Incorporating mobile apps into patient care programs can add immense value. Mobile apps enable data collection when a patient is beyond the walls of a doctor’s office and equip clinicians with new and relevant patient data. Patient engagement apps also provide a mechanism to “nudge” patients to encourage adherence to their care programs. These additional data and increased patient adherence can enable more personalized care,¹ and ultimately can lead to improved outcomes. For example, a meta-analysis of 1,657 patients with diabetes showed a 5% reduction in hemoglobin A_1c (HbA_1c) values for those who used a diabetes-related app.² The literature also shows positive results for heart failure, weight management, smoking reduction, and lifestyle improvement.^3-5 Given their value, why aren’t patient engagement apps more routinely integrated into patient care programs?

From a software development perspective, mobile apps are fairly easy to create. However, from a user retention standpoint, creating an app with a large, sustainable userbase is challenging.⁵ User retention is measured in monthly active users. We are familiar with unused apps collecting digital dust on our smartphone home screens. A 2019 study showed that 25% of people typically use an application only once,⁶ and health care apps are not an exception. There are hundreds of thousands of mobile health apps on the market, but only 7% of these applications have more than 50,000 monthly active users. Further, 62% of digital health apps have less than 1,000 monthly active users.⁷

Using a new app daily or several times weekly requires new habit formation. Anyone who has tried to incorporate a new routine into their daily life knows how difficult habit formation can be. However, ObGyn patients may be particularly well suited to incorporate ObGyn-related apps into their care, given how many women already use mobile applications to track their menstrual cycles. A recent survey found that across all age groups, 47% of women use a mobile phone app to track their menstrual cycle,⁸ compared with 8% of US adults who regularly use an app to measure general health metrics.⁷ This removes one of the largest obstacles of market penetration since the habit of using an app for ObGyn purposes has already been established. As such, it presents an exciting opportunity to capitalize on the userbase already leveraging mobile apps to track their cycles and expand the patient engagement footprint into additional features that can broaden care to create a seamless, holistic patient application for ObGyn patient care.

One can envision a future in which a patient is “prescribed” an ObGyn app during their ObGyn appointment. Within the app, the patient can track their health data, engage with health providers, and gain access to educational materials. The clinician would be able to access data captured in the patient app at an aggregate level to analyze trends over time.

Current, patient-facing ObGyn mobile apps available for download on smartphones are for targeted aspects of ObGyn health. For example, there are separate apps for menstrual cycle tracking, contraception education, and medication adherence tracking. In the future, it would be ideal for clinicians and patients to have access to a single, holistic ObGyn mobile app that supports the end-to-end ObGyn patient journey, one in which clinicians could turn modules on or off given specific patient concerns. The technology for this type of holistic patient engagement platform exists, but unfortunately it is not as simple as downloading a mobile app. Standing up an end-to-end patient engagement platform requires enterprise-wide buy-in, tailoring user workflows, and building out integrations (eg, integrating provider dashboards into the existing electronic health record system). Full-scale solutions are powerful, but they can be expensive and time consuming to stand up. Until there is a more streamlined, outside-the-box ObGyn-tailored solution, there are patientfacing mobile apps available to support your patients for specific concerns.

Continue to: The top 3 recommended menstrual cycle tracking apps...

The top 3 recommended menstrual cycle tracking apps from Moglia and colleagues⁹ are listed in Dr. Chen’s article, “Top free menstrual cycle tracking apps for your patients.”¹⁰ The top 3 recommended contraception education mobile apps from Lunde and colleagues¹¹ are listed in TABLE 1 and are detailed with a shortened version of the APPLICATIONS scoring system, APPLI (app comprehensiveness, price, platform, literature use, important special features).¹² The top 3 recommended patient medication adherence mobile apps from the study by Santo and colleagues¹³ are listed in TABLE 2. The apps in the Stoyanov et al¹⁴ study were evaluated using the 23-item Mobile App Rating System scale. ●

Incorporating mobile apps into patient care programs can add immense value. Mobile apps enable data collection when a patient is beyond the walls of a doctor’s office and equip clinicians with new and relevant patient data. Patient engagement apps also provide a mechanism to “nudge” patients to encourage adherence to their care programs. These additional data and increased patient adherence can enable more personalized care,¹ and ultimately can lead to improved outcomes. For example, a meta-analysis of 1,657 patients with diabetes showed a 5% reduction in hemoglobin A_1c (HbA_1c) values for those who used a diabetes-related app.² The literature also shows positive results for heart failure, weight management, smoking reduction, and lifestyle improvement.^3-5 Given their value, why aren’t patient engagement apps more routinely integrated into patient care programs?

From a software development perspective, mobile apps are fairly easy to create. However, from a user retention standpoint, creating an app with a large, sustainable userbase is challenging.⁵ User retention is measured in monthly active users. We are familiar with unused apps collecting digital dust on our smartphone home screens. A 2019 study showed that 25% of people typically use an application only once,⁶ and health care apps are not an exception. There are hundreds of thousands of mobile health apps on the market, but only 7% of these applications have more than 50,000 monthly active users. Further, 62% of digital health apps have less than 1,000 monthly active users.⁷

Using a new app daily or several times weekly requires new habit formation. Anyone who has tried to incorporate a new routine into their daily life knows how difficult habit formation can be. However, ObGyn patients may be particularly well suited to incorporate ObGyn-related apps into their care, given how many women already use mobile applications to track their menstrual cycles. A recent survey found that across all age groups, 47% of women use a mobile phone app to track their menstrual cycle,⁸ compared with 8% of US adults who regularly use an app to measure general health metrics.⁷ This removes one of the largest obstacles of market penetration since the habit of using an app for ObGyn purposes has already been established. As such, it presents an exciting opportunity to capitalize on the userbase already leveraging mobile apps to track their cycles and expand the patient engagement footprint into additional features that can broaden care to create a seamless, holistic patient application for ObGyn patient care.

One can envision a future in which a patient is “prescribed” an ObGyn app during their ObGyn appointment. Within the app, the patient can track their health data, engage with health providers, and gain access to educational materials. The clinician would be able to access data captured in the patient app at an aggregate level to analyze trends over time.

Current, patient-facing ObGyn mobile apps available for download on smartphones are for targeted aspects of ObGyn health. For example, there are separate apps for menstrual cycle tracking, contraception education, and medication adherence tracking. In the future, it would be ideal for clinicians and patients to have access to a single, holistic ObGyn mobile app that supports the end-to-end ObGyn patient journey, one in which clinicians could turn modules on or off given specific patient concerns. The technology for this type of holistic patient engagement platform exists, but unfortunately it is not as simple as downloading a mobile app. Standing up an end-to-end patient engagement platform requires enterprise-wide buy-in, tailoring user workflows, and building out integrations (eg, integrating provider dashboards into the existing electronic health record system). Full-scale solutions are powerful, but they can be expensive and time consuming to stand up. Until there is a more streamlined, outside-the-box ObGyn-tailored solution, there are patientfacing mobile apps available to support your patients for specific concerns.

Continue to: The top 3 recommended menstrual cycle tracking apps...

The top 3 recommended menstrual cycle tracking apps from Moglia and colleagues⁹ are listed in Dr. Chen’s article, “Top free menstrual cycle tracking apps for your patients.”¹⁰ The top 3 recommended contraception education mobile apps from Lunde and colleagues¹¹ are listed in TABLE 1 and are detailed with a shortened version of the APPLICATIONS scoring system, APPLI (app comprehensiveness, price, platform, literature use, important special features).¹² The top 3 recommended patient medication adherence mobile apps from the study by Santo and colleagues¹³ are listed in TABLE 2. The apps in the Stoyanov et al¹⁴ study were evaluated using the 23-item Mobile App Rating System scale. ●

Incorporating mobile apps into patient care programs can add immense value. Mobile apps enable data collection when a patient is beyond the walls of a doctor’s office and equip clinicians with new and relevant patient data. Patient engagement apps also provide a mechanism to “nudge” patients to encourage adherence to their care programs. These additional data and increased patient adherence can enable more personalized care,¹ and ultimately can lead to improved outcomes. For example, a meta-analysis of 1,657 patients with diabetes showed a 5% reduction in hemoglobin A_1c (HbA_1c) values for those who used a diabetes-related app.² The literature also shows positive results for heart failure, weight management, smoking reduction, and lifestyle improvement.^3-5 Given their value, why aren’t patient engagement apps more routinely integrated into patient care programs?

From a software development perspective, mobile apps are fairly easy to create. However, from a user retention standpoint, creating an app with a large, sustainable userbase is challenging.⁵ User retention is measured in monthly active users. We are familiar with unused apps collecting digital dust on our smartphone home screens. A 2019 study showed that 25% of people typically use an application only once,⁶ and health care apps are not an exception. There are hundreds of thousands of mobile health apps on the market, but only 7% of these applications have more than 50,000 monthly active users. Further, 62% of digital health apps have less than 1,000 monthly active users.⁷

Using a new app daily or several times weekly requires new habit formation. Anyone who has tried to incorporate a new routine into their daily life knows how difficult habit formation can be. However, ObGyn patients may be particularly well suited to incorporate ObGyn-related apps into their care, given how many women already use mobile applications to track their menstrual cycles. A recent survey found that across all age groups, 47% of women use a mobile phone app to track their menstrual cycle,⁸ compared with 8% of US adults who regularly use an app to measure general health metrics.⁷ This removes one of the largest obstacles of market penetration since the habit of using an app for ObGyn purposes has already been established. As such, it presents an exciting opportunity to capitalize on the userbase already leveraging mobile apps to track their cycles and expand the patient engagement footprint into additional features that can broaden care to create a seamless, holistic patient application for ObGyn patient care.

One can envision a future in which a patient is “prescribed” an ObGyn app during their ObGyn appointment. Within the app, the patient can track their health data, engage with health providers, and gain access to educational materials. The clinician would be able to access data captured in the patient app at an aggregate level to analyze trends over time.

Current, patient-facing ObGyn mobile apps available for download on smartphones are for targeted aspects of ObGyn health. For example, there are separate apps for menstrual cycle tracking, contraception education, and medication adherence tracking. In the future, it would be ideal for clinicians and patients to have access to a single, holistic ObGyn mobile app that supports the end-to-end ObGyn patient journey, one in which clinicians could turn modules on or off given specific patient concerns. The technology for this type of holistic patient engagement platform exists, but unfortunately it is not as simple as downloading a mobile app. Standing up an end-to-end patient engagement platform requires enterprise-wide buy-in, tailoring user workflows, and building out integrations (eg, integrating provider dashboards into the existing electronic health record system). Full-scale solutions are powerful, but they can be expensive and time consuming to stand up. Until there is a more streamlined, outside-the-box ObGyn-tailored solution, there are patientfacing mobile apps available to support your patients for specific concerns.

Continue to: The top 3 recommended menstrual cycle tracking apps...

The top 3 recommended menstrual cycle tracking apps from Moglia and colleagues⁹ are listed in Dr. Chen’s article, “Top free menstrual cycle tracking apps for your patients.”¹⁰ The top 3 recommended contraception education mobile apps from Lunde and colleagues¹¹ are listed in TABLE 1 and are detailed with a shortened version of the APPLICATIONS scoring system, APPLI (app comprehensiveness, price, platform, literature use, important special features).¹² The top 3 recommended patient medication adherence mobile apps from the study by Santo and colleagues¹³ are listed in TABLE 2. The apps in the Stoyanov et al¹⁴ study were evaluated using the 23-item Mobile App Rating System scale. ●

Patients who have received liver transplants or have advanced liver fibrosis may not get adequate protection against COVID-19 from two doses of the Pfizer vaccine, researchers say.

Physicians should test these patients and consider administering a third vaccine dose for those with low levels of antibodies to the SARS-CoV-2 virus, said Rifaat Safadi, MD, director of the Liver Unit in the Institute of Gastroenterology and Liver Diseases at Hadassah Hebrew University Medical Center, Jerusalem.

“If they are not responding, if the serology is going down to zero over the next year, you should revaccinate them or boost them,” Dr. Safadi said in an interview.

The suggestion contradicts the U.S. Food and Drug Administration, which issued a recommendation on May 19 against using antibody tests to check the effectiveness of vaccination against the virus and has not approved a three-dose regimen or booster of any SARS-CoV-2 vaccine.

But Dr. Safadi said he is more convinced by the data, which he presented at the meeting sponsored by the European Association for the Study of the Liver, than by the FDA’s recommendation.

“I’m not sure how scientific this recommendation is,” he said.

Several SARS-CoV-2 vaccines have proven highly effective in clinical trials and real-world studies. But some vaccinated people have sickened and even died from breakthrough infections, despite receiving Pfizer’s and Moderna’s mRNA vaccines, which have produced the most impressive results.

Few researchers have explored whether patients with weakened immune systems achieve the same level of protection as the general population. Fibrosis impairs the immune function of the liver, and people with transplants take immunosuppressant drugs to prevent rejection of the transplant.
 

New data on vaccine efficacy in the immunocompromised

To address this knowledge gap, Dr. Safadi and his colleagues measured antibodies (immunoglobulins) to the spike protein in the virus (S IgG) in vaccinated people who had liver transplants and in other vaccinated people whose liver fibrosis they had assessed with blood tests and biopsies.

About 32 of 90 people who received liver transplants at Hadassah University Medical Center and had received the Pfizer vaccine had an anti–S IgG less than 19 AU/mL, the researchers’ cutoff for a “good” antibody response to the vaccine.

Five other vaccinated people with liver transplants were diagnosed with COVID-19 after receiving the vaccine, one after the first dose and four after the second dose. Altogether, this added up to a 41.1% failure rate of the vaccine, Dr. Safadi said.

To determine the effectiveness of the vaccine in a larger population, Dr. Safadi and colleagues measured the S IgG levels in 719 employees of Hadassah University Medical Center who had received their second doses of the vaccine at least 7 days before (72% had received it 14 days before).

Of these, 708 (98.5%) had titers greater than 19 AU/mL.

Another eight (1.1%) had titers less than 12 AU/mL, which the researchers defined as a negative response. All eight had suppressed immune systems: two had kidney transplants, one had rheumatoid arthritis, two had lymphoma, two had metabolic syndrome, and one had both multiple sclerosis and metabolic syndrome.

The remaining three (0.4%) had S IgG titers from 12 to 19 AU/mL. Of this group, one person each had hemodialysis and cardiovascular disease, rheumatoid arthritis, cryoglobulinemia, and metabolic syndrome.

Of those patients with S IgG titers greater than 19 AU/mL, Fibrosis-4 (Fib-4) scores were available for 501 (the Fib-4 score is a measure of liver fibrosis based on levels of aspartate aminotransferase and alanine aminotransferase, platelet counts, and age). Those with higher Fib-4 scores had lower mean S IgG levels. Of those with Fib-4 scores less than 1.3, 68.0% had S IgG titers greater than 200 AU/mL, and of those with Fib-4 scores greater than 2, 44.2% had S IgG titers greater than 200 AU/mL. The difference was statistically significant (P = .002).

The researchers found a similar correlation when they measured liver health by biopsy for 140 vaccinated people with nonalcoholic fatty liver disease (NAFLD). They found that lower NAFLD activity scores corresponded to higher S IgG titers. Using FibroScan, they also found a trend toward lower S IgG titers with higher fibrosis kilopascals.

In addition, Dr. Safadi and colleagues noted that older age and male sex correlated with lower S IgG titers.
 

Differing opinions on value of antibody titers, third doses

The virus is likely to remain a threat for a year or more to come, and antibody tests may give some indication of who is likely to have the longest-lasting protection, Dr. Safadi said.

“I believe that stronger responders will maintain longer, while the weaker responders will maintain shorter and maybe will need a third shot at some time,” he added.

Pauline Vetter, MD, an infectious disease specialist at Geneva University Hospitals, questioned whether antibody titers can be used to estimate an individual’s level of resistance to the virus. There is some evidence that higher titers correlate with better protection, but it’s not clear to what degree, she said.

“There’s no definitive cutoff,” Dr. Vetter said in an interview. “I can’t say if you have more than a titer of 5, then you’re protected or you’re more protected – or if you have less, then you’re not protected.”

Testing to see whether a person has any S IgG antibodies at all following a vaccination might be worthwhile, she said. She noted that people who know that they did not have an antibody response may be more careful.

Dr. Vetter concluded that not enough is yet known to recommend a third dose or booster for people whose immunity is suppressed.

“There might be a benefit in these populations. But the question is, when and in which situations?” she said.

Dr. Vetter and Dr. Safadi have disclosed no relevant financial relationships.

Patients who have received liver transplants or have advanced liver fibrosis may not get adequate protection against COVID-19 from two doses of the Pfizer vaccine, researchers say.

Physicians should test these patients and consider administering a third vaccine dose for those with low levels of antibodies to the SARS-CoV-2 virus, said Rifaat Safadi, MD, director of the Liver Unit in the Institute of Gastroenterology and Liver Diseases at Hadassah Hebrew University Medical Center, Jerusalem.

“If they are not responding, if the serology is going down to zero over the next year, you should revaccinate them or boost them,” Dr. Safadi said in an interview.

The suggestion contradicts the U.S. Food and Drug Administration, which issued a recommendation on May 19 against using antibody tests to check the effectiveness of vaccination against the virus and has not approved a three-dose regimen or booster of any SARS-CoV-2 vaccine.

But Dr. Safadi said he is more convinced by the data, which he presented at the meeting sponsored by the European Association for the Study of the Liver, than by the FDA’s recommendation.

“I’m not sure how scientific this recommendation is,” he said.

Several SARS-CoV-2 vaccines have proven highly effective in clinical trials and real-world studies. But some vaccinated people have sickened and even died from breakthrough infections, despite receiving Pfizer’s and Moderna’s mRNA vaccines, which have produced the most impressive results.

Few researchers have explored whether patients with weakened immune systems achieve the same level of protection as the general population. Fibrosis impairs the immune function of the liver, and people with transplants take immunosuppressant drugs to prevent rejection of the transplant.
 

New data on vaccine efficacy in the immunocompromised

To address this knowledge gap, Dr. Safadi and his colleagues measured antibodies (immunoglobulins) to the spike protein in the virus (S IgG) in vaccinated people who had liver transplants and in other vaccinated people whose liver fibrosis they had assessed with blood tests and biopsies.

About 32 of 90 people who received liver transplants at Hadassah University Medical Center and had received the Pfizer vaccine had an anti–S IgG less than 19 AU/mL, the researchers’ cutoff for a “good” antibody response to the vaccine.

Five other vaccinated people with liver transplants were diagnosed with COVID-19 after receiving the vaccine, one after the first dose and four after the second dose. Altogether, this added up to a 41.1% failure rate of the vaccine, Dr. Safadi said.

To determine the effectiveness of the vaccine in a larger population, Dr. Safadi and colleagues measured the S IgG levels in 719 employees of Hadassah University Medical Center who had received their second doses of the vaccine at least 7 days before (72% had received it 14 days before).

Of these, 708 (98.5%) had titers greater than 19 AU/mL.

Another eight (1.1%) had titers less than 12 AU/mL, which the researchers defined as a negative response. All eight had suppressed immune systems: two had kidney transplants, one had rheumatoid arthritis, two had lymphoma, two had metabolic syndrome, and one had both multiple sclerosis and metabolic syndrome.

The remaining three (0.4%) had S IgG titers from 12 to 19 AU/mL. Of this group, one person each had hemodialysis and cardiovascular disease, rheumatoid arthritis, cryoglobulinemia, and metabolic syndrome.

Of those patients with S IgG titers greater than 19 AU/mL, Fibrosis-4 (Fib-4) scores were available for 501 (the Fib-4 score is a measure of liver fibrosis based on levels of aspartate aminotransferase and alanine aminotransferase, platelet counts, and age). Those with higher Fib-4 scores had lower mean S IgG levels. Of those with Fib-4 scores less than 1.3, 68.0% had S IgG titers greater than 200 AU/mL, and of those with Fib-4 scores greater than 2, 44.2% had S IgG titers greater than 200 AU/mL. The difference was statistically significant (P = .002).

The researchers found a similar correlation when they measured liver health by biopsy for 140 vaccinated people with nonalcoholic fatty liver disease (NAFLD). They found that lower NAFLD activity scores corresponded to higher S IgG titers. Using FibroScan, they also found a trend toward lower S IgG titers with higher fibrosis kilopascals.

In addition, Dr. Safadi and colleagues noted that older age and male sex correlated with lower S IgG titers.
 

Differing opinions on value of antibody titers, third doses

The virus is likely to remain a threat for a year or more to come, and antibody tests may give some indication of who is likely to have the longest-lasting protection, Dr. Safadi said.

“I believe that stronger responders will maintain longer, while the weaker responders will maintain shorter and maybe will need a third shot at some time,” he added.

Pauline Vetter, MD, an infectious disease specialist at Geneva University Hospitals, questioned whether antibody titers can be used to estimate an individual’s level of resistance to the virus. There is some evidence that higher titers correlate with better protection, but it’s not clear to what degree, she said.

“There’s no definitive cutoff,” Dr. Vetter said in an interview. “I can’t say if you have more than a titer of 5, then you’re protected or you’re more protected – or if you have less, then you’re not protected.”

Testing to see whether a person has any S IgG antibodies at all following a vaccination might be worthwhile, she said. She noted that people who know that they did not have an antibody response may be more careful.

Dr. Vetter concluded that not enough is yet known to recommend a third dose or booster for people whose immunity is suppressed.

“There might be a benefit in these populations. But the question is, when and in which situations?” she said.

Dr. Vetter and Dr. Safadi have disclosed no relevant financial relationships.

Patients who have received liver transplants or have advanced liver fibrosis may not get adequate protection against COVID-19 from two doses of the Pfizer vaccine, researchers say.

Physicians should test these patients and consider administering a third vaccine dose for those with low levels of antibodies to the SARS-CoV-2 virus, said Rifaat Safadi, MD, director of the Liver Unit in the Institute of Gastroenterology and Liver Diseases at Hadassah Hebrew University Medical Center, Jerusalem.

“If they are not responding, if the serology is going down to zero over the next year, you should revaccinate them or boost them,” Dr. Safadi said in an interview.

The suggestion contradicts the U.S. Food and Drug Administration, which issued a recommendation on May 19 against using antibody tests to check the effectiveness of vaccination against the virus and has not approved a three-dose regimen or booster of any SARS-CoV-2 vaccine.

But Dr. Safadi said he is more convinced by the data, which he presented at the meeting sponsored by the European Association for the Study of the Liver, than by the FDA’s recommendation.

“I’m not sure how scientific this recommendation is,” he said.

Several SARS-CoV-2 vaccines have proven highly effective in clinical trials and real-world studies. But some vaccinated people have sickened and even died from breakthrough infections, despite receiving Pfizer’s and Moderna’s mRNA vaccines, which have produced the most impressive results.

Few researchers have explored whether patients with weakened immune systems achieve the same level of protection as the general population. Fibrosis impairs the immune function of the liver, and people with transplants take immunosuppressant drugs to prevent rejection of the transplant.
 

New data on vaccine efficacy in the immunocompromised

To address this knowledge gap, Dr. Safadi and his colleagues measured antibodies (immunoglobulins) to the spike protein in the virus (S IgG) in vaccinated people who had liver transplants and in other vaccinated people whose liver fibrosis they had assessed with blood tests and biopsies.

About 32 of 90 people who received liver transplants at Hadassah University Medical Center and had received the Pfizer vaccine had an anti–S IgG less than 19 AU/mL, the researchers’ cutoff for a “good” antibody response to the vaccine.

Five other vaccinated people with liver transplants were diagnosed with COVID-19 after receiving the vaccine, one after the first dose and four after the second dose. Altogether, this added up to a 41.1% failure rate of the vaccine, Dr. Safadi said.

To determine the effectiveness of the vaccine in a larger population, Dr. Safadi and colleagues measured the S IgG levels in 719 employees of Hadassah University Medical Center who had received their second doses of the vaccine at least 7 days before (72% had received it 14 days before).

Of these, 708 (98.5%) had titers greater than 19 AU/mL.

Another eight (1.1%) had titers less than 12 AU/mL, which the researchers defined as a negative response. All eight had suppressed immune systems: two had kidney transplants, one had rheumatoid arthritis, two had lymphoma, two had metabolic syndrome, and one had both multiple sclerosis and metabolic syndrome.

The remaining three (0.4%) had S IgG titers from 12 to 19 AU/mL. Of this group, one person each had hemodialysis and cardiovascular disease, rheumatoid arthritis, cryoglobulinemia, and metabolic syndrome.

Of those patients with S IgG titers greater than 19 AU/mL, Fibrosis-4 (Fib-4) scores were available for 501 (the Fib-4 score is a measure of liver fibrosis based on levels of aspartate aminotransferase and alanine aminotransferase, platelet counts, and age). Those with higher Fib-4 scores had lower mean S IgG levels. Of those with Fib-4 scores less than 1.3, 68.0% had S IgG titers greater than 200 AU/mL, and of those with Fib-4 scores greater than 2, 44.2% had S IgG titers greater than 200 AU/mL. The difference was statistically significant (P = .002).

The researchers found a similar correlation when they measured liver health by biopsy for 140 vaccinated people with nonalcoholic fatty liver disease (NAFLD). They found that lower NAFLD activity scores corresponded to higher S IgG titers. Using FibroScan, they also found a trend toward lower S IgG titers with higher fibrosis kilopascals.

In addition, Dr. Safadi and colleagues noted that older age and male sex correlated with lower S IgG titers.
 

Differing opinions on value of antibody titers, third doses

The virus is likely to remain a threat for a year or more to come, and antibody tests may give some indication of who is likely to have the longest-lasting protection, Dr. Safadi said.

“I believe that stronger responders will maintain longer, while the weaker responders will maintain shorter and maybe will need a third shot at some time,” he added.

Pauline Vetter, MD, an infectious disease specialist at Geneva University Hospitals, questioned whether antibody titers can be used to estimate an individual’s level of resistance to the virus. There is some evidence that higher titers correlate with better protection, but it’s not clear to what degree, she said.

“There’s no definitive cutoff,” Dr. Vetter said in an interview. “I can’t say if you have more than a titer of 5, then you’re protected or you’re more protected – or if you have less, then you’re not protected.”

Testing to see whether a person has any S IgG antibodies at all following a vaccination might be worthwhile, she said. She noted that people who know that they did not have an antibody response may be more careful.

Dr. Vetter concluded that not enough is yet known to recommend a third dose or booster for people whose immunity is suppressed.

“There might be a benefit in these populations. But the question is, when and in which situations?” she said.

Dr. Vetter and Dr. Safadi have disclosed no relevant financial relationships.

The Janus kinase inhibitor tofacitinib reduces the risk of both death and respiratory failure in hospitalized adults with COVID-19 pneumonia, a new Brazilian study has found.

“Whether the use of JAK inhibitors is superior or additive to other specific immunomodulatory therapies in patients hospitalized with COVID-19 remains to be determined,” Patrícia O. Guimarães, MD, PhD, of the Hospital Israelita Albert Einstein in São Paulo, and coauthors wrote. The study was published in the New England Journal of Medicine.

The results of previous trials that tested JAK inhibitors as therapies for COVID-19 have been mixed. The second iteration of the Adaptive COVID-19 Treatment Trial (ACTT-2) found that a combination treatment of baricitinib and the Food and Drug Administration–authorized remdesivir was superior to remdesivir alone, but ACTT-4 – which compared baricitinib plus remdesivir with dexamethasone plus remdesivir – was stopped for futility in April 2021.

To assess the efficacy and safety of tofacitinib as a potential treatment for COVID-19, the researchers launched a randomized, double-blind trial made up of 289 patients from 15 sites in Brazil. The Study of Tofacitinib in Hospitalized Patients with COVID-19 Pneumonia (STOP-COVID) split its participants into two groups: one (n = 144) received 10 mg of oral tofacitinib twice daily and the other (n = 145) received placebo. Treatment was to be administered for up to 14 days or until hospital discharge. The participants’ mean age was 56 years, and 34.9% were women.

Over 89% of participants received glucocorticoids during hospitalization, a significant increase, compared with ACTT-2’s 12%. Through 28 days, death or respiratory failure occurred in 18.1% of the tofacitinib group and in 29.0% of the placebo group (risk ratio, 0.63; 95% confidence interval, 0.41-0.97; P = .04). Death from any cause occurred in 2.8% of the tofacitinib group and 5.5% of the placebo group (hazard ratio, 0.49; 95% CI, 0.15-1.63). The median number of days that treatment was administered was 5 in the tofacitinib group and 6 in the placebo group, and the median duration of hospital and ICU stays were similar across groups.

On the eight-level National Institute of Allergy and Infectious Diseases ordinal scale of disease severity, the proportional odds of having a worse score with tofacitinib, compared with placebo, was 0.6 (95% CI, 0.36-1.00) at day 14 and 0.54 (95% CI, 0.27-1.06) at day 28. Adverse events occurred in 26.1% of the tofacitinib group and 22.5% of the placebo group, with serious adverse events occurring in 20 patients (14.1%) on tofacitinib and 17 patients (12%) on placebo. Patients on tofacitinib suffered from events like deep vein thrombosis, acute myocardial infarction, ventricular tachycardia, and myocarditis, each of which affected one person, while one placebo patient each suffered from hemorrhagic stroke and cardiogenic shock. The incidence of serious infection was 3.5% in the tofacitinib group and 4.2% in the placebo group.
 

Timing may be everything

“There is a lot of interest in repurposing a variety of disease-modifying antirheumatic drugs for the treatment of COVID-19, which includes JAK inhibitors,” Zachary S. Wallace, MD, of the rheumatology unit at Massachusetts General Hospital, Boston, said in an interview. “The ACTT-2 data was compelling; it did suggest perhaps a benefit associated with baricitinib for COVID. This study certainly is more compelling.”

“For many people, there is this hyperinflammatory response in COVID-19 that seems to drive a lot of the morbidity and mortality that we see,” he added. “I think we all hypothesize that some of our treatments may be beneficial there. The challenge that we face is figuring out when the best time is to administer these medicines, and whether they need to be administered as part of a cocktail of therapy.”

Along those lines, Dr. Wallace cited a recent study he coauthored in which rheumatoid arthritis patients who were on JAK inhibitors at baseline had worse COVID-19 severity. But he emphasized that, despite their differing findings, the two studies are not irreconcilable.

“What this might speak to is, the timing of your exposure may be really important,” he said. “At the time of your initial infection, you may need certain aspects of your immune system that a JAK inhibitor may interfere with. But when you initiate a JAK inhibitor, once that phase is complete and you’re in this hyperinflammatory phase, you may have more benefit to target and treat the intense inflammation that we observe in patients who have COVID.”

He also offered up another variable potentially in play: different JAK inhibitors having different targets among the JAK receptors. “It may be that targeting specific JAKs is more beneficial when it comes to treating the hyperinflammatory response of COVID-19.”

The trial was sponsored by Pfizer. Several authors acknowledged potential conflicts of interest, including receiving grants and personal fees from Pfizer and various other pharmaceutical companies.

The Janus kinase inhibitor tofacitinib reduces the risk of both death and respiratory failure in hospitalized adults with COVID-19 pneumonia, a new Brazilian study has found.

“Whether the use of JAK inhibitors is superior or additive to other specific immunomodulatory therapies in patients hospitalized with COVID-19 remains to be determined,” Patrícia O. Guimarães, MD, PhD, of the Hospital Israelita Albert Einstein in São Paulo, and coauthors wrote. The study was published in the New England Journal of Medicine.

The results of previous trials that tested JAK inhibitors as therapies for COVID-19 have been mixed. The second iteration of the Adaptive COVID-19 Treatment Trial (ACTT-2) found that a combination treatment of baricitinib and the Food and Drug Administration–authorized remdesivir was superior to remdesivir alone, but ACTT-4 – which compared baricitinib plus remdesivir with dexamethasone plus remdesivir – was stopped for futility in April 2021.

To assess the efficacy and safety of tofacitinib as a potential treatment for COVID-19, the researchers launched a randomized, double-blind trial made up of 289 patients from 15 sites in Brazil. The Study of Tofacitinib in Hospitalized Patients with COVID-19 Pneumonia (STOP-COVID) split its participants into two groups: one (n = 144) received 10 mg of oral tofacitinib twice daily and the other (n = 145) received placebo. Treatment was to be administered for up to 14 days or until hospital discharge. The participants’ mean age was 56 years, and 34.9% were women.

Over 89% of participants received glucocorticoids during hospitalization, a significant increase, compared with ACTT-2’s 12%. Through 28 days, death or respiratory failure occurred in 18.1% of the tofacitinib group and in 29.0% of the placebo group (risk ratio, 0.63; 95% confidence interval, 0.41-0.97; P = .04). Death from any cause occurred in 2.8% of the tofacitinib group and 5.5% of the placebo group (hazard ratio, 0.49; 95% CI, 0.15-1.63). The median number of days that treatment was administered was 5 in the tofacitinib group and 6 in the placebo group, and the median duration of hospital and ICU stays were similar across groups.

On the eight-level National Institute of Allergy and Infectious Diseases ordinal scale of disease severity, the proportional odds of having a worse score with tofacitinib, compared with placebo, was 0.6 (95% CI, 0.36-1.00) at day 14 and 0.54 (95% CI, 0.27-1.06) at day 28. Adverse events occurred in 26.1% of the tofacitinib group and 22.5% of the placebo group, with serious adverse events occurring in 20 patients (14.1%) on tofacitinib and 17 patients (12%) on placebo. Patients on tofacitinib suffered from events like deep vein thrombosis, acute myocardial infarction, ventricular tachycardia, and myocarditis, each of which affected one person, while one placebo patient each suffered from hemorrhagic stroke and cardiogenic shock. The incidence of serious infection was 3.5% in the tofacitinib group and 4.2% in the placebo group.
 

Timing may be everything

“There is a lot of interest in repurposing a variety of disease-modifying antirheumatic drugs for the treatment of COVID-19, which includes JAK inhibitors,” Zachary S. Wallace, MD, of the rheumatology unit at Massachusetts General Hospital, Boston, said in an interview. “The ACTT-2 data was compelling; it did suggest perhaps a benefit associated with baricitinib for COVID. This study certainly is more compelling.”

“For many people, there is this hyperinflammatory response in COVID-19 that seems to drive a lot of the morbidity and mortality that we see,” he added. “I think we all hypothesize that some of our treatments may be beneficial there. The challenge that we face is figuring out when the best time is to administer these medicines, and whether they need to be administered as part of a cocktail of therapy.”

Along those lines, Dr. Wallace cited a recent study he coauthored in which rheumatoid arthritis patients who were on JAK inhibitors at baseline had worse COVID-19 severity. But he emphasized that, despite their differing findings, the two studies are not irreconcilable.

“What this might speak to is, the timing of your exposure may be really important,” he said. “At the time of your initial infection, you may need certain aspects of your immune system that a JAK inhibitor may interfere with. But when you initiate a JAK inhibitor, once that phase is complete and you’re in this hyperinflammatory phase, you may have more benefit to target and treat the intense inflammation that we observe in patients who have COVID.”

He also offered up another variable potentially in play: different JAK inhibitors having different targets among the JAK receptors. “It may be that targeting specific JAKs is more beneficial when it comes to treating the hyperinflammatory response of COVID-19.”

The trial was sponsored by Pfizer. Several authors acknowledged potential conflicts of interest, including receiving grants and personal fees from Pfizer and various other pharmaceutical companies.

The Janus kinase inhibitor tofacitinib reduces the risk of both death and respiratory failure in hospitalized adults with COVID-19 pneumonia, a new Brazilian study has found.

“Whether the use of JAK inhibitors is superior or additive to other specific immunomodulatory therapies in patients hospitalized with COVID-19 remains to be determined,” Patrícia O. Guimarães, MD, PhD, of the Hospital Israelita Albert Einstein in São Paulo, and coauthors wrote. The study was published in the New England Journal of Medicine.

The results of previous trials that tested JAK inhibitors as therapies for COVID-19 have been mixed. The second iteration of the Adaptive COVID-19 Treatment Trial (ACTT-2) found that a combination treatment of baricitinib and the Food and Drug Administration–authorized remdesivir was superior to remdesivir alone, but ACTT-4 – which compared baricitinib plus remdesivir with dexamethasone plus remdesivir – was stopped for futility in April 2021.

To assess the efficacy and safety of tofacitinib as a potential treatment for COVID-19, the researchers launched a randomized, double-blind trial made up of 289 patients from 15 sites in Brazil. The Study of Tofacitinib in Hospitalized Patients with COVID-19 Pneumonia (STOP-COVID) split its participants into two groups: one (n = 144) received 10 mg of oral tofacitinib twice daily and the other (n = 145) received placebo. Treatment was to be administered for up to 14 days or until hospital discharge. The participants’ mean age was 56 years, and 34.9% were women.

Over 89% of participants received glucocorticoids during hospitalization, a significant increase, compared with ACTT-2’s 12%. Through 28 days, death or respiratory failure occurred in 18.1% of the tofacitinib group and in 29.0% of the placebo group (risk ratio, 0.63; 95% confidence interval, 0.41-0.97; P = .04). Death from any cause occurred in 2.8% of the tofacitinib group and 5.5% of the placebo group (hazard ratio, 0.49; 95% CI, 0.15-1.63). The median number of days that treatment was administered was 5 in the tofacitinib group and 6 in the placebo group, and the median duration of hospital and ICU stays were similar across groups.

On the eight-level National Institute of Allergy and Infectious Diseases ordinal scale of disease severity, the proportional odds of having a worse score with tofacitinib, compared with placebo, was 0.6 (95% CI, 0.36-1.00) at day 14 and 0.54 (95% CI, 0.27-1.06) at day 28. Adverse events occurred in 26.1% of the tofacitinib group and 22.5% of the placebo group, with serious adverse events occurring in 20 patients (14.1%) on tofacitinib and 17 patients (12%) on placebo. Patients on tofacitinib suffered from events like deep vein thrombosis, acute myocardial infarction, ventricular tachycardia, and myocarditis, each of which affected one person, while one placebo patient each suffered from hemorrhagic stroke and cardiogenic shock. The incidence of serious infection was 3.5% in the tofacitinib group and 4.2% in the placebo group.
 

Timing may be everything

“There is a lot of interest in repurposing a variety of disease-modifying antirheumatic drugs for the treatment of COVID-19, which includes JAK inhibitors,” Zachary S. Wallace, MD, of the rheumatology unit at Massachusetts General Hospital, Boston, said in an interview. “The ACTT-2 data was compelling; it did suggest perhaps a benefit associated with baricitinib for COVID. This study certainly is more compelling.”

“For many people, there is this hyperinflammatory response in COVID-19 that seems to drive a lot of the morbidity and mortality that we see,” he added. “I think we all hypothesize that some of our treatments may be beneficial there. The challenge that we face is figuring out when the best time is to administer these medicines, and whether they need to be administered as part of a cocktail of therapy.”

Along those lines, Dr. Wallace cited a recent study he coauthored in which rheumatoid arthritis patients who were on JAK inhibitors at baseline had worse COVID-19 severity. But he emphasized that, despite their differing findings, the two studies are not irreconcilable.

“What this might speak to is, the timing of your exposure may be really important,” he said. “At the time of your initial infection, you may need certain aspects of your immune system that a JAK inhibitor may interfere with. But when you initiate a JAK inhibitor, once that phase is complete and you’re in this hyperinflammatory phase, you may have more benefit to target and treat the intense inflammation that we observe in patients who have COVID.”

He also offered up another variable potentially in play: different JAK inhibitors having different targets among the JAK receptors. “It may be that targeting specific JAKs is more beneficial when it comes to treating the hyperinflammatory response of COVID-19.”

The trial was sponsored by Pfizer. Several authors acknowledged potential conflicts of interest, including receiving grants and personal fees from Pfizer and various other pharmaceutical companies.

Statin therapy likely didn’t lead to dementia or even mild cognitive impairment (MCI) in older patients taking the drugs for cardiovascular (CV) primary prevention in a post hoc analysis of a trial that required normal cognitive ability for entry.

Nor did statins, whether lipophilic or hydrophilic, appear to influence changes in cognition or affect separate domains of mental performance, such as memory, language ability, or executive function, over the trial’s follow-up, which averaged almost 5 years.

Although such findings aren’t novel – they are consistent with observations from a number of earlier studies – the new analysis included a possible signal for a statin association with new-onset dementia in a subgroup of more than 18,000 patients. Researchers attribute the retrospective finding, from a trial not designed to explore the issue, to confounding or chance.

Still, the adjusted risk for dementia seemed to go up by a third among statin users who at baseline placed in the lowest quartile for cognitive function, based on a composite test score, in the ASPREE trial, a test of primary-prevention low-dose aspirin in patients 65 or older. The better the baseline cognitive score by quartile, the lower the risk for dementia ( interaction P < .001).

The bottom-quartile association of statins with dementia was driven by new diagnoses of Alzheimer’s disease, as opposed to the study’s other “mixed presentation” dementia subtype, wrote the authors of analysis, published June 21, 2021, in the Journal of the American College of Cardiology), led by Zhen Zhou, PhD, Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.

“I wouldn’t overinterpret that,” said senior author Mark R. Nelson, MBBS, PhD, of the same institution. Indeed, it should be “reassuring” for physicians prescribing statins to older patients that there was no overall statin effect on cognition or new-onset dementia, he said in an interview.

“This is a post hoc analysis within a dataset, although a very-high-quality dataset, it must be said.” The patients were prospectively followed for a range of cognition domains, and the results were adjudicated, Dr. Nelson observed. Although the question of statins and dementia risk is thought to be largely settled, the analysis “was just too tempting not to do.”

On the basis of the current analysis and the bulk of preceding evidence, “lipid lowering in the short term does not appear to result in improvement or deterioration of cognition irrespective of baseline LDL cholesterol levels and medication used,” Christie M. Ballantyne, MD, and Vijay Nambi, MD, PhD, both from Baylor College of Medicine, Houston, wrote in an accompanying editorial.

The current study “provides additional information that the lipo- or hydrophilicity of the statin does not affect changes in cognition. However, the potential increased risk for Alzheimer’s disease, especially among patients with baseline cognitive impairment, requires further investigation.”

The current analysis is reassuring that the likelihood of such statin effects on cognition “is vanishingly small,” Neil J. Stone MD, Northwestern University, Chicago, said in an interview. In fact, its primary finding of no such association “best summarizes what we know in 2021 about statin therapy” after exploration of the issue in a number of prospective trials and systematic reviews, said Dr. Stone, who was not a coauthor on the report.

The observed interaction between statin use and baseline neurocognitive ability “is hypothesis raising at best. It should be explored in randomized, controlled trials that can look at this question in an unbiased manner,” he agreed.

If patients believe or suspect that a statin is causing symptoms that suggest cognitive dysfunction, “what they really need to do is to stop it for 3 weeks and check out other causes. And in rechallenging, the guidelines say, if they think that it’s causing a memory problem that occurs anecdotally, then they can be given another statin, usually, which doesn’t cause it.”

ASPREE compared daily low-dose aspirin with placebo in a community-based older population numbering about 19,000 in Australia and the United States. Patients were initially without known CV disease, dementia, or physical disabilities. It did not randomize patients by statin therapy.

Of note, entry to the trial required a score of at least 78 on the Modified Mini-Mental State Examination (3MS), corresponding to normal cognition.

Aspirin showed no significant benefit for disability-free survival, an endpoint that included death and dementia, or CV events over a median of 4.7 years. It was associated with slightly more cases of major hemorrhage, as previously reported.

A subsequent ASPREE analysis suggested that the aspirin had no effect on risks of mild cognitive impairment, cognitive decline, or dementia.

Of the 18,846 patients in the current post hoc analysis, the average age of the patients was 74 years, and 56.4% were women; 31.3% were taking statins at baseline. The incidence of dementia per 1,000 person-years for those taking statins in comparison with those not taking statins was 6.91 and 6.48, respectively. Any cognitive changes were tracked by the 3MS and three other validated tests in different domains of cognition, with results contributing to the composite score.

The corresponding incidence of dementia considered probable Alzheimer’s disease was 2.97 and 2.65 for those receiving versus not receiving statins, respectively. The incidence of dementia with mixed presentation was 3.94 and 3.84, respectively.

There were no significant differences in risk for dementia overall or for either dementia subtype in multivariate analyses. Adjustments included demographics, CV lifestyle risk factors, family medical history, including dementia, ASPREE randomization group, and individual scores on the four tests of cognition.

Results for development of MCI mirrored those for dementia, as did results stratified for baseline lipids and for use of lipophilic statins, such as atorvastatin or simvastatin versus hydrophilic statins, including pravastatin and rosuvastatin.

Significant interactions were observed between composite cognitive scores and statin therapy at baseline; as scores increased, indicating better cognitive performance, the risks for dementia and its subtypes went down. Statins were associated with incident dementia at the lowest cognitive performance quartile.

That association is probably a function of the cohort’s advanced age, Dr. Nelson said. “If you get into old age, and you’ve got high cognitive scores, you’ve probably got protective factors. That’s how I would interpret that.”

Dr. Ballantyne and Dr. Nambi also emphasized the difficulties of controlling for potential biases even with extensive covariate adjustments. The statin dosages at which patients were treated were not part of the analysis, “and achieved LDL [cholesterol levels over the study period were not known,” they wrote.

“Furthermore, patients who were treated with statins were more likely to have diabetes, hypertension, chronic kidney disease, and obesity, all of which are known to increase risk for cognitive decline, and, as might have been predicted, statin users therefore had significantly lower scores for global cognition and episodic memory.”

Dr. Nelson pointed to an ongoing prospective atorvastatin trial that includes dementia in its primary endpoint and should be “the definitive study.” STAREE (Statin Therapy for Reducing Events in the Elderly) is running throughout Australia with a projected enrollment of 18,000 and primary completion by the end of 2022. “We’ve already enrolled 8,000 patients.”

Less far along is the PREVENTABLE (Pragmatic Evaluation of Events and Benefits of Lipid-Lowering in Older Adults) trial, based in the United States and also randomizing to atorvastatin or placebo, that will have an estimated 20,000 older patients and completion in 5 years. The primary endpoint is new dementia or persistent disability.

Both trials “are powered to enable firm conclusions concerning any statin effects,” said Dr. Ballantyne and Dr. Nambi. “In the meantime, practicing clinicians can have confidence and share with their patients that short-term lipid-lowering therapy in older patients, including with statins, is unlikely to have a major impact on cognition.”

ASPREE was supported by grants from the U.S. National Institute on Aging and the National Cancer Institute and the National Health and Medical Research Council of Australia, by Monash University, and by the Victorian Cancer Agency. Dr. Nelson reported receiving honoraria from Sanofi and Amgen; support from Bayer for ASPREE; and grant support for STAREE. Disclosures for the other authors are in the report. Dr. Ballantyne disclosed grant and research support from Abbott Diagnostic, Akcea, Amgen, Esperion, Ionis, Novartis, Regeneron, and Roche Diagnostics; and consulting for Abbott Diagnostics, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Corvidia, Denka Seiken, Esperion, Genentech, Gilead, Matinas BioPharma, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostics, and Sanofi-Synthelabo. Dr. Nambi is a coinvestigator on a provisional patent along with Baylor College of Medicine and Roche on the use of biomarkers to predict heart failure, and a site principal investigator for studies sponsored by Amgen and Merck. Dr. Stone had no disclosures.

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

Statin therapy likely didn’t lead to dementia or even mild cognitive impairment (MCI) in older patients taking the drugs for cardiovascular (CV) primary prevention in a post hoc analysis of a trial that required normal cognitive ability for entry.

Nor did statins, whether lipophilic or hydrophilic, appear to influence changes in cognition or affect separate domains of mental performance, such as memory, language ability, or executive function, over the trial’s follow-up, which averaged almost 5 years.

Although such findings aren’t novel – they are consistent with observations from a number of earlier studies – the new analysis included a possible signal for a statin association with new-onset dementia in a subgroup of more than 18,000 patients. Researchers attribute the retrospective finding, from a trial not designed to explore the issue, to confounding or chance.

Still, the adjusted risk for dementia seemed to go up by a third among statin users who at baseline placed in the lowest quartile for cognitive function, based on a composite test score, in the ASPREE trial, a test of primary-prevention low-dose aspirin in patients 65 or older. The better the baseline cognitive score by quartile, the lower the risk for dementia ( interaction P < .001).

The bottom-quartile association of statins with dementia was driven by new diagnoses of Alzheimer’s disease, as opposed to the study’s other “mixed presentation” dementia subtype, wrote the authors of analysis, published June 21, 2021, in the Journal of the American College of Cardiology), led by Zhen Zhou, PhD, Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.

“I wouldn’t overinterpret that,” said senior author Mark R. Nelson, MBBS, PhD, of the same institution. Indeed, it should be “reassuring” for physicians prescribing statins to older patients that there was no overall statin effect on cognition or new-onset dementia, he said in an interview.

“This is a post hoc analysis within a dataset, although a very-high-quality dataset, it must be said.” The patients were prospectively followed for a range of cognition domains, and the results were adjudicated, Dr. Nelson observed. Although the question of statins and dementia risk is thought to be largely settled, the analysis “was just too tempting not to do.”

On the basis of the current analysis and the bulk of preceding evidence, “lipid lowering in the short term does not appear to result in improvement or deterioration of cognition irrespective of baseline LDL cholesterol levels and medication used,” Christie M. Ballantyne, MD, and Vijay Nambi, MD, PhD, both from Baylor College of Medicine, Houston, wrote in an accompanying editorial.

The current study “provides additional information that the lipo- or hydrophilicity of the statin does not affect changes in cognition. However, the potential increased risk for Alzheimer’s disease, especially among patients with baseline cognitive impairment, requires further investigation.”

The current analysis is reassuring that the likelihood of such statin effects on cognition “is vanishingly small,” Neil J. Stone MD, Northwestern University, Chicago, said in an interview. In fact, its primary finding of no such association “best summarizes what we know in 2021 about statin therapy” after exploration of the issue in a number of prospective trials and systematic reviews, said Dr. Stone, who was not a coauthor on the report.

The observed interaction between statin use and baseline neurocognitive ability “is hypothesis raising at best. It should be explored in randomized, controlled trials that can look at this question in an unbiased manner,” he agreed.

If patients believe or suspect that a statin is causing symptoms that suggest cognitive dysfunction, “what they really need to do is to stop it for 3 weeks and check out other causes. And in rechallenging, the guidelines say, if they think that it’s causing a memory problem that occurs anecdotally, then they can be given another statin, usually, which doesn’t cause it.”

ASPREE compared daily low-dose aspirin with placebo in a community-based older population numbering about 19,000 in Australia and the United States. Patients were initially without known CV disease, dementia, or physical disabilities. It did not randomize patients by statin therapy.

Of note, entry to the trial required a score of at least 78 on the Modified Mini-Mental State Examination (3MS), corresponding to normal cognition.

Aspirin showed no significant benefit for disability-free survival, an endpoint that included death and dementia, or CV events over a median of 4.7 years. It was associated with slightly more cases of major hemorrhage, as previously reported.

A subsequent ASPREE analysis suggested that the aspirin had no effect on risks of mild cognitive impairment, cognitive decline, or dementia.

Of the 18,846 patients in the current post hoc analysis, the average age of the patients was 74 years, and 56.4% were women; 31.3% were taking statins at baseline. The incidence of dementia per 1,000 person-years for those taking statins in comparison with those not taking statins was 6.91 and 6.48, respectively. Any cognitive changes were tracked by the 3MS and three other validated tests in different domains of cognition, with results contributing to the composite score.

The corresponding incidence of dementia considered probable Alzheimer’s disease was 2.97 and 2.65 for those receiving versus not receiving statins, respectively. The incidence of dementia with mixed presentation was 3.94 and 3.84, respectively.

There were no significant differences in risk for dementia overall or for either dementia subtype in multivariate analyses. Adjustments included demographics, CV lifestyle risk factors, family medical history, including dementia, ASPREE randomization group, and individual scores on the four tests of cognition.

Results for development of MCI mirrored those for dementia, as did results stratified for baseline lipids and for use of lipophilic statins, such as atorvastatin or simvastatin versus hydrophilic statins, including pravastatin and rosuvastatin.

Significant interactions were observed between composite cognitive scores and statin therapy at baseline; as scores increased, indicating better cognitive performance, the risks for dementia and its subtypes went down. Statins were associated with incident dementia at the lowest cognitive performance quartile.

That association is probably a function of the cohort’s advanced age, Dr. Nelson said. “If you get into old age, and you’ve got high cognitive scores, you’ve probably got protective factors. That’s how I would interpret that.”

Dr. Ballantyne and Dr. Nambi also emphasized the difficulties of controlling for potential biases even with extensive covariate adjustments. The statin dosages at which patients were treated were not part of the analysis, “and achieved LDL [cholesterol levels over the study period were not known,” they wrote.

“Furthermore, patients who were treated with statins were more likely to have diabetes, hypertension, chronic kidney disease, and obesity, all of which are known to increase risk for cognitive decline, and, as might have been predicted, statin users therefore had significantly lower scores for global cognition and episodic memory.”

Dr. Nelson pointed to an ongoing prospective atorvastatin trial that includes dementia in its primary endpoint and should be “the definitive study.” STAREE (Statin Therapy for Reducing Events in the Elderly) is running throughout Australia with a projected enrollment of 18,000 and primary completion by the end of 2022. “We’ve already enrolled 8,000 patients.”

Less far along is the PREVENTABLE (Pragmatic Evaluation of Events and Benefits of Lipid-Lowering in Older Adults) trial, based in the United States and also randomizing to atorvastatin or placebo, that will have an estimated 20,000 older patients and completion in 5 years. The primary endpoint is new dementia or persistent disability.

Both trials “are powered to enable firm conclusions concerning any statin effects,” said Dr. Ballantyne and Dr. Nambi. “In the meantime, practicing clinicians can have confidence and share with their patients that short-term lipid-lowering therapy in older patients, including with statins, is unlikely to have a major impact on cognition.”

ASPREE was supported by grants from the U.S. National Institute on Aging and the National Cancer Institute and the National Health and Medical Research Council of Australia, by Monash University, and by the Victorian Cancer Agency. Dr. Nelson reported receiving honoraria from Sanofi and Amgen; support from Bayer for ASPREE; and grant support for STAREE. Disclosures for the other authors are in the report. Dr. Ballantyne disclosed grant and research support from Abbott Diagnostic, Akcea, Amgen, Esperion, Ionis, Novartis, Regeneron, and Roche Diagnostics; and consulting for Abbott Diagnostics, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Corvidia, Denka Seiken, Esperion, Genentech, Gilead, Matinas BioPharma, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostics, and Sanofi-Synthelabo. Dr. Nambi is a coinvestigator on a provisional patent along with Baylor College of Medicine and Roche on the use of biomarkers to predict heart failure, and a site principal investigator for studies sponsored by Amgen and Merck. Dr. Stone had no disclosures.

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

Statin therapy likely didn’t lead to dementia or even mild cognitive impairment (MCI) in older patients taking the drugs for cardiovascular (CV) primary prevention in a post hoc analysis of a trial that required normal cognitive ability for entry.

Nor did statins, whether lipophilic or hