Kari Oakes

CHICAGO – A large Danish registry-based study has confirmed an increased risk of acute pancreatitis for patients taking certain antithyroid drugs.

After 6 months of methimazole use, the odds ratio for acute pancreatitis was 2.02, with a nonsignificant risk elevation for propylthiouracil use after a similar duration, Laszlo Hegedüs, MD, reported at the annual meeting of the American Thyroid Association.

“Ongoing methimazole, but not propylthiouracil, use is associated with an increased risk of acute pancreatitis,” he said.

Dr. Hegedüs, professor of endocrinology and metabolism at the University of Odense (Denmark), said that the European Medicines Association has noted postmarketing reports of acute pancreatitis in patients who received the antithyroid drug methimazole, as well as its prodrug, carbimazole. The agency has accordingly contraindicated antithyroid drug use for patients who previously experienced acute pancreatitis after receiving one of these drugs, advising that methimazole should be “discontinued immediately” should a patient develop acute pancreatitis.

However, investigation of the antithyroid drug–pancreatitis association had been limited to aggregating those case reports, so Dr. Hegedüs and colleagues decided to use Danish medical record and registry data to investigate the association in a nationwide, controlled study that looked at both duration of therapy and total antithyroid drug use.

During the period from 1995-2018, a total of 118,649 patients who used antithyroid drugs were found in the 5.5 million individuals in the Statistics Denmark registry. Dr. Hegedüs and his colleagues also pulled in patient registry and national prescription registry data, as well as civil vital statistics data.

Of those who used antithyroid drugs, 103,825 patients used methimazole, and 14,824 used propylthiouracil. The researchers found 43,580 instances of hospitalization for first-time acute pancreatitis in the pooled antithyroid drug data. Of those, however, just 226 (0.5%) occurred in patients using methimazole, and 19 (0.04%) in those using propylthiouracil at the time of pancreatitis onset.

To ascertain the risk of acute pancreatitis in patients using antithyroid drugs for various durations, Dr. Hegedüs and his colleagues used a case-crossover study design. In the case-crossover technique, patients served as their own controls, because each patient was both exposed and not exposed to antithyroid drugs at some point during the study period. Antithyroid drugs are well suited to this study design, explained Dr. Hegedüs, because they are given for a limited time. A case-crossover design can be used with a small sample size and effectively controls for potentially confounding variables.

The odds ratio for acute pancreatitis in methimazole users after 3 months of exposure was 1.51, with a 95% confidence interval of 1.12-2.02. After 3 months of propylthiouracil exposure, the odds ratio for acute pancreatitis was 1.16 (95% CI 0.46-2.3). At 6 months, the odds ratio of 2.02 for methimazole was similarly statistically significant (95% CI, 1.50-2.78), whereas the odds ratio of 1.40 for propylthiouracil use was not significant (95% CI, 0.58-3.34).

The researchers also wanted to find out whether the cumulative drug dose affected the risk of acute pancreatitis, so they drew from the antithyroid drug population to conduct a case-control study. Here, the investigators matched data from four control patients to each case of acute pancreatitis. The researchers also controlled for sex, age, comorbidities, and prior use of drugs associated with pancreatitis.

Overall, 20% of the 692 methimazole users and their controls were men, as were 16% of the 108 propylthiouracil users, in the case-control study.

Just more than half of patients overall had a total dose exposure of 200 to 1,200 defined daily dose (DDD) – a measure developed by the World Health Organization to denote the assumed average adult dose per day of a medication – with about a quarter of patients receiving a total antithyroid drug dose more than 1,200 DDD and about 20% receiving a dose exposure of less than 200 DDD. The risk of acute pancreatitis did not increase with increased total exposure to antithyroid drugs.

“There is no evidence of a cumulative dose effect of either methimazole or propylthiouracil on the risk of acute pancreatitis,” said Dr. Hegedüs. However, “the warning of the European Medicines Agency seems justified,” he added. “The frequency of acute pancreatitis in acute methimazole users is of a similar magnitude [to that] reported for agranulocytosis,” a known, dire complication of antithyroid drug use. Patients should be advised of the potential complication and informed of signs and symptoms of acute pancreatitis, he said.

Dr. Hegedüs noted that the study had the advantage of using validated epidemiologic methods to look at drug exposure and outcomes at a nationwide scale. However, the registries from which the data were drawn also have limitations. The investigators could not determine the severity of hyperthyroidism, he said, and the relatively rare occurrence of acute pancreatitis meant that there was not sufficient statistical power to look at the subgroup of individuals who had Grave’s disease and to compare them with those with nodular toxic goiter.

He advised conducting a confirmatory study in an independent cohort, as well as further investigating the yet unknown mechanism of action for the link between the antithyroid drug and acute pancreatitis.

Dr. Hegedüs reported that he had no relevant conflicts of interest and reported no outside sources of funding.

Help your patients understand the symptoms, treatments and complications of pancreatitis by sharing AGA patient education at https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.  

SOURCE: Hegedüs, L. et al. ATA 2019, Short Call Oral Abstract 6 .

CHICAGO – A large Danish registry-based study has confirmed an increased risk of acute pancreatitis for patients taking certain antithyroid drugs.

After 6 months of methimazole use, the odds ratio for acute pancreatitis was 2.02, with a nonsignificant risk elevation for propylthiouracil use after a similar duration, Laszlo Hegedüs, MD, reported at the annual meeting of the American Thyroid Association.

“Ongoing methimazole, but not propylthiouracil, use is associated with an increased risk of acute pancreatitis,” he said.

Dr. Hegedüs, professor of endocrinology and metabolism at the University of Odense (Denmark), said that the European Medicines Association has noted postmarketing reports of acute pancreatitis in patients who received the antithyroid drug methimazole, as well as its prodrug, carbimazole. The agency has accordingly contraindicated antithyroid drug use for patients who previously experienced acute pancreatitis after receiving one of these drugs, advising that methimazole should be “discontinued immediately” should a patient develop acute pancreatitis.

However, investigation of the antithyroid drug–pancreatitis association had been limited to aggregating those case reports, so Dr. Hegedüs and colleagues decided to use Danish medical record and registry data to investigate the association in a nationwide, controlled study that looked at both duration of therapy and total antithyroid drug use.

During the period from 1995-2018, a total of 118,649 patients who used antithyroid drugs were found in the 5.5 million individuals in the Statistics Denmark registry. Dr. Hegedüs and his colleagues also pulled in patient registry and national prescription registry data, as well as civil vital statistics data.

Of those who used antithyroid drugs, 103,825 patients used methimazole, and 14,824 used propylthiouracil. The researchers found 43,580 instances of hospitalization for first-time acute pancreatitis in the pooled antithyroid drug data. Of those, however, just 226 (0.5%) occurred in patients using methimazole, and 19 (0.04%) in those using propylthiouracil at the time of pancreatitis onset.

To ascertain the risk of acute pancreatitis in patients using antithyroid drugs for various durations, Dr. Hegedüs and his colleagues used a case-crossover study design. In the case-crossover technique, patients served as their own controls, because each patient was both exposed and not exposed to antithyroid drugs at some point during the study period. Antithyroid drugs are well suited to this study design, explained Dr. Hegedüs, because they are given for a limited time. A case-crossover design can be used with a small sample size and effectively controls for potentially confounding variables.

The odds ratio for acute pancreatitis in methimazole users after 3 months of exposure was 1.51, with a 95% confidence interval of 1.12-2.02. After 3 months of propylthiouracil exposure, the odds ratio for acute pancreatitis was 1.16 (95% CI 0.46-2.3). At 6 months, the odds ratio of 2.02 for methimazole was similarly statistically significant (95% CI, 1.50-2.78), whereas the odds ratio of 1.40 for propylthiouracil use was not significant (95% CI, 0.58-3.34).

The researchers also wanted to find out whether the cumulative drug dose affected the risk of acute pancreatitis, so they drew from the antithyroid drug population to conduct a case-control study. Here, the investigators matched data from four control patients to each case of acute pancreatitis. The researchers also controlled for sex, age, comorbidities, and prior use of drugs associated with pancreatitis.

Overall, 20% of the 692 methimazole users and their controls were men, as were 16% of the 108 propylthiouracil users, in the case-control study.

Just more than half of patients overall had a total dose exposure of 200 to 1,200 defined daily dose (DDD) – a measure developed by the World Health Organization to denote the assumed average adult dose per day of a medication – with about a quarter of patients receiving a total antithyroid drug dose more than 1,200 DDD and about 20% receiving a dose exposure of less than 200 DDD. The risk of acute pancreatitis did not increase with increased total exposure to antithyroid drugs.

“There is no evidence of a cumulative dose effect of either methimazole or propylthiouracil on the risk of acute pancreatitis,” said Dr. Hegedüs. However, “the warning of the European Medicines Agency seems justified,” he added. “The frequency of acute pancreatitis in acute methimazole users is of a similar magnitude [to that] reported for agranulocytosis,” a known, dire complication of antithyroid drug use. Patients should be advised of the potential complication and informed of signs and symptoms of acute pancreatitis, he said.

Dr. Hegedüs noted that the study had the advantage of using validated epidemiologic methods to look at drug exposure and outcomes at a nationwide scale. However, the registries from which the data were drawn also have limitations. The investigators could not determine the severity of hyperthyroidism, he said, and the relatively rare occurrence of acute pancreatitis meant that there was not sufficient statistical power to look at the subgroup of individuals who had Grave’s disease and to compare them with those with nodular toxic goiter.

He advised conducting a confirmatory study in an independent cohort, as well as further investigating the yet unknown mechanism of action for the link between the antithyroid drug and acute pancreatitis.

Dr. Hegedüs reported that he had no relevant conflicts of interest and reported no outside sources of funding.

Help your patients understand the symptoms, treatments and complications of pancreatitis by sharing AGA patient education at https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.  

SOURCE: Hegedüs, L. et al. ATA 2019, Short Call Oral Abstract 6 .

CHICAGO – A large Danish registry-based study has confirmed an increased risk of acute pancreatitis for patients taking certain antithyroid drugs.

After 6 months of methimazole use, the odds ratio for acute pancreatitis was 2.02, with a nonsignificant risk elevation for propylthiouracil use after a similar duration, Laszlo Hegedüs, MD, reported at the annual meeting of the American Thyroid Association.

“Ongoing methimazole, but not propylthiouracil, use is associated with an increased risk of acute pancreatitis,” he said.

Dr. Hegedüs, professor of endocrinology and metabolism at the University of Odense (Denmark), said that the European Medicines Association has noted postmarketing reports of acute pancreatitis in patients who received the antithyroid drug methimazole, as well as its prodrug, carbimazole. The agency has accordingly contraindicated antithyroid drug use for patients who previously experienced acute pancreatitis after receiving one of these drugs, advising that methimazole should be “discontinued immediately” should a patient develop acute pancreatitis.

However, investigation of the antithyroid drug–pancreatitis association had been limited to aggregating those case reports, so Dr. Hegedüs and colleagues decided to use Danish medical record and registry data to investigate the association in a nationwide, controlled study that looked at both duration of therapy and total antithyroid drug use.

During the period from 1995-2018, a total of 118,649 patients who used antithyroid drugs were found in the 5.5 million individuals in the Statistics Denmark registry. Dr. Hegedüs and his colleagues also pulled in patient registry and national prescription registry data, as well as civil vital statistics data.

Of those who used antithyroid drugs, 103,825 patients used methimazole, and 14,824 used propylthiouracil. The researchers found 43,580 instances of hospitalization for first-time acute pancreatitis in the pooled antithyroid drug data. Of those, however, just 226 (0.5%) occurred in patients using methimazole, and 19 (0.04%) in those using propylthiouracil at the time of pancreatitis onset.

To ascertain the risk of acute pancreatitis in patients using antithyroid drugs for various durations, Dr. Hegedüs and his colleagues used a case-crossover study design. In the case-crossover technique, patients served as their own controls, because each patient was both exposed and not exposed to antithyroid drugs at some point during the study period. Antithyroid drugs are well suited to this study design, explained Dr. Hegedüs, because they are given for a limited time. A case-crossover design can be used with a small sample size and effectively controls for potentially confounding variables.

The odds ratio for acute pancreatitis in methimazole users after 3 months of exposure was 1.51, with a 95% confidence interval of 1.12-2.02. After 3 months of propylthiouracil exposure, the odds ratio for acute pancreatitis was 1.16 (95% CI 0.46-2.3). At 6 months, the odds ratio of 2.02 for methimazole was similarly statistically significant (95% CI, 1.50-2.78), whereas the odds ratio of 1.40 for propylthiouracil use was not significant (95% CI, 0.58-3.34).

The researchers also wanted to find out whether the cumulative drug dose affected the risk of acute pancreatitis, so they drew from the antithyroid drug population to conduct a case-control study. Here, the investigators matched data from four control patients to each case of acute pancreatitis. The researchers also controlled for sex, age, comorbidities, and prior use of drugs associated with pancreatitis.

Overall, 20% of the 692 methimazole users and their controls were men, as were 16% of the 108 propylthiouracil users, in the case-control study.

Just more than half of patients overall had a total dose exposure of 200 to 1,200 defined daily dose (DDD) – a measure developed by the World Health Organization to denote the assumed average adult dose per day of a medication – with about a quarter of patients receiving a total antithyroid drug dose more than 1,200 DDD and about 20% receiving a dose exposure of less than 200 DDD. The risk of acute pancreatitis did not increase with increased total exposure to antithyroid drugs.

“There is no evidence of a cumulative dose effect of either methimazole or propylthiouracil on the risk of acute pancreatitis,” said Dr. Hegedüs. However, “the warning of the European Medicines Agency seems justified,” he added. “The frequency of acute pancreatitis in acute methimazole users is of a similar magnitude [to that] reported for agranulocytosis,” a known, dire complication of antithyroid drug use. Patients should be advised of the potential complication and informed of signs and symptoms of acute pancreatitis, he said.

Dr. Hegedüs noted that the study had the advantage of using validated epidemiologic methods to look at drug exposure and outcomes at a nationwide scale. However, the registries from which the data were drawn also have limitations. The investigators could not determine the severity of hyperthyroidism, he said, and the relatively rare occurrence of acute pancreatitis meant that there was not sufficient statistical power to look at the subgroup of individuals who had Grave’s disease and to compare them with those with nodular toxic goiter.

He advised conducting a confirmatory study in an independent cohort, as well as further investigating the yet unknown mechanism of action for the link between the antithyroid drug and acute pancreatitis.

Dr. Hegedüs reported that he had no relevant conflicts of interest and reported no outside sources of funding.

Help your patients understand the symptoms, treatments and complications of pancreatitis by sharing AGA patient education at https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.  

SOURCE: Hegedüs, L. et al. ATA 2019, Short Call Oral Abstract 6 .

CHICAGO – A gastroenterologist-founded tech firm is making big waves in digital health care as Rx.Health, a spinoff from Mount Sinai Hospitals, New York, partners with the American Gastroenterological Association and other professional societies to deliver health solutions to the palms of patients’ hands.

Kari Oakes/MDedge News

“I would make the argument that disruption doesn’t have to come from the West Coast. It can come from savvy East Coasters, as well as Midwesterners, as well as Southerners,” said Ashish Atreja, MD, MPH, chief innovation officer of medicine at Mount Sinai Hospitals, New York.

At his home institution, where Dr. Atreja also serves on the gastroenterology faculty at the Icahn School of Medicine, the discussion about digital health began as Mount Sinai experienced rapid expansion. “So that has been a learning ground for us – to say, ‘What is happening across different hospitals? How are we going to standardize care?’ ” he said, speaking at the AGA Partners in Value Meeting.

“We’re looking at digital health to do it,” and the digital initiative dovetails perfectly with the strong value-based health mission of Mount Sinai, he added. “We say that, if our hospital beds are filled, then we are failing,” although the institution’s biggest revenue stream is from inpatient care. “We really have to look beyond the four walls of the hospital to provide care.”

The digital innovation laboratory at Mount Sinai was set up about 6 years ago, making it one of the first such centers in the country. It took about a year to build a team that had the technical skills to build apps in house, but once the ball got rolling, “it has been a fascinating journey,” said Dr. Atreja.
 

Innovation doesn’t always mean adoption

When Dr. Atreja and his colleagues took apps that were powerful data collection tools and put them out for general patient use, “We only saw 6% adoption ... because the patients forgot the names. They mistyped the names. They got lost in 60,000 apps. They forgot the activation code.

“And even if they got all of this, 20% of patients didn’t have space in their smartphones anyway.”

That’s when Dr. Atreja and his collaborators realized they didn’t really have an innovation problem, but rather a transformation problem – they needed to change the existing digital patchwork into a clinically meaningful intervention.

At this turning point, the Mount Sinai digital innovation team realized physicians could use evidence-based apps “and actually prescribe them – much the same way that you prescribe medication. ... So this was our ‘aha’ moment 3 years ago,” said Dr. Atreja.

Now, at Mount Sinai, apps are integrated with the electronic health record and can be prescribed with a few clicks. With the integrated digital prescription platform, patient activation of the apps has increased to 92%, said Dr. Atreja.

Currently, about 25 projects using this integrated system are being initiated within the Mount Sinai health system, and 35-50 external projects are underway in association with Rx.Health, a spin-off of the Mount Sinai efforts. Dr. Atreja serves as chief strategy officer for Rx.Health.

In all, 22 health systems are using the app platform at present, which bundles many facets of digital health – health education, remote monitoring, telehealth, secure messaging, to name a few.

The unified platform, said Dr. Atreja, “allows all of us – clinicians, business drivers, tech, researchers – to become creators and digital practitioners.”
 

Case study: Colonoscopy

After a particularly discouraging day in the endoscopy suite in which six of seven patients had inadequate bowel preparation for colonoscopy, Dr. Atreja dug a little further into Mount Sinai’s endoscopy data. “I realized we were losing one million dollars a year because of no-shows and inadequate bowel preparation,” he said.

A higher success rate could be achieved with bowel preparation if enough staff time is dedicated to repeat phone calls, he conceded. “But you are spending $300,000 just on a brute force solution” of massive staff resources, he said.

In the Mount Sinai example, when all missed opportunities are considered, “you’re looking at 4 to 5 million dollars that we’re leaking because we are not able to engage patients at the right time.”

Gastrointestinal procedures are a major source for revenue leaks, he said. Patients may miss procedures or be late; up to 1 in 4 patients may have poor bowel preparation, and sometimes patients arrive without a plan for a ride home after a procedure that requires sedation.

Other care gaps include the 30%-70% of patients who don’t return at recommended screening intervals, and patients who have positive fecal immunohistochemical testing but don’t receive a colonoscopy. Some patients have colonoscopies ordered, but never scheduled, and still others are never offered any colorectal cancer surveillance testing at all.

It’s no wonder patients are confused, said Dr. Atreja, providing an example of one center’s colonoscopy preparation instructions for split-dose polyethylene glycol bowel preparation. Patients must closely follow a full page of bullet points to be completed at precise time intervals. “One in four patients actually loses the paper by the time they need it before the procedure,” he said. Another 40% don’t look at instructions until it’s too late to prepare adequately or to line up an escort to bring them home post procedure.

