Kari Oakes

LAS VEGAS – Patients with systemic sclerosis, mixed connective tissue disease, and Ehlers-Danlos syndrome who have a gastrointestinal symptom cluster that includes bloating, early satiety, and postprandial “brain fog” may be suffering from small intestine bacterial overgrowth, or SIBO.

This treatable condition occurs when enteric flora from the colon creep north into the small intestine, which is usually a relatively sterile environment. In addition to the bloating, dyspepsia, and nausea that SIBO can cause, patients may have an erratic bowel movement pattern, and can occasionally suffer from vitamin deficiencies and weight loss, Ali Rezaie, MD, said at the annual Perspectives in Rheumatic Diseases held by the Global Academy for Medical Education.

“SIBO is not a primary disease,” said Dr. Rezaie, professor of gastroenterology at Cedars-Sinai Medical Center, Los Angeles, and lead author of a 2016 review on the diagnosis and treatment of SIBO (Curr Gastroenterol Rep. 2016 Feb;18[2]:8).

For patients with scleroderma or mixed connective tissue diseases as well as hypermobility disorders such as Ehlers-Danlos syndrome, the small bowel dysmotility associated with their conditions is often the primary disease. However, diabetes-associated gastroparesis and the presence of anti-vinculin and anti-CdtB antibodies in irritable bowel syndrome patients can also cause dysmotility, provoking SIBO.

Surgical procedures that can set patients up for SIBO include gastric bypass and ileocecal resection; medications such as opioids and anticholinergic or antidiarrheal medications also can be SIBO risk factors. Finally, chronic proton pump inhibitor use, autoimmune gastritis, and gastrectomy can all reduce gastric acid secretion, permitting bacterial overgrowth in the small intestine.

Normally, jejunal contents have around 100 colony-forming units (CFU) per mL, with Lactobacillus and Streptococcus predominating. However, in SIBO, there are more bacteria in the small intestine – greater than 1,000 CFU/mL – and enteric flora predominate.

Depending on the species predominating, an excess of hydrogen or methane may be produced during bacterial fermentation of food in the small intestine, Dr. Rezaie said. Though the preferred method for diagnosis is small-bowel aspiration, “this is an invasive, costly, and time-consuming procedure,” he said.

By contrast, breath testing is noninvasive and inexpensive, and detects excess levels of hydrogen or methane on the breath when performed at a fixed time after the patient is fed a bolus of lactulose or glucose. The test is diagnostic for SIBO because “the sole source of methane and hydrogen [as H₂] in our body is from the bacterial metabolism,” Dr. Rezaie said.

SIBO breath testing is considered positive if there are 10 or greater parts per million of methane at any time point, or if hydrogen levels rise by at least 20 parts per million within 90 minutes of the bolus feed.

The treatment for SIBO can be thought of in three phases, Dr. Rezaie said in an interview, referencing the consensus statement. The three treatment stages include induction of remission, maintenance of remission, and treatment of recurrence, should it recur.

Therapy for induction of remission is guided by the breath test results. If excessive methane production is not detected, then a broad-spectrum antibiotic such as amoxicillin, ciprofloxacin, trimethoprim-sulfamethoxazole, or rifaximin can be given for 14 days. If excess methane is detected, then the broad spectrum antibiotic should be combined with neomycin 500 mg by mouth for 14 days as well.

If a clinical response occurs, then a maintenance strategy can include restricting highly fermentable foods, using promotility drugs such as low-dose macrolides, tegaserod, or other 5HT₄ agonists, and ongoing vigilance for recurrent symptoms. If there’s a primary cause that can be remedied – for example, stopping a proton pump inhibitor or lysing identifiable intestinal lesions – then those factors can be addressed during remission as well.

For patients who can’t be brought into remission with one antibiotic course, another course of alternative antibiotics can be considered. Some patients may benefit from an elemental diet.

Managing recurrences involves further rounds of antibiotics together with optimizing motility and addressing other risk factors.

In terms of how SIBO affects management of the primary rheumatologic disease, patients should try to avoid frequent use of nonsteroidal anti-inflammatory drugs because of the potential for further untoward effects on a disrupted gut. However, there’s no reason to alter medical therapy otherwise, and biologic therapy “is generally well-tolerated in patients with small intestine bacterial overgrowth,” Dr. Rezaie said.

He pointed out that rheumatology patients can have so many medical issues that gastrointestinal symptoms may not rise to the surface, so a thorough review of systems should include careful questioning about digestive health. “Rheumatologists need to incorporate this knowledge into the management of their patients,” he said. “It’s a quality of life issue.”

Dr. Rezaie reported having received honoraria and consulted for Valeant Pharmaceuticals. Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – Patients with systemic sclerosis, mixed connective tissue disease, and Ehlers-Danlos syndrome who have a gastrointestinal symptom cluster that includes bloating, early satiety, and postprandial “brain fog” may be suffering from small intestine bacterial overgrowth, or SIBO.

This treatable condition occurs when enteric flora from the colon creep north into the small intestine, which is usually a relatively sterile environment. In addition to the bloating, dyspepsia, and nausea that SIBO can cause, patients may have an erratic bowel movement pattern, and can occasionally suffer from vitamin deficiencies and weight loss, Ali Rezaie, MD, said at the annual Perspectives in Rheumatic Diseases held by the Global Academy for Medical Education.

“SIBO is not a primary disease,” said Dr. Rezaie, professor of gastroenterology at Cedars-Sinai Medical Center, Los Angeles, and lead author of a 2016 review on the diagnosis and treatment of SIBO (Curr Gastroenterol Rep. 2016 Feb;18[2]:8).

For patients with scleroderma or mixed connective tissue diseases as well as hypermobility disorders such as Ehlers-Danlos syndrome, the small bowel dysmotility associated with their conditions is often the primary disease. However, diabetes-associated gastroparesis and the presence of anti-vinculin and anti-CdtB antibodies in irritable bowel syndrome patients can also cause dysmotility, provoking SIBO.

Surgical procedures that can set patients up for SIBO include gastric bypass and ileocecal resection; medications such as opioids and anticholinergic or antidiarrheal medications also can be SIBO risk factors. Finally, chronic proton pump inhibitor use, autoimmune gastritis, and gastrectomy can all reduce gastric acid secretion, permitting bacterial overgrowth in the small intestine.

Normally, jejunal contents have around 100 colony-forming units (CFU) per mL, with Lactobacillus and Streptococcus predominating. However, in SIBO, there are more bacteria in the small intestine – greater than 1,000 CFU/mL – and enteric flora predominate.

Depending on the species predominating, an excess of hydrogen or methane may be produced during bacterial fermentation of food in the small intestine, Dr. Rezaie said. Though the preferred method for diagnosis is small-bowel aspiration, “this is an invasive, costly, and time-consuming procedure,” he said.

By contrast, breath testing is noninvasive and inexpensive, and detects excess levels of hydrogen or methane on the breath when performed at a fixed time after the patient is fed a bolus of lactulose or glucose. The test is diagnostic for SIBO because “the sole source of methane and hydrogen [as H₂] in our body is from the bacterial metabolism,” Dr. Rezaie said.

SIBO breath testing is considered positive if there are 10 or greater parts per million of methane at any time point, or if hydrogen levels rise by at least 20 parts per million within 90 minutes of the bolus feed.

The treatment for SIBO can be thought of in three phases, Dr. Rezaie said in an interview, referencing the consensus statement. The three treatment stages include induction of remission, maintenance of remission, and treatment of recurrence, should it recur.

Therapy for induction of remission is guided by the breath test results. If excessive methane production is not detected, then a broad-spectrum antibiotic such as amoxicillin, ciprofloxacin, trimethoprim-sulfamethoxazole, or rifaximin can be given for 14 days. If excess methane is detected, then the broad spectrum antibiotic should be combined with neomycin 500 mg by mouth for 14 days as well.

If a clinical response occurs, then a maintenance strategy can include restricting highly fermentable foods, using promotility drugs such as low-dose macrolides, tegaserod, or other 5HT₄ agonists, and ongoing vigilance for recurrent symptoms. If there’s a primary cause that can be remedied – for example, stopping a proton pump inhibitor or lysing identifiable intestinal lesions – then those factors can be addressed during remission as well.

For patients who can’t be brought into remission with one antibiotic course, another course of alternative antibiotics can be considered. Some patients may benefit from an elemental diet.

Managing recurrences involves further rounds of antibiotics together with optimizing motility and addressing other risk factors.

In terms of how SIBO affects management of the primary rheumatologic disease, patients should try to avoid frequent use of nonsteroidal anti-inflammatory drugs because of the potential for further untoward effects on a disrupted gut. However, there’s no reason to alter medical therapy otherwise, and biologic therapy “is generally well-tolerated in patients with small intestine bacterial overgrowth,” Dr. Rezaie said.

He pointed out that rheumatology patients can have so many medical issues that gastrointestinal symptoms may not rise to the surface, so a thorough review of systems should include careful questioning about digestive health. “Rheumatologists need to incorporate this knowledge into the management of their patients,” he said. “It’s a quality of life issue.”

Dr. Rezaie reported having received honoraria and consulted for Valeant Pharmaceuticals. Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – Patients with systemic sclerosis, mixed connective tissue disease, and Ehlers-Danlos syndrome who have a gastrointestinal symptom cluster that includes bloating, early satiety, and postprandial “brain fog” may be suffering from small intestine bacterial overgrowth, or SIBO.

This treatable condition occurs when enteric flora from the colon creep north into the small intestine, which is usually a relatively sterile environment. In addition to the bloating, dyspepsia, and nausea that SIBO can cause, patients may have an erratic bowel movement pattern, and can occasionally suffer from vitamin deficiencies and weight loss, Ali Rezaie, MD, said at the annual Perspectives in Rheumatic Diseases held by the Global Academy for Medical Education.

“SIBO is not a primary disease,” said Dr. Rezaie, professor of gastroenterology at Cedars-Sinai Medical Center, Los Angeles, and lead author of a 2016 review on the diagnosis and treatment of SIBO (Curr Gastroenterol Rep. 2016 Feb;18[2]:8).

For patients with scleroderma or mixed connective tissue diseases as well as hypermobility disorders such as Ehlers-Danlos syndrome, the small bowel dysmotility associated with their conditions is often the primary disease. However, diabetes-associated gastroparesis and the presence of anti-vinculin and anti-CdtB antibodies in irritable bowel syndrome patients can also cause dysmotility, provoking SIBO.

Surgical procedures that can set patients up for SIBO include gastric bypass and ileocecal resection; medications such as opioids and anticholinergic or antidiarrheal medications also can be SIBO risk factors. Finally, chronic proton pump inhibitor use, autoimmune gastritis, and gastrectomy can all reduce gastric acid secretion, permitting bacterial overgrowth in the small intestine.

Normally, jejunal contents have around 100 colony-forming units (CFU) per mL, with Lactobacillus and Streptococcus predominating. However, in SIBO, there are more bacteria in the small intestine – greater than 1,000 CFU/mL – and enteric flora predominate.

Depending on the species predominating, an excess of hydrogen or methane may be produced during bacterial fermentation of food in the small intestine, Dr. Rezaie said. Though the preferred method for diagnosis is small-bowel aspiration, “this is an invasive, costly, and time-consuming procedure,” he said.

By contrast, breath testing is noninvasive and inexpensive, and detects excess levels of hydrogen or methane on the breath when performed at a fixed time after the patient is fed a bolus of lactulose or glucose. The test is diagnostic for SIBO because “the sole source of methane and hydrogen [as H₂] in our body is from the bacterial metabolism,” Dr. Rezaie said.

SIBO breath testing is considered positive if there are 10 or greater parts per million of methane at any time point, or if hydrogen levels rise by at least 20 parts per million within 90 minutes of the bolus feed.

