To the Editor:

With a trend toward increasing pass/fail medical school curricula, residency program directors (PDs) have relied on the US Medical Licensing Examination (USMLE) Step 1 as an objective measurement of applicant achievement, which is particularly true in competitive subspecialties such as dermatology, plastic surgery, orthopedic surgery, ophthalmology, and neurosurgery, in which reported Step 1 scores are consistently the highest among matched applicants.¹ Program directors in dermatology have indicated that Step 1 scores are a priority when considering an applicant.² However, among PDs, the general perception of plans to change Step 1 scores to pass/fail has largely been negative.³ Although the impact of this change on the dermatology residency selection process remains unknown, we undertook a study to determine dermatology PDs’ perspectives on the scoring change and discuss its potential implications among all competitive specialties.

A 19-question survey was designed that assessed PD demographics and opinions of the changes and potential implications of the Step 1 scoring change (eTable). A list of current US dermatology PDs at osteopathic and allopathic programs was obtained through the 2019-2020 Accreditation Council for Graduate Medical Education list of accredited programs. Surveys were piloted at our institution to assess for internal validity and misleading questions, and then were distributed electronically through REDCap software (https://www.project-redcap.org/). All responses were kept anonymous. Institutional review board approval was obtained. Variables were assessed with means, proportions, and CIs. Results were deemed statistically significant with nonoverlapping 99% CIs (P<.01).

In dermatology and other competitive specialties, in which USMLE Step 1 scores have become an important consideration, PDs and residency programs will need to identify additional metrics to compare applicants. Examples include research productivity, grades on relevant rotations, and shelf examination scores. Although more reliable subjective measures, such as interviews and performance on away rotations, are already important, they may become of greater significance.

The findings of our survey suggest that PDs are skeptical about changes to Step 1 and more diligence is necessary to maintain a fair and impartial selection process. Increased emphasis on other objective measurements, such as shelf examination scores, graded curricular components, and research productivity, could help maintain an unbiased approach. With changes to USMLE Step 1 expected to be implemented in the 2022 application cycle, programs may need to explore additional options to maintain reliable and transparent applicant review practices.

To the Editor:

With a trend toward increasing pass/fail medical school curricula, residency program directors (PDs) have relied on the US Medical Licensing Examination (USMLE) Step 1 as an objective measurement of applicant achievement, which is particularly true in competitive subspecialties such as dermatology, plastic surgery, orthopedic surgery, ophthalmology, and neurosurgery, in which reported Step 1 scores are consistently the highest among matched applicants.¹ Program directors in dermatology have indicated that Step 1 scores are a priority when considering an applicant.² However, among PDs, the general perception of plans to change Step 1 scores to pass/fail has largely been negative.³ Although the impact of this change on the dermatology residency selection process remains unknown, we undertook a study to determine dermatology PDs’ perspectives on the scoring change and discuss its potential implications among all competitive specialties.

A 19-question survey was designed that assessed PD demographics and opinions of the changes and potential implications of the Step 1 scoring change (eTable). A list of current US dermatology PDs at osteopathic and allopathic programs was obtained through the 2019-2020 Accreditation Council for Graduate Medical Education list of accredited programs. Surveys were piloted at our institution to assess for internal validity and misleading questions, and then were distributed electronically through REDCap software (https://www.project-redcap.org/). All responses were kept anonymous. Institutional review board approval was obtained. Variables were assessed with means, proportions, and CIs. Results were deemed statistically significant with nonoverlapping 99% CIs (P<.01).

In dermatology and other competitive specialties, in which USMLE Step 1 scores have become an important consideration, PDs and residency programs will need to identify additional metrics to compare applicants. Examples include research productivity, grades on relevant rotations, and shelf examination scores. Although more reliable subjective measures, such as interviews and performance on away rotations, are already important, they may become of greater significance.

The findings of our survey suggest that PDs are skeptical about changes to Step 1 and more diligence is necessary to maintain a fair and impartial selection process. Increased emphasis on other objective measurements, such as shelf examination scores, graded curricular components, and research productivity, could help maintain an unbiased approach. With changes to USMLE Step 1 expected to be implemented in the 2022 application cycle, programs may need to explore additional options to maintain reliable and transparent applicant review practices.

To the Editor:

With a trend toward increasing pass/fail medical school curricula, residency program directors (PDs) have relied on the US Medical Licensing Examination (USMLE) Step 1 as an objective measurement of applicant achievement, which is particularly true in competitive subspecialties such as dermatology, plastic surgery, orthopedic surgery, ophthalmology, and neurosurgery, in which reported Step 1 scores are consistently the highest among matched applicants.¹ Program directors in dermatology have indicated that Step 1 scores are a priority when considering an applicant.² However, among PDs, the general perception of plans to change Step 1 scores to pass/fail has largely been negative.³ Although the impact of this change on the dermatology residency selection process remains unknown, we undertook a study to determine dermatology PDs’ perspectives on the scoring change and discuss its potential implications among all competitive specialties.

A 19-question survey was designed that assessed PD demographics and opinions of the changes and potential implications of the Step 1 scoring change (eTable). A list of current US dermatology PDs at osteopathic and allopathic programs was obtained through the 2019-2020 Accreditation Council for Graduate Medical Education list of accredited programs. Surveys were piloted at our institution to assess for internal validity and misleading questions, and then were distributed electronically through REDCap software (https://www.project-redcap.org/). All responses were kept anonymous. Institutional review board approval was obtained. Variables were assessed with means, proportions, and CIs. Results were deemed statistically significant with nonoverlapping 99% CIs (P<.01).

In dermatology and other competitive specialties, in which USMLE Step 1 scores have become an important consideration, PDs and residency programs will need to identify additional metrics to compare applicants. Examples include research productivity, grades on relevant rotations, and shelf examination scores. Although more reliable subjective measures, such as interviews and performance on away rotations, are already important, they may become of greater significance.

The findings of our survey suggest that PDs are skeptical about changes to Step 1 and more diligence is necessary to maintain a fair and impartial selection process. Increased emphasis on other objective measurements, such as shelf examination scores, graded curricular components, and research productivity, could help maintain an unbiased approach. With changes to USMLE Step 1 expected to be implemented in the 2022 application cycle, programs may need to explore additional options to maintain reliable and transparent applicant review practices.

Converge 2021 session

Febrile Infant Update

Presenter

Russell J. McCulloh, MD

Session summary

Infections in infants aged younger than 90 days have been the subject of intense study in pediatric hospital medicine for many years. With the guidance of our talented presenter Dr. Russell McCulloh of Children’s Hospital & Medical Center in Omaha, Neb., the audience explored the historical perspective and evolution of this scientific question, including successes, special situations, newer screening tests, and description of cutting-edge scoring tools and platforms.

The challenge – Tens of thousands of infants present for care in the setting of fever each year. We know that our physical exam and history-taking skills are unlikely to be helpful in risk stratification. We have been guided by the desire to separate serious bacterial infection (SBI: bone infection, meningitis, pneumonia, urinary tract infection, bacteremia, enteritis) from invasive bacterial infection (IBI: meningitis and bacteremia). Data has shown that no test is 100% sensitive or specific, therefore we have to balance risk of disease to cost and invasiveness of tests. Important questions include whether to test and how to stratify by age, who to admit, and who to provide antibiotics.

The wins and exceptions – Fortunately, the early Boston, Philadelphia, and Rochester criteria set the stage for safely reducing testing. The current American College of Emergency Physicians guidelines for infants aged 29-90 days allows for lumbar puncture to be optional knowing that a look back using prior criteria identified no cases of meningitis in the low risk group. Similarly, in low-risk infants aged less that 29 days in nearly 4,000 cases there were just 2 infants with meningitis. Universal screening of moms for Group B Streptococcus with delivery of antibiotics in appropriate cases has dramatically decreased incidence of SBI. The Hib and pneumovax vaccines have likewise decreased incidence of SBI. Exceptions persist, including knowledge that infants with herpes simplex virus disease will not have fever in 50% of cases and that risk of HSV transmission is highest (25%-60% transmission) in mothers with primary disease. Given risk of HSV CNS disease after 1 week of age, in any high-risk infant less than 21 days, the mantra remains to test and treat.

The cutting edge – Thanks to ongoing research, we now have the PECARN and REVISE study groups to further aid decision-making. With PECARN we know that SBI in infants is extremely unlikely (negative predictive value, 99.7%) with a negative urinalysis , absolute neutrophil count less than 4,090, and procalcitonin less than 1.71. REVISE has revealed that infants with positive viral testing are unlikely to have SBI (7%-12%), particularly with influenza and RSV disease. Procalcitonin has also recently been shown to be an effective tool to rule out disease with the highest negative predictive value among available inflammatory markers. The just-published Aronson rule identifies a scoring system for IBI (using age less than 21 days/1pt; temp 38-38.4° C/2pt; >38.5° C/4pt; abnormal urinalysis/3pt; and absolute neutrophil count >5185/2pt) where any score greater than2 provides a sensitivity of 98.8% and NPV in validation studies of 99.4%. Likewise, multiplex polymerase chain reaction testing of spinal fluid has allowed for additional insight in pretreated cases and has helped us to remove antibiotic treatment from cases where parechovirus and enterovirus are positive because of the low risk for concomitant bacterial meningitis. As we await the release of revised national American Academy of Pediatrics guidelines, it is safe to say great progress has been made in the care of young febrile infants with shorter length of stay and fewer tests for all.

Key takeaways

• Numerous screening tests, rules, and scoring tools have been created to improve identification of infants with IBI, a low-frequency, high-morbidity event. The most recent with negative predictive values of 99.7% and 99.4% are the PECARN and Aronson scoring tools.
• Recent studies of the febrile infant population indicate that the odds of UTI or bacteremia in infants with respiratory symptoms is low, particularly for RSV and influenza.
• Among newer tests developed, a negative procalcitonin has the highest negative predictive value.
• Viral pathogens identified on cerebrospinal fluid molecular testing can be helpful in pretreated cases and indicative of low likelihood of bacterial meningitis allowing for observation off of antibiotics.

Dr. King is a hospitalist, associate director for medical education and associate program director for the pediatrics residency program at Children’s Minnesota in Minneapolis. She has shared some of her resident teaching, presentation skills, and peer-coaching work on a national level.

Converge 2021 session

Febrile Infant Update

Presenter

Russell J. McCulloh, MD

Session summary

Infections in infants aged younger than 90 days have been the subject of intense study in pediatric hospital medicine for many years. With the guidance of our talented presenter Dr. Russell McCulloh of Children’s Hospital & Medical Center in Omaha, Neb., the audience explored the historical perspective and evolution of this scientific question, including successes, special situations, newer screening tests, and description of cutting-edge scoring tools and platforms.

The challenge – Tens of thousands of infants present for care in the setting of fever each year. We know that our physical exam and history-taking skills are unlikely to be helpful in risk stratification. We have been guided by the desire to separate serious bacterial infection (SBI: bone infection, meningitis, pneumonia, urinary tract infection, bacteremia, enteritis) from invasive bacterial infection (IBI: meningitis and bacteremia). Data has shown that no test is 100% sensitive or specific, therefore we have to balance risk of disease to cost and invasiveness of tests. Important questions include whether to test and how to stratify by age, who to admit, and who to provide antibiotics.

The wins and exceptions – Fortunately, the early Boston, Philadelphia, and Rochester criteria set the stage for safely reducing testing. The current American College of Emergency Physicians guidelines for infants aged 29-90 days allows for lumbar puncture to be optional knowing that a look back using prior criteria identified no cases of meningitis in the low risk group. Similarly, in low-risk infants aged less that 29 days in nearly 4,000 cases there were just 2 infants with meningitis. Universal screening of moms for Group B Streptococcus with delivery of antibiotics in appropriate cases has dramatically decreased incidence of SBI. The Hib and pneumovax vaccines have likewise decreased incidence of SBI. Exceptions persist, including knowledge that infants with herpes simplex virus disease will not have fever in 50% of cases and that risk of HSV transmission is highest (25%-60% transmission) in mothers with primary disease. Given risk of HSV CNS disease after 1 week of age, in any high-risk infant less than 21 days, the mantra remains to test and treat.

The cutting edge – Thanks to ongoing research, we now have the PECARN and REVISE study groups to further aid decision-making. With PECARN we know that SBI in infants is extremely unlikely (negative predictive value, 99.7%) with a negative urinalysis , absolute neutrophil count less than 4,090, and procalcitonin less than 1.71. REVISE has revealed that infants with positive viral testing are unlikely to have SBI (7%-12%), particularly with influenza and RSV disease. Procalcitonin has also recently been shown to be an effective tool to rule out disease with the highest negative predictive value among available inflammatory markers. The just-published Aronson rule identifies a scoring system for IBI (using age less than 21 days/1pt; temp 38-38.4° C/2pt; >38.5° C/4pt; abnormal urinalysis/3pt; and absolute neutrophil count >5185/2pt) where any score greater than2 provides a sensitivity of 98.8% and NPV in validation studies of 99.4%. Likewise, multiplex polymerase chain reaction testing of spinal fluid has allowed for additional insight in pretreated cases and has helped us to remove antibiotic treatment from cases where parechovirus and enterovirus are positive because of the low risk for concomitant bacterial meningitis. As we await the release of revised national American Academy of Pediatrics guidelines, it is safe to say great progress has been made in the care of young febrile infants with shorter length of stay and fewer tests for all.

Key takeaways

• Numerous screening tests, rules, and scoring tools have been created to improve identification of infants with IBI, a low-frequency, high-morbidity event. The most recent with negative predictive values of 99.7% and 99.4% are the PECARN and Aronson scoring tools.
• Recent studies of the febrile infant population indicate that the odds of UTI or bacteremia in infants with respiratory symptoms is low, particularly for RSV and influenza.
• Among newer tests developed, a negative procalcitonin has the highest negative predictive value.
• Viral pathogens identified on cerebrospinal fluid molecular testing can be helpful in pretreated cases and indicative of low likelihood of bacterial meningitis allowing for observation off of antibiotics.

Dr. King is a hospitalist, associate director for medical education and associate program director for the pediatrics residency program at Children’s Minnesota in Minneapolis. She has shared some of her resident teaching, presentation skills, and peer-coaching work on a national level.

Converge 2021 session

Febrile Infant Update

Presenter

Russell J. McCulloh, MD

Session summary

Infections in infants aged younger than 90 days have been the subject of intense study in pediatric hospital medicine for many years. With the guidance of our talented presenter Dr. Russell McCulloh of Children’s Hospital & Medical Center in Omaha, Neb., the audience explored the historical perspective and evolution of this scientific question, including successes, special situations, newer screening tests, and description of cutting-edge scoring tools and platforms.

The challenge – Tens of thousands of infants present for care in the setting of fever each year. We know that our physical exam and history-taking skills are unlikely to be helpful in risk stratification. We have been guided by the desire to separate serious bacterial infection (SBI: bone infection, meningitis, pneumonia, urinary tract infection, bacteremia, enteritis) from invasive bacterial infection (IBI: meningitis and bacteremia). Data has shown that no test is 100% sensitive or specific, therefore we have to balance risk of disease to cost and invasiveness of tests. Important questions include whether to test and how to stratify by age, who to admit, and who to provide antibiotics.

The wins and exceptions – Fortunately, the early Boston, Philadelphia, and Rochester criteria set the stage for safely reducing testing. The current American College of Emergency Physicians guidelines for infants aged 29-90 days allows for lumbar puncture to be optional knowing that a look back using prior criteria identified no cases of meningitis in the low risk group. Similarly, in low-risk infants aged less that 29 days in nearly 4,000 cases there were just 2 infants with meningitis. Universal screening of moms for Group B Streptococcus with delivery of antibiotics in appropriate cases has dramatically decreased incidence of SBI. The Hib and pneumovax vaccines have likewise decreased incidence of SBI. Exceptions persist, including knowledge that infants with herpes simplex virus disease will not have fever in 50% of cases and that risk of HSV transmission is highest (25%-60% transmission) in mothers with primary disease. Given risk of HSV CNS disease after 1 week of age, in any high-risk infant less than 21 days, the mantra remains to test and treat.