This scenario, he said, shows that “it’s not in the science of medicine, but in the practice of medicine, that we are failing. ... So how about we completely change the game and create a real-time digital navigation for the patient?”

The digital alternative to the slip of paper is a real-time patient navigation tool that guides patients through the entire colonoscopy preparation process. “Based on where the patient is at that point in time, and the procedure, and the bowel prep,” the app gives the patient timely and relevant information: what the procedure is like, why bowel preparation is important, and how preparation is correctly performed, explained Dr. Atreja.

A reminder to arrange an escort arrives on the patient’s phone a full 10 days before the procedure, with subsequent nudges. Patients even receive driving and parking directions. The day before the procedure, a last-minute query checks on transportation. “So we’re working with Uber to actually make an ... integration with Uber so they can pick up the patient if they have transportation issues.”

Post procedure, patients are asked about their experiences, and a plan for appropriate patient recall is integrated into the app as well. “The best part is, this has not been designed by anyone [other] than those in the health system. Because we already know the recommended guidelines, we know the best practices.” This, he said, is where the value of digital apps is truly created.

Early evidence gleaned from a dashboard that’s part of the digital health solution from one site using the app shows a 24% improvement in bowel preparation. Importantly, the rate of aborted procedures has been cut in half, and patient satisfaction rates are at 93%.
 

The endoscopy suite as digital transformation center

Now, in partnership with AGA, Dr. Atreja and his collaborators are planning a roll-out to multiple sites to see whether the savings and return on investment are replicated at other endoscopy sites. The vision expands beyond reducing revenue leaks to creating “digital transformation centers,” he said.

Digital health solutions such as this afford powerful opportunity for data collection, not only for practice optimization but also for research, said Dr. Atreja. He cited the example of endoscopic retrograde cholangiopancreatography, where procedural details could be linked to postprocedural admission rates in the service of fine-tuning one of the endoscopist’s greatest procedural challenges.

“You can create all of those clinical trial networks for devices right on the fly,” he said. In devising a clinical trial for an app-based intervention for anxiety – prevalent in those with irritable bowel disease – Dr. Atreja and his colleagues opened trial enrollment at 8 a.m., hoping to enroll 20 patients. By the end of the day, over 200 had enrolled. “We over-subscribed our trial by 10 times” in 1 day using the digital platform, he said.

Dr. Atreja is currently working with the American College of Cardiology on digital solutions for home monitoring of heart failure patients. “Partnerships with other health systems and societies are key for learning and rapid transformation – a rising tide lifts all boats,” said Dr. Atreja. “Digital medicine is not digital medicine. It is medicine. Because the practice of medicine is medicine.”

Dr. Atreja reported receiving funding from AbbVie, Janssen, Pfizer, Takeda, Astrazeneca, UCB, and Roche; the RxUniverse app has been licensed from the Icahn School of Medicine at Mount Sinai to Rx.Health.

AGA has partnered with RxHealth to support gastroenterologists’ ability to provide patient care and improve patient adherence by creating up-to-date, evidenced-based digital tools that can be prescribed at point of care. Dr. John I. Allen, the Editor in Chief of GI & Hepatology News, is on the advisory board of RxHealth and recused himself from review and approval of this story. Learn more about the program and how to become a pioneer site at https://rx.health/GI or [email protected] .

[email protected]

CHICAGO – A gastroenterologist-founded tech firm is making big waves in digital health care as Rx.Health, a spinoff from Mount Sinai Hospitals, New York, partners with the American Gastroenterological Association and other professional societies to deliver health solutions to the palms of patients’ hands.

Kari Oakes/MDedge News

“I would make the argument that disruption doesn’t have to come from the West Coast. It can come from savvy East Coasters, as well as Midwesterners, as well as Southerners,” said Ashish Atreja, MD, MPH, chief innovation officer of medicine at Mount Sinai Hospitals, New York.

At his home institution, where Dr. Atreja also serves on the gastroenterology faculty at the Icahn School of Medicine, the discussion about digital health began as Mount Sinai experienced rapid expansion. “So that has been a learning ground for us – to say, ‘What is happening across different hospitals? How are we going to standardize care?’ ” he said, speaking at the AGA Partners in Value Meeting.

“We’re looking at digital health to do it,” and the digital initiative dovetails perfectly with the strong value-based health mission of Mount Sinai, he added. “We say that, if our hospital beds are filled, then we are failing,” although the institution’s biggest revenue stream is from inpatient care. “We really have to look beyond the four walls of the hospital to provide care.”

The digital innovation laboratory at Mount Sinai was set up about 6 years ago, making it one of the first such centers in the country. It took about a year to build a team that had the technical skills to build apps in house, but once the ball got rolling, “it has been a fascinating journey,” said Dr. Atreja.
 

Innovation doesn’t always mean adoption

When Dr. Atreja and his colleagues took apps that were powerful data collection tools and put them out for general patient use, “We only saw 6% adoption ... because the patients forgot the names. They mistyped the names. They got lost in 60,000 apps. They forgot the activation code.

“And even if they got all of this, 20% of patients didn’t have space in their smartphones anyway.”

That’s when Dr. Atreja and his collaborators realized they didn’t really have an innovation problem, but rather a transformation problem – they needed to change the existing digital patchwork into a clinically meaningful intervention.

At this turning point, the Mount Sinai digital innovation team realized physicians could use evidence-based apps “and actually prescribe them – much the same way that you prescribe medication. ... So this was our ‘aha’ moment 3 years ago,” said Dr. Atreja.

Now, at Mount Sinai, apps are integrated with the electronic health record and can be prescribed with a few clicks. With the integrated digital prescription platform, patient activation of the apps has increased to 92%, said Dr. Atreja.

Currently, about 25 projects using this integrated system are being initiated within the Mount Sinai health system, and 35-50 external projects are underway in association with Rx.Health, a spin-off of the Mount Sinai efforts. Dr. Atreja serves as chief strategy officer for Rx.Health.

In all, 22 health systems are using the app platform at present, which bundles many facets of digital health – health education, remote monitoring, telehealth, secure messaging, to name a few.

The unified platform, said Dr. Atreja, “allows all of us – clinicians, business drivers, tech, researchers – to become creators and digital practitioners.”
 

Case study: Colonoscopy

After a particularly discouraging day in the endoscopy suite in which six of seven patients had inadequate bowel preparation for colonoscopy, Dr. Atreja dug a little further into Mount Sinai’s endoscopy data. “I realized we were losing one million dollars a year because of no-shows and inadequate bowel preparation,” he said.

A higher success rate could be achieved with bowel preparation if enough staff time is dedicated to repeat phone calls, he conceded. “But you are spending $300,000 just on a brute force solution” of massive staff resources, he said.

In the Mount Sinai example, when all missed opportunities are considered, “you’re looking at 4 to 5 million dollars that we’re leaking because we are not able to engage patients at the right time.”

Gastrointestinal procedures are a major source for revenue leaks, he said. Patients may miss procedures or be late; up to 1 in 4 patients may have poor bowel preparation, and sometimes patients arrive without a plan for a ride home after a procedure that requires sedation.

Other care gaps include the 30%-70% of patients who don’t return at recommended screening intervals, and patients who have positive fecal immunohistochemical testing but don’t receive a colonoscopy. Some patients have colonoscopies ordered, but never scheduled, and still others are never offered any colorectal cancer surveillance testing at all.

It’s no wonder patients are confused, said Dr. Atreja, providing an example of one center’s colonoscopy preparation instructions for split-dose polyethylene glycol bowel preparation. Patients must closely follow a full page of bullet points to be completed at precise time intervals. “One in four patients actually loses the paper by the time they need it before the procedure,” he said. Another 40% don’t look at instructions until it’s too late to prepare adequately or to line up an escort to bring them home post procedure.

This scenario, he said, shows that “it’s not in the science of medicine, but in the practice of medicine, that we are failing. ... So how about we completely change the game and create a real-time digital navigation for the patient?”

The digital alternative to the slip of paper is a real-time patient navigation tool that guides patients through the entire colonoscopy preparation process. “Based on where the patient is at that point in time, and the procedure, and the bowel prep,” the app gives the patient timely and relevant information: what the procedure is like, why bowel preparation is important, and how preparation is correctly performed, explained Dr. Atreja.

A reminder to arrange an escort arrives on the patient’s phone a full 10 days before the procedure, with subsequent nudges. Patients even receive driving and parking directions. The day before the procedure, a last-minute query checks on transportation. “So we’re working with Uber to actually make an ... integration with Uber so they can pick up the patient if they have transportation issues.”

Post procedure, patients are asked about their experiences, and a plan for appropriate patient recall is integrated into the app as well. “The best part is, this has not been designed by anyone [other] than those in the health system. Because we already know the recommended guidelines, we know the best practices.” This, he said, is where the value of digital apps is truly created.

Early evidence gleaned from a dashboard that’s part of the digital health solution from one site using the app shows a 24% improvement in bowel preparation. Importantly, the rate of aborted procedures has been cut in half, and patient satisfaction rates are at 93%.
 

The endoscopy suite as digital transformation center

Now, in partnership with AGA, Dr. Atreja and his collaborators are planning a roll-out to multiple sites to see whether the savings and return on investment are replicated at other endoscopy sites. The vision expands beyond reducing revenue leaks to creating “digital transformation centers,” he said.

Digital health solutions such as this afford powerful opportunity for data collection, not only for practice optimization but also for research, said Dr. Atreja. He cited the example of endoscopic retrograde cholangiopancreatography, where procedural details could be linked to postprocedural admission rates in the service of fine-tuning one of the endoscopist’s greatest procedural challenges.

“You can create all of those clinical trial networks for devices right on the fly,” he said. In devising a clinical trial for an app-based intervention for anxiety – prevalent in those with irritable bowel disease – Dr. Atreja and his colleagues opened trial enrollment at 8 a.m., hoping to enroll 20 patients. By the end of the day, over 200 had enrolled. “We over-subscribed our trial by 10 times” in 1 day using the digital platform, he said.

Dr. Atreja is currently working with the American College of Cardiology on digital solutions for home monitoring of heart failure patients. “Partnerships with other health systems and societies are key for learning and rapid transformation – a rising tide lifts all boats,” said Dr. Atreja. “Digital medicine is not digital medicine. It is medicine. Because the practice of medicine is medicine.”

Dr. Atreja reported receiving funding from AbbVie, Janssen, Pfizer, Takeda, Astrazeneca, UCB, and Roche; the RxUniverse app has been licensed from the Icahn School of Medicine at Mount Sinai to Rx.Health.

AGA has partnered with RxHealth to support gastroenterologists’ ability to provide patient care and improve patient adherence by creating up-to-date, evidenced-based digital tools that can be prescribed at point of care. Dr. John I. Allen, the Editor in Chief of GI & Hepatology News, is on the advisory board of RxHealth and recused himself from review and approval of this story. Learn more about the program and how to become a pioneer site at https://rx.health/GI or [email protected] .

[email protected]

CHICAGO – A gastroenterologist-founded tech firm is making big waves in digital health care as Rx.Health, a spinoff from Mount Sinai Hospitals, New York, partners with the American Gastroenterological Association and other professional societies to deliver health solutions to the palms of patients’ hands.

Kari Oakes/MDedge News

“I would make the argument that disruption doesn’t have to come from the West Coast. It can come from savvy East Coasters, as well as Midwesterners, as well as Southerners,” said Ashish Atreja, MD, MPH, chief innovation officer of medicine at Mount Sinai Hospitals, New York.

At his home institution, where Dr. Atreja also serves on the gastroenterology faculty at the Icahn School of Medicine, the discussion about digital health began as Mount Sinai experienced rapid expansion. “So that has been a learning ground for us – to say, ‘What is happening across different hospitals? How are we going to standardize care?’ ” he said, speaking at the AGA Partners in Value Meeting.

“We’re looking at digital health to do it,” and the digital initiative dovetails perfectly with the strong value-based health mission of Mount Sinai, he added. “We say that, if our hospital beds are filled, then we are failing,” although the institution’s biggest revenue stream is from inpatient care. “We really have to look beyond the four walls of the hospital to provide care.”

The digital innovation laboratory at Mount Sinai was set up about 6 years ago, making it one of the first such centers in the country. It took about a year to build a team that had the technical skills to build apps in house, but once the ball got rolling, “it has been a fascinating journey,” said Dr. Atreja.
 

Innovation doesn’t always mean adoption

When Dr. Atreja and his colleagues took apps that were powerful data collection tools and put them out for general patient use, “We only saw 6% adoption ... because the patients forgot the names. They mistyped the names. They got lost in 60,000 apps. They forgot the activation code.

“And even if they got all of this, 20% of patients didn’t have space in their smartphones anyway.”

That’s when Dr. Atreja and his collaborators realized they didn’t really have an innovation problem, but rather a transformation problem – they needed to change the existing digital patchwork into a clinically meaningful intervention.

At this turning point, the Mount Sinai digital innovation team realized physicians could use evidence-based apps “and actually prescribe them – much the same way that you prescribe medication. ... So this was our ‘aha’ moment 3 years ago,” said Dr. Atreja.

Now, at Mount Sinai, apps are integrated with the electronic health record and can be prescribed with a few clicks. With the integrated digital prescription platform, patient activation of the apps has increased to 92%, said Dr. Atreja.

Currently, about 25 projects using this integrated system are being initiated within the Mount Sinai health system, and 35-50 external projects are underway in association with Rx.Health, a spin-off of the Mount Sinai efforts. Dr. Atreja serves as chief strategy officer for Rx.Health.

In all, 22 health systems are using the app platform at present, which bundles many facets of digital health – health education, remote monitoring, telehealth, secure messaging, to name a few.

The unified platform, said Dr. Atreja, “allows all of us – clinicians, business drivers, tech, researchers – to become creators and digital practitioners.”
 

Case study: Colonoscopy

After a particularly discouraging day in the endoscopy suite in which six of seven patients had inadequate bowel preparation for colonoscopy, Dr. Atreja dug a little further into Mount Sinai’s endoscopy data. “I realized we were losing one million dollars a year because of no-shows and inadequate bowel preparation,” he said.

A higher success rate could be achieved with bowel preparation if enough staff time is dedicated to repeat phone calls, he conceded. “But you are spending $300,000 just on a brute force solution” of massive staff resources, he said.

In the Mount Sinai example, when all missed opportunities are considered, “you’re looking at 4 to 5 million dollars that we’re leaking because we are not able to engage patients at the right time.”

Gastrointestinal procedures are a major source for revenue leaks, he said. Patients may miss procedures or be late; up to 1 in 4 patients may have poor bowel preparation, and sometimes patients arrive without a plan for a ride home after a procedure that requires sedation.

Other care gaps include the 30%-70% of patients who don’t return at recommended screening intervals, and patients who have positive fecal immunohistochemical testing but don’t receive a colonoscopy. Some patients have colonoscopies ordered, but never scheduled, and still others are never offered any colorectal cancer surveillance testing at all.

It’s no wonder patients are confused, said Dr. Atreja, providing an example of one center’s colonoscopy preparation instructions for split-dose polyethylene glycol bowel preparation. Patients must closely follow a full page of bullet points to be completed at precise time intervals. “One in four patients actually loses the paper by the time they need it before the procedure,” he said. Another 40% don’t look at instructions until it’s too late to prepare adequately or to line up an escort to bring them home post procedure.

This scenario, he said, shows that “it’s not in the science of medicine, but in the practice of medicine, that we are failing. ... So how about we completely change the game and create a real-time digital navigation for the patient?”

The digital alternative to the slip of paper is a real-time patient navigation tool that guides patients through the entire colonoscopy preparation process. “Based on where the patient is at that point in time, and the procedure, and the bowel prep,” the app gives the patient timely and relevant information: what the procedure is like, why bowel preparation is important, and how preparation is correctly performed, explained Dr. Atreja.

A reminder to arrange an escort arrives on the patient’s phone a full 10 days before the procedure, with subsequent nudges. Patients even receive driving and parking directions. The day before the procedure, a last-minute query checks on transportation. “So we’re working with Uber to actually make an ... integration with Uber so they can pick up the patient if they have transportation issues.”

Post procedure, patients are asked about their experiences, and a plan for appropriate patient recall is integrated into the app as well. “The best part is, this has not been designed by anyone [other] than those in the health system. Because we already know the recommended guidelines, we know the best practices.” This, he said, is where the value of digital apps is truly created.

Early evidence gleaned from a dashboard that’s part of the digital health solution from one site using the app shows a 24% improvement in bowel preparation. Importantly, the rate of aborted procedures has been cut in half, and patient satisfaction rates are at 93%.
 

The endoscopy suite as digital transformation center

Now, in partnership with AGA, Dr. Atreja and his collaborators are planning a roll-out to multiple sites to see whether the savings and return on investment are replicated at other endoscopy sites. The vision expands beyond reducing revenue leaks to creating “digital transformation centers,” he said.

Digital health solutions such as this afford powerful opportunity for data collection, not only for practice optimization but also for research, said Dr. Atreja. He cited the example of endoscopic retrograde cholangiopancreatography, where procedural details could be linked to postprocedural admission rates in the service of fine-tuning one of the endoscopist’s greatest procedural challenges.

“You can create all of those clinical trial networks for devices right on the fly,” he said. In devising a clinical trial for an app-based intervention for anxiety – prevalent in those with irritable bowel disease – Dr. Atreja and his colleagues opened trial enrollment at 8 a.m., hoping to enroll 20 patients. By the end of the day, over 200 had enrolled. “We over-subscribed our trial by 10 times” in 1 day using the digital platform, he said.

Dr. Atreja is currently working with the American College of Cardiology on digital solutions for home monitoring of heart failure patients. “Partnerships with other health systems and societies are key for learning and rapid transformation – a rising tide lifts all boats,” said Dr. Atreja. “Digital medicine is not digital medicine. It is medicine. Because the practice of medicine is medicine.”

Dr. Atreja reported receiving funding from AbbVie, Janssen, Pfizer, Takeda, Astrazeneca, UCB, and Roche; the RxUniverse app has been licensed from the Icahn School of Medicine at Mount Sinai to Rx.Health.

AGA has partnered with RxHealth to support gastroenterologists’ ability to provide patient care and improve patient adherence by creating up-to-date, evidenced-based digital tools that can be prescribed at point of care. Dr. John I. Allen, the Editor in Chief of GI & Hepatology News, is on the advisory board of RxHealth and recused himself from review and approval of this story. Learn more about the program and how to become a pioneer site at https://rx.health/GI or [email protected] .

[email protected]

CHICAGO – A large Danish registry-based study has confirmed an increased risk of acute pancreatitis for patients taking certain antithyroid drugs.

After 6 months of methimazole use, the odds ratio for acute pancreatitis was 2.02, with a nonsignificant risk elevation for propylthiouracil use after a similar duration, Laszlo Hegedüs, MD, reported at the annual meeting of the American Thyroid Association.

“Ongoing methimazole, but not propylthiouracil, use is associated with an increased risk of acute pancreatitis,” he said.