The treatment for SIBO can be thought of in three phases, Dr. Rezaie said in an interview, referencing the consensus statement. The three treatment stages include induction of remission, maintenance of remission, and treatment of recurrence, should it recur.

Therapy for induction of remission is guided by the breath test results. If excessive methane production is not detected, then a broad-spectrum antibiotic such as amoxicillin, ciprofloxacin, trimethoprim-sulfamethoxazole, or rifaximin can be given for 14 days. If excess methane is detected, then the broad spectrum antibiotic should be combined with neomycin 500 mg by mouth for 14 days as well.

If a clinical response occurs, then a maintenance strategy can include restricting highly fermentable foods, using promotility drugs such as low-dose macrolides, tegaserod, or other 5HT₄ agonists, and ongoing vigilance for recurrent symptoms. If there’s a primary cause that can be remedied – for example, stopping a proton pump inhibitor or lysing identifiable intestinal lesions – then those factors can be addressed during remission as well.

For patients who can’t be brought into remission with one antibiotic course, another course of alternative antibiotics can be considered. Some patients may benefit from an elemental diet.

Managing recurrences involves further rounds of antibiotics together with optimizing motility and addressing other risk factors.

In terms of how SIBO affects management of the primary rheumatologic disease, patients should try to avoid frequent use of nonsteroidal anti-inflammatory drugs because of the potential for further untoward effects on a disrupted gut. However, there’s no reason to alter medical therapy otherwise, and biologic therapy “is generally well-tolerated in patients with small intestine bacterial overgrowth,” Dr. Rezaie said.

He pointed out that rheumatology patients can have so many medical issues that gastrointestinal symptoms may not rise to the surface, so a thorough review of systems should include careful questioning about digestive health. “Rheumatologists need to incorporate this knowledge into the management of their patients,” he said. “It’s a quality of life issue.”

Dr. Rezaie reported having received honoraria and consulted for Valeant Pharmaceuticals. Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – Pay attention to GI symptoms in your scleroderma patients. Gut involvement in scleroderma, a result of vasculopathy and fibrosis affecting the GI tract, is common and can be debilitating, said Daniel Furst, MD.

Speaking at the annual Perspectives in Rheumatologic Diseases presented by the Global Academy for Medical Education, Dr. Furst said that the progression often begins at the mouth and esophagus, and progresses through the digestive system, eventually reaching the rectum and anus.

“You think about motility issues early on, in the esophagus,” and early oral symptoms can include mouth dryness, said Dr. Furst, who is associated with the University of California, Los Angeles, the University of Washington, Seattle, and the University of Florence (Italy).

As scleroderma begins to affect the midgut, Dr. Furst said that the secondary results of the decrease in motility are symptoms such as heartburn, nausea, vomiting, and early satiety.

“When you have a decrease in motility, then the normal ... housekeeping waves of the midgut and the colon are decreased,” he said. Bacteria from the colon can then invade the small bowel, causing overgrowth of the midgut by species not normally seen there. Not only gas, but also malnutrition can eventually result, he said.

When scleroderma affects the lower gut, patients can have bloating, diarrhea, and constipation, and finally, incontinence of the bowel, a condition with often devastating psychosocial consequences.

The choice of promotility agents depends on the area affected; erythromycin and metoclopramide help in the upper GI tract, while tegaserod can be helpful in the lower gut.

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – Pay attention to GI symptoms in your scleroderma patients. Gut involvement in scleroderma, a result of vasculopathy and fibrosis affecting the GI tract, is common and can be debilitating, said Daniel Furst, MD.

Speaking at the annual Perspectives in Rheumatologic Diseases presented by the Global Academy for Medical Education, Dr. Furst said that the progression often begins at the mouth and esophagus, and progresses through the digestive system, eventually reaching the rectum and anus.

“You think about motility issues early on, in the esophagus,” and early oral symptoms can include mouth dryness, said Dr. Furst, who is associated with the University of California, Los Angeles, the University of Washington, Seattle, and the University of Florence (Italy).

As scleroderma begins to affect the midgut, Dr. Furst said that the secondary results of the decrease in motility are symptoms such as heartburn, nausea, vomiting, and early satiety.

“When you have a decrease in motility, then the normal ... housekeeping waves of the midgut and the colon are decreased,” he said. Bacteria from the colon can then invade the small bowel, causing overgrowth of the midgut by species not normally seen there. Not only gas, but also malnutrition can eventually result, he said.

When scleroderma affects the lower gut, patients can have bloating, diarrhea, and constipation, and finally, incontinence of the bowel, a condition with often devastating psychosocial consequences.

The choice of promotility agents depends on the area affected; erythromycin and metoclopramide help in the upper GI tract, while tegaserod can be helpful in the lower gut.

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – Pay attention to GI symptoms in your scleroderma patients. Gut involvement in scleroderma, a result of vasculopathy and fibrosis affecting the GI tract, is common and can be debilitating, said Daniel Furst, MD.

Speaking at the annual Perspectives in Rheumatologic Diseases presented by the Global Academy for Medical Education, Dr. Furst said that the progression often begins at the mouth and esophagus, and progresses through the digestive system, eventually reaching the rectum and anus.

“You think about motility issues early on, in the esophagus,” and early oral symptoms can include mouth dryness, said Dr. Furst, who is associated with the University of California, Los Angeles, the University of Washington, Seattle, and the University of Florence (Italy).

As scleroderma begins to affect the midgut, Dr. Furst said that the secondary results of the decrease in motility are symptoms such as heartburn, nausea, vomiting, and early satiety.

“When you have a decrease in motility, then the normal ... housekeeping waves of the midgut and the colon are decreased,” he said. Bacteria from the colon can then invade the small bowel, causing overgrowth of the midgut by species not normally seen there. Not only gas, but also malnutrition can eventually result, he said.

When scleroderma affects the lower gut, patients can have bloating, diarrhea, and constipation, and finally, incontinence of the bowel, a condition with often devastating psychosocial consequences.

The choice of promotility agents depends on the area affected; erythromycin and metoclopramide help in the upper GI tract, while tegaserod can be helpful in the lower gut.

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – Dermatologists need to be alert for amyotrophic dermatomyositis in patients with rash where lupus might be considered, because of the need for vigilant surveillance for cancer and lung disease in this population.

Ruth Ann Vleugels, MD, walked attendees through a series of dermatomyositis diagnostic pearls at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

“When a patient has dermatomyositis but doesn’t have muscle disease, you really have to rely on the skin findings,” since you’re lacking the tipoff of muscle disease at presentation, Dr. Vleugels, professor of dermatology at Brigham and Women’s Hospital, Boston, said in an interview. This is especially true because, on biopsy, “the pathological findings are identical to that of lupus,” she said.

Dr. Vleugels emphasized that it’s important not to miss a more subtle, less violaceous heliotrope eruption, especially in lighter-skinned patients; similarly, Gottron’s papules are not always papular and limited to the knuckle pads, but can be more macular and linear, with psoriasiform scaling. Nail findings such as dilated capillary loops with dystrophic and hypertrophied cuticles are also a big clue. Photodistributed erythema – the “shawl sign” – can be subtle, but offers additional support for a dermatomyositis diagnosis.

Though the erythematous midface rash of lupus resembles a dermatomyositis rash in many ways, there’s a critical differentiator of the two rashes, Dr. Vleugels said. “In dermatomyositis patients, it very classically hugs, or involves, the nasolabial folds, whereas in our systemic lupus patients, the erythema of the cheeks spares the nasolabial folds.”

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – Dermatologists need to be alert for amyotrophic dermatomyositis in patients with rash where lupus might be considered, because of the need for vigilant surveillance for cancer and lung disease in this population.

Ruth Ann Vleugels, MD, walked attendees through a series of dermatomyositis diagnostic pearls at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

“When a patient has dermatomyositis but doesn’t have muscle disease, you really have to rely on the skin findings,” since you’re lacking the tipoff of muscle disease at presentation, Dr. Vleugels, professor of dermatology at Brigham and Women’s Hospital, Boston, said in an interview. This is especially true because, on biopsy, “the pathological findings are identical to that of lupus,” she said.

Dr. Vleugels emphasized that it’s important not to miss a more subtle, less violaceous heliotrope eruption, especially in lighter-skinned patients; similarly, Gottron’s papules are not always papular and limited to the knuckle pads, but can be more macular and linear, with psoriasiform scaling. Nail findings such as dilated capillary loops with dystrophic and hypertrophied cuticles are also a big clue. Photodistributed erythema – the “shawl sign” – can be subtle, but offers additional support for a dermatomyositis diagnosis.

Though the erythematous midface rash of lupus resembles a dermatomyositis rash in many ways, there’s a critical differentiator of the two rashes, Dr. Vleugels said. “In dermatomyositis patients, it very classically hugs, or involves, the nasolabial folds, whereas in our systemic lupus patients, the erythema of the cheeks spares the nasolabial folds.”

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – Dermatologists need to be alert for amyotrophic dermatomyositis in patients with rash where lupus might be considered, because of the need for vigilant surveillance for cancer and lung disease in this population.

Ruth Ann Vleugels, MD, walked attendees through a series of dermatomyositis diagnostic pearls at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

“When a patient has dermatomyositis but doesn’t have muscle disease, you really have to rely on the skin findings,” since you’re lacking the tipoff of muscle disease at presentation, Dr. Vleugels, professor of dermatology at Brigham and Women’s Hospital, Boston, said in an interview. This is especially true because, on biopsy, “the pathological findings are identical to that of lupus,” she said.

Dr. Vleugels emphasized that it’s important not to miss a more subtle, less violaceous heliotrope eruption, especially in lighter-skinned patients; similarly, Gottron’s papules are not always papular and limited to the knuckle pads, but can be more macular and linear, with psoriasiform scaling. Nail findings such as dilated capillary loops with dystrophic and hypertrophied cuticles are also a big clue. Photodistributed erythema – the “shawl sign” – can be subtle, but offers additional support for a dermatomyositis diagnosis.

Though the erythematous midface rash of lupus resembles a dermatomyositis rash in many ways, there’s a critical differentiator of the two rashes, Dr. Vleugels said. “In dermatomyositis patients, it very classically hugs, or involves, the nasolabial folds, whereas in our systemic lupus patients, the erythema of the cheeks spares the nasolabial folds.”

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – When genetic risk and lifestyle risk factors collide with the baseline systemic inflammation of rheumatoid arthritis (RA), cardiovascular risk increases significantly. Helping patients to manage risk for cardiovascular disease (CVD) requires getting comfortable in making risk assessments and counseling patients about medication and lifestyle options, especially for patients who are not actively being managed by primary care physicians.

Jon Giles, MD, said that a large portion of the elevated risk for CVD in patients with RA is “driven by the fact that [RA] patients have more atherosclerosis.”

Dr. Giles, professor of medicine at Columbia University, New York, said that other CVD risk factors can boost the risk further. “If you have diabetes, smoking, high blood pressure, elevated lipids in your blood – if you have a combination of those plus inflammation, it makes that risk even higher,” Dr. Giles said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

“There’s definitely a lot of data that suggests that, as rheumatologists, we’re not doing a very good job of screening and treating for cardiovascular disease and risk,” Dr. Giles said in an interview at the meeting. He suggests that his fellow rheumatologists become comfortable with screening and treatment guidelines for cardiovascular disease. For selected patients, coronary CT or carotid ultrasound may be valuable in guiding decision making, since very low LDL cholesterol may be correlated with an increased risk of CVD for some patients with RA.

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – When genetic risk and lifestyle risk factors collide with the baseline systemic inflammation of rheumatoid arthritis (RA), cardiovascular risk increases significantly. Helping patients to manage risk for cardiovascular disease (CVD) requires getting comfortable in making risk assessments and counseling patients about medication and lifestyle options, especially for patients who are not actively being managed by primary care physicians.

