements,” he said. “Stroke survivors should always consult with their neurologist or healthcare professional regarding diet after a stroke.”

The study was funded by the National Key Technology Research and Development Program of the Ministry of Science and Technology of the People’s Republic of China and Shijiazhuang Pharmaceutical Group dl-3-butylphthalide Pharmaceutical. Several authors are employed with Beijing Tiantan Hospital and the Beijing Institute of Brain Disorders. Dr. Lackland reported no relevant financial relationships.

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

In May 2021, a nurse at UnitedHealthcare called a colleague to share some welcome news about a problem the two had been grappling with for weeks.

United provided the health insurance plan for students at Penn State University. It was a large and potentially lucrative account: lots of young, healthy students paying premiums in, not too many huge medical reimbursements going out.

But one student was costing United a lot of money. Christopher McNaughton suffered from a crippling case of ulcerative colitis – an ailment that caused him to develop severe arthritis, debilitating diarrhea, numbing fatigue, and life-threatening blood clots. His medical bills were running nearly $2 million a year.

United had flagged Mr. McNaughton’s case as a “high dollar account,” and the company was reviewing whether it needed to keep paying for the expensive cocktail of drugs crafted by a Mayo Clinic specialist that had brought Mr. McNaughton’s disease under control after he’d been through years of misery.

On the 2021 phone call, which was recorded by the company, nurse Victoria Kavanaugh told her colleague that a doctor contracted by United to review the case had concluded that Mr. McNaughton’s treatment was “not medically necessary.” Her colleague, Dave Opperman, reacted to the news with a long laugh.

“I knew that was coming,” said Mr. Opperman, who heads up a United subsidiary that brokered the health insurance contract between United and Penn State. “I did too,” Ms. Kavanaugh replied.

Mr. Opperman then complained about Mr. McNaughton’s mother, whom he referred to as “this woman,” for “screaming and yelling” and “throwing tantrums” during calls with United.

The pair agreed that any appeal of the United doctor’s denial of the treatment would be a waste of the family’s time and money.

“We’re still gonna say no,” Mr. Opperman said.

More than 200 million Americans are covered by private health insurance. But data from state and federal regulators shows that insurers reject about 1 in 7 claims for treatment. Many people, faced with fighting insurance companies, simply give up: One study found that Americans file formal appeals on only 0.1% of claims denied by insurers under the Affordable Care Act.

Insurers have wide discretion in crafting what is covered by their policies, beyond some basic services mandated by federal and state law. They often deny claims for services that they deem not “medically necessary.”

When United refused to pay for Mr. McNaughton’s treatment for that reason, his family did something unusual. They fought back with a lawsuit, which uncovered a trove of materials, including internal emails and tape-recorded exchanges among company employees. Those records offer an extraordinary behind-the-scenes look at how one of America’s leading health care insurers relentlessly fought to reduce spending on care, even as its profits rose to record levels.

As United reviewed Mr. McNaughton’s treatment, he and his family were often in the dark about what was happening or their rights. Meanwhile, United employees misrepresented critical findings and ignored warnings from doctors about the risks of altering Mr. McNaughton’s drug plan.

At one point, court records show, United inaccurately reported to Penn State and the family that Mr. McNaughton’s doctor had agreed to lower the doses of his medication. Another time, a doctor paid by United concluded that denying payments for Mr. McNaughton’s treatment could put his health at risk, but the company buried his report and did not consider its findings. The insurer did, however, consider a report submitted by a company doctor who rubber-stamped the recommendation of a United nurse to reject paying for the treatment.

United declined to answer specific questions about the case, even after Mr. McNaughton signed a release provided by the insurer to allow it to discuss details of his interactions with the company. United noted that it ultimately paid for all of Mr. McNaughton’s treatments. In a written response, United spokesperson Maria Gordon Shydlo wrote that the company’s guiding concern was Mr. McNaughton’s well-being.

“Mr. McNaughton’s treatment involves medication dosages that far exceed [Food and Drug Administration] guidelines,” the statement said. “In cases like this, we review treatment plans based on current clinical guidelines to help ensure patient safety.”

But the records reviewed by ProPublica show that United had another, equally urgent goal in dealing with Mr. McNaughton. In emails, officials calculated what Mr. McNaughton was costing them to keep his crippling disease at bay and how much they would save if they forced him to undergo a cheaper treatment that had already failed him. As the family pressed the company to back down, first through Penn State and then through a lawsuit, the United officials handling the case bristled.

“This is just unbelievable,” Ms. Kavanaugh said of Mr. McNaughton’s family in one call to discuss his case. ”They’re just really pushing the envelope, and I’m surprised, like I don’t even know what to say.”
 

The same meal every day

Now 31, Mr. McNaughton grew up in State College, Pa., just blocks from the Penn State campus. Both of his parents are faculty members at the university.

In the winter of 2014, Mr. McNaughton was halfway through his junior year at Bard College in New York. At 6 feet, 4 inches tall, he was a guard on the basketball team and had started most of the team’s games since the start of his sophomore year. He was majoring in psychology.

When Mr. McNaughton returned to school after the winter holiday break, he started to experience frequent bouts of bloody diarrhea. After just a few days on campus, he went home to State College, where doctors diagnosed him with a severe case of ulcerative colitis.

A chronic inflammatory bowel disease that causes swelling and ulcers in the digestive tract, ulcerative colitis has no cure, and ongoing treatment is needed to alleviate symptoms and prevent serious health complications. The majority of cases produce mild to moderate symptoms. Mr. McNaughton’s case was severe.

Treatments for ulcerative colitis include steroids and special drugs known as biologics that work to reduce inflammation in the large intestine.

Mr. McNaughton, however, failed to get meaningful relief from the drugs his doctors initially prescribed. He was experiencing bloody diarrhea up to 20 times a day, with such severe stomach pain that he spent much of his day curled up on a couch. He had little appetite and lost 50 pounds. Severe anemia left him fatigued. He suffered from other conditions related to his colitis, including crippling arthritis. He was hospitalized several times to treat dangerous blood clots.

For 2 years, in an effort to help alleviate his symptoms, he ate the same meals every day: Rice Chex cereal and scrambled eggs for breakfast, a cup of white rice with plain chicken breast for lunch, and a similar meal for dinner, occasionally swapping in tilapia.

His hometown doctors referred him to a specialist at the University of Pittsburgh, who tried unsuccessfully to bring his disease under control. That doctor ended up referring Mr. McNaughton to Edward V. Loftus Jr., MD, at the Mayo Clinic in Rochester, Minn., which has been ranked as the best gastroenterology hospital in the country every year since 1990 by U.S. News & World Report.

For his first visit with Dr. Loftus in May 2015, Mr. McNaughton and his mother, Janice Light, charted hospitals along the 900-mile drive from Pennsylvania to Minnesota in case they needed medical help along the way.

Mornings were the hardest. Mr. McNaughton often spent several hours in the bathroom at the start of the day. To prepare for his meeting with Dr. Loftus, he set his alarm for 3:30 a.m. so he could be ready for the 7:30 a.m. appointment. Even with that preparation, he had to stop twice to use a bathroom on the 5-minute walk from the hotel to the clinic. When they met, Dr. Loftus looked at Mr. McNaughton and told him that he appeared incapacitated. It was, he told the student, as if Mr. McNaughton were chained to the bathroom, with no outside life. He had not been able to return to school and spent most days indoors, managing his symptoms as best he could.

Mr. McNaughton had tried a number of medications by this point, none of which worked. This pattern would repeat itself during the first couple of years that Dr. Loftus treated him.

In addition to trying to find a treatment that would bring Mr. McNaughton’s colitis into remission, Dr. Loftus wanted to wean him off the steroid prednisone, which he had been taking since his initial diagnosis in 2014. The drug is commonly prescribed to colitis patients to control inflammation, but prolonged use can lead to severe side effects including cataracts, osteoporosis, increased risk of infection, and fatigue. Mr. McNaughton also experienced “moon face,” a side effect caused by the shifting of fat deposits that results in the face becoming puffy and rounder.

In 2018, Dr. Loftus and Mr. McNaughton decided to try an unusual regimen. Many patients with inflammatory bowel diseases such as colitis take a single biologic drug as treatment. Whereas traditional drugs are chemically synthesized, biologics are manufactured in living systems, such as plant or animal cells. A year’s supply of an individual biologic drug can cost up to $500,000. They are often given through infusions in a medical facility, which adds to the cost.

Mr. McNaughton had tried individual biologics, and then two in combination, without much success. He and Dr. Loftus then agreed to try two biologic drugs together at doses well above those recommended by the Food and Drug Administration. The federal Agency for Healthcare Research and Quality estimates one in five prescriptions written today are for off-label uses.

There are drawbacks to the practice. Since some uses and doses of particular drugs have not been extensively studied, the risks and efficacy of using them off-label are not well known. Also, some drug manufacturers have improperly pushed off-label usage of their products to boost sales despite little or no evidence to support their use in those situations. Like many leading experts and researchers in his field, Dr. Loftus has been paid to do consulting related to the biologic drugs taken by Mr. McNaughton. The payments related to those drugs have ranged from a total of $1,440 in 2020 to $51,235 in 2018. Dr. Loftus said much of his work with pharmaceutical companies was related to conducting clinical trials on new drugs.

In cases of off-label prescribing, patients are depending upon their doctors’ expertise and experience with the drug. “In this case, I was comfortable that the potential benefits to Chris outweighed the risks,” Dr. Loftus said.

There was evidence that the treatment plan for Mr. McNaughton might work, including studies that had found dual biologic therapy to be efficacious and safe. The two drugs he takes, Entyvio and Remicade, have the same purpose – to reduce inflammation in the large intestine – but each works differently in the body. Remicade, marketed by Janssen Biotech, targets a protein that causes inflammation. Entyvio, made by Takeda Pharmaceuticals, works by preventing an excess of white blood cells from entering into the gastrointestinal tract.

As for any suggestion by United doctors that his treatment plan for Mr. McNaughton was out of bounds or dangerous, Dr. Loftus said “my treatment of Chris was not clinically inappropriate – as was shown by Chris’ positive outcome.”

The unusual high-dose combination of two biologic drugs produced a remarkable change in Mr. McNaughton. He no longer had blood in his stool, and his trips to the bathroom were cut from 20 times a day to 3 or 4. He was able to eat different foods and put on weight. He had more energy. He tapered off prednisone.

“If you told me in 2015 that I would be living like this, I would have asked where do I sign up,” Mr. McNaughton said of the change he experienced with the new drug regimen.

When he first started the new treatment, Mr. McNaughton was covered under his family’s plan, and all his bills were paid. Mr. McNaughton enrolled at the university in 2020. Before switching to United’s plan for students, Mr. McNaughton and his parents consulted with a health advocacy service offered to faculty members. A benefits specialist assured them the drugs taken by Mr. McNaughton would be covered by United.

Mr. McNaughton joined the student plan in July 2020, and his infusions that month and the following month were paid for by United. In September, the insurer indicated payment on his claims was “pending,” something it did for his other claims that came in during the rest of the year.

Mr. McNaughton and his family were worried. They called United to make sure there wasn’t a problem; the insurer told them, they said, that it only needed to check his medical records. When the family called again, United told them it had the documentation needed, they said. United, in a court filing last year, said it received two calls from the family and each time indicated that all of the necessary medical records had not yet been received.

In January 2021, Mr. McNaughton received a new explanation of benefits for the prior months. All of the claims for his care, beginning in September, were no longer “pending.” They were stamped “DENIED.” The total outstanding bill for his treatment was $807,086.

When Mr. McNaughton’s mother reached a United customer service representative the next day to ask why bills that had been paid in the summer were being denied for the fall, the representative told her the account was being reviewed because of “a high dollar amount on the claims,” according to a recording of the call.


 

Misrepresentations

With United refusing to pay, the family was terrified of being stuck with medical bills that would bankrupt them and deprive Mr. McNaughton of treatment that they considered miraculous.

They turned to Penn State for help. Ms. Light and Mr. McNaughton’s father, David McNaughton, hoped their position as faculty members would make the school more willing to intervene on their behalf.

“After more than 30 years on faculty, my husband and I know that this is not how Penn State would want its students to be treated,” Ms. Light wrote to a school official in February 2021.

In response to questions from ProPublica, Penn State spokesperson Lisa Powers wrote that “supporting the health and well-being of our students is always of primary importance” and that “our hearts go out to any student and family impacted by a serious medical condition.” The university, she wrote, does “not comment on students’ individual circumstances or disclose information from their records.” Mr. McNaughton offered to grant Penn State whatever permissions it needed to speak about his case with ProPublica. The school, however, wrote that it would not comment “even if confidentiality has been waived.”

The family appealed to school administrators. Because the effectiveness of biologics wanes in some patients if doses are skipped, Mr. McNaughton and his parents were worried about even a delay in treatment. His doctor wrote that if he missed scheduled infusions of the drugs, there was “a high likelihood they would no longer be effective.”

During a conference call arranged by Penn State officials on March 5, 2021, United agreed to pay for Mr. McNaughton’s care through the end of the plan year that August. Penn State immediately notified the family of the “wonderful news” while also apologizing for “the stress this has caused Chris and your family.”

Behind the scenes, Mr. McNaughton’s review had “gone all the way to the top” at United’s student health plan division, Ms. Kavanaugh, the nurse, said in a recorded conversation.

The family’s relief was short-lived. A month later, United started another review of Mr. McNaughton’s care, overseen by Ms. Kavanaugh, to determine if it would pay for the treatment in the upcoming plan year.

The nurse sent the Mr. McNaughton case to a company called Medical Review Institute of America. Insurers often turn to companies like MRIoA to review coverage decisions involving expensive treatments or specialized care.

Ms. Kavanaugh, who was assigned to a special investigations unit at United, let her feelings about the matter be known in a recorded telephone call with a representative of MRIoA.

“This school apparently is a big client of ours,” she said. She then shared her opinion of Mr. McNaughton’s treatment. “Really this is a case of a kid who’s getting a drug way too much, like too much of a dose,” Ms. Kavanaugh said. She said it was “insane that they would even think that this is reasonable” and “to be honest with you, they’re awfully pushy considering that we are paying through the end of this school year.”

On a call with an outside contractor, the United nurse claimed Mr. McNaughton was on a higher dose of medication than the FDA approved, which is a common practice.

MRIoA sent the case to Vikas Pabby, MD, a gastroenterologist at UCLA Health and a professor at the university’s medical school. His May 2021 review of Mr. McNaughton’s case was just one of more than 300 Dr. Pabby did for MRIoA that month, for which he was paid $23,000 in total, according to a log of his work produced in the lawsuit.

In a May 4, 2021, report, Dr. Pabby concluded Mr. McNaughton’s treatment was not medically necessary, because United’s policies for the two drugs taken by Mr. McNaughton did not support using them in combination.

Insurers spell out what services they cover in plan policies, lengthy documents that can be confusing and difficult to understand. Many policies, such as Mr. McNaughton’s, contain a provision that treatments and procedures must be “medically necessary” in order to be covered. The definition of medically necessary differs by plan. Some don’t even define the term. Mr. McNaughton’s policy contains a five-part definition, including that the treatment must be “in accordance with the standards of good medical policy” and “the most appropriate supply or level of service which can be safely provided.”

Behind the scenes at United, Mr. Opperman and Ms. Kavanaugh agreed that if Mr. McNaughton were to appeal Dr. Pabby’s decision, the insurer would simply rule against him. “I just think it’s a waste of money and time to appeal and send it to another one when we know we’re gonna get the same answer,” Mr. Opperman said, according to a recording in court files. At Mr. Opperman’s urging, United decided to skip the usual appeals process and arrange for Dr. Pabby to have a so-called “peer-to-peer” discussion with Dr. Loftus, the Mayo physician treating Mr. McNaughton. Such a conversation, in which a patient’s doctor talks with an insurance company’s doctor to advocate for the prescribed treatment, usually occurs only after a customer has appealed a denial and the appeal has been rejected.

When Ms. Kavanaugh called Dr. Loftus’ office to set up a conversation with Dr. Pabby, she explained it was an urgent matter and had been requested by Mr. McNaughton. “You know I’ve just gotten to know Christopher,” she explained, although she had never spoken with him. “We’re trying to advocate and help and get this peer-to-peer set up.”

Mr. McNaughton, meanwhile, had no idea at the time that a United doctor had decided his treatment was unnecessary and that the insurer was trying to set up a phone call with his physician.

In the peer-to-peer conversation, Dr. Loftus told Dr. Pabby that Mr. McNaughton had “a very complicated case” and that lower doses had not worked for him, according to an internal MRIoA memo.

Following his conversation with Dr. Loftus, Dr. Pabby created a second report for United. He recommended the insurer pay for both drugs, but at reduced doses. He added new language saying that the safety of using both drugs at the higher levels “is not established.”

When Ms. Kavanaugh shared the May 12 decision from Dr. Pabby with others at United, her boss responded with an email calling it “great news.”

Then Mr. Opperman sent an email that puzzled the McNaughtons.

In it, Mr. Opperman claimed that Dr. Loftus and Dr. Pabby had agreed that Mr. McNaughton should be on significantly lower doses of both drugs. He said Dr. Loftus “will work with the patient to start titrating them down to a normal dose range.” Mr. Opperman wrote that United would cover Mr. McNaughton’s treatment in the coming year, but only at the reduced doses. Mr. Opperman did not respond to emails and phone messages seeking comment.

Mr. McNaughton didn’t believe a word of it. He had already tried and failed treatment with those drugs at lower doses, and it was Dr. Loftus who had upped the doses, leading to his remission from severe colitis.

The only thing that made sense to Mr. McNaughton was that the treatment United said it would now pay for was dramatically cheaper – saving the company at least hundreds of thousands of dollars a year – than his prescribed treatment because it sliced the size of the doses by more than half.

When the family contacted Dr. Loftus for an explanation, they were outraged by what they heard. Dr. Loftus told them that he had never recommended lowering the dosage. In a letter, Dr. Loftus wrote that changing Mr. McNaughton’s treatment “would have serious detrimental effects on both his short term and long term health and could potentially involve life threatening complications. This would ultimately incur far greater medical costs. Chris was on the doses suggested by United Healthcare before, and they were not at all effective.”

It would not be until the lawsuit that it would become clear how Dr. Loftus’ conversations had been so seriously misrepresented.

Under questioning by Mr. McNaughton’s lawyers, Ms. Kavanaugh acknowledged that she was the source of the incorrect claim that Mr. McNaughton’s doctor had agreed to a change in treatment.

“I incorrectly made an assumption that they had come to some sort of agreement,” she said in a deposition last August. “It was my first peer-to-peer. I did not realize that that simply does not occur.”

Ms. Kavanaugh did not respond to emails and telephone messages seeking comment.

When the McNaughtons first learned of Mr. Opperman’s inaccurate report of the phone call with Dr. Loftus, it unnerved them. They started to question if their case would be fairly reviewed.

“When we got the denial and they lied about what Dr. Loftus said, it just hit me that none of this matters,” Mr. McNaughton said. “They will just say or do anything to get rid of me. It delegitimized the entire review process. When I got that denial, I was crushed.”


 

A buried report

While the family tried to sort out the inaccurate report, United continued putting the McNaughton case in front of more company doctors.

On May 21, 2021, United sent the case to one of its own doctors, Nady Cates, MD, for an additional review. The review was marked “escalated issue.” Dr. Cates is a United medical director, a title used by many insurers for physicians who review cases. It is work he has been doing as an employee of health insurers since 1989 and at United since 2010. He has not practiced medicine since the early 1990s.

Dr. Cates, in a deposition, said he stopped seeing patients because of the long hours involved and because “AIDS was coming around then. I was seeing a lot of military folks who had venereal diseases, and I guess I was concerned about being exposed.” He transitioned to reviewing paperwork for the insurance industry, he said, because “I guess I was a chicken.”

When he had practiced, Dr. Cates said, he hadn’t treated patients with ulcerative colitis and had referred those cases to a gastroenterologist.

He said his review of Mr. McNaughton’s case primarily involved reading a United nurse’s recommendation to deny his care and making sure “that there wasn’t a decimal place that was out of line.” He said he copied and pasted the nurse’s recommendation and typed “agree” on his review of Mr. McNaughton’s case.

Dr. Cates said that he does about a hundred reviews a week. He said that in his reviews he typically checks to see if any medications are prescribed in accordance with the insurer’s guidelines, and if not, he denies it. United’s policies, he said, prevented him from considering that Mr. McNaughton had failed other treatments or that Dr. Loftus was a leading expert in his field.

“You are giving zero weight to the treating doctor’s opinion on the necessity of the treatment regimen?” a lawyer asked Dr. Cates in his deposition. He responded, “Yeah.”

Attempts to contact Dr. Cates for comment were unsuccessful.

At the same time Dr. Cates was looking at Mr. McNaughton’s case, yet another review was underway at MRIoA. United said it sent the case back to MRIoA after the insurer received the letter from Dr. Loftus warning of the life-threatening complications that might occur if the dosages were reduced.

On May 24, 2021, the new report requested by MRIoA arrived. It came to a completely different conclusion than all of the previous reviews.

Nitin Kumar, MD, a gastroenterologist in Illinois, concluded that Mr. McNaughton’s established treatment plan was not only medically necessary and appropriate but that lowering his doses “can result in a lack of effective therapy of Ulcerative Colitis, with complications of uncontrolled disease (including dysplasia leading to colorectal cancer), flare, hospitalization, need for surgery, and toxic megacolon.”

Unlike other doctors who produced reports for United, Dr. Kumar discussed the harm that Mr. McNaughton might suffer if United required him to change his treatment. “His disease is significantly severe, with diagnosis at a young age,” Dr. Kumar wrote. “He has failed every biologic medication class recommended by guidelines. Therefore, guidelines can no longer be applied in this case.” He cited six studies of patients using two biologic drugs together and wrote that they revealed no significant safety issues and found the therapy to be “broadly successful.”

When Ms. Kavanaugh learned of Dr. Kumar’s report, she quickly moved to quash it and get the case returned to Dr. Pabby, according to her deposition.

In a recorded telephone call, Ms. Kavanaugh told an MRIoA representative that “I had asked that this go back through Dr. Pabby, and it went through a different doctor and they had a much different result.” After further discussion, the MRIoA representative agreed to send the case back to Dr. Pabby. “I appreciate that,” Ms. Kavanaugh replied. “I just want to make sure, because, I mean, it’s obviously a very different result than what we’ve been getting on this case.”

MRIoA case notes show that at 7:04 a.m. on May 25, 2021, Dr. Pabby was assigned to take a look at the case for the third time. At 7:27 a.m., the notes indicate, Dr. Pabby again rejected Mr. McNaughton’s treatment plan. While noting it was “difficult to control” Mr. McNaughton’s ulcerative colitis, Dr. Pabby added that his doses “far exceed what is approved by literature” and that the “safety of the requested doses is not supported by literature.”

In a deposition, Ms. Kavanaugh said that after she opened the Kumar report and read that he was supporting Mr. McNaughton’s current treatment plan, she immediately spoke to her supervisor, who told her to call MRIoA and have the case sent back to Dr. Pabby for review.

Ms. Kavanaugh said she didn’t save a copy of the Kumar report, nor did she forward it to anyone at United or to officials at Penn State who had been inquiring about the McNaughton case. “I didn’t because it shouldn’t have existed,” she said. “It should have gone back to Dr. Pabby.”

When asked if the Kumar report caused her any concerns given his warning that Mr. McNaughton risked cancer or hospitalization if his regimen were changed, Ms. Kavanaugh said she didn’t read his full report. “I saw that it was not the correct doctor, I saw the initial outcome and I was asked to send it back,” she said. Ms. Kavanaugh added, “I have a lot of empathy for this member, but it needed to go back to the peer-to-peer reviewer.”

In a court filing, United said Ms. Kavanaugh was correct in insisting that Dr. Pabby conduct the review and that MRIoA confirmed that Dr. Pabby should have been the one doing the review.

The Kumar report was not provided to Mr. McNaughton when his lawyer, Jonathan M. Gesk, first asked United and MRIoA for any reviews of the case. Mr. Gesk discovered it by accident when he was listening to a recorded telephone call produced by United in which Ms. Kavanaugh mentioned a report number Mr. Gesk had not heard before. He then called MRIoA, which confirmed the report existed and eventually provided it to him.

Dr. Pabby asked ProPublica to direct any questions about his involvement in the matter to MRIoA. The company did not respond to questions from ProPublica about the case.
 

A sense of hopelessness

When Mr. McNaughton enrolled at Penn State in 2020, it brought a sense of normalcy that he had lost when he was first diagnosed with colitis. He still needed monthly hours-long infusions and suffered occasional flare-ups and symptoms, but he was attending classes in person and living a life similar to the one he had before his diagnosis.

It was a striking contrast to the previous 6 years, which he had spent largely confined to his parents’ house in State College. The frequent bouts of diarrhea made it difficult to go out. He didn’t talk much to friends and spent as much time as he could studying potential treatments and reviewing ongoing clinical trials. He tried to keep up with the occasional online course, but his disease made it difficult to make any real progress toward a degree.

United, in correspondence with Mr. McNaughton, noted that its review of his care was “not a treatment decision. Treatment decisions are made between you and your physician.” But by threatening not to pay for his medications, or only to pay for a different regimen, Mr. McNaughton said, United was in fact attempting to dictate his treatment. From his perspective, the insurer was playing doctor, making decisions without ever examining him or even speaking to him.

The idea of changing his treatment or stopping it altogether caused constant worry for Mr. McNaughton, exacerbating his colitis and triggering physical symptoms, according to his doctors. Those included a large ulcer on his leg and welts under his skin on his thighs and shin that made his leg muscles stiff and painful to the point where he couldn’t bend his leg or walk properly. There were daily migraines and severe stomach pain. “I was consumed with this situation,” Mr. McNaughton said. “My path was unconventional, but I was proud of myself for fighting back and finishing school and getting my life back on track. I thought they were singling me out. My biggest fear was going back to the hell.”

Mr. McNaughton said he contemplated suicide on several occasions, dreading a return to a life where he was housebound or hospitalized.

Mr. McNaughton and his parents talked about his possibly moving to Canada where his grandmother lived and seeking treatment there under the nation’s government health plan.

Dr. Loftus connected Mr. McNaughton with a psychologist who specializes in helping patients with chronic digestive diseases.

The psychologist, Tiffany Taft, PsyD, said Mr. McNaughton was not an unusual case. About one in three patients with diseases like colitis suffer from medical trauma or PTSD related to it, she said, often the result of issues related to getting appropriate treatment approved by insurers.