Dr. Hegedüs, professor of endocrinology and metabolism at the University of Southern Denmark, Odense, said that the European Medicines Agency has noted a few postmarketing reports of acute pancreatitis in patients who received the antithyroid drug methimazole, as well as its prodrug, carbimazole. The agency has accordingly contraindicated antithyroid drug use for patients who previously experienced acute pancreatitis after receiving this drug, advising that methimazole should be “discontinued immediately” should a patient develop acute pancreatitis.

However, investigation of the antithyroid drug–pancreatitis association had been limited to aggregating those case reports, so Dr. Hegedüs and colleagues decided to use Danish medical record and registry data to investigate the association in a nationwide, controlled study that looked at both duration of therapy and total antithyroid drug use.

During the period from 1995-2018, a total of 118,649 patients who used antithyroid drugs were found in the 5.5 million individuals in the Statistics Denmark registry. Dr. Hegedüs and his colleagues also pulled in patient registry and national prescription registry data, as well as civil vital statistics data.

Of those who used antithyroid drugs, 103,825 patients used methimazole, and 14,824 used propylthiouracil. The researchers found 43,580 instances of hospitalization for first-time acute pancreatitis in the pooled antithyroid drug data. Of those, however, just 226 (0.5%) occurred in patients using methimazole, and 19 (0.04%) in those using propylthiouracil at the time of pancreatitis onset.

To ascertain the risk of acute pancreatitis in patients using antithyroid drugs for various durations, Dr. Hegedüs and his colleagues used a case-crossover study design. In the case-crossover technique, patients served as their own controls, because each patient was both exposed and not exposed to antithyroid drugs at some point during the study period. Antithyroid drugs are well suited to this study design, explained Dr. Hegedüs, because they are given for a limited time. A case-crossover design can be used with a small sample size and effectively controls for potentially confounding variables.

The odds ratio for acute pancreatitis in methimazole users after 3 months of exposure was 1.51, with a 95% confidence interval of 1.12-2.02. After 3 months of propylthiouracil exposure, the odds ratio for acute pancreatitis was 1.16 (95% CI 0.46-2.3). At 6 months, the odds ratio of 2.02 for methimazole was similarly statistically significant (95% CI, 1.50-2.78), whereas the odds ratio of 1.40 for propylthiouracil use was not significant (95% CI, 0.58-3.34).

The researchers also wanted to find out whether the cumulative drug dose affected the risk of acute pancreatitis, so they drew from the antithyroid drug population to conduct a case-control study. Here, the investigators matched data from four control patients to each case of acute pancreatitis. The researchers also controlled for sex, age, comorbidities, and prior use of drugs associated with pancreatitis.

Overall, 20% of the 692 methimazole users and their controls were men, as were 16% of the 108 propylthiouracil users, in the case-control study.

Just more than half of patients overall had a total dose exposure of 200 to 1,200 defined daily dose (DDD) – a measure developed by the World Health Organization to denote the assumed average adult dose per day of a medication – with about a quarter of patients receiving a total antithyroid drug dose more than 1,200 DDD and about 20% receiving a dose exposure of less than 200 DDD. The risk of acute pancreatitis did not increase with increased total exposure to antithyroid drugs.

“There is no evidence of a cumulative dose effect of either methimazole or propylthiouracil on the risk of acute pancreatitis,” said Dr. Hegedüs. However, “the warning of the European Medicines Agency seems justified,” he added. “The frequency of acute pancreatitis in acute methimazole users is of a similar magnitude [to that] reported for agranulocytosis,” a known, dire complication of antithyroid drug use. Patients should be advised of the potential complication and informed of signs and symptoms of acute pancreatitis, he said.

Dr. Hegedüs noted that the study had the advantage of using validated epidemiologic methods to look at drug exposure and outcomes at a nationwide scale. However, the registries from which the data were drawn also have limitations. The investigators could not determine the severity of hyperthyroidism, he said, and the relatively rare occurrence of acute pancreatitis meant that there was not sufficient statistical power to look at the subgroup of individuals who had Graves disease and to compare them with those with nodular toxic goiter.

He advised conducting a confirmatory study in an independent cohort, as well as further investigating the yet unknown mechanism of action for the link between the antithyroid drug and acute pancreatitis.

Dr. Hegedüs reported that he had no relevant conflicts of interest and reported no outside sources of funding.
 

SOURCE: Hegedüs, L. et al. ATA 2019, Short Call Oral Abstract 6 .

CHICAGO – A large Danish registry-based study has confirmed an increased risk of acute pancreatitis for patients taking certain antithyroid drugs.

After 6 months of methimazole use, the odds ratio for acute pancreatitis was 2.02, with a nonsignificant risk elevation for propylthiouracil use after a similar duration, Laszlo Hegedüs, MD, reported at the annual meeting of the American Thyroid Association.

“Ongoing methimazole, but not propylthiouracil, use is associated with an increased risk of acute pancreatitis,” he said.

Dr. Hegedüs, professor of endocrinology and metabolism at the University of Southern Denmark, Odense, said that the European Medicines Agency has noted a few postmarketing reports of acute pancreatitis in patients who received the antithyroid drug methimazole, as well as its prodrug, carbimazole. The agency has accordingly contraindicated antithyroid drug use for patients who previously experienced acute pancreatitis after receiving this drug, advising that methimazole should be “discontinued immediately” should a patient develop acute pancreatitis.

However, investigation of the antithyroid drug–pancreatitis association had been limited to aggregating those case reports, so Dr. Hegedüs and colleagues decided to use Danish medical record and registry data to investigate the association in a nationwide, controlled study that looked at both duration of therapy and total antithyroid drug use.

During the period from 1995-2018, a total of 118,649 patients who used antithyroid drugs were found in the 5.5 million individuals in the Statistics Denmark registry. Dr. Hegedüs and his colleagues also pulled in patient registry and national prescription registry data, as well as civil vital statistics data.

Of those who used antithyroid drugs, 103,825 patients used methimazole, and 14,824 used propylthiouracil. The researchers found 43,580 instances of hospitalization for first-time acute pancreatitis in the pooled antithyroid drug data. Of those, however, just 226 (0.5%) occurred in patients using methimazole, and 19 (0.04%) in those using propylthiouracil at the time of pancreatitis onset.

To ascertain the risk of acute pancreatitis in patients using antithyroid drugs for various durations, Dr. Hegedüs and his colleagues used a case-crossover study design. In the case-crossover technique, patients served as their own controls, because each patient was both exposed and not exposed to antithyroid drugs at some point during the study period. Antithyroid drugs are well suited to this study design, explained Dr. Hegedüs, because they are given for a limited time. A case-crossover design can be used with a small sample size and effectively controls for potentially confounding variables.

The odds ratio for acute pancreatitis in methimazole users after 3 months of exposure was 1.51, with a 95% confidence interval of 1.12-2.02. After 3 months of propylthiouracil exposure, the odds ratio for acute pancreatitis was 1.16 (95% CI 0.46-2.3). At 6 months, the odds ratio of 2.02 for methimazole was similarly statistically significant (95% CI, 1.50-2.78), whereas the odds ratio of 1.40 for propylthiouracil use was not significant (95% CI, 0.58-3.34).

The researchers also wanted to find out whether the cumulative drug dose affected the risk of acute pancreatitis, so they drew from the antithyroid drug population to conduct a case-control study. Here, the investigators matched data from four control patients to each case of acute pancreatitis. The researchers also controlled for sex, age, comorbidities, and prior use of drugs associated with pancreatitis.

Overall, 20% of the 692 methimazole users and their controls were men, as were 16% of the 108 propylthiouracil users, in the case-control study.

Just more than half of patients overall had a total dose exposure of 200 to 1,200 defined daily dose (DDD) – a measure developed by the World Health Organization to denote the assumed average adult dose per day of a medication – with about a quarter of patients receiving a total antithyroid drug dose more than 1,200 DDD and about 20% receiving a dose exposure of less than 200 DDD. The risk of acute pancreatitis did not increase with increased total exposure to antithyroid drugs.

“There is no evidence of a cumulative dose effect of either methimazole or propylthiouracil on the risk of acute pancreatitis,” said Dr. Hegedüs. However, “the warning of the European Medicines Agency seems justified,” he added. “The frequency of acute pancreatitis in acute methimazole users is of a similar magnitude [to that] reported for agranulocytosis,” a known, dire complication of antithyroid drug use. Patients should be advised of the potential complication and informed of signs and symptoms of acute pancreatitis, he said.

Dr. Hegedüs noted that the study had the advantage of using validated epidemiologic methods to look at drug exposure and outcomes at a nationwide scale. However, the registries from which the data were drawn also have limitations. The investigators could not determine the severity of hyperthyroidism, he said, and the relatively rare occurrence of acute pancreatitis meant that there was not sufficient statistical power to look at the subgroup of individuals who had Graves disease and to compare them with those with nodular toxic goiter.

He advised conducting a confirmatory study in an independent cohort, as well as further investigating the yet unknown mechanism of action for the link between the antithyroid drug and acute pancreatitis.

Dr. Hegedüs reported that he had no relevant conflicts of interest and reported no outside sources of funding.
 

SOURCE: Hegedüs, L. et al. ATA 2019, Short Call Oral Abstract 6 .

CHICAGO – A large Danish registry-based study has confirmed an increased risk of acute pancreatitis for patients taking certain antithyroid drugs.

After 6 months of methimazole use, the odds ratio for acute pancreatitis was 2.02, with a nonsignificant risk elevation for propylthiouracil use after a similar duration, Laszlo Hegedüs, MD, reported at the annual meeting of the American Thyroid Association.

“Ongoing methimazole, but not propylthiouracil, use is associated with an increased risk of acute pancreatitis,” he said.

Dr. Hegedüs, professor of endocrinology and metabolism at the University of Southern Denmark, Odense, said that the European Medicines Agency has noted a few postmarketing reports of acute pancreatitis in patients who received the antithyroid drug methimazole, as well as its prodrug, carbimazole. The agency has accordingly contraindicated antithyroid drug use for patients who previously experienced acute pancreatitis after receiving this drug, advising that methimazole should be “discontinued immediately” should a patient develop acute pancreatitis.

However, investigation of the antithyroid drug–pancreatitis association had been limited to aggregating those case reports, so Dr. Hegedüs and colleagues decided to use Danish medical record and registry data to investigate the association in a nationwide, controlled study that looked at both duration of therapy and total antithyroid drug use.

During the period from 1995-2018, a total of 118,649 patients who used antithyroid drugs were found in the 5.5 million individuals in the Statistics Denmark registry. Dr. Hegedüs and his colleagues also pulled in patient registry and national prescription registry data, as well as civil vital statistics data.

Of those who used antithyroid drugs, 103,825 patients used methimazole, and 14,824 used propylthiouracil. The researchers found 43,580 instances of hospitalization for first-time acute pancreatitis in the pooled antithyroid drug data. Of those, however, just 226 (0.5%) occurred in patients using methimazole, and 19 (0.04%) in those using propylthiouracil at the time of pancreatitis onset.

To ascertain the risk of acute pancreatitis in patients using antithyroid drugs for various durations, Dr. Hegedüs and his colleagues used a case-crossover study design. In the case-crossover technique, patients served as their own controls, because each patient was both exposed and not exposed to antithyroid drugs at some point during the study period. Antithyroid drugs are well suited to this study design, explained Dr. Hegedüs, because they are given for a limited time. A case-crossover design can be used with a small sample size and effectively controls for potentially confounding variables.

The odds ratio for acute pancreatitis in methimazole users after 3 months of exposure was 1.51, with a 95% confidence interval of 1.12-2.02. After 3 months of propylthiouracil exposure, the odds ratio for acute pancreatitis was 1.16 (95% CI 0.46-2.3). At 6 months, the odds ratio of 2.02 for methimazole was similarly statistically significant (95% CI, 1.50-2.78), whereas the odds ratio of 1.40 for propylthiouracil use was not significant (95% CI, 0.58-3.34).

The researchers also wanted to find out whether the cumulative drug dose affected the risk of acute pancreatitis, so they drew from the antithyroid drug population to conduct a case-control study. Here, the investigators matched data from four control patients to each case of acute pancreatitis. The researchers also controlled for sex, age, comorbidities, and prior use of drugs associated with pancreatitis.

Overall, 20% of the 692 methimazole users and their controls were men, as were 16% of the 108 propylthiouracil users, in the case-control study.

Just more than half of patients overall had a total dose exposure of 200 to 1,200 defined daily dose (DDD) – a measure developed by the World Health Organization to denote the assumed average adult dose per day of a medication – with about a quarter of patients receiving a total antithyroid drug dose more than 1,200 DDD and about 20% receiving a dose exposure of less than 200 DDD. The risk of acute pancreatitis did not increase with increased total exposure to antithyroid drugs.

“There is no evidence of a cumulative dose effect of either methimazole or propylthiouracil on the risk of acute pancreatitis,” said Dr. Hegedüs. However, “the warning of the European Medicines Agency seems justified,” he added. “The frequency of acute pancreatitis in acute methimazole users is of a similar magnitude [to that] reported for agranulocytosis,” a known, dire complication of antithyroid drug use. Patients should be advised of the potential complication and informed of signs and symptoms of acute pancreatitis, he said.

Dr. Hegedüs noted that the study had the advantage of using validated epidemiologic methods to look at drug exposure and outcomes at a nationwide scale. However, the registries from which the data were drawn also have limitations. The investigators could not determine the severity of hyperthyroidism, he said, and the relatively rare occurrence of acute pancreatitis meant that there was not sufficient statistical power to look at the subgroup of individuals who had Graves disease and to compare them with those with nodular toxic goiter.

He advised conducting a confirmatory study in an independent cohort, as well as further investigating the yet unknown mechanism of action for the link between the antithyroid drug and acute pancreatitis.

Dr. Hegedüs reported that he had no relevant conflicts of interest and reported no outside sources of funding.
 

SOURCE: Hegedüs, L. et al. ATA 2019, Short Call Oral Abstract 6 .

CHICAGO – Overall survival for patients with anaplastic thyroid cancer was boosted when their care facilitated a rapid work-up, comprehensive treatment planning, and integrated implementation of multimodal therapies.

Median survival for participants in a specialized program who have been able to benefit from targeted therapy and immunotherapy now stands at 16 months, with 43% of patients surviving 2 years or more, said Anastasios Maniakas, MD, at the annual meeting of the American Thyroid Association.

Median survival was 8 months during 2000-2013, before the program, dubbed FAST (Facilitating Anaplastic Thyroid Cancer Specialized Treatment), was initiated at the University of Texas MD Anderson Cancer Center, Houston.

These increased survival rates were driven primarily by better targeting of mutation-specific therapy and by immunotherapy, said Dr. Maniakas, a fellow in head and neck surgery at the center. This targeting, in turn, was facilitated by timely staging and genetic work-up, as well as appropriate clinical trial enrollment.

As word has spread about the program, referrals went up by 44%, said Dr. Maniakas. Members of the FAST team include representatives from oncologic endocrinology, head and neck surgery, radiation oncology, pathology, and basic science.

Historically, anaplastic thyroid cancer (ATC) has had a 12-month overall survival rate of less than 30% for patients who have advanced disease, said Dr. Maniakas, citing a recent analysis showing that, in 1,567 ATC cases, the median survival was just 4 months, and the 6-month survival rate was 35%.

The FAST team’s engagement starts with rapid intake whereby patients see a physician within 3-5 days of initial contact with the center, explained Dr. Maniakas. A prescheduled work-up is completed within another 3-7 days. It includes basic lab work, cell-free DNA testing, BRAF immunohistochemistry, and molecular testing. Additional consults and appropriate medical imaging for staging are also included in the initial work-up.

With these data in hand, physicians meet again with patients in a treatment-planning clinic to assess eligibility for participation in a clinical trial. Patients will otherwise receive standard-of-care therapy that may include surgery or BRAF-directed therapy. However, said Dr. Maniakas, the FAST approach has resulted in a boost of more than 30% in clinical trial participation by ATC patients. Adjunctive therapies are also tailored to patients under the care of the FAST team, which may include stereotactic body-radiation therapy, surgery, and immunotherapy.

The team is tracking a cohort of patients who received surgery with or without radiation therapy, preceded by neoadjuvant BRAF/MEK inhibitor therapy – an approach used since 2017. Of 20 patients who were positive for BRAF-V600E, 16 are still alive at a median 1.21 years of follow-up since diagnosis, said Dr. Maniakas. The median survival time for those who did not receive surgery is 0.8 years, whereas the median survival has not been reached for those who also had surgery.

Molecular testing and initial screening of ATC patients is an essential component of the cancer center’s precision medicine approach, said Dr. Maniakas. “Genetic profiling has become a key player in ATC management and survival.”

In looking at outcomes at the cancer center, Dr. Maniakas and his collaborators divided the patients into three groups. The first included 227 patients seen during 2000-2013, before the program was initiated. The 100 participants in the second group initiated treatment sometime during 2014-2016, after the program was launched but before the targeted therapy and immunotherapy trial was fully implemented. Since 2017, 152 participants in the third group have had the opportunity to participate in the clinical trial, as well as receiving surgery with or without radiation therapy after neoadjuvant immunotherapy.

Since 2017, 97% of ATC patients have had genetic profiling done. Most patients are receiving rapid determination of BRAF-V600E status with immunohistochemistry, with results available in a few days, followed by liquid biopsy (available in about 2 weeks), and then next-generation sequencing. Results for the latter, considered the gold standard, can take up to 3 weeks.

Patients participating in the program were aged a mean 65 years at diagnosis, and just over half were men. The number of patients receiving targeted therapy has continued to rise, said Dr. Maniakas. From 2000 to 2013, just 9% of patients received targeted therapy; from 2014 to 2016, that figure rose to 43%; and since 2017, 61% of patients have received targeted therapy (P less than .001).

“Landmark changes in the management of ATC patients as a whole have had a direct impact to the significant increase in overall survival,” said Dr. Maniakas.

He added that the cancer center’s experience could inform future ATC guidelines. Patients with this deadliest of thyroid cancers should all have rapid molecular testing, followed by timely, targeted therapy. Clinical trial eligibility should be considered for all patients. Finally, guideline authors should take note of the ongoing favorable survival rates seen for patients receiving surgery after neoadjuvant therapy.

Dr. Maniakas reported no outside sources of funding and that he had no relevant disclosures.
 

SOURCE: Maniakas A et al. ATA 2019, Short Call Oral Abstract 9.

CHICAGO – Overall survival for patients with anaplastic thyroid cancer was boosted when their care facilitated a rapid work-up, comprehensive treatment planning, and integrated implementation of multimodal therapies.

Median survival for participants in a specialized program who have been able to benefit from targeted therapy and immunotherapy now stands at 16 months, with 43% of patients surviving 2 years or more, said Anastasios Maniakas, MD, at the annual meeting of the American Thyroid Association.

Median survival was 8 months during 2000-2013, before the program, dubbed FAST (Facilitating Anaplastic Thyroid Cancer Specialized Treatment), was initiated at the University of Texas MD Anderson Cancer Center, Houston.

These increased survival rates were driven primarily by better targeting of mutation-specific therapy and by immunotherapy, said Dr. Maniakas, a fellow in head and neck surgery at the center. This targeting, in turn, was facilitated by timely staging and genetic work-up, as well as appropriate clinical trial enrollment.

As word has spread about the program, referrals went up by 44%, said Dr. Maniakas. Members of the FAST team include representatives from oncologic endocrinology, head and neck surgery, radiation oncology, pathology, and basic science.

Historically, anaplastic thyroid cancer (ATC) has had a 12-month overall survival rate of less than 30% for patients who have advanced disease, said Dr. Maniakas, citing a recent analysis showing that, in 1,567 ATC cases, the median survival was just 4 months, and the 6-month survival rate was 35%.

The FAST team’s engagement starts with rapid intake whereby patients see a physician within 3-5 days of initial contact with the center, explained Dr. Maniakas. A prescheduled work-up is completed within another 3-7 days. It includes basic lab work, cell-free DNA testing, BRAF immunohistochemistry, and molecular testing. Additional consults and appropriate medical imaging for staging are also included in the initial work-up.

With these data in hand, physicians meet again with patients in a treatment-planning clinic to assess eligibility for participation in a clinical trial. Patients will otherwise receive standard-of-care therapy that may include surgery or BRAF-directed therapy. However, said Dr. Maniakas, the FAST approach has resulted in a boost of more than 30% in clinical trial participation by ATC patients. Adjunctive therapies are also tailored to patients under the care of the FAST team, which may include stereotactic body-radiation therapy, surgery, and immunotherapy.

The team is tracking a cohort of patients who received surgery with or without radiation therapy, preceded by neoadjuvant BRAF/MEK inhibitor therapy – an approach used since 2017. Of 20 patients who were positive for BRAF-V600E, 16 are still alive at a median 1.21 years of follow-up since diagnosis, said Dr. Maniakas. The median survival time for those who did not receive surgery is 0.8 years, whereas the median survival has not been reached for those who also had surgery.

Molecular testing and initial screening of ATC patients is an essential component of the cancer center’s precision medicine approach, said Dr. Maniakas. “Genetic profiling has become a key player in ATC management and survival.”

In looking at outcomes at the cancer center, Dr. Maniakas and his collaborators divided the patients into three groups. The first included 227 patients seen during 2000-2013, before the program was initiated. The 100 participants in the second group initiated treatment sometime during 2014-2016, after the program was launched but before the targeted therapy and immunotherapy trial was fully implemented. Since 2017, 152 participants in the third group have had the opportunity to participate in the clinical trial, as well as receiving surgery with or without radiation therapy after neoadjuvant immunotherapy.

Since 2017, 97% of ATC patients have had genetic profiling done. Most patients are receiving rapid determination of BRAF-V600E status with immunohistochemistry, with results available in a few days, followed by liquid biopsy (available in about 2 weeks), and then next-generation sequencing. Results for the latter, considered the gold standard, can take up to 3 weeks.

Patients participating in the program were aged a mean 65 years at diagnosis, and just over half were men. The number of patients receiving targeted therapy has continued to rise, said Dr. Maniakas. From 2000 to 2013, just 9% of patients received targeted therapy; from 2014 to 2016, that figure rose to 43%; and since 2017, 61% of patients have received targeted therapy (P less than .001).

“Landmark changes in the management of ATC patients as a whole have had a direct impact to the significant increase in overall survival,” said Dr. Maniakas.

He added that the cancer center’s experience could inform future ATC guidelines. Patients with this deadliest of thyroid cancers should all have rapid molecular testing, followed by timely, targeted therapy. Clinical trial eligibility should be considered for all patients. Finally, guideline authors should take note of the ongoing favorable survival rates seen for patients receiving surgery after neoadjuvant therapy.

Dr. Maniakas reported no outside sources of funding and that he had no relevant disclosures.
 

SOURCE: Maniakas A et al. ATA 2019, Short Call Oral Abstract 9.

CHICAGO – Overall survival for patients with anaplastic thyroid cancer was boosted when their care facilitated a rapid work-up, comprehensive treatment planning, and integrated implementation of multimodal therapies.

Median survival for participants in a specialized program who have been able to benefit from targeted therapy and immunotherapy now stands at 16 months, with 43% of patients surviving 2 years or more, said Anastasios Maniakas, MD, at the annual meeting of the American Thyroid Association.

Median survival was 8 months during 2000-2013, before the program, dubbed FAST (Facilitating Anaplastic Thyroid Cancer Specialized Treatment), was initiated at the University of Texas MD Anderson Cancer Center, Houston.

These increased survival rates were driven primarily by better targeting of mutation-specific therapy and by immunotherapy, said Dr. Maniakas, a fellow in head and neck surgery at the center. This targeting, in turn, was facilitated by timely staging and genetic work-up, as well as appropriate clinical trial enrollment.

As word has spread about the program, referrals went up by 44%, said Dr. Maniakas. Members of the FAST team include representatives from oncologic endocrinology, head and neck surgery, radiation oncology, pathology, and basic science.

Historically, anaplastic thyroid cancer (ATC) has had a 12-month overall survival rate of less than 30% for patients who have advanced disease, said Dr. Maniakas, citing a recent analysis showing that, in 1,567 ATC cases, the median survival was just 4 months, and the 6-month survival rate was 35%.

The FAST team’s engagement starts with rapid intake whereby patients see a physician within 3-5 days of initial contact with the center, explained Dr. Maniakas. A prescheduled work-up is completed within another 3-7 days. It includes basic lab work, cell-free DNA testing, BRAF immunohistochemistry, and molecular testing. Additional consults and appropriate medical imaging for staging are also included in the initial work-up.

With these data in hand, physicians meet again with patients in a treatment-planning clinic to assess eligibility for participation in a clinical trial. Patients will otherwise receive standard-of-care therapy that may include surgery or BRAF-directed therapy. However, said Dr. Maniakas, the FAST approach has resulted in a boost of more than 30% in clinical trial participation by ATC patients. Adjunctive therapies are also tailored to patients under the care of the FAST team, which may include stereotactic body-radiation therapy, surgery, and immunotherapy.

The team is tracking a cohort of patients who received surgery with or without radiation therapy, preceded by neoadjuvant BRAF/MEK inhibitor therapy – an approach used since 2017. Of 20 patients who were positive for BRAF-V600E, 16 are still alive at a median 1.21 years of follow-up since diagnosis, said Dr. Maniakas. The median survival time for those who did not receive surgery is 0.8 years, whereas the median survival has not been reached for those who also had surgery.

Molecular testing and initial screening of ATC patients is an essential component of the cancer center’s precision medicine approach, said Dr. Maniakas. “Genetic profiling has become a key player in ATC management and survival.”

In looking at outcomes at the cancer center, Dr. Maniakas and his collaborators divided the patients into three groups. The first included 227 patients seen during 2000-2013, before the program was initiated. The 100 participants in the second group initiated treatment sometime during 2014-2016, after the program was launched but before the targeted therapy and immunotherapy trial was fully implemented. Since 2017, 152 participants in the third group have had the opportunity to participate in the clinical trial, as well as receiving surgery with or without radiation therapy after neoadjuvant immunotherapy.

Since 2017, 97% of ATC patients have had genetic profiling done. Most patients are receiving rapid determination of BRAF-V600E status with immunohistochemistry, with results available in a few days, followed by liquid biopsy (available in about 2 weeks), and then next-generation sequencing. Results for the latter, considered the gold standard, can take up to 3 weeks.

Patients participating in the program were aged a mean 65 years at diagnosis, and just over half were men. The number of patients receiving targeted therapy has continued to rise, said Dr. Maniakas. From 2000 to 2013, just 9% of patients received targeted therapy; from 2014 to 2016, that figure rose to 43%; and since 2017, 61% of patients have received targeted therapy (P less than .001).

“Landmark changes in the management of ATC patients as a whole have had a direct impact to the significant increase in overall survival,” said Dr. Maniakas.

He added that the cancer center’s experience could inform future ATC guidelines. Patients with this deadliest of thyroid cancers should all have rapid molecular testing, followed by timely, targeted therapy. Clinical trial eligibility should be considered for all patients. Finally, guideline authors should take note of the ongoing favorable survival rates seen for patients receiving surgery after neoadjuvant therapy.

Dr. Maniakas reported no outside sources of funding and that he had no relevant disclosures.
 

SOURCE: Maniakas A et al. ATA 2019, Short Call Oral Abstract 9.

CHICAGO – Is your practice ready for telemedicine – and should you dive in?

Once you and your practice managers work through regulatory, legal, and technical details, having a robust telemedicine practice can boost patient and clinician satisfaction – and the bottom line, said Theresa Lee, MD, a gastroenterologist in private practice in Lone Tree, Colorado, speaking at the 2019 AGA Partners in Value meeting.

Kari Oakes/MDedge News

The general field of telehealth – in which images might be shared or patients might message their care team for medication refills – is a broad term, said Dr. Lee. She explained that telemedicine is narrowly defined for Medicare and Medicaid reimbursement purposes as “two-way, real-time interactive communication between the patient and the physician or practitioner at [a] distant site ... that includes, at a minimum, audio and video equipment.” This is the video visit that many people think of when they imagine telemedicine, she said.

There’s increasing acceptance of telehealth services, said Dr. Lee, with a recent online poll showing that two-thirds of those surveyed would be willing to use telehealth; this would translate to about 24 million Americans who would be potential telehealth patients. And a 2019 survey of internal medicine physicians showed that more than half are working in practices in which telehealth is used in some capacity. Both patients and clinicians can benefit in a telehealth relationship, said Dr. Lee. The lack of physical travel and the potential for access after normal clinic hours can be a real boon for patients; “So how does this help us? How does it improve practice and make our lives easier?” she asked. Telehealth services can lead to improved efficiency, patient satisfaction and retention, and the ability to stand out in a market, especially if a practice can initiate telehealth services now, during the rapid growth and adoption phase for this newer technology.

“You want to make sure you really understand what some of the legal issues are surrounding telehealth and telemedicine,” said Dr. Lee, to ensure compliance with state and federal laws. There can be barriers to practicing across state lines; some states require an initial in-person visit, or the signing of a consent form, before initiating telemedicine; others may limit controlled substance prescribing via telemedicine.

And the mode of communication matters, said Dr. Lee: “Why can’t we just use Facetime to call our patients? The first thing to think about is privacy, and unauthorized access to data,” so it’s critical to do your research and use fully HIPAA-compliant communications technology.

Technology – and pricing plans – can vary widely, she added. “There’s some benefit to including technology that integrates with other clinical programs;” the platform Dr. Lee’s group chose communicates with their EHR for such functions as scheduling.

Pricing models can vary; a common scheme charges a per-user monthly fee, though blanket-fee plans also exist. Some telemedicine platforms use a hybrid pricing model that charges a flat fee up to a certain number of users and then adds a per-user fee after that.

Best practices to manage liability include continuing to maintain high standards of compliance after attorney consultation and notifying your practice’s malpractice insurance carrier, said Dr. Lee.

Reimbursement is on the upswing, as insurers see the benefits of telemedicine, and employers see their patients needing less time off work for appointments, and there are fewer emergency department visits for after-hours problems. Medicaid reimbursement is fairly straightforward, but Medicare is more restrictive and requires the beneficiary to be in a rural originating site.

Coding for a telemedicine visit is strictly based on face-to-face time spent in video conference, said Dr. Lee, at levels on par with time-based coding for office visits. “But you’re not including that time you spend doing chart review and not including the time you spend coordinating care.”

Dr. Lee’s own experience with telemedicine began in late 2016, when the 22-physician general gastroenterology group looked into it as a way to increase growth.

During the first half of the next year, the gastroenterology group’s administrative leaders and an engaged physician proponent vetted a number of telemedicine companies, and the group tried the leading candidates’ technologies.

By mid-2017, the comprehensive gastroenterology group, which also employs six advanced-practice clinicians, was piloting video visits with a group of four physicians. “One of those physicians was actually one of my partners who had sustained an Achilles tendon injury, so wasn’t really coming to the office post surgery. He was starting to use this at home, to do video visits, and everything went pretty smoothly with that,” said Dr. Lee.

When this trial was successful, the group went all in, with on-boarding of clinicians accomplished by the end of the year, site visits and 1:1 training provided by the telemedicine platform providers.

The practice is seeing video visits continue to grow in popularity, among both patients and clinicians, said Dr. Lee. She shared some tips and lessons learned from her practice.

There’s currently no formal protocol that selects patients for participation in the telemedicine program at Dr. Lee’s clinic. Providers may offer video visits to patients, and triage nurses also can suggest that patients ask their provider about them; flyers in waiting rooms and exam rooms encourage patients to ask about the possibility.

The practice maintains a telehealth committee that includes the practice’s president and administrator, about three core physicians who are strong telehealth champions, and additional physicians who are high telehealth users. The committee also folds in the office and information technology managers to make sure issues of workflow, billing, and technology are addressed.

Some practical considerations can pose challenges to a successful telemedicine program, said Dr. Lee. Connectivity problems on the patient end are fairly frequent, and no-shows also can be a problem. On the clinic side, not all clinicians have embraced video visits. For these low users, telemedicine may not represent a good value proposition. However, she said, they are seeing more and more clinicians come on board with video visits as word gets out of the generally positive experiences others are having.

Dr. Lee suggested several ways to up telemedicine utilization and make it work within your practice. “Identify which patient would benefit most,” she said – this might be patients with inflammatory bowel disease who mostly need medication management, or patients with limited mobility or who live far away. Staff can also help a patient get a same-day visit by scheduling a video visit with an available clinician. By mentioning video visits as an option for uncomplicated issues or a way to get a rapid read on a new concern, clinicians can get patients thinking about telemedicine as an appealing option.

In some clinics, exam room space can limit clinician productivity, and scheduling a block of video visits when space is tight can be a great solution. Clinicians can optimize their schedules if they incorporate video visits, said Dr. Lee, citing the example of a physician assistant in her practice who stacks video visits in the evening hours, so she’s able to be with her preschool-aged children during the day. After-hours video visits have been popular among patients too, said Dr. Lee, so the scheduling flexibility may help with both patient and provider retention, and be a practice differentiator.

“There’s great potential for value through improved patient satisfaction, provider efficiency, improved health care outcomes, and cost efficiency,” she said.

Dr. Lee reported that she had no relevant disclosures.

AGA has partnered with SupportedPatientTM, a HIPAA-secure telemedicine platform. It allows you to expand your practice and connect your patients with additional specialists. Learn more at https://www.gastro.org/practice-guidance/practice-updates/supportedpatient .

[email protected]

CHICAGO – Is your practice ready for telemedicine – and should you dive in?

Once you and your practice managers work through regulatory, legal, and technical details, having a robust telemedicine practice can boost patient and clinician satisfaction – and the bottom line, said Theresa Lee, MD, a gastroenterologist in private practice in Lone Tree, Colorado, speaking at the 2019 AGA Partners in Value meeting.

Kari Oakes/MDedge News

The general field of telehealth – in which images might be shared or patients might message their care team for medication refills – is a broad term, said Dr. Lee. She explained that telemedicine is narrowly defined for Medicare and Medicaid reimbursement purposes as “two-way, real-time interactive communication between the patient and the physician or practitioner at [a] distant site ... that includes, at a minimum, audio and video equipment.” This is the video visit that many people think of when they imagine telemedicine, she said.

There’s increasing acceptance of telehealth services, said Dr. Lee, with a recent online poll showing that two-thirds of those surveyed would be willing to use telehealth; this would translate to about 24 million Americans who would be potential telehealth patients. And a 2019 survey of internal medicine physicians showed that more than half are working in practices in which telehealth is used in some capacity. Both patients and clinicians can benefit in a telehealth relationship, said Dr. Lee. The lack of physical travel and the potential for access after normal clinic hours can be a real boon for patients; “So how does this help us? How does it improve practice and make our lives easier?” she asked. Telehealth services can lead to improved efficiency, patient satisfaction and retention, and the ability to stand out in a market, especially if a practice can initiate telehealth services now, during the rapid growth and adoption phase for this newer technology.

“You want to make sure you really understand what some of the legal issues are surrounding telehealth and telemedicine,” said Dr. Lee, to ensure compliance with state and federal laws. There can be barriers to practicing across state lines; some states require an initial in-person visit, or the signing of a consent form, before initiating telemedicine; others may limit controlled substance prescribing via telemedicine.

And the mode of communication matters, said Dr. Lee: “Why can’t we just use Facetime to call our patients? The first thing to think about is privacy, and unauthorized access to data,” so it’s critical to do your research and use fully HIPAA-compliant communications technology.

Technology – and pricing plans – can vary widely, she added. “There’s some benefit to including technology that integrates with other clinical programs;” the platform Dr. Lee’s group chose communicates with their EHR for such functions as scheduling.

Pricing models can vary; a common scheme charges a per-user monthly fee, though blanket-fee plans also exist. Some telemedicine platforms use a hybrid pricing model that charges a flat fee up to a certain number of users and then adds a per-user fee after that.

Best practices to manage liability include continuing to maintain high standards of compliance after attorney consultation and notifying your practice’s malpractice insurance carrier, said Dr. Lee.

Reimbursement is on the upswing, as insurers see the benefits of telemedicine, and employers see their patients needing less time off work for appointments, and there are fewer emergency department visits for after-hours problems. Medicaid reimbursement is fairly straightforward, but Medicare is more restrictive and requires the beneficiary to be in a rural originating site.

Coding for a telemedicine visit is strictly based on face-to-face time spent in video conference, said Dr. Lee, at levels on par with time-based coding for office visits. “But you’re not including that time you spend doing chart review and not including the time you spend coordinating care.”

Dr. Lee’s own experience with telemedicine began in late 2016, when the 22-physician general gastroenterology group looked into it as a way to increase growth.

During the first half of the next year, the gastroenterology group’s administrative leaders and an engaged physician proponent vetted a number of telemedicine companies, and the group tried the leading candidates’ technologies.

By mid-2017, the comprehensive gastroenterology group, which also employs six advanced-practice clinicians, was piloting video visits with a group of four physicians. “One of those physicians was actually one of my partners who had sustained an Achilles tendon injury, so wasn’t really coming to the office post surgery. He was starting to use this at home, to do video visits, and everything went pretty smoothly with that,” said Dr. Lee.

When this trial was successful, the group went all in, with on-boarding of clinicians accomplished by the end of the year, site visits and 1:1 training provided by the telemedicine platform providers.

The practice is seeing video visits continue to grow in popularity, among both patients and clinicians, said Dr. Lee. She shared some tips and lessons learned from her practice.

There’s currently no formal protocol that selects patients for participation in the telemedicine program at Dr. Lee’s clinic. Providers may offer video visits to patients, and triage nurses also can suggest that patients ask their provider about them; flyers in waiting rooms and exam rooms encourage patients to ask about the possibility.

The practice maintains a telehealth committee that includes the practice’s president and administrator, about three core physicians who are strong telehealth champions, and additional physicians who are high telehealth users. The committee also folds in the office and information technology managers to make sure issues of workflow, billing, and technology are addressed.