Jon Giles, MD, said that a large portion of the elevated risk for CVD in patients with RA is “driven by the fact that [RA] patients have more atherosclerosis.”

Dr. Giles, professor of medicine at Columbia University, New York, said that other CVD risk factors can boost the risk further. “If you have diabetes, smoking, high blood pressure, elevated lipids in your blood – if you have a combination of those plus inflammation, it makes that risk even higher,” Dr. Giles said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

“There’s definitely a lot of data that suggests that, as rheumatologists, we’re not doing a very good job of screening and treating for cardiovascular disease and risk,” Dr. Giles said in an interview at the meeting. He suggests that his fellow rheumatologists become comfortable with screening and treatment guidelines for cardiovascular disease. For selected patients, coronary CT or carotid ultrasound may be valuable in guiding decision making, since very low LDL cholesterol may be correlated with an increased risk of CVD for some patients with RA.

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – When genetic risk and lifestyle risk factors collide with the baseline systemic inflammation of rheumatoid arthritis (RA), cardiovascular risk increases significantly. Helping patients to manage risk for cardiovascular disease (CVD) requires getting comfortable in making risk assessments and counseling patients about medication and lifestyle options, especially for patients who are not actively being managed by primary care physicians.

Jon Giles, MD, said that a large portion of the elevated risk for CVD in patients with RA is “driven by the fact that [RA] patients have more atherosclerosis.”

Dr. Giles, professor of medicine at Columbia University, New York, said that other CVD risk factors can boost the risk further. “If you have diabetes, smoking, high blood pressure, elevated lipids in your blood – if you have a combination of those plus inflammation, it makes that risk even higher,” Dr. Giles said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

“There’s definitely a lot of data that suggests that, as rheumatologists, we’re not doing a very good job of screening and treating for cardiovascular disease and risk,” Dr. Giles said in an interview at the meeting. He suggests that his fellow rheumatologists become comfortable with screening and treatment guidelines for cardiovascular disease. For selected patients, coronary CT or carotid ultrasound may be valuable in guiding decision making, since very low LDL cholesterol may be correlated with an increased risk of CVD for some patients with RA.

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – Change in federal reimbursement for physicians is coming. Though the change is inevitable, physicians still have to weigh choices about when they might want to jump in with both feet, since entry into the full incentive payment system will be optional – for a time.

The Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) is “basically a reorganization of all of these disparate reward and penalty systems” that have existed within the federal health care reimbursement landscape, said Joseph S. Eastern, MD. “The idea was to collect them all within one system.”

The new system is called the Medicare Incentive Payment System, or MIPS. Physicians are already familiar with many MIPS components, including meaningful use of the electronic health record, “which everybody thought was going away, but it isn’t,” said Dr. Eastern, a dermatologist in private practice in Belleville, N.J., who’s affiliated with Seton Hall University, South Orange, N.J. Also included are the Physician Quality Reimbursement System (PQRS) and the value-based modifier system.

MIPS is designed so that “you’ll either get a reward or a penalty depending on how well you do, compared with other physicians,” said Dr. Eastern, speaking at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

The alternative, he said, is to opt for one of the Alternative Payment Models, or APMs. However, details about APMs are “really up in the air, because a lot of them have either not been doing very well, or have not been very well defined,” so that physicians often don’t currently have enough data to make an informed choice. He expects the APM landscape to sort out over the next year or two.

Opting not to comply and take the 1%-3% cut in Medicare reimbursement associated with noncompliance might make sense for just a few physicians, though it might seem tempting, Dr. Eastern said in a video interview. Since the penalties will escalate significantly over the next few years, he feels that only physicians who are considering retiring soon or selling their practices should consider opting out.

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – Change in federal reimbursement for physicians is coming. Though the change is inevitable, physicians still have to weigh choices about when they might want to jump in with both feet, since entry into the full incentive payment system will be optional – for a time.

The Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) is “basically a reorganization of all of these disparate reward and penalty systems” that have existed within the federal health care reimbursement landscape, said Joseph S. Eastern, MD. “The idea was to collect them all within one system.”

The new system is called the Medicare Incentive Payment System, or MIPS. Physicians are already familiar with many MIPS components, including meaningful use of the electronic health record, “which everybody thought was going away, but it isn’t,” said Dr. Eastern, a dermatologist in private practice in Belleville, N.J., who’s affiliated with Seton Hall University, South Orange, N.J. Also included are the Physician Quality Reimbursement System (PQRS) and the value-based modifier system.

MIPS is designed so that “you’ll either get a reward or a penalty depending on how well you do, compared with other physicians,” said Dr. Eastern, speaking at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

The alternative, he said, is to opt for one of the Alternative Payment Models, or APMs. However, details about APMs are “really up in the air, because a lot of them have either not been doing very well, or have not been very well defined,” so that physicians often don’t currently have enough data to make an informed choice. He expects the APM landscape to sort out over the next year or two.

Opting not to comply and take the 1%-3% cut in Medicare reimbursement associated with noncompliance might make sense for just a few physicians, though it might seem tempting, Dr. Eastern said in a video interview. Since the penalties will escalate significantly over the next few years, he feels that only physicians who are considering retiring soon or selling their practices should consider opting out.

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – Change in federal reimbursement for physicians is coming. Though the change is inevitable, physicians still have to weigh choices about when they might want to jump in with both feet, since entry into the full incentive payment system will be optional – for a time.

The Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) is “basically a reorganization of all of these disparate reward and penalty systems” that have existed within the federal health care reimbursement landscape, said Joseph S. Eastern, MD. “The idea was to collect them all within one system.”

The new system is called the Medicare Incentive Payment System, or MIPS. Physicians are already familiar with many MIPS components, including meaningful use of the electronic health record, “which everybody thought was going away, but it isn’t,” said Dr. Eastern, a dermatologist in private practice in Belleville, N.J., who’s affiliated with Seton Hall University, South Orange, N.J. Also included are the Physician Quality Reimbursement System (PQRS) and the value-based modifier system.

MIPS is designed so that “you’ll either get a reward or a penalty depending on how well you do, compared with other physicians,” said Dr. Eastern, speaking at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

The alternative, he said, is to opt for one of the Alternative Payment Models, or APMs. However, details about APMs are “really up in the air, because a lot of them have either not been doing very well, or have not been very well defined,” so that physicians often don’t currently have enough data to make an informed choice. He expects the APM landscape to sort out over the next year or two.

Opting not to comply and take the 1%-3% cut in Medicare reimbursement associated with noncompliance might make sense for just a few physicians, though it might seem tempting, Dr. Eastern said in a video interview. Since the penalties will escalate significantly over the next few years, he feels that only physicians who are considering retiring soon or selling their practices should consider opting out.

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – Although biologics have transformed treatment of many rheumatologic disorders, their structure and mechanism of action can come with immunogenic baggage. “They’re proteins; consequently, one can expect immunogenicity,” said Daniel Furst, MD, speaking at the annual Perspectives in Rheumatic Diseases held by the Global Academy for Medical Education.

Immunogenicity can increase clearance of drugs; it can also interfere with the function of the drug. Although physicians may be tempted to think that developing an antidrug antibody to a specific drug is the principal cause for lack of efficacy in an individual patient, “in fact, it’s not that simple,” said Dr. Furst. “There are comorbidities, other drugs, which can affect the immunogenicity itself; there’s even the specific epitope that’s being affected by the drug antibody, which may or may not result in neutralization and an effect.”

In the broad class of tumor necrosis factor inhibitors (TNFIs), about 30% of patients taking adalimumab or infliximab will develop autoantibodies. This is higher than the 10% rate of autoantibody development for other TNFIs.

For non-TNFIs, including abatacept, tocilizumab, and rituximab, “the incidence of immunogenicity is significantly lower,” on the order of 1%-5%, said Dr. Furst, who has appointments at the University of California, Los Angeles, the University of Washington, Seattle, and the University of Florence, Italy.

Still, “there’s reasonable evidence that antidrug antibodies to TNFIs decrease efficacy and increase toxicity, particularly skin reactions,” he said.

Global Academy for Medical Education and this organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – Although biologics have transformed treatment of many rheumatologic disorders, their structure and mechanism of action can come with immunogenic baggage. “They’re proteins; consequently, one can expect immunogenicity,” said Daniel Furst, MD, speaking at the annual Perspectives in Rheumatic Diseases held by the Global Academy for Medical Education.

Immunogenicity can increase clearance of drugs; it can also interfere with the function of the drug. Although physicians may be tempted to think that developing an antidrug antibody to a specific drug is the principal cause for lack of efficacy in an individual patient, “in fact, it’s not that simple,” said Dr. Furst. “There are comorbidities, other drugs, which can affect the immunogenicity itself; there’s even the specific epitope that’s being affected by the drug antibody, which may or may not result in neutralization and an effect.”

In the broad class of tumor necrosis factor inhibitors (TNFIs), about 30% of patients taking adalimumab or infliximab will develop autoantibodies. This is higher than the 10% rate of autoantibody development for other TNFIs.

For non-TNFIs, including abatacept, tocilizumab, and rituximab, “the incidence of immunogenicity is significantly lower,” on the order of 1%-5%, said Dr. Furst, who has appointments at the University of California, Los Angeles, the University of Washington, Seattle, and the University of Florence, Italy.

Still, “there’s reasonable evidence that antidrug antibodies to TNFIs decrease efficacy and increase toxicity, particularly skin reactions,” he said.

Global Academy for Medical Education and this organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – Although biologics have transformed treatment of many rheumatologic disorders, their structure and mechanism of action can come with immunogenic baggage. “They’re proteins; consequently, one can expect immunogenicity,” said Daniel Furst, MD, speaking at the annual Perspectives in Rheumatic Diseases held by the Global Academy for Medical Education.

Immunogenicity can increase clearance of drugs; it can also interfere with the function of the drug. Although physicians may be tempted to think that developing an antidrug antibody to a specific drug is the principal cause for lack of efficacy in an individual patient, “in fact, it’s not that simple,” said Dr. Furst. “There are comorbidities, other drugs, which can affect the immunogenicity itself; there’s even the specific epitope that’s being affected by the drug antibody, which may or may not result in neutralization and an effect.”

In the broad class of tumor necrosis factor inhibitors (TNFIs), about 30% of patients taking adalimumab or infliximab will develop autoantibodies. This is higher than the 10% rate of autoantibody development for other TNFIs.

For non-TNFIs, including abatacept, tocilizumab, and rituximab, “the incidence of immunogenicity is significantly lower,” on the order of 1%-5%, said Dr. Furst, who has appointments at the University of California, Los Angeles, the University of Washington, Seattle, and the University of Florence, Italy.

Still, “there’s reasonable evidence that antidrug antibodies to TNFIs decrease efficacy and increase toxicity, particularly skin reactions,” he said.

Global Academy for Medical Education and this organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – When rheumatologists consider a differential diagnosis that includes seronegative rheumatoid arthritis, they should also consider chikungunya, according to Len Calabrese, DO.

The patient who presents with weeks to months of unexplained arthralgia and perhaps arthritis and a negative autoimmune panel deserves consideration of chikungunya or another arbovirus, said Dr. Calabrese, speaking at the annual Perspectives in Rheumatic Diseases held by the Global Academy for Medical Education.

Among the mosquito-borne arboviruses now in play in the Western Hemisphere, chikungunya is particularly likely to cause long-lasting and sometimes debilitating joint pain weeks and even months after initial infection.

An alphavirus, chikungunya virus makes most affected individuals quite ill, and serum IgG and IgM titers persist long after infection. Testing is straightforward, as long as the virus is a candidate diagnosis, Dr. Calabrese said.

In addition to obtaining an accurate travel history, said Dr. Calabrese, physicians should consider the possibility of autochthonous transmission, which occurs when an infected individual who returns from an endemic area is bitten by mosquitoes once home. Flares of autochthonous transmission can result in pockets of locally heavy transmission far from the zones where chikungunya usually resides.

Dr. Calabrese is chair of clinical immunology and chair of osteopathic research and education at the Cleveland Clinic, and he reported no relevant financial disclosures.

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – When rheumatologists consider a differential diagnosis that includes seronegative rheumatoid arthritis, they should also consider chikungunya, according to Len Calabrese, DO.

The patient who presents with weeks to months of unexplained arthralgia and perhaps arthritis and a negative autoimmune panel deserves consideration of chikungunya or another arbovirus, said Dr. Calabrese, speaking at the annual Perspectives in Rheumatic Diseases held by the Global Academy for Medical Education.

Among the mosquito-borne arboviruses now in play in the Western Hemisphere, chikungunya is particularly likely to cause long-lasting and sometimes debilitating joint pain weeks and even months after initial infection.

An alphavirus, chikungunya virus makes most affected individuals quite ill, and serum IgG and IgM titers persist long after infection. Testing is straightforward, as long as the virus is a candidate diagnosis, Dr. Calabrese said.

In addition to obtaining an accurate travel history, said Dr. Calabrese, physicians should consider the possibility of autochthonous transmission, which occurs when an infected individual who returns from an endemic area is bitten by mosquitoes once home. Flares of autochthonous transmission can result in pockets of locally heavy transmission far from the zones where chikungunya usually resides.

Dr. Calabrese is chair of clinical immunology and chair of osteopathic research and education at the Cleveland Clinic, and he reported no relevant financial disclosures.

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – When rheumatologists consider a differential diagnosis that includes seronegative rheumatoid arthritis, they should also consider chikungunya, according to Len Calabrese, DO.

The patient who presents with weeks to months of unexplained arthralgia and perhaps arthritis and a negative autoimmune panel deserves consideration of chikungunya or another arbovirus, said Dr. Calabrese, speaking at the annual Perspectives in Rheumatic Diseases held by the Global Academy for Medical Education.

Among the mosquito-borne arboviruses now in play in the Western Hemisphere, chikungunya is particularly likely to cause long-lasting and sometimes debilitating joint pain weeks and even months after initial infection.

An alphavirus, chikungunya virus makes most affected individuals quite ill, and serum IgG and IgM titers persist long after infection. Testing is straightforward, as long as the virus is a candidate diagnosis, Dr. Calabrese said.

In addition to obtaining an accurate travel history, said Dr. Calabrese, physicians should consider the possibility of autochthonous transmission, which occurs when an infected individual who returns from an endemic area is bitten by mosquitoes once home. Flares of autochthonous transmission can result in pockets of locally heavy transmission far from the zones where chikungunya usually resides.

Dr. Calabrese is chair of clinical immunology and chair of osteopathic research and education at the Cleveland Clinic, and he reported no relevant financial disclosures.

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

BOSTON – A medication management strategy to minimize the effect of drug-drug interactions (DDIs) between warfarin and common antimicrobials resulted in significantly greater time within therapeutic range for anticoagulation, as well as a numerically smaller, but nonsignificant, number of bleeding events.

After implementation of a comprehensive inpatient and postdischarge guideline to manage DDIs between warfarin and 16 antibiotics, antivirals, or antifungal medications, patients’ in-hospital time within therapeutic range (TWTR) increased to 72% from 50% preimplementation (P = .043). Warfarin TWTR also improved across care transitions after the guidelines were implemented, rising to 70% from 46% (P = .012). No bleeding events occurred in the group studied after the guidelines were instituted, compared with four events in the comparator preguidelines group (P = .11).

Nghi Ha, PharmD, MPH, and his collaborators sought to determine whether formalizing a process to manage potentially dangerous antimicrobial-warfarin DDIs made a difference in achieving more TWTR for patients, as determined by international normalized ratio (INR) values. Dr. Ha, a clinical pharmacist at University of Michigan Health System, Ann Arbor, presented the results during a poster session at the annual meeting of the American Society for Microbiology.

Secondary outcome measures studied by Dr. Ha and his associates included the incidence of thrombosis or major bleeding events, as well as tracking documentation of medications and the anticoagulation plan in progress and discharge notes.

Patients were included if they were at least 18 years old, and if they were on 3 days or more of an antimicrobial with potential for DDI with warfarin. Patients who were also newly on other medications with the potential for significant DDI with warfarin were excluded to minimize the potential for confounding.

Dr. Ha and his collaborators characterized the study as a retrospective, single-center, quasi-experimental design of a pharmacist-run anticoagulation service. The study examined endpoints before and after implementation of comprehensive guidelines, and included 78 preguideline and 31 postguideline patients.

The guidelines drafted by the investigators and tested in their study included empiric adjustment of warfarin dosing for patients who were placed on an antibiotic with high potential to increase INR. These included many azoles and sulfamethoxazole/trimethoprim, for which initial warfarin doses were empirically reduced 20%-30% for patients whose INRs were therapeutic at the start of antimicrobial therapy. For ciprofloxacin, erythromycin, clarithromycin, and isoniazid, the guidelines recommended initial empiric warfarin dose reductions of 10%-15%.

Patients whose INRs were subtherapeutic at the beginning of therapy and who received these antimicrobials were continued on their maintenance warfarin dosing, but were monitored for rising INRs over the first 48 hours, for consideration of dosing adjustment as needed. Individuals with supratherapeutic INRs at the beginning of antimicrobial dosing had their warfarin doses reduced or held by a more aggressive algorithm based on their initial INR, and based on the potential of the antimicrobial to increase INR.

On discharge, patients were either reverted to their previous warfarin regimen if they had been stable on that regimen, or had their inpatient warfarin dosing increased by 10%-20%.

Drugs that were deemed to have moderate potential to increase INR included doxycycline, levofloxacin, moxifloxacin, quinupristin/dalfopristin, telaprevir, boceprevir, and simeprevir. For these medications, the protocol recommended no initial dose adjustment, but recommended monitoring of INR to consider a dose reduction if needed. On hospital discharge, patients who had been on these medications were to resume their previous warfarin dosing.

Antimicrobials with potential to decrease INR included nafcillin, for which the protocol recommended empiric warfarin dose increases of 25%-50%, starting 3-5 days after nafcillin was begun. Patients on rifampin or rifabutin were to increase their warfarin by 20%-30%, also 3-5 days after beginning the antibiotics. Patients on ritonavir alone, or any protease inhibitor given for HIV along with ritonavir, were closely monitored, but no empiric dosing adjustments were made.

Patients with initial subtherapeutic INRs had dosing increased by 30%-50% for nafcillin and 20%-30% for rifampin and rifabutin. A stepped algorithm for dose adjustment or withholding was also developed for these medications to treat patients with initial supratherapeutic INRs. Patients on these medications were to resume their previous warfarin dosing, with monitoring and adjustment if they had not been previously stable.

Documentation of antimicrobial-warfarin DDI in the anticoagulation service discharge summary improved significantly once the guidelines were implemented (40% compared with 14%, P = .02). There was not a significant improvement in DDI documentation in daily progress notes.

The comprehensive intervention included the formulation of guidelines and requirements to document the medication interaction in the medical chart. Other interventions included training for clinical pharmacists and the development of pocket cards and flyers to educate team members about the new guidelines. The electronic health record had triggers built and implemented to prompt consideration of warfarin/antimicrobial DDIs as well.

Dr. Ha and his coauthors noted that the uncontrolled nature of the pre-post study design was one limitation of the study. Also, the real-world design of the study meant that investigators could not control for diet, comorbidities, and other factors that have the potential to affect INR. “Implementing a process to identify high-risk antimicrobial-warfarin DDIs and provide guidelines for empiric warfarin dose adjustment … can improve INR time within therapeutic range,” noted Dr. Ha and his coauthors.

The study authors reported no external sources of funding and no conflicts of interest.

[email protected]

On Twitter @karioakes

BOSTON – A medication management strategy to minimize the effect of drug-drug interactions (DDIs) between warfarin and common antimicrobials resulted in significantly greater time within therapeutic range for anticoagulation, as well as a numerically smaller, but nonsignificant, number of bleeding events.

After implementation of a comprehensive inpatient and postdischarge guideline to manage DDIs between warfarin and 16 antibiotics, antivirals, or antifungal medications, patients’ in-hospital time within therapeutic range (TWTR) increased to 72% from 50% preimplementation (P = .043). Warfarin TWTR also improved across care transitions after the guidelines were implemented, rising to 70% from 46% (P = .012). No bleeding events occurred in the group studied after the guidelines were instituted, compared with four events in the comparator preguidelines group (P = .11).

Nghi Ha, PharmD, MPH, and his collaborators sought to determine whether formalizing a process to manage potentially dangerous antimicrobial-warfarin DDIs made a difference in achieving more TWTR for patients, as determined by international normalized ratio (INR) values. Dr. Ha, a clinical pharmacist at University of Michigan Health System, Ann Arbor, presented the results during a poster session at the annual meeting of the American Society for Microbiology.

Secondary outcome measures studied by Dr. Ha and his associates included the incidence of thrombosis or major bleeding events, as well as tracking documentation of medications and the anticoagulation plan in progress and discharge notes.

Patients were included if they were at least 18 years old, and if they were on 3 days or more of an antimicrobial with potential for DDI with warfarin. Patients who were also newly on other medications with the potential for significant DDI with warfarin were excluded to minimize the potential for confounding.

Dr. Ha and his collaborators characterized the study as a retrospective, single-center, quasi-experimental design of a pharmacist-run anticoagulation service. The study examined endpoints before and after implementation of comprehensive guidelines, and included 78 preguideline and 31 postguideline patients.

The guidelines drafted by the investigators and tested in their study included empiric adjustment of warfarin dosing for patients who were placed on an antibiotic with high potential to increase INR. These included many azoles and sulfamethoxazole/trimethoprim, for which initial warfarin doses were empirically reduced 20%-30% for patients whose INRs were therapeutic at the start of antimicrobial therapy. For ciprofloxacin, erythromycin, clarithromycin, and isoniazid, the guidelines recommended initial empiric warfarin dose reductions of 10%-15%.

Patients whose INRs were subtherapeutic at the beginning of therapy and who received these antimicrobials were continued on their maintenance warfarin dosing, but were monitored for rising INRs over the first 48 hours, for consideration of dosing adjustment as needed. Individuals with supratherapeutic INRs at the beginning of antimicrobial dosing had their warfarin doses reduced or held by a more aggressive algorithm based on their initial INR, and based on the potential of the antimicrobial to increase INR.

On discharge, patients were either reverted to their previous warfarin regimen if they had been stable on that regimen, or had their inpatient warfarin dosing increased by 10%-20%.

Drugs that were deemed to have moderate potential to increase INR included doxycycline, levofloxacin, moxifloxacin, quinupristin/dalfopristin, telaprevir, boceprevir, and simeprevir. For these medications, the protocol recommended no initial dose adjustment, but recommended monitoring of INR to consider a dose reduction if needed. On hospital discharge, patients who had been on these medications were to resume their previous warfarin dosing.

Antimicrobials with potential to decrease INR included nafcillin, for which the protocol recommended empiric warfarin dose increases of 25%-50%, starting 3-5 days after nafcillin was begun. Patients on rifampin or rifabutin were to increase their warfarin by 20%-30%, also 3-5 days after beginning the antibiotics. Patients on ritonavir alone, or any protease inhibitor given for HIV along with ritonavir, were closely monitored, but no empiric dosing adjustments were made.

Patients with initial subtherapeutic INRs had dosing increased by 30%-50% for nafcillin and 20%-30% for rifampin and rifabutin. A stepped algorithm for dose adjustment or withholding was also developed for these medications to treat patients with initial supratherapeutic INRs. Patients on these medications were to resume their previous warfarin dosing, with monitoring and adjustment if they had not been previously stable.

Documentation of antimicrobial-warfarin DDI in the anticoagulation service discharge summary improved significantly once the guidelines were implemented (40% compared with 14%, P = .02). There was not a significant improvement in DDI documentation in daily progress notes.

The comprehensive intervention included the formulation of guidelines and requirements to document the medication interaction in the medical chart. Other interventions included training for clinical pharmacists and the development of pocket cards and flyers to educate team members about the new guidelines. The electronic health record had triggers built and implemented to prompt consideration of warfarin/antimicrobial DDIs as well.

Dr. Ha and his coauthors noted that the uncontrolled nature of the pre-post study design was one limitation of the study. Also, the real-world design of the study meant that investigators could not control for diet, comorbidities, and other factors that have the potential to affect INR. “Implementing a process to identify high-risk antimicrobial-warfarin DDIs and provide guidelines for empiric warfarin dose adjustment … can improve INR time within therapeutic range,” noted Dr. Ha and his coauthors.

The study authors reported no external sources of funding and no conflicts of interest.

[email protected]

On Twitter @karioakes

BOSTON – A medication management strategy to minimize the effect of drug-drug interactions (DDIs) between warfarin and common antimicrobials resulted in significantly greater time within therapeutic range for anticoagulation, as well as a numerically smaller, but nonsignificant, number of bleeding events.

After implementation of a comprehensive inpatient and postdischarge guideline to manage DDIs between warfarin and 16 antibiotics, antivirals, or antifungal medications, patients’ in-hospital time within therapeutic range (TWTR) increased to 72% from 50% preimplementation (P = .043). Warfarin TWTR also improved across care transitions after the guidelines were implemented, rising to 70% from 46% (P = .012). No bleeding events occurred in the group studied after the guidelines were instituted, compared with four events in the comparator preguidelines group (P = .11).

Nghi Ha, PharmD, MPH, and his collaborators sought to determine whether formalizing a process to manage potentially dangerous antimicrobial-warfarin DDIs made a difference in achieving more TWTR for patients, as determined by international normalized ratio (INR) values. Dr. Ha, a clinical pharmacist at University of Michigan Health System, Ann Arbor, presented the results during a poster session at the annual meeting of the American Society for Microbiology.

Secondary outcome measures studied by Dr. Ha and his associates included the incidence of thrombosis or major bleeding events, as well as tracking documentation of medications and the anticoagulation plan in progress and discharge notes.

Patients were included if they were at least 18 years old, and if they were on 3 days or more of an antimicrobial with potential for DDI with warfarin. Patients who were also newly on other medications with the potential for significant DDI with warfarin were excluded to minimize the potential for confounding.

Dr. Ha and his collaborators characterized the study as a retrospective, single-center, quasi-experimental design of a pharmacist-run anticoagulation service. The study examined endpoints before and after implementation of comprehensive guidelines, and included 78 preguideline and 31 postguideline patients.

The guidelines drafted by the investigators and tested in their study included empiric adjustment of warfarin dosing for patients who were placed on an antibiotic with high potential to increase INR. These included many azoles and sulfamethoxazole/trimethoprim, for which initial warfarin doses were empirically reduced 20%-30% for patients whose INRs were therapeutic at the start of antimicrobial therapy. For ciprofloxacin, erythromycin, clarithromycin, and isoniazid, the guidelines recommended initial empiric warfarin dose reductions of 10%-15%.

Patients whose INRs were subtherapeutic at the beginning of therapy and who received these antimicrobials were continued on their maintenance warfarin dosing, but were monitored for rising INRs over the first 48 hours, for consideration of dosing adjustment as needed. Individuals with supratherapeutic INRs at the beginning of antimicrobial dosing had their warfarin doses reduced or held by a more aggressive algorithm based on their initial INR, and based on the potential of the antimicrobial to increase INR.

On discharge, patients were either reverted to their previous warfarin regimen if they had been stable on that regimen, or had their inpatient warfarin dosing increased by 10%-20%.

Drugs that were deemed to have moderate potential to increase INR included doxycycline, levofloxacin, moxifloxacin, quinupristin/dalfopristin, telaprevir, boceprevir, and simeprevir. For these medications, the protocol recommended no initial dose adjustment, but recommended monitoring of INR to consider a dose reduction if needed. On hospital discharge, patients who had been on these medications were to resume their previous warfarin dosing.

Antimicrobials with potential to decrease INR included nafcillin, for which the protocol recommended empiric warfarin dose increases of 25%-50%, starting 3-5 days after nafcillin was begun. Patients on rifampin or rifabutin were to increase their warfarin by 20%-30%, also 3-5 days after beginning the antibiotics. Patients on ritonavir alone, or any protease inhibitor given for HIV along with ritonavir, were closely monitored, but no empiric dosing adjustments were made.

Patients with initial subtherapeutic INRs had dosing increased by 30%-50% for nafcillin and 20%-30% for rifampin and rifabutin. A stepped algorithm for dose adjustment or withholding was also developed for these medications to treat patients with initial supratherapeutic INRs. Patients on these medications were to resume their previous warfarin dosing, with monitoring and adjustment if they had not been previously stable.

Documentation of antimicrobial-warfarin DDI in the anticoagulation service discharge summary improved significantly once the guidelines were implemented (40% compared with 14%, P = .02). There was not a significant improvement in DDI documentation in daily progress notes.

The comprehensive intervention included the formulation of guidelines and requirements to document the medication interaction in the medical chart. Other interventions included training for clinical pharmacists and the development of pocket cards and flyers to educate team members about the new guidelines. The electronic health record had triggers built and implemented to prompt consideration of warfarin/antimicrobial DDIs as well.

Dr. Ha and his coauthors noted that the uncontrolled nature of the pre-post study design was one limitation of the study. Also, the real-world design of the study meant that investigators could not control for diet, comorbidities, and other factors that have the potential to affect INR. “Implementing a process to identify high-risk antimicrobial-warfarin DDIs and provide guidelines for empiric warfarin dose adjustment … can improve INR time within therapeutic range,” noted Dr. Ha and his coauthors.

The study authors reported no external sources of funding and no conflicts of interest.

[email protected]

On Twitter @karioakes

MINNEAPOLIS – Missed diagnoses, lack of care coordination, and security concerns were among the gaps in care that appeared when research personnel with simulated skin problems used direct-to-consumer (DTC) sites for telemedicine consults in a recently published study that highlighted potential drawbacks of this technology.

While telemedicine “has potential to expand access, and the medical literature is filled with examples of telehealth systems providing quality care,” the authors of the study concluded, their results “raise doubts about the quality of skin disease diagnosis and treatment being provided by a variety of DTC telemedicine websites and apps” (JAMA Dermatol. 2016;152[7]:768-775).

Karen Edison, MD, a dermatologist and telemedicine pioneer, shared results of the study that addressed the quality of DTC teledermatology, a rapidly growing market, at the annual meeting of the Society for Pediatric Dermatology. The DTC telemedicine care model provides direct patient access to providers through a web portal or app, without referrals from a primary physician or via insurance or managed care.

Dr. Edison, chair of the department of dermatology at the University of Missouri–Columbia, a study coauthor with over 20 years of teledermatology experience, said that she herself has recently begun seeing established patients live via video conferencing, with several successful “e-visit” experiences over the last several months.

In addition, she has about 3 years’ experience in“store-and-forward” teledermatology, where notes and relevant clinical images from an office visit are forwarded to a specialist, who then initiates a clinician-to-clinician consult to provide expertise in difficult cases or when resources are lacking. Live interactive and store-and-forward teledermatology have both been shown to be reliable for diagnosis and management, based on a “large body of evidence,” said Dr. Edison, citing a 2015 American Telemedicine Association statement.

However, the reliability of DTC care has been less well studied, she pointed out.

In an interview, Jack Resneck Jr., MD, the study’s lead author, agreed. “Physicians by our nature are innovators and will embrace new technologies whose quality and value are proven, but DTC telehealth isn’t there yet,” said Dr. Resneck, professor and vice-chair of dermatology, at the University of California, San Francisco.

To simulate a realistic patient experience and assess aspects of quality of care in DTC teledermatology, he, Dr. Edison, and their coinvestigators devised a study that had study personnel pose as patients to seek care for one of six skin conditions. They limited e-visits to websites or apps that offered services to California residents and excluded sites that required an interactive video visit, or that served patients insured by a particular insurance company or by a particular brick-and-mortar health care organization.

The “patients” initially submitted a universal history of present illness for a given condition, and had up to three photos available for submission. They also had supplemental medical history and review of systems information available that they would provide only if prompted by the provider.

A total of 16 telemedicine sites received a total of 62 submissions from the study personnel. Security issues arose almost immediately, Dr. Edison said at the meeting. “No site asked for photo ID or attempted to confirm identity,” and no site attempted to verify the authenticity of the submitted photos.

Twenty-seven of the providers were dermatologists, and an additional eight were internal medicine or family practice physicians. The remainder came from a variety of specialties. Six visits were conducted by seven nonphysician providers (three physician assistants from dermatology settings, and four nondermatology nurse practitioners).

When it came to the actual patient encounter, only one in three clinicians asked for a review of previous symptoms or a pertinent review of systems. “None asked relevant follow-up questions,” Dr. Edison said. Just under half of the providers asked female patients whether they could be pregnant or were lactating. Of the 14 encounters where pregnancy category C or higher drugs were prescribed, six providers (43%) discussed pregnancy risk.

For four of the simulated patient encounters, clinicians diagnosed a skin condition without asking for any photographs. No patients were referred for laboratory testing.

One of the cases was a 28-year-old woman who described a long history of inflammatory acne; the additional information, which no site requested, was that the patient also had hypertrichosis and irregular menses, as well as a mother with diabetes. This history would have led to a polycystic ovarian syndrome (PCOS) diagnosis, had it been elicited.

This was one of many such instances, and, in addition to PCOS, major diagnoses were missed, including secondary syphilis, eczema herpeticum, and gram-negative folliculitis.

Issues of transparency also arose: In two-thirds of the encounters, clinicians were assigned with no opportunity for patient input or choice. Licensure information was provided by about a quarter of providers overall. Of the U.S.-licensed physicians, just under half provided their board certification status. “Patient choice of their treating physician is part of our medical code of ethics, and we were surprised that these websites with multiple clinicians on staff assigned a clinician without patient choice in most encounters,” they added.

Telemedicine services provided the clinician’s geographic location in 61% of the encounters, and the investigators were able to identify the location of the clinician for 57 encounters. Of these, 35 were within the state of California, six were in India, and two were in Sweden; the rest were in other U.S. states. “Despite claims that they were not providing health care services, we believe that two DTC telemedicine websites headquartered in California but using foreign clinicians were engaged in the practice of medicine without a state license, as they clearly provided diagnoses and treatment recommendations,” they pointed out.

The geographic spread between patient and provider may have contributed to the lack of care coordination seen in the study, Dr. Resneck said in the interview, noting that most DTC providers “didn’t offer to send records to a patient’s existing local doctors.” When complications or follow-up care are needed, he added, “those distant clinicians often don’t have local contacts and are unable to facilitate needed appointments.”

In the study, the authors acknowledged a significant limitation of the study, their inability to “assess whether clinicians seeing these patients in traditional in-person encounters would have performed better on diagnostic accuracy.” However, they felt that their experience showed that the additional data that would have led to a correct diagnosis “typically emerge in the give-and-take of obtaining a history in the office setting.”

Telemedicine in all its forms can be expected to grow. At the meeting, Dr. Edison said that recently, the Stage 2 Meaningful Use requirement that at least 5% of a practice’s patients send a secure electronic message to their provider has been an impetus for increased adoption of teledermatology. And that can be a good thing. “Early access to our expertise saves patients from suffering, saves lives, and saves money,” she commented.

For Dr. Resneck, the early access should be part of the patient’s existing network of care, when possible, and he’s frustrated by the lack of continuity his study highlighted. “Many insurers are currently contracting with the fragmented DTC services we studied for their enrollees, while refusing to cover follow-up telehealth visits with a patient’s existing doctors, and that’s a problem,” he said.

Quality can’t be sacrificed for easy access, Dr. Edison agreed. “The same standard of care applies in teledermatology as in in-person health care,” she said.

Dr. Edison said that study personnel did not falsify their identities, and no prescriptions were actually filled. The visits were paid for by prepaid debit cards funded by the American Academy of Dermatology (study personnel claimed to be uninsured). Dr. Resneck serves on the board of the American Medical Association, and both Dr. Resneck and Dr. Edison serve on the AAD’s Telemedicine Task Force.

[email protected]

On Twitter @karioakes

MINNEAPOLIS – Missed diagnoses, lack of care coordination, and security concerns were among the gaps in care that appeared when research personnel with simulated skin problems used direct-to-consumer (DTC) sites for telemedicine consults in a recently published study that highlighted potential drawbacks of this technology.

While telemedicine “has potential to expand access, and the medical literature is filled with examples of telehealth systems providing quality care,” the authors of the study concluded, their results “raise doubts about the quality of skin disease diagnosis and treatment being provided by a variety of DTC telemedicine websites and apps” (JAMA Dermatol. 2016;152[7]:768-775).

Karen Edison, MD, a dermatologist and telemedicine pioneer, shared results of the study that addressed the quality of DTC teledermatology, a rapidly growing market, at the annual meeting of the Society for Pediatric Dermatology. The DTC telemedicine care model provides direct patient access to providers through a web portal or app, without referrals from a primary physician or via insurance or managed care.

Dr. Edison, chair of the department of dermatology at the University of Missouri–Columbia, a study coauthor with over 20 years of teledermatology experience, said that she herself has recently begun seeing established patients live via video conferencing, with several successful “e-visit” experiences over the last several months.

In addition, she has about 3 years’ experience in“store-and-forward” teledermatology, where notes and relevant clinical images from an office visit are forwarded to a specialist, who then initiates a clinician-to-clinician consult to provide expertise in difficult cases or when resources are lacking. Live interactive and store-and-forward teledermatology have both been shown to be reliable for diagnosis and management, based on a “large body of evidence,” said Dr. Edison, citing a 2015 American Telemedicine Association statement.

However, the reliability of DTC care has been less well studied, she pointed out.

In an interview, Jack Resneck Jr., MD, the study’s lead author, agreed. “Physicians by our nature are innovators and will embrace new technologies whose quality and value are proven, but DTC telehealth isn’t there yet,” said Dr. Resneck, professor and vice-chair of dermatology, at the University of California, San Francisco.

To simulate a realistic patient experience and assess aspects of quality of care in DTC teledermatology, he, Dr. Edison, and their coinvestigators devised a study that had study personnel pose as patients to seek care for one of six skin conditions. They limited e-visits to websites or apps that offered services to California residents and excluded sites that required an interactive video visit, or that served patients insured by a particular insurance company or by a particular brick-and-mortar health care organization.

The “patients” initially submitted a universal history of present illness for a given condition, and had up to three photos available for submission. They also had supplemental medical history and review of systems information available that they would provide only if prompted by the provider.

A total of 16 telemedicine sites received a total of 62 submissions from the study personnel. Security issues arose almost immediately, Dr. Edison said at the meeting. “No site asked for photo ID or attempted to confirm identity,” and no site attempted to verify the authenticity of the submitted photos.

Twenty-seven of the providers were dermatologists, and an additional eight were internal medicine or family practice physicians. The remainder came from a variety of specialties. Six visits were conducted by seven nonphysician providers (three physician assistants from dermatology settings, and four nondermatology nurse practitioners).

When it came to the actual patient encounter, only one in three clinicians asked for a review of previous symptoms or a pertinent review of systems. “None asked relevant follow-up questions,” Dr. Edison said. Just under half of the providers asked female patients whether they could be pregnant or were lactating. Of the 14 encounters where pregnancy category C or higher drugs were prescribed, six providers (43%) discussed pregnancy risk.

For four of the simulated patient encounters, clinicians diagnosed a skin condition without asking for any photographs. No patients were referred for laboratory testing.

One of the cases was a 28-year-old woman who described a long history of inflammatory acne; the additional information, which no site requested, was that the patient also had hypertrichosis and irregular menses, as well as a mother with diabetes. This history would have led to a polycystic ovarian syndrome (PCOS) diagnosis, had it been elicited.

This was one of many such instances, and, in addition to PCOS, major diagnoses were missed, including secondary syphilis, eczema herpeticum, and gram-negative folliculitis.

Issues of transparency also arose: In two-thirds of the encounters, clinicians were assigned with no opportunity for patient input or choice. Licensure information was provided by about a quarter of providers overall. Of the U.S.-licensed physicians, just under half provided their board certification status. “Patient choice of their treating physician is part of our medical code of ethics, and we were surprised that these websites with multiple clinicians on staff assigned a clinician without patient choice in most encounters,” they added.

Telemedicine services provided the clinician’s geographic location in 61% of the encounters, and the investigators were able to identify the location of the clinician for 57 encounters. Of these, 35 were within the state of California, six were in India, and two were in Sweden; the rest were in other U.S. states. “Despite claims that they were not providing health care services, we believe that two DTC telemedicine websites headquartered in California but using foreign clinicians were engaged in the practice of medicine without a state license, as they clearly provided diagnoses and treatment recommendations,” they pointed out.

The geographic spread between patient and provider may have contributed to the lack of care coordination seen in the study, Dr. Resneck said in the interview, noting that most DTC providers “didn’t offer to send records to a patient’s existing local doctors.” When complications or follow-up care are needed, he added, “those distant clinicians often don’t have local contacts and are unable to facilitate needed appointments.”

In the study, the authors acknowledged a significant limitation of the study, their inability to “assess whether clinicians seeing these patients in traditional in-person encounters would have performed better on diagnostic accuracy.” However, they felt that their experience showed that the additional data that would have led to a correct diagnosis “typically emerge in the give-and-take of obtaining a history in the office setting.”

Telemedicine in all its forms can be expected to grow. At the meeting, Dr. Edison said that recently, the Stage 2 Meaningful Use requirement that at least 5% of a practice’s patients send a secure electronic message to their provider has been an impetus for increased adoption of teledermatology. And that can be a good thing. “Early access to our expertise saves patients from suffering, saves lives, and saves money,” she commented.

For Dr. Resneck, the early access should be part of the patient’s existing network of care, when possible, and he’s frustrated by the lack of continuity his study highlighted. “Many insurers are currently contracting with the fragmented DTC services we studied for their enrollees, while refusing to cover follow-up telehealth visits with a patient’s existing doctors, and that’s a problem,” he said.

Quality can’t be sacrificed for easy access, Dr. Edison agreed. “The same standard of care applies in teledermatology as in in-person health care,” she said.

Dr. Edison said that study personnel did not falsify their identities, and no prescriptions were actually filled. The visits were paid for by prepaid debit cards funded by the American Academy of Dermatology (study personnel claimed to be uninsured). Dr. Resneck serves on the board of the American Medical Association, and both Dr. Resneck and Dr. Edison serve on the AAD’s Telemedicine Task Force.

[email protected]

On Twitter @karioakes

MINNEAPOLIS – Missed diagnoses, lack of care coordination, and security concerns were among the gaps in care that appeared when research personnel with simulated skin problems used direct-to-consumer (DTC) sites for telemedicine consults in a recently published study that highlighted potential drawbacks of this technology.

While telemedicine “has potential to expand access, and the medical literature is filled with examples of telehealth systems providing quality care,” the authors of the study concluded, their results “raise doubts about the quality of skin disease diagnosis and treatment being provided by a variety of DTC telemedicine websites and apps” (JAMA Dermatol. 2016;152[7]:768-775).

Karen Edison, MD, a dermatologist and telemedicine pioneer, shared results of the study that addressed the quality of DTC teledermatology, a rapidly growing market, at the annual meeting of the Society for Pediatric Dermatology. The DTC telemedicine care model provides direct patient access to providers through a web portal or app, without referrals from a primary physician or via insurance or managed care.

Dr. Edison, chair of the department of dermatology at the University of Missouri–Columbia, a study coauthor with over 20 years of teledermatology experience, said that she herself has recently begun seeing established patients live via video conferencing, with several successful “e-visit” experiences over the last several months.

In addition, she has about 3 years’ experience in“store-and-forward” teledermatology, where notes and relevant clinical images from an office visit are forwarded to a specialist, who then initiates a clinician-to-clinician consult to provide expertise in difficult cases or when resources are lacking. Live interactive and store-and-forward teledermatology have both been shown to be reliable for diagnosis and management, based on a “large body of evidence,” said Dr. Edison, citing a 2015 American Telemedicine Association statement.

However, the reliability of DTC care has been less well studied, she pointed out.

In an interview, Jack Resneck Jr., MD, the study’s lead author, agreed. “Physicians by our nature are innovators and will embrace new technologies whose quality and value are proven, but DTC telehealth isn’t there yet,” said Dr. Resneck, professor and vice-chair of dermatology, at the University of California, San Francisco.

To simulate a realistic patient experience and assess aspects of quality of care in DTC teledermatology, he, Dr. Edison, and their coinvestigators devised a study that had study personnel pose as patients to seek care for one of six skin conditions. They limited e-visits to websites or apps that offered services to California residents and excluded sites that required an interactive video visit, or that served patients insured by a particular insurance company or by a particular brick-and-mortar health care organization.

The “patients” initially submitted a universal history of present illness for a given condition, and had up to three photos available for submission. They also had supplemental medical history and review of systems information available that they would provide only if prompted by the provider.

A total of 16 telemedicine sites received a total of 62 submissions from the study personnel. Security issues arose almost immediately, Dr. Edison said at the meeting. “No site asked for photo ID or attempted to confirm identity,” and no site attempted to verify the authenticity of the submitted photos.

Twenty-seven of the providers were dermatologists, and an additional eight were internal medicine or family practice physicians. The remainder came from a variety of specialties. Six visits were conducted by seven nonphysician providers (three physician assistants from dermatology settings, and four nondermatology nurse practitioners).

When it came to the actual patient encounter, only one in three clinicians asked for a review of previous symptoms or a pertinent review of systems. “None asked relevant follow-up questions,” Dr. Edison said. Just under half of the providers asked female patients whether they could be pregnant or were lactating. Of the 14 encounters where pregnancy category C or higher drugs were prescribed, six providers (43%) discussed pregnancy risk.

For four of the simulated patient encounters, clinicians diagnosed a skin condition without asking for any photographs. No patients were referred for laboratory testing.

One of the cases was a 28-year-old woman who described a long history of inflammatory acne; the additional information, which no site requested, was that the patient also had hypertrichosis and irregular menses, as well as a mother with diabetes. This history would have led to a polycystic ovarian syndrome (PCOS) diagnosis, had it been elicited.

This was one of many such instances, and, in addition to PCOS, major diagnoses were missed, including secondary syphilis, eczema herpeticum, and gram-negative folliculitis.

Issues of transparency also arose: In two-thirds of the encounters, clinicians were assigned with no opportunity for patient input or choice. Licensure information was provided by about a quarter of providers overall. Of the U.S.-licensed physicians, just under half provided their board certification status. “Patient choice of their treating physician is part of our medical code of ethics, and we were surprised that these websites with multiple clinicians on staff assigned a clinician without patient choice in most encounters,” they added.