“You get into hopelessness,” she said of the depression that accompanies fighting with insurance companies over care. “They feel like ‘I can’t fix that. I am screwed.’ When you can’t control things with what an insurance company is doing, anxiety, PTSD and depression get mixed together.”

In the case of Mr. McNaughton, Dr. Taft said, he was being treated by one of the best gastroenterologists in the world, was doing well with his treatment, and then was suddenly notified he might be on the hook for nearly a million dollars in medical charges without access to his medications. “It sends you immediately into panic about all these horrific things that could happen,” Dr. Taft said. The physical and mental symptoms Mr. McNaughton suffered after his care was threatened were “triggered” by the stress he experienced, she said.

In early June 2021, United informed Mr. McNaughton in a letter that it would not cover the cost of his treatment regimen in the next academic year, starting in August. The insurer said it would pay only for a treatment plan that called for a significant reduction in the doses of the drugs he took.

United wrote that the decision came after his “records have been reviewed three times and the medical reviewers have concluded that the medication as prescribed does not meet the Medical Necessity requirement of the plan.”

In August 2021, Mr. McNaughton filed a federal lawsuit accusing United of acting in bad faith and unreasonably making treatment decisions based on financial concerns and not what was the best and most effective treatment. It claims United had a duty to find information that supported Mr. McNaughton’s claim for treatment rather than looking for ways to deny coverage.

United, in a court filing, said it did not breach any duty it owed to Mr. McNaughton and acted in good faith. On Sept. 20, 2021, a month after filing the lawsuit, and with United again balking at paying for his treatment, Mr. McNaughton asked a judge to grant a temporary restraining order requiring United to pay for his care. With the looming threat of a court hearing on the motion, United quickly agreed to cover the cost of Mr. McNaughton’s treatment through the end of the 2021-2022 academic year. It also dropped a demand requiring Mr. McNaughton to settle the matter as a condition of the insurer paying for his treatment as prescribed by Dr. Loftus, according to an email sent by United’s lawyer.
 

The cost of treatment

It is not surprising that insurers are carefully scrutinizing the care of patients treated with biologics, which are among the most expensive medications on the market. Biologics are considered specialty drugs, a class that includes the best-selling Humira, used to treat arthritis. Specialty drug spending in the United States is expected to reach $505 billion in 2023, according to an estimate from Optum, United’s health services division. The Institute for Clinical and Economic Review, a nonprofit that analyzes the value of drugs, found in 2020 that the biologic drugs used to treat patients like Mr. McNaughton are often effective but overpriced for their therapeutic benefit. To be judged cost-effective by ICER, the biologics should sell at a steep discount to their current market price, the panel found.

A panel convened by ICER to review its analysis cautioned that insurance coverage “should be structured to prevent situations in which patients are forced to choose a treatment approach on the basis of cost.” ICER also found examples where insurance company policies failed to keep pace with updates to clinical practice guidelines based on emerging research.

United officials did not make the cost of treatment an issue when discussing Mr. McNaughton’s care with Penn State administrators or the family.

Bill Truxal, the president of UnitedHealthcare StudentResources, the company’s student health plan division, told a Penn State official that the insurer wanted the “best for the student” and it had “nothing to do with cost,” according to notes the official took of the conversation.

Behind the scenes, however, the price of Mr. McNaughton’s care was front and center at United.

In one email, Mr. Opperman asked about the cost difference if the insurer insisted on paying only for greatly reduced doses of the biologic drugs. Ms. Kavanaugh responded that the insurer had paid $1.1 million in claims for Mr. McNaughton’s care as of the middle of May 2021. If the reduced doses had been in place, the amount would have been cut to $260,218, she wrote.

United was keeping close tabs on Mr. McNaughton at the highest levels of the company. On Aug. 2, 2021, Mr. Opperman notified Mr. Truxal and a United lawyer that Mr. McNaughton “has just purchased the plan again for the 21-22 school year.”

A month later, Ms. Kavanaugh shared another calculation with United executives showing that the insurer spent over $1.7 million on Mr. McNaughton in the prior plan year.

United officials strategized about how to best explain why it was reviewing Mr. McNaughton’s drug regimen, according to an internal email. They pointed to a justification often used by health insurers when denying claims. “As the cost of healthcare continues to climb to soaring heights, it has been determined that a judicious review of these drugs should be included” in order to “make healthcare more affordable for our members,” Ms. Kavanaugh offered as a potential talking point in an April 23, 2021, email.

Three days later, UnitedHealth Group filed an annual statement with the U.S. Securities and Exchange Commission disclosing its pay for top executives in the prior year. Then-CEO David Wichmann was paid $17.9 million in salary and other compensation in 2020. Wichmann retired early the following year, and his total compensation that year exceeded $140 million, according to calculations in a compensation database maintained by the Star Tribune in Minneapolis. The newspaper said the amount was the most paid to an executive in the state since it started tracking pay more than 2 decades ago. About $110 million of that total came from Wichmann exercising stock options accumulated during his stewardship.

The McNaughtons were well aware of the financial situation at United. They looked at publicly available financial results and annual reports. Last year, United reported a profit of $20.1 billion on revenues of $324.2 billion.

When discussing the case with Penn State, Ms. Light said, she told university administrators that United could pay for a year of her son’s treatment using just minutes’ worth of profit.
 

‘Betrayed’

Mr. McNaughton has been able to continue receiving his infusions for now, anyway. In October, United notified him it was once again reviewing his care, although the insurer quickly reversed course when his lawyer intervened. United, in a court filing, said the review was a mistake and that it had erred in putting Mr. McNaughton’s claims into pending status.

Mr. McNaughton said he is fortunate his parents were employed at the same school he was attending, which was critical in getting the attention of administrators there. But that help had its limits.

In June 2021, just a week after United told Mr. McNaughton it would not cover his treatment plan in the upcoming plan year, Penn State essentially walked away from the matter.

In an email to the McNaughtons and United, Penn State Associate Vice President for Student Affairs Andrea Dowhower wrote that administrators “have observed an unfortunate breakdown in communication” between Mr. McNaughton and his family and the university health insurance plan, “which appears from our perspective to have resulted in a standstill between the two parties.” While she proposed some potential steps to help settle the matter, she wrote that “Penn State’s role in this process is as a resource for students like Chris who, for whatever reason, have experienced difficulty navigating the complex world of health insurance.” The university’s role “is limited,” she wrote, and the school “simply must leave” the issue of the best treatment for Mr. McNaughton to “the appropriate health care professionals.”

In a statement, a Penn State spokesperson wrote that “as a third party in this arrangement, the University’s role is limited and Penn State officials can only help a student manage an issue based on information that a student/family, medical personnel, and/or insurance provider give – with the hope that all information is accurate and that the lines of communication remain open between the insured and the insurer.”

Penn State declined to provide financial information about the plan. However, the university and United share at least one tie that they have not publicly disclosed.

When the McNaughtons first reached out to the university for help, they were referred to the school’s student health insurance coordinator. The official, Heather Klinger, wrote in an email to the family in February 2021 that “I appreciate your trusting me to resolve this for you.”

In April 2022, United began paying Ms. Klinger’s salary, an arrangement which is not noted on the university website. Ms. Klinger appears in the online staff directory on the Penn State University Health Services web page, and has a university phone number, a university address, and a Penn State email listed as her contact. The school said she has maintained a part-time status with the university to allow her to access relevant data systems at both the university and United.

The university said students “benefit” from having a United employee to handle questions about insurance coverage and that the arrangement is “not uncommon” for student health plans.

The family was dismayed to learn that Ms. Klinger was now a full-time employee of United.

“We did feel betrayed,” Ms. Light said. Ms. Klinger did not respond to an email seeking comment.

Mr. McNaughton’s fight to maintain his treatment regimen has come at a cost of time, debilitating stress, and depression. “My biggest fear is realizing I might have to do this every year of my life,” he said.

Mr. McNaughton said one motivation for his lawsuit was to expose how insurers like United make decisions about what care they will pay for and what they will not. The case remains pending, a court docket shows.

He has been accepted to Penn State’s law school. He hopes to become a health care lawyer working for patients who find themselves in situations similar to his.

He plans to re-enroll in the United health care plan when he starts school next fall.

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive the biggest stories as soon as they’re published.

In May 2021, a nurse at UnitedHealthcare called a colleague to share some welcome news about a problem the two had been grappling with for weeks.

United provided the health insurance plan for students at Penn State University. It was a large and potentially lucrative account: lots of young, healthy students paying premiums in, not too many huge medical reimbursements going out.

But one student was costing United a lot of money. Christopher McNaughton suffered from a crippling case of ulcerative colitis – an ailment that caused him to develop severe arthritis, debilitating diarrhea, numbing fatigue, and life-threatening blood clots. His medical bills were running nearly $2 million a year.

United had flagged Mr. McNaughton’s case as a “high dollar account,” and the company was reviewing whether it needed to keep paying for the expensive cocktail of drugs crafted by a Mayo Clinic specialist that had brought Mr. McNaughton’s disease under control after he’d been through years of misery.

On the 2021 phone call, which was recorded by the company, nurse Victoria Kavanaugh told her colleague that a doctor contracted by United to review the case had concluded that Mr. McNaughton’s treatment was “not medically necessary.” Her colleague, Dave Opperman, reacted to the news with a long laugh.

“I knew that was coming,” said Mr. Opperman, who heads up a United subsidiary that brokered the health insurance contract between United and Penn State. “I did too,” Ms. Kavanaugh replied.

Mr. Opperman then complained about Mr. McNaughton’s mother, whom he referred to as “this woman,” for “screaming and yelling” and “throwing tantrums” during calls with United.

The pair agreed that any appeal of the United doctor’s denial of the treatment would be a waste of the family’s time and money.

“We’re still gonna say no,” Mr. Opperman said.

More than 200 million Americans are covered by private health insurance. But data from state and federal regulators shows that insurers reject about 1 in 7 claims for treatment. Many people, faced with fighting insurance companies, simply give up: One study found that Americans file formal appeals on only 0.1% of claims denied by insurers under the Affordable Care Act.

Insurers have wide discretion in crafting what is covered by their policies, beyond some basic services mandated by federal and state law. They often deny claims for services that they deem not “medically necessary.”

When United refused to pay for Mr. McNaughton’s treatment for that reason, his family did something unusual. They fought back with a lawsuit, which uncovered a trove of materials, including internal emails and tape-recorded exchanges among company employees. Those records offer an extraordinary behind-the-scenes look at how one of America’s leading health care insurers relentlessly fought to reduce spending on care, even as its profits rose to record levels.

As United reviewed Mr. McNaughton’s treatment, he and his family were often in the dark about what was happening or their rights. Meanwhile, United employees misrepresented critical findings and ignored warnings from doctors about the risks of altering Mr. McNaughton’s drug plan.

At one point, court records show, United inaccurately reported to Penn State and the family that Mr. McNaughton’s doctor had agreed to lower the doses of his medication. Another time, a doctor paid by United concluded that denying payments for Mr. McNaughton’s treatment could put his health at risk, but the company buried his report and did not consider its findings. The insurer did, however, consider a report submitted by a company doctor who rubber-stamped the recommendation of a United nurse to reject paying for the treatment.

United declined to answer specific questions about the case, even after Mr. McNaughton signed a release provided by the insurer to allow it to discuss details of his interactions with the company. United noted that it ultimately paid for all of Mr. McNaughton’s treatments. In a written response, United spokesperson Maria Gordon Shydlo wrote that the company’s guiding concern was Mr. McNaughton’s well-being.

“Mr. McNaughton’s treatment involves medication dosages that far exceed [Food and Drug Administration] guidelines,” the statement said. “In cases like this, we review treatment plans based on current clinical guidelines to help ensure patient safety.”

But the records reviewed by ProPublica show that United had another, equally urgent goal in dealing with Mr. McNaughton. In emails, officials calculated what Mr. McNaughton was costing them to keep his crippling disease at bay and how much they would save if they forced him to undergo a cheaper treatment that had already failed him. As the family pressed the company to back down, first through Penn State and then through a lawsuit, the United officials handling the case bristled.

“This is just unbelievable,” Ms. Kavanaugh said of Mr. McNaughton’s family in one call to discuss his case. ”They’re just really pushing the envelope, and I’m surprised, like I don’t even know what to say.”
 

The same meal every day

Now 31, Mr. McNaughton grew up in State College, Pa., just blocks from the Penn State campus. Both of his parents are faculty members at the university.

In the winter of 2014, Mr. McNaughton was halfway through his junior year at Bard College in New York. At 6 feet, 4 inches tall, he was a guard on the basketball team and had started most of the team’s games since the start of his sophomore year. He was majoring in psychology.

When Mr. McNaughton returned to school after the winter holiday break, he started to experience frequent bouts of bloody diarrhea. After just a few days on campus, he went home to State College, where doctors diagnosed him with a severe case of ulcerative colitis.

A chronic inflammatory bowel disease that causes swelling and ulcers in the digestive tract, ulcerative colitis has no cure, and ongoing treatment is needed to alleviate symptoms and prevent serious health complications. The majority of cases produce mild to moderate symptoms. Mr. McNaughton’s case was severe.

Treatments for ulcerative colitis include steroids and special drugs known as biologics that work to reduce inflammation in the large intestine.

Mr. McNaughton, however, failed to get meaningful relief from the drugs his doctors initially prescribed. He was experiencing bloody diarrhea up to 20 times a day, with such severe stomach pain that he spent much of his day curled up on a couch. He had little appetite and lost 50 pounds. Severe anemia left him fatigued. He suffered from other conditions related to his colitis, including crippling arthritis. He was hospitalized several times to treat dangerous blood clots.

For 2 years, in an effort to help alleviate his symptoms, he ate the same meals every day: Rice Chex cereal and scrambled eggs for breakfast, a cup of white rice with plain chicken breast for lunch, and a similar meal for dinner, occasionally swapping in tilapia.

His hometown doctors referred him to a specialist at the University of Pittsburgh, who tried unsuccessfully to bring his disease under control. That doctor ended up referring Mr. McNaughton to Edward V. Loftus Jr., MD, at the Mayo Clinic in Rochester, Minn., which has been ranked as the best gastroenterology hospital in the country every year since 1990 by U.S. News & World Report.

For his first visit with Dr. Loftus in May 2015, Mr. McNaughton and his mother, Janice Light, charted hospitals along the 900-mile drive from Pennsylvania to Minnesota in case they needed medical help along the way.

Mornings were the hardest. Mr. McNaughton often spent several hours in the bathroom at the start of the day. To prepare for his meeting with Dr. Loftus, he set his alarm for 3:30 a.m. so he could be ready for the 7:30 a.m. appointment. Even with that preparation, he had to stop twice to use a bathroom on the 5-minute walk from the hotel to the clinic. When they met, Dr. Loftus looked at Mr. McNaughton and told him that he appeared incapacitated. It was, he told the student, as if Mr. McNaughton were chained to the bathroom, with no outside life. He had not been able to return to school and spent most days indoors, managing his symptoms as best he could.

Mr. McNaughton had tried a number of medications by this point, none of which worked. This pattern would repeat itself during the first couple of years that Dr. Loftus treated him.

In addition to trying to find a treatment that would bring Mr. McNaughton’s colitis into remission, Dr. Loftus wanted to wean him off the steroid prednisone, which he had been taking since his initial diagnosis in 2014. The drug is commonly prescribed to colitis patients to control inflammation, but prolonged use can lead to severe side effects including cataracts, osteoporosis, increased risk of infection, and fatigue. Mr. McNaughton also experienced “moon face,” a side effect caused by the shifting of fat deposits that results in the face becoming puffy and rounder.

In 2018, Dr. Loftus and Mr. McNaughton decided to try an unusual regimen. Many patients with inflammatory bowel diseases such as colitis take a single biologic drug as treatment. Whereas traditional drugs are chemically synthesized, biologics are manufactured in living systems, such as plant or animal cells. A year’s supply of an individual biologic drug can cost up to $500,000. They are often given through infusions in a medical facility, which adds to the cost.

Mr. McNaughton had tried individual biologics, and then two in combination, without much success. He and Dr. Loftus then agreed to try two biologic drugs together at doses well above those recommended by the Food and Drug Administration. The federal Agency for Healthcare Research and Quality estimates one in five prescriptions written today are for off-label uses.

There are drawbacks to the practice. Since some uses and doses of particular drugs have not been extensively studied, the risks and efficacy of using them off-label are not well known. Also, some drug manufacturers have improperly pushed off-label usage of their products to boost sales despite little or no evidence to support their use in those situations. Like many leading experts and researchers in his field, Dr. Loftus has been paid to do consulting related to the biologic drugs taken by Mr. McNaughton. The payments related to those drugs have ranged from a total of $1,440 in 2020 to $51,235 in 2018. Dr. Loftus said much of his work with pharmaceutical companies was related to conducting clinical trials on new drugs.

In cases of off-label prescribing, patients are depending upon their doctors’ expertise and experience with the drug. “In this case, I was comfortable that the potential benefits to Chris outweighed the risks,” Dr. Loftus said.

There was evidence that the treatment plan for Mr. McNaughton might work, including studies that had found dual biologic therapy to be efficacious and safe. The two drugs he takes, Entyvio and Remicade, have the same purpose – to reduce inflammation in the large intestine – but each works differently in the body. Remicade, marketed by Janssen Biotech, targets a protein that causes inflammation. Entyvio, made by Takeda Pharmaceuticals, works by preventing an excess of white blood cells from entering into the gastrointestinal tract.

As for any suggestion by United doctors that his treatment plan for Mr. McNaughton was out of bounds or dangerous, Dr. Loftus said “my treatment of Chris was not clinically inappropriate – as was shown by Chris’ positive outcome.”

The unusual high-dose combination of two biologic drugs produced a remarkable change in Mr. McNaughton. He no longer had blood in his stool, and his trips to the bathroom were cut from 20 times a day to 3 or 4. He was able to eat different foods and put on weight. He had more energy. He tapered off prednisone.

“If you told me in 2015 that I would be living like this, I would have asked where do I sign up,” Mr. McNaughton said of the change he experienced with the new drug regimen.

When he first started the new treatment, Mr. McNaughton was covered under his family’s plan, and all his bills were paid. Mr. McNaughton enrolled at the university in 2020. Before switching to United’s plan for students, Mr. McNaughton and his parents consulted with a health advocacy service offered to faculty members. A benefits specialist assured them the drugs taken by Mr. McNaughton would be covered by United.

Mr. McNaughton joined the student plan in July 2020, and his infusions that month and the following month were paid for by United. In September, the insurer indicated payment on his claims was “pending,” something it did for his other claims that came in during the rest of the year.

Mr. McNaughton and his family were worried. They called United to make sure there wasn’t a problem; the insurer told them, they said, that it only needed to check his medical records. When the family called again, United told them it had the documentation needed, they said. United, in a court filing last year, said it received two calls from the family and each time indicated that all of the necessary medical records had not yet been received.

In January 2021, Mr. McNaughton received a new explanation of benefits for the prior months. All of the claims for his care, beginning in September, were no longer “pending.” They were stamped “DENIED.” The total outstanding bill for his treatment was $807,086.

When Mr. McNaughton’s mother reached a United customer service representative the next day to ask why bills that had been paid in the summer were being denied for the fall, the representative told her the account was being reviewed because of “a high dollar amount on the claims,” according to a recording of the call.


 

Misrepresentations

With United refusing to pay, the family was terrified of being stuck with medical bills that would bankrupt them and deprive Mr. McNaughton of treatment that they considered miraculous.

They turned to Penn State for help. Ms. Light and Mr. McNaughton’s father, David McNaughton, hoped their position as faculty members would make the school more willing to intervene on their behalf.

“After more than 30 years on faculty, my husband and I know that this is not how Penn State would want its students to be treated,” Ms. Light wrote to a school official in February 2021.

In response to questions from ProPublica, Penn State spokesperson Lisa Powers wrote that “supporting the health and well-being of our students is always of primary importance” and that “our hearts go out to any student and family impacted by a serious medical condition.” The university, she wrote, does “not comment on students’ individual circumstances or disclose information from their records.” Mr. McNaughton offered to grant Penn State whatever permissions it needed to speak about his case with ProPublica. The school, however, wrote that it would not comment “even if confidentiality has been waived.”

The family appealed to school administrators. Because the effectiveness of biologics wanes in some patients if doses are skipped, Mr. McNaughton and his parents were worried about even a delay in treatment. His doctor wrote that if he missed scheduled infusions of the drugs, there was “a high likelihood they would no longer be effective.”

During a conference call arranged by Penn State officials on March 5, 2021, United agreed to pay for Mr. McNaughton’s care through the end of the plan year that August. Penn State immediately notified the family of the “wonderful news” while also apologizing for “the stress this has caused Chris and your family.”

Behind the scenes, Mr. McNaughton’s review had “gone all the way to the top” at United’s student health plan division, Ms. Kavanaugh, the nurse, said in a recorded conversation.

The family’s relief was short-lived. A month later, United started another review of Mr. McNaughton’s care, overseen by Ms. Kavanaugh, to determine if it would pay for the treatment in the upcoming plan year.

The nurse sent the Mr. McNaughton case to a company called Medical Review Institute of America. Insurers often turn to companies like MRIoA to review coverage decisions involving expensive treatments or specialized care.

Ms. Kavanaugh, who was assigned to a special investigations unit at United, let her feelings about the matter be known in a recorded telephone call with a representative of MRIoA.

“This school apparently is a big client of ours,” she said. She then shared her opinion of Mr. McNaughton’s treatment. “Really this is a case of a kid who’s getting a drug way too much, like too much of a dose,” Ms. Kavanaugh said. She said it was “insane that they would even think that this is reasonable” and “to be honest with you, they’re awfully pushy considering that we are paying through the end of this school year.”

On a call with an outside contractor, the United nurse claimed Mr. McNaughton was on a higher dose of medication than the FDA approved, which is a common practice.

MRIoA sent the case to Vikas Pabby, MD, a gastroenterologist at UCLA Health and a professor at the university’s medical school. His May 2021 review of Mr. McNaughton’s case was just one of more than 300 Dr. Pabby did for MRIoA that month, for which he was paid $23,000 in total, according to a log of his work produced in the lawsuit.

In a May 4, 2021, report, Dr. Pabby concluded Mr. McNaughton’s treatment was not medically necessary, because United’s policies for the two drugs taken by Mr. McNaughton did not support using them in combination.

Insurers spell out what services they cover in plan policies, lengthy documents that can be confusing and difficult to understand. Many policies, such as Mr. McNaughton’s, contain a provision that treatments and procedures must be “medically necessary” in order to be covered. The definition of medically necessary differs by plan. Some don’t even define the term. Mr. McNaughton’s policy contains a five-part definition, including that the treatment must be “in accordance with the standards of good medical policy” and “the most appropriate supply or level of service which can be safely provided.”

Behind the scenes at United, Mr. Opperman and Ms. Kavanaugh agreed that if Mr. McNaughton were to appeal Dr. Pabby’s decision, the insurer would simply rule against him. “I just think it’s a waste of money and time to appeal and send it to another one when we know we’re gonna get the same answer,” Mr. Opperman said, according to a recording in court files. At Mr. Opperman’s urging, United decided to skip the usual appeals process and arrange for Dr. Pabby to have a so-called “peer-to-peer” discussion with Dr. Loftus, the Mayo physician treating Mr. McNaughton. Such a conversation, in which a patient’s doctor talks with an insurance company’s doctor to advocate for the prescribed treatment, usually occurs only after a customer has appealed a denial and the appeal has been rejected.

When Ms. Kavanaugh called Dr. Loftus’ office to set up a conversation with Dr. Pabby, she explained it was an urgent matter and had been requested by Mr. McNaughton. “You know I’ve just gotten to know Christopher,” she explained, although she had never spoken with him. “We’re trying to advocate and help and get this peer-to-peer set up.”

Mr. McNaughton, meanwhile, had no idea at the time that a United doctor had decided his treatment was unnecessary and that the insurer was trying to set up a phone call with his physician.

In the peer-to-peer conversation, Dr. Loftus told Dr. Pabby that Mr. McNaughton had “a very complicated case” and that lower doses had not worked for him, according to an internal MRIoA memo.

Following his conversation with Dr. Loftus, Dr. Pabby created a second report for United. He recommended the insurer pay for both drugs, but at reduced doses. He added new language saying that the safety of using both drugs at the higher levels “is not established.”

When Ms. Kavanaugh shared the May 12 decision from Dr. Pabby with others at United, her boss responded with an email calling it “great news.”

Then Mr. Opperman sent an email that puzzled the McNaughtons.

In it, Mr. Opperman claimed that Dr. Loftus and Dr. Pabby had agreed that Mr. McNaughton should be on significantly lower doses of both drugs. He said Dr. Loftus “will work with the patient to start titrating them down to a normal dose range.” Mr. Opperman wrote that United would cover Mr. McNaughton’s treatment in the coming year, but only at the reduced doses. Mr. Opperman did not respond to emails and phone messages seeking comment.

Mr. McNaughton didn’t believe a word of it. He had already tried and failed treatment with those drugs at lower doses, and it was Dr. Loftus who had upped the doses, leading to his remission from severe colitis.

The only thing that made sense to Mr. McNaughton was that the treatment United said it would now pay for was dramatically cheaper – saving the company at least hundreds of thousands of dollars a year – than his prescribed treatment because it sliced the size of the doses by more than half.

When the family contacted Dr. Loftus for an explanation, they were outraged by what they heard. Dr. Loftus told them that he had never recommended lowering the dosage. In a letter, Dr. Loftus wrote that changing Mr. McNaughton’s treatment “would have serious detrimental effects on both his short term and long term health and could potentially involve life threatening complications. This would ultimately incur far greater medical costs. Chris was on the doses suggested by United Healthcare before, and they were not at all effective.”

It would not be until the lawsuit that it would become clear how Dr. Loftus’ conversations had been so seriously misrepresented.

Under questioning by Mr. McNaughton’s lawyers, Ms. Kavanaugh acknowledged that she was the source of the incorrect claim that Mr. McNaughton’s doctor had agreed to a change in treatment.

“I incorrectly made an assumption that they had come to some sort of agreement,” she said in a deposition last August. “It was my first peer-to-peer. I did not realize that that simply does not occur.”

Ms. Kavanaugh did not respond to emails and telephone messages seeking comment.

When the McNaughtons first learned of Mr. Opperman’s inaccurate report of the phone call with Dr. Loftus, it unnerved them. They started to question if their case would be fairly reviewed.

“When we got the denial and they lied about what Dr. Loftus said, it just hit me that none of this matters,” Mr. McNaughton said. “They will just say or do anything to get rid of me. It delegitimized the entire review process. When I got that denial, I was crushed.”


 

A buried report

While the family tried to sort out the inaccurate report, United continued putting the McNaughton case in front of more company doctors.

On May 21, 2021, United sent the case to one of its own doctors, Nady Cates, MD, for an additional review. The review was marked “escalated issue.” Dr. Cates is a United medical director, a title used by many insurers for physicians who review cases. It is work he has been doing as an employee of health insurers since 1989 and at United since 2010. He has not practiced medicine since the early 1990s.

Dr. Cates, in a deposition, said he stopped seeing patients because of the long hours involved and because “AIDS was coming around then. I was seeing a lot of military folks who had venereal diseases, and I guess I was concerned about being exposed.” He transitioned to reviewing paperwork for the insurance industry, he said, because “I guess I was a chicken.”

When he had practiced, Dr. Cates said, he hadn’t treated patients with ulcerative colitis and had referred those cases to a gastroenterologist.

He said his review of Mr. McNaughton’s case primarily involved reading a United nurse’s recommendation to deny his care and making sure “that there wasn’t a decimal place that was out of line.” He said he copied and pasted the nurse’s recommendation and typed “agree” on his review of Mr. McNaughton’s case.

Dr. Cates said that he does about a hundred reviews a week. He said that in his reviews he typically checks to see if any medications are prescribed in accordance with the insurer’s guidelines, and if not, he denies it. United’s policies, he said, prevented him from considering that Mr. McNaughton had failed other treatments or that Dr. Loftus was a leading expert in his field.

“You are giving zero weight to the treating doctor’s opinion on the necessity of the treatment regimen?” a lawyer asked Dr. Cates in his deposition. He responded, “Yeah.”

Attempts to contact Dr. Cates for comment were unsuccessful.

At the same time Dr. Cates was looking at Mr. McNaughton’s case, yet another review was underway at MRIoA. United said it sent the case back to MRIoA after the insurer received the letter from Dr. Loftus warning of the life-threatening complications that might occur if the dosages were reduced.

On May 24, 2021, the new report requested by MRIoA arrived. It came to a completely different conclusion than all of the previous reviews.

Nitin Kumar, MD, a gastroenterologist in Illinois, concluded that Mr. McNaughton’s established treatment plan was not only medically necessary and appropriate but that lowering his doses “can result in a lack of effective therapy of Ulcerative Colitis, with complications of uncontrolled disease (including dysplasia leading to colorectal cancer), flare, hospitalization, need for surgery, and toxic megacolon.”

Unlike other doctors who produced reports for United, Dr. Kumar discussed the harm that Mr. McNaughton might suffer if United required him to change his treatment. “His disease is significantly severe, with diagnosis at a young age,” Dr. Kumar wrote. “He has failed every biologic medication class recommended by guidelines. Therefore, guidelines can no longer be applied in this case.” He cited six studies of patients using two biologic drugs together and wrote that they revealed no significant safety issues and found the therapy to be “broadly successful.”

When Ms. Kavanaugh learned of Dr. Kumar’s report, she quickly moved to quash it and get the case returned to Dr. Pabby, according to her deposition.

In a recorded telephone call, Ms. Kavanaugh told an MRIoA representative that “I had asked that this go back through Dr. Pabby, and it went through a different doctor and they had a much different result.” After further discussion, the MRIoA representative agreed to send the case back to Dr. Pabby. “I appreciate that,” Ms. Kavanaugh replied. “I just want to make sure, because, I mean, it’s obviously a very different result than what we’ve been getting on this case.”

MRIoA case notes show that at 7:04 a.m. on May 25, 2021, Dr. Pabby was assigned to take a look at the case for the third time. At 7:27 a.m., the notes indicate, Dr. Pabby again rejected Mr. McNaughton’s treatment plan. While noting it was “difficult to control” Mr. McNaughton’s ulcerative colitis, Dr. Pabby added that his doses “far exceed what is approved by literature” and that the “safety of the requested doses is not supported by literature.”

In a deposition, Ms. Kavanaugh said that after she opened the Kumar report and read that he was supporting Mr. McNaughton’s current treatment plan, she immediately spoke to her supervisor, who told her to call MRIoA and have the case sent back to Dr. Pabby for review.

Ms. Kavanaugh said she didn’t save a copy of the Kumar report, nor did she forward it to anyone at United or to officials at Penn State who had been inquiring about the McNaughton case. “I didn’t because it shouldn’t have existed,” she said. “It should have gone back to Dr. Pabby.”

When asked if the Kumar report caused her any concerns given his warning that Mr. McNaughton risked cancer or hospitalization if his regimen were changed, Ms. Kavanaugh said she didn’t read his full report. “I saw that it was not the correct doctor, I saw the initial outcome and I was asked to send it back,” she said. Ms. Kavanaugh added, “I have a lot of empathy for this member, but it needed to go back to the peer-to-peer reviewer.”

In a court filing, United said Ms. Kavanaugh was correct in insisting that Dr. Pabby conduct the review and that MRIoA confirmed that Dr. Pabby should have been the one doing the review.

The Kumar report was not provided to Mr. McNaughton when his lawyer, Jonathan M. Gesk, first asked United and MRIoA for any reviews of the case. Mr. Gesk discovered it by accident when he was listening to a recorded telephone call produced by United in which Ms. Kavanaugh mentioned a report number Mr. Gesk had not heard before. He then called MRIoA, which confirmed the report existed and eventually provided it to him.

Dr. Pabby asked ProPublica to direct any questions about his involvement in the matter to MRIoA. The company did not respond to questions from ProPublica about the case.
 

A sense of hopelessness

When Mr. McNaughton enrolled at Penn State in 2020, it brought a sense of normalcy that he had lost when he was first diagnosed with colitis. He still needed monthly hours-long infusions and suffered occasional flare-ups and symptoms, but he was attending classes in person and living a life similar to the one he had before his diagnosis.

It was a striking contrast to the previous 6 years, which he had spent largely confined to his parents’ house in State College. The frequent bouts of diarrhea made it difficult to go out. He didn’t talk much to friends and spent as much time as he could studying potential treatments and reviewing ongoing clinical trials. He tried to keep up with the occasional online course, but his disease made it difficult to make any real progress toward a degree.

United, in correspondence with Mr. McNaughton, noted that its review of his care was “not a treatment decision. Treatment decisions are made between you and your physician.” But by threatening not to pay for his medications, or only to pay for a different regimen, Mr. McNaughton said, United was in fact attempting to dictate his treatment. From his perspective, the insurer was playing doctor, making decisions without ever examining him or even speaking to him.

The idea of changing his treatment or stopping it altogether caused constant worry for Mr. McNaughton, exacerbating his colitis and triggering physical symptoms, according to his doctors. Those included a large ulcer on his leg and welts under his skin on his thighs and shin that made his leg muscles stiff and painful to the point where he couldn’t bend his leg or walk properly. There were daily migraines and severe stomach pain. “I was consumed with this situation,” Mr. McNaughton said. “My path was unconventional, but I was proud of myself for fighting back and finishing school and getting my life back on track. I thought they were singling me out. My biggest fear was going back to the hell.”

Mr. McNaughton said he contemplated suicide on several occasions, dreading a return to a life where he was housebound or hospitalized.

Mr. McNaughton and his parents talked about his possibly moving to Canada where his grandmother lived and seeking treatment there under the nation’s government health plan.

Dr. Loftus connected Mr. McNaughton with a psychologist who specializes in helping patients with chronic digestive diseases.

The psychologist, Tiffany Taft, PsyD, said Mr. McNaughton was not an unusual case. About one in three patients with diseases like colitis suffer from medical trauma or PTSD related to it, she said, often the result of issues related to getting appropriate treatment approved by insurers.

“You get into hopelessness,” she said of the depression that accompanies fighting with insurance companies over care. “They feel like ‘I can’t fix that. I am screwed.’ When you can’t control things with what an insurance company is doing, anxiety, PTSD and depression get mixed together.”

In the case of Mr. McNaughton, Dr. Taft said, he was being treated by one of the best gastroenterologists in the world, was doing well with his treatment, and then was suddenly notified he might be on the hook for nearly a million dollars in medical charges without access to his medications. “It sends you immediately into panic about all these horrific things that could happen,” Dr. Taft said. The physical and mental symptoms Mr. McNaughton suffered after his care was threatened were “triggered” by the stress he experienced, she said.

In early June 2021, United informed Mr. McNaughton in a letter that it would not cover the cost of his treatment regimen in the next academic year, starting in August. The insurer said it would pay only for a treatment plan that called for a significant reduction in the doses of the drugs he took.

United wrote that the decision came after his “records have been reviewed three times and the medical reviewers have concluded that the medication as prescribed does not meet the Medical Necessity requirement of the plan.”

In August 2021, Mr. McNaughton filed a federal lawsuit accusing United of acting in bad faith and unreasonably making treatment decisions based on financial concerns and not what was the best and most effective treatment. It claims United had a duty to find information that supported Mr. McNaughton’s claim for treatment rather than looking for ways to deny coverage.

United, in a court filing, said it did not breach any duty it owed to Mr. McNaughton and acted in good faith. On Sept. 20, 2021, a month after filing the lawsuit, and with United again balking at paying for his treatment, Mr. McNaughton asked a judge to grant a temporary restraining order requiring United to pay for his care. With the looming threat of a court hearing on the motion, United quickly agreed to cover the cost of Mr. McNaughton’s treatment through the end of the 2021-2022 academic year. It also dropped a demand requiring Mr. McNaughton to settle the matter as a condition of the insurer paying for his treatment as prescribed by Dr. Loftus, according to an email sent by United’s lawyer.
 

The cost of treatment

It is not surprising that insurers are carefully scrutinizing the care of patients treated with biologics, which are among the most expensive medications on the market. Biologics are considered specialty drugs, a class that includes the best-selling Humira, used to treat arthritis. Specialty drug spending in the United States is expected to reach $505 billion in 2023, according to an estimate from Optum, United’s health services division. The Institute for Clinical and Economic Review, a nonprofit that analyzes the value of drugs, found in 2020 that the biologic drugs used to treat patients like Mr. McNaughton are often effective but overpriced for their therapeutic benefit. To be judged cost-effective by ICER, the biologics should sell at a steep discount to their current market price, the panel found.

A panel convened by ICER to review its analysis cautioned that insurance coverage “should be structured to prevent situations in which patients are forced to choose a treatment approach on the basis of cost.” ICER also found examples where insurance company policies failed to keep pace with updates to clinical practice guidelines based on emerging research.

United officials did not make the cost of treatment an issue when discussing Mr. McNaughton’s care with Penn State administrators or the family.

Bill Truxal, the president of UnitedHealthcare StudentResources, the company’s student health plan division, told a Penn State official that the insurer wanted the “best for the student” and it had “nothing to do with cost,” according to notes the official took of the conversation.

Behind the scenes, however, the price of Mr. McNaughton’s care was front and center at United.

In one email, Mr. Opperman asked about the cost difference if the insurer insisted on paying only for greatly reduced doses of the biologic drugs. Ms. Kavanaugh responded that the insurer had paid $1.1 million in claims for Mr. McNaughton’s care as of the middle of May 2021. If the reduced doses had been in place, the amount would have been cut to $260,218, she wrote.

United was keeping close tabs on Mr. McNaughton at the highest levels of the company. On Aug. 2, 2021, Mr. Opperman notified Mr. Truxal and a United lawyer that Mr. McNaughton “has just purchased the plan again for the 21-22 school year.”

A month later, Ms. Kavanaugh shared another calculation with United executives showing that the insurer spent over $1.7 million on Mr. McNaughton in the prior plan year.

United officials strategized about how to best explain why it was reviewing Mr. McNaughton’s drug regimen, according to an internal email. They pointed to a justification often used by health insurers when denying claims. “As the cost of healthcare continues to climb to soaring heights, it has been determined that a judicious review of these drugs should be included” in order to “make healthcare more affordable for our members,” Ms. Kavanaugh offered as a potential talking point in an April 23, 2021, email.

Three days later, UnitedHealth Group filed an annual statement with the U.S. Securities and Exchange Commission disclosing its pay for top executives in the prior year. Then-CEO David Wichmann was paid $17.9 million in salary and other compensation in 2020. Wichmann retired early the following year, and his total compensation that year exceeded $140 million, according to calculations in a compensation database maintained by the Star Tribune in Minneapolis. The newspaper said the amount was the most paid to an executive in the state since it started tracking pay more than 2 decades ago. About $110 million of that total came from Wichmann exercising stock options accumulated during his stewardship.

The McNaughtons were well aware of the financial situation at United. They looked at publicly available financial results and annual reports. Last year, United reported a profit of $20.1 billion on revenues of $324.2 billion.

When discussing the case with Penn State, Ms. Light said, she told university administrators that United could pay for a year of her son’s treatment using just minutes’ worth of profit.
 

‘Betrayed’

Mr. McNaughton has been able to continue receiving his infusions for now, anyway. In October, United notified him it was once again reviewing his care, although the insurer quickly reversed course when his lawyer intervened. United, in a court filing, said the review was a mistake and that it had erred in putting Mr. McNaughton’s claims into pending status.

Mr. McNaughton said he is fortunate his parents were employed at the same school he was attending, which was critical in getting the attention of administrators there. But that help had its limits.

In June 2021, just a week after United told Mr. McNaughton it would not cover his treatment plan in the upcoming plan year, Penn State essentially walked away from the matter.

In an email to the McNaughtons and United, Penn State Associate Vice President for Student Affairs Andrea Dowhower wrote that administrators “have observed an unfortunate breakdown in communication” between Mr. McNaughton and his family and the university health insurance plan, “which appears from our perspective to have resulted in a standstill between the two parties.” While she proposed some potential steps to help settle the matter, she wrote that “Penn State’s role in this process is as a resource for students like Chris who, for whatever reason, have experienced difficulty navigating the complex world of health insurance.” The university’s role “is limited,” she wrote, and the school “simply must leave” the issue of the best treatment for Mr. McNaughton to “the appropriate health care professionals.”

In a statement, a Penn State spokesperson wrote that “as a third party in this arrangement, the University’s role is limited and Penn State officials can only help a student manage an issue based on information that a student/family, medical personnel, and/or insurance provider give – with the hope that all information is accurate and that the lines of communication remain open between the insured and the insurer.”

Penn State declined to provide financial information about the plan. However, the university and United share at least one tie that they have not publicly disclosed.

When the McNaughtons first reached out to the university for help, they were referred to the school’s student health insurance coordinator. The official, Heather Klinger, wrote in an email to the family in February 2021 that “I appreciate your trusting me to resolve this for you.”

In April 2022, United began paying Ms. Klinger’s salary, an arrangement which is not noted on the university website. Ms. Klinger appears in the online staff directory on the Penn State University Health Services web page, and has a university phone number, a university address, and a Penn State email listed as her contact. The school said she has maintained a part-time status with the university to allow her to access relevant data systems at both the university and United.

The university said students “benefit” from having a United employee to handle questions about insurance coverage and that the arrangement is “not uncommon” for student health plans.

The family was dismayed to learn that Ms. Klinger was now a full-time employee of United.

“We did feel betrayed,” Ms. Light said. Ms. Klinger did not respond to an email seeking comment.

Mr. McNaughton’s fight to maintain his treatment regimen has come at a cost of time, debilitating stress, and depression. “My biggest fear is realizing I might have to do this every year of my life,” he said.

Mr. McNaughton said one motivation for his lawsuit was to expose how insurers like United make decisions about what care they will pay for and what they will not. The case remains pending, a court docket shows.

He has been accepted to Penn State’s law school. He hopes to become a health care lawyer working for patients who find themselves in situations similar to his.

He plans to re-enroll in the United health care plan when he starts school next fall.

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive the biggest stories as soon as they’re published.

In May 2021, a nurse at UnitedHealthcare called a colleague to share some welcome news about a problem the two had been grappling with for weeks.

United provided the health insurance plan for students at Penn State University. It was a large and potentially lucrative account: lots of young, healthy students paying premiums in, not too many huge medical reimbursements going out.

But one student was costing United a lot of money. Christopher McNaughton suffered from a crippling case of ulcerative colitis – an ailment that caused him to develop severe arthritis, debilitating diarrhea, numbing fatigue, and life-threatening blood clots. His medical bills were running nearly $2 million a year.

United had flagged Mr. McNaughton’s case as a “high dollar account,” and the company was reviewing whether it needed to keep paying for the expensive cocktail of drugs crafted by a Mayo Clinic specialist that had brought Mr. McNaughton’s disease under control after he’d been through years of misery.

On the 2021 phone call, which was recorded by the company, nurse Victoria Kavanaugh told her colleague that a doctor contracted by United to review the case had concluded that Mr. McNaughton’s treatment was “not medically necessary.” Her colleague, Dave Opperman, reacted to the news with a long laugh.

“I knew that was coming,” said Mr. Opperman, who heads up a United subsidiary that brokered the health insurance contract between United and Penn State. “I did too,” Ms. Kavanaugh replied.

Mr. Opperman then complained about Mr. McNaughton’s mother, whom he referred to as “this woman,” for “screaming and yelling” and “throwing tantrums” during calls with United.

The pair agreed that any appeal of the United doctor’s denial of the treatment would be a waste of the family’s time and money.

“We’re still gonna say no,” Mr. Opperman said.

More than 200 million Americans are covered by private health insurance. But data from state and federal regulators shows that insurers reject about 1 in 7 claims for treatment. Many people, faced with fighting insurance companies, simply give up: One study found that Americans file formal appeals on only 0.1% of claims denied by insurers under the Affordable Care Act.

Insurers have wide discretion in crafting what is covered by their policies, beyond some basic services mandated by federal and state law. They often deny claims for services that they deem not “medically necessary.”

When United refused to pay for Mr. McNaughton’s treatment for that reason, his family did something unusual. They fought back with a lawsuit, which uncovered a trove of materials, including internal emails and tape-recorded exchanges among company employees. Those records offer an extraordinary behind-the-scenes look at how one of America’s leading health care insurers relentlessly fought to reduce spending on care, even as its profits rose to record levels.

As United reviewed Mr. McNaughton’s treatment, he and his family were often in the dark about what was happening or their rights. Meanwhile, United employees misrepresented critical findings and ignored warnings from doctors about the risks of altering Mr. McNaughton’s drug plan.

At one point, court records show, United inaccurately reported to Penn State and the family that Mr. McNaughton’s doctor had agreed to lower the doses of his medication. Another time, a doctor paid by United concluded that denying payments for Mr. McNaughton’s treatment could put his health at risk, but the company buried his report and did not consider its findings. The insurer did, however, consider a report submitted by a company doctor who rubber-stamped the recommendation of a United nurse to reject paying for the treatment.

United declined to answer specific questions about the case, even after Mr. McNaughton signed a release provided by the insurer to allow it to discuss details of his interactions with the company. United noted that it ultimately paid for all of Mr. McNaughton’s treatments. In a written response, United spokesperson Maria Gordon Shydlo wrote that the company’s guiding concern was Mr. McNaughton’s well-being.

“Mr. McNaughton’s treatment involves medication dosages that far exceed [Food and Drug Administration] guidelines,” the statement said. “In cases like this, we review treatment plans based on current clinical guidelines to help ensure patient safety.”

But the records reviewed by ProPublica show that United had another, equally urgent goal in dealing with Mr. McNaughton. In emails, officials calculated what Mr. McNaughton was costing them to keep his crippling disease at bay and how much they would save if they forced him to undergo a cheaper treatment that had already failed him. As the family pressed the company to back down, first through Penn State and then through a lawsuit, the United officials handling the case bristled.

“This is just unbelievable,” Ms. Kavanaugh said of Mr. McNaughton’s family in one call to discuss his case. ”They’re just really pushing the envelope, and I’m surprised, like I don’t even know what to say.”
 

The same meal every day

Now 31, Mr. McNaughton grew up in State College, Pa., just blocks from the Penn State campus. Both of his parents are faculty members at the university.

In the winter of 2014, Mr. McNaughton was halfway through his junior year at Bard College in New York. At 6 feet, 4 inches tall, he was a guard on the basketball team and had started most of the team’s games since the start of his sophomore year. He was majoring in psychology.

When Mr. McNaughton returned to school after the winter holiday break, he started to experience frequent bouts of bloody diarrhea. After just a few days on campus, he went home to State College, where doctors diagnosed him with a severe case of ulcerative colitis.

A chronic inflammatory bowel disease that causes swelling and ulcers in the digestive tract, ulcerative colitis has no cure, and ongoing treatment is needed to alleviate symptoms and prevent serious health complications. The majority of cases produce mild to moderate symptoms. Mr. McNaughton’s case was severe.

Treatments for ulcerative colitis include steroids and special drugs known as biologics that work to reduce inflammation in the large intestine.

Mr. McNaughton, however, failed to get meaningful relief from the drugs his doctors initially prescribed. He was experiencing bloody diarrhea up to 20 times a day, with such severe stomach pain that he spent much of his day curled up on a couch. He had little appetite and lost 50 pounds. Severe anemia left him fatigued. He suffered from other conditions related to his colitis, including crippling arthritis. He was hospitalized several times to treat dangerous blood clots.

For 2 years, in an effort to help alleviate his symptoms, he ate the same meals every day: Rice Chex cereal and scrambled eggs for breakfast, a cup of white rice with plain chicken breast for lunch, and a similar meal for dinner, occasionally swapping in tilapia.

His hometown doctors referred him to a specialist at the University of Pittsburgh, who tried unsuccessfully to bring his disease under control. That doctor ended up referring Mr. McNaughton to Edward V. Loftus Jr., MD, at the Mayo Clinic in Rochester, Minn., which has been ranked as the best gastroenterology hospital in the country every year since 1990 by U.S. News & World Report.

For his first visit with Dr. Loftus in May 2015, Mr. McNaughton and his mother, Janice Light, charted hospitals along the 900-mile drive from Pennsylvania to Minnesota in case they needed medical help along the way.

Mornings were the hardest. Mr. McNaughton often spent several hours in the bathroom at the start of the day. To prepare for his meeting with Dr. Loftus, he set his alarm for 3:30 a.m. so he could be ready for the 7:30 a.m. appointment. Even with that preparation, he had to stop twice to use a bathroom on the 5-minute walk from the hotel to the clinic. When they met, Dr. Loftus looked at Mr. McNaughton and told him that he appeared incapacitated. It was, he told the student, as if Mr. McNaughton were chained to the bathroom, with no outside life. He had not been able to return to school and spent most days indoors, managing his symptoms as best he could.

Mr. McNaughton had tried a number of medications by this point, none of which worked. This pattern would repeat itself during the first couple of years that Dr. Loftus treated him.

In addition to trying to find a treatment that would bring Mr. McNaughton’s colitis into remission, Dr. Loftus wanted to wean him off the steroid prednisone, which he had been taking since his initial diagnosis in 2014. The drug is commonly prescribed to colitis patients to control inflammation, but prolonged use can lead to severe side effects including cataracts, osteoporosis, increased risk of infection, and fatigue. Mr. McNaughton also experienced “moon face,” a side effect caused by the shifting of fat deposits that results in the face becoming puffy and rounder.

In 2018, Dr. Loftus and Mr. McNaughton decided to try an unusual regimen. Many patients with inflammatory bowel diseases such as colitis take a single biologic drug as treatment. Whereas traditional drugs are chemically synthesized, biologics are manufactured in living systems, such as plant or animal cells. A year’s supply of an individual biologic drug can cost up to $500,000. They are often given through infusions in a medical facility, which adds to the cost.

Mr. McNaughton had tried individual biologics, and then two in combination, without much success. He and Dr. Loftus then agreed to try two biologic drugs together at doses well above those recommended by the Food and Drug Administration. The federal Agency for Healthcare Research and Quality estimates one in five prescriptions written today are for off-label uses.

There are drawbacks to the practice. Since some uses and doses of particular drugs have not been extensively studied, the risks and efficacy of using them off-label are not well known. Also, some drug manufacturers have improperly pushed off-label usage of their products to boost sales despite little or no evidence to support their use in those situations. Like many leading experts and researchers in his field, Dr. Loftus has been paid to do consulting related to the biologic drugs taken by Mr. McNaughton. The payments related to those drugs have ranged from a total of $1,440 in 2020 to $51,235 in 2018. Dr. Loftus said much of his work with pharmaceutical companies was related to conducting clinical trials on new drugs.

In cases of off-label prescribing, patients are depending upon their doctors’ expertise and experience with the drug. “In this case, I was comfortable that the potential benefits to Chris outweighed the risks,” Dr. Loftus said.

There was evidence that the treatment plan for Mr. McNaughton might work, including studies that had found dual biologic therapy to be efficacious and safe. The two drugs he takes, Entyvio and Remicade, have the same purpose – to reduce inflammation in the large intestine – but each works differently in the body. Remicade, marketed by Janssen Biotech, targets a protein that causes inflammation. Entyvio, made by Takeda Pharmaceuticals, works by preventing an excess of white blood cells from entering into the gastrointestinal tract.

As for any suggestion by United doctors that his treatment plan for Mr. McNaughton was out of bounds or dangerous, Dr. Loftus said “my treatment of Chris was not clinically inappropriate – as was shown by Chris’ positive outcome.”

The unusual high-dose combination of two biologic drugs produced a remarkable change in Mr. McNaughton. He no longer had blood in his stool, and his trips to the bathroom were cut from 20 times a day to 3 or 4. He was able to eat different foods and put on weight. He had more energy. He tapered off prednisone.

“If you told me in 2015 that I would be living like this, I would have asked where do I sign up,” Mr. McNaughton said of the change he experienced with the new drug regimen.

When he first started the new treatment, Mr. McNaughton was covered under his family’s plan, and all his bills were paid. Mr. McNaughton enrolled at the university in 2020. Before switching to United’s plan for students, Mr. McNaughton and his parents consulted with a health advocacy service offered to faculty members. A benefits specialist assured them the drugs taken by Mr. McNaughton would be covered by United.

Mr. McNaughton joined the student plan in July 2020, and his infusions that month and the following month were paid for by United. In September, the insurer indicated payment on his claims was “pending,” something it did for his other claims that came in during the rest of the year.

Mr. McNaughton and his family were worried. They called United to make sure there wasn’t a problem; the insurer told them, they said, that it only needed to check his medical records. When the family called again, United told them it had the documentation needed, they said. United, in a court filing last year, said it received two calls from the family and each time indicated that all of the necessary medical records had not yet been received.

In January 2021, Mr. McNaughton received a new explanation of benefits for the prior months. All of the claims for his care, beginning in September, were no longer “pending.” They were stamped “DENIED.” The total outstanding bill for his treatment was $807,086.

When Mr. McNaughton’s mother reached a United customer service representative the next day to ask why bills that had been paid in the summer were being denied for the fall, the representative told her the account was being reviewed because of “a high dollar amount on the claims,” according to a recording of the call.


 

Misrepresentations

With United refusing to pay, the family was terrified of being stuck with medical bills that would bankrupt them and deprive Mr. McNaughton of treatment that they considered miraculous.

They turned to Penn State for help. Ms. Light and Mr. McNaughton’s father, David McNaughton, hoped their position as faculty members would make the school more willing to intervene on their behalf.

“After more than 30 years on faculty, my husband and I know that this is not how Penn State would want its students to be treated,” Ms. Light wrote to a school official in February 2021.

In response to questions from ProPublica, Penn State spokesperson Lisa Powers wrote that “supporting the health and well-being of our students is always of primary importance” and that “our hearts go out to any student and family impacted by a serious medical condition.” The university, she wrote, does “not comment on students’ individual circumstances or disclose information from their records.” Mr. McNaughton offered to grant Penn State whatever permissions it needed to speak about his case with ProPublica. The school, however, wrote that it would not comment “even if confidentiality has been waived.”

The family appealed to school administrators. Because the effectiveness of biologics wanes in some patients if doses are skipped, Mr. McNaughton and his parents were worried about even a delay in treatment. His doctor wrote that if he missed scheduled infusions of the drugs, there was “a high likelihood they would no longer be effective.”

During a conference call arranged by Penn State officials on March 5, 2021, United agreed to pay for Mr. McNaughton’s care through the end of the plan year that August. Penn State immediately notified the family of the “wonderful news” while also apologizing for “the stress this has caused Chris and your family.”

Behind the scenes, Mr. McNaughton’s review had “gone all the way to the top” at United’s student health plan division, Ms. Kavanaugh, the nurse, said in a recorded conversation.

The family’s relief was short-lived. A month later, United started another review of Mr. McNaughton’s care, overseen by Ms. Kavanaugh, to determine if it would pay for the treatment in the upcoming plan year.

The nurse sent the Mr. McNaughton case to a company called Medical Review Institute of America. Insurers often turn to companies like MRIoA to review coverage decisions involving expensive treatments or specialized care.

Ms. Kavanaugh, who was assigned to a special investigations unit at United, let her feelings about the matter be known in a recorded telephone call with a representative of MRIoA.

“This school apparently is a big client of ours,” she said. She then shared her opinion of Mr. McNaughton’s treatment. “Really this is a case of a kid who’s getting a drug way too much, like too much of a dose,” Ms. Kavanaugh said. She said it was “insane that they would even think that this is reasonable” and “to be honest with you, they’re awfully pushy considering that we are paying through the end of this school year.”

On a call with an outside contractor, the United nurse claimed Mr. McNaughton was on a higher dose of medication than the FDA approved, which is a common practice.

MRIoA sent the case to Vikas Pabby, MD, a gastroenterologist at UCLA Health and a professor at the university’s medical school. His May 2021 review of Mr. McNaughton’s case was just one of more than 300 Dr. Pabby did for MRIoA that month, for which he was paid $23,000 in total, according to a log of his work produced in the lawsuit.

In a May 4, 2021, report, Dr. Pabby concluded Mr. McNaughton’s treatment was not medically necessary, because United’s policies for the two drugs taken by Mr. McNaughton did not support using them in combination.

Insurers spell out what services they cover in plan policies, lengthy documents that can be confusing and difficult to understand. Many policies, such as Mr. McNaughton’s, contain a provision that treatments and procedures must be “medically necessary” in order to be covered. The definition of medically necessary differs by plan. Some don’t even define the term. Mr. McNaughton’s policy contains a five-part definition, including that the treatment must be “in accordance with the standards of good medical policy” and “the most appropriate supply or level of service which can be safely provided.”

Behind the scenes at United, Mr. Opperman and Ms. Kavanaugh agreed that if Mr. McNaughton were to appeal Dr. Pabby’s decision, the insurer would simply rule against him. “I just think it’s a waste of money and time to appeal and send it to another one when we know we’re gonna get the same answer,” Mr. Opperman said, according to a recording in court files. At Mr. Opperman’s urging, United decided to skip the usual appeals process and arrange for Dr. Pabby to have a so-called “peer-to-peer” discussion with Dr. Loftus, the Mayo physician treating Mr. McNaughton. Such a conversation, in which a patient’s doctor talks with an insurance company’s doctor to advocate for the prescribed treatment, usually occurs only after a customer has appealed a denial and the appeal has been rejected.

When Ms. Kavanaugh called Dr. Loftus’ office to set up a conversation with Dr. Pabby, she explained it was an urgent matter and had been requested by Mr. McNaughton. “You know I’ve just gotten to know Christopher,” she explained, although she had never spoken with him. “We’re trying to advocate and help and get this peer-to-peer set up.”

Mr. McNaughton, meanwhile, had no idea at the time that a United doctor had decided his treatment was unnecessary and that the insurer was trying to set up a phone call with his physician.

In the peer-to-peer conversation, Dr. Loftus told Dr. Pabby that Mr. McNaughton had “a very complicated case” and that lower doses had not worked for him, according to an internal MRIoA memo.

Following his conversation with Dr. Loftus, Dr. Pabby created a second report for United. He recommended the insurer pay for both drugs, but at reduced doses. He added new language saying that the safety of using both drugs at the higher levels “is not established.”

When Ms. Kavanaugh shared the May 12 decision from Dr. Pabby with others at United, her boss responded with an email calling it “great news.”

Then Mr. Opperman sent an email that puzzled the McNaughtons.

In it, Mr. Opperman claimed that Dr. Loftus and Dr. Pabby had agreed that Mr. McNaughton should be on significantly lower doses of both drugs. He said Dr. Loftus “will work with the patient to start titrating them down to a normal dose range.” Mr. Opperman wrote that United would cover Mr. McNaughton’s treatment in the coming year, but only at the reduced doses. Mr. Opperman did not respond to emails and phone messages seeking comment.

Mr. McNaughton didn’t believe a word of it. He had already tried and failed treatment with those drugs at lower doses, and it was Dr. Loftus who had upped the doses, leading to his remission from severe colitis.

The only thing that made sense to Mr. McNaughton was that the treatment United said it would now pay for was dramatically cheaper – saving the company at least hundreds of thousands of dollars a year – than his prescribed treatment because it sliced the size of the doses by more than half.

When the family contacted Dr. Loftus for an explanation, they were outraged by what they heard. Dr. Loftus told them that he had never recommended lowering the dosage. In a letter, Dr. Loftus wrote that changing Mr. McNaughton’s treatment “would have serious detrimental effects on both his short term and long term health and could potentially involve life threatening complications. This would ultimately incur far greater medical costs. Chris was on the doses suggested by United Healthcare before, and they were not at all effective.”

It would not be until the lawsuit that it would become clear how Dr. Loftus’ conversations had been so seriously misrepresented.

Under questioning by Mr. McNaughton’s lawyers, Ms. Kavanaugh acknowledged that she was the source of the incorrect claim that Mr. McNaughton’s doctor had agreed to a change in treatment.

“I incorrectly made an assumption that they had come to some sort of agreement,” she said in a deposition last August. “It was my first peer-to-peer. I did not realize that that simply does not occur.”

Ms. Kavanaugh did not respond to emails and telephone messages seeking comment.

When the McNaughtons first learned of Mr. Opperman’s inaccurate report of the phone call with Dr. Loftus, it unnerved them. They started to question if their case would be fairly reviewed.

“When we got the denial and they lied about what Dr. Loftus said, it just hit me that none of this matters,” Mr. McNaughton said. “They will just say or do anything to get rid of me. It delegitimized the entire review process. When I got that denial, I was crushed.”


 

A buried report

While the family tried to sort out the inaccurate report, United continued putting the McNaughton case in front of more company doctors.

On May 21, 2021, United sent the case to one of its own doctors, Nady Cates, MD, for an additional review. The review was marked “escalated issue.” Dr. Cates is a United medical director, a title used by many insurers for physicians who review cases. It is work he has been doing as an employee of health insurers since 1989 and at United since 2010. He has not practiced medicine since the early 1990s.

Dr. Cates, in a deposition, said he stopped seeing patients because of the long hours involved and because “AIDS was coming around then. I was seeing a lot of military folks who had venereal diseases, and I guess I was concerned about being exposed.” He transitioned to reviewing paperwork for the insurance industry, he said, because “I guess I was a chicken.”

When he had practiced, Dr. Cates said, he hadn’t treated patients with ulcerative colitis and had referred those cases to a gastroenterologist.

He said his review of Mr. McNaughton’s case primarily involved reading a United nurse’s recommendation to deny his care and making sure “that there wasn’t a decimal place that was out of line.” He said he copied and pasted the nurse’s recommendation and typed “agree” on his review of Mr. McNaughton’s case.

Dr. Cates said that he does about a hundred reviews a week. He said that in his reviews he typically checks to see if any medications are prescribed in accordance with the insurer’s guidelines, and if not, he denies it. United’s policies, he said, prevented him from considering that Mr. McNaughton had failed other treatments or that Dr. Loftus was a leading expert in his field.

“You are giving zero weight to the treating doctor’s opinion on the necessity of the treatment regimen?” a lawyer asked Dr. Cates in his deposition. He responded, “Yeah.”

Attempts to contact Dr. Cates for comment were unsuccessful.

At the same time Dr. Cates was looking at Mr. McNaughton’s case, yet another review was underway at MRIoA. United said it sent the case back to MRIoA after the insurer received the letter from Dr. Loftus warning of the life-threatening complications that might occur if the dosages were reduced.

On May 24, 2021, the new report requested by MRIoA arrived. It came to a completely different conclusion than all of the previous reviews.

Nitin Kumar, MD, a gastroenterologist in Illinois, concluded that Mr. McNaughton’s established treatment plan was not only medically necessary and appropriate but that lowering his doses “can result in a lack of effective therapy of Ulcerative Colitis, with complications of uncontrolled disease (including dysplasia leading to colorectal cancer), flare, hospitalization, need for surgery, and toxic megacolon.”

Unlike other doctors who produced reports for United, Dr. Kumar discussed the harm that Mr. McNaughton might suffer if United required him to change his treatment. “His disease is significantly severe, with diagnosis at a young age,” Dr. Kumar wrote. “He has failed every biologic medication class recommended by guidelines. Therefore, guidelines can no longer be applied in this case.” He cited six studies of patients using two biologic drugs together and wrote that they revealed no significant safety issues and found the therapy to be “broadly successful.”

When Ms. Kavanaugh learned of Dr. Kumar’s report, she quickly moved to quash it and get the case returned to Dr. Pabby, according to her deposition.

In a recorded telephone call, Ms. Kavanaugh told an MRIoA representative that “I had asked that this go back through Dr. Pabby, and it went through a different doctor and they had a much different result.” After further discussion, the MRIoA representative agreed to send the case back to Dr. Pabby. “I appreciate that,” Ms. Kavanaugh replied. “I just want to make sure, because, I mean, it’s obviously a very different result than what we’ve been getting on this case.”

MRIoA case notes show that at 7:04 a.m. on May 25, 2021, Dr. Pabby was assigned to take a look at the case for the third time. At 7:27 a.m., the notes indicate, Dr. Pabby again rejected Mr. McNaughton’s treatment plan. While noting it was “difficult to control” Mr. McNaughton’s ulcerative colitis, Dr. Pabby added that his doses “far exceed what is approved by literature” and that the “safety of the requested doses is not supported by literature.”

In a deposition, Ms. Kavanaugh said that after she opened the Kumar report and read that he was supporting Mr. McNaughton’s current treatment plan, she immediately spoke to her supervisor, who told her to call MRIoA and have the case sent back to Dr. Pabby for review.

Ms. Kavanaugh said she didn’t save a copy of the Kumar report, nor did she forward it to anyone at United or to officials at Penn State who had been inquiring about the McNaughton case. “I didn’t because it shouldn’t have existed,” she said. “It should have gone back to Dr. Pabby.”

When asked if the Kumar report caused her any concerns given his warning that Mr. McNaughton risked cancer or hospitalization if his regimen were changed, Ms. Kavanaugh said she didn’t read his full report. “I saw that it was not the correct doctor, I saw the initial outcome and I was asked to send it back,” she said. Ms. Kavanaugh added, “I have a lot of empathy for this member, but it needed to go back to the peer-to-peer reviewer.”

In a court filing, United said Ms. Kavanaugh was correct in insisting that Dr. Pabby conduct the review and that MRIoA confirmed that Dr. Pabby should have been the one doing the review.

The Kumar report was not provided to Mr. McNaughton when his lawyer, Jonathan M. Gesk, first asked United and MRIoA for any reviews of the case. Mr. Gesk discovered it by accident when he was listening to a recorded telephone call produced by United in which Ms. Kavanaugh mentioned a report number Mr. Gesk had not heard before. He then called MRIoA, which confirmed the report existed and eventually provided it to him.

Dr. Pabby asked ProPublica to direct any questions about his involvement in the matter to MRIoA. The company did not respond to questions from ProPublica about the case.
 

A sense of hopelessness

When Mr. McNaughton enrolled at Penn State in 2020, it brought a sense of normalcy that he had lost when he was first diagnosed with colitis. He still needed monthly hours-long infusions and suffered occasional flare-ups and symptoms, but he was attending classes in person and living a life similar to the one he had before his diagnosis.

It was a striking contrast to the previous 6 years, which he had spent largely confined to his parents’ house in State College. The frequent bouts of diarrhea made it difficult to go out. He didn’t talk much to friends and spent as much time as he could studying potential treatments and reviewing ongoing clinical trials. He tried to keep up with the occasional online course, but his disease made it difficult to make any real progress toward a degree.

United, in correspondence with Mr. McNaughton, noted that its review of his care was “not a treatment decision. Treatment decisions are made between you and your physician.” But by threatening not to pay for his medications, or only to pay for a different regimen, Mr. McNaughton said, United was in fact attempting to dictate his treatment. From his perspective, the insurer was playing doctor, making decisions without ever examining him or even speaking to him.

The idea of changing his treatment or stopping it altogether caused constant worry for Mr. McNaughton, exacerbating his colitis and triggering physical symptoms, according to his doctors. Those included a large ulcer on his leg and welts under his skin on his thighs and shin that made his leg muscles stiff and painful to the point where he couldn’t bend his leg or walk properly. There were daily migraines and severe stomach pain. “I was consumed with this situation,” Mr. McNaughton said. “My path was unconventional, but I was proud of myself for fighting back and finishing school and getting my life back on track. I thought they were singling me out. My biggest fear was going back to the hell.”

Mr. McNaughton said he contemplated suicide on several occasions, dreading a return to a life where he was housebound or hospitalized.

Mr. McNaughton and his parents talked about his possibly moving to Canada where his grandmother lived and seeking treatment there under the nation’s government health plan.

Dr. Loftus connected Mr. McNaughton with a psychologist who specializes in helping patients with chronic digestive diseases.

The psychologist, Tiffany Taft, PsyD, said Mr. McNaughton was not an unusual case. About one in three patients with diseases like colitis suffer from medical trauma or PTSD related to it, she said, often the result of issues related to getting appropriate treatment approved by insurers.

“You get into hopelessness,” she said of the depression that accompanies fighting with insurance companies over care. “They feel like ‘I can’t fix that. I am screwed.’ When you can’t control things with what an insurance company is doing, anxiety, PTSD and depression get mixed together.”

In the case of Mr. McNaughton, Dr. Taft said, he was being treated by one of the best gastroenterologists in the world, was doing well with his treatment, and then was suddenly notified he might be on the hook for nearly a million dollars in medical charges without access to his medications. “It sends you immediately into panic about all these horrific things that could happen,” Dr. Taft said. The physical and mental symptoms Mr. McNaughton suffered after his care was threatened were “triggered” by the stress he experienced, she said.

In early June 2021, United informed Mr. McNaughton in a letter that it would not cover the cost of his treatment regimen in the next academic year, starting in August. The insurer said it would pay only for a treatment plan that called for a significant reduction in the doses of the drugs he took.

United wrote that the decision came after his “records have been reviewed three times and the medical reviewers have concluded that the medication as prescribed does not meet the Medical Necessity requirement of the plan.”

In August 2021, Mr. McNaughton filed a federal lawsuit accusing United of acting in bad faith and unreasonably making treatment decisions based on financial concerns and not what was the best and most effective treatment. It claims United had a duty to find information that supported Mr. McNaughton’s claim for treatment rather than looking for ways to deny coverage.

United, in a court filing, said it did not breach any duty it owed to Mr. McNaughton and acted in good faith. On Sept. 20, 2021, a month after filing the lawsuit, and with United again balking at paying for his treatment, Mr. McNaughton asked a judge to grant a temporary restraining order requiring United to pay for his care. With the looming threat of a court hearing on the motion, United quickly agreed to cover the cost of Mr. McNaughton’s treatment through the end of the 2021-2022 academic year. It also dropped a demand requiring Mr. McNaughton to settle the matter as a condition of the insurer paying for his treatment as prescribed by Dr. Loftus, according to an email sent by United’s lawyer.
 

The cost of treatment

It is not surprising that insurers are carefully scrutinizing the care of patients treated with biologics, which are among the most expensive medications on the market. Biologics are considered specialty drugs, a class that includes the best-selling Humira, used to treat arthritis. Specialty drug spending in the United States is expected to reach $505 billion in 2023, according to an estimate from Optum, United’s health services division. The Institute for Clinical and Economic Review, a nonprofit that analyzes the value of drugs, found in 2020 that the biologic drugs used to treat patients like Mr. McNaughton are often effective but overpriced for their therapeutic benefit. To be judged cost-effective by ICER, the biologics should sell at a steep discount to their current market price, the panel found.

A panel convened by ICER to review its analysis cautioned that insurance coverage “should be structured to prevent situations in which patients are forced to choose a treatment approach on the basis of cost.” ICER also found examples where insurance company policies failed to keep pace with updates to clinical practice guidelines based on emerging research.

United officials did not make the cost of treatment an issue when discussing Mr. McNaughton’s care with Penn State administrators or the family.

Bill Truxal, the president of UnitedHealthcare StudentResources, the company’s student health plan division, told a Penn State official that the insurer wanted the “best for the student” and it had “nothing to do with cost,” according to notes the official took of the conversation.

Behind the scenes, however, the price of Mr. McNaughton’s care was front and center at United.

In one email, Mr. Opperman asked about the cost difference if the insurer insisted on paying only for greatly reduced doses of the biologic drugs. Ms. Kavanaugh responded that the insurer had paid $1.1 million in claims for Mr. McNaughton’s care as of the middle of May 2021. If the reduced doses had been in place, the amount would have been cut to $260,218, she wrote.

United was keeping close tabs on Mr. McNaughton at the highest levels of the company. On Aug. 2, 2021, Mr. Opperman notified Mr. Truxal and a United lawyer that Mr. McNaughton “has just purchased the plan again for the 21-22 school year.”

A month later, Ms. Kavanaugh shared another calculation with United executives showing that the insurer spent over $1.7 million on Mr. McNaughton in the prior plan year.

United officials strategized about how to best explain why it was reviewing Mr. McNaughton’s drug regimen, according to an internal email. They pointed to a justification often used by health insurers when denying claims. “As the cost of healthcare continues to climb to soaring heights, it has been determined that a judicious review of these drugs should be included” in order to “make healthcare more affordable for our members,” Ms. Kavanaugh offered as a potential talking point in an April 23, 2021, email.

Three days later, UnitedHealth Group filed an annual statement with the U.S. Securities and Exchange Commission disclosing its pay for top executives in the prior year. Then-CEO David Wichmann was paid $17.9 million in salary and other compensation in 2020. Wichmann retired early the following year, and his total compensation that year exceeded $140 million, according to calculations in a compensation database maintained by the Star Tribune in Minneapolis. The newspaper said the amount was the most paid to an executive in the state since it started tracking pay more than 2 decades ago. About $110 million of that total came from Wichmann exercising stock options accumulated during his stewardship.

The McNaughtons were well aware of the financial situation at United. They looked at publicly available financial results and annual reports. Last year, United reported a profit of $20.1 billion on revenues of $324.2 billion.

When discussing the case with Penn State, Ms. Light said, she told university administrators that United could pay for a year of her son’s treatment using just minutes’ worth of profit.
 

‘Betrayed’

Mr. McNaughton has been able to continue receiving his infusions for now, anyway. In October, United notified him it was once again reviewing his care, although the insurer quickly reversed course when his lawyer intervened. United, in a court filing, said the review was a mistake and that it had erred in putting Mr. McNaughton’s claims into pending status.

Mr. McNaughton said he is fortunate his parents were employed at the same school he was attending, which was critical in getting the attention of administrators there. But that help had its limits.

In June 2021, just a week after United told Mr. McNaughton it would not cover his treatment plan in the upcoming plan year, Penn State essentially walked away from the matter.

In an email to the McNaughtons and United, Penn State Associate Vice President for Student Affairs Andrea Dowhower wrote that administrators “have observed an unfortunate breakdown in communication” between Mr. McNaughton and his family and the university health insurance plan, “which appears from our perspective to have resulted in a standstill between the two parties.” While she proposed some potential steps to help settle the matter, she wrote that “Penn State’s role in this process is as a resource for students like Chris who, for whatever reason, have experienced difficulty navigating the complex world of health insurance.” The university’s role “is limited,” she wrote, and the school “simply must leave” the issue of the best treatment for Mr. McNaughton to “the appropriate health care professionals.”

In a statement, a Penn State spokesperson wrote that “as a third party in this arrangement, the University’s role is limited and Penn State officials can only help a student manage an issue based on information that a student/family, medical personnel, and/or insurance provider give – with the hope that all information is accurate and that the lines of communication remain open between the insured and the insurer.”

Penn State declined to provide financial information about the plan. However, the university and United share at least one tie that they have not publicly disclosed.

When the McNaughtons first reached out to the university for help, they were referred to the school’s student health insurance coordinator. The official, Heather Klinger, wrote in an email to the family in February 2021 that “I appreciate your trusting me to resolve this for you.”

In April 2022, United began paying Ms. Klinger’s salary, an arrangement which is not noted on the university website. Ms. Klinger appears in the online staff directory on the Penn State University Health Services web page, and has a university phone number, a university address, and a Penn State email listed as her contact. The school said she has maintained a part-time status with the university to allow her to access relevant data systems at both the university and United.

The university said students “benefit” from having a United employee to handle questions about insurance coverage and that the arrangement is “not uncommon” for student health plans.

The family was dismayed to learn that Ms. Klinger was now a full-time employee of United.

“We did feel betrayed,” Ms. Light said. Ms. Klinger did not respond to an email seeking comment.

Mr. McNaughton’s fight to maintain his treatment regimen has come at a cost of time, debilitating stress, and depression. “My biggest fear is realizing I might have to do this every year of my life,” he said.

Mr. McNaughton said one motivation for his lawsuit was to expose how insurers like United make decisions about what care they will pay for and what they will not. The case remains pending, a court docket shows.

He has been accepted to Penn State’s law school. He hopes to become a health care lawyer working for patients who find themselves in situations similar to his.

He plans to re-enroll in the United health care plan when he starts school next fall.

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive the biggest stories as soon as they’re published.

When 2022 began, we started seeing some light at the end of the COVID-19 tunnel. Vaccines were widely available, and even with new variants of the virus still occasionally emerging, the rates of severe morbidity and mortality appeared to be decreasing.

Expectedly, journals appeared to start moving more toward mainstream topics and publications rather than what seemed like a major focus on COVID-19 publications. The resulting literature was fantastic. This past year brought some outstanding publications related to emergency medicine that are practice changers.

Several of those topics were discussed in a prior Emergency Medicine Viewpoint from this news organization, and many more of the research advances of 2022 will be discussed in the near future. However, in this Viewpoint, I would like to present my annual review of my three “must-read” articles of the past year.

As in past years, I am choosing reviews of the literature rather than original research articles (which, all too often, become outdated or debunked within a few years). I choose these articles in the hopes that readers will not simply settle for my brief reviews of the key points but instead will feel compelled to download and read the entire articles. These publications address common conditions and quandaries we face in the daily practice of emergency medicine and are practice-changing.
 

Myocardial dysfunction after cardiac arrest: Tips and pitfalls

The management of post–cardiac arrest patients remains a hot topic in the resuscitation literature as we continue to understand that the immediate post-arrest period is critical to patient outcome.

Ortuno and colleagues reviewed the current literature on post-arrest care and wrote an outstanding summary of how to optimally care for these patients. More specifically, they focused on post-arrest patients who demonstrate continued shock, or “post–cardiac arrest myocardial dysfunction” (PCAMD).

They propose three mechanisms for the pathogenesis of PCAMD: ischemia reperfusion phenomenon, systemic inflammatory response, and increased catecholamine release

I will skip through the details of the pathophysiology that they describe in the article, but I certainly do recommend that everyone review their descriptions.

Management of these patients begins with a good hemodynamic assessment, which includes clinical markers of perfusion (blood pressure, capillary refill), ECG, and point-of-care ultrasound (POCUS). If the initial assessment reveals an obvious cause of the cardiac arrest (e.g., massive pulmonary embolism, myocardial infarction, pericardial tamponade), then the underlying cause should be treated expeditiously.

In the absence of an obvious treatable cause of the shock, the fluid status and cardiac function should be addressed with POCUS. If the patient is hypovolemic, intravenous fluids should be administered. If the fluid status is adequate, POCUS should be used to estimate the patient’s ventricular function. If the ventricle appears to be hyperdynamic with good contractility, shock should be treated with norepinephrine. On the other hand, if the ventricle is hypodynamic, dobutamine should be substituted for norepinephrine or, more often, added to norepinephrine.

The above represents a simplified summary of the critical points, but the authors do delve into further detail and also discuss some other options for therapies, including steroids, coronary revascularization, extracorporeal membrane oxygenation, and so on. The review is very thoughtful, thorough, and definitely worth a full read.
 

Top myths of diagnosis and management of infectious diseases in hospital medicine

Most, if not all of us in medicine, have heard the saying that 50% of what we learn in medical school (or residency) will turn out to be wrong. I certainly believe in this concept and consequently, like many of you, I enjoy reading about myths and misconceptions that we have been taught. With that in mind, I have to say that I love this article because it seems to have been written specifically to address what I was taught!