Some practical considerations can pose challenges to a successful telemedicine program, said Dr. Lee. Connectivity problems on the patient end are fairly frequent, and no-shows also can be a problem. On the clinic side, not all clinicians have embraced video visits. For these low users, telemedicine may not represent a good value proposition. However, she said, they are seeing more and more clinicians come on board with video visits as word gets out of the generally positive experiences others are having.

Dr. Lee suggested several ways to up telemedicine utilization and make it work within your practice. “Identify which patient would benefit most,” she said – this might be patients with inflammatory bowel disease who mostly need medication management, or patients with limited mobility or who live far away. Staff can also help a patient get a same-day visit by scheduling a video visit with an available clinician. By mentioning video visits as an option for uncomplicated issues or a way to get a rapid read on a new concern, clinicians can get patients thinking about telemedicine as an appealing option.

In some clinics, exam room space can limit clinician productivity, and scheduling a block of video visits when space is tight can be a great solution. Clinicians can optimize their schedules if they incorporate video visits, said Dr. Lee, citing the example of a physician assistant in her practice who stacks video visits in the evening hours, so she’s able to be with her preschool-aged children during the day. After-hours video visits have been popular among patients too, said Dr. Lee, so the scheduling flexibility may help with both patient and provider retention, and be a practice differentiator.

“There’s great potential for value through improved patient satisfaction, provider efficiency, improved health care outcomes, and cost efficiency,” she said.

Dr. Lee reported that she had no relevant disclosures.

AGA has partnered with SupportedPatientTM, a HIPAA-secure telemedicine platform. It allows you to expand your practice and connect your patients with additional specialists. Learn more at https://www.gastro.org/practice-guidance/practice-updates/supportedpatient .

[email protected]

CHICAGO – Is your practice ready for telemedicine – and should you dive in?

Once you and your practice managers work through regulatory, legal, and technical details, having a robust telemedicine practice can boost patient and clinician satisfaction – and the bottom line, said Theresa Lee, MD, a gastroenterologist in private practice in Lone Tree, Colorado, speaking at the 2019 AGA Partners in Value meeting.

Kari Oakes/MDedge News

The general field of telehealth – in which images might be shared or patients might message their care team for medication refills – is a broad term, said Dr. Lee. She explained that telemedicine is narrowly defined for Medicare and Medicaid reimbursement purposes as “two-way, real-time interactive communication between the patient and the physician or practitioner at [a] distant site ... that includes, at a minimum, audio and video equipment.” This is the video visit that many people think of when they imagine telemedicine, she said.

There’s increasing acceptance of telehealth services, said Dr. Lee, with a recent online poll showing that two-thirds of those surveyed would be willing to use telehealth; this would translate to about 24 million Americans who would be potential telehealth patients. And a 2019 survey of internal medicine physicians showed that more than half are working in practices in which telehealth is used in some capacity. Both patients and clinicians can benefit in a telehealth relationship, said Dr. Lee. The lack of physical travel and the potential for access after normal clinic hours can be a real boon for patients; “So how does this help us? How does it improve practice and make our lives easier?” she asked. Telehealth services can lead to improved efficiency, patient satisfaction and retention, and the ability to stand out in a market, especially if a practice can initiate telehealth services now, during the rapid growth and adoption phase for this newer technology.

“You want to make sure you really understand what some of the legal issues are surrounding telehealth and telemedicine,” said Dr. Lee, to ensure compliance with state and federal laws. There can be barriers to practicing across state lines; some states require an initial in-person visit, or the signing of a consent form, before initiating telemedicine; others may limit controlled substance prescribing via telemedicine.

And the mode of communication matters, said Dr. Lee: “Why can’t we just use Facetime to call our patients? The first thing to think about is privacy, and unauthorized access to data,” so it’s critical to do your research and use fully HIPAA-compliant communications technology.

Technology – and pricing plans – can vary widely, she added. “There’s some benefit to including technology that integrates with other clinical programs;” the platform Dr. Lee’s group chose communicates with their EHR for such functions as scheduling.

Pricing models can vary; a common scheme charges a per-user monthly fee, though blanket-fee plans also exist. Some telemedicine platforms use a hybrid pricing model that charges a flat fee up to a certain number of users and then adds a per-user fee after that.

Best practices to manage liability include continuing to maintain high standards of compliance after attorney consultation and notifying your practice’s malpractice insurance carrier, said Dr. Lee.

Reimbursement is on the upswing, as insurers see the benefits of telemedicine, and employers see their patients needing less time off work for appointments, and there are fewer emergency department visits for after-hours problems. Medicaid reimbursement is fairly straightforward, but Medicare is more restrictive and requires the beneficiary to be in a rural originating site.

Coding for a telemedicine visit is strictly based on face-to-face time spent in video conference, said Dr. Lee, at levels on par with time-based coding for office visits. “But you’re not including that time you spend doing chart review and not including the time you spend coordinating care.”

Dr. Lee’s own experience with telemedicine began in late 2016, when the 22-physician general gastroenterology group looked into it as a way to increase growth.

During the first half of the next year, the gastroenterology group’s administrative leaders and an engaged physician proponent vetted a number of telemedicine companies, and the group tried the leading candidates’ technologies.

By mid-2017, the comprehensive gastroenterology group, which also employs six advanced-practice clinicians, was piloting video visits with a group of four physicians. “One of those physicians was actually one of my partners who had sustained an Achilles tendon injury, so wasn’t really coming to the office post surgery. He was starting to use this at home, to do video visits, and everything went pretty smoothly with that,” said Dr. Lee.

When this trial was successful, the group went all in, with on-boarding of clinicians accomplished by the end of the year, site visits and 1:1 training provided by the telemedicine platform providers.

The practice is seeing video visits continue to grow in popularity, among both patients and clinicians, said Dr. Lee. She shared some tips and lessons learned from her practice.

There’s currently no formal protocol that selects patients for participation in the telemedicine program at Dr. Lee’s clinic. Providers may offer video visits to patients, and triage nurses also can suggest that patients ask their provider about them; flyers in waiting rooms and exam rooms encourage patients to ask about the possibility.

The practice maintains a telehealth committee that includes the practice’s president and administrator, about three core physicians who are strong telehealth champions, and additional physicians who are high telehealth users. The committee also folds in the office and information technology managers to make sure issues of workflow, billing, and technology are addressed.

Some practical considerations can pose challenges to a successful telemedicine program, said Dr. Lee. Connectivity problems on the patient end are fairly frequent, and no-shows also can be a problem. On the clinic side, not all clinicians have embraced video visits. For these low users, telemedicine may not represent a good value proposition. However, she said, they are seeing more and more clinicians come on board with video visits as word gets out of the generally positive experiences others are having.

Dr. Lee suggested several ways to up telemedicine utilization and make it work within your practice. “Identify which patient would benefit most,” she said – this might be patients with inflammatory bowel disease who mostly need medication management, or patients with limited mobility or who live far away. Staff can also help a patient get a same-day visit by scheduling a video visit with an available clinician. By mentioning video visits as an option for uncomplicated issues or a way to get a rapid read on a new concern, clinicians can get patients thinking about telemedicine as an appealing option.

In some clinics, exam room space can limit clinician productivity, and scheduling a block of video visits when space is tight can be a great solution. Clinicians can optimize their schedules if they incorporate video visits, said Dr. Lee, citing the example of a physician assistant in her practice who stacks video visits in the evening hours, so she’s able to be with her preschool-aged children during the day. After-hours video visits have been popular among patients too, said Dr. Lee, so the scheduling flexibility may help with both patient and provider retention, and be a practice differentiator.

“There’s great potential for value through improved patient satisfaction, provider efficiency, improved health care outcomes, and cost efficiency,” she said.

Dr. Lee reported that she had no relevant disclosures.

AGA has partnered with SupportedPatientTM, a HIPAA-secure telemedicine platform. It allows you to expand your practice and connect your patients with additional specialists. Learn more at https://www.gastro.org/practice-guidance/practice-updates/supportedpatient .

[email protected]

CHICAGO – A new image-analysis algorithm for benign thyroid nodules that uses a technique similar to facial recognition showed good sensitivity and specificity, with the potential to reduce biopsies by more than 50%.

The negative predictive value of the ultrasound analysis algorithm was 93.2%, a figure approximating the false-negative rate of about 5% that is seen in fine-needle aspiration of thyroid nodules, said Johnson Thomas, MD, at the annual meeting of the American Thyroid Association.

“Millions of people have thyroid nodules,” many of which are detected incidentally, said Dr. Thomas, an endocrinologist with the Mercy health care system in Springfield, Mo. Fewer than 10% of thyroid nodules turn out to be malignant, but each year, millions of patients undergo biopsies to determine the status of their thyroid nodules.

Faced with evaluating a thyroid nodule, an endocrinologist can currently turn to a risk-stratification scheme, such as those developed by the American College of Radiology and the American Thyroid Association. However, there’s a big subjective component to risk stratification – significant inter- and intraobserver variation has been observed, said Dr. Thomas, and not all nodules are classifiable. The result is a system that still has low specificity and positive predictive value, he said.

Even after a decision to proceed to biopsy, one in seven thyroid nodule biopsies will not produce a definitive diagnosis, he said.

“We are doing millions of thyroid biopsies based on very subjective criteria to find thyroid cancer in a very small percentage of the population, with an invasive technique that may not be diagnostic one out of seven times,” Dr. Thomas said in summing up the current medical situation as he sees it.

Dr. Thomas, who writes his own computer code, said he was searching for a reliable and explainable noninvasive technique, and one that lacked subjective room for error, to address the thyroid nodule problem.

The question was whether an artificial intelligence (AI) algorithm could match radiologist performance in classifying thyroid nodules according to the characteristics of their ultrasound images.

Other algorithms use AI to predict which nodules are malignant, but they function as “black boxes” – a common criticism of AI. The outside observer cannot ordinarily see how the AI algorithm “knows” what it knows. This characteristic of AI poses at least a theoretical problem when such algorithms are used for diagnosis or medical decision making.

Dr. Thomas’s* approach was to use a set of training data to allow the algorithm he constructed to see 2,025 images from a total of 482 nodules. The thyroid nodules used for training had been subjected to biopsy or excised in surgery, so they all had a definitive status of being benign or malignant.

Then, after the algorithm was refined, a set of 103 nodules with known malignancy status was used to test the algorithm’s sensitivity and specificity.

The algorithm, dubbed AiBx, used a convolutional neural network to build a unique image vector for each nodule. The AiBx algorithm then looked at the training database to find the “nearest neighbors,” or the images it found to be the most similar to those of the nodule being examined.

For example, said Dr. Thomas, a test image of a benign nodule would have an output from the AiBx analysis of three similar images from the database – all benign. Hence, rather than making a black-box call of whether a nodule is benign or malignant, the algorithm merely says: “This nodule resembles a benign nodule in our database.” The interpreting physician can then use the algorithm as a decision aid with confidence.

The overall accuracy of AiBx was 81.5%, sensitivity was 87.8%, and specificity was 78.5%. Positive predictive value was 65.9%.

As more images are added to the database, AiBx can easily be retrained and refined, said Dr. Thomas.

“It’s intuitive and explainable,” he added, noting that the algorithm is also a good teaching tool for residents and fellows.

“This AI model can be deployed as an app, integrated with [medical imaging systems] or hosted as a website. By using image-similarity AI models we can eliminate subjectivity and decrease the number of unnecessary biopsies,” he explained in the abstract accompanying the presentation.

However, he said that the algorithm as it currently stands has limitations: It has been tested on only 103 images thus far, and there’s the potential for selection bias.

Dr. Thomas* reported that, although he developed the AiBx algorithm, he has not drawn income or royalties from it. He reported no other relevant conflicts of interest.
 

SOURCE: Thomas* J et al. ATA 2019, Oral Abstract 27.

*Correction, 21/11/2019: An earlier version of this story misstated Dr. Thomas's last name.

CHICAGO – A new image-analysis algorithm for benign thyroid nodules that uses a technique similar to facial recognition showed good sensitivity and specificity, with the potential to reduce biopsies by more than 50%.

The negative predictive value of the ultrasound analysis algorithm was 93.2%, a figure approximating the false-negative rate of about 5% that is seen in fine-needle aspiration of thyroid nodules, said Johnson Thomas, MD, at the annual meeting of the American Thyroid Association.

“Millions of people have thyroid nodules,” many of which are detected incidentally, said Dr. Thomas, an endocrinologist with the Mercy health care system in Springfield, Mo. Fewer than 10% of thyroid nodules turn out to be malignant, but each year, millions of patients undergo biopsies to determine the status of their thyroid nodules.

Faced with evaluating a thyroid nodule, an endocrinologist can currently turn to a risk-stratification scheme, such as those developed by the American College of Radiology and the American Thyroid Association. However, there’s a big subjective component to risk stratification – significant inter- and intraobserver variation has been observed, said Dr. Thomas, and not all nodules are classifiable. The result is a system that still has low specificity and positive predictive value, he said.

Even after a decision to proceed to biopsy, one in seven thyroid nodule biopsies will not produce a definitive diagnosis, he said.

“We are doing millions of thyroid biopsies based on very subjective criteria to find thyroid cancer in a very small percentage of the population, with an invasive technique that may not be diagnostic one out of seven times,” Dr. Thomas said in summing up the current medical situation as he sees it.

Dr. Thomas, who writes his own computer code, said he was searching for a reliable and explainable noninvasive technique, and one that lacked subjective room for error, to address the thyroid nodule problem.

The question was whether an artificial intelligence (AI) algorithm could match radiologist performance in classifying thyroid nodules according to the characteristics of their ultrasound images.

Other algorithms use AI to predict which nodules are malignant, but they function as “black boxes” – a common criticism of AI. The outside observer cannot ordinarily see how the AI algorithm “knows” what it knows. This characteristic of AI poses at least a theoretical problem when such algorithms are used for diagnosis or medical decision making.

Dr. Thomas’s* approach was to use a set of training data to allow the algorithm he constructed to see 2,025 images from a total of 482 nodules. The thyroid nodules used for training had been subjected to biopsy or excised in surgery, so they all had a definitive status of being benign or malignant.

Then, after the algorithm was refined, a set of 103 nodules with known malignancy status was used to test the algorithm’s sensitivity and specificity.

The algorithm, dubbed AiBx, used a convolutional neural network to build a unique image vector for each nodule. The AiBx algorithm then looked at the training database to find the “nearest neighbors,” or the images it found to be the most similar to those of the nodule being examined.

For example, said Dr. Thomas, a test image of a benign nodule would have an output from the AiBx analysis of three similar images from the database – all benign. Hence, rather than making a black-box call of whether a nodule is benign or malignant, the algorithm merely says: “This nodule resembles a benign nodule in our database.” The interpreting physician can then use the algorithm as a decision aid with confidence.

The overall accuracy of AiBx was 81.5%, sensitivity was 87.8%, and specificity was 78.5%. Positive predictive value was 65.9%.

As more images are added to the database, AiBx can easily be retrained and refined, said Dr. Thomas.

“It’s intuitive and explainable,” he added, noting that the algorithm is also a good teaching tool for residents and fellows.

“This AI model can be deployed as an app, integrated with [medical imaging systems] or hosted as a website. By using image-similarity AI models we can eliminate subjectivity and decrease the number of unnecessary biopsies,” he explained in the abstract accompanying the presentation.

However, he said that the algorithm as it currently stands has limitations: It has been tested on only 103 images thus far, and there’s the potential for selection bias.

Dr. Thomas* reported that, although he developed the AiBx algorithm, he has not drawn income or royalties from it. He reported no other relevant conflicts of interest.
 

SOURCE: Thomas* J et al. ATA 2019, Oral Abstract 27.

*Correction, 21/11/2019: An earlier version of this story misstated Dr. Thomas's last name.

CHICAGO – A new image-analysis algorithm for benign thyroid nodules that uses a technique similar to facial recognition showed good sensitivity and specificity, with the potential to reduce biopsies by more than 50%.

The negative predictive value of the ultrasound analysis algorithm was 93.2%, a figure approximating the false-negative rate of about 5% that is seen in fine-needle aspiration of thyroid nodules, said Johnson Thomas, MD, at the annual meeting of the American Thyroid Association.

“Millions of people have thyroid nodules,” many of which are detected incidentally, said Dr. Thomas, an endocrinologist with the Mercy health care system in Springfield, Mo. Fewer than 10% of thyroid nodules turn out to be malignant, but each year, millions of patients undergo biopsies to determine the status of their thyroid nodules.

Faced with evaluating a thyroid nodule, an endocrinologist can currently turn to a risk-stratification scheme, such as those developed by the American College of Radiology and the American Thyroid Association. However, there’s a big subjective component to risk stratification – significant inter- and intraobserver variation has been observed, said Dr. Thomas, and not all nodules are classifiable. The result is a system that still has low specificity and positive predictive value, he said.

Even after a decision to proceed to biopsy, one in seven thyroid nodule biopsies will not produce a definitive diagnosis, he said.

“We are doing millions of thyroid biopsies based on very subjective criteria to find thyroid cancer in a very small percentage of the population, with an invasive technique that may not be diagnostic one out of seven times,” Dr. Thomas said in summing up the current medical situation as he sees it.

Dr. Thomas, who writes his own computer code, said he was searching for a reliable and explainable noninvasive technique, and one that lacked subjective room for error, to address the thyroid nodule problem.

The question was whether an artificial intelligence (AI) algorithm could match radiologist performance in classifying thyroid nodules according to the characteristics of their ultrasound images.

Other algorithms use AI to predict which nodules are malignant, but they function as “black boxes” – a common criticism of AI. The outside observer cannot ordinarily see how the AI algorithm “knows” what it knows. This characteristic of AI poses at least a theoretical problem when such algorithms are used for diagnosis or medical decision making.

Dr. Thomas’s* approach was to use a set of training data to allow the algorithm he constructed to see 2,025 images from a total of 482 nodules. The thyroid nodules used for training had been subjected to biopsy or excised in surgery, so they all had a definitive status of being benign or malignant.

Then, after the algorithm was refined, a set of 103 nodules with known malignancy status was used to test the algorithm’s sensitivity and specificity.

The algorithm, dubbed AiBx, used a convolutional neural network to build a unique image vector for each nodule. The AiBx algorithm then looked at the training database to find the “nearest neighbors,” or the images it found to be the most similar to those of the nodule being examined.

For example, said Dr. Thomas, a test image of a benign nodule would have an output from the AiBx analysis of three similar images from the database – all benign. Hence, rather than making a black-box call of whether a nodule is benign or malignant, the algorithm merely says: “This nodule resembles a benign nodule in our database.” The interpreting physician can then use the algorithm as a decision aid with confidence.

The overall accuracy of AiBx was 81.5%, sensitivity was 87.8%, and specificity was 78.5%. Positive predictive value was 65.9%.

As more images are added to the database, AiBx can easily be retrained and refined, said Dr. Thomas.

“It’s intuitive and explainable,” he added, noting that the algorithm is also a good teaching tool for residents and fellows.

“This AI model can be deployed as an app, integrated with [medical imaging systems] or hosted as a website. By using image-similarity AI models we can eliminate subjectivity and decrease the number of unnecessary biopsies,” he explained in the abstract accompanying the presentation.

However, he said that the algorithm as it currently stands has limitations: It has been tested on only 103 images thus far, and there’s the potential for selection bias.

Dr. Thomas* reported that, although he developed the AiBx algorithm, he has not drawn income or royalties from it. He reported no other relevant conflicts of interest.
 

SOURCE: Thomas* J et al. ATA 2019, Oral Abstract 27.

*Correction, 21/11/2019: An earlier version of this story misstated Dr. Thomas's last name.

PARIS – Over the course of years and decades, lower LDL cholesterol levels and lower systolic blood pressure can reduce the lifetime risk of cardiovascular disease by up to 80%, according to a new study.

SilverV/thinkstockphotos

“What we found is that lifetime exposure to the combination of lower LDL and lower systolic blood pressure is associated with independent, additive, and dose-dependent effects on the lifetime risk of cardiovascular disease,” said the study’s senior author, Brian Ference, MD, speaking at the annual congress of the European Society of Cardiology. “The data seem to confirm that most cardiovascular events are preventable, and suggest that most cardiovascular events can be prevented, with prolonged exposure to modestly lower LDL cholesterol and systolic blood pressure.”

Any reduction of LDL-C and systolic blood pressure (SBP), in any combination, was associated with a lower lifetime risk of cardiovascular disease (CVD) in the study, which took advantage of the United Kingdom’s large Biobank to identify individuals with genetically lower LDL-C and blood pressure levels. The relationship was dose-dependent and showed a log-linear relationship to the combined absolute LDL-C and SBP differences, said Dr. Ference, professor and executive director of the Centre for Naturally Randomised Trials at the University of Cambridge, England.

The results validate current guidelines that focus on a lifetime approach to cardiovascular risk reduction and support a focus on therapeutic lifestyle interventions for individuals at all levels of risk for cardiovascular events, said Dr. Ference. He foresees the results shaping new risk-estimating algorithms and informing the next round of prevention guidelines.

Previous studies had suggested that long-term exposure to lower levels of LDL-C and lower systolic blood pressure reduced cardiovascular risk, but the association hadn’t been fully quantified. Ideally, said Dr. Ference, the question would be answered by a long-term randomized controlled trial, but it would be decades before meaningful data would accrue, and such a trial is unlikely to be conducted.

Using data from 438,952 Biobank participants, Dr. Ference and coinvestigators sought to quantify the association between LDL-C, systolic blood pressure, and atherosclerotic CVD. Taking advantage of genetic variants known to be associated with both lower LDL-C and lower systolic blood pressure, the researchers constructed a “natural randomization” trial. This trial design is also known as Mendelian randomization.

First, the entire study population was randomized into those with exome variants associated with higher or lower LDL-C, which resulted in a mean 15-mg/dL difference between the arms. Then, each LDL-C arm was randomized into groups with exome variants associated with higher or lower SBP, resulting in a difference of 2.9-3 mm Hg between the blood pressure arms within each LDL arm. This randomization yielded a reference group, a group with lower LDL-C, a group with lower SBP, and a group with lower LDL-C and SBP.

For the total population, the mean LDL-C was 138 mg/dL, and the mean SBP was 137.8 mm Hg.

A total of 24,980 participants had coronary revascularization, a nonfatal myocardial infarction (MI), or coronary death – the composite primary outcome measure of major coronary events.

“What we found is that long-term exposure to the combination of 1 mmol/L [about 39 mg/dL] lower LDL and 10 mm/Hg lower blood pressure is associated with an 80% lifetime reduction in risk of cardiovascular events, a 75% reduction in the risk of MI, and 68% reduction in the long-term risk of cardiovascular death,” said Dr. Ference.

By breaking participants out into separate quartiles of LDL-C and SBP levels, and examining outcomes for each quartile independently, Dr. Ference and collaborators were able to ascertain that the salutary effects of lower LDL-C and SBP were independent of each other.

Looking at individual cardiovascular outcomes, “The effect of combined exposure to both lower LDL and lower systolic blood pressure appear to be quite similar across multiple composite cardiovascular outcomes,” said Dr. Ference; benefit was seen in risk of MI, stroke, and other vascular events.

Plotting out the amount of risk reduction against the genetic scores for LDL-C and SBP reduction showed a proportional relationship that was logarithmically linear. “These large proportional reductions in risk really suggest that, for LDL, systolic blood pressure, and their combination, the benefit really depends both on the magnitude and the duration of the exposure,” said Dr. Ference. The effect was seen regardless of age, gender, body mass index, and diabetes status; being a smoker slightly attenuated the effects of LDL-C and SBP.

The mean participant age was 65 years, and women made up 54% of the study population. Aside from lipid values and systolic blood pressure, there were no significant between-group differences.

From these findings, what message can clinicians take to their patients? “Benefit is a much greater motivator, rather than the nebulous concept of risk,” said Dr. Ference. “So if we begin to crystallize and give an estimate of how much someone can benefit – either from adhering to a healthy lifestyle, with specific goals for LDL and blood pressure reductions, or from encouraging them to remain compliant with their therapies, achieving those corresponding goals – we can quantify their expected clinical benefit and encourage them to invest in their health over the long term.”

Dr. Ference said that the actual mechanism by which lipids and blood pressure are lowered matters less than the amount and duration of lowering: “These data are really agnostic as to the mechanism by which either blood pressure or LDL – or apo-B–containing lipoproteins generally – and blood pressure are reduced. It really suggests that whatever mechanism by which an individual person can most effectively lower their LDL and blood pressure, that’s the best one for that person, if they can maintain that over time.”

Dr. Ference reported financial relationships, including research contracts, consulting arrangements, receipt of royalties, and being an owner or stockholder of more than a dozen pharmaceutical companies. The study was funded by the United Kingdom’s National Institute of Health Research and Medical Research Council, and by the British Heart Foundation.

[email protected]

SOURCE: Ference B. et al. ESC Congress 2019, Hot Line Session 3.

PARIS – Over the course of years and decades, lower LDL cholesterol levels and lower systolic blood pressure can reduce the lifetime risk of cardiovascular disease by up to 80%, according to a new study.

SilverV/thinkstockphotos

“What we found is that lifetime exposure to the combination of lower LDL and lower systolic blood pressure is associated with independent, additive, and dose-dependent effects on the lifetime risk of cardiovascular disease,” said the study’s senior author, Brian Ference, MD, speaking at the annual congress of the European Society of Cardiology. “The data seem to confirm that most cardiovascular events are preventable, and suggest that most cardiovascular events can be prevented, with prolonged exposure to modestly lower LDL cholesterol and systolic blood pressure.”

Any reduction of LDL-C and systolic blood pressure (SBP), in any combination, was associated with a lower lifetime risk of cardiovascular disease (CVD) in the study, which took advantage of the United Kingdom’s large Biobank to identify individuals with genetically lower LDL-C and blood pressure levels. The relationship was dose-dependent and showed a log-linear relationship to the combined absolute LDL-C and SBP differences, said Dr. Ference, professor and executive director of the Centre for Naturally Randomised Trials at the University of Cambridge, England.

The results validate current guidelines that focus on a lifetime approach to cardiovascular risk reduction and support a focus on therapeutic lifestyle interventions for individuals at all levels of risk for cardiovascular events, said Dr. Ference. He foresees the results shaping new risk-estimating algorithms and informing the next round of prevention guidelines.

Previous studies had suggested that long-term exposure to lower levels of LDL-C and lower systolic blood pressure reduced cardiovascular risk, but the association hadn’t been fully quantified. Ideally, said Dr. Ference, the question would be answered by a long-term randomized controlled trial, but it would be decades before meaningful data would accrue, and such a trial is unlikely to be conducted.

Using data from 438,952 Biobank participants, Dr. Ference and coinvestigators sought to quantify the association between LDL-C, systolic blood pressure, and atherosclerotic CVD. Taking advantage of genetic variants known to be associated with both lower LDL-C and lower systolic blood pressure, the researchers constructed a “natural randomization” trial. This trial design is also known as Mendelian randomization.

First, the entire study population was randomized into those with exome variants associated with higher or lower LDL-C, which resulted in a mean 15-mg/dL difference between the arms. Then, each LDL-C arm was randomized into groups with exome variants associated with higher or lower SBP, resulting in a difference of 2.9-3 mm Hg between the blood pressure arms within each LDL arm. This randomization yielded a reference group, a group with lower LDL-C, a group with lower SBP, and a group with lower LDL-C and SBP.

For the total population, the mean LDL-C was 138 mg/dL, and the mean SBP was 137.8 mm Hg.

A total of 24,980 participants had coronary revascularization, a nonfatal myocardial infarction (MI), or coronary death – the composite primary outcome measure of major coronary events.

“What we found is that long-term exposure to the combination of 1 mmol/L [about 39 mg/dL] lower LDL and 10 mm/Hg lower blood pressure is associated with an 80% lifetime reduction in risk of cardiovascular events, a 75% reduction in the risk of MI, and 68% reduction in the long-term risk of cardiovascular death,” said Dr. Ference.

By breaking participants out into separate quartiles of LDL-C and SBP levels, and examining outcomes for each quartile independently, Dr. Ference and collaborators were able to ascertain that the salutary effects of lower LDL-C and SBP were independent of each other.

Looking at individual cardiovascular outcomes, “The effect of combined exposure to both lower LDL and lower systolic blood pressure appear to be quite similar across multiple composite cardiovascular outcomes,” said Dr. Ference; benefit was seen in risk of MI, stroke, and other vascular events.

Plotting out the amount of risk reduction against the genetic scores for LDL-C and SBP reduction showed a proportional relationship that was logarithmically linear. “These large proportional reductions in risk really suggest that, for LDL, systolic blood pressure, and their combination, the benefit really depends both on the magnitude and the duration of the exposure,” said Dr. Ference. The effect was seen regardless of age, gender, body mass index, and diabetes status; being a smoker slightly attenuated the effects of LDL-C and SBP.

The mean participant age was 65 years, and women made up 54% of the study population. Aside from lipid values and systolic blood pressure, there were no significant between-group differences.

From these findings, what message can clinicians take to their patients? “Benefit is a much greater motivator, rather than the nebulous concept of risk,” said Dr. Ference. “So if we begin to crystallize and give an estimate of how much someone can benefit – either from adhering to a healthy lifestyle, with specific goals for LDL and blood pressure reductions, or from encouraging them to remain compliant with their therapies, achieving those corresponding goals – we can quantify their expected clinical benefit and encourage them to invest in their health over the long term.”

Dr. Ference said that the actual mechanism by which lipids and blood pressure are lowered matters less than the amount and duration of lowering: “These data are really agnostic as to the mechanism by which either blood pressure or LDL – or apo-B–containing lipoproteins generally – and blood pressure are reduced. It really suggests that whatever mechanism by which an individual person can most effectively lower their LDL and blood pressure, that’s the best one for that person, if they can maintain that over time.”

Dr. Ference reported financial relationships, including research contracts, consulting arrangements, receipt of royalties, and being an owner or stockholder of more than a dozen pharmaceutical companies. The study was funded by the United Kingdom’s National Institute of Health Research and Medical Research Council, and by the British Heart Foundation.

[email protected]

SOURCE: Ference B. et al. ESC Congress 2019, Hot Line Session 3.

PARIS – Over the course of years and decades, lower LDL cholesterol levels and lower systolic blood pressure can reduce the lifetime risk of cardiovascular disease by up to 80%, according to a new study.

SilverV/thinkstockphotos

“What we found is that lifetime exposure to the combination of lower LDL and lower systolic blood pressure is associated with independent, additive, and dose-dependent effects on the lifetime risk of cardiovascular disease,” said the study’s senior author, Brian Ference, MD, speaking at the annual congress of the European Society of Cardiology. “The data seem to confirm that most cardiovascular events are preventable, and suggest that most cardiovascular events can be prevented, with prolonged exposure to modestly lower LDL cholesterol and systolic blood pressure.”

Any reduction of LDL-C and systolic blood pressure (SBP), in any combination, was associated with a lower lifetime risk of cardiovascular disease (CVD) in the study, which took advantage of the United Kingdom’s large Biobank to identify individuals with genetically lower LDL-C and blood pressure levels. The relationship was dose-dependent and showed a log-linear relationship to the combined absolute LDL-C and SBP differences, said Dr. Ference, professor and executive director of the Centre for Naturally Randomised Trials at the University of Cambridge, England.

The results validate current guidelines that focus on a lifetime approach to cardiovascular risk reduction and support a focus on therapeutic lifestyle interventions for individuals at all levels of risk for cardiovascular events, said Dr. Ference. He foresees the results shaping new risk-estimating algorithms and informing the next round of prevention guidelines.

Previous studies had suggested that long-term exposure to lower levels of LDL-C and lower systolic blood pressure reduced cardiovascular risk, but the association hadn’t been fully quantified. Ideally, said Dr. Ference, the question would be answered by a long-term randomized controlled trial, but it would be decades before meaningful data would accrue, and such a trial is unlikely to be conducted.

Using data from 438,952 Biobank participants, Dr. Ference and coinvestigators sought to quantify the association between LDL-C, systolic blood pressure, and atherosclerotic CVD. Taking advantage of genetic variants known to be associated with both lower LDL-C and lower systolic blood pressure, the researchers constructed a “natural randomization” trial. This trial design is also known as Mendelian randomization.

First, the entire study population was randomized into those with exome variants associated with higher or lower LDL-C, which resulted in a mean 15-mg/dL difference between the arms. Then, each LDL-C arm was randomized into groups with exome variants associated with higher or lower SBP, resulting in a difference of 2.9-3 mm Hg between the blood pressure arms within each LDL arm. This randomization yielded a reference group, a group with lower LDL-C, a group with lower SBP, and a group with lower LDL-C and SBP.

For the total population, the mean LDL-C was 138 mg/dL, and the mean SBP was 137.8 mm Hg.

A total of 24,980 participants had coronary revascularization, a nonfatal myocardial infarction (MI), or coronary death – the composite primary outcome measure of major coronary events.

“What we found is that long-term exposure to the combination of 1 mmol/L [about 39 mg/dL] lower LDL and 10 mm/Hg lower blood pressure is associated with an 80% lifetime reduction in risk of cardiovascular events, a 75% reduction in the risk of MI, and 68% reduction in the long-term risk of cardiovascular death,” said Dr. Ference.

By breaking participants out into separate quartiles of LDL-C and SBP levels, and examining outcomes for each quartile independently, Dr. Ference and collaborators were able to ascertain that the salutary effects of lower LDL-C and SBP were independent of each other.

Looking at individual cardiovascular outcomes, “The effect of combined exposure to both lower LDL and lower systolic blood pressure appear to be quite similar across multiple composite cardiovascular outcomes,” said Dr. Ference; benefit was seen in risk of MI, stroke, and other vascular events.

Plotting out the amount of risk reduction against the genetic scores for LDL-C and SBP reduction showed a proportional relationship that was logarithmically linear. “These large proportional reductions in risk really suggest that, for LDL, systolic blood pressure, and their combination, the benefit really depends both on the magnitude and the duration of the exposure,” said Dr. Ference. The effect was seen regardless of age, gender, body mass index, and diabetes status; being a smoker slightly attenuated the effects of LDL-C and SBP.

The mean participant age was 65 years, and women made up 54% of the study population. Aside from lipid values and systolic blood pressure, there were no significant between-group differences.

From these findings, what message can clinicians take to their patients? “Benefit is a much greater motivator, rather than the nebulous concept of risk,” said Dr. Ference. “So if we begin to crystallize and give an estimate of how much someone can benefit – either from adhering to a healthy lifestyle, with specific goals for LDL and blood pressure reductions, or from encouraging them to remain compliant with their therapies, achieving those corresponding goals – we can quantify their expected clinical benefit and encourage them to invest in their health over the long term.”

Dr. Ference said that the actual mechanism by which lipids and blood pressure are lowered matters less than the amount and duration of lowering: “These data are really agnostic as to the mechanism by which either blood pressure or LDL – or apo-B–containing lipoproteins generally – and blood pressure are reduced. It really suggests that whatever mechanism by which an individual person can most effectively lower their LDL and blood pressure, that’s the best one for that person, if they can maintain that over time.”

Dr. Ference reported financial relationships, including research contracts, consulting arrangements, receipt of royalties, and being an owner or stockholder of more than a dozen pharmaceutical companies. The study was funded by the United Kingdom’s National Institute of Health Research and Medical Research Council, and by the British Heart Foundation.

[email protected]

SOURCE: Ference B. et al. ESC Congress 2019, Hot Line Session 3.

CHICAGO – Many patients with thyroid cancer can be sent home after lateral neck dissections with few or no opioids, in the experience of an institution that made a sea change in opioid prescribing practices.

Kari Oakes/MDedge News

Between 2012 to mid-2019, Oregon Health & Science University (OHSU), Portland, saw 243 patients who received lateral neck dissections for thyroid cancer and were opioid naive. Before a shift in prescribing practices in early 2017, 5.3% of patients were discharged without opioids after lateral neck dissections for thyroid cancer, whereas after the shift, 41.7% of patients went home on an opioid-free regimen, James Y. Lim, MD, an endocrine surgeon and assistant professor at the university, said during a poster presentation at the annual meeting of the American Thyroid Association.

The initiative, led by Maisie L. Shindo, MD, was started at the OHSU Thyroid and Parathyroid Center in late 2016 in an effort to reduce the number of opioid prescriptions in postoperative patients, Dr. Lim explained in an interview after his presentation. Dr. Shindo, coauthor of the study, directs the thyroid and parathyroid surgery department at the university.

“Before the initiative, standard postoperative pain control consisted of opioids. However, it was common for patients to mention that they did not need them at all,” said Dr. Lim. “Our prescribing practices today reflect the ability to maintain patient comfort without having to resort to opioids. We are able to keep more than 90% of our patients comfortable with a multimodal approach to pain,” he said.

Dr. Lim and colleagues used a retrospective record review to tally how many opioids were initially prescribed at discharge after lateral neck dissections for thyroid cancer, along with the number and quantity of refills for opioids after discharge. Opioid doses were converted to morphine milligram equivalents (MME), and dosing patterns were compared for the periods before and after Feb. 1, 2017, when operating surgeons changed opioid prescribing patterns. These two subgroups were termed group 1 and group 2, respectively.

In all, 143 of the total 243 patients included in the study were women, and the mean age at the time of surgery was 47 years. Patients in group 1 had 170 surgeries, and those in group 2 had 103 surgeries.

Group 1 patients received a mean 295.4 MME after surgery, and group 2 patients received a mean 85.89 MME, though there was wide variation in discharge prescribing within each group. The absolute difference between the pre- and postinitiative groups was 209.51 MME (95% confidence interval, 157.8-261.2), for an effect size of 1.08. The MME figures for each group reflected both discharge medication and any refills or rescue prescriptions that were required.