Telemedicine services provided the clinician’s geographic location in 61% of the encounters, and the investigators were able to identify the location of the clinician for 57 encounters. Of these, 35 were within the state of California, six were in India, and two were in Sweden; the rest were in other U.S. states. “Despite claims that they were not providing health care services, we believe that two DTC telemedicine websites headquartered in California but using foreign clinicians were engaged in the practice of medicine without a state license, as they clearly provided diagnoses and treatment recommendations,” they pointed out.

The geographic spread between patient and provider may have contributed to the lack of care coordination seen in the study, Dr. Resneck said in the interview, noting that most DTC providers “didn’t offer to send records to a patient’s existing local doctors.” When complications or follow-up care are needed, he added, “those distant clinicians often don’t have local contacts and are unable to facilitate needed appointments.”

In the study, the authors acknowledged a significant limitation of the study, their inability to “assess whether clinicians seeing these patients in traditional in-person encounters would have performed better on diagnostic accuracy.” However, they felt that their experience showed that the additional data that would have led to a correct diagnosis “typically emerge in the give-and-take of obtaining a history in the office setting.”

Telemedicine in all its forms can be expected to grow. At the meeting, Dr. Edison said that recently, the Stage 2 Meaningful Use requirement that at least 5% of a practice’s patients send a secure electronic message to their provider has been an impetus for increased adoption of teledermatology. And that can be a good thing. “Early access to our expertise saves patients from suffering, saves lives, and saves money,” she commented.

For Dr. Resneck, the early access should be part of the patient’s existing network of care, when possible, and he’s frustrated by the lack of continuity his study highlighted. “Many insurers are currently contracting with the fragmented DTC services we studied for their enrollees, while refusing to cover follow-up telehealth visits with a patient’s existing doctors, and that’s a problem,” he said.

Quality can’t be sacrificed for easy access, Dr. Edison agreed. “The same standard of care applies in teledermatology as in in-person health care,” she said.

Dr. Edison said that study personnel did not falsify their identities, and no prescriptions were actually filled. The visits were paid for by prepaid debit cards funded by the American Academy of Dermatology (study personnel claimed to be uninsured). Dr. Resneck serves on the board of the American Medical Association, and both Dr. Resneck and Dr. Edison serve on the AAD’s Telemedicine Task Force.

[email protected]

On Twitter @karioakes

FROM AN FDA ADVISORY PANEL MEETING

The majority of attendees at a joint meeting of two Food and Drug Administration advisory committees voted Sept. 14 to eliminate the black box warning about neuropsychiatric risks for the smoking cessation drug varenicline.

Panelists weighed the need for greater adoption of effective smoking cessation interventions against the possibility that varenicline (Chantix) might increase the risk of such serious adverse events (AEs) as aggression and suicidal behavior. In assessing findings of a clinical trial designed to sort out neuropsychiatric risk, they also had to wade through differing interpretations of the clinical trial data presented by the drug’s sponsor and the FDA.

Members of the Psychopharmacologic Drugs Advisory and the Drug Safety and Risk Management committees heard Chantix’s sponsor, Pfizer, present results of the postmarketing EAGLES trial. The global multisite trial compared varenicline with bupropion, also approved for smoking cessation, as well as with nicotine replacement therapy and placebo.

Of the 19 voting advisory committee members, 10 voted in favor of eliminating the boxed warning, while 4 members voted for a modification of the existing boxed warning, and 5 voted to retain the warning. The vote represents a reversal for the committees. In 2014, the joint panels recommended retaining the black box warning on the drug. The FDA usually follows the recommendations of its advisory panels, but the recommendations are not binding.

The boxed warning, which advises prescribers of the potential for “serious neuropsychiatric events,” arose from individual postmarketing reports of agitation, hostility, depressed mood, and suicidal ideation and behavior. Though postmarketing observational studies had not shown a consistent signal for increased risk of neuropsychiatric events, a plausible psychopharmacologic mechanism existed for the reports, and a clinical trial examining neuropsychiatric safety was designed to settle the question.

The primary objectives of EAGLES were to assess the risk of “clinically significant” AEs for individuals using varenicline, bupropion, nicotine replacement, or placebo, and to determine whether a past history of psychiatric disorders increased the risk of neuropsychiatric AEs when either prescription medication was used for smoking cessation.

A total of 8,000 patients were randomized 1:1:1:1 to receive varenicline, bupropion, nicotine replacement via patch, or placebo. The double blind, triple dummy design meant that all patients took pills and applied a patch daily. Each study arm was evenly divided so that half of the participants had a prior psychiatric diagnosis of a mood, anxiety, psychotic, or personality disorder. Overall, 70.7% of the psychiatric cohort had a mood disorder, and just under half were receiving a psychotropic medication at baseline.

The other half of patients in each study arm had no current or past psychiatric diagnoses. Approximately 80% of participants completed the trial overall.

The FDA and Pfizer worked together to develop a composite neuropsychiatric safety endpoint that broadly included the postmarketing AEs that had been reported for varenicline. The composite was designed to increase sensitivity, but only “moderate” or “severe” events were included in the analysis to increase specificity by minimizing inclusion of symptoms that might be attributable to nicotine withdrawal.

Results were similar across treatment arms for the primary composite endpoint, with higher incidence of events for the psychiatric cohort regardless of treatment, according to Pfizer’s analysis of the data. Since the study was not designed with a specific hypothesis, the results were not expressed in terms of statistical significance, but rather in risk differences with accompanying confidence intervals (CIs). The confidence interval crossed zero for all study drugs (including nicotine), except when varenicline was compared with placebo in the nonpsychiatric cohort (risk difference, 1.28; 95% CI, –2.40 to –0.15).

Overall, Pfizer found that about 2% of smokers without mental illness experienced neuropsychiatric AEs, compared with 5%-7% in the psychiatric cohort, regardless of treatment arm.

The FDA also found a small decrease in AEs for varenicline when compared with placebo in those without mental illness, and a higher incidence of neuropsychiatric events for those patients with mental illness who took varenicline and bupropion than those on placebo. In the FDA’s analysis, 6.5% of those on varenicline and 6.7% of those on bupropion met the primary composite AE endpoint. However, the FDA found that severe neuropsychiatric events and scoring on the Columbia Suicide Severity Rating Scale (C-SSRS), though lower for participants without mental illness, were similar across treatment arms in both cohorts.

Reporting problems also complicated the panel’s task. As the FDA conceived it, said Celia Winchell, MD, each AE was to be accompanied by a narrative that captured not just test scores and coded clinician assessments, but also the verbatim patient report and any other relevant data, such as the police report of a traffic accident, or family members’ appraisals of the event. Instead, she said, many of the reports appeared to have been automatically generated and were lacking in detail. Compared with other studies she’s reviewed, “The quality of the narratives that were submitted were unusually uninformative,” said Dr. Winchell, clinical team leader in the FDA’s Division of Anesthesia, Analgesia, and Addiction Products (DAAAP).

Clinical trials were run at 139 sites in 16 countries, treating a total of 8,058 patients. Despite Pfizer’s extensive efforts to standardize adverse event categorization and reporting, the FDA and some panelists remained concerned that language difficulty and cultural variation in interpreting neuropsychiatric symptoms may have resulted in miscategorization or underreporting of such events. In addition, Pfizer’s own surveillance revealed data reporting problems at two overseas sites that resulted in those sites’ data being eliminated from analysis.

All of the trial data, together with a review of several observational studies, had to be weighed against the individual and public health risks of smoking. Individuals with serious mental illness are significantly more likely to smoke heavily and to relapse after quitting compared with the general population. Yet, those individuals are less likely to be prescribed medication to help stop smoking, Anne Eden Evins, MD, director of the Center for Addiction Medicine at Massachusetts General Hospital, Boston, said in her testimony on Pfizer’s behalf.

“The implication of EAGLES is that we can offer treatment to all smokers, including those with stable mental illness,” she said. “It is imperative we find ways to increase use of the most effective smoking cessation treatment for our patients who try time and again to quit smoking.”

Many committee members agreed, providing anecdotal evidence that the current boxed warning deters both prescribers and patients from considering varenicline for smoking cessation in patients with mental illness.

For David Pickar, MD, who voted to remove the warning, the decision was easy. “I have no ambivalence, whatsoever,” he said. “The risk-benefit ratio to me is as clear as anything I have seen. I have never, ever, ever seen a schizophrenia patient on this drug,” said Dr. Pickar, a psychiatrist affiliated with the Uniformed Services University of the Health Sciences, Bethesda, Md.

However, many panelists were disturbed by the variability seen between sites during the clinical trials and by the lack of depth in Pfizer’s adverse events reporting. Said Rajesh Narendran, MD, professor of radiology and psychiatry at the University of Pittsburgh: “I don’t think the trial was conducted with the same cleanliness and elegance” of a trial for a new drug application. “I wasn’t fully reassured, and I think that removing the black box does send the wrong message that this is now a safe drug,” he said.

Although the joint committees’ chair, Ruth Murphey Parker, MD, voted for modification of the boxed warning, she agreed. “I also felt that removal of the black box would be a signal for safety,” she said.

Others who voted for modification felt that prescribers should talk to their patients about risks and benefits. Said Christianne Roumie, MD, professor of internal medicine and pediatrics at Vanderbilt University, Nashville, Tenn., and a staff physician at Veterans Affairs Tennessee Valley Healthcare System, also in Nashville: “As a clinician, I always have the discussion. This should be a conversation and not ... carte blanche.”

[email protected]

On Twitter @karioakes

FROM AN FDA ADVISORY PANEL MEETING

The majority of attendees at a joint meeting of two Food and Drug Administration advisory committees voted Sept. 14 to eliminate the black box warning about neuropsychiatric risks for the smoking cessation drug varenicline.

Panelists weighed the need for greater adoption of effective smoking cessation interventions against the possibility that varenicline (Chantix) might increase the risk of such serious adverse events (AEs) as aggression and suicidal behavior. In assessing findings of a clinical trial designed to sort out neuropsychiatric risk, they also had to wade through differing interpretations of the clinical trial data presented by the drug’s sponsor and the FDA.

Members of the Psychopharmacologic Drugs Advisory and the Drug Safety and Risk Management committees heard Chantix’s sponsor, Pfizer, present results of the postmarketing EAGLES trial. The global multisite trial compared varenicline with bupropion, also approved for smoking cessation, as well as with nicotine replacement therapy and placebo.

Of the 19 voting advisory committee members, 10 voted in favor of eliminating the boxed warning, while 4 members voted for a modification of the existing boxed warning, and 5 voted to retain the warning. The vote represents a reversal for the committees. In 2014, the joint panels recommended retaining the black box warning on the drug. The FDA usually follows the recommendations of its advisory panels, but the recommendations are not binding.

The boxed warning, which advises prescribers of the potential for “serious neuropsychiatric events,” arose from individual postmarketing reports of agitation, hostility, depressed mood, and suicidal ideation and behavior. Though postmarketing observational studies had not shown a consistent signal for increased risk of neuropsychiatric events, a plausible psychopharmacologic mechanism existed for the reports, and a clinical trial examining neuropsychiatric safety was designed to settle the question.

The primary objectives of EAGLES were to assess the risk of “clinically significant” AEs for individuals using varenicline, bupropion, nicotine replacement, or placebo, and to determine whether a past history of psychiatric disorders increased the risk of neuropsychiatric AEs when either prescription medication was used for smoking cessation.

A total of 8,000 patients were randomized 1:1:1:1 to receive varenicline, bupropion, nicotine replacement via patch, or placebo. The double blind, triple dummy design meant that all patients took pills and applied a patch daily. Each study arm was evenly divided so that half of the participants had a prior psychiatric diagnosis of a mood, anxiety, psychotic, or personality disorder. Overall, 70.7% of the psychiatric cohort had a mood disorder, and just under half were receiving a psychotropic medication at baseline.

The other half of patients in each study arm had no current or past psychiatric diagnoses. Approximately 80% of participants completed the trial overall.