The cutting edge – Thanks to ongoing research, we now have the PECARN and REVISE study groups to further aid decision-making. With PECARN we know that SBI in infants is extremely unlikely (negative predictive value, 99.7%) with a negative urinalysis , absolute neutrophil count less than 4,090, and procalcitonin less than 1.71. REVISE has revealed that infants with positive viral testing are unlikely to have SBI (7%-12%), particularly with influenza and RSV disease. Procalcitonin has also recently been shown to be an effective tool to rule out disease with the highest negative predictive value among available inflammatory markers. The just-published Aronson rule identifies a scoring system for IBI (using age less than 21 days/1pt; temp 38-38.4° C/2pt; >38.5° C/4pt; abnormal urinalysis/3pt; and absolute neutrophil count >5185/2pt) where any score greater than2 provides a sensitivity of 98.8% and NPV in validation studies of 99.4%. Likewise, multiplex polymerase chain reaction testing of spinal fluid has allowed for additional insight in pretreated cases and has helped us to remove antibiotic treatment from cases where parechovirus and enterovirus are positive because of the low risk for concomitant bacterial meningitis. As we await the release of revised national American Academy of Pediatrics guidelines, it is safe to say great progress has been made in the care of young febrile infants with shorter length of stay and fewer tests for all.

Key takeaways

• Numerous screening tests, rules, and scoring tools have been created to improve identification of infants with IBI, a low-frequency, high-morbidity event. The most recent with negative predictive values of 99.7% and 99.4% are the PECARN and Aronson scoring tools.
• Recent studies of the febrile infant population indicate that the odds of UTI or bacteremia in infants with respiratory symptoms is low, particularly for RSV and influenza.
• Among newer tests developed, a negative procalcitonin has the highest negative predictive value.
• Viral pathogens identified on cerebrospinal fluid molecular testing can be helpful in pretreated cases and indicative of low likelihood of bacterial meningitis allowing for observation off of antibiotics.

Dr. King is a hospitalist, associate director for medical education and associate program director for the pediatrics residency program at Children’s Minnesota in Minneapolis. She has shared some of her resident teaching, presentation skills, and peer-coaching work on a national level.

Practice Gap

Many cutaneous surgery wounds can be closed primarily; however, in certain cases, other repair options might be appropriate and should be evaluated on a case-by-case basis with input from the patient. Defects on the dorsal aspect of the hands—where nonmelanoma skin cancer is common and reserve tissue is limited—often heal by secondary intention with good cosmetic and functional results. Patients often express a desire to reduce the time spent in the surgical suite and restrictions on postoperative activity, making secondary intention healing more appealing. An additional advantage is obviation of the need to remove additional tissue in the form of Burow triangles, which would lead to a longer wound. The major disadvantage of secondary intention healing is longer time to wound maturity; we often minimize this disadvantage with purse-string closure to decrease the size of the wound defect, which can be done quickly and without removing additional tissue.

The Technique

An elderly man had 3 nonmelanoma skin cancers—all on the dorsal aspect of the left hand—that were treated on the same day, leaving 3 similar wound defects after Mohs micrographic surgery. The wound defects (distal to proximal) measured 12 mm, 12 mm, and 10 mm in diameter (Figure 1) and were repaired by primary closure, secondary intention, and purse-string circumferential closure, respectively. Purse-string closure¹ was performed with a 4-0 polyglactin 901 suture and left to heal without external sutures (Figure 2). Figure 3 shows the 3 types of repairs immediately following closure. All wounds healed with excellent and essentially equivalent cosmetic results, with excellent patient satisfaction at 6-month follow-up (Figure 4).

Practical Implications

Our case illustrates different modalities of wound repair during precisely the same time frame and essentially on the same location. Skin of the dorsal hand often is tight; depending on the size of the defect, large primary closure can be tedious to perform, can lead to increased wound tension and risk of dehiscence, and can be uncomfortable for the patient during healing. However, primary closure typically will lead to faster healing.

Secondary intention healing and purse-string closure require less surgery and therefore cost less; these modalities yield similar cosmesis and satisfaction. In the appropriate context, secondary intention has been highlighted as a suitable alternative to primary closure^2-4; in our experience (and that of others⁵), patient satisfaction is not diminished with healing by secondary intention. Purse-string closure also can minimize wound size and healing time.

For small shallow wounds on the dorsal hand, dermatologic surgeons should have confidence that secondary intention healing, with or without wound reduction using purse-string repair, likely will lead to acceptable cosmetic and functional results. Of course, repair should be tailored to the circumstances and wishes of the individual patient.

Practice Gap

Many cutaneous surgery wounds can be closed primarily; however, in certain cases, other repair options might be appropriate and should be evaluated on a case-by-case basis with input from the patient. Defects on the dorsal aspect of the hands—where nonmelanoma skin cancer is common and reserve tissue is limited—often heal by secondary intention with good cosmetic and functional results. Patients often express a desire to reduce the time spent in the surgical suite and restrictions on postoperative activity, making secondary intention healing more appealing. An additional advantage is obviation of the need to remove additional tissue in the form of Burow triangles, which would lead to a longer wound. The major disadvantage of secondary intention healing is longer time to wound maturity; we often minimize this disadvantage with purse-string closure to decrease the size of the wound defect, which can be done quickly and without removing additional tissue.

The Technique

An elderly man had 3 nonmelanoma skin cancers—all on the dorsal aspect of the left hand—that were treated on the same day, leaving 3 similar wound defects after Mohs micrographic surgery. The wound defects (distal to proximal) measured 12 mm, 12 mm, and 10 mm in diameter (Figure 1) and were repaired by primary closure, secondary intention, and purse-string circumferential closure, respectively. Purse-string closure¹ was performed with a 4-0 polyglactin 901 suture and left to heal without external sutures (Figure 2). Figure 3 shows the 3 types of repairs immediately following closure. All wounds healed with excellent and essentially equivalent cosmetic results, with excellent patient satisfaction at 6-month follow-up (Figure 4).

Practical Implications

Our case illustrates different modalities of wound repair during precisely the same time frame and essentially on the same location. Skin of the dorsal hand often is tight; depending on the size of the defect, large primary closure can be tedious to perform, can lead to increased wound tension and risk of dehiscence, and can be uncomfortable for the patient during healing. However, primary closure typically will lead to faster healing.

Secondary intention healing and purse-string closure require less surgery and therefore cost less; these modalities yield similar cosmesis and satisfaction. In the appropriate context, secondary intention has been highlighted as a suitable alternative to primary closure^2-4; in our experience (and that of others⁵), patient satisfaction is not diminished with healing by secondary intention. Purse-string closure also can minimize wound size and healing time.

For small shallow wounds on the dorsal hand, dermatologic surgeons should have confidence that secondary intention healing, with or without wound reduction using purse-string repair, likely will lead to acceptable cosmetic and functional results. Of course, repair should be tailored to the circumstances and wishes of the individual patient.

Practice Gap

Many cutaneous surgery wounds can be closed primarily; however, in certain cases, other repair options might be appropriate and should be evaluated on a case-by-case basis with input from the patient. Defects on the dorsal aspect of the hands—where nonmelanoma skin cancer is common and reserve tissue is limited—often heal by secondary intention with good cosmetic and functional results. Patients often express a desire to reduce the time spent in the surgical suite and restrictions on postoperative activity, making secondary intention healing more appealing. An additional advantage is obviation of the need to remove additional tissue in the form of Burow triangles, which would lead to a longer wound. The major disadvantage of secondary intention healing is longer time to wound maturity; we often minimize this disadvantage with purse-string closure to decrease the size of the wound defect, which can be done quickly and without removing additional tissue.

The Technique

An elderly man had 3 nonmelanoma skin cancers—all on the dorsal aspect of the left hand—that were treated on the same day, leaving 3 similar wound defects after Mohs micrographic surgery. The wound defects (distal to proximal) measured 12 mm, 12 mm, and 10 mm in diameter (Figure 1) and were repaired by primary closure, secondary intention, and purse-string circumferential closure, respectively. Purse-string closure¹ was performed with a 4-0 polyglactin 901 suture and left to heal without external sutures (Figure 2). Figure 3 shows the 3 types of repairs immediately following closure. All wounds healed with excellent and essentially equivalent cosmetic results, with excellent patient satisfaction at 6-month follow-up (Figure 4).

Practical Implications

Our case illustrates different modalities of wound repair during precisely the same time frame and essentially on the same location. Skin of the dorsal hand often is tight; depending on the size of the defect, large primary closure can be tedious to perform, can lead to increased wound tension and risk of dehiscence, and can be uncomfortable for the patient during healing. However, primary closure typically will lead to faster healing.

Secondary intention healing and purse-string closure require less surgery and therefore cost less; these modalities yield similar cosmesis and satisfaction. In the appropriate context, secondary intention has been highlighted as a suitable alternative to primary closure^2-4; in our experience (and that of others⁵), patient satisfaction is not diminished with healing by secondary intention. Purse-string closure also can minimize wound size and healing time.

For small shallow wounds on the dorsal hand, dermatologic surgeons should have confidence that secondary intention healing, with or without wound reduction using purse-string repair, likely will lead to acceptable cosmetic and functional results. Of course, repair should be tailored to the circumstances and wishes of the individual patient.

Opioids were prescribed most often for vitiligo, hemangioma, pemphigus, atopic dermatitis, and psoriasis, according to a study that used national ambulatory care data to evaluate pain medication use at dermatology visits.

“Overall, opioid prescribing rates among dermatologists were low. However, dermatologists should remain aware of risk factors for long-term opioid use and consider using nonnarcotic or nonpharmacologic interventions when possible,” Sarah P. Pourali, a medical student at Vanderbilt University, Nashville, said at the annual meeting of the Society for Investigative Dermatology, where she presented the results.

Ms. Pourali said that although Mohs surgery and dermatologic procedures are the focus of “much of the literature” concerning opioid use in dermatology, there are limited data on medication prescribing patterns for other skin conditions treated by dermatologists.

She and her colleagues performed a cross-sectional study using data from the National Ambulatory Medical Care Survey (NAMCS) from 2009 to 2016 on 288,462,610 weighted dermatology visits. The researchers used International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes to identify dermatologic diseases. They also identified and grouped oral pain medication into the following categories: opiate analgesics, nonsteroidal anti-inflammatory drugs, acetaminophen, and gabapentin. A linear regression analysis was used to evaluate pain medicine prescribing each year, and the researchers used a logistic regression analysis to explore how opiate prescriptions were connected to patient clinical characteristics. The analysis was adjusted for age, gender, race, ethnicity, and region.

Overall, most dermatology visits were for patients older than 65 years (36.2%) and 45-64 years old (32.1%). Over half of the dermatologist visits were for women (56.4%) and most (92.2%) visits were for patients who were White (5.1 % were for patients who were Black); most were non-Hispanic or Latino (93.5%). Most dermatology visits were in the South (35.4%) and West (25.2%), followed by the Northeast (21.9%) and Midwest (17.5%).

Opioids were prescribed in 1.3% of the visits, Ms. Pourali said. In addition, 4.7% of visits included an NSAID prescription, 0.7% an acetaminophen prescription, and 0.6% a gabapentin prescription.

Dermatologic procedure visits accounted for 43.1% of opioid prescriptions, she noted. The most common skin conditions for which opioids were prescribed included vitiligo (10.3%), hemangioma (3.8%), pemphigus (3.6%), atopic dermatitis (3.4%), and psoriasis (2.5%).

Although patients older than 65 years accounted for 36.2% of visits to dermatologists, 58.5% of opioids prescribed by dermatologists were for patients in this age group. “We hypothesize that this may be due to a higher proportion of older patients requiring skin cancer surgeries where a lot of opioids are prescribed within dermatology,” Ms. Pourali said.

The highest population-adjusted prescription rates for opiates were in the Northeast and Western regions of the United States, which “partially corroborates” previous studies that have found “higher rates of opioid prescribing in the southern and western U.S.,” she noted.

When evaluating risk-factors for long-term opiate use, Ms. Pourali and colleagues found opioids were also prescribed in 13.2% of visits where a benzodiazepine was prescribed (adjusted odds ratio, 8.17; 95% confidence interval, 5.3-12.7), 8.4% of visits where the patient had a substance abuse disorder (adjusted OR, 9.40; 95% CI, 2.0-44.4), 5.2% of visits with a patient who had depression (adjusted OR, 3.28; 95% CI, 2.0-5.4), and 2.4% of visits with a patient who used tobacco (adjusted OR, 1.09; 95% CI, 1.0-1.1).

Consider nonopioid postoperative pain management options

In an interview, Sailesh Konda, MD, associate clinical professor of dermatology and director of Mohs surgery and surgical dermatology at the University of Florida, Gainesville, who was not involved with the research, noted the finding in the study that vitiligo, hemangioma, pemphigus, AD, and psoriasis were diagnoses with the highest rates of opioid prescription was surprising. “In general, these are conditions that are not routinely managed with opioids,” he said.

NAMCS contains a primary diagnosis field and space for four additional diagnoses such as chronic conditions, as well as thirty fields for medications. “If an opioid was prescribed at a visit, it could have been prescribed for any of the diagnoses related to the visit,” Dr. Konda said. “Additionally, for those opioid prescriptions associated with dermatologic procedures, it would have been helpful to have a breakdown of the specific procedures.”

Dr. Konda compared these results to a recent study of opioid prescribing patterns in the dermatology Medicare population, which found that 93.9% of the top 1% of opioid prescribers were dermatologists working in a surgical practice.

He said that recommendations for opioid prescribing should be developed for general dermatology as they have been for Mohs surgery and dermatologic surgery. For dermatologists currently prescribing opioids, he recommended monitoring prescribing patterns and to “consider nonopioid interventions, such as acetaminophen plus ibuprofen, which has been found to effectively control postoperative pain with fewer complications.”

Ms. Pourali reports no relevant financial disclosures. Her coauthors included the principal investigator, April Armstrong, MD, MPH, professor of dermatology, University of Southern California, Los Angeles. Dr. Konda reports no relevant financial disclosures.

Opioids were prescribed most often for vitiligo, hemangioma, pemphigus, atopic dermatitis, and psoriasis, according to a study that used national ambulatory care data to evaluate pain medication use at dermatology visits.

“Overall, opioid prescribing rates among dermatologists were low. However, dermatologists should remain aware of risk factors for long-term opioid use and consider using nonnarcotic or nonpharmacologic interventions when possible,” Sarah P. Pourali, a medical student at Vanderbilt University, Nashville, said at the annual meeting of the Society for Investigative Dermatology, where she presented the results.

Ms. Pourali said that although Mohs surgery and dermatologic procedures are the focus of “much of the literature” concerning opioid use in dermatology, there are limited data on medication prescribing patterns for other skin conditions treated by dermatologists.

She and her colleagues performed a cross-sectional study using data from the National Ambulatory Medical Care Survey (NAMCS) from 2009 to 2016 on 288,462,610 weighted dermatology visits. The researchers used International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes to identify dermatologic diseases. They also identified and grouped oral pain medication into the following categories: opiate analgesics, nonsteroidal anti-inflammatory drugs, acetaminophen, and gabapentin. A linear regression analysis was used to evaluate pain medicine prescribing each year, and the researchers used a logistic regression analysis to explore how opiate prescriptions were connected to patient clinical characteristics. The analysis was adjusted for age, gender, race, ethnicity, and region.

Overall, most dermatology visits were for patients older than 65 years (36.2%) and 45-64 years old (32.1%). Over half of the dermatologist visits were for women (56.4%) and most (92.2%) visits were for patients who were White (5.1 % were for patients who were Black); most were non-Hispanic or Latino (93.5%). Most dermatology visits were in the South (35.4%) and West (25.2%), followed by the Northeast (21.9%) and Midwest (17.5%).

Opioids were prescribed in 1.3% of the visits, Ms. Pourali said. In addition, 4.7% of visits included an NSAID prescription, 0.7% an acetaminophen prescription, and 0.6% a gabapentin prescription.

Dermatologic procedure visits accounted for 43.1% of opioid prescriptions, she noted. The most common skin conditions for which opioids were prescribed included vitiligo (10.3%), hemangioma (3.8%), pemphigus (3.6%), atopic dermatitis (3.4%), and psoriasis (2.5%).

Although patients older than 65 years accounted for 36.2% of visits to dermatologists, 58.5% of opioids prescribed by dermatologists were for patients in this age group. “We hypothesize that this may be due to a higher proportion of older patients requiring skin cancer surgeries where a lot of opioids are prescribed within dermatology,” Ms. Pourali said.

The highest population-adjusted prescription rates for opiates were in the Northeast and Western regions of the United States, which “partially corroborates” previous studies that have found “higher rates of opioid prescribing in the southern and western U.S.,” she noted.

When evaluating risk-factors for long-term opiate use, Ms. Pourali and colleagues found opioids were also prescribed in 13.2% of visits where a benzodiazepine was prescribed (adjusted odds ratio, 8.17; 95% confidence interval, 5.3-12.7), 8.4% of visits where the patient had a substance abuse disorder (adjusted OR, 9.40; 95% CI, 2.0-44.4), 5.2% of visits with a patient who had depression (adjusted OR, 3.28; 95% CI, 2.0-5.4), and 2.4% of visits with a patient who used tobacco (adjusted OR, 1.09; 95% CI, 1.0-1.1).

Consider nonopioid postoperative pain management options

In an interview, Sailesh Konda, MD, associate clinical professor of dermatology and director of Mohs surgery and surgical dermatology at the University of Florida, Gainesville, who was not involved with the research, noted the finding in the study that vitiligo, hemangioma, pemphigus, AD, and psoriasis were diagnoses with the highest rates of opioid prescription was surprising. “In general, these are conditions that are not routinely managed with opioids,” he said.

NAMCS contains a primary diagnosis field and space for four additional diagnoses such as chronic conditions, as well as thirty fields for medications. “If an opioid was prescribed at a visit, it could have been prescribed for any of the diagnoses related to the visit,” Dr. Konda said. “Additionally, for those opioid prescriptions associated with dermatologic procedures, it would have been helpful to have a breakdown of the specific procedures.”

Dr. Konda compared these results to a recent study of opioid prescribing patterns in the dermatology Medicare population, which found that 93.9% of the top 1% of opioid prescribers were dermatologists working in a surgical practice.

He said that recommendations for opioid prescribing should be developed for general dermatology as they have been for Mohs surgery and dermatologic surgery. For dermatologists currently prescribing opioids, he recommended monitoring prescribing patterns and to “consider nonopioid interventions, such as acetaminophen plus ibuprofen, which has been found to effectively control postoperative pain with fewer complications.”

Ms. Pourali reports no relevant financial disclosures. Her coauthors included the principal investigator, April Armstrong, MD, MPH, professor of dermatology, University of Southern California, Los Angeles. Dr. Konda reports no relevant financial disclosures.

Opioids were prescribed most often for vitiligo, hemangioma, pemphigus, atopic dermatitis, and psoriasis, according to a study that used national ambulatory care data to evaluate pain medication use at dermatology visits.

“Overall, opioid prescribing rates among dermatologists were low. However, dermatologists should remain aware of risk factors for long-term opioid use and consider using nonnarcotic or nonpharmacologic interventions when possible,” Sarah P. Pourali, a medical student at Vanderbilt University, Nashville, said at the annual meeting of the Society for Investigative Dermatology, where she presented the results.

Ms. Pourali said that although Mohs surgery and dermatologic procedures are the focus of “much of the literature” concerning opioid use in dermatology, there are limited data on medication prescribing patterns for other skin conditions treated by dermatologists.

She and her colleagues performed a cross-sectional study using data from the National Ambulatory Medical Care Survey (NAMCS) from 2009 to 2016 on 288,462,610 weighted dermatology visits. The researchers used International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes to identify dermatologic diseases. They also identified and grouped oral pain medication into the following categories: opiate analgesics, nonsteroidal anti-inflammatory drugs, acetaminophen, and gabapentin. A linear regression analysis was used to evaluate pain medicine prescribing each year, and the researchers used a logistic regression analysis to explore how opiate prescriptions were connected to patient clinical characteristics. The analysis was adjusted for age, gender, race, ethnicity, and region.

Overall, most dermatology visits were for patients older than 65 years (36.2%) and 45-64 years old (32.1%). Over half of the dermatologist visits were for women (56.4%) and most (92.2%) visits were for patients who were White (5.1 % were for patients who were Black); most were non-Hispanic or Latino (93.5%). Most dermatology visits were in the South (35.4%) and West (25.2%), followed by the Northeast (21.9%) and Midwest (17.5%).

Opioids were prescribed in 1.3% of the visits, Ms. Pourali said. In addition, 4.7% of visits included an NSAID prescription, 0.7% an acetaminophen prescription, and 0.6% a gabapentin prescription.

Dermatologic procedure visits accounted for 43.1% of opioid prescriptions, she noted. The most common skin conditions for which opioids were prescribed included vitiligo (10.3%), hemangioma (3.8%), pemphigus (3.6%), atopic dermatitis (3.4%), and psoriasis (2.5%).

Although patients older than 65 years accounted for 36.2% of visits to dermatologists, 58.5% of opioids prescribed by dermatologists were for patients in this age group. “We hypothesize that this may be due to a higher proportion of older patients requiring skin cancer surgeries where a lot of opioids are prescribed within dermatology,” Ms. Pourali said.

The highest population-adjusted prescription rates for opiates were in the Northeast and Western regions of the United States, which “partially corroborates” previous studies that have found “higher rates of opioid prescribing in the southern and western U.S.,” she noted.

When evaluating risk-factors for long-term opiate use, Ms. Pourali and colleagues found opioids were also prescribed in 13.2% of visits where a benzodiazepine was prescribed (adjusted odds ratio, 8.17; 95% confidence interval, 5.3-12.7), 8.4% of visits where the patient had a substance abuse disorder (adjusted OR, 9.40; 95% CI, 2.0-44.4), 5.2% of visits with a patient who had depression (adjusted OR, 3.28; 95% CI, 2.0-5.4), and 2.4% of visits with a patient who used tobacco (adjusted OR, 1.09; 95% CI, 1.0-1.1).

Consider nonopioid postoperative pain management options

In an interview, Sailesh Konda, MD, associate clinical professor of dermatology and director of Mohs surgery and surgical dermatology at the University of Florida, Gainesville, who was not involved with the research, noted the finding in the study that vitiligo, hemangioma, pemphigus, AD, and psoriasis were diagnoses with the highest rates of opioid prescription was surprising. “In general, these are conditions that are not routinely managed with opioids,” he said.

NAMCS contains a primary diagnosis field and space for four additional diagnoses such as chronic conditions, as well as thirty fields for medications. “If an opioid was prescribed at a visit, it could have been prescribed for any of the diagnoses related to the visit,” Dr. Konda said. “Additionally, for those opioid prescriptions associated with dermatologic procedures, it would have been helpful to have a breakdown of the specific procedures.”

Dr. Konda compared these results to a recent study of opioid prescribing patterns in the dermatology Medicare population, which found that 93.9% of the top 1% of opioid prescribers were dermatologists working in a surgical practice.

He said that recommendations for opioid prescribing should be developed for general dermatology as they have been for Mohs surgery and dermatologic surgery. For dermatologists currently prescribing opioids, he recommended monitoring prescribing patterns and to “consider nonopioid interventions, such as acetaminophen plus ibuprofen, which has been found to effectively control postoperative pain with fewer complications.”

Ms. Pourali reports no relevant financial disclosures. Her coauthors included the principal investigator, April Armstrong, MD, MPH, professor of dermatology, University of Southern California, Los Angeles. Dr. Konda reports no relevant financial disclosures.

The investigational, novel, injected once-weekly “twincretin” tirzepatide met its primary efficacy endpoint of significantly cutting hemoglobin A1c as well as its secondary weight-loss endpoint in patients with type 2 diabetes when compared with control patients in top-line results from each of five discrete pivotal trials.

Courtesy Joslin Diabetes Center

The company developing tirzepatide, Lilly, announced these results in a series of four press releases issued during December 2020–May 2021. Scientific reports on the outcomes from four of these trials are scheduled during the American Diabetes Association’s Scientific Sessions being held virtually in late June 2021, with results from the fifth on track for a report during the annual meeting of the European Association for the Study of Diabetes in September 2021.

Tirzepatide is a “twincretin” because it combines in a single molecule two different gut-hormone activities. It works as both a glucagonlike peptide–1 receptor agonist (GLP-1 RA) and as an agent that mimics the glucose-dependent insulinotropic polypeptide (GIP).

While diabetologists qualified their comments on these results because of the limited scope and format of the five reports to date, they also expressed enthusiasm over what the press releases said.
 

Results give hope

“It’s quite exciting, but of course we would like to go by the data that’s presented” at upcoming meetings, commented Robert A. Gabbay, MD, PhD, chief science and medical officer of the American Diabetes Association in Arlington, Va. “The idea of GLP-1 and GIP activities working together has been out there for a while, but without any therapeutic options that leverage this,” he said in an interview.

“The preliminary results give us hope that tirzepatide will be a very effective glucose-lowering agent, perhaps the most effective among all options currently available, including insulin,” commented Ildiko Lingvay, MD, a diabetologist and professor at the University of Texas Southwestern Medical Center, Dallas. “Tirzepatide might have the added benefit of clinically meaningful weight loss,” and “the adverse event profile seems to be in line with what we are accustomed to with the GLP-1 RA class. I look forward to seeing the full results. Tirzepatide promises to be a great addition for type 2 diabetes,” Dr. Lingvay said in an interview.
 

A rare head-to-head against semaglutide

The five phase 3, randomized controlled trials described by Lilly in its four press releases all belong to the SURPASS series of studies for this agent. Perhaps the most intriguing of the five were results from SURPASS-2, announced in a release on March 4. This trial randomized 1,879 patients from the United States or any of seven other countries to 40 weeks of open-label treatment with one of three different dosages of tirzepatide administered by injection once weekly, or to the control group that received a weekly 1-mg injection of semaglutide (Ozempic), the highest dosage approved for controlling glycemia in patients with type 2 diabetes at the time the study launched.

In SURPASS-2 all three tested dosages of tirzepatide led to a significantly larger reduction, from baseline in A1c, compared with semaglutide, after 40 weeks, according to the Lilly release. Each of the three tirzepatide dosages also led to significantly greater weight loss from baseline, compared with semaglutide, and significantly greater percentages of patients who achieved an A1c of less than 7%, compared with semaglutide.

As an example, the highest tested tirzepatide dosage of 15 mg weekly led to an average A1c reduction from baseline of 2.46% and an average weight loss from baseline of 12.4 kg; 92% of patients achieved an A1c of less than 7%, and 51% had their A1c fall below 5.7% which indicates completely normalization of glycemic control. By comparison, the patients randomized to treatment with semaglutide had an average 1.86% reduction in their A1c level from baseline and a 6.2-kg average cut in body weight from baseline; 81% achieved an A1c of less than 7%, and 20% reached an A1c of less than 5.7%.
 

There are caveats

While these findings are notable as a rare example of an industry-sponsored head-to-head comparison of two new agents, the study comes with a few important asterisks.

First, it was open label, a curious limitation given that both agents are delivered by the same delivery method and schedule. “I cannot conclude based on this study that tirzepatide is superior because it was open label,” commented Anastassia Amaro, MD, medical director of Penn Metabolic Medicine at the University of Pennsylvania, Philadelphia.

“The gold standard is the double-blind study. An open-label design is a limitation,” agreed Dr. Gabbay.

A second caveat is that the Food and Drug Administration recently approved a higher dosage of semaglutide (2.4 g once/week) for treating overweight or obesity in patients with type 2 diabetes and in those without diabetes but a different weight-related condition such as hypertension of hypercholesterolemia. This means that the tested comparator dosage of 1 mg/week is no longer the maximum that most patients treated with semaglutide for glycemic control can receive.

“The inevitable question” about this comparison study is “what about a higher semaglutide dose,” and how might tirzepatide perform relative to that, said Dr. Gabbay. The recently approved higher dosage of semaglutide “adds an interesting wrinkle.”

Lilly has launched a series of studies testing tirzepatide as a treatment for overweight or obesity in people without diabetes, but the results are not expected until sometime in 2022 or 2023.

And there’s a third caveat: Semaglutide has already shown its value for cardiovascular risk reduction in patients with type 2 diabetes in the SUSTAIN 6 trial with nearly 3,300 randomized patients followed for 2 years and reported in 2016. The cardiovascular outcomes trial for tirzepatide, SURPASS-CVOT with more than 12,000 patients with type 2 diabetes, is underway but its results are not expected until 2024.

Despite these important limitations, a blinded comparison of tirzepatide and higher-dose semaglutide is unlikely, Dr. Amaro predicted. “It’s not worth the expense,” she said in an interview. A more likely scenario will be that, if tirzepatide enters the U.S. market, decisions on whether to treat patients with it or semaglutide will pivot on factors like the cost for treatment to individual patients based on their insurance coverage and tolerability, suggested both Dr. Amaro and Dr. Gabbay. “Physicians will need to develop a sense for tirzepatide: Do patients tolerate it and are they happy using it?” Dr. Amaro said.
 

Tirzepatide versus insulin, or on top of insulin

The other four trials in patients with type 2 diabetes reported by Lilly in releases included SURPASS-1, which randomized 478 patients to treatment with tirzepatide or placebo as monotherapy; SURPASS-3, which randomized 1,444 patients to tirzepatide or insulin degludec (Tresiba) on top of background treatment with metformin; SURPASS-4, which randomized 2,002 patients with high cardiovascular disease risk to treatment with tirzepatide or insulin glargine (Lantus) on top of background treatment with one to three different oral drugs; and SURPASS-5, which randomized 475 patients to treatment with tirzepatide or placebo on top of background treatment with insulin glargine and optional addition of metformin. Altogether, the five trials randomized nearly 6,300 patients.

The studies that compared tirzepatide against two different types of insulin, and the third that tested tirzepatide on top of insulin glargine, are especially notable. “It’s good to see that the combination [of tirzepatide and insulin glargine] works without causing major adverse events,” said Dr. Amaro.

“These are fair and helpful comparisons. I applaud Lilly for doing the right kind of comparisons,” said Dr. Gabbay.

In total, the five studies “provide evidence that tirzepatide will be effective at all stages of type 2 diabetes and can safely be used in combination with other glucose-lowering agents, including insulin,” said Dr. Lingvay. The studies with active comparator agents “allow us to compare tirzepatide’s efficacy against established therapies.”

The SURPASS trials were sponsored by Lilly, which is developing tirzepatide. Dr. Gabbay had no relevant disclosures. Dr. Lingvay has received research funds, consulting and advisory fees, or other support from Lilly as well as from several other companies including Novo Nordisk, which markets semaglutide (Ozempic) and insulin degludec (Tresiba), and Sanofi, which markets insulin glargine (Lantus). Dr. Amaro has received research funding from Lilly and from Fractyl, and has been a consultant to and received research funding from Novo Nordisk.

[email protected]

The investigational, novel, injected once-weekly “twincretin” tirzepatide met its primary efficacy endpoint of significantly cutting hemoglobin A1c as well as its secondary weight-loss endpoint in patients with type 2 diabetes when compared with control patients in top-line results from each of five discrete pivotal trials.

Courtesy Joslin Diabetes Center

The company developing tirzepatide, Lilly, announced these results in a series of four press releases issued during December 2020–May 2021. Scientific reports on the outcomes from four of these trials are scheduled during the American Diabetes Association’s Scientific Sessions being held virtually in late June 2021, with results from the fifth on track for a report during the annual meeting of the European Association for the Study of Diabetes in September 2021.

Tirzepatide is a “twincretin” because it combines in a single molecule two different gut-hormone activities. It works as both a glucagonlike peptide–1 receptor agonist (GLP-1 RA) and as an agent that mimics the glucose-dependent insulinotropic polypeptide (GIP).

While diabetologists qualified their comments on these results because of the limited scope and format of the five reports to date, they also expressed enthusiasm over what the press releases said.
 

Results give hope

“It’s quite exciting, but of course we would like to go by the data that’s presented” at upcoming meetings, commented Robert A. Gabbay, MD, PhD, chief science and medical officer of the American Diabetes Association in Arlington, Va. “The idea of GLP-1 and GIP activities working together has been out there for a while, but without any therapeutic options that leverage this,” he said in an interview.

“The preliminary results give us hope that tirzepatide will be a very effective glucose-lowering agent, perhaps the most effective among all options currently available, including insulin,” commented Ildiko Lingvay, MD, a diabetologist and professor at the University of Texas Southwestern Medical Center, Dallas. “Tirzepatide might have the added benefit of clinically meaningful weight loss,” and “the adverse event profile seems to be in line with what we are accustomed to with the GLP-1 RA class. I look forward to seeing the full results. Tirzepatide promises to be a great addition for type 2 diabetes,” Dr. Lingvay said in an interview.
 

A rare head-to-head against semaglutide

The five phase 3, randomized controlled trials described by Lilly in its four press releases all belong to the SURPASS series of studies for this agent. Perhaps the most intriguing of the five were results from SURPASS-2, announced in a release on March 4. This trial randomized 1,879 patients from the United States or any of seven other countries to 40 weeks of open-label treatment with one of three different dosages of tirzepatide administered by injection once weekly, or to the control group that received a weekly 1-mg injection of semaglutide (Ozempic), the highest dosage approved for controlling glycemia in patients with type 2 diabetes at the time the study launched.

In SURPASS-2 all three tested dosages of tirzepatide led to a significantly larger reduction, from baseline in A1c, compared with semaglutide, after 40 weeks, according to the Lilly release. Each of the three tirzepatide dosages also led to significantly greater weight loss from baseline, compared with semaglutide, and significantly greater percentages of patients who achieved an A1c of less than 7%, compared with semaglutide.

As an example, the highest tested tirzepatide dosage of 15 mg weekly led to an average A1c reduction from baseline of 2.46% and an average weight loss from baseline of 12.4 kg; 92% of patients achieved an A1c of less than 7%, and 51% had their A1c fall below 5.7% which indicates completely normalization of glycemic control. By comparison, the patients randomized to treatment with semaglutide had an average 1.86% reduction in their A1c level from baseline and a 6.2-kg average cut in body weight from baseline; 81% achieved an A1c of less than 7%, and 20% reached an A1c of less than 5.7%.
 

There are caveats

While these findings are notable as a rare example of an industry-sponsored head-to-head comparison of two new agents, the study comes with a few important asterisks.

First, it was open label, a curious limitation given that both agents are delivered by the same delivery method and schedule. “I cannot conclude based on this study that tirzepatide is superior because it was open label,” commented Anastassia Amaro, MD, medical director of Penn Metabolic Medicine at the University of Pennsylvania, Philadelphia.

“The gold standard is the double-blind study. An open-label design is a limitation,” agreed Dr. Gabbay.

A second caveat is that the Food and Drug Administration recently approved a higher dosage of semaglutide (2.4 g once/week) for treating overweight or obesity in patients with type 2 diabetes and in those without diabetes but a different weight-related condition such as hypertension of hypercholesterolemia. This means that the tested comparator dosage of 1 mg/week is no longer the maximum that most patients treated with semaglutide for glycemic control can receive.

“The inevitable question” about this comparison study is “what about a higher semaglutide dose,” and how might tirzepatide perform relative to that, said Dr. Gabbay. The recently approved higher dosage of semaglutide “adds an interesting wrinkle.”

Lilly has launched a series of studies testing tirzepatide as a treatment for overweight or obesity in people without diabetes, but the results are not expected until sometime in 2022 or 2023.

And there’s a third caveat: Semaglutide has already shown its value for cardiovascular risk reduction in patients with type 2 diabetes in the SUSTAIN 6 trial with nearly 3,300 randomized patients followed for 2 years and reported in 2016. The cardiovascular outcomes trial for tirzepatide, SURPASS-CVOT with more than 12,000 patients with type 2 diabetes, is underway but its results are not expected until 2024.

Despite these important limitations, a blinded comparison of tirzepatide and higher-dose semaglutide is unlikely, Dr. Amaro predicted. “It’s not worth the expense,” she said in an interview. A more likely scenario will be that, if tirzepatide enters the U.S. market, decisions on whether to treat patients with it or semaglutide will pivot on factors like the cost for treatment to individual patients based on their insurance coverage and tolerability, suggested both Dr. Amaro and Dr. Gabbay. “Physicians will need to develop a sense for tirzepatide: Do patients tolerate it and are they happy using it?” Dr. Amaro said.
 

Tirzepatide versus insulin, or on top of insulin

The other four trials in patients with type 2 diabetes reported by Lilly in releases included SURPASS-1, which randomized 478 patients to treatment with tirzepatide or placebo as monotherapy; SURPASS-3, which randomized 1,444 patients to tirzepatide or insulin degludec (Tresiba) on top of background treatment with metformin; SURPASS-4, which randomized 2,002 patients with high cardiovascular disease risk to treatment with tirzepatide or insulin glargine (Lantus) on top of background treatment with one to three different oral drugs; and SURPASS-5, which randomized 475 patients to treatment with tirzepatide or placebo on top of background treatment with insulin glargine and optional addition of metformin. Altogether, the five trials randomized nearly 6,300 patients.

The studies that compared tirzepatide against two different types of insulin, and the third that tested tirzepatide on top of insulin glargine, are especially notable. “It’s good to see that the combination [of tirzepatide and insulin glargine] works without causing major adverse events,” said Dr. Amaro.

“These are fair and helpful comparisons. I applaud Lilly for doing the right kind of comparisons,” said Dr. Gabbay.

In total, the five studies “provide evidence that tirzepatide will be effective at all stages of type 2 diabetes and can safely be used in combination with other glucose-lowering agents, including insulin,” said Dr. Lingvay. The studies with active comparator agents “allow us to compare tirzepatide’s efficacy against established therapies.”

The SURPASS trials were sponsored by Lilly, which is developing tirzepatide. Dr. Gabbay had no relevant disclosures. Dr. Lingvay has received research funds, consulting and advisory fees, or other support from Lilly as well as from several other companies including Novo Nordisk, which markets semaglutide (Ozempic) and insulin degludec (Tresiba), and Sanofi, which markets insulin glargine (Lantus). Dr. Amaro has received research funding from Lilly and from Fractyl, and has been a consultant to and received research funding from Novo Nordisk.

[email protected]

The investigational, novel, injected once-weekly “twincretin” tirzepatide met its primary efficacy endpoint of significantly cutting hemoglobin A1c as well as its secondary weight-loss endpoint in patients with type 2 diabetes when compared with control patients in top-line results from each of five discrete pivotal trials.

Courtesy Joslin Diabetes Center

The company developing tirzepatide, Lilly, announced these results in a series of four press releases issued during December 2020–May 2021. Scientific reports on the outcomes from four of these trials are scheduled during the American Diabetes Association’s Scientific Sessions being held virtually in late June 2021, with results from the fifth on track for a report during the annual meeting of the European Association for the Study of Diabetes in September 2021.

Tirzepatide is a “twincretin” because it combines in a single molecule two different gut-hormone activities. It works as both a glucagonlike peptide–1 receptor agonist (GLP-1 RA) and as an agent that mimics the glucose-dependent insulinotropic polypeptide (GIP).

While diabetologists qualified their comments on these results because of the limited scope and format of the five reports to date, they also expressed enthusiasm over what the press releases said.
 

Results give hope

“It’s quite exciting, but of course we would like to go by the data that’s presented” at upcoming meetings, commented Robert A. Gabbay, MD, PhD, chief science and medical officer of the American Diabetes Association in Arlington, Va. “The idea of GLP-1 and GIP activities working together has been out there for a while, but without any therapeutic options that leverage this,” he said in an interview.

“The preliminary results give us hope that tirzepatide will be a very effective glucose-lowering agent, perhaps the most effective among all options currently available, including insulin,” commented Ildiko Lingvay, MD, a diabetologist and professor at the University of Texas Southwestern Medical Center, Dallas. “Tirzepatide might have the added benefit of clinically meaningful weight loss,” and “the adverse event profile seems to be in line with what we are accustomed to with the GLP-1 RA class. I look forward to seeing the full results. Tirzepatide promises to be a great addition for type 2 diabetes,” Dr. Lingvay said in an interview.
 

A rare head-to-head against semaglutide

The five phase 3, randomized controlled trials described by Lilly in its four press releases all belong to the SURPASS series of studies for this agent. Perhaps the most intriguing of the five were results from SURPASS-2, announced in a release on March 4. This trial randomized 1,879 patients from the United States or any of seven other countries to 40 weeks of open-label treatment with one of three different dosages of tirzepatide administered by injection once weekly, or to the control group that received a weekly 1-mg injection of semaglutide (Ozempic), the highest dosage approved for controlling glycemia in patients with type 2 diabetes at the time the study launched.

In SURPASS-2 all three tested dosages of tirzepatide led to a significantly larger reduction, from baseline in A1c, compared with semaglutide, after 40 weeks, according to the Lilly release. Each of the three tirzepatide dosages also led to significantly greater weight loss from baseline, compared with semaglutide, and significantly greater percentages of patients who achieved an A1c of less than 7%, compared with semaglutide.

As an example, the highest tested tirzepatide dosage of 15 mg weekly led to an average A1c reduction from baseline of 2.46% and an average weight loss from baseline of 12.4 kg; 92% of patients achieved an A1c of less than 7%, and 51% had their A1c fall below 5.7% which indicates completely normalization of glycemic control. By comparison, the patients randomized to treatment with semaglutide had an average 1.86% reduction in their A1c level from baseline and a 6.2-kg average cut in body weight from baseline; 81% achieved an A1c of less than 7%, and 20% reached an A1c of less than 5.7%.
 

There are caveats

While these findings are notable as a rare example of an industry-sponsored head-to-head comparison of two new agents, the study comes with a few important asterisks.

First, it was open label, a curious limitation given that both agents are delivered by the same delivery method and schedule. “I cannot conclude based on this study that tirzepatide is superior because it was open label,” commented Anastassia Amaro, MD, medical director of Penn Metabolic Medicine at the University of Pennsylvania, Philadelphia.

“The gold standard is the double-blind study. An open-label design is a limitation,” agreed Dr. Gabbay.

A second caveat is that the Food and Drug Administration recently approved a higher dosage of semaglutide (2.4 g once/week) for treating overweight or obesity in patients with type 2 diabetes and in those without diabetes but a different weight-related condition such as hypertension of hypercholesterolemia. This means that the tested comparator dosage of 1 mg/week is no longer the maximum that most patients treated with semaglutide for glycemic control can receive.

“The inevitable question” about this comparison study is “what about a higher semaglutide dose,” and how might tirzepatide perform relative to that, said Dr. Gabbay. The recently approved higher dosage of semaglutide “adds an interesting wrinkle.”

Lilly has launched a series of studies testing tirzepatide as a treatment for overweight or obesity in people without diabetes, but the results are not expected until sometime in 2022 or 2023.

And there’s a third caveat: Semaglutide has already shown its value for cardiovascular risk reduction in patients with type 2 diabetes in the SUSTAIN 6 trial with nearly 3,300 randomized patients followed for 2 years and reported in 2016. The cardiovascular outcomes trial for tirzepatide, SURPASS-CVOT with more than 12,000 patients with type 2 diabetes, is underway but its results are not expected until 2024.

Despite these important limitations, a blinded comparison of tirzepatide and higher-dose semaglutide is unlikely, Dr. Amaro predicted. “It’s not worth the expense,” she said in an interview. A more likely scenario will be that, if tirzepatide enters the U.S. market, decisions on whether to treat patients with it or semaglutide will pivot on factors like the cost for treatment to individual patients based on their insurance coverage and tolerability, suggested both Dr. Amaro and Dr. Gabbay. “Physicians will need to develop a sense for tirzepatide: Do patients tolerate it and are they happy using it?” Dr. Amaro said.
 

Tirzepatide versus insulin, or on top of insulin

The other four trials in patients with type 2 diabetes reported by Lilly in releases included SURPASS-1, which randomized 478 patients to treatment with tirzepatide or placebo as monotherapy; SURPASS-3, which randomized 1,444 patients to tirzepatide or insulin degludec (Tresiba) on top of background treatment with metformin; SURPASS-4, which randomized 2,002 patients with high cardiovascular disease risk to treatment with tirzepatide or insulin glargine (Lantus) on top of background treatment with one to three different oral drugs; and SURPASS-5, which randomized 475 patients to treatment with tirzepatide or placebo on top of background treatment with insulin glargine and optional addition of metformin. Altogether, the five trials randomized nearly 6,300 patients.

The studies that compared tirzepatide against two different types of insulin, and the third that tested tirzepatide on top of insulin glargine, are especially notable. “It’s good to see that the combination [of tirzepatide and insulin glargine] works without causing major adverse events,” said Dr. Amaro.

“These are fair and helpful comparisons. I applaud Lilly for doing the right kind of comparisons,” said Dr. Gabbay.

In total, the five studies “provide evidence that tirzepatide will be effective at all stages of type 2 diabetes and can safely be used in combination with other glucose-lowering agents, including insulin,” said Dr. Lingvay. The studies with active comparator agents “allow us to compare tirzepatide’s efficacy against established therapies.”

The SURPASS trials were sponsored by Lilly, which is developing tirzepatide. Dr. Gabbay had no relevant disclosures. Dr. Lingvay has received research funds, consulting and advisory fees, or other support from Lilly as well as from several other companies including Novo Nordisk, which markets semaglutide (Ozempic) and insulin degludec (Tresiba), and Sanofi, which markets insulin glargine (Lantus). Dr. Amaro has received research funding from Lilly and from Fractyl, and has been a consultant to and received research funding from Novo Nordisk.

[email protected]

The Diagnosis: Paraneoplastic Acanthosis Nigricans 

Histopathologic examination demonstrated verrucous epidermal hyperplasia (Figure, A). Fungal organisms were identified with an Alcian blue and periodic acid-Schiff stain (Figure, B). The organisms demonstrated a vertical orientation in relation to the mucosal surface, which was consistent with candidal organisms.  

Given the rapid eruption of these plaques, the distribution on the oral and palmar surfaces (tripe palms), and the minimal improvement with both systemic steroids and antifungal treatment, a diagnosis of paraneoplastic acanthosis nigricans with secondary candidal infection was made. Drug-induced cheilitis was considered; however, improvement with discontinuation of the suspected offending drug would have been expected. Although chronic mucocutaneous candidiasis was possible, more prompt improvement upon initiation of systemic antifungal therapy would have been observed. Oral Crohn disease should be included in the differential, but it was unlikely given the lack of granulomas on pathology and absence of history of gastrointestinal tract symptoms. Melkersson-Rosenthal syndrome also was unlikely given the lack of facial nerve palsy as well as the lack of granulomas on pathology. Furthermore, none of these options would be associated with tripe palms, as seen in our patient.  

Acanthosis nigricans is a localized skin disorder characterized by hyperpigmented velvety plaques arising in flexural and intertriginous regions. Although most cases (80%) are associated with idiopathic or benign conditions, the link between acanthosis nigricans and an underlying malignancy has been well documented.^1-3 Most commonly associated with an underlying intra-abdominal malignancy (often gastric carcinoma), the lesions of paraneoplastic acanthosis nigricans are indistinguishable from their benign counterparts^.1,4 When the condition presents abruptly and extensively in a nonobese patient, prompt workup for malignancy should be initiated. Rapid onset and atypical distribution (ie, palmar, perioral, or mucosal) more commonly is associated with a paraneoplastic etiology.^5,6 

Histopathology for acanthosis nigricans shows hyperkeratosis and epidermal papillomatosis. Horn pseudocyst formation is possible, but usually no hyperpigmentation is observed. The findings typically are indistinguishable from seborrheic keratoses, epidermal nevi, or lesions of confluent and reticulated papillomatosis of Gougerot and Carteaud.² 

The underlying pathogenesis of acanthosis nigricans is poorly understood. In the benign subtype, insulin resistance commonly has been described. In the paraneoplastic subtype, it is proposed that the tumor produces a transforming growth factor that mimics epidermal growth factor and leads to keratinocyte proliferation.^7,8 Paraneoplastic acanthosis nigricans has the potential to arise at any point of tumor development, further contributing to the diagnostic challenge. Treatment of the skin lesions involves management of the underlying malignancy. Unfortunately, many such malignancies often are at an advanced stage, and subsequent prognosis is poor.² 

The Diagnosis: Paraneoplastic Acanthosis Nigricans 

Histopathologic examination demonstrated verrucous epidermal hyperplasia (Figure, A). Fungal organisms were identified with an Alcian blue and periodic acid-Schiff stain (Figure, B). The organisms demonstrated a vertical orientation in relation to the mucosal surface, which was consistent with candidal organisms.  

Given the rapid eruption of these plaques, the distribution on the oral and palmar surfaces (tripe palms), and the minimal improvement with both systemic steroids and antifungal treatment, a diagnosis of paraneoplastic acanthosis nigricans with secondary candidal infection was made. Drug-induced cheilitis was considered; however, improvement with discontinuation of the suspected offending drug would have been expected. Although chronic mucocutaneous candidiasis was possible, more prompt improvement upon initiation of systemic antifungal therapy would have been observed. Oral Crohn disease should be included in the differential, but it was unlikely given the lack of granulomas on pathology and absence of history of gastrointestinal tract symptoms. Melkersson-Rosenthal syndrome also was unlikely given the lack of facial nerve palsy as well as the lack of granulomas on pathology. Furthermore, none of these options would be associated with tripe palms, as seen in our patient.  

Acanthosis nigricans is a localized skin disorder characterized by hyperpigmented velvety plaques arising in flexural and intertriginous regions. Although most cases (80%) are associated with idiopathic or benign conditions, the link between acanthosis nigricans and an underlying malignancy has been well documented.^1-3 Most commonly associated with an underlying intra-abdominal malignancy (often gastric carcinoma), the lesions of paraneoplastic acanthosis nigricans are indistinguishable from their benign counterparts^.1,4 When the condition presents abruptly and extensively in a nonobese patient, prompt workup for malignancy should be initiated. Rapid onset and atypical distribution (ie, palmar, perioral, or mucosal) more commonly is associated with a paraneoplastic etiology.^5,6 

Histopathology for acanthosis nigricans shows hyperkeratosis and epidermal papillomatosis. Horn pseudocyst formation is possible, but usually no hyperpigmentation is observed. The findings typically are indistinguishable from seborrheic keratoses, epidermal nevi, or lesions of confluent and reticulated papillomatosis of Gougerot and Carteaud.² 

The underlying pathogenesis of acanthosis nigricans is poorly understood. In the benign subtype, insulin resistance commonly has been described. In the paraneoplastic subtype, it is proposed that the tumor produces a transforming growth factor that mimics epidermal growth factor and leads to keratinocyte proliferation.^7,8 Paraneoplastic acanthosis nigricans has the potential to arise at any point of tumor development, further contributing to the diagnostic challenge. Treatment of the skin lesions involves management of the underlying malignancy. Unfortunately, many such malignancies often are at an advanced stage, and subsequent prognosis is poor.² 

The Diagnosis: Paraneoplastic Acanthosis Nigricans 

Histopathologic examination demonstrated verrucous epidermal hyperplasia (Figure, A). Fungal organisms were identified with an Alcian blue and periodic acid-Schiff stain (Figure, B). The organisms demonstrated a vertical orientation in relation to the mucosal surface, which was consistent with candidal organisms.  

Given the rapid eruption of these plaques, the distribution on the oral and palmar surfaces (tripe palms), and the minimal improvement with both systemic steroids and antifungal treatment, a diagnosis of paraneoplastic acanthosis nigricans with secondary candidal infection was made. Drug-induced cheilitis was considered; however, improvement with discontinuation of the suspected offending drug would have been expected. Although chronic mucocutaneous candidiasis was possible, more prompt improvement upon initiation of systemic antifungal therapy would have been observed. Oral Crohn disease should be included in the differential, but it was unlikely given the lack of granulomas on pathology and absence of history of gastrointestinal tract symptoms. Melkersson-Rosenthal syndrome also was unlikely given the lack of facial nerve palsy as well as the lack of granulomas on pathology. Furthermore, none of these options would be associated with tripe palms, as seen in our patient.  

Acanthosis nigricans is a localized skin disorder characterized by hyperpigmented velvety plaques arising in flexural and intertriginous regions. Although most cases (80%) are associated with idiopathic or benign conditions, the link between acanthosis nigricans and an underlying malignancy has been well documented.^1-3 Most commonly associated with an underlying intra-abdominal malignancy (often gastric carcinoma), the lesions of paraneoplastic acanthosis nigricans are indistinguishable from their benign counterparts^.1,4 When the condition presents abruptly and extensively in a nonobese patient, prompt workup for malignancy should be initiated. Rapid onset and atypical distribution (ie, palmar, perioral, or mucosal) more commonly is associated with a paraneoplastic etiology.^5,6 

Histopathology for acanthosis nigricans shows hyperkeratosis and epidermal papillomatosis. Horn pseudocyst formation is possible, but usually no hyperpigmentation is observed. The findings typically are indistinguishable from seborrheic keratoses, epidermal nevi, or lesions of confluent and reticulated papillomatosis of Gougerot and Carteaud.² 

The underlying pathogenesis of acanthosis nigricans is poorly understood. In the benign subtype, insulin resistance commonly has been described. In the paraneoplastic subtype, it is proposed that the tumor produces a transforming growth factor that mimics epidermal growth factor and leads to keratinocyte proliferation.^7,8 Paraneoplastic acanthosis nigricans has the potential to arise at any point of tumor development, further contributing to the diagnostic challenge. Treatment of the skin lesions involves management of the underlying malignancy. Unfortunately, many such malignancies often are at an advanced stage, and subsequent prognosis is poor.² 

Experts assessed different chemopreventive agents meant to reduce the incidence of colorectal neoplasia and associated mortality based on whether these agents were effective and safe, but they found few fit both criteria, according to a new clinical practice update from the American Gastroenterological Association.

That said, the update does advise that clinicians use low-dose aspirin therapy in patients who are younger than 70 years with at least a 10-year life expectancy, are not at high risk for bleeding, and have at least a 10% cardiovascular disease risk over the next decade.

This best practice advice statement reflects “high-quality trial data” for this patient population and also echoes U.S. Preventive Services Task Force recommendations, wrote Peter S. Liang, MD, MPH, and his associates on behalf of the American Gastroenterological Association. However, they note that low-dose aspirin therapy has shown inconsistent results for older patients and that its chemopreventive benefits always should be weighed against an individual’s bleeding risk.

Published in Clinical Gastroenterology and Hepatology, the clinical practice update also recommends considering low-dose aspirin therapy for patients with a history of colorectal neoplasia, based on data from several trials in which daily doses of 81-325 mg were associated with a significantly lower likelihood of recurrence of earlier-stage adenomas (the findings did not extend to patients with more advanced lesions). Evidence on sessile serrated polyps is sparser, but there is some indication for a benefit in this setting, the experts noted.

Their best-practice advice also covers nonaspirin nonsteroidal anti-inflammatory drugs, metformin, calcium, vitamin D, folic acid, and statins. Among these agents, only metformin receives even a conditional green light. “Because of the results of a large number of observational studies, a small adenoma trial, as well as a favorable safety profile, metformin may be considered for chemoprevention against colorectal neoplasia in individuals with diabetes,” the experts concluded. Support for this best-practice advice includes a meta-analysis of colorectal cancer–specific survival in 17 observational studies, a meta-analysis of colorectal cancer incidence in 14 observational studies, and a randomized, placebo-controlled trial in which 250 mg daily metformin was safe and associated with a 40% lower risk of recurrent adenoma.

For calcium, study findings have been mixed, and a recent large clinical trial found no overall benefit for adenoma prevention. Because high-dose calcium has been linked to kidney toxicity, hypercalcemia, and prostate cancer, its risks likely outweigh any benefits, the experts concluded. Vitamin D (as monotherapy or with calcium) also has shown no overall benefit for preventing adenomas or sessile serrated lesions. A large ongoing, randomized trial will examine colorectal cancer incidence among adults receiving 5 years of oral vitamin D or placebo, but its results will not be available until at least 2025.

Nonsteroidal anti-inflammatory drugs are not recommended to prevent colorectal neoplasia among average-risk individuals. Cyclooxygenase-2 inhibitors pose “substantial cardiovascular risks,” while nonselective NSAIDs are associated with a significantly increased risk for gastrointestinal bleeding. Meta-analyses have shown no benefit of folic acid for preventing colorectal neoplasia, and observational studies on statins have produced only mixed results.

No funding sources were reported. The experts reported having no conflicts of interest.

Experts assessed different chemopreventive agents meant to reduce the incidence of colorectal neoplasia and associated mortality based on whether these agents were effective and safe, but they found few fit both criteria, according to a new clinical practice update from the American Gastroenterological Association.

That said, the update does advise that clinicians use low-dose aspirin therapy in patients who are younger than 70 years with at least a 10-year life expectancy, are not at high risk for bleeding, and have at least a 10% cardiovascular disease risk over the next decade.

This best practice advice statement reflects “high-quality trial data” for this patient population and also echoes U.S. Preventive Services Task Force recommendations, wrote Peter S. Liang, MD, MPH, and his associates on behalf of the American Gastroenterological Association. However, they note that low-dose aspirin therapy has shown inconsistent results for older patients and that its chemopreventive benefits always should be weighed against an individual’s bleeding risk.

Published in Clinical Gastroenterology and Hepatology, the clinical practice update also recommends considering low-dose aspirin therapy for patients with a history of colorectal neoplasia, based on data from several trials in which daily doses of 81-325 mg were associated with a significantly lower likelihood of recurrence of earlier-stage adenomas (the findings did not extend to patients with more advanced lesions). Evidence on sessile serrated polyps is sparser, but there is some indication for a benefit in this setting, the experts noted.

Their best-practice advice also covers nonaspirin nonsteroidal anti-inflammatory drugs, metformin, calcium, vitamin D, folic acid, and statins. Among these agents, only metformin receives even a conditional green light. “Because of the results of a large number of observational studies, a small adenoma trial, as well as a favorable safety profile, metformin may be considered for chemoprevention against colorectal neoplasia in individuals with diabetes,” the experts concluded. Support for this best-practice advice includes a meta-analysis of colorectal cancer–specific survival in 17 observational studies, a meta-analysis of colorectal cancer incidence in 14 observational studies, and a randomized, placebo-controlled trial in which 250 mg daily metformin was safe and associated with a 40% lower risk of recurrent adenoma.

For calcium, study findings have been mixed, and a recent large clinical trial found no overall benefit for adenoma prevention. Because high-dose calcium has been linked to kidney toxicity, hypercalcemia, and prostate cancer, its risks likely outweigh any benefits, the experts concluded. Vitamin D (as monotherapy or with calcium) also has shown no overall benefit for preventing adenomas or sessile serrated lesions. A large ongoing, randomized trial will examine colorectal cancer incidence among adults receiving 5 years of oral vitamin D or placebo, but its results will not be available until at least 2025.

Nonsteroidal anti-inflammatory drugs are not recommended to prevent colorectal neoplasia among average-risk individuals. Cyclooxygenase-2 inhibitors pose “substantial cardiovascular risks,” while nonselective NSAIDs are associated with a significantly increased risk for gastrointestinal bleeding. Meta-analyses have shown no benefit of folic acid for preventing colorectal neoplasia, and observational studies on statins have produced only mixed results.

No funding sources were reported. The experts reported having no conflicts of interest.

Experts assessed different chemopreventive agents meant to reduce the incidence of colorectal neoplasia and associated mortality based on whether these agents were effective and safe, but they found few fit both criteria, according to a new clinical practice update from the American Gastroenterological Association.

That said, the update does advise that clinicians use low-dose aspirin therapy in patients who are younger than 70 years with at least a 10-year life expectancy, are not at high risk for bleeding, and have at least a 10% cardiovascular disease risk over the next decade.

This best practice advice statement reflects “high-quality trial data” for this patient population and also echoes U.S. Preventive Services Task Force recommendations, wrote Peter S. Liang, MD, MPH, and his associates on behalf of the American Gastroenterological Association. However, they note that low-dose aspirin therapy has shown inconsistent results for older patients and that its chemopreventive benefits always should be weighed against an individual’s bleeding risk.

Published in Clinical Gastroenterology and Hepatology, the clinical practice update also recommends considering low-dose aspirin therapy for patients with a history of colorectal neoplasia, based on data from several trials in which daily doses of 81-325 mg were associated with a significantly lower likelihood of recurrence of earlier-stage adenomas (the findings did not extend to patients with more advanced lesions). Evidence on sessile serrated polyps is sparser, but there is some indication for a benefit in this setting, the experts noted.

Their best-practice advice also covers nonaspirin nonsteroidal anti-inflammatory drugs, metformin, calcium, vitamin D, folic acid, and statins. Among these agents, only metformin receives even a conditional green light. “Because of the results of a large number of observational studies, a small adenoma trial, as well as a favorable safety profile, metformin may be considered for chemoprevention against colorectal neoplasia in individuals with diabetes,” the experts concluded. Support for this best-practice advice includes a meta-analysis of colorectal cancer–specific survival in 17 observational studies, a meta-analysis of colorectal cancer incidence in 14 observational studies, and a randomized, placebo-controlled trial in which 250 mg daily metformin was safe and associated with a 40% lower risk of recurrent adenoma.

For calcium, study findings have been mixed, and a recent large clinical trial found no overall benefit for adenoma prevention. Because high-dose calcium has been linked to kidney toxicity, hypercalcemia, and prostate cancer, its risks likely outweigh any benefits, the experts concluded. Vitamin D (as monotherapy or with calcium) also has shown no overall benefit for preventing adenomas or sessile serrated lesions. A large ongoing, randomized trial will examine colorectal cancer incidence among adults receiving 5 years of oral vitamin D or placebo, but its results will not be available until at least 2025.

Nonsteroidal anti-inflammatory drugs are not recommended to prevent colorectal neoplasia among average-risk individuals. Cyclooxygenase-2 inhibitors pose “substantial cardiovascular risks,” while nonselective NSAIDs are associated with a significantly increased risk for gastrointestinal bleeding. Meta-analyses have shown no benefit of folic acid for preventing colorectal neoplasia, and observational studies on statins have produced only mixed results.

No funding sources were reported. The experts reported having no conflicts of interest.

Tumor necrosis factor inhibitors reduce both spinal and sacroiliac radiographic progression in early axial spondyloarthritis (axSpA), but the effects take time.

According to data from the German Spondyloarthritis Inception Cohort (GESPIC), it could take 2-4 years after the initiation of TNF inhibitor treatment before x-rays will show any sign of a benefit in either the spine or sacroiliac joints (SIJ).

“The association between anti-TNF treatment and the retardation of radiographic spinal progression in spondyloarthritis appears to be time-shifted,” GESPIC study investigator Denis Poddubnyy, MD, said at the annual European Congress of Rheumatology.

Reporting the spinal findings, Dr. Poddubnyy, who is head of the rheumatology department at Campus Benjamin Franklin of the Charité University Hospital in Berlin noted that “at least 4 years of observation is required” to see an effect of TNF inhibitors on new bone formation. “This might be related to the intermediate and long-lasting process of bone repair that follows the resolution of inflammation and precedes the development of new bone,” he suggested.

The effect on the SIJ may precede the spinal damage, so it’s important to look at how anti-inflammatory treatment might affect the SIJ, Dr. Poddubnyy said in an interview. Results from the SIJ analysis, which were presented by Murat Torgutalp, MD, suggested that there might be a 2-year time lag between TNFi treatment and being able to see something on x-rays.

“Everybody in the past focused on the spine, considering that spinal changes are functionally more relevant than changes in the SIJ,” Dr. Poddubnyy observed.

Structural damage in the spine and SIJ in radiographic axSpA probably occur by different processes, he explained. While it’s more to do with new bone formation in the spine, it’s more to do with erosive damage followed by repair in the SIJ. “It is very likely that in the majority of patients we see that those two processes are somehow disconnected in time,” he suggested.

The GESPIC cohort provides a good base from which to examine the effects of TNF inhibitors on radiographic progression in patients with axSpA for several reasons, observed Dr. Poddubnyy. For one it was established in 2000, so “well before the introduction of TNF-alpha inhibitors.” That means that almost all patients would have been put on TNF inhibitors while enrolled in the cohort, he said, “so we could really follow up them prospectively for a few years.” In fact, just nine patients had been treated with TNF inhibitors at baseline.

Spinal findings

Although TNF inhibitors are widely accepted to be effective anti-inflammatory drugs that can relieve patients’ spinal symptoms, there were inconclusive data on whether they can also have an impact on radiographic progression.

To look at the possible immediate or later effect of TNF inhibitors on spinal radiographic progression, the GESPIC investigators looked at sets of radiographs, taken at least 2 years apart over a 10-year period, from 266 patients, 77 of whom who had been treated with a TNF inhibitor for at least 12 months or more. Overall, there were 103 2-year intervals covered by TNF inhibitor treatment of any duration, and 78 intervals in which treatment had lasted for at least 12 months.

“This cohort included patients with quite early disease, including both nonradiographic and radiographic forms,” Dr. Poddubnyy said, adding that some patients had been treated with a TNF inhibitor for up to 10 years.

While there were no significant changes in radiographic progression as measured using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) between patients who had and who had not received at least 12 months’ TNF inhibitor therapy in the first 2 years, there was a substantial difference after 4 years.

The mSASSS change in scores over 2 years in patients who were and were not treated with a TNF inhibitor for 12 months or more were a respective 0.35 and 0.81 (P = .047) considering treatment in the previous 2-year treatment period, and 0.33 and 0.77 (also P = .047) considering treatment in the prior 2-year treatment period and the current 2-year period.

“Our interpretation is that within the first 2 years we see a resolution of inflammation, a process of repair, maybe even a process of bone formation, but then if you continue this inflammation control for longer than 2 years, then we see the effect on structural damage,” Dr. Poddubnyy said.

SIJ findings

The SIJ analysis included 301 patients who had at least two sets of radiographs taken every 2 years over a 10-year follow-up period, 87 (28.9%) of whom had been treated with at least one TNF inhibitor during follow-up.

Radiographic SIJ progression was defined as the change in the sacroiliitis sum score over 2 years. Calculations considered both the current 2-year period and the previous 2-year period, as well as any use of TNF inhibitors or more than 12 months’ use.

There were no significant differences in sacroiliitis sum scores comparing people who were and were not treated with TNF inhibitors for at least 12 months in the current 2-year period. However, when the previous 2-year period was looked at there was a significant difference in the score between those who had and had not been treated for 12 or more months (0.15 vs. 0.27, respectively; P = .024).

“These data indicate that TNF inhibitors have a late effect,” Dr. Torgutalp said. “You cannot observe the effect of the TNF inhibitor on radiographic progression in the same interval, you have to wait to see this effect in the next interval,” he explained. That means that when a patient uses a TNF inhibitor, you must wait to see the effect on SIJ progression in the subsequent 2 years, he qualified.

Lessons for practice

“If we control inflammation, we might control structural damage progression,” Dr. Poddubnyy said.

If this is the case, then it is likely that other drugs that control inflammation in axSpA will have a similar effect, such as those that target interleukin-17 or Janus kinases. This is something in the future to look at in the GESPIC cohort once enough patient-years of data are available.

Early treatment is probably important, Dr. Poddubnyy suggested, “because in patients with early disease we can expect not that much structural damage at baseline.” Starting treatment early, at the inflammatory stage rather than at the stage where there was a lot of damage already there, could yield better results, he proposed.

“As a clinician, as a researcher, I would be really interested in demonstrating in a prospective, clinical trial that treating patients to target, achieving a remission, would be associated with retardation of structural damage progression. This has only been shown in observational studies so far, so this is an open question.”

Questions on adjustments made for confounding factors

Questions on the spinal presentation included whether there were any differences in NSAID use, to which Dr. Poddubnyy responded, “Patients on TNF inhibitors normally reduce NSAIDs. We adjusted, therefore, for NSAID use.”

The SIJ presentation garnered more questioning. Dr. Torgutalp qualified that both radiographic and nonradiographic patients had been included in the analysis, and “we observe the same effect.”

Asked how clinically relevant the findings were, he noted that, “to the best of our knowledge, this is the first data for sacroiliac joint progression.” The data for spinal progression seem to “reconcile the results from previous investigators,” where there had been some conflicting data on whether 2 or 4 years’ TNF-inhibitor therapy had any effect on radiographic progression.

“I don’t think you’ve adjusted for the baseline level of damage of the SIJ?” queried Pedro Machado, MD, of University College London Hospital. “As you know, in the spine, but also at the SIJ level, the baseline level of damage is usually one of the strongest predictors of further damage.”

This is not something that was adjusted for, Dr. Torgutalp conceded. “We will do it for further analysis,” he said.

Since 2010, GESPIC has been supported by grants from AbbVie. Dr. Poddubnyy reported financial relationships with AbbVie and numerous other pharmaceutical companies. Dr. Torgutalp had no relevant disclosures.

Tumor necrosis factor inhibitors reduce both spinal and sacroiliac radiographic progression in early axial spondyloarthritis (axSpA), but the effects take time.

According to data from the German Spondyloarthritis Inception Cohort (GESPIC), it could take 2-4 years after the initiation of TNF inhibitor treatment before x-rays will show any sign of a benefit in either the spine or sacroiliac joints (SIJ).

“The association between anti-TNF treatment and the retardation of radiographic spinal progression in spondyloarthritis appears to be time-shifted,” GESPIC study investigator Denis Poddubnyy, MD, said at the annual European Congress of Rheumatology.

Reporting the spinal findings, Dr. Poddubnyy, who is head of the rheumatology department at Campus Benjamin Franklin of the Charité University Hospital in Berlin noted that “at least 4 years of observation is required” to see an effect of TNF inhibitors on new bone formation. “This might be related to the intermediate and long-lasting process of bone repair that follows the resolution of inflammation and precedes the development of new bone,” he suggested.

The effect on the SIJ may precede the spinal damage, so it’s important to look at how anti-inflammatory treatment might affect the SIJ, Dr. Poddubnyy said in an interview. Results from the SIJ analysis, which were presented by Murat Torgutalp, MD, suggested that there might be a 2-year time lag between TNFi treatment and being able to see something on x-rays.

“Everybody in the past focused on the spine, considering that spinal changes are functionally more relevant than changes in the SIJ,” Dr. Poddubnyy observed.

Structural damage in the spine and SIJ in radiographic axSpA probably occur by different processes, he explained. While it’s more to do with new bone formation in the spine, it’s more to do with erosive damage followed by repair in the SIJ. “It is very likely that in the majority of patients we see that those two processes are somehow disconnected in time,” he suggested.

The GESPIC cohort provides a good base from which to examine the effects of TNF inhibitors on radiographic progression in patients with axSpA for several reasons, observed Dr. Poddubnyy. For one it was established in 2000, so “well before the introduction of TNF-alpha inhibitors.” That means that almost all patients would have been put on TNF inhibitors while enrolled in the cohort, he said, “so we could really follow up them prospectively for a few years.” In fact, just nine patients had been treated with TNF inhibitors at baseline.

Spinal findings

Although TNF inhibitors are widely accepted to be effective anti-inflammatory drugs that can relieve patients’ spinal symptoms, there were inconclusive data on whether they can also have an impact on radiographic progression.

To look at the possible immediate or later effect of TNF inhibitors on spinal radiographic progression, the GESPIC investigators looked at sets of radiographs, taken at least 2 years apart over a 10-year period, from 266 patients, 77 of whom who had been treated with a TNF inhibitor for at least 12 months or more. Overall, there were 103 2-year intervals covered by TNF inhibitor treatment of any duration, and 78 intervals in which treatment had lasted for at least 12 months.

“This cohort included patients with quite early disease, including both nonradiographic and radiographic forms,” Dr. Poddubnyy said, adding that some patients had been treated with a TNF inhibitor for up to 10 years.

While there were no significant changes in radiographic progression as measured using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) between patients who had and who had not received at least 12 months’ TNF inhibitor therapy in the first 2 years, there was a substantial difference after 4 years.

The mSASSS change in scores over 2 years in patients who were and were not treated with a TNF inhibitor for 12 months or more were a respective 0.35 and 0.81 (P = .047) considering treatment in the previous 2-year treatment period, and 0.33 and 0.77 (also P = .047) considering treatment in the prior 2-year treatment period and the current 2-year period.

“Our interpretation is that within the first 2 years we see a resolution of inflammation, a process of repair, maybe even a process of bone formation, but then if you continue this inflammation control for longer than 2 years, then we see the effect on structural damage,” Dr. Poddubnyy said.

SIJ findings

The SIJ analysis included 301 patients who had at least two sets of radiographs taken every 2 years over a 10-year follow-up period, 87 (28.9%) of whom had been treated with at least one TNF inhibitor during follow-up.

Radiographic SIJ progression was defined as the change in the sacroiliitis sum score over 2 years. Calculations considered both the current 2-year period and the previous 2-year period, as well as any use of TNF inhibitors or more than 12 months’ use.

There were no significant differences in sacroiliitis sum scores comparing people who were and were not treated with TNF inhibitors for at least 12 months in the current 2-year period. However, when the previous 2-year period was looked at there was a significant difference in the score between those who had and had not been treated for 12 or more months (0.15 vs. 0.27, respectively; P = .024).

“These data indicate that TNF inhibitors have a late effect,” Dr. Torgutalp said. “You cannot observe the effect of the TNF inhibitor on radiographic progression in the same interval, you have to wait to see this effect in the next interval,” he explained. That means that when a patient uses a TNF inhibitor, you must wait to see the effect on SIJ progression in the subsequent 2 years, he qualified.

Lessons for practice

“If we control inflammation, we might control structural damage progression,” Dr. Poddubnyy said.

If this is the case, then it is likely that other drugs that control inflammation in axSpA will have a similar effect, such as those that target interleukin-17 or Janus kinases. This is something in the future to look at in the GESPIC cohort once enough patient-years of data are available.

Early treatment is probably important, Dr. Poddubnyy suggested, “because in patients with early disease we can expect not that much structural damage at baseline.” Starting treatment early, at the inflammatory stage rather than at the stage where there was a lot of damage already there, could yield better results, he proposed.

“As a clinician, as a researcher, I would be really interested in demonstrating in a prospective, clinical trial that treating patients to target, achieving a remission, would be associated with retardation of structural damage progression. This has only been shown in observational studies so far, so this is an open question.”

Questions on adjustments made for confounding factors

Questions on the spinal presentation included whether there were any differences in NSAID use, to which Dr. Poddubnyy responded, “Patients on TNF inhibitors normally reduce NSAIDs. We adjusted, therefore, for NSAID use.”

The SIJ presentation garnered more questioning. Dr. Torgutalp qualified that both radiographic and nonradiographic patients had been included in the analysis, and “we observe the same effect.”

Asked how clinically relevant the findings were, he noted that, “to the best of our knowledge, this is the first data for sacroiliac joint progression.” The data for spinal progression seem to “reconcile the results from previous investigators,” where there had been some conflicting data on whether 2 or 4 years’ TNF-inhibitor therapy had any effect on radiographic progression.

“I don’t think you’ve adjusted for the baseline level of damage of the SIJ?” queried Pedro Machado, MD, of University College London Hospital. “As you know, in the spine, but also at the SIJ level, the baseline level of damage is usually one of the strongest predictors of further damage.”

This is not something that was adjusted for, Dr. Torgutalp conceded. “We will do it for further analysis,” he said.

Since 2010, GESPIC has been supported by grants from AbbVie. Dr. Poddubnyy reported financial relationships with AbbVie and numerous other pharmaceutical companies. Dr. Torgutalp had no relevant disclosures.

Tumor necrosis factor inhibitors reduce both spinal and sacroiliac radiographic progression in early axial spondyloarthritis (axSpA), but the effects take time.

According to data from the German Spondyloarthritis Inception Cohort (GESPIC), it could take 2-4 years after the initiation of TNF inhibitor treatment before x-rays will show any sign of a benefit in either the spine or sacroiliac joints (SIJ).

“The association between anti-TNF treatment and the retardation of radiographic spinal progression in spondyloarthritis appears to be time-shifted,” GESPIC study investigator Denis Poddubnyy, MD, said at the annual European Congress of Rheumatology.

Reporting the spinal findings, Dr. Poddubnyy, who is head of the rheumatology department at Campus Benjamin Franklin of the Charité University Hospital in Berlin noted that “at least 4 years of observation is required” to see an effect of TNF inhibitors on new bone formation. “This might be related to the intermediate and long-lasting process of bone repair that follows the resolution of inflammation and precedes the development of new bone,” he suggested.

The effect on the SIJ may precede the spinal damage, so it’s important to look at how anti-inflammatory treatment might affect the SIJ, Dr. Poddubnyy said in an interview. Results from the SIJ analysis, which were presented by Murat Torgutalp, MD, suggested that there might be a 2-year time lag between TNFi treatment and being able to see something on x-rays.

“Everybody in the past focused on the spine, considering that spinal changes are functionally more relevant than changes in the SIJ,” Dr. Poddubnyy observed.

Structural damage in the spine and SIJ in radiographic axSpA probably occur by different processes, he explained. While it’s more to do with new bone formation in the spine, it’s more to do with erosive damage followed by repair in the SIJ. “It is very likely that in the majority of patients we see that those two processes are somehow disconnected in time,” he suggested.

The GESPIC cohort provides a good base from which to examine the effects of TNF inhibitors on radiographic progression in patients with axSpA for several reasons, observed Dr. Poddubnyy. For one it was established in 2000, so “well before the introduction of TNF-alpha inhibitors.” That means that almost all patients would have been put on TNF inhibitors while enrolled in the cohort, he said, “so we could really follow up them prospectively for a few years.” In fact, just nine patients had been treated with TNF inhibitors at baseline.

Spinal findings

Although TNF inhibitors are widely accepted to be effective anti-inflammatory drugs that can relieve patients’ spinal symptoms, there were inconclusive data on whether they can also have an impact on radiographic progression.

To look at the possible immediate or later effect of TNF inhibitors on spinal radiographic progression, the GESPIC investigators looked at sets of radiographs, taken at least 2 years apart over a 10-year period, from 266 patients, 77 of whom who had been treated with a TNF inhibitor for at least 12 months or more. Overall, there were 103 2-year intervals covered by TNF inhibitor treatment of any duration, and 78 intervals in which treatment had lasted for at least 12 months.

“This cohort included patients with quite early disease, including both nonradiographic and radiographic forms,” Dr. Poddubnyy said, adding that some patients had been treated with a TNF inhibitor for up to 10 years.

While there were no significant changes in radiographic progression as measured using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) between patients who had and who had not received at least 12 months’ TNF inhibitor therapy in the first 2 years, there was a substantial difference after 4 years.

The mSASSS change in scores over 2 years in patients who were and were not treated with a TNF inhibitor for 12 months or more were a respective 0.35 and 0.81 (P = .047) considering treatment in the previous 2-year treatment period, and 0.33 and 0.77 (also P = .047) considering treatment in the prior 2-year treatment period and the current 2-year period.

“Our interpretation is that within the first 2 years we see a resolution of inflammation, a process of repair, maybe even a process of bone formation, but then if you continue this inflammation control for longer than 2 years, then we see the effect on structural damage,” Dr. Poddubnyy said.

SIJ findings

The SIJ analysis included 301 patients who had at least two sets of radiographs taken every 2 years over a 10-year follow-up period, 87 (28.9%) of whom had been treated with at least one TNF inhibitor during follow-up.

Radiographic SIJ progression was defined as the change in the sacroiliitis sum score over 2 years. Calculations considered both the current 2-year period and the previous 2-year period, as well as any use of TNF inhibitors or more than 12 months’ use.

There were no significant differences in sacroiliitis sum scores comparing people who were and were not treated with TNF inhibitors for at least 12 months in the current 2-year period. However, when the previous 2-year period was looked at there was a significant difference in the score between those who had and had not been treated for 12 or more months (0.15 vs. 0.27, respectively; P = .024).

“These data indicate that TNF inhibitors have a late effect,” Dr. Torgutalp said. “You cannot observe the effect of the TNF inhibitor on radiographic progression in the same interval, you have to wait to see this effect in the next interval,” he explained. That means that when a patient uses a TNF inhibitor, you must wait to see the effect on SIJ progression in the subsequent 2 years, he qualified.

Lessons for practice

“If we control inflammation, we might control structural damage progression,” Dr. Poddubnyy said.

If this is the case, then it is likely that other drugs that control inflammation in axSpA will have a similar effect, such as those that target interleukin-17 or Janus kinases. This is something in the future to look at in the GESPIC cohort once enough patient-years of data are available.

Early treatment is probably important, Dr. Poddubnyy suggested, “because in patients with early disease we can expect not that much structural damage at baseline.” Starting treatment early, at the inflammatory stage rather than at the stage where there was a lot of damage already there, could yield better results, he proposed.

“As a clinician, as a researcher, I would be really interested in demonstrating in a prospective, clinical trial that treating patients to target, achieving a remission, would be associated with retardation of structural damage progression. This has only been shown in observational studies so far, so this is an open question.”

Questions on adjustments made for confounding factors

Questions on the spinal presentation included whether there were any differences in NSAID use, to which Dr. Poddubnyy responded, “Patients on TNF inhibitors normally reduce NSAIDs. We adjusted, therefore, for NSAID use.”

The SIJ presentation garnered more questioning. Dr. Torgutalp qualified that both radiographic and nonradiographic patients had been included in the analysis, and “we observe the same effect.”

Asked how clinically relevant the findings were, he noted that, “to the best of our knowledge, this is the first data for sacroiliac joint progression.” The data for spinal progression seem to “reconcile the results from previous investigators,” where there had been some conflicting data on whether 2 or 4 years’ TNF-inhibitor therapy had any effect on radiographic progression.

“I don’t think you’ve adjusted for the baseline level of damage of the SIJ?” queried Pedro Machado, MD, of University College London Hospital. “As you know, in the spine, but also at the SIJ level, the baseline level of damage is usually one of the strongest predictors of further damage.”

This is not something that was adjusted for, Dr. Torgutalp conceded. “We will do it for further analysis,” he said.

Since 2010, GESPIC has been supported by grants from AbbVie. Dr. Poddubnyy reported financial relationships with AbbVie and numerous other pharmaceutical companies. Dr. Torgutalp had no relevant disclosures.

Three or more weeks of oral anticoagulation (OAC) sometimes isn’t up to the job of clearing any potentially embolic left atrial (LA) thrombi before procedures like cardioversion or catheter ablation in patients with atrial fibrillation (AF). Such OAC-defiant LA thrombi aren’t common, nor are they rare enough to ignore, suggests a new meta-analysis that might also have identified features that predispose to them.

Such predictors of LA clots that persist despite OAC could potentially guide selective use of transesophageal echocardiography (TEE) instead of more routine policies to either use or not use TEE for thrombus rule-out before rhythm-control procedures, researchers propose.

Their prevalence was about 2.7% among the study’s more than 14,000 patients who received at least 3 weeks of OAC with either vitamin K antagonists (VKA) or direct oral anticoagulants (DOAC) before undergoing TEE.

But OAC-resistant LA thrombi were two- to four-times as common in patients with than without certain features, including AF other than paroxysmal and higher CHADS2 and CHA2DS2-VASc stroke risk-stratification scores.

“TEE imaging in select patients at an elevated risk of LA thrombus, despite anticoagulation status, may be a reasonable approach to minimize the risk of thromboembolic complications following cardioversion or catheter ablation,” propose the study’s authors, led by Antony Lurie, BMSC, Population Health Research Institute, Hamilton, Ont. Their report was published in the June 15 issue of the Journal of the American College of Cardiology.

Guidelines don’t encourage TEE before cardioversion in patients who have been on OAC for at least 3 weeks, the group notes, and policies on TEE use before AF ablation vary widely regardless of anticoagulation status.

The current study suggests that 3 weeks of OAC isn’t enough for a substantial number of patients, who might be put at thromboembolic risk if TEE were to be skipped before rhythm-control procedures.

Conversely, many patients unlikely to have LA thrombi get preprocedure TEE anyway. That can happen “irrespective of how long they’ve been anticoagulated, their pattern of atrial fibrillation, or their stroke risk,” senior author Jorge A. Wong, MD, MPH, Population Health Research Institute and McMaster University, Hamilton, Ont., told this news organization.

But “TEE is an invasive imaging modality, so it is associated with small element of risk.” The current study, Dr. Wong said, points to potential risk-stratification tools clinicians might use to guide more selective TEE screening.

“At sites where TEEs are done all the time for patients undergoing ablation, one could use several of these risk markers to perhaps tailor use of TEE in individuals,” Dr. Wong said. “For example, in people with paroxysmal atrial fibrillation, we found that the risk of left atrial appendage clot was approximately 1% or less.” Screening by TEE might reasonably be avoided in such patients.

“Fortunately, continued oral anticoagulation already yields low peri-procedural stroke rates,” observes an accompanying editorial from Paulus Kirchhof, MD, and Christoph Sinning, MD, from the University Heart & Vascular Center and German Centre of Cardiovascular Research, Hamburg.

“Based on this new analysis of existing data, a risk-based use of TEE imaging in anticoagulated patients could enable further improvement in the safe delivery of rhythm control interventions in patients with AF,” the editorialists agree.

The meta-analysis covered 10 prospective and 25 retrospective studies with a total of 14,653 patients that reported whether LA thrombus was present in patients with AF or atrial flutter (AFL) who underwent TEE after at least 3 weeks of VKA or DOAC therapy. Reports for 30 of the studies identified patients by rhythm-control procedure, and the remaining five didn’t specify TEE indications.

The weighted mean prevalence of LA thrombus at TEE was 2.73% (95% confidence interval, 1.95%-3.80%). The finding was not significantly changed in separate sensitivity analyses, the report says, including one limited to studies with low risk of bias and others excluding patients with valvular AF, interrupted OAC, heparin bridging, or subtherapeutic anticoagulation, respectively.

Patients treated with VKA and DOACs showed similar prevalences of LA thrombi, with means of 2.80% and 3.12%, respectively (P = .674). The prevalence was significantly higher in patients:

• with nonparoxysmal than with paroxysmal AF/AFL (4.81% vs. 1.03%; P < .001)
• undergoing cardioversion than ablation (5.55% vs. 1.65; P < .001)
• with CHA2DS2-VASc scores of at least 3 than with scores of 2 or less (6.31% vs. 1.06%; P < .001).

A limitation of the study, observe Dr. Kirchhof and Dr. Sinning, “is that all patients had a clinical indication for a TEE, which might be a selection bias. When a thrombus was found on TEE, clinical judgment led to postponing of the procedure,” thereby avoiding potential thromboembolism.

“Thus, the paper cannot demonstrate that presence of a thrombus on TEE is related to peri-procedural ischemic stroke,” they write.

The literature puts the risk for stroke or systemic embolism at well under 1% for patients anticoagulated with either VKA or DOACs for at least 3 weeks prior to cardioversion, in contrast to the nearly 3% prevalence of LA appendage thrombus by TEE in the current analysis, Dr. Wong observed.

“So we’re seeing a lot more left atrial appendage thrombus than we would see stroke,” but there wasn’t a way to determine whether that increases the stroke risk, he agreed.Dr. Wong, Dr. Lurie, and the other authors report no relevant conflicts. Dr. Kirchhof discloses receiving partial support “from several drug and device companies active in atrial fibrillation” and to being listed as inventor on two AF-related patents held by the University of Birmingham. Dr. Sinning reports no relevant relationships. 

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

Three or more weeks of oral anticoagulation (OAC) sometimes isn’t up to the job of clearing any potentially embolic left atrial (LA) thrombi before procedures like cardioversion or catheter ablation in patients with atrial fibrillation (AF). Such OAC-defiant LA thrombi aren’t common, nor are they rare enough to ignore, suggests a new meta-analysis that might also have identified features that predispose to them.

Such predictors of LA clots that persist despite OAC could potentially guide selective use of transesophageal echocardiography (TEE) instead of more routine policies to either use or not use TEE for thrombus rule-out before rhythm-control procedures, researchers propose.

Their prevalence was about 2.7% among the study’s more than 14,000 patients who received at least 3 weeks of OAC with either vitamin K antagonists (VKA) or direct oral anticoagulants (DOAC) before undergoing TEE.

But OAC-resistant LA thrombi were two- to four-times as common in patients with than without certain features, including AF other than paroxysmal and higher CHADS2 and CHA2DS2-VASc stroke risk-stratification scores.

“TEE imaging in select patients at an elevated risk of LA thrombus, despite anticoagulation status, may be a reasonable approach to minimize the risk of thromboembolic complications following cardioversion or catheter ablation,” propose the study’s authors, led by Antony Lurie, BMSC, Population Health Research Institute, Hamilton, Ont. Their report was published in the June 15 issue of the Journal of the American College of Cardiology.

Guidelines don’t encourage TEE before cardioversion in patients who have been on OAC for at least 3 weeks, the group notes, and policies on TEE use before AF ablation vary widely regardless of anticoagulation status.

The current study suggests that 3 weeks of OAC isn’t enough for a substantial number of patients, who might be put at thromboembolic risk if TEE were to be skipped before rhythm-control procedures.

Conversely, many patients unlikely to have LA thrombi get preprocedure TEE anyway. That can happen “irrespective of how long they’ve been anticoagulated, their pattern of atrial fibrillation, or their stroke risk,” senior author Jorge A. Wong, MD, MPH, Population Health Research Institute and McMaster University, Hamilton, Ont., told this news organization.

But “TEE is an invasive imaging modality, so it is associated with small element of risk.” The current study, Dr. Wong said, points to potential risk-stratification tools clinicians might use to guide more selective TEE screening.

“At sites where TEEs are done all the time for patients undergoing ablation, one could use several of these risk markers to perhaps tailor use of TEE in individuals,” Dr. Wong said. “For example, in people with paroxysmal atrial fibrillation, we found that the risk of left atrial appendage clot was approximately 1% or less.” Screening by TEE might reasonably be avoided in such patients.

“Fortunately, continued oral anticoagulation already yields low peri-procedural stroke rates,” observes an accompanying editorial from Paulus Kirchhof, MD, and Christoph Sinning, MD, from the University Heart & Vascular Center and German Centre of Cardiovascular Research, Hamburg.

“Based on this new analysis of existing data, a risk-based use of TEE imaging in anticoagulated patients could enable further improvement in the safe delivery of rhythm control interventions in patients with AF,” the editorialists agree.

The meta-analysis covered 10 prospective and 25 retrospective studies with a total of 14,653 patients that reported whether LA thrombus was present in patients with AF or atrial flutter (AFL) who underwent TEE after at least 3 weeks of VKA or DOAC therapy. Reports for 30 of the studies identified patients by rhythm-control procedure, and the remaining five didn’t specify TEE indications.

The weighted mean prevalence of LA thrombus at TEE was 2.73% (95% confidence interval, 1.95%-3.80%). The finding was not significantly changed in separate sensitivity analyses, the report says, including one limited to studies with low risk of bias and others excluding patients with valvular AF, interrupted OAC, heparin bridging, or subtherapeutic anticoagulation, respectively.

Patients treated with VKA and DOACs showed similar prevalences of LA thrombi, with means of 2.80% and 3.12%, respectively (P = .674). The prevalence was significantly higher in patients:

• with nonparoxysmal than with paroxysmal AF/AFL (4.81% vs. 1.03%; P < .001)
• undergoing cardioversion than ablation (5.55% vs. 1.65; P < .001)
• with CHA2DS2-VASc scores of at least 3 than with scores of 2 or less (6.31% vs. 1.06%; P < .001).

A limitation of the study, observe Dr. Kirchhof and Dr. Sinning, “is that all patients had a clinical indication for a TEE, which might be a selection bias. When a thrombus was found on TEE, clinical judgment led to postponing of the procedure,” thereby avoiding potential thromboembolism.

“Thus, the paper cannot demonstrate that presence of a thrombus on TEE is related to peri-procedural ischemic stroke,” they write.

The literature puts the risk for stroke or systemic embolism at well under 1% for patients anticoagulated with either VKA or DOACs for at least 3 weeks prior to cardioversion, in contrast to the nearly 3% prevalence of LA appendage thrombus by TEE in the current analysis, Dr. Wong observed.

“So we’re seeing a lot more left atrial appendage thrombus than we would see stroke,” but there wasn’t a way to determine whether that increases the stroke risk, he agreed.Dr. Wong, Dr. Lurie, and the other authors report no relevant conflicts. Dr. Kirchhof discloses receiving partial support “from several drug and device companies active in atrial fibrillation” and to being listed as inventor on two AF-related patents held by the University of Birmingham. Dr. Sinning reports no relevant relationships. 

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

Three or more weeks of oral anticoagulation (OAC) sometimes isn’t up to the job of clearing any potentially embolic left atrial (LA) thrombi before procedures like cardioversion or catheter ablation in patients with atrial fibrillation (AF). Such OAC-defiant LA thrombi aren’t common, nor are they rare enough to ignore, suggests a new meta-analysis that might also have identified features that predispose to them.

Such predictors of LA clots that persist despite OAC could potentially guide selective use of transesophageal echocardiography (TEE) instead of more routine policies to either use or not use TEE for thrombus rule-out before rhythm-control procedures, researchers propose.

Their prevalence was about 2.7% among the study’s more than 14,000 patients who received at least 3 weeks of OAC with either vitamin K antagonists (VKA) or direct oral anticoagulants (DOAC) before undergoing TEE.

But OAC-resistant LA thrombi were two- to four-times as common in patients with than without certain features, including AF other than paroxysmal and higher CHADS2 and CHA2DS2-VASc stroke risk-stratification scores.

“TEE imaging in select patients at an elevated risk of LA thrombus, despite anticoagulation status, may be a reasonable approach to minimize the risk of thromboembolic complications following cardioversion or catheter ablation,” propose the study’s authors, led by Antony Lurie, BMSC, Population Health Research Institute, Hamilton, Ont. Their report was published in the June 15 issue of the Journal of the American College of Cardiology.

Guidelines don’t encourage TEE before cardioversion in patients who have been on OAC for at least 3 weeks, the group notes, and policies on TEE use before AF ablation vary widely regardless of anticoagulation status.

The current study suggests that 3 weeks of OAC isn’t enough for a substantial number of patients, who might be put at thromboembolic risk if TEE were to be skipped before rhythm-control procedures.

Conversely, many patients unlikely to have LA thrombi get preprocedure TEE anyway. That can happen “irrespective of how long they’ve been anticoagulated, their pattern of atrial fibrillation, or their stroke risk,” senior author Jorge A. Wong, MD, MPH, Population Health Research Institute and McMaster University, Hamilton, Ont., told this news organization.

But “TEE is an invasive imaging modality, so it is associated with small element of risk.” The current study, Dr. Wong said, points to potential risk-stratification tools clinicians might use to guide more selective TEE screening.

“At sites where TEEs are done all the time for patients undergoing ablation, one could use several of these risk markers to perhaps tailor use of TEE in individuals,” Dr. Wong said. “For example, in people with paroxysmal atrial fibrillation, we found that the risk of left atrial appendage clot was approximately 1% or less.” Screening by TEE might reasonably be avoided in such patients.

“Fortunately, continued oral anticoagulation already yields low peri-procedural stroke rates,” observes an accompanying editorial from Paulus Kirchhof, MD, and Christoph Sinning, MD, from the University Heart & Vascular Center and German Centre of Cardiovascular Research, Hamburg.

“Based on this new analysis of existing data, a risk-based use of TEE imaging in anticoagulated patients could enable further improvement in the safe delivery of rhythm control interventions in patients with AF,” the editorialists agree.

The meta-analysis covered 10 prospective and 25 retrospective studies with a total of 14,653 patients that reported whether LA thrombus was present in patients with AF or atrial flutter (AFL) who underwent TEE after at least 3 weeks of VKA or DOAC therapy. Reports for 30 of the studies identified patients by rhythm-control procedure, and the remaining five didn’t specify TEE indications.

The weighted mean prevalence of LA thrombus at TEE was 2.73% (95% confidence interval, 1.95%-3.80%). The finding was not significantly changed in separate sensitivity analyses, the report says, including one limited to studies with low risk of bias and others excluding patients with valvular AF, interrupted OAC, heparin bridging, or subtherapeutic anticoagulation, respectively.

Patients treated with VKA and DOACs showed similar prevalences of LA thrombi, with means of 2.80% and 3.12%, respectively (P = .674). The prevalence was significantly higher in patients:

• with nonparoxysmal than with paroxysmal AF/AFL (4.81% vs. 1.03%; P < .001)
• undergoing cardioversion than ablation (5.55% vs. 1.65; P < .001)
• with CHA2DS2-VASc scores of at least 3 than with scores of 2 or less (6.31% vs. 1.06%; P < .001).

A limitation of the study, observe Dr. Kirchhof and Dr. Sinning, “is that all patients had a clinical indication for a TEE, which might be a selection bias. When a thrombus was found on TEE, clinical judgment led to postponing of the procedure,” thereby avoiding potential thromboembolism.

“Thus, the paper cannot demonstrate that presence of a thrombus on TEE is related to peri-procedural ischemic stroke,” they write.

The literature puts the risk for stroke or systemic embolism at well under 1% for patients anticoagulated with either VKA or DOACs for at least 3 weeks prior to cardioversion, in contrast to the nearly 3% prevalence of LA appendage thrombus by TEE in the current analysis, Dr. Wong observed.

“So we’re seeing a lot more left atrial appendage thrombus than we would see stroke,” but there wasn’t a way to determine whether that increases the stroke risk, he agreed.Dr. Wong, Dr. Lurie, and the other authors report no relevant conflicts. Dr. Kirchhof discloses receiving partial support “from several drug and device companies active in atrial fibrillation” and to being listed as inventor on two AF-related patents held by the University of Birmingham. Dr. Sinning reports no relevant relationships. 

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

Graduates of international medical schools died from COVID-19 in disproportionate numbers in the United States in 2020, researchers report.

“I’ve always felt that international medical graduates [IMGs] in America are largely invisible,” said senior author Abraham Verghese, MD, MFA, an infectious disease specialist at Stanford (Calif.) University. “Everyone is aware that there are foreign doctors, but very few are aware of how many there are and also how vital they are to providing health care in America.”

IMGs made up 25% of all U.S. physicians in 2020 but accounted for 45% of those whose deaths had been attributed to COVID-19 through Nov. 23, 2020, Deendayal Dinakarpandian, MD, PhD, clinical associate professor of medicine at Stanford (Calif.) University, and colleagues report in JAMA Network Open.

IMGs are more likely to work in places where the incidence of COVID-19 is high and in facilities with fewer resources, Dr. Verghese said in an interview. “So, it’s not surprising that they were on the front lines when this thing came along,” he said.

To see whether their vulnerability affected their risk for death, Dr. Dinakarpandian and colleagues collected data from Nov. 23, 2020, from three sources of information regarding deaths among physicians: MedPage Today, which used investigative and voluntary reporting; Medscape, which used voluntary reporting of verifiable information; and a collaboration of The Guardian and Kaiser Health News, which used investigative reporting.

The Medscape project was launched on April 1, 2020. The MedPage Today and The Guardian/Kaiser Health News projects were launched on April 8, 2020.

Dr. Verghese and colleagues researched obituaries and news articles referenced by the three projects to verify their data. They used DocInfo to ascertain the deceased physicians’ medical schools.

After eliminating duplications from the lists, the researchers counted 132 physician deaths in 28 states. Of these, 59 physicians had graduated from medical schools outside the United States, a death toll 1.8 times higher than the proportion of IMGs among U.S. physicians (95% confidence interval, 1.52-2.21; P < .001).

New York, New Jersey, and Florida accounted for 66% of the deaths among IMGs but for only 45% of the deaths among U.S. medical school graduates.

Within each state, the proportion of IMGs among deceased physicians was not statistically different from their proportion among physicians in those states, with the exception of New York.

Two-thirds of the physicians’ deaths occurred in states where IMGs make up a larger proportion of physicians than in the nation as a whole. In these states, the incidence of COVID-19 was high at the start of the pandemic.

In New York, IMGs accounted for 60% of physician deaths, which was 1.62 times higher (95% CI, 1.26-2.09; P = .005) than the 37% among New York physicians overall.

Physicians who were trained abroad frequently can’t get into the most prestigious residency programs or into the highest paid specialties and are more likely to serve in primary care, Dr. Verghese said. Overall, 60% of the physicians who died of COVID-19 worked in primary care.

IMGs often staff hospitals serving low-income communities and communities of color, which were hardest hit by the pandemic and where personal protective equipment was hard to obtain, said Dr. Verghese.

In addition to these risks, IMGs sometimes endure racism, said Dr. Verghese, who obtained his medical degree at Madras Medical College, Chennai, India. “We’ve actually seen in the COVID era, in keeping with the sort of political tone that was set in Washington, that there’s been a lot more abuses of both foreign physicians and foreign looking physicians – even if they’re not foreign trained – and nurses by patients who have been given license. And I want to acknowledge the heroism of all these physicians.”

The study was partially funded by the Presence Center at Stanford. Dr. Verghese is a regular contributor to Medscape. He served on the advisory board for Gilead Sciences, serves as a speaker or a member of a speakers bureau for Leigh Bureau, and receives royalties from Penguin Random House and Simon & Schuster.

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

Graduates of international medical schools died from COVID-19 in disproportionate numbers in the United States in 2020, researchers report.

“I’ve always felt that international medical graduates [IMGs] in America are largely invisible,” said senior author Abraham Verghese, MD, MFA, an infectious disease specialist at Stanford (Calif.) University. “Everyone is aware that there are foreign doctors, but very few are aware of how many there are and also how vital they are to providing health care in America.”

IMGs made up 25% of all U.S. physicians in 2020 but accounted for 45% of those whose deaths had been attributed to COVID-19 through Nov. 23, 2020, Deendayal Dinakarpandian, MD, PhD, clinical associate professor of medicine at Stanford (Calif.) University, and colleagues report in JAMA Network Open.

IMGs are more likely to work in places where the incidence of COVID-19 is high and in facilities with fewer resources, Dr. Verghese said in an interview. “So, it’s not surprising that they were on the front lines when this thing came along,” he said.

To see whether their vulnerability affected their risk for death, Dr. Dinakarpandian and colleagues collected data from Nov. 23, 2020, from three sources of information regarding deaths among physicians: MedPage Today, which used investigative and voluntary reporting; Medscape, which used voluntary reporting of verifiable information; and a collaboration of The Guardian and Kaiser Health News, which used investigative reporting.

The Medscape project was launched on April 1, 2020. The MedPage Today and The Guardian/Kaiser Health News projects were launched on April 8, 2020.

Dr. Verghese and colleagues researched obituaries and news articles referenced by the three projects to verify their data. They used DocInfo to ascertain the deceased physicians’ medical schools.

After eliminating duplications from the lists, the researchers counted 132 physician deaths in 28 states. Of these, 59 physicians had graduated from medical schools outside the United States, a death toll 1.8 times higher than the proportion of IMGs among U.S. physicians (95% confidence interval, 1.52-2.21; P < .001).

New York, New Jersey, and Florida accounted for 66% of the deaths among IMGs but for only 45% of the deaths among U.S. medical school graduates.

Within each state, the proportion of IMGs among deceased physicians was not statistically different from their proportion among physicians in those states, with the exception of New York.

Two-thirds of the physicians’ deaths occurred in states where IMGs make up a larger proportion of physicians than in the nation as a whole. In these states, the incidence of COVID-19 was high at the start of the pandemic.

In New York, IMGs accounted for 60% of physician deaths, which was 1.62 times higher (95% CI, 1.26-2.09; P = .005) than the 37% among New York physicians overall.

Physicians who were trained abroad frequently can’t get into the most prestigious residency programs or into the highest paid specialties and are more likely to serve in primary care, Dr. Verghese said. Overall, 60% of the physicians who died of COVID-19 worked in primary care.

IMGs often staff hospitals serving low-income communities and communities of color, which were hardest hit by the pandemic and where personal protective equipment was hard to obtain, said Dr. Verghese.

In addition to these risks, IMGs sometimes endure racism, said Dr. Verghese, who obtained his medical degree at Madras Medical College, Chennai, India. “We’ve actually seen in the COVID era, in keeping with the sort of political tone that was set in Washington, that there’s been a lot more abuses of both foreign physicians and foreign looking physicians – even if they’re not foreign trained – and nurses by patients who have been given license. And I want to acknowledge the heroism of all these physicians.”

The study was partially funded by the Presence Center at Stanford. Dr. Verghese is a regular contributor to Medscape. He served on the advisory board for Gilead Sciences, serves as a speaker or a member of a speakers bureau for Leigh Bureau, and receives royalties from Penguin Random House and Simon & Schuster.

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

Graduates of international medical schools died from COVID-19 in disproportionate numbers in the United States in 2020, researchers report.

“I’ve always felt that international medical graduates [IMGs] in America are largely invisible,” said senior author Abraham Verghese, MD, MFA, an infectious disease specialist at Stanford (Calif.) University. “Everyone is aware that there are foreign doctors, but very few are aware of how many there are and also how vital they are to providing health care in America.”

IMGs made up 25% of all U.S. physicians in 2020 but accounted for 45% of those whose deaths had been attributed to COVID-19 through Nov. 23, 2020, Deendayal Dinakarpandian, MD, PhD, clinical associate professor of medicine at Stanford (Calif.) University, and colleagues report in JAMA Network Open.

IMGs are more likely to work in places where the incidence of COVID-19 is high and in facilities with fewer resources, Dr. Verghese said in an interview. “So, it’s not surprising that they were on the front lines when this thing came along,” he said.

To see whether their vulnerability affected their risk for death, Dr. Dinakarpandian and colleagues collected data from Nov. 23, 2020, from three sources of information regarding deaths among physicians: MedPage Today, which used investigative and voluntary reporting; Medscape, which used voluntary reporting of verifiable information; and a collaboration of The Guardian and Kaiser Health News, which used investigative reporting.

The Medscape project was launched on April 1, 2020. The MedPage Today and The Guardian/Kaiser Health News projects were launched on April 8, 2020.

Dr. Verghese and colleagues researched obituaries and news articles referenced by the three projects to verify their data. They used DocInfo to ascertain the deceased physicians’ medical schools.

After eliminating duplications from the lists, the researchers counted 132 physician deaths in 28 states. Of these, 59 physicians had graduated from medical schools outside the United States, a death toll 1.8 times higher than the proportion of IMGs among U.S. physicians (95% confidence interval, 1.52-2.21; P < .001).

New York, New Jersey, and Florida accounted for 66% of the deaths among IMGs but for only 45% of the deaths among U.S. medical school graduates.

Within each state, the proportion of IMGs among deceased physicians was not statistically different from their proportion among physicians in those states, with the exception of New York.

Two-thirds of the physicians’ deaths occurred in states where IMGs make up a larger proportion of physicians than in the nation as a whole. In these states, the incidence of COVID-19 was high at the start of the pandemic.

In New York, IMGs accounted for 60% of physician deaths, which was 1.62 times higher (95% CI, 1.26-2.09; P = .005) than the 37% among New York physicians overall.

Physicians who were trained abroad frequently can’t get into the most prestigious residency programs or into the highest paid specialties and are more likely to serve in primary care, Dr. Verghese said. Overall, 60% of the physicians who died of COVID-19 worked in primary care.

IMGs often staff hospitals serving low-income communities and communities of color, which were hardest hit by the pandemic and where personal protective equipment was hard to obtain, said Dr. Verghese.

In addition to these risks, IMGs sometimes endure racism, said Dr. Verghese, who obtained his medical degree at Madras Medical College, Chennai, India. “We’ve actually seen in the COVID era, in keeping with the sort of political tone that was set in Washington, that there’s been a lot more abuses of both foreign physicians and foreign looking physicians – even if they’re not foreign trained – and nurses by patients who have been given license. And I want to acknowledge the heroism of all these physicians.”

The study was partially funded by the Presence Center at Stanford. Dr. Verghese is a regular contributor to Medscape. He served on the advisory board for Gilead Sciences, serves as a speaker or a member of a speakers bureau for Leigh Bureau, and receives royalties from Penguin Random House and Simon & Schuster.

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