This author group, consisting mostly of clinical PharmDs who are experts in antibiotic use, provide us with an evidence-based discussion of myths and pitfalls in how antibiotics are often used in current clinical practice. The authors review their top 10 myths involving the use of antibiotics in treating infections in the hospital setting. A few of these relate more to the inpatient setting, but here are my favorite emergency department (ED)–related myths that they address:

• “Antibiotics do no harm.” The authors address the risk-benefit of antibiotics based on assumed vs. confirmed infections, including a brief discussion of adverse drug effects.
• “Antibiotic durations of 7, 14, or 21 days are typically necessary.” The authors address appropriate duration of antibiotic use and the fact that unnecessarily long durations of use can lead to resistance. They also provide reassurance that some infections can be treated with quite short durations of antibiotics.
• “If one drug is good, two (or more!) is better.” The use of multiple antibiotics, often with overlapping bacterial coverage, is rampant in medicine and further increases the risk for adverse drug effects and resistance.
• “Oral antibiotics are not as good as intravenous antibiotics for hospitalized patients.” This is definitely a myth that I learned. I recall being taught by many senior physicians that anyone sick enough for admission should be treated with intravenous antibiotics. As it turns out, absorption and effectiveness of most oral antibiotics is just as good as intravenous antibiotics, and the oral formulations are often safer.
• “A history of a penicillin allergy means the patient can never receive a beta-lactam antibiotic.” This is a myth that was debunked quite a few years ago, but it seems that many clinicians still need a reminder.

The authors included five more myths that are worth the read. This is an article that needs to be disseminated among all hospital clinicians.
 

Guidelines for low-risk, recurrent abdominal pain in the emergency department

The Society for Academic Emergency Medicine (SAEM) recently initiated a program focused on creating evidence-based approaches to challenging chief complaints and presentations in the emergency department (ED). In 2021, they published an approach to managing patients with recurrent, low-risk chest pain in the ED. This past year, they published their second guideline, focused on the management of patients with low-risk, recurrent abdominal pain in the ED.

Recurrent low-risk abdominal pain is a common and vexing presentation to EDs around the world, and there is little prior published guidance. Do all of these patients need repeat imaging? How do we manage their pain? Are there nonabdominal conditions that should be considered?

Broder and colleagues did a fantastic review of the current literature and, on behalf of SAEM, have provided a rational approach to optimal management of these patients. The four major questions they addressed, with brief summaries of their recommendations, are:

• Should adult ED patients with low-risk, recurrent and previously undifferentiated abdominal pain receive a repeat CT abdomen-pelvis (CTAP) after a negative CTAP within the past 12 months? This is a typical question that we all ponder when managing these patients. Unfortunately, the writing group found insufficient evidence to definitively identify populations in whom CTAP was recommended vs could be safely withheld. It is a bit disappointing that there is no definite answer to the question. On the other hand, it is reassuring to know that the world’s best evidence essentially says that it is perfectly appropriate to use your own good clinical judgment.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain with a negative CTAP receive additional imaging with abdominal ultrasound? In this case, the writing group found enough evidence, though low-level, to suggest against routine ultrasound in the absence of concern specifically for pelvic or hepatobiliary pathology. Like most tests, ultrasound is best used when there are specific concerns rather than being used in an undifferentiated fashion.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive screening for depression/anxiety? The writing group found enough evidence, though low-level again, to suggest that screening for depression and/or anxiety be performed during the ED evaluation. This could lead to successful therapy for the abdominal pain.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive nonopioid and/or nonpharmacologic analgesics? The writing group found little evidence to suggest for or against these analgesics, but they made a consensus recommendation suggesting an opioid-minimizing strategy for pain control.

Although the final recommendations of the writing group were not definitive or based on the strongest level of evidence, I find it helpful to have this guidance, nevertheless, on behalf of a major national organization. I also find it helpful to know that even with the best evidence available, optimal patient care will often boil down to physician experience and gestalt. I should also add that the overall article is chock-full of pearls and helpful information that will further inform the readers’ decisions, and so the full version is definitely worth the read.
 

In summary

There you have it – my three favorite practice-changing articles of 2022. Although I have tried to provide key points here, the full discussions of those key points in the published articles will provide a great deal more education than I can offer in this brief write-up, and so I strongly encourage everyone to read the full versions. Please be sure to include in the comments section your own pick for favorite or must-read articles from the past year.

Amal Mattu, MD, is a professor, vice chair of education, and codirector of the emergency cardiology fellowship in the department of emergency medicine at the University of Maryland, Baltimore. She reported no relevant conflicts of interest.

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

When 2022 began, we started seeing some light at the end of the COVID-19 tunnel. Vaccines were widely available, and even with new variants of the virus still occasionally emerging, the rates of severe morbidity and mortality appeared to be decreasing.

Expectedly, journals appeared to start moving more toward mainstream topics and publications rather than what seemed like a major focus on COVID-19 publications. The resulting literature was fantastic. This past year brought some outstanding publications related to emergency medicine that are practice changers.

Several of those topics were discussed in a prior Emergency Medicine Viewpoint from this news organization, and many more of the research advances of 2022 will be discussed in the near future. However, in this Viewpoint, I would like to present my annual review of my three “must-read” articles of the past year.

As in past years, I am choosing reviews of the literature rather than original research articles (which, all too often, become outdated or debunked within a few years). I choose these articles in the hopes that readers will not simply settle for my brief reviews of the key points but instead will feel compelled to download and read the entire articles. These publications address common conditions and quandaries we face in the daily practice of emergency medicine and are practice-changing.
 

Myocardial dysfunction after cardiac arrest: Tips and pitfalls

The management of post–cardiac arrest patients remains a hot topic in the resuscitation literature as we continue to understand that the immediate post-arrest period is critical to patient outcome.

Ortuno and colleagues reviewed the current literature on post-arrest care and wrote an outstanding summary of how to optimally care for these patients. More specifically, they focused on post-arrest patients who demonstrate continued shock, or “post–cardiac arrest myocardial dysfunction” (PCAMD).

They propose three mechanisms for the pathogenesis of PCAMD: ischemia reperfusion phenomenon, systemic inflammatory response, and increased catecholamine release

I will skip through the details of the pathophysiology that they describe in the article, but I certainly do recommend that everyone review their descriptions.

Management of these patients begins with a good hemodynamic assessment, which includes clinical markers of perfusion (blood pressure, capillary refill), ECG, and point-of-care ultrasound (POCUS). If the initial assessment reveals an obvious cause of the cardiac arrest (e.g., massive pulmonary embolism, myocardial infarction, pericardial tamponade), then the underlying cause should be treated expeditiously.

In the absence of an obvious treatable cause of the shock, the fluid status and cardiac function should be addressed with POCUS. If the patient is hypovolemic, intravenous fluids should be administered. If the fluid status is adequate, POCUS should be used to estimate the patient’s ventricular function. If the ventricle appears to be hyperdynamic with good contractility, shock should be treated with norepinephrine. On the other hand, if the ventricle is hypodynamic, dobutamine should be substituted for norepinephrine or, more often, added to norepinephrine.

The above represents a simplified summary of the critical points, but the authors do delve into further detail and also discuss some other options for therapies, including steroids, coronary revascularization, extracorporeal membrane oxygenation, and so on. The review is very thoughtful, thorough, and definitely worth a full read.
 

Top myths of diagnosis and management of infectious diseases in hospital medicine

Most, if not all of us in medicine, have heard the saying that 50% of what we learn in medical school (or residency) will turn out to be wrong. I certainly believe in this concept and consequently, like many of you, I enjoy reading about myths and misconceptions that we have been taught. With that in mind, I have to say that I love this article because it seems to have been written specifically to address what I was taught!

This author group, consisting mostly of clinical PharmDs who are experts in antibiotic use, provide us with an evidence-based discussion of myths and pitfalls in how antibiotics are often used in current clinical practice. The authors review their top 10 myths involving the use of antibiotics in treating infections in the hospital setting. A few of these relate more to the inpatient setting, but here are my favorite emergency department (ED)–related myths that they address:

• “Antibiotics do no harm.” The authors address the risk-benefit of antibiotics based on assumed vs. confirmed infections, including a brief discussion of adverse drug effects.
• “Antibiotic durations of 7, 14, or 21 days are typically necessary.” The authors address appropriate duration of antibiotic use and the fact that unnecessarily long durations of use can lead to resistance. They also provide reassurance that some infections can be treated with quite short durations of antibiotics.
• “If one drug is good, two (or more!) is better.” The use of multiple antibiotics, often with overlapping bacterial coverage, is rampant in medicine and further increases the risk for adverse drug effects and resistance.
• “Oral antibiotics are not as good as intravenous antibiotics for hospitalized patients.” This is definitely a myth that I learned. I recall being taught by many senior physicians that anyone sick enough for admission should be treated with intravenous antibiotics. As it turns out, absorption and effectiveness of most oral antibiotics is just as good as intravenous antibiotics, and the oral formulations are often safer.
• “A history of a penicillin allergy means the patient can never receive a beta-lactam antibiotic.” This is a myth that was debunked quite a few years ago, but it seems that many clinicians still need a reminder.

The authors included five more myths that are worth the read. This is an article that needs to be disseminated among all hospital clinicians.
 

Guidelines for low-risk, recurrent abdominal pain in the emergency department

The Society for Academic Emergency Medicine (SAEM) recently initiated a program focused on creating evidence-based approaches to challenging chief complaints and presentations in the emergency department (ED). In 2021, they published an approach to managing patients with recurrent, low-risk chest pain in the ED. This past year, they published their second guideline, focused on the management of patients with low-risk, recurrent abdominal pain in the ED.

Recurrent low-risk abdominal pain is a common and vexing presentation to EDs around the world, and there is little prior published guidance. Do all of these patients need repeat imaging? How do we manage their pain? Are there nonabdominal conditions that should be considered?

Broder and colleagues did a fantastic review of the current literature and, on behalf of SAEM, have provided a rational approach to optimal management of these patients. The four major questions they addressed, with brief summaries of their recommendations, are:

• Should adult ED patients with low-risk, recurrent and previously undifferentiated abdominal pain receive a repeat CT abdomen-pelvis (CTAP) after a negative CTAP within the past 12 months? This is a typical question that we all ponder when managing these patients. Unfortunately, the writing group found insufficient evidence to definitively identify populations in whom CTAP was recommended vs could be safely withheld. It is a bit disappointing that there is no definite answer to the question. On the other hand, it is reassuring to know that the world’s best evidence essentially says that it is perfectly appropriate to use your own good clinical judgment.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain with a negative CTAP receive additional imaging with abdominal ultrasound? In this case, the writing group found enough evidence, though low-level, to suggest against routine ultrasound in the absence of concern specifically for pelvic or hepatobiliary pathology. Like most tests, ultrasound is best used when there are specific concerns rather than being used in an undifferentiated fashion.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive screening for depression/anxiety? The writing group found enough evidence, though low-level again, to suggest that screening for depression and/or anxiety be performed during the ED evaluation. This could lead to successful therapy for the abdominal pain.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive nonopioid and/or nonpharmacologic analgesics? The writing group found little evidence to suggest for or against these analgesics, but they made a consensus recommendation suggesting an opioid-minimizing strategy for pain control.

Although the final recommendations of the writing group were not definitive or based on the strongest level of evidence, I find it helpful to have this guidance, nevertheless, on behalf of a major national organization. I also find it helpful to know that even with the best evidence available, optimal patient care will often boil down to physician experience and gestalt. I should also add that the overall article is chock-full of pearls and helpful information that will further inform the readers’ decisions, and so the full version is definitely worth the read.
 

In summary

There you have it – my three favorite practice-changing articles of 2022. Although I have tried to provide key points here, the full discussions of those key points in the published articles will provide a great deal more education than I can offer in this brief write-up, and so I strongly encourage everyone to read the full versions. Please be sure to include in the comments section your own pick for favorite or must-read articles from the past year.

Amal Mattu, MD, is a professor, vice chair of education, and codirector of the emergency cardiology fellowship in the department of emergency medicine at the University of Maryland, Baltimore. She reported no relevant conflicts of interest.

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

When 2022 began, we started seeing some light at the end of the COVID-19 tunnel. Vaccines were widely available, and even with new variants of the virus still occasionally emerging, the rates of severe morbidity and mortality appeared to be decreasing.

Expectedly, journals appeared to start moving more toward mainstream topics and publications rather than what seemed like a major focus on COVID-19 publications. The resulting literature was fantastic. This past year brought some outstanding publications related to emergency medicine that are practice changers.

Several of those topics were discussed in a prior Emergency Medicine Viewpoint from this news organization, and many more of the research advances of 2022 will be discussed in the near future. However, in this Viewpoint, I would like to present my annual review of my three “must-read” articles of the past year.

As in past years, I am choosing reviews of the literature rather than original research articles (which, all too often, become outdated or debunked within a few years). I choose these articles in the hopes that readers will not simply settle for my brief reviews of the key points but instead will feel compelled to download and read the entire articles. These publications address common conditions and quandaries we face in the daily practice of emergency medicine and are practice-changing.
 

Myocardial dysfunction after cardiac arrest: Tips and pitfalls

The management of post–cardiac arrest patients remains a hot topic in the resuscitation literature as we continue to understand that the immediate post-arrest period is critical to patient outcome.

Ortuno and colleagues reviewed the current literature on post-arrest care and wrote an outstanding summary of how to optimally care for these patients. More specifically, they focused on post-arrest patients who demonstrate continued shock, or “post–cardiac arrest myocardial dysfunction” (PCAMD).

They propose three mechanisms for the pathogenesis of PCAMD: ischemia reperfusion phenomenon, systemic inflammatory response, and increased catecholamine release

I will skip through the details of the pathophysiology that they describe in the article, but I certainly do recommend that everyone review their descriptions.

Management of these patients begins with a good hemodynamic assessment, which includes clinical markers of perfusion (blood pressure, capillary refill), ECG, and point-of-care ultrasound (POCUS). If the initial assessment reveals an obvious cause of the cardiac arrest (e.g., massive pulmonary embolism, myocardial infarction, pericardial tamponade), then the underlying cause should be treated expeditiously.

In the absence of an obvious treatable cause of the shock, the fluid status and cardiac function should be addressed with POCUS. If the patient is hypovolemic, intravenous fluids should be administered. If the fluid status is adequate, POCUS should be used to estimate the patient’s ventricular function. If the ventricle appears to be hyperdynamic with good contractility, shock should be treated with norepinephrine. On the other hand, if the ventricle is hypodynamic, dobutamine should be substituted for norepinephrine or, more often, added to norepinephrine.

The above represents a simplified summary of the critical points, but the authors do delve into further detail and also discuss some other options for therapies, including steroids, coronary revascularization, extracorporeal membrane oxygenation, and so on. The review is very thoughtful, thorough, and definitely worth a full read.
 

Top myths of diagnosis and management of infectious diseases in hospital medicine

Most, if not all of us in medicine, have heard the saying that 50% of what we learn in medical school (or residency) will turn out to be wrong. I certainly believe in this concept and consequently, like many of you, I enjoy reading about myths and misconceptions that we have been taught. With that in mind, I have to say that I love this article because it seems to have been written specifically to address what I was taught!

This author group, consisting mostly of clinical PharmDs who are experts in antibiotic use, provide us with an evidence-based discussion of myths and pitfalls in how antibiotics are often used in current clinical practice. The authors review their top 10 myths involving the use of antibiotics in treating infections in the hospital setting. A few of these relate more to the inpatient setting, but here are my favorite emergency department (ED)–related myths that they address:

• “Antibiotics do no harm.” The authors address the risk-benefit of antibiotics based on assumed vs. confirmed infections, including a brief discussion of adverse drug effects.
• “Antibiotic durations of 7, 14, or 21 days are typically necessary.” The authors address appropriate duration of antibiotic use and the fact that unnecessarily long durations of use can lead to resistance. They also provide reassurance that some infections can be treated with quite short durations of antibiotics.
• “If one drug is good, two (or more!) is better.” The use of multiple antibiotics, often with overlapping bacterial coverage, is rampant in medicine and further increases the risk for adverse drug effects and resistance.
• “Oral antibiotics are not as good as intravenous antibiotics for hospitalized patients.” This is definitely a myth that I learned. I recall being taught by many senior physicians that anyone sick enough for admission should be treated with intravenous antibiotics. As it turns out, absorption and effectiveness of most oral antibiotics is just as good as intravenous antibiotics, and the oral formulations are often safer.
• “A history of a penicillin allergy means the patient can never receive a beta-lactam antibiotic.” This is a myth that was debunked quite a few years ago, but it seems that many clinicians still need a reminder.

The authors included five more myths that are worth the read. This is an article that needs to be disseminated among all hospital clinicians.
 

Guidelines for low-risk, recurrent abdominal pain in the emergency department

The Society for Academic Emergency Medicine (SAEM) recently initiated a program focused on creating evidence-based approaches to challenging chief complaints and presentations in the emergency department (ED). In 2021, they published an approach to managing patients with recurrent, low-risk chest pain in the ED. This past year, they published their second guideline, focused on the management of patients with low-risk, recurrent abdominal pain in the ED.

Recurrent low-risk abdominal pain is a common and vexing presentation to EDs around the world, and there is little prior published guidance. Do all of these patients need repeat imaging? How do we manage their pain? Are there nonabdominal conditions that should be considered?

Broder and colleagues did a fantastic review of the current literature and, on behalf of SAEM, have provided a rational approach to optimal management of these patients. The four major questions they addressed, with brief summaries of their recommendations, are:

• Should adult ED patients with low-risk, recurrent and previously undifferentiated abdominal pain receive a repeat CT abdomen-pelvis (CTAP) after a negative CTAP within the past 12 months? This is a typical question that we all ponder when managing these patients. Unfortunately, the writing group found insufficient evidence to definitively identify populations in whom CTAP was recommended vs could be safely withheld. It is a bit disappointing that there is no definite answer to the question. On the other hand, it is reassuring to know that the world’s best evidence essentially says that it is perfectly appropriate to use your own good clinical judgment.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain with a negative CTAP receive additional imaging with abdominal ultrasound? In this case, the writing group found enough evidence, though low-level, to suggest against routine ultrasound in the absence of concern specifically for pelvic or hepatobiliary pathology. Like most tests, ultrasound is best used when there are specific concerns rather than being used in an undifferentiated fashion.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive screening for depression/anxiety? The writing group found enough evidence, though low-level again, to suggest that screening for depression and/or anxiety be performed during the ED evaluation. This could lead to successful therapy for the abdominal pain.
• Should adult ED patients with low-risk, recurrent, and previously undifferentiated abdominal pain receive nonopioid and/or nonpharmacologic analgesics? The writing group found little evidence to suggest for or against these analgesics, but they made a consensus recommendation suggesting an opioid-minimizing strategy for pain control.

Although the final recommendations of the writing group were not definitive or based on the strongest level of evidence, I find it helpful to have this guidance, nevertheless, on behalf of a major national organization. I also find it helpful to know that even with the best evidence available, optimal patient care will often boil down to physician experience and gestalt. I should also add that the overall article is chock-full of pearls and helpful information that will further inform the readers’ decisions, and so the full version is definitely worth the read.
 

In summary

There you have it – my three favorite practice-changing articles of 2022. Although I have tried to provide key points here, the full discussions of those key points in the published articles will provide a great deal more education than I can offer in this brief write-up, and so I strongly encourage everyone to read the full versions. Please be sure to include in the comments section your own pick for favorite or must-read articles from the past year.

Amal Mattu, MD, is a professor, vice chair of education, and codirector of the emergency cardiology fellowship in the department of emergency medicine at the University of Maryland, Baltimore. She reported no relevant conflicts of interest.

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

Patients with thrombotic antiphospholipid syndrome are better treated with a vitamin K antagonist, such as warfarin, rather than a direct oral anticoagulant (DOAC), a new systematic review and meta-analysis suggests.

“Our study is showing that in randomized controlled trials in patients with thrombotic antiphospholipid syndrome, the risk of arterial thrombotic events, particularly stroke, is significantly increased with DOACs vs. vitamin K antagonists,” senior author, Behnood Bikdeli, MD, Brigham and Women’s Hospital, Boston, told this news organization. “These results probably suggest that DOACs are not the optimal regimen for patients with thrombotic antiphospholipid syndrome.”

The study was published online in the Journal of the American College of Cardiology.
 

Autoimmune disorder

Thrombotic antiphospholipid syndrome is a systemic autoimmune disorder characterized by recurrent arterial and/or venous thrombotic events.

Dr. Bikdeli estimates that antiphospholipid syndrome is the cause of 50,000-100,000 strokes, 100,000 cases of myocardial infarction, and 30,000 cases of deep vein thrombosis every year.

“It is a serious condition, and these are a high-risk and complex group of patients,” he said.

The standard treatment has been anticoagulation with a vitamin K antagonist such as warfarin. “But this is a cumbersome treatment, with many drug interactions and the need for INR [International Normalized Ratio] monitoring, which can be difficult to manage in patients with antiphospholipid syndrome as there can sometimes be falsely abnormal numbers,” Dr. Bikdeli noted. “Because of these challenges, it looked very promising to explore the use of DOACs in this population.”

Four main randomized trials have been conducted to investigate the use of DOACs in antiphospholipid syndrome – three with rivaroxaban and one with apixaban. “These trials were all quite small and, while they did not show definite results, some of them suggested nonsignificant findings of slightly worse outcomes for DOACs vs. vitamin K antagonists. But there is a lot of uncertainty, and it is difficult to look at subgroups in such small trials,” Dr. Bikdeli said. “There are many questions remaining about whether we should use DOACs in patients with antiphospholipid syndrome and, if so, which particular subgroups.”

The authors therefore performed a systematic review and meta-analysis of randomized controlled trials that compared DOACs with vitamin K antagonists in patients with antiphospholipid syndrome. They also contacted the principal investigators of the trials to obtain additional unpublished aggregate level data on specific subgroups.

Four open-label randomized controlled trials involving 472 patients were included in the meta-analysis.

Overall, the use of DOACs, compared with vitamin K antagonists, was associated with increased odds of subsequent arterial thrombotic events (odds ratio, 5.43; P < .001), especially stroke.

The odds of subsequent venous thrombotic events or major bleeding were not significantly different between the two groups. Most findings were consistent within subgroups.

“Our results show that use of DOACs vs. vitamin K antagonists is associated with increased risk of arterial thrombotic events – a risk that is primarily driven by a significant increase in the risk of stroke,” Dr. Bikdeli commented.

When looking at subgroups of interest, it was previously thought that DOACs may not be so effective in the so-called “triple-positive” antiphospholipid patients. These patients have three different types of antibodies and have the highest risk of thrombosis, Dr. Bikdeli noted.

“But one of the interesting findings of our study is that the results are actually consistent in women vs. men and in people who have triple-positive antibodies and those who had double- or single-positive antibodies,” he said. “Our analyses did not show effect modification by antibody subgroups. They suggest similar trends towards worse outcomes in all subgroups.”   

“From these results, I would be similarly concerned to use DOACs even if someone has double-positive or single-positive antiphospholipid antibodies,” he added.

Dr. Bikdeli said he would still recommend shared decision-making with patients. “If I have a patient who has thrombotic antiphospholipid syndrome, I would share my reservation about DOACs, but there are multiple factors that come into decision-making. If someone has difficulty with checking INRs, we may make an informed choice and still use a DOAC, but patients need to know that there is likely an excess risk of subsequent arterial events with DOACs, compared with a vitamin K antagonist.”

He noted that it is still not completely clear on the situation for people with single-positive antiphospholipid syndrome or the type of antibody that is present. It is also possible that a higher dose of DOAC could be more effective, a strategy that is being investigated in a separate randomized trial currently ongoing.

“But for routine practice I would have concerns about using DOACs in antiphospholipid syndrome patients in general,” he said. “For triple positive there is more data and greater concern, but I wouldn’t give a pass for a double- or single-positive patient either.”

The reason why DOACs would be less effective than vitamin K antagonists in antiphospholipid syndrome is not known.

“That is the million-dollar question,” Dr. Bikdeli commented. “DOACs have been such helpful drugs for many patients and clinicians as well. But we have seen that they are not optimal in a series of scenarios now – patients with mechanical heart valves, patients with rheumatic [atrial fibrillaton], and now patients with thrombotic antiphospholipid syndrome.”

One hypothesis is that these patients have some more components of inflammation and are more prone to blood clots, and because vitamin K antagonists work at several parts of the coagulation cascade, they might be more successful, compared with the more targeted DOAC therapy. “But I think we need more studies to fully understand this,” he said.

‘Important implications’

In an accompanying editorial,Mark A. Crowther, MD, McMaster University, Hamilton, Ont., and Aubrey E. Jones, PharmD, and Daniel M. Witt, PharmD, both of the University of Utah College of Pharmacy, Salt Lake City, say that: “As the quality of the evidence was rated ‘high’ for the arterial thrombosis outcome and ‘moderate’ for the venous thrombosis and bleeding outcomes, these results should lead to a revision of evidence-based guidelines to recommend against using DOACs as an option for most patients with thrombotic antiphospholipid syndrome.”

They add that this recommendation for vitamin K antagonists also applies to patients previously thought to be at lower risk from antiphospholipid syndrome – including those with only one or two positive serological tests and those with only prior venous thrombosis.

The editorialists point out that this will have important implications, particularly for the accurate diagnosis of antiphospholipid syndrome, including confirmation and documentation of positive laboratory tests at least 12 weeks after the initial positive test.

They recommend that while awaiting confirmatory testing, patients with suspected antiphospholipid syndrome should avoid DOACs, and that “strong consideration” should be given to switching essentially all antiphospholipid syndrome patients currently receiving DOACs to vitamin K antagonists.

Dr. Bikdeli is a consulting expert, on behalf of the plaintiff, for litigation related to two specific brand models of IVC filters and is supported by the Scott Schoen and Nancy Adams IGNITE Award from the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital and a Career Development Award from the American Heart Association and VIVA Physicians. Dr. Crowther has received personal funding from AstraZeneca, Precision Biologics, Hemostasis Reference Laboratories, Syneos Health, Bayer, Pfizer, and CSL Behring; and holds the Leo Pharma Chair in Thromboembolism Research, which is endowed at McMaster University. Dr. Jones is supported by a career development award from the National Heart, Lung, and Blood Institute; and Dr. Witt is supported by grant funding from the Agency for Healthcare Research and Quality.

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

Patients with thrombotic antiphospholipid syndrome are better treated with a vitamin K antagonist, such as warfarin, rather than a direct oral anticoagulant (DOAC), a new systematic review and meta-analysis suggests.

“Our study is showing that in randomized controlled trials in patients with thrombotic antiphospholipid syndrome, the risk of arterial thrombotic events, particularly stroke, is significantly increased with DOACs vs. vitamin K antagonists,” senior author, Behnood Bikdeli, MD, Brigham and Women’s Hospital, Boston, told this news organization. “These results probably suggest that DOACs are not the optimal regimen for patients with thrombotic antiphospholipid syndrome.”

The study was published online in the Journal of the American College of Cardiology.
 

Autoimmune disorder

Thrombotic antiphospholipid syndrome is a systemic autoimmune disorder characterized by recurrent arterial and/or venous thrombotic events.

Dr. Bikdeli estimates that antiphospholipid syndrome is the cause of 50,000-100,000 strokes, 100,000 cases of myocardial infarction, and 30,000 cases of deep vein thrombosis every year.

“It is a serious condition, and these are a high-risk and complex group of patients,” he said.

The standard treatment has been anticoagulation with a vitamin K antagonist such as warfarin. “But this is a cumbersome treatment, with many drug interactions and the need for INR [International Normalized Ratio] monitoring, which can be difficult to manage in patients with antiphospholipid syndrome as there can sometimes be falsely abnormal numbers,” Dr. Bikdeli noted. “Because of these challenges, it looked very promising to explore the use of DOACs in this population.”

Four main randomized trials have been conducted to investigate the use of DOACs in antiphospholipid syndrome – three with rivaroxaban and one with apixaban. “These trials were all quite small and, while they did not show definite results, some of them suggested nonsignificant findings of slightly worse outcomes for DOACs vs. vitamin K antagonists. But there is a lot of uncertainty, and it is difficult to look at subgroups in such small trials,” Dr. Bikdeli said. “There are many questions remaining about whether we should use DOACs in patients with antiphospholipid syndrome and, if so, which particular subgroups.”

The authors therefore performed a systematic review and meta-analysis of randomized controlled trials that compared DOACs with vitamin K antagonists in patients with antiphospholipid syndrome. They also contacted the principal investigators of the trials to obtain additional unpublished aggregate level data on specific subgroups.

Four open-label randomized controlled trials involving 472 patients were included in the meta-analysis.

Overall, the use of DOACs, compared with vitamin K antagonists, was associated with increased odds of subsequent arterial thrombotic events (odds ratio, 5.43; P < .001), especially stroke.

The odds of subsequent venous thrombotic events or major bleeding were not significantly different between the two groups. Most findings were consistent within subgroups.

“Our results show that use of DOACs vs. vitamin K antagonists is associated with increased risk of arterial thrombotic events – a risk that is primarily driven by a significant increase in the risk of stroke,” Dr. Bikdeli commented.

When looking at subgroups of interest, it was previously thought that DOACs may not be so effective in the so-called “triple-positive” antiphospholipid patients. These patients have three different types of antibodies and have the highest risk of thrombosis, Dr. Bikdeli noted.

“But one of the interesting findings of our study is that the results are actually consistent in women vs. men and in people who have triple-positive antibodies and those who had double- or single-positive antibodies,” he said. “Our analyses did not show effect modification by antibody subgroups. They suggest similar trends towards worse outcomes in all subgroups.”   

“From these results, I would be similarly concerned to use DOACs even if someone has double-positive or single-positive antiphospholipid antibodies,” he added.

Dr. Bikdeli said he would still recommend shared decision-making with patients. “If I have a patient who has thrombotic antiphospholipid syndrome, I would share my reservation about DOACs, but there are multiple factors that come into decision-making. If someone has difficulty with checking INRs, we may make an informed choice and still use a DOAC, but patients need to know that there is likely an excess risk of subsequent arterial events with DOACs, compared with a vitamin K antagonist.”

He noted that it is still not completely clear on the situation for people with single-positive antiphospholipid syndrome or the type of antibody that is present. It is also possible that a higher dose of DOAC could be more effective, a strategy that is being investigated in a separate randomized trial currently ongoing.

“But for routine practice I would have concerns about using DOACs in antiphospholipid syndrome patients in general,” he said. “For triple positive there is more data and greater concern, but I wouldn’t give a pass for a double- or single-positive patient either.”

The reason why DOACs would be less effective than vitamin K antagonists in antiphospholipid syndrome is not known.

“That is the million-dollar question,” Dr. Bikdeli commented. “DOACs have been such helpful drugs for many patients and clinicians as well. But we have seen that they are not optimal in a series of scenarios now – patients with mechanical heart valves, patients with rheumatic [atrial fibrillaton], and now patients with thrombotic antiphospholipid syndrome.”

One hypothesis is that these patients have some more components of inflammation and are more prone to blood clots, and because vitamin K antagonists work at several parts of the coagulation cascade, they might be more successful, compared with the more targeted DOAC therapy. “But I think we need more studies to fully understand this,” he said.

‘Important implications’

In an accompanying editorial,Mark A. Crowther, MD, McMaster University, Hamilton, Ont., and Aubrey E. Jones, PharmD, and Daniel M. Witt, PharmD, both of the University of Utah College of Pharmacy, Salt Lake City, say that: “As the quality of the evidence was rated ‘high’ for the arterial thrombosis outcome and ‘moderate’ for the venous thrombosis and bleeding outcomes, these results should lead to a revision of evidence-based guidelines to recommend against using DOACs as an option for most patients with thrombotic antiphospholipid syndrome.”

They add that this recommendation for vitamin K antagonists also applies to patients previously thought to be at lower risk from antiphospholipid syndrome – including those with only one or two positive serological tests and those with only prior venous thrombosis.

The editorialists point out that this will have important implications, particularly for the accurate diagnosis of antiphospholipid syndrome, including confirmation and documentation of positive laboratory tests at least 12 weeks after the initial positive test.

They recommend that while awaiting confirmatory testing, patients with suspected antiphospholipid syndrome should avoid DOACs, and that “strong consideration” should be given to switching essentially all antiphospholipid syndrome patients currently receiving DOACs to vitamin K antagonists.

Dr. Bikdeli is a consulting expert, on behalf of the plaintiff, for litigation related to two specific brand models of IVC filters and is supported by the Scott Schoen and Nancy Adams IGNITE Award from the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital and a Career Development Award from the American Heart Association and VIVA Physicians. Dr. Crowther has received personal funding from AstraZeneca, Precision Biologics, Hemostasis Reference Laboratories, Syneos Health, Bayer, Pfizer, and CSL Behring; and holds the Leo Pharma Chair in Thromboembolism Research, which is endowed at McMaster University. Dr. Jones is supported by a career development award from the National Heart, Lung, and Blood Institute; and Dr. Witt is supported by grant funding from the Agency for Healthcare Research and Quality.

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

Patients with thrombotic antiphospholipid syndrome are better treated with a vitamin K antagonist, such as warfarin, rather than a direct oral anticoagulant (DOAC), a new systematic review and meta-analysis suggests.

“Our study is showing that in randomized controlled trials in patients with thrombotic antiphospholipid syndrome, the risk of arterial thrombotic events, particularly stroke, is significantly increased with DOACs vs. vitamin K antagonists,” senior author, Behnood Bikdeli, MD, Brigham and Women’s Hospital, Boston, told this news organization. “These results probably suggest that DOACs are not the optimal regimen for patients with thrombotic antiphospholipid syndrome.”

The study was published online in the Journal of the American College of Cardiology.
 

Autoimmune disorder

Thrombotic antiphospholipid syndrome is a systemic autoimmune disorder characterized by recurrent arterial and/or venous thrombotic events.

Dr. Bikdeli estimates that antiphospholipid syndrome is the cause of 50,000-100,000 strokes, 100,000 cases of myocardial infarction, and 30,000 cases of deep vein thrombosis every year.

“It is a serious condition, and these are a high-risk and complex group of patients,” he said.

The standard treatment has been anticoagulation with a vitamin K antagonist such as warfarin. “But this is a cumbersome treatment, with many drug interactions and the need for INR [International Normalized Ratio] monitoring, which can be difficult to manage in patients with antiphospholipid syndrome as there can sometimes be falsely abnormal numbers,” Dr. Bikdeli noted. “Because of these challenges, it looked very promising to explore the use of DOACs in this population.”

Four main randomized trials have been conducted to investigate the use of DOACs in antiphospholipid syndrome – three with rivaroxaban and one with apixaban. “These trials were all quite small and, while they did not show definite results, some of them suggested nonsignificant findings of slightly worse outcomes for DOACs vs. vitamin K antagonists. But there is a lot of uncertainty, and it is difficult to look at subgroups in such small trials,” Dr. Bikdeli said. “There are many questions remaining about whether we should use DOACs in patients with antiphospholipid syndrome and, if so, which particular subgroups.”

The authors therefore performed a systematic review and meta-analysis of randomized controlled trials that compared DOACs with vitamin K antagonists in patients with antiphospholipid syndrome. They also contacted the principal investigators of the trials to obtain additional unpublished aggregate level data on specific subgroups.

Four open-label randomized controlled trials involving 472 patients were included in the meta-analysis.

Overall, the use of DOACs, compared with vitamin K antagonists, was associated with increased odds of subsequent arterial thrombotic events (odds ratio, 5.43; P < .001), especially stroke.

The odds of subsequent venous thrombotic events or major bleeding were not significantly different between the two groups. Most findings were consistent within subgroups.

“Our results show that use of DOACs vs. vitamin K antagonists is associated with increased risk of arterial thrombotic events – a risk that is primarily driven by a significant increase in the risk of stroke,” Dr. Bikdeli commented.

When looking at subgroups of interest, it was previously thought that DOACs may not be so effective in the so-called “triple-positive” antiphospholipid patients. These patients have three different types of antibodies and have the highest risk of thrombosis, Dr. Bikdeli noted.

“But one of the interesting findings of our study is that the results are actually consistent in women vs. men and in people who have triple-positive antibodies and those who had double- or single-positive antibodies,” he said. “Our analyses did not show effect modification by antibody subgroups. They suggest similar trends towards worse outcomes in all subgroups.”   

“From these results, I would be similarly concerned to use DOACs even if someone has double-positive or single-positive antiphospholipid antibodies,” he added.

Dr. Bikdeli said he would still recommend shared decision-making with patients. “If I have a patient who has thrombotic antiphospholipid syndrome, I would share my reservation about DOACs, but there are multiple factors that come into decision-making. If someone has difficulty with checking INRs, we may make an informed choice and still use a DOAC, but patients need to know that there is likely an excess risk of subsequent arterial events with DOACs, compared with a vitamin K antagonist.”

He noted that it is still not completely clear on the situation for people with single-positive antiphospholipid syndrome or the type of antibody that is present. It is also possible that a higher dose of DOAC could be more effective, a strategy that is being investigated in a separate randomized trial currently ongoing.

“But for routine practice I would have concerns about using DOACs in antiphospholipid syndrome patients in general,” he said. “For triple positive there is more data and greater concern, but I wouldn’t give a pass for a double- or single-positive patient either.”

The reason why DOACs would be less effective than vitamin K antagonists in antiphospholipid syndrome is not known.

“That is the million-dollar question,” Dr. Bikdeli commented. “DOACs have been such helpful drugs for many patients and clinicians as well. But we have seen that they are not optimal in a series of scenarios now – patients with mechanical heart valves, patients with rheumatic [atrial fibrillaton], and now patients with thrombotic antiphospholipid syndrome.”

One hypothesis is that these patients have some more components of inflammation and are more prone to blood clots, and because vitamin K antagonists work at several parts of the coagulation cascade, they might be more successful, compared with the more targeted DOAC therapy. “But I think we need more studies to fully understand this,” he said.

‘Important implications’

In an accompanying editorial,Mark A. Crowther, MD, McMaster University, Hamilton, Ont., and Aubrey E. Jones, PharmD, and Daniel M. Witt, PharmD, both of the University of Utah College of Pharmacy, Salt Lake City, say that: “As the quality of the evidence was rated ‘high’ for the arterial thrombosis outcome and ‘moderate’ for the venous thrombosis and bleeding outcomes, these results should lead to a revision of evidence-based guidelines to recommend against using DOACs as an option for most patients with thrombotic antiphospholipid syndrome.”

They add that this recommendation for vitamin K antagonists also applies to patients previously thought to be at lower risk from antiphospholipid syndrome – including those with only one or two positive serological tests and those with only prior venous thrombosis.

The editorialists point out that this will have important implications, particularly for the accurate diagnosis of antiphospholipid syndrome, including confirmation and documentation of positive laboratory tests at least 12 weeks after the initial positive test.

They recommend that while awaiting confirmatory testing, patients with suspected antiphospholipid syndrome should avoid DOACs, and that “strong consideration” should be given to switching essentially all antiphospholipid syndrome patients currently receiving DOACs to vitamin K antagonists.

Dr. Bikdeli is a consulting expert, on behalf of the plaintiff, for litigation related to two specific brand models of IVC filters and is supported by the Scott Schoen and Nancy Adams IGNITE Award from the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital and a Career Development Award from the American Heart Association and VIVA Physicians. Dr. Crowther has received personal funding from AstraZeneca, Precision Biologics, Hemostasis Reference Laboratories, Syneos Health, Bayer, Pfizer, and CSL Behring; and holds the Leo Pharma Chair in Thromboembolism Research, which is endowed at McMaster University. Dr. Jones is supported by a career development award from the National Heart, Lung, and Blood Institute; and Dr. Witt is supported by grant funding from the Agency for Healthcare Research and Quality.

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

A majority of hospitalized patients at low risk for venous thromboembolism were unnecessarily treated with medication, based on data from more than 400 individuals.

Prevention of venous thromboembolism (VTE) is important, and current guidelines from the American College of Chest Physicians suggest that patients with high or moderate risk for VTE be treated with mechanical prophylaxis, and that pharmacological prophylaxis is not recommended for patients at high risk for bleeding, said Hui Chong Lau, MD, in a presentation at the annual meeting of the American College of Chest Physicians (CHEST).

However, the nature of VTE prophylaxis using a risk assessment score has not been explored, said Dr. Lau, a third-year resident in internal medicine at Crozer-Chester Medical Center, Upland, Penn.

Low-molecular-weight heparin (LWMH) and intermittent pneumatic compression are often used to reduce VTE risk during hospitalization, but for patients with low VTE risk, prophylaxis is not necessarily recommended, he said. In fact, overuse of chemical prophylaxis in low-risk patients can increase bleeding risk and contribute to patient discomfort in the form of additional needle sticks while hospitalized, Dr. Lau said in the presentation.

“We wanted to see how well physicians in the hospital used a risk assessment model to stratify patients,” and how well the patients were assigned to the correct prophylaxis, he explained.

Dr. Lau and colleagues reviewed data from 469 adult patients hospitalized at a single medical center who were hospitalized between January 2021 and June 2021. The researchers retrospectively performed risk assessment using the Padua prediction score. A score of less than 4 was considered low risk for VTE, and a score of 4 or higher was considered high risk.

In the study population, 180 patients were identified as low risk and 289 were considered high risk.

Based on the Padua score, 95% of the patients at high risk were on the correct prophylaxis, Dr. Lau said.

A total of 193 high-risk patients were on heparin. However, many of these patients had good kidney function, and could have been treated with enoxaparin instead; “this would have spared them two needle sticks per day,” Dr. Lau noted.

Of the 180 low-risk patients, 168 (93.3%) were on chemical prophylaxis, and should have been on mechanical prophylaxis, he said. Only 10 patients (5%) who were considered low risk were placed on mechanical prophylaxis.

Overall, 3.6% of all patients who received chemical VTE prophylaxis developed bleeding.

The results were limited by the retrospective design and use of data from a single center. However, the findings emphasize the need for better attention to VTE risk when considering prophylaxis, said Dr. Lau. “We have to have risk assessment every day,” during a hospital stay, and adjust treatment accordingly, he said.

“We are likely overusing chemical VTE prophylaxis in low-risk patients,” he concluded.

Additional research is needed to better understand the potential consequences of overusing chemical VTE, including not only bleeding risk, but also financial costs and patient discomfort, he said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

A majority of hospitalized patients at low risk for venous thromboembolism were unnecessarily treated with medication, based on data from more than 400 individuals.

Prevention of venous thromboembolism (VTE) is important, and current guidelines from the American College of Chest Physicians suggest that patients with high or moderate risk for VTE be treated with mechanical prophylaxis, and that pharmacological prophylaxis is not recommended for patients at high risk for bleeding, said Hui Chong Lau, MD, in a presentation at the annual meeting of the American College of Chest Physicians (CHEST).

However, the nature of VTE prophylaxis using a risk assessment score has not been explored, said Dr. Lau, a third-year resident in internal medicine at Crozer-Chester Medical Center, Upland, Penn.

Low-molecular-weight heparin (LWMH) and intermittent pneumatic compression are often used to reduce VTE risk during hospitalization, but for patients with low VTE risk, prophylaxis is not necessarily recommended, he said. In fact, overuse of chemical prophylaxis in low-risk patients can increase bleeding risk and contribute to patient discomfort in the form of additional needle sticks while hospitalized, Dr. Lau said in the presentation.

“We wanted to see how well physicians in the hospital used a risk assessment model to stratify patients,” and how well the patients were assigned to the correct prophylaxis, he explained.

Dr. Lau and colleagues reviewed data from 469 adult patients hospitalized at a single medical center who were hospitalized between January 2021 and June 2021. The researchers retrospectively performed risk assessment using the Padua prediction score. A score of less than 4 was considered low risk for VTE, and a score of 4 or higher was considered high risk.

In the study population, 180 patients were identified as low risk and 289 were considered high risk.

Based on the Padua score, 95% of the patients at high risk were on the correct prophylaxis, Dr. Lau said.

A total of 193 high-risk patients were on heparin. However, many of these patients had good kidney function, and could have been treated with enoxaparin instead; “this would have spared them two needle sticks per day,” Dr. Lau noted.

Of the 180 low-risk patients, 168 (93.3%) were on chemical prophylaxis, and should have been on mechanical prophylaxis, he said. Only 10 patients (5%) who were considered low risk were placed on mechanical prophylaxis.

Overall, 3.6% of all patients who received chemical VTE prophylaxis developed bleeding.

The results were limited by the retrospective design and use of data from a single center. However, the findings emphasize the need for better attention to VTE risk when considering prophylaxis, said Dr. Lau. “We have to have risk assessment every day,” during a hospital stay, and adjust treatment accordingly, he said.

“We are likely overusing chemical VTE prophylaxis in low-risk patients,” he concluded.

Additional research is needed to better understand the potential consequences of overusing chemical VTE, including not only bleeding risk, but also financial costs and patient discomfort, he said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

A majority of hospitalized patients at low risk for venous thromboembolism were unnecessarily treated with medication, based on data from more than 400 individuals.

Prevention of venous thromboembolism (VTE) is important, and current guidelines from the American College of Chest Physicians suggest that patients with high or moderate risk for VTE be treated with mechanical prophylaxis, and that pharmacological prophylaxis is not recommended for patients at high risk for bleeding, said Hui Chong Lau, MD, in a presentation at the annual meeting of the American College of Chest Physicians (CHEST).

However, the nature of VTE prophylaxis using a risk assessment score has not been explored, said Dr. Lau, a third-year resident in internal medicine at Crozer-Chester Medical Center, Upland, Penn.

Low-molecular-weight heparin (LWMH) and intermittent pneumatic compression are often used to reduce VTE risk during hospitalization, but for patients with low VTE risk, prophylaxis is not necessarily recommended, he said. In fact, overuse of chemical prophylaxis in low-risk patients can increase bleeding risk and contribute to patient discomfort in the form of additional needle sticks while hospitalized, Dr. Lau said in the presentation.

“We wanted to see how well physicians in the hospital used a risk assessment model to stratify patients,” and how well the patients were assigned to the correct prophylaxis, he explained.

Dr. Lau and colleagues reviewed data from 469 adult patients hospitalized at a single medical center who were hospitalized between January 2021 and June 2021. The researchers retrospectively performed risk assessment using the Padua prediction score. A score of less than 4 was considered low risk for VTE, and a score of 4 or higher was considered high risk.

In the study population, 180 patients were identified as low risk and 289 were considered high risk.

Based on the Padua score, 95% of the patients at high risk were on the correct prophylaxis, Dr. Lau said.

A total of 193 high-risk patients were on heparin. However, many of these patients had good kidney function, and could have been treated with enoxaparin instead; “this would have spared them two needle sticks per day,” Dr. Lau noted.

Of the 180 low-risk patients, 168 (93.3%) were on chemical prophylaxis, and should have been on mechanical prophylaxis, he said. Only 10 patients (5%) who were considered low risk were placed on mechanical prophylaxis.

Overall, 3.6% of all patients who received chemical VTE prophylaxis developed bleeding.

The results were limited by the retrospective design and use of data from a single center. However, the findings emphasize the need for better attention to VTE risk when considering prophylaxis, said Dr. Lau. “We have to have risk assessment every day,” during a hospital stay, and adjust treatment accordingly, he said.

“We are likely overusing chemical VTE prophylaxis in low-risk patients,” he concluded.

Additional research is needed to better understand the potential consequences of overusing chemical VTE, including not only bleeding risk, but also financial costs and patient discomfort, he said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Add unprovoked venous thromboembolic events to the list of potential consequences of severe obstructive sleep apnea.

That conclusion comes from a study showing that patients with obstructive sleep apnea (OSA) who had the longest nocturnal hypoxemia episodes had a twofold risk for venous thromboembolic events.

The association between nocturnal hypoxemia and VTE was strongest among patients who did not use continuous positive airway pressure (CPAP) systems, reported Wojciech Trzepizur, MD, of Angers University Hospital, France.

Previous studies have suggested links between OSA and both cancer and cognitive decline, but this is the first study to investigate the association between OSA and the incidence of unprovoked VTE, he reported in an oral abstract session at the annual congress of the European Respiratory Society.

“We found that those who spent more than 6% of their nighttime with levels of oxygen in their blood below 90% of normal had an almost twofold risk of developing VTEs compared to patients without oxygen deprivation,” he said.

Dr. Trzepizur and colleagues conducted a retrospective study linking cohort data to an administrative health database. They identified unprovoked VTE in patients with a suspicion for OSA and no previous VTE.

They created Cox proportional hazard models to assess the association of unprovoked VTE with apnea hypopnea index (AHI) measures and nocturnal hypoxemia markers, including the time patients spent below 90% oxygen saturation (T90), oxygen desaturation index (ODI), and hypoxic burden, defined as the total area under the respiratory event-related desaturation curve.

They found that after a median follow-up of 6.3 years, 104 out of 7,355 patients had an unprovoked VTE. In an unadjusted hazard model, there were significant associations between VTE and T90, as well as with hypoxic burden, but not with either AHI or ODI.

However, in an analysis adjusted for age, gender, body mass index, alcohol intake, hypertension, depression, history of cardiovascular disease, statin use, type of sleep study, study site, and CPAP adherence, the investigators found that only T90 remained a significant independent predictor of VTE, with a hazard ratio of 1.06, P = .02.

The association between T90 and VTE strengthened as the time spent below 90% saturation increased. Patients in the highest tercile, who spent more than 6% of the time undersaturated, had an HR for VTE of 1.95 (P = .02), compared with patients with a T90 less than 1%.

There were no significant differences in VTE risk between patients who used CPAP for more than 4 hours per night and those who either used the devices for less than 4 hours or refused CPAP.

“We see that T90 seems to be a strong parameter,” said session comoderator Raphael Heinzer, MD, MPH, of Lausanne University Hospital, Switzerland.

Dr. Heinzer’s comoderator, Silke Ryan, MD, of University College Dublin, pointed out that although T90 was the main predictor of responses, Dr. Trzepizur and colleagues did not control for other pulmonary diseases.

“Obviously, there could be an influence of other hypoxic-related diseases,” she said, and recommended controlling for this in future studies.

Winfried Randerath, MD, of the Bethanien Hospital at the University of Cologne, Germany, head of the ERS specialist group on sleep disordered breathing, said that this study and others presented at the meeting “show worrying associations between obstructive sleep apnea and important diseases that affect survival and quality of life.

“While they cannot prove that OSA causes any of these health problems, people should be made aware of these links and should try to make lifestyle changes in order to reduce their risk of OSA, for instance, by maintaining a healthy weight. However, if OSA is suspected, definite diagnosis and treatment should be initiated. We look forward to further research that may help to clarify whether OSA may be causing some of the health problems seen in these studies,” said Dr. Randerath, who was not involved with the study.

The study was supported by a grant from Institut de Recherche en Santé Respiratoire des Pays de la Loire (IRSR), Beaucouzé, France. Dr. Trzepizur, Dr. Heinzer, Dr. Ryan and Dr. Randerath reported no relevant financial relationships.

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

Add unprovoked venous thromboembolic events to the list of potential consequences of severe obstructive sleep apnea.

That conclusion comes from a study showing that patients with obstructive sleep apnea (OSA) who had the longest nocturnal hypoxemia episodes had a twofold risk for venous thromboembolic events.

The association between nocturnal hypoxemia and VTE was strongest among patients who did not use continuous positive airway pressure (CPAP) systems, reported Wojciech Trzepizur, MD, of Angers University Hospital, France.

Previous studies have suggested links between OSA and both cancer and cognitive decline, but this is the first study to investigate the association between OSA and the incidence of unprovoked VTE, he reported in an oral abstract session at the annual congress of the European Respiratory Society.

“We found that those who spent more than 6% of their nighttime with levels of oxygen in their blood below 90% of normal had an almost twofold risk of developing VTEs compared to patients without oxygen deprivation,” he said.

Dr. Trzepizur and colleagues conducted a retrospective study linking cohort data to an administrative health database. They identified unprovoked VTE in patients with a suspicion for OSA and no previous VTE.

They created Cox proportional hazard models to assess the association of unprovoked VTE with apnea hypopnea index (AHI) measures and nocturnal hypoxemia markers, including the time patients spent below 90% oxygen saturation (T90), oxygen desaturation index (ODI), and hypoxic burden, defined as the total area under the respiratory event-related desaturation curve.

They found that after a median follow-up of 6.3 years, 104 out of 7,355 patients had an unprovoked VTE. In an unadjusted hazard model, there were significant associations between VTE and T90, as well as with hypoxic burden, but not with either AHI or ODI.

However, in an analysis adjusted for age, gender, body mass index, alcohol intake, hypertension, depression, history of cardiovascular disease, statin use, type of sleep study, study site, and CPAP adherence, the investigators found that only T90 remained a significant independent predictor of VTE, with a hazard ratio of 1.06, P = .02.

The association between T90 and VTE strengthened as the time spent below 90% saturation increased. Patients in the highest tercile, who spent more than 6% of the time undersaturated, had an HR for VTE of 1.95 (P = .02), compared with patients with a T90 less than 1%.

There were no significant differences in VTE risk between patients who used CPAP for more than 4 hours per night and those who either used the devices for less than 4 hours or refused CPAP.

“We see that T90 seems to be a strong parameter,” said session comoderator Raphael Heinzer, MD, MPH, of Lausanne University Hospital, Switzerland.

Dr. Heinzer’s comoderator, Silke Ryan, MD, of University College Dublin, pointed out that although T90 was the main predictor of responses, Dr. Trzepizur and colleagues did not control for other pulmonary diseases.

“Obviously, there could be an influence of other hypoxic-related diseases,” she said, and recommended controlling for this in future studies.

Winfried Randerath, MD, of the Bethanien Hospital at the University of Cologne, Germany, head of the ERS specialist group on sleep disordered breathing, said that this study and others presented at the meeting “show worrying associations between obstructive sleep apnea and important diseases that affect survival and quality of life.

“While they cannot prove that OSA causes any of these health problems, people should be made aware of these links and should try to make lifestyle changes in order to reduce their risk of OSA, for instance, by maintaining a healthy weight. However, if OSA is suspected, definite diagnosis and treatment should be initiated. We look forward to further research that may help to clarify whether OSA may be causing some of the health problems seen in these studies,” said Dr. Randerath, who was not involved with the study.

The study was supported by a grant from Institut de Recherche en Santé Respiratoire des Pays de la Loire (IRSR), Beaucouzé, France. Dr. Trzepizur, Dr. Heinzer, Dr. Ryan and Dr. Randerath reported no relevant financial relationships.

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

Add unprovoked venous thromboembolic events to the list of potential consequences of severe obstructive sleep apnea.

That conclusion comes from a study showing that patients with obstructive sleep apnea (OSA) who had the longest nocturnal hypoxemia episodes had a twofold risk for venous thromboembolic events.

The association between nocturnal hypoxemia and VTE was strongest among patients who did not use continuous positive airway pressure (CPAP) systems, reported Wojciech Trzepizur, MD, of Angers University Hospital, France.

Previous studies have suggested links between OSA and both cancer and cognitive decline, but this is the first study to investigate the association between OSA and the incidence of unprovoked VTE, he reported in an oral abstract session at the annual congress of the European Respiratory Society.

“We found that those who spent more than 6% of their nighttime with levels of oxygen in their blood below 90% of normal had an almost twofold risk of developing VTEs compared to patients without oxygen deprivation,” he said.

Dr. Trzepizur and colleagues conducted a retrospective study linking cohort data to an administrative health database. They identified unprovoked VTE in patients with a suspicion for OSA and no previous VTE.

They created Cox proportional hazard models to assess the association of unprovoked VTE with apnea hypopnea index (AHI) measures and nocturnal hypoxemia markers, including the time patients spent below 90% oxygen saturation (T90), oxygen desaturation index (ODI), and hypoxic burden, defined as the total area under the respiratory event-related desaturation curve.

They found that after a median follow-up of 6.3 years, 104 out of 7,355 patients had an unprovoked VTE. In an unadjusted hazard model, there were significant associations between VTE and T90, as well as with hypoxic burden, but not with either AHI or ODI.

However, in an analysis adjusted for age, gender, body mass index, alcohol intake, hypertension, depression, history of cardiovascular disease, statin use, type of sleep study, study site, and CPAP adherence, the investigators found that only T90 remained a significant independent predictor of VTE, with a hazard ratio of 1.06, P = .02.

The association between T90 and VTE strengthened as the time spent below 90% saturation increased. Patients in the highest tercile, who spent more than 6% of the time undersaturated, had an HR for VTE of 1.95 (P = .02), compared with patients with a T90 less than 1%.

There were no significant differences in VTE risk between patients who used CPAP for more than 4 hours per night and those who either used the devices for less than 4 hours or refused CPAP.

“We see that T90 seems to be a strong parameter,” said session comoderator Raphael Heinzer, MD, MPH, of Lausanne University Hospital, Switzerland.

Dr. Heinzer’s comoderator, Silke Ryan, MD, of University College Dublin, pointed out that although T90 was the main predictor of responses, Dr. Trzepizur and colleagues did not control for other pulmonary diseases.

“Obviously, there could be an influence of other hypoxic-related diseases,” she said, and recommended controlling for this in future studies.

Winfried Randerath, MD, of the Bethanien Hospital at the University of Cologne, Germany, head of the ERS specialist group on sleep disordered breathing, said that this study and others presented at the meeting “show worrying associations between obstructive sleep apnea and important diseases that affect survival and quality of life.

“While they cannot prove that OSA causes any of these health problems, people should be made aware of these links and should try to make lifestyle changes in order to reduce their risk of OSA, for instance, by maintaining a healthy weight. However, if OSA is suspected, definite diagnosis and treatment should be initiated. We look forward to further research that may help to clarify whether OSA may be causing some of the health problems seen in these studies,” said Dr. Randerath, who was not involved with the study.

The study was supported by a grant from Institut de Recherche en Santé Respiratoire des Pays de la Loire (IRSR), Beaucouzé, France. Dr. Trzepizur, Dr. Heinzer, Dr. Ryan and Dr. Randerath reported no relevant financial relationships.

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

Treatment with Janus kinase (JAK) inhibitors does not appear to be associated with an increased risk of venous thromboembolism (VTE) in patients with atopic dermatitis (AD), according to a new systemic review and meta-analysis, published online in JAMA Dermatology.

“These findings may provide a reference for clinicians in prescribing JAK inhibitors for patients with AD,” Tai-Li Chen, MD, of Taipei (Taiwan) Veterans General Hospital, Taipei, and colleagues wrote in the study.

The results shed some welcome light on treatment for this dermatologic population, for whom enthusiasm about JAK inhibitors was dampened by the addition of a boxed warning to the labels of JAK inhibitors last year, required by the Food and Drug Administration. The warning, which describes an increased risk of “serious heart-related events such as heart attack or stroke, cancer, blood clots, and death” was triggered by results of the ORAL Surveillance study of patients with rheumatoid arthritis (RA) treated with tofacitinib.

The boxed warning is also included in the labels of topical ruxolitinib, a JAK inhibitor approved by the FDA for mild to moderate AD in 2021, and in the labels of two oral JAK inhibitors, upadacitinib and abrocitinib, approved by the FDA for treating moderate to severe AD in January 2022.

Despite the new findings, some dermatologists are still urging caution.

“All the JAK inhibitor trials are short term. I still think the precautionary principle applies and we need to counsel on the risks of JAKs,” tweeted Aaron Drucker, MD, a dermatologist at Women’s College Hospital, and associate professor at the University of Toronto. “It is great to have these as options for our patients. But we need to be aware of the risks associated with this class of medications, counsel patients about them when we are informing them of the risks and benefits of treatment options, and wait for more data specific to this population to make even more informed decisions,” he told this news organization.

The meta-analysis examined both the risk of incident VTE in untreated patients with AD compared with non-AD patients, as well as the risk of VTE in AD patients treated with JAK inhibitors compared with those on either placebo or dupilumab. Four JAK inhibitors were studied: abrocitinib, baricitinib (under FDA review for AD), upadacitinib, and SHR0302 (in clinical trials).

Two studies (458,206 participants) found the overall incidence rate of VTE for patients with AD was 0.23 events per 100 patient-years. The risk was did not differ from that in non-AD patients (pooled hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.62-1.45).

Another 15 studies included 8,787 participants with AD and found no significant differences in the rates of VTE in AD patients treated with JAK inhibitors (0.05%) versus those treated with placebo or dupilumab (0.03%). However “with the increasing applications of JAK inhibitors in AD, more clinical data are needed to identify patients at high risk for VTE,” noted the authors.

“We need more, long-term data,” agreed Dr. Drucker, adding that a major issue is the short-term nature of AD trials to date (generally up to 16 weeks), which “don’t provide adequate reassurance.” He said although the FDA’s boxed warning was prompted by a trial in RA patients treated with tofacitinib (a less selective JAK inhibitor than those approved by the FDA for AD), and the same risks have not been demonstrated specifically for the JAK inhibitors used for a patients with AD, he still remains cautious.

While agreeing on the need for more long-term data, Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center, Portland, said that the new findings should “provide reassurance” to dermatologists and are “consonant with recent published meta-analyses reporting no increased VTE risk in patients with psoriasis, RA, or inflammatory bowel disease treated with JAK inhibitors” in Arthritis & Rheumatology, and Mayo Clinic Proceedings.

In an interview, Dr. Blauvelt said that safety profiles emerging for the newer JAK inhibitors, which block JAK 1/2, have been overshadowed by the older RA data for tofacitinib – which is a JAK 1/3 inhibitor, “despite emerging long-term, monotherapy, clinical study data for dermatologic diseases showing no or rare risks of developing severe adverse events outlined in the boxed warnings.”

Both Dr. Blauvelt and Dr. Drucker pointed out that people with RA tend to have more comorbidities than those with AD that would predispose them to adverse events. In fact, “approximately 75% of patients in the ORAL Surveillance study were also on concomitant methotrexate and/or prednisone, which can greatly confound safety results,” said Dr. Blauvelt.

The study authors did not report any disclosures. No funding source for the study was provided. Dr. Drucker has no relevant disclosures. Dr. Blauvelt has been a clinical study investigator in trials for AD treatments, including JAK inhibitors; his disclosures include serving as a speaker, scientific adviser, and/or clinical study investigator for multiple companies including AbbVie, Arcutis, Bristol-Myers Squibb, Pfizer, Incyte, Regeneron, Sanofi Genzyme, and UCB Pharma.

Treatment with Janus kinase (JAK) inhibitors does not appear to be associated with an increased risk of venous thromboembolism (VTE) in patients with atopic dermatitis (AD), according to a new systemic review and meta-analysis, published online in JAMA Dermatology.

“These findings may provide a reference for clinicians in prescribing JAK inhibitors for patients with AD,” Tai-Li Chen, MD, of Taipei (Taiwan) Veterans General Hospital, Taipei, and colleagues wrote in the study.

The results shed some welcome light on treatment for this dermatologic population, for whom enthusiasm about JAK inhibitors was dampened by the addition of a boxed warning to the labels of JAK inhibitors last year, required by the Food and Drug Administration. The warning, which describes an increased risk of “serious heart-related events such as heart attack or stroke, cancer, blood clots, and death” was triggered by results of the ORAL Surveillance study of patients with rheumatoid arthritis (RA) treated with tofacitinib.

The boxed warning is also included in the labels of topical ruxolitinib, a JAK inhibitor approved by the FDA for mild to moderate AD in 2021, and in the labels of two oral JAK inhibitors, upadacitinib and abrocitinib, approved by the FDA for treating moderate to severe AD in January 2022.

Despite the new findings, some dermatologists are still urging caution.

“All the JAK inhibitor trials are short term. I still think the precautionary principle applies and we need to counsel on the risks of JAKs,” tweeted Aaron Drucker, MD, a dermatologist at Women’s College Hospital, and associate professor at the University of Toronto. “It is great to have these as options for our patients. But we need to be aware of the risks associated with this class of medications, counsel patients about them when we are informing them of the risks and benefits of treatment options, and wait for more data specific to this population to make even more informed decisions,” he told this news organization.

The meta-analysis examined both the risk of incident VTE in untreated patients with AD compared with non-AD patients, as well as the risk of VTE in AD patients treated with JAK inhibitors compared with those on either placebo or dupilumab. Four JAK inhibitors were studied: abrocitinib, baricitinib (under FDA review for AD), upadacitinib, and SHR0302 (in clinical trials).

Two studies (458,206 participants) found the overall incidence rate of VTE for patients with AD was 0.23 events per 100 patient-years. The risk was did not differ from that in non-AD patients (pooled hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.62-1.45).

Another 15 studies included 8,787 participants with AD and found no significant differences in the rates of VTE in AD patients treated with JAK inhibitors (0.05%) versus those treated with placebo or dupilumab (0.03%). However “with the increasing applications of JAK inhibitors in AD, more clinical data are needed to identify patients at high risk for VTE,” noted the authors.

“We need more, long-term data,” agreed Dr. Drucker, adding that a major issue is the short-term nature of AD trials to date (generally up to 16 weeks), which “don’t provide adequate reassurance.” He said although the FDA’s boxed warning was prompted by a trial in RA patients treated with tofacitinib (a less selective JAK inhibitor than those approved by the FDA for AD), and the same risks have not been demonstrated specifically for the JAK inhibitors used for a patients with AD, he still remains cautious.

While agreeing on the need for more long-term data, Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center, Portland, said that the new findings should “provide reassurance” to dermatologists and are “consonant with recent published meta-analyses reporting no increased VTE risk in patients with psoriasis, RA, or inflammatory bowel disease treated with JAK inhibitors” in Arthritis & Rheumatology, and Mayo Clinic Proceedings.

In an interview, Dr. Blauvelt said that safety profiles emerging for the newer JAK inhibitors, which block JAK 1/2, have been overshadowed by the older RA data for tofacitinib – which is a JAK 1/3 inhibitor, “despite emerging long-term, monotherapy, clinical study data for dermatologic diseases showing no or rare risks of developing severe adverse events outlined in the boxed warnings.”

Both Dr. Blauvelt and Dr. Drucker pointed out that people with RA tend to have more comorbidities than those with AD that would predispose them to adverse events. In fact, “approximately 75% of patients in the ORAL Surveillance study were also on concomitant methotrexate and/or prednisone, which can greatly confound safety results,” said Dr. Blauvelt.

The study authors did not report any disclosures. No funding source for the study was provided. Dr. Drucker has no relevant disclosures. Dr. Blauvelt has been a clinical study investigator in trials for AD treatments, including JAK inhibitors; his disclosures include serving as a speaker, scientific adviser, and/or clinical study investigator for multiple companies including AbbVie, Arcutis, Bristol-Myers Squibb, Pfizer, Incyte, Regeneron, Sanofi Genzyme, and UCB Pharma.

Treatment with Janus kinase (JAK) inhibitors does not appear to be associated with an increased risk of venous thromboembolism (VTE) in patients with atopic dermatitis (AD), according to a new systemic review and meta-analysis, published online in JAMA Dermatology.

“These findings may provide a reference for clinicians in prescribing JAK inhibitors for patients with AD,” Tai-Li Chen, MD, of Taipei (Taiwan) Veterans General Hospital, Taipei, and colleagues wrote in the study.

The results shed some welcome light on treatment for this dermatologic population, for whom enthusiasm about JAK inhibitors was dampened by the addition of a boxed warning to the labels of JAK inhibitors last year, required by the Food and Drug Administration. The warning, which describes an increased risk of “serious heart-related events such as heart attack or stroke, cancer, blood clots, and death” was triggered by results of the ORAL Surveillance study of patients with rheumatoid arthritis (RA) treated with tofacitinib.

The boxed warning is also included in the labels of topical ruxolitinib, a JAK inhibitor approved by the FDA for mild to moderate AD in 2021, and in the labels of two oral JAK inhibitors, upadacitinib and abrocitinib, approved by the FDA for treating moderate to severe AD in January 2022.

Despite the new findings, some dermatologists are still urging caution.

“All the JAK inhibitor trials are short term. I still think the precautionary principle applies and we need to counsel on the risks of JAKs,” tweeted Aaron Drucker, MD, a dermatologist at Women’s College Hospital, and associate professor at the University of Toronto. “It is great to have these as options for our patients. But we need to be aware of the risks associated with this class of medications, counsel patients about them when we are informing them of the risks and benefits of treatment options, and wait for more data specific to this population to make even more informed decisions,” he told this news organization.

The meta-analysis examined both the risk of incident VTE in untreated patients with AD compared with non-AD patients, as well as the risk of VTE in AD patients treated with JAK inhibitors compared with those on either placebo or dupilumab. Four JAK inhibitors were studied: abrocitinib, baricitinib (under FDA review for AD), upadacitinib, and SHR0302 (in clinical trials).

Two studies (458,206 participants) found the overall incidence rate of VTE for patients with AD was 0.23 events per 100 patient-years. The risk was did not differ from that in non-AD patients (pooled hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.62-1.45).

Another 15 studies included 8,787 participants with AD and found no significant differences in the rates of VTE in AD patients treated with JAK inhibitors (0.05%) versus those treated with placebo or dupilumab (0.03%). However “with the increasing applications of JAK inhibitors in AD, more clinical data are needed to identify patients at high risk for VTE,” noted the authors.

“We need more, long-term data,” agreed Dr. Drucker, adding that a major issue is the short-term nature of AD trials to date (generally up to 16 weeks), which “don’t provide adequate reassurance.” He said although the FDA’s boxed warning was prompted by a trial in RA patients treated with tofacitinib (a less selective JAK inhibitor than those approved by the FDA for AD), and the same risks have not been demonstrated specifically for the JAK inhibitors used for a patients with AD, he still remains cautious.

While agreeing on the need for more long-term data, Andrew Blauvelt, MD, MBA, president of Oregon Medical Research Center, Portland, said that the new findings should “provide reassurance” to dermatologists and are “consonant with recent published meta-analyses reporting no increased VTE risk in patients with psoriasis, RA, or inflammatory bowel disease treated with JAK inhibitors” in Arthritis & Rheumatology, and Mayo Clinic Proceedings.

In an interview, Dr. Blauvelt said that safety profiles emerging for the newer JAK inhibitors, which block JAK 1/2, have been overshadowed by the older RA data for tofacitinib – which is a JAK 1/3 inhibitor, “despite emerging long-term, monotherapy, clinical study data for dermatologic diseases showing no or rare risks of developing severe adverse events outlined in the boxed warnings.”

Both Dr. Blauvelt and Dr. Drucker pointed out that people with RA tend to have more comorbidities than those with AD that would predispose them to adverse events. In fact, “approximately 75% of patients in the ORAL Surveillance study were also on concomitant methotrexate and/or prednisone, which can greatly confound safety results,” said Dr. Blauvelt.

The study authors did not report any disclosures. No funding source for the study was provided. Dr. Drucker has no relevant disclosures. Dr. Blauvelt has been a clinical study investigator in trials for AD treatments, including JAK inhibitors; his disclosures include serving as a speaker, scientific adviser, and/or clinical study investigator for multiple companies including AbbVie, Arcutis, Bristol-Myers Squibb, Pfizer, Incyte, Regeneron, Sanofi Genzyme, and UCB Pharma.

Updated clinical practice guidelines for the treatment and prevention of venous thromboembolism for patients with cancer, including those with cancer and COVID-19, have been released by the International Initiative on Thrombosis and Cancer (ITAC), an academic working group of VTE experts.

“Because patients with cancer have a baseline increased risk of VTE, compared with patients without cancer, the combination of both COVID-19 and cancer – and its effect on VTE risk and treatment – is of concern,” said the authors, led by Dominique Farge, MD, PhD, Nord Universite de Paris.

The updated 2022 ITAC guidelines cover new evidence on the treatment and prophylaxis of cancer-associated thrombosis, including for patients with cancer and COVID-19, they added.

The new guidelines were published online in The Lancet Oncology.

“Cancer-associated VTE remains an important clinical problem, associated with increased morbidity and mortality,” Dr. Farge and colleagues observed.

“The ITAC guidelines’ companion free web-based mobile application will assist the practicing clinician with decision making at various levels to provide optimal care of patients with cancer to treat and prevent VTE,” they emphasized. More information is available at itaccme.com.
 

Cancer patients with COVID

The new section of the guidelines notes that the treatment and prevention of VTE for cancer patients infected with SARS-CoV-2 remain the same as for patients without COVID.

Whether or not cancer patients with COVID-19 are hospitalized, have been discharged, or are ambulatory, they should be assessed for the risk of VTE, as should any other patient. For cancer patients with COVID-19 who are hospitalized, pharmacologic prophylaxis should be given at the same dose and anticoagulant type as for hospitalized cancer patients who do not have COVID-19.

Following discharge, VTE prophylaxis is not advised for cancer patients infected with SARS-CoV-2, and routine primary pharmacologic prophylaxis of VTE for ambulatory patients with COVID-19 is also not recommended, the authors noted.
 

Initial treatment of established VTE

Initial treatment of established VTE for up to 10 days of anticoagulation should include low-molecular-weight heparin (LMWH) when creatinine clearance is at least 30 mL/min.

“A regimen of LMWH, taken once per day, is recommended unless a twice-per-day regimen is required because of patients’ characteristics,” the authors noted. These characteristics include a high risk of bleeding, moderate renal failure, and the need for technical intervention, including surgery.

If a twice-a-day regimen is required, only enoxaparin at a dose of 1 mg/kg twice daily can be used, the authors cautioned.

For patients with a low risk of gastrointestinal or genitourinary bleeding, rivaroxaban (Xarelto) or apixaban (Eliquis) can be given in the first 10 days, as well as edoxaban (Lixiana). The latter should be started after at least 5 days of parenteral anticoagulation, provided creatinine clearance is at least 30 mL/min.

“Unfractionated heparin as well as fondaparinux (GlaxoSmithKline) can be also used for the initial treatment of established VTE when LMWH or direct oral anticoagulants are contraindicated,” Dr. Farge and colleagues wrote.

Thrombolysis can be considered on a case-by-case basis, although physicians must pay attention to specific contraindications, especially bleeding risk.

“In the initial treatment of VTE, inferior vena cava filters might be considered when anticoagulant treatment is contraindicated or, in the case of pulmonary embolism, when recurrence occurs under optimal anticoagulation,” the authors noted.
 

Maintenance VTE treatment

For maintenance therapy, which the authors define as early maintenance for up to 6 months and long-term maintenance beyond 6 months, they point out that LMWHs are preferred over vitamin K antagonists for the treatment of VTE when the creatinine clearance is again at least 30 mL/min.

Any of the direct oral anticoagulants (DOAs) – edoxaban, rivaroxaban, or apixaban – is also recommended for the same patients, provided there is no risk of inducing a strong drug-drug interaction or GI absorption is impaired.

However, the DOAs should be used with caution for patients with GI malignancies, especially upper GI cancers, because data show there is an increased risk of GI bleeding with both edoxaban and rivaroxaban.

“LMWH or direct oral anticoagulants should be used for a minimum of 6 months to treat established VTE in patients with cancer,” the authors wrote.

“After 6 months, termination or continuation of anticoagulation (LMWH, direct oral anticoagulants, or vitamin K antagonists) should be based on individual evaluation of the benefit-risk ratio,” they added.
 

Treatment of VTE recurrence

The guideline authors explain that three options can be considered in the event of VTE recurrence. These include an increase in the LMWH dose by 20%-25%, or a switch to a DOA, or, if patients are taking a DOA, a switch to an LMWH. If the patient is taking a vitamin K antagonist, it can be switched to either an LMWH or a DOA.

For treatment of catheter-related thrombosis, anticoagulant treatment is recommended for a minimum of 3 months and as long as the central venous catheter is in place. In this setting, the LMWHs are recommended.

The central venous catheter can be kept in place if it is functional, well positioned, and is not infected, provided there is good resolution of symptoms under close surveillance while anticoagulants are being administered.

In surgically treated patients, the LMWH, given once a day, to patients with a serum creatinine concentration of at least 30 mL/min can be used to prevent VTE. Alternatively, VTE can be prevented by the use low-dose unfractionated heparin, given three times a day.

“Pharmacological prophylaxis should be started 2-12 h preoperatively and continued for at least 7–10 days,” Dr. Farge and colleagues advised. In this setting, there is insufficient evidence to support the use of fondaparinux or a DOA as an alternative to an LMWH for the prophylaxis of postoperative VTE. “Use of the highest prophylactic dose of LMWH to prevent postoperative VTE in patients with cancer is recommended,” the authors advised.

Furthermore, extended prophylaxis of at least 4 weeks with LMWH is advised to prevent postoperative VTE after major abdominal or pelvic surgery. Mechanical methods are not recommended except when pharmacologic methods are contraindicated. Inferior vena cava filters are also not recommended for routine prophylaxis.
 

Patients with reduced mobility

For medically treated hospitalized patients with cancer whose mobility is reduced, the authors recommend prophylaxis with either an LMWH or fondaparinux, provided their creatinine clearance is at least 30 mL/min. These patients can also be treated with unfractionated heparin, they add.

In contrast, DOAs are not recommended – at least not routinely – in this setting, the authors cautioned. Primary pharmacologic prophylaxis of VTE with either LMWH or DOAs – either rivaroxaban or apixaban – is indicated in ambulatory patients with locally advanced or metastatic pancreatic cancer who are receiving systemic anticancer therapy, provided they are at low risk of bleeding.

However, primary pharmacologic prophylaxis with LMWH is not recommended outside of a clinical trial for patients with locally advanced or metastatic lung cancer who are undergoing systemic anticancer therapy, even for patients who are at low risk of bleeding.

For ambulatory patients who are receiving systemic anticancer therapy and who are at intermediate risk of VTE, primary prophylaxis with rivaroxaban or apixaban is recommended for those with myeloma who are receiving immunomodulatory therapy plus steroids or other systemic therapies.

In this setting, oral anticoagulants should consist of a vitamin K antagonist, given at low or therapeutic doses, or apixaban, given at prophylactic doses. Alternatively, LMWH, given at prophylactic doses, or low-dose aspirin, given at a dose of 100 mg/day, can be used.
 

Catheter-related thrombosis

Use of anticoagulation for routine prophylaxis of catheter-related thrombosis is not recommended. Catheters should be inserted on the right side in the jugular vein, and the distal extremity of the central catheter should be located at the junction of the superior vena cava and the right atrium. “In patients requiring central venous catheters, we suggest the use of implanted ports over peripheral inserted central catheter lines,” the authors noted.

The authors described a number of unique situations regarding the treatment of VTE. These situations include patients with a brain tumor, for whom treatment of established VTE should favor either LMWH or a DOA. The authors also recommended the use of LMWH or unfractionated heparin, started postoperatively, for the prevention of VTE for patients undergoing neurosurgery.

In contrast, pharmacologic prophylaxis of VTE in medically treated patients with a brain tumor who are not undergoing neurosurgery is not recommended. “In the presence of severe renal failure...we suggest using unfractionated heparin followed by early vitamin K antagonists (possibly from day 1) or LMWH adjusted to anti-Xa concentration of the treatment of established VTE,” Dr. Farge and colleagues wrote.

Anticoagulant treatment is also recommended for a minimum of 3 months for children with symptomatic catheter-related thrombosis and as long as the central venous catheter is in place. For children with acute lymphoblastic leukemia who are undergoing induction chemotherapy, LMWH is also recommended as thromboprophylaxis.

For children who require a central venous catheter, the authors suggested that physicians use implanted ports over peripherally inserted central lines.

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

Updated clinical practice guidelines for the treatment and prevention of venous thromboembolism for patients with cancer, including those with cancer and COVID-19, have been released by the International Initiative on Thrombosis and Cancer (ITAC), an academic working group of VTE experts.

“Because patients with cancer have a baseline increased risk of VTE, compared with patients without cancer, the combination of both COVID-19 and cancer – and its effect on VTE risk and treatment – is of concern,” said the authors, led by Dominique Farge, MD, PhD, Nord Universite de Paris.

The updated 2022 ITAC guidelines cover new evidence on the treatment and prophylaxis of cancer-associated thrombosis, including for patients with cancer and COVID-19, they added.

The new guidelines were published online in The Lancet Oncology.

“Cancer-associated VTE remains an important clinical problem, associated with increased morbidity and mortality,” Dr. Farge and colleagues observed.

“The ITAC guidelines’ companion free web-based mobile application will assist the practicing clinician with decision making at various levels to provide optimal care of patients with cancer to treat and prevent VTE,” they emphasized. More information is available at itaccme.com.
 

Cancer patients with COVID

The new section of the guidelines notes that the treatment and prevention of VTE for cancer patients infected with SARS-CoV-2 remain the same as for patients without COVID.

Whether or not cancer patients with COVID-19 are hospitalized, have been discharged, or are ambulatory, they should be assessed for the risk of VTE, as should any other patient. For cancer patients with COVID-19 who are hospitalized, pharmacologic prophylaxis should be given at the same dose and anticoagulant type as for hospitalized cancer patients who do not have COVID-19.

Following discharge, VTE prophylaxis is not advised for cancer patients infected with SARS-CoV-2, and routine primary pharmacologic prophylaxis of VTE for ambulatory patients with COVID-19 is also not recommended, the authors noted.
 

Initial treatment of established VTE

Initial treatment of established VTE for up to 10 days of anticoagulation should include low-molecular-weight heparin (LMWH) when creatinine clearance is at least 30 mL/min.

“A regimen of LMWH, taken once per day, is recommended unless a twice-per-day regimen is required because of patients’ characteristics,” the authors noted. These characteristics include a high risk of bleeding, moderate renal failure, and the need for technical intervention, including surgery.

If a twice-a-day regimen is required, only enoxaparin at a dose of 1 mg/kg twice daily can be used, the authors cautioned.

For patients with a low risk of gastrointestinal or genitourinary bleeding, rivaroxaban (Xarelto) or apixaban (Eliquis) can be given in the first 10 days, as well as edoxaban (Lixiana). The latter should be started after at least 5 days of parenteral anticoagulation, provided creatinine clearance is at least 30 mL/min.

“Unfractionated heparin as well as fondaparinux (GlaxoSmithKline) can be also used for the initial treatment of established VTE when LMWH or direct oral anticoagulants are contraindicated,” Dr. Farge and colleagues wrote.

Thrombolysis can be considered on a case-by-case basis, although physicians must pay attention to specific contraindications, especially bleeding risk.

“In the initial treatment of VTE, inferior vena cava filters might be considered when anticoagulant treatment is contraindicated or, in the case of pulmonary embolism, when recurrence occurs under optimal anticoagulation,” the authors noted.
 

Maintenance VTE treatment

For maintenance therapy, which the authors define as early maintenance for up to 6 months and long-term maintenance beyond 6 months, they point out that LMWHs are preferred over vitamin K antagonists for the treatment of VTE when the creatinine clearance is again at least 30 mL/min.

Any of the direct oral anticoagulants (DOAs) – edoxaban, rivaroxaban, or apixaban – is also recommended for the same patients, provided there is no risk of inducing a strong drug-drug interaction or GI absorption is impaired.

However, the DOAs should be used with caution for patients with GI malignancies, especially upper GI cancers, because data show there is an increased risk of GI bleeding with both edoxaban and rivaroxaban.

“LMWH or direct oral anticoagulants should be used for a minimum of 6 months to treat established VTE in patients with cancer,” the authors wrote.

“After 6 months, termination or continuation of anticoagulation (LMWH, direct oral anticoagulants, or vitamin K antagonists) should be based on individual evaluation of the benefit-risk ratio,” they added.
 

Treatment of VTE recurrence

The guideline authors explain that three options can be considered in the event of VTE recurrence. These include an increase in the LMWH dose by 20%-25%, or a switch to a DOA, or, if patients are taking a DOA, a switch to an LMWH. If the patient is taking a vitamin K antagonist, it can be switched to either an LMWH or a DOA.

For treatment of catheter-related thrombosis, anticoagulant treatment is recommended for a minimum of 3 months and as long as the central venous catheter is in place. In this setting, the LMWHs are recommended.

The central venous catheter can be kept in place if it is functional, well positioned, and is not infected, provided there is good resolution of symptoms under close surveillance while anticoagulants are being administered.

In surgically treated patients, the LMWH, given once a day, to patients with a serum creatinine concentration of at least 30 mL/min can be used to prevent VTE. Alternatively, VTE can be prevented by the use low-dose unfractionated heparin, given three times a day.

“Pharmacological prophylaxis should be started 2-12 h preoperatively and continued for at least 7–10 days,” Dr. Farge and colleagues advised. In this setting, there is insufficient evidence to support the use of fondaparinux or a DOA as an alternative to an LMWH for the prophylaxis of postoperative VTE. “Use of the highest prophylactic dose of LMWH to prevent postoperative VTE in patients with cancer is recommended,” the authors advised.

Furthermore, extended prophylaxis of at least 4 weeks with LMWH is advised to prevent postoperative VTE after major abdominal or pelvic surgery. Mechanical methods are not recommended except when pharmacologic methods are contraindicated. Inferior vena cava filters are also not recommended for routine prophylaxis.
 

Patients with reduced mobility

For medically treated hospitalized patients with cancer whose mobility is reduced, the authors recommend prophylaxis with either an LMWH or fondaparinux, provided their creatinine clearance is at least 30 mL/min. These patients can also be treated with unfractionated heparin, they add.

In contrast, DOAs are not recommended – at least not routinely – in this setting, the authors cautioned. Primary pharmacologic prophylaxis of VTE with either LMWH or DOAs – either rivaroxaban or apixaban – is indicated in ambulatory patients with locally advanced or metastatic pancreatic cancer who are receiving systemic anticancer therapy, provided they are at low risk of bleeding.

However, primary pharmacologic prophylaxis with LMWH is not recommended outside of a clinical trial for patients with locally advanced or metastatic lung cancer who are undergoing systemic anticancer therapy, even for patients who are at low risk of bleeding.

For ambulatory patients who are receiving systemic anticancer therapy and who are at intermediate risk of VTE, primary prophylaxis with rivaroxaban or apixaban is recommended for those with myeloma who are receiving immunomodulatory therapy plus steroids or other systemic therapies.

In this setting, oral anticoagulants should consist of a vitamin K antagonist, given at low or therapeutic doses, or apixaban, given at prophylactic doses. Alternatively, LMWH, given at prophylactic doses, or low-dose aspirin, given at a dose of 100 mg/day, can be used.
 

Catheter-related thrombosis

Use of anticoagulation for routine prophylaxis of catheter-related thrombosis is not recommended. Catheters should be inserted on the right side in the jugular vein, and the distal extremity of the central catheter should be located at the junction of the superior vena cava and the right atrium. “In patients requiring central venous catheters, we suggest the use of implanted ports over peripheral inserted central catheter lines,” the authors noted.

The authors described a number of unique situations regarding the treatment of VTE. These situations include patients with a brain tumor, for whom treatment of established VTE should favor either LMWH or a DOA. The authors also recommended the use of LMWH or unfractionated heparin, started postoperatively, for the prevention of VTE for patients undergoing neurosurgery.

In contrast, pharmacologic prophylaxis of VTE in medically treated patients with a brain tumor who are not undergoing neurosurgery is not recommended. “In the presence of severe renal failure...we suggest using unfractionated heparin followed by early vitamin K antagonists (possibly from day 1) or LMWH adjusted to anti-Xa concentration of the treatment of established VTE,” Dr. Farge and colleagues wrote.

Anticoagulant treatment is also recommended for a minimum of 3 months for children with symptomatic catheter-related thrombosis and as long as the central venous catheter is in place. For children with acute lymphoblastic leukemia who are undergoing induction chemotherapy, LMWH is also recommended as thromboprophylaxis.

For children who require a central venous catheter, the authors suggested that physicians use implanted ports over peripherally inserted central lines.

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

Updated clinical practice guidelines for the treatment and prevention of venous thromboembolism for patients with cancer, including those with cancer and COVID-19, have been released by the International Initiative on Thrombosis and Cancer (ITAC), an academic working group of VTE experts.

“Because patients with cancer have a baseline increased risk of VTE, compared with patients without cancer, the combination of both COVID-19 and cancer – and its effect on VTE risk and treatment – is of concern,” said the authors, led by Dominique Farge, MD, PhD, Nord Universite de Paris.

The updated 2022 ITAC guidelines cover new evidence on the treatment and prophylaxis of cancer-associated thrombosis, including for patients with cancer and COVID-19, they added.

The new guidelines were published online in The Lancet Oncology.

“Cancer-associated VTE remains an important clinical problem, associated with increased morbidity and mortality,” Dr. Farge and colleagues observed.

“The ITAC guidelines’ companion free web-based mobile application will assist the practicing clinician with decision making at various levels to provide optimal care of patients with cancer to treat and prevent VTE,” they emphasized. More information is available at itaccme.com.
 

Cancer patients with COVID

The new section of the guidelines notes that the treatment and prevention of VTE for cancer patients infected with SARS-CoV-2 remain the same as for patients without COVID.

Whether or not cancer patients with COVID-19 are hospitalized, have been discharged, or are ambulatory, they should be assessed for the risk of VTE, as should any other patient. For cancer patients with COVID-19 who are hospitalized, pharmacologic prophylaxis should be given at the same dose and anticoagulant type as for hospitalized cancer patients who do not have COVID-19.

Following discharge, VTE prophylaxis is not advised for cancer patients infected with SARS-CoV-2, and routine primary pharmacologic prophylaxis of VTE for ambulatory patients with COVID-19 is also not recommended, the authors noted.
 

Initial treatment of established VTE

Initial treatment of established VTE for up to 10 days of anticoagulation should include low-molecular-weight heparin (LMWH) when creatinine clearance is at least 30 mL/min.

“A regimen of LMWH, taken once per day, is recommended unless a twice-per-day regimen is required because of patients’ characteristics,” the authors noted. These characteristics include a high risk of bleeding, moderate renal failure, and the need for technical intervention, including surgery.

If a twice-a-day regimen is required, only enoxaparin at a dose of 1 mg/kg twice daily can be used, the authors cautioned.

For patients with a low risk of gastrointestinal or genitourinary bleeding, rivaroxaban (Xarelto) or apixaban (Eliquis) can be given in the first 10 days, as well as edoxaban (Lixiana). The latter should be started after at least 5 days of parenteral anticoagulation, provided creatinine clearance is at least 30 mL/min.

“Unfractionated heparin as well as fondaparinux (GlaxoSmithKline) can be also used for the initial treatment of established VTE when LMWH or direct oral anticoagulants are contraindicated,” Dr. Farge and colleagues wrote.

Thrombolysis can be considered on a case-by-case basis, although physicians must pay attention to specific contraindications, especially bleeding risk.

“In the initial treatment of VTE, inferior vena cava filters might be considered when anticoagulant treatment is contraindicated or, in the case of pulmonary embolism, when recurrence occurs under optimal anticoagulation,” the authors noted.
 

Maintenance VTE treatment

For maintenance therapy, which the authors define as early maintenance for up to 6 months and long-term maintenance beyond 6 months, they point out that LMWHs are preferred over vitamin K antagonists for the treatment of VTE when the creatinine clearance is again at least 30 mL/min.

Any of the direct oral anticoagulants (DOAs) – edoxaban, rivaroxaban, or apixaban – is also recommended for the same patients, provided there is no risk of inducing a strong drug-drug interaction or GI absorption is impaired.

However, the DOAs should be used with caution for patients with GI malignancies, especially upper GI cancers, because data show there is an increased risk of GI bleeding with both edoxaban and rivaroxaban.

“LMWH or direct oral anticoagulants should be used for a minimum of 6 months to treat established VTE in patients with cancer,” the authors wrote.

“After 6 months, termination or continuation of anticoagulation (LMWH, direct oral anticoagulants, or vitamin K antagonists) should be based on individual evaluation of the benefit-risk ratio,” they added.
 

Treatment of VTE recurrence

The guideline authors explain that three options can be considered in the event of VTE recurrence. These include an increase in the LMWH dose by 20%-25%, or a switch to a DOA, or, if patients are taking a DOA, a switch to an LMWH. If the patient is taking a vitamin K antagonist, it can be switched to either an LMWH or a DOA.

For treatment of catheter-related thrombosis, anticoagulant treatment is recommended for a minimum of 3 months and as long as the central venous catheter is in place. In this setting, the LMWHs are recommended.

The central venous catheter can be kept in place if it is functional, well positioned, and is not infected, provided there is good resolution of symptoms under close surveillance while anticoagulants are being administered.

In surgically treated patients, the LMWH, given once a day, to patients with a serum creatinine concentration of at least 30 mL/min can be used to prevent VTE. Alternatively, VTE can be prevented by the use low-dose unfractionated heparin, given three times a day.

“Pharmacological prophylaxis should be started 2-12 h preoperatively and continued for at least 7–10 days,” Dr. Farge and colleagues advised. In this setting, there is insufficient evidence to support the use of fondaparinux or a DOA as an alternative to an LMWH for the prophylaxis of postoperative VTE. “Use of the highest prophylactic dose of LMWH to prevent postoperative VTE in patients with cancer is recommended,” the authors advised.

Furthermore, extended prophylaxis of at least 4 weeks with LMWH is advised to prevent postoperative VTE after major abdominal or pelvic surgery. Mechanical methods are not recommended except when pharmacologic methods are contraindicated. Inferior vena cava filters are also not recommended for routine prophylaxis.
 

Patients with reduced mobility

For medically treated hospitalized patients with cancer whose mobility is reduced, the authors recommend prophylaxis with either an LMWH or fondaparinux, provided their creatinine clearance is at least 30 mL/min. These patients can also be treated with unfractionated heparin, they add.

In contrast, DOAs are not recommended – at least not routinely – in this setting, the authors cautioned. Primary pharmacologic prophylaxis of VTE with either LMWH or DOAs – either rivaroxaban or apixaban – is indicated in ambulatory patients with locally advanced or metastatic pancreatic cancer who are receiving systemic anticancer therapy, provided they are at low risk of bleeding.

However, primary pharmacologic prophylaxis with LMWH is not recommended outside of a clinical trial for patients with locally advanced or metastatic lung cancer who are undergoing systemic anticancer therapy, even for patients who are at low risk of bleeding.

For ambulatory patients who are receiving systemic anticancer therapy and who are at intermediate risk of VTE, primary prophylaxis with rivaroxaban or apixaban is recommended for those with myeloma who are receiving immunomodulatory therapy plus steroids or other systemic therapies.

In this setting, oral anticoagulants should consist of a vitamin K antagonist, given at low or therapeutic doses, or apixaban, given at prophylactic doses. Alternatively, LMWH, given at prophylactic doses, or low-dose aspirin, given at a dose of 100 mg/day, can be used.
 

Catheter-related thrombosis

Use of anticoagulation for routine prophylaxis of catheter-related thrombosis is not recommended. Catheters should be inserted on the right side in the jugular vein, and the distal extremity of the central catheter should be located at the junction of the superior vena cava and the right atrium. “In patients requiring central venous catheters, we suggest the use of implanted ports over peripheral inserted central catheter lines,” the authors noted.

The authors described a number of unique situations regarding the treatment of VTE. These situations include patients with a brain tumor, for whom treatment of established VTE should favor either LMWH or a DOA. The authors also recommended the use of LMWH or unfractionated heparin, started postoperatively, for the prevention of VTE for patients undergoing neurosurgery.

In contrast, pharmacologic prophylaxis of VTE in medically treated patients with a brain tumor who are not undergoing neurosurgery is not recommended. “In the presence of severe renal failure...we suggest using unfractionated heparin followed by early vitamin K antagonists (possibly from day 1) or LMWH adjusted to anti-Xa concentration of the treatment of established VTE,” Dr. Farge and colleagues wrote.

Anticoagulant treatment is also recommended for a minimum of 3 months for children with symptomatic catheter-related thrombosis and as long as the central venous catheter is in place. For children with acute lymphoblastic leukemia who are undergoing induction chemotherapy, LMWH is also recommended as thromboprophylaxis.

For children who require a central venous catheter, the authors suggested that physicians use implanted ports over peripherally inserted central lines.

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

Researchers from the Centers for Disease Control and Prevention report that children and teenagers with long COVID have about twice the risk of getting serious outcomes, compared to others without COVID.

Heart inflammation; a blood clot in the lung; or a blood clot in the lower leg, thigh, or pelvis were the most common bad outcomes in a new study. Even though the risk was higher for these and some other serious events, the overall numbers were small.

“Many of these conditions were rare or uncommon among children in this analysis, but even a small increase in these conditions is notable,” a CDC new release stated.

The investigators said their findings stress the importance of COVID-19 vaccination in Americans under the age of 18.

The study was published online in the CDC’s Morbidity and Mortality Weekly Report.
 

Less is known about long COVID in children

Lyudmyla Kompaniyets, PhD, and colleagues noted that most research on long COVID to date has been done in adults, so little information is available about the risks to Americans ages 17 and younger.

To learn more, they compared post–COVID-19 symptoms and conditions between 781,419 children and teenagers with confirmed COVID-19 to another 2,344,257 without COVID-19. They looked at medical claims and laboratory data for these children and teenagers from March 1, 2020, through Jan. 31, 2022, to see who got any of 15 specific outcomes linked to long COVID-19.

Long COVID was defined as a condition where symptoms that last for or begin at least 4 weeks after a COVID-19 diagnosis.

Compared to children with no history of a COVID-19 diagnosis, the long COVID-19 group was 101% more likely to have an acute pulmonary embolism, 99% more likely to have myocarditis or cardiomyopathy, 87% more likely to have a venous thromboembolic event, 32% more likely to have acute and unspecified renal failure, and 23% more likely to have type 1 diabetes.

“This report points to the fact that the risks of COVID infection itself, both in terms of the acute effects, MIS-C [multisystem inflammatory syndrome in children], as well as the long-term effects, are real, are concerning, and are potentially very serious,” said Stuart Berger, MD, chair of the American Academy of Pediatrics Section on Cardiology and Cardiac Surgery.

“The message that we should take away from this is that we should be very keen on all the methods of prevention for COVID, especially the vaccine,” said Dr. Berger, chief of cardiology in the department of pediatrics at Northwestern University in Chicago.


 

A ‘wake-up call’

The study findings are “sobering” and are “a reminder of the seriousness of COVID infection,” says Gregory Poland, MD, an infectious disease expert at the Mayo Clinic in Rochester, Minn.

“When you look in particular at the more serious complications from COVID in this young age group, those are life-altering complications that will have consequences and ramifications throughout their lives,” he said.

“I would take this as a serious wake-up call to parents [at a time when] the immunization rates in younger children are so pitifully low,” Dr. Poland said.
 

Still early days

The study is suggestive but not definitive, said Peter Katona, MD, professor of medicine and infectious diseases expert at the UCLA Fielding School of Public Health.

It’s still too early to draw conclusions about long COVID, including in children, because many questions remain, he said: Should long COVID be defined as symptoms at 1 month or 3 months after infection? How do you define brain fog?

Dr. Katona and colleagues are studying long COVID intervention among students at UCLA to answer some of these questions, including the incidence and effect of early intervention.

The study had “at least seven limitations,” the researchers noted. Among them was the use of medical claims data that noted long COVID outcomes but not how severe they were; some people in the no COVID group might have had the illness but not been diagnosed; and the researchers did not adjust for vaccination status.

Dr. Poland noted that the study was done during surges in COVID variants including Delta and Omicron. In other words, any long COVID effects linked to more recent variants such as BA.5 or BA.2.75 are unknown.

A version of this article first appeared on WebMD.com.

Researchers from the Centers for Disease Control and Prevention report that children and teenagers with long COVID have about twice the risk of getting serious outcomes, compared to others without COVID.

Heart inflammation; a blood clot in the lung; or a blood clot in the lower leg, thigh, or pelvis were the most common bad outcomes in a new study. Even though the risk was higher for these and some other serious events, the overall numbers were small.

“Many of these conditions were rare or uncommon among children in this analysis, but even a small increase in these conditions is notable,” a CDC new release stated.

The investigators said their findings stress the importance of COVID-19 vaccination in Americans under the age of 18.

The study was published online in the CDC’s Morbidity and Mortality Weekly Report.
 

Less is known about long COVID in children

Lyudmyla Kompaniyets, PhD, and colleagues noted that most research on long COVID to date has been done in adults, so little information is available about the risks to Americans ages 17 and younger.

To learn more, they compared post–COVID-19 symptoms and conditions between 781,419 children and teenagers with confirmed COVID-19 to another 2,344,257 without COVID-19. They looked at medical claims and laboratory data for these children and teenagers from March 1, 2020, through Jan. 31, 2022, to see who got any of 15 specific outcomes linked to long COVID-19.

Long COVID was defined as a condition where symptoms that last for or begin at least 4 weeks after a COVID-19 diagnosis.

Compared to children with no history of a COVID-19 diagnosis, the long COVID-19 group was 101% more likely to have an acute pulmonary embolism, 99% more likely to have myocarditis or cardiomyopathy, 87% more likely to have a venous thromboembolic event, 32% more likely to have acute and unspecified renal failure, and 23% more likely to have type 1 diabetes.

“This report points to the fact that the risks of COVID infection itself, both in terms of the acute effects, MIS-C [multisystem inflammatory syndrome in children], as well as the long-term effects, are real, are concerning, and are potentially very serious,” said Stuart Berger, MD, chair of the American Academy of Pediatrics Section on Cardiology and Cardiac Surgery.

“The message that we should take away from this is that we should be very keen on all the methods of prevention for COVID, especially the vaccine,” said Dr. Berger, chief of cardiology in the department of pediatrics at Northwestern University in Chicago.


 

A ‘wake-up call’

The study findings are “sobering” and are “a reminder of the seriousness of COVID infection,” says Gregory Poland, MD, an infectious disease expert at the Mayo Clinic in Rochester, Minn.

“When you look in particular at the more serious complications from COVID in this young age group, those are life-altering complications that will have consequences and ramifications throughout their lives,” he said.

“I would take this as a serious wake-up call to parents [at a time when] the immunization rates in younger children are so pitifully low,” Dr. Poland said.
 

Still early days

The study is suggestive but not definitive, said Peter Katona, MD, professor of medicine and infectious diseases expert at the UCLA Fielding School of Public Health.

It’s still too early to draw conclusions about long COVID, including in children, because many questions remain, he said: Should long COVID be defined as symptoms at 1 month or 3 months after infection? How do you define brain fog?

Dr. Katona and colleagues are studying long COVID intervention among students at UCLA to answer some of these questions, including the incidence and effect of early intervention.

The study had “at least seven limitations,” the researchers noted. Among them was the use of medical claims data that noted long COVID outcomes but not how severe they were; some people in the no COVID group might have had the illness but not been diagnosed; and the researchers did not adjust for vaccination status.

Dr. Poland noted that the study was done during surges in COVID variants including Delta and Omicron. In other words, any long COVID effects linked to more recent variants such as BA.5 or BA.2.75 are unknown.

A version of this article first appeared on WebMD.com.

Researchers from the Centers for Disease Control and Prevention report that children and teenagers with long COVID have about twice the risk of getting serious outcomes, compared to others without COVID.

Heart inflammation; a blood clot in the lung; or a blood clot in the lower leg, thigh, or pelvis were the most common bad outcomes in a new study. Even though the risk was higher for these and some other serious events, the overall numbers were small.

“Many of these conditions were rare or uncommon among children in this analysis, but even a small increase in these conditions is notable,” a CDC new release stated.

The investigators said their findings stress the importance of COVID-19 vaccination in Americans under the age of 18.

The study was published online in the CDC’s Morbidity and Mortality Weekly Report.
 

Less is known about long COVID in children

Lyudmyla Kompaniyets, PhD, and colleagues noted that most research on long COVID to date has been done in adults, so little information is available about the risks to Americans ages 17 and younger.

To learn more, they compared post–COVID-19 symptoms and conditions between 781,419 children and teenagers with confirmed COVID-19 to another 2,344,257 without COVID-19. They looked at medical claims and laboratory data for these children and teenagers from March 1, 2020, through Jan. 31, 2022, to see who got any of 15 specific outcomes linked to long COVID-19.

Long COVID was defined as a condition where symptoms that last for or begin at least 4 weeks after a COVID-19 diagnosis.

Compared to children with no history of a COVID-19 diagnosis, the long COVID-19 group was 101% more likely to have an acute pulmonary embolism, 99% more likely to have myocarditis or cardiomyopathy, 87% more likely to have a venous thromboembolic event, 32% more likely to have acute and unspecified renal failure, and 23% more likely to have type 1 diabetes.

“This report points to the fact that the risks of COVID infection itself, both in terms of the acute effects, MIS-C [multisystem inflammatory syndrome in children], as well as the long-term effects, are real, are concerning, and are potentially very serious,” said Stuart Berger, MD, chair of the American Academy of Pediatrics Section on Cardiology and Cardiac Surgery.

“The message that we should take away from this is that we should be very keen on all the methods of prevention for COVID, especially the vaccine,” said Dr. Berger, chief of cardiology in the department of pediatrics at Northwestern University in Chicago.


 

A ‘wake-up call’

The study findings are “sobering” and are “a reminder of the seriousness of COVID infection,” says Gregory Poland, MD, an infectious disease expert at the Mayo Clinic in Rochester, Minn.

“When you look in particular at the more serious complications from COVID in this young age group, those are life-altering complications that will have consequences and ramifications throughout their lives,” he said.

“I would take this as a serious wake-up call to parents [at a time when] the immunization rates in younger children are so pitifully low,” Dr. Poland said.
 

Still early days

The study is suggestive but not definitive, said Peter Katona, MD, professor of medicine and infectious diseases expert at the UCLA Fielding School of Public Health.

It’s still too early to draw conclusions about long COVID, including in children, because many questions remain, he said: Should long COVID be defined as symptoms at 1 month or 3 months after infection? How do you define brain fog?

Dr. Katona and colleagues are studying long COVID intervention among students at UCLA to answer some of these questions, including the incidence and effect of early intervention.

The study had “at least seven limitations,” the researchers noted. Among them was the use of medical claims data that noted long COVID outcomes but not how severe they were; some people in the no COVID group might have had the illness but not been diagnosed; and the researchers did not adjust for vaccination status.

Dr. Poland noted that the study was done during surges in COVID variants including Delta and Omicron. In other words, any long COVID effects linked to more recent variants such as BA.5 or BA.2.75 are unknown.

A version of this article first appeared on WebMD.com.