The FDA and Pfizer worked together to develop a composite neuropsychiatric safety endpoint that broadly included the postmarketing AEs that had been reported for varenicline. The composite was designed to increase sensitivity, but only “moderate” or “severe” events were included in the analysis to increase specificity by minimizing inclusion of symptoms that might be attributable to nicotine withdrawal.

Results were similar across treatment arms for the primary composite endpoint, with higher incidence of events for the psychiatric cohort regardless of treatment, according to Pfizer’s analysis of the data. Since the study was not designed with a specific hypothesis, the results were not expressed in terms of statistical significance, but rather in risk differences with accompanying confidence intervals (CIs). The confidence interval crossed zero for all study drugs (including nicotine), except when varenicline was compared with placebo in the nonpsychiatric cohort (risk difference, 1.28; 95% CI, –2.40 to –0.15).

Overall, Pfizer found that about 2% of smokers without mental illness experienced neuropsychiatric AEs, compared with 5%-7% in the psychiatric cohort, regardless of treatment arm.

The FDA also found a small decrease in AEs for varenicline when compared with placebo in those without mental illness, and a higher incidence of neuropsychiatric events for those patients with mental illness who took varenicline and bupropion than those on placebo. In the FDA’s analysis, 6.5% of those on varenicline and 6.7% of those on bupropion met the primary composite AE endpoint. However, the FDA found that severe neuropsychiatric events and scoring on the Columbia Suicide Severity Rating Scale (C-SSRS), though lower for participants without mental illness, were similar across treatment arms in both cohorts.

Reporting problems also complicated the panel’s task. As the FDA conceived it, said Celia Winchell, MD, each AE was to be accompanied by a narrative that captured not just test scores and coded clinician assessments, but also the verbatim patient report and any other relevant data, such as the police report of a traffic accident, or family members’ appraisals of the event. Instead, she said, many of the reports appeared to have been automatically generated and were lacking in detail. Compared with other studies she’s reviewed, “The quality of the narratives that were submitted were unusually uninformative,” said Dr. Winchell, clinical team leader in the FDA’s Division of Anesthesia, Analgesia, and Addiction Products (DAAAP).

Clinical trials were run at 139 sites in 16 countries, treating a total of 8,058 patients. Despite Pfizer’s extensive efforts to standardize adverse event categorization and reporting, the FDA and some panelists remained concerned that language difficulty and cultural variation in interpreting neuropsychiatric symptoms may have resulted in miscategorization or underreporting of such events. In addition, Pfizer’s own surveillance revealed data reporting problems at two overseas sites that resulted in those sites’ data being eliminated from analysis.

All of the trial data, together with a review of several observational studies, had to be weighed against the individual and public health risks of smoking. Individuals with serious mental illness are significantly more likely to smoke heavily and to relapse after quitting compared with the general population. Yet, those individuals are less likely to be prescribed medication to help stop smoking, Anne Eden Evins, MD, director of the Center for Addiction Medicine at Massachusetts General Hospital, Boston, said in her testimony on Pfizer’s behalf.

“The implication of EAGLES is that we can offer treatment to all smokers, including those with stable mental illness,” she said. “It is imperative we find ways to increase use of the most effective smoking cessation treatment for our patients who try time and again to quit smoking.”

Many committee members agreed, providing anecdotal evidence that the current boxed warning deters both prescribers and patients from considering varenicline for smoking cessation in patients with mental illness.

For David Pickar, MD, who voted to remove the warning, the decision was easy. “I have no ambivalence, whatsoever,” he said. “The risk-benefit ratio to me is as clear as anything I have seen. I have never, ever, ever seen a schizophrenia patient on this drug,” said Dr. Pickar, a psychiatrist affiliated with the Uniformed Services University of the Health Sciences, Bethesda, Md.

However, many panelists were disturbed by the variability seen between sites during the clinical trials and by the lack of depth in Pfizer’s adverse events reporting. Said Rajesh Narendran, MD, professor of radiology and psychiatry at the University of Pittsburgh: “I don’t think the trial was conducted with the same cleanliness and elegance” of a trial for a new drug application. “I wasn’t fully reassured, and I think that removing the black box does send the wrong message that this is now a safe drug,” he said.

Although the joint committees’ chair, Ruth Murphey Parker, MD, voted for modification of the boxed warning, she agreed. “I also felt that removal of the black box would be a signal for safety,” she said.

Others who voted for modification felt that prescribers should talk to their patients about risks and benefits. Said Christianne Roumie, MD, professor of internal medicine and pediatrics at Vanderbilt University, Nashville, Tenn., and a staff physician at Veterans Affairs Tennessee Valley Healthcare System, also in Nashville: “As a clinician, I always have the discussion. This should be a conversation and not ... carte blanche.”

[email protected]

On Twitter @karioakes

FROM AN FDA ADVISORY PANEL MEETING

The majority of attendees at a joint meeting of two Food and Drug Administration advisory committees voted Sept. 14 to eliminate the black box warning about neuropsychiatric risks for the smoking cessation drug varenicline.

Panelists weighed the need for greater adoption of effective smoking cessation interventions against the possibility that varenicline (Chantix) might increase the risk of such serious adverse events (AEs) as aggression and suicidal behavior. In assessing findings of a clinical trial designed to sort out neuropsychiatric risk, they also had to wade through differing interpretations of the clinical trial data presented by the drug’s sponsor and the FDA.

Members of the Psychopharmacologic Drugs Advisory and the Drug Safety and Risk Management committees heard Chantix’s sponsor, Pfizer, present results of the postmarketing EAGLES trial. The global multisite trial compared varenicline with bupropion, also approved for smoking cessation, as well as with nicotine replacement therapy and placebo.

Of the 19 voting advisory committee members, 10 voted in favor of eliminating the boxed warning, while 4 members voted for a modification of the existing boxed warning, and 5 voted to retain the warning. The vote represents a reversal for the committees. In 2014, the joint panels recommended retaining the black box warning on the drug. The FDA usually follows the recommendations of its advisory panels, but the recommendations are not binding.

The boxed warning, which advises prescribers of the potential for “serious neuropsychiatric events,” arose from individual postmarketing reports of agitation, hostility, depressed mood, and suicidal ideation and behavior. Though postmarketing observational studies had not shown a consistent signal for increased risk of neuropsychiatric events, a plausible psychopharmacologic mechanism existed for the reports, and a clinical trial examining neuropsychiatric safety was designed to settle the question.

The primary objectives of EAGLES were to assess the risk of “clinically significant” AEs for individuals using varenicline, bupropion, nicotine replacement, or placebo, and to determine whether a past history of psychiatric disorders increased the risk of neuropsychiatric AEs when either prescription medication was used for smoking cessation.

A total of 8,000 patients were randomized 1:1:1:1 to receive varenicline, bupropion, nicotine replacement via patch, or placebo. The double blind, triple dummy design meant that all patients took pills and applied a patch daily. Each study arm was evenly divided so that half of the participants had a prior psychiatric diagnosis of a mood, anxiety, psychotic, or personality disorder. Overall, 70.7% of the psychiatric cohort had a mood disorder, and just under half were receiving a psychotropic medication at baseline.

The other half of patients in each study arm had no current or past psychiatric diagnoses. Approximately 80% of participants completed the trial overall.

The FDA and Pfizer worked together to develop a composite neuropsychiatric safety endpoint that broadly included the postmarketing AEs that had been reported for varenicline. The composite was designed to increase sensitivity, but only “moderate” or “severe” events were included in the analysis to increase specificity by minimizing inclusion of symptoms that might be attributable to nicotine withdrawal.

Results were similar across treatment arms for the primary composite endpoint, with higher incidence of events for the psychiatric cohort regardless of treatment, according to Pfizer’s analysis of the data. Since the study was not designed with a specific hypothesis, the results were not expressed in terms of statistical significance, but rather in risk differences with accompanying confidence intervals (CIs). The confidence interval crossed zero for all study drugs (including nicotine), except when varenicline was compared with placebo in the nonpsychiatric cohort (risk difference, 1.28; 95% CI, –2.40 to –0.15).

Overall, Pfizer found that about 2% of smokers without mental illness experienced neuropsychiatric AEs, compared with 5%-7% in the psychiatric cohort, regardless of treatment arm.

The FDA also found a small decrease in AEs for varenicline when compared with placebo in those without mental illness, and a higher incidence of neuropsychiatric events for those patients with mental illness who took varenicline and bupropion than those on placebo. In the FDA’s analysis, 6.5% of those on varenicline and 6.7% of those on bupropion met the primary composite AE endpoint. However, the FDA found that severe neuropsychiatric events and scoring on the Columbia Suicide Severity Rating Scale (C-SSRS), though lower for participants without mental illness, were similar across treatment arms in both cohorts.

Reporting problems also complicated the panel’s task. As the FDA conceived it, said Celia Winchell, MD, each AE was to be accompanied by a narrative that captured not just test scores and coded clinician assessments, but also the verbatim patient report and any other relevant data, such as the police report of a traffic accident, or family members’ appraisals of the event. Instead, she said, many of the reports appeared to have been automatically generated and were lacking in detail. Compared with other studies she’s reviewed, “The quality of the narratives that were submitted were unusually uninformative,” said Dr. Winchell, clinical team leader in the FDA’s Division of Anesthesia, Analgesia, and Addiction Products (DAAAP).

Clinical trials were run at 139 sites in 16 countries, treating a total of 8,058 patients. Despite Pfizer’s extensive efforts to standardize adverse event categorization and reporting, the FDA and some panelists remained concerned that language difficulty and cultural variation in interpreting neuropsychiatric symptoms may have resulted in miscategorization or underreporting of such events. In addition, Pfizer’s own surveillance revealed data reporting problems at two overseas sites that resulted in those sites’ data being eliminated from analysis.

All of the trial data, together with a review of several observational studies, had to be weighed against the individual and public health risks of smoking. Individuals with serious mental illness are significantly more likely to smoke heavily and to relapse after quitting compared with the general population. Yet, those individuals are less likely to be prescribed medication to help stop smoking, Anne Eden Evins, MD, director of the Center for Addiction Medicine at Massachusetts General Hospital, Boston, said in her testimony on Pfizer’s behalf.

“The implication of EAGLES is that we can offer treatment to all smokers, including those with stable mental illness,” she said. “It is imperative we find ways to increase use of the most effective smoking cessation treatment for our patients who try time and again to quit smoking.”

Many committee members agreed, providing anecdotal evidence that the current boxed warning deters both prescribers and patients from considering varenicline for smoking cessation in patients with mental illness.

For David Pickar, MD, who voted to remove the warning, the decision was easy. “I have no ambivalence, whatsoever,” he said. “The risk-benefit ratio to me is as clear as anything I have seen. I have never, ever, ever seen a schizophrenia patient on this drug,” said Dr. Pickar, a psychiatrist affiliated with the Uniformed Services University of the Health Sciences, Bethesda, Md.

However, many panelists were disturbed by the variability seen between sites during the clinical trials and by the lack of depth in Pfizer’s adverse events reporting. Said Rajesh Narendran, MD, professor of radiology and psychiatry at the University of Pittsburgh: “I don’t think the trial was conducted with the same cleanliness and elegance” of a trial for a new drug application. “I wasn’t fully reassured, and I think that removing the black box does send the wrong message that this is now a safe drug,” he said.

Although the joint committees’ chair, Ruth Murphey Parker, MD, voted for modification of the boxed warning, she agreed. “I also felt that removal of the black box would be a signal for safety,” she said.

Others who voted for modification felt that prescribers should talk to their patients about risks and benefits. Said Christianne Roumie, MD, professor of internal medicine and pediatrics at Vanderbilt University, Nashville, Tenn., and a staff physician at Veterans Affairs Tennessee Valley Healthcare System, also in Nashville: “As a clinician, I always have the discussion. This should be a conversation and not ... carte blanche.”

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