“Decreasing the volume of opioids prescribed at discharge will decrease waste and reduce potential for addiction,” the authors noted.

As far as is known, “this is the first study that seeks to identify the extent of opioid needs after an extensive neck dissection for thyroid cancer operation,” said Dr. Lim, who added that he has been surprised at how well patients do after surgery. He said he and other surgeons had expected patients to have more pain from lateral neck dissections than they seem to experience.

“There have been studies, including from our own institution, that reported the relatively small need for opioids after a central neck procedure, such as a total thyroidectomy,” Dr. Lim said. “Our study showed that those requirements remain low even with more extensive lateral neck dissections. In the last 8 months of the study, more than 70% of patients with lateral neck dissections did not require opioids on discharge.”

Dr. Lim said that he and the rest of the care team advise patients to ramp up nonpharmacologic options, including ibuprofen, acetaminophen, ice packs, and throat lozenges – all of which can make a big difference in postoperative comfort.

Paying attention to how patients fare during an inpatient stay or even same-day procedures can help physicians estimate postdischarge needs, said Dr. Lim: “For our lateral neck dissections, patients usually stay overnight, and we can get a pretty good estimate of how their pain is being managed off opioids. For same-day procedures, it requires evaluating the patient before discharge and reassessing the pain needs at that time.”

Helping patients and their families understand the postoperative course and what level of discomfort they can expect has helped in the effort to minimize opioid use, Dr. Lim said. Overall, patients, family, and staff have received the changes “very well,” he added.

Practices that are considering a move toward opioid-free or opioid-sparing regimens after surgery should know that “it does require buy-in from all members of the medical team as well as the patients,” Dr. Lim emphasized.

“It starts at the initial surgical consultation, with surgeons educating patients on what to expect in terms of postoperative discomfort and pain. Patients are informed that they will have some discomfort and mild pain that is generally controlled with nonopioid, over-the-counter medications and cold therapy to the surgical site,” he explained.

“It requires education of the nurses and residents to encourage moving away from using opioids as a first-line therapy,” but it’s worth the hard work to get to a point where patients are going home with few, or no, opioids, said Dr. Lim. “Ultimately, patients are happier and are often relieved that their pain can be controlled without opioids,” he said.

Dr. Shindo is the senior author of a related study examining opioid reduction in neck dissection for a variety of head and neck cancers. In that study, she and her coauthors found that opioid requirements vary by cancer type. In an upcoming manuscript, the researchers are aiming to characterize typical opioid requirements for commonly performed procedures, to provide surgeons with evidence-based baselines for appropriate, but not excessive, opioid prescribing.

Dr. Lim reported no outside sources of funding. He, Dr. Shindo, and a third author reported that they had no conflicts of interest.

[email protected]

SOURCE: Lim J et al. ATA 2019, Poster 401.

CHICAGO – Many patients with thyroid cancer can be sent home after lateral neck dissections with few or no opioids, in the experience of an institution that made a sea change in opioid prescribing practices.

Kari Oakes/MDedge News

Between 2012 to mid-2019, Oregon Health & Science University (OHSU), Portland, saw 243 patients who received lateral neck dissections for thyroid cancer and were opioid naive. Before a shift in prescribing practices in early 2017, 5.3% of patients were discharged without opioids after lateral neck dissections for thyroid cancer, whereas after the shift, 41.7% of patients went home on an opioid-free regimen, James Y. Lim, MD, an endocrine surgeon and assistant professor at the university, said during a poster presentation at the annual meeting of the American Thyroid Association.

The initiative, led by Maisie L. Shindo, MD, was started at the OHSU Thyroid and Parathyroid Center in late 2016 in an effort to reduce the number of opioid prescriptions in postoperative patients, Dr. Lim explained in an interview after his presentation. Dr. Shindo, coauthor of the study, directs the thyroid and parathyroid surgery department at the university.

“Before the initiative, standard postoperative pain control consisted of opioids. However, it was common for patients to mention that they did not need them at all,” said Dr. Lim. “Our prescribing practices today reflect the ability to maintain patient comfort without having to resort to opioids. We are able to keep more than 90% of our patients comfortable with a multimodal approach to pain,” he said.

Dr. Lim and colleagues used a retrospective record review to tally how many opioids were initially prescribed at discharge after lateral neck dissections for thyroid cancer, along with the number and quantity of refills for opioids after discharge. Opioid doses were converted to morphine milligram equivalents (MME), and dosing patterns were compared for the periods before and after Feb. 1, 2017, when operating surgeons changed opioid prescribing patterns. These two subgroups were termed group 1 and group 2, respectively.

In all, 143 of the total 243 patients included in the study were women, and the mean age at the time of surgery was 47 years. Patients in group 1 had 170 surgeries, and those in group 2 had 103 surgeries.

Group 1 patients received a mean 295.4 MME after surgery, and group 2 patients received a mean 85.89 MME, though there was wide variation in discharge prescribing within each group. The absolute difference between the pre- and postinitiative groups was 209.51 MME (95% confidence interval, 157.8-261.2), for an effect size of 1.08. The MME figures for each group reflected both discharge medication and any refills or rescue prescriptions that were required.

“Decreasing the volume of opioids prescribed at discharge will decrease waste and reduce potential for addiction,” the authors noted.

As far as is known, “this is the first study that seeks to identify the extent of opioid needs after an extensive neck dissection for thyroid cancer operation,” said Dr. Lim, who added that he has been surprised at how well patients do after surgery. He said he and other surgeons had expected patients to have more pain from lateral neck dissections than they seem to experience.

“There have been studies, including from our own institution, that reported the relatively small need for opioids after a central neck procedure, such as a total thyroidectomy,” Dr. Lim said. “Our study showed that those requirements remain low even with more extensive lateral neck dissections. In the last 8 months of the study, more than 70% of patients with lateral neck dissections did not require opioids on discharge.”

Dr. Lim said that he and the rest of the care team advise patients to ramp up nonpharmacologic options, including ibuprofen, acetaminophen, ice packs, and throat lozenges – all of which can make a big difference in postoperative comfort.

Paying attention to how patients fare during an inpatient stay or even same-day procedures can help physicians estimate postdischarge needs, said Dr. Lim: “For our lateral neck dissections, patients usually stay overnight, and we can get a pretty good estimate of how their pain is being managed off opioids. For same-day procedures, it requires evaluating the patient before discharge and reassessing the pain needs at that time.”

Helping patients and their families understand the postoperative course and what level of discomfort they can expect has helped in the effort to minimize opioid use, Dr. Lim said. Overall, patients, family, and staff have received the changes “very well,” he added.

Practices that are considering a move toward opioid-free or opioid-sparing regimens after surgery should know that “it does require buy-in from all members of the medical team as well as the patients,” Dr. Lim emphasized.

“It starts at the initial surgical consultation, with surgeons educating patients on what to expect in terms of postoperative discomfort and pain. Patients are informed that they will have some discomfort and mild pain that is generally controlled with nonopioid, over-the-counter medications and cold therapy to the surgical site,” he explained.

“It requires education of the nurses and residents to encourage moving away from using opioids as a first-line therapy,” but it’s worth the hard work to get to a point where patients are going home with few, or no, opioids, said Dr. Lim. “Ultimately, patients are happier and are often relieved that their pain can be controlled without opioids,” he said.

Dr. Shindo is the senior author of a related study examining opioid reduction in neck dissection for a variety of head and neck cancers. In that study, she and her coauthors found that opioid requirements vary by cancer type. In an upcoming manuscript, the researchers are aiming to characterize typical opioid requirements for commonly performed procedures, to provide surgeons with evidence-based baselines for appropriate, but not excessive, opioid prescribing.

Dr. Lim reported no outside sources of funding. He, Dr. Shindo, and a third author reported that they had no conflicts of interest.

[email protected]

SOURCE: Lim J et al. ATA 2019, Poster 401.

CHICAGO – Many patients with thyroid cancer can be sent home after lateral neck dissections with few or no opioids, in the experience of an institution that made a sea change in opioid prescribing practices.

Kari Oakes/MDedge News

Between 2012 to mid-2019, Oregon Health & Science University (OHSU), Portland, saw 243 patients who received lateral neck dissections for thyroid cancer and were opioid naive. Before a shift in prescribing practices in early 2017, 5.3% of patients were discharged without opioids after lateral neck dissections for thyroid cancer, whereas after the shift, 41.7% of patients went home on an opioid-free regimen, James Y. Lim, MD, an endocrine surgeon and assistant professor at the university, said during a poster presentation at the annual meeting of the American Thyroid Association.

The initiative, led by Maisie L. Shindo, MD, was started at the OHSU Thyroid and Parathyroid Center in late 2016 in an effort to reduce the number of opioid prescriptions in postoperative patients, Dr. Lim explained in an interview after his presentation. Dr. Shindo, coauthor of the study, directs the thyroid and parathyroid surgery department at the university.

“Before the initiative, standard postoperative pain control consisted of opioids. However, it was common for patients to mention that they did not need them at all,” said Dr. Lim. “Our prescribing practices today reflect the ability to maintain patient comfort without having to resort to opioids. We are able to keep more than 90% of our patients comfortable with a multimodal approach to pain,” he said.

Dr. Lim and colleagues used a retrospective record review to tally how many opioids were initially prescribed at discharge after lateral neck dissections for thyroid cancer, along with the number and quantity of refills for opioids after discharge. Opioid doses were converted to morphine milligram equivalents (MME), and dosing patterns were compared for the periods before and after Feb. 1, 2017, when operating surgeons changed opioid prescribing patterns. These two subgroups were termed group 1 and group 2, respectively.

In all, 143 of the total 243 patients included in the study were women, and the mean age at the time of surgery was 47 years. Patients in group 1 had 170 surgeries, and those in group 2 had 103 surgeries.

Group 1 patients received a mean 295.4 MME after surgery, and group 2 patients received a mean 85.89 MME, though there was wide variation in discharge prescribing within each group. The absolute difference between the pre- and postinitiative groups was 209.51 MME (95% confidence interval, 157.8-261.2), for an effect size of 1.08. The MME figures for each group reflected both discharge medication and any refills or rescue prescriptions that were required.

“Decreasing the volume of opioids prescribed at discharge will decrease waste and reduce potential for addiction,” the authors noted.

As far as is known, “this is the first study that seeks to identify the extent of opioid needs after an extensive neck dissection for thyroid cancer operation,” said Dr. Lim, who added that he has been surprised at how well patients do after surgery. He said he and other surgeons had expected patients to have more pain from lateral neck dissections than they seem to experience.

“There have been studies, including from our own institution, that reported the relatively small need for opioids after a central neck procedure, such as a total thyroidectomy,” Dr. Lim said. “Our study showed that those requirements remain low even with more extensive lateral neck dissections. In the last 8 months of the study, more than 70% of patients with lateral neck dissections did not require opioids on discharge.”

Dr. Lim said that he and the rest of the care team advise patients to ramp up nonpharmacologic options, including ibuprofen, acetaminophen, ice packs, and throat lozenges – all of which can make a big difference in postoperative comfort.

Paying attention to how patients fare during an inpatient stay or even same-day procedures can help physicians estimate postdischarge needs, said Dr. Lim: “For our lateral neck dissections, patients usually stay overnight, and we can get a pretty good estimate of how their pain is being managed off opioids. For same-day procedures, it requires evaluating the patient before discharge and reassessing the pain needs at that time.”

Helping patients and their families understand the postoperative course and what level of discomfort they can expect has helped in the effort to minimize opioid use, Dr. Lim said. Overall, patients, family, and staff have received the changes “very well,” he added.

Practices that are considering a move toward opioid-free or opioid-sparing regimens after surgery should know that “it does require buy-in from all members of the medical team as well as the patients,” Dr. Lim emphasized.

“It starts at the initial surgical consultation, with surgeons educating patients on what to expect in terms of postoperative discomfort and pain. Patients are informed that they will have some discomfort and mild pain that is generally controlled with nonopioid, over-the-counter medications and cold therapy to the surgical site,” he explained.

“It requires education of the nurses and residents to encourage moving away from using opioids as a first-line therapy,” but it’s worth the hard work to get to a point where patients are going home with few, or no, opioids, said Dr. Lim. “Ultimately, patients are happier and are often relieved that their pain can be controlled without opioids,” he said.

Dr. Shindo is the senior author of a related study examining opioid reduction in neck dissection for a variety of head and neck cancers. In that study, she and her coauthors found that opioid requirements vary by cancer type. In an upcoming manuscript, the researchers are aiming to characterize typical opioid requirements for commonly performed procedures, to provide surgeons with evidence-based baselines for appropriate, but not excessive, opioid prescribing.

Dr. Lim reported no outside sources of funding. He, Dr. Shindo, and a third author reported that they had no conflicts of interest.

[email protected]

SOURCE: Lim J et al. ATA 2019, Poster 401.

CHICAGO – Current dosing recommendations for thyroid replacement during immune checkpoint inhibitor therapy may overshoot the mark, both for patients with preexisting and de novo hypothyroidism.

Kari Oakes/MDedge News

The real-world data, presented by Megan Kristan, MD, at the annual meeting of the American Thyroid Association, refine recommendations for dosing by body weight for levothyroxine in patients receiving checkpoint inhibitor therapy.

Immune checkpoint inhibitors stand a good chance of turning the tide against melanoma, some lung cancers, and other malignancies that have long been considered lethal. However, as more patients are exposed to the therapies, endocrinologists are seeing a wave of thyroid abnormalities, and must decide when, and at what doses, to treat hypothyroidism, said Dr. Kristan, a diabetes, endocrinology, and nutrition fellow at the University of Maryland, Baltimore.

Six checkpoint inhibitors are currently approved to hit a variety of molecular targets, and the prevalence of thyroid toxicity and hypothyroidism across the drug class ranges from a reported 9% to 40%, said Dr. Kristan.

The acknowledged thyroid toxicity of these drugs led the American Society for Clinical Oncology (ASCO) to issue guidelines advising that oncologists obtain baseline thyroid function tests before initiating checkpoint inhibitors, and that values be rechecked frequently – every 4-6 weeks – during therapy.

The guidelines advise dosing levothyroxine at approximately 1.6 mcg/kg per day, based on ideal patient body weight. The recommendation is limited to patients without risk factors, and approximates full levothyroxine replacement.

However, some patients enter cancer treatment with hypothyroidism, and some develop it de novo after beginning checkpoint inhibitor therapy. It is not known how best to treat each group, said Dr. Kristan.

To help answer that question, she and her collaborators at Georgetown University Hospital, McLean, Va., made use of a database drawn from five hospitals to perform a retrospective chart review. They looked at 822 patients who had received checkpoint inhibitor therapy, and from those patients, they selected 118 who had a diagnosis of hypothyroidism, or who received a prescription for levothyroxine during the 8-year study period.

The investigators assembled all available relevant data for each patient, including thyroid function tests, levothyroxine dosing, type of cancer, and type of therapy. They sorted participants into those who had received a diagnosis of hypothyroidism before or after receiving the first dose of checkpoint inhibitor therapy.

At baseline, 81 patients had preexisting hypothyroidism and were receiving a mean levothyroxine dose of 88.2 mcg. After treatment, the mean dose was 94.3 mcg, a nonsignificant difference. The median dose for this group remained at 88 mcg through treatment.

For the 37 patients who developed hypothyroidism de novo during checkpoint inhibitor therapy, the final observed levothyroxine dose was 71.2 mcg.

The mean age of the patients at baseline was 69 years. About half were women, and 91% were white. Either nivolumab or pembrolizumab was used in 72% of patients, making them the most commonly used checkpoint inhibitors, though 90% of patients received combination therapy. Taken together, melanoma and lung cancer accounted for about two-thirds of the cancers seen.

For both groups, the on-treatment levothyroxine dose was considerably lower than the ASCO-recommended, weight-based dosing, which would have been 122.9 mcg for those with preexisting hypothyroidism and 115.7 mcg for those who developed hypothyroidism on treatment (P less than .001 for both).

Dr. Kristan noted that thyroid stimulating hormone (TSH) values for patients with pretreatment hypothyroidism peaked between weeks 12 and 20, though there was no preemptive adjustment of levothyroxine dosing.

For those who developed on-treatment hypothyroidism, TSH values peaked at a series of times, at about weeks 8, 16, and 32. These waves of TSH elevation, she said, support the 4- to 6-week follow-up interval recommended in the ASCO guidelines.

However, she said, patients with de novo hypothyroidism “should not be started on the 1.6-mcg/kg-a-day weight-based dosing.” The cohort with de novo hypothyroidism in Dr. Kristan’s analysis required a daily dose of about 1 mcg/kg, she said. These real-world results support the idea that many patients on checkpoint inhibitors retain some thyroid reserve.

Dr. Kristan said that based on these findings, she and her collaborators recommend monitoring thyroid function every 4-6 weeks for patients taking immune checkpoint inhibitors. Patients with preexisting thyroid disease should not have an empiric adjustment of levothyroxine dose on checkpoint inhibitor initiation. For patients who develop thyroiditis after starting therapy, initiating a dose at 1 mcg/kg per day of ideal body weight is a good place to start, and treatment response should be monitored.

The study was limited by its retrospective nature and the small sample size, acknowledged Dr. Kristan. In addition, there were confounding variables and different frequencies of testing across institutions, and antibody status was not available and may have affected the results. Testing was performable for all participants.

Dr. Kristan said that the analysis opens up areas for further study, such as which patient populations are at risk for developing thyroid toxicity, what baseline characteristics can help predict which patients develop toxicity, and whether particular checkpoint inhibitors are more likely to cause toxicity. In addition, she said, a subset of patients will develop hyperthyroidism on checkpoint inhibitor therapy, and little is known about how to treat that complication.

Dr. Kristan reported no conflicts of interest. The research she presented was completed during her residency at Georgetown University.
 

SOURCE: Kristan M et al. ATA 2019, Oral Abstract 25.

CHICAGO – Current dosing recommendations for thyroid replacement during immune checkpoint inhibitor therapy may overshoot the mark, both for patients with preexisting and de novo hypothyroidism.

Kari Oakes/MDedge News

The real-world data, presented by Megan Kristan, MD, at the annual meeting of the American Thyroid Association, refine recommendations for dosing by body weight for levothyroxine in patients receiving checkpoint inhibitor therapy.

Immune checkpoint inhibitors stand a good chance of turning the tide against melanoma, some lung cancers, and other malignancies that have long been considered lethal. However, as more patients are exposed to the therapies, endocrinologists are seeing a wave of thyroid abnormalities, and must decide when, and at what doses, to treat hypothyroidism, said Dr. Kristan, a diabetes, endocrinology, and nutrition fellow at the University of Maryland, Baltimore.

Six checkpoint inhibitors are currently approved to hit a variety of molecular targets, and the prevalence of thyroid toxicity and hypothyroidism across the drug class ranges from a reported 9% to 40%, said Dr. Kristan.

The acknowledged thyroid toxicity of these drugs led the American Society for Clinical Oncology (ASCO) to issue guidelines advising that oncologists obtain baseline thyroid function tests before initiating checkpoint inhibitors, and that values be rechecked frequently – every 4-6 weeks – during therapy.

The guidelines advise dosing levothyroxine at approximately 1.6 mcg/kg per day, based on ideal patient body weight. The recommendation is limited to patients without risk factors, and approximates full levothyroxine replacement.

However, some patients enter cancer treatment with hypothyroidism, and some develop it de novo after beginning checkpoint inhibitor therapy. It is not known how best to treat each group, said Dr. Kristan.

To help answer that question, she and her collaborators at Georgetown University Hospital, McLean, Va., made use of a database drawn from five hospitals to perform a retrospective chart review. They looked at 822 patients who had received checkpoint inhibitor therapy, and from those patients, they selected 118 who had a diagnosis of hypothyroidism, or who received a prescription for levothyroxine during the 8-year study period.

The investigators assembled all available relevant data for each patient, including thyroid function tests, levothyroxine dosing, type of cancer, and type of therapy. They sorted participants into those who had received a diagnosis of hypothyroidism before or after receiving the first dose of checkpoint inhibitor therapy.

At baseline, 81 patients had preexisting hypothyroidism and were receiving a mean levothyroxine dose of 88.2 mcg. After treatment, the mean dose was 94.3 mcg, a nonsignificant difference. The median dose for this group remained at 88 mcg through treatment.

For the 37 patients who developed hypothyroidism de novo during checkpoint inhibitor therapy, the final observed levothyroxine dose was 71.2 mcg.

The mean age of the patients at baseline was 69 years. About half were women, and 91% were white. Either nivolumab or pembrolizumab was used in 72% of patients, making them the most commonly used checkpoint inhibitors, though 90% of patients received combination therapy. Taken together, melanoma and lung cancer accounted for about two-thirds of the cancers seen.

For both groups, the on-treatment levothyroxine dose was considerably lower than the ASCO-recommended, weight-based dosing, which would have been 122.9 mcg for those with preexisting hypothyroidism and 115.7 mcg for those who developed hypothyroidism on treatment (P less than .001 for both).

Dr. Kristan noted that thyroid stimulating hormone (TSH) values for patients with pretreatment hypothyroidism peaked between weeks 12 and 20, though there was no preemptive adjustment of levothyroxine dosing.

For those who developed on-treatment hypothyroidism, TSH values peaked at a series of times, at about weeks 8, 16, and 32. These waves of TSH elevation, she said, support the 4- to 6-week follow-up interval recommended in the ASCO guidelines.

However, she said, patients with de novo hypothyroidism “should not be started on the 1.6-mcg/kg-a-day weight-based dosing.” The cohort with de novo hypothyroidism in Dr. Kristan’s analysis required a daily dose of about 1 mcg/kg, she said. These real-world results support the idea that many patients on checkpoint inhibitors retain some thyroid reserve.

Dr. Kristan said that based on these findings, she and her collaborators recommend monitoring thyroid function every 4-6 weeks for patients taking immune checkpoint inhibitors. Patients with preexisting thyroid disease should not have an empiric adjustment of levothyroxine dose on checkpoint inhibitor initiation. For patients who develop thyroiditis after starting therapy, initiating a dose at 1 mcg/kg per day of ideal body weight is a good place to start, and treatment response should be monitored.

The study was limited by its retrospective nature and the small sample size, acknowledged Dr. Kristan. In addition, there were confounding variables and different frequencies of testing across institutions, and antibody status was not available and may have affected the results. Testing was performable for all participants.

Dr. Kristan said that the analysis opens up areas for further study, such as which patient populations are at risk for developing thyroid toxicity, what baseline characteristics can help predict which patients develop toxicity, and whether particular checkpoint inhibitors are more likely to cause toxicity. In addition, she said, a subset of patients will develop hyperthyroidism on checkpoint inhibitor therapy, and little is known about how to treat that complication.

Dr. Kristan reported no conflicts of interest. The research she presented was completed during her residency at Georgetown University.
 

SOURCE: Kristan M et al. ATA 2019, Oral Abstract 25.

CHICAGO – Current dosing recommendations for thyroid replacement during immune checkpoint inhibitor therapy may overshoot the mark, both for patients with preexisting and de novo hypothyroidism.

Kari Oakes/MDedge News

The real-world data, presented by Megan Kristan, MD, at the annual meeting of the American Thyroid Association, refine recommendations for dosing by body weight for levothyroxine in patients receiving checkpoint inhibitor therapy.

Immune checkpoint inhibitors stand a good chance of turning the tide against melanoma, some lung cancers, and other malignancies that have long been considered lethal. However, as more patients are exposed to the therapies, endocrinologists are seeing a wave of thyroid abnormalities, and must decide when, and at what doses, to treat hypothyroidism, said Dr. Kristan, a diabetes, endocrinology, and nutrition fellow at the University of Maryland, Baltimore.

Six checkpoint inhibitors are currently approved to hit a variety of molecular targets, and the prevalence of thyroid toxicity and hypothyroidism across the drug class ranges from a reported 9% to 40%, said Dr. Kristan.

The acknowledged thyroid toxicity of these drugs led the American Society for Clinical Oncology (ASCO) to issue guidelines advising that oncologists obtain baseline thyroid function tests before initiating checkpoint inhibitors, and that values be rechecked frequently – every 4-6 weeks – during therapy.

The guidelines advise dosing levothyroxine at approximately 1.6 mcg/kg per day, based on ideal patient body weight. The recommendation is limited to patients without risk factors, and approximates full levothyroxine replacement.

However, some patients enter cancer treatment with hypothyroidism, and some develop it de novo after beginning checkpoint inhibitor therapy. It is not known how best to treat each group, said Dr. Kristan.

To help answer that question, she and her collaborators at Georgetown University Hospital, McLean, Va., made use of a database drawn from five hospitals to perform a retrospective chart review. They looked at 822 patients who had received checkpoint inhibitor therapy, and from those patients, they selected 118 who had a diagnosis of hypothyroidism, or who received a prescription for levothyroxine during the 8-year study period.

The investigators assembled all available relevant data for each patient, including thyroid function tests, levothyroxine dosing, type of cancer, and type of therapy. They sorted participants into those who had received a diagnosis of hypothyroidism before or after receiving the first dose of checkpoint inhibitor therapy.

At baseline, 81 patients had preexisting hypothyroidism and were receiving a mean levothyroxine dose of 88.2 mcg. After treatment, the mean dose was 94.3 mcg, a nonsignificant difference. The median dose for this group remained at 88 mcg through treatment.

For the 37 patients who developed hypothyroidism de novo during checkpoint inhibitor therapy, the final observed levothyroxine dose was 71.2 mcg.

The mean age of the patients at baseline was 69 years. About half were women, and 91% were white. Either nivolumab or pembrolizumab was used in 72% of patients, making them the most commonly used checkpoint inhibitors, though 90% of patients received combination therapy. Taken together, melanoma and lung cancer accounted for about two-thirds of the cancers seen.

For both groups, the on-treatment levothyroxine dose was considerably lower than the ASCO-recommended, weight-based dosing, which would have been 122.9 mcg for those with preexisting hypothyroidism and 115.7 mcg for those who developed hypothyroidism on treatment (P less than .001 for both).

Dr. Kristan noted that thyroid stimulating hormone (TSH) values for patients with pretreatment hypothyroidism peaked between weeks 12 and 20, though there was no preemptive adjustment of levothyroxine dosing.

For those who developed on-treatment hypothyroidism, TSH values peaked at a series of times, at about weeks 8, 16, and 32. These waves of TSH elevation, she said, support the 4- to 6-week follow-up interval recommended in the ASCO guidelines.

However, she said, patients with de novo hypothyroidism “should not be started on the 1.6-mcg/kg-a-day weight-based dosing.” The cohort with de novo hypothyroidism in Dr. Kristan’s analysis required a daily dose of about 1 mcg/kg, she said. These real-world results support the idea that many patients on checkpoint inhibitors retain some thyroid reserve.

Dr. Kristan said that based on these findings, she and her collaborators recommend monitoring thyroid function every 4-6 weeks for patients taking immune checkpoint inhibitors. Patients with preexisting thyroid disease should not have an empiric adjustment of levothyroxine dose on checkpoint inhibitor initiation. For patients who develop thyroiditis after starting therapy, initiating a dose at 1 mcg/kg per day of ideal body weight is a good place to start, and treatment response should be monitored.

The study was limited by its retrospective nature and the small sample size, acknowledged Dr. Kristan. In addition, there were confounding variables and different frequencies of testing across institutions, and antibody status was not available and may have affected the results. Testing was performable for all participants.

Dr. Kristan said that the analysis opens up areas for further study, such as which patient populations are at risk for developing thyroid toxicity, what baseline characteristics can help predict which patients develop toxicity, and whether particular checkpoint inhibitors are more likely to cause toxicity. In addition, she said, a subset of patients will develop hyperthyroidism on checkpoint inhibitor therapy, and little is known about how to treat that complication.

Dr. Kristan reported no conflicts of interest. The research she presented was completed during her residency at Georgetown University.
 

SOURCE: Kristan M et al. ATA 2019, Oral Abstract 25.

CHICAGO – Higher levels of triiodothyronine (T3) were seen in combatants with PTSD, compared with patients whose PTSD arose from other adverse experiences, according to findings from a systematic review and meta-analysis.

Patients with combat-related PTSD had higher levels of free T3 and total T3, compared with control participants who had experienced childhood or sexual abuse or were a wartime refugee without PTSD (FT3, 0.36 pg/mL higher, and total T3, 31.6 ng/mL higher, respectively; P = .0004 and P less than .00001).

“We found statistically higher free T3 and total T3 levels in patients with [combat-related] PTSD, compared with controls,” said Freddy J.K. Toloza, MD, in an interview during a poster session of the annual meeting of the American Thyroid Association.

However, he noted that there were no overall differences in thyroid-stimulating hormone, free tetraiodothyronine (T4), and total T4 levels between individuals with PTSD and the non-PTSD control participants. In addition, though free and total T3 levels were significantly higher for the overall PTSD cohort than for control participants, the differences were driven by the studies that included combat-exposed individuals.

Dr. Toloza and colleagues included 10 observational studies in their final review and meta-analysis. Five studies looked at war veterans; the others examined individuals who had experienced child abuse or sexual abuse, who were refugees, or who were from the general population.

For inclusion, the studies had to report both mean values and standard deviations for standard thyroid-hormone test values in patients with PTSD, compared with a non-PTSD control group. These included 373 patients with PTSD and 301 control participants. Just under half (47%) were women. None of the studies, wrote the investigators, “compared rates of overt/subclinical thyroid disease between groups.”

There are known links between many endocrine disorders and psychiatric conditions, said Dr. Toloza, but the interplay between disordered thyroid function and neuropsychiatric problems is still being examined. Looking at PTSD is important because it’s estimated that 6%-9% of the U.S. adult population has experienced PTSD over the course of a lifetime.

Levels of thyroid hormones in the systematic review and meta-analysis were still within normal range for the participants with PTSD, acknowledged Dr. Toloza, a research fellow in the division of endocrinology and metabolism at University of Arkansas for Medical Sciences, Little Rock.

However, even though there was no sign of frank thyroid disease in the PTSD population, the elevated T3 levels seen in the analysis are consistent with other studies showing a correlation between higher T3 levels and more-severe PTSD.

It is not known exactly why significant increases in the levels of total and free T3 were seen only in the combat-exposed PTSD population, Dr. Toloza said. “The type of trauma trigger may influence the adaptive responses to stress and might result in diverse thyroid alterations.”

Elevated catecholamine levels, seen in individuals with PTSD, can increase peripheral conversion of T4 to T3, explained Dr. Toloza. Ongoing catecholamine elevation may account for the isolated elevation in T3 levels in the PTSD population. Beta1-adrenergic blockade is an accepted pharmacologic strategy to help alleviate PTSD symptoms.

Dr. Toloza and coinvestigators did not have access to data that would have allowed them to ascertain what types of injuries were sustained by individuals with combat-related PTSD, but he noted in response to a question, that it would be worthwhile to see whether combatants who were blast exposed had different thyroid hormone values than those who were not, because hypothalamic injury is common in blast. This is a future direction Dr. Toloza wishes to pursue.

“Our findings add to the growing literature suggesting that thyroid function changes may be associated with PTSD,” the investigators wrote, but “further research is needed to ascertain the role of thyroid function alterations in PTSD.”

Dr. Toloza reported no financial disclosures or conflicts of interest.

CHICAGO – Higher levels of triiodothyronine (T3) were seen in combatants with PTSD, compared with patients whose PTSD arose from other adverse experiences, according to findings from a systematic review and meta-analysis.

Patients with combat-related PTSD had higher levels of free T3 and total T3, compared with control participants who had experienced childhood or sexual abuse or were a wartime refugee without PTSD (FT3, 0.36 pg/mL higher, and total T3, 31.6 ng/mL higher, respectively; P = .0004 and P less than .00001).

“We found statistically higher free T3 and total T3 levels in patients with [combat-related] PTSD, compared with controls,” said Freddy J.K. Toloza, MD, in an interview during a poster session of the annual meeting of the American Thyroid Association.

However, he noted that there were no overall differences in thyroid-stimulating hormone, free tetraiodothyronine (T4), and total T4 levels between individuals with PTSD and the non-PTSD control participants. In addition, though free and total T3 levels were significantly higher for the overall PTSD cohort than for control participants, the differences were driven by the studies that included combat-exposed individuals.

Dr. Toloza and colleagues included 10 observational studies in their final review and meta-analysis. Five studies looked at war veterans; the others examined individuals who had experienced child abuse or sexual abuse, who were refugees, or who were from the general population.

For inclusion, the studies had to report both mean values and standard deviations for standard thyroid-hormone test values in patients with PTSD, compared with a non-PTSD control group. These included 373 patients with PTSD and 301 control participants. Just under half (47%) were women. None of the studies, wrote the investigators, “compared rates of overt/subclinical thyroid disease between groups.”

There are known links between many endocrine disorders and psychiatric conditions, said Dr. Toloza, but the interplay between disordered thyroid function and neuropsychiatric problems is still being examined. Looking at PTSD is important because it’s estimated that 6%-9% of the U.S. adult population has experienced PTSD over the course of a lifetime.

Levels of thyroid hormones in the systematic review and meta-analysis were still within normal range for the participants with PTSD, acknowledged Dr. Toloza, a research fellow in the division of endocrinology and metabolism at University of Arkansas for Medical Sciences, Little Rock.

However, even though there was no sign of frank thyroid disease in the PTSD population, the elevated T3 levels seen in the analysis are consistent with other studies showing a correlation between higher T3 levels and more-severe PTSD.

It is not known exactly why significant increases in the levels of total and free T3 were seen only in the combat-exposed PTSD population, Dr. Toloza said. “The type of trauma trigger may influence the adaptive responses to stress and might result in diverse thyroid alterations.”

Elevated catecholamine levels, seen in individuals with PTSD, can increase peripheral conversion of T4 to T3, explained Dr. Toloza. Ongoing catecholamine elevation may account for the isolated elevation in T3 levels in the PTSD population. Beta1-adrenergic blockade is an accepted pharmacologic strategy to help alleviate PTSD symptoms.

Dr. Toloza and coinvestigators did not have access to data that would have allowed them to ascertain what types of injuries were sustained by individuals with combat-related PTSD, but he noted in response to a question, that it would be worthwhile to see whether combatants who were blast exposed had different thyroid hormone values than those who were not, because hypothalamic injury is common in blast. This is a future direction Dr. Toloza wishes to pursue.

“Our findings add to the growing literature suggesting that thyroid function changes may be associated with PTSD,” the investigators wrote, but “further research is needed to ascertain the role of thyroid function alterations in PTSD.”

Dr. Toloza reported no financial disclosures or conflicts of interest.

CHICAGO – Higher levels of triiodothyronine (T3) were seen in combatants with PTSD, compared with patients whose PTSD arose from other adverse experiences, according to findings from a systematic review and meta-analysis.

Patients with combat-related PTSD had higher levels of free T3 and total T3, compared with control participants who had experienced childhood or sexual abuse or were a wartime refugee without PTSD (FT3, 0.36 pg/mL higher, and total T3, 31.6 ng/mL higher, respectively; P = .0004 and P less than .00001).

“We found statistically higher free T3 and total T3 levels in patients with [combat-related] PTSD, compared with controls,” said Freddy J.K. Toloza, MD, in an interview during a poster session of the annual meeting of the American Thyroid Association.

However, he noted that there were no overall differences in thyroid-stimulating hormone, free tetraiodothyronine (T4), and total T4 levels between individuals with PTSD and the non-PTSD control participants. In addition, though free and total T3 levels were significantly higher for the overall PTSD cohort than for control participants, the differences were driven by the studies that included combat-exposed individuals.

Dr. Toloza and colleagues included 10 observational studies in their final review and meta-analysis. Five studies looked at war veterans; the others examined individuals who had experienced child abuse or sexual abuse, who were refugees, or who were from the general population.

For inclusion, the studies had to report both mean values and standard deviations for standard thyroid-hormone test values in patients with PTSD, compared with a non-PTSD control group. These included 373 patients with PTSD and 301 control participants. Just under half (47%) were women. None of the studies, wrote the investigators, “compared rates of overt/subclinical thyroid disease between groups.”

There are known links between many endocrine disorders and psychiatric conditions, said Dr. Toloza, but the interplay between disordered thyroid function and neuropsychiatric problems is still being examined. Looking at PTSD is important because it’s estimated that 6%-9% of the U.S. adult population has experienced PTSD over the course of a lifetime.

Levels of thyroid hormones in the systematic review and meta-analysis were still within normal range for the participants with PTSD, acknowledged Dr. Toloza, a research fellow in the division of endocrinology and metabolism at University of Arkansas for Medical Sciences, Little Rock.

However, even though there was no sign of frank thyroid disease in the PTSD population, the elevated T3 levels seen in the analysis are consistent with other studies showing a correlation between higher T3 levels and more-severe PTSD.

It is not known exactly why significant increases in the levels of total and free T3 were seen only in the combat-exposed PTSD population, Dr. Toloza said. “The type of trauma trigger may influence the adaptive responses to stress and might result in diverse thyroid alterations.”

Elevated catecholamine levels, seen in individuals with PTSD, can increase peripheral conversion of T4 to T3, explained Dr. Toloza. Ongoing catecholamine elevation may account for the isolated elevation in T3 levels in the PTSD population. Beta1-adrenergic blockade is an accepted pharmacologic strategy to help alleviate PTSD symptoms.

Dr. Toloza and coinvestigators did not have access to data that would have allowed them to ascertain what types of injuries were sustained by individuals with combat-related PTSD, but he noted in response to a question, that it would be worthwhile to see whether combatants who were blast exposed had different thyroid hormone values than those who were not, because hypothalamic injury is common in blast. This is a future direction Dr. Toloza wishes to pursue.

“Our findings add to the growing literature suggesting that thyroid function changes may be associated with PTSD,” the investigators wrote, but “further research is needed to ascertain the role of thyroid function alterations in PTSD.”

Dr. Toloza reported no financial disclosures or conflicts of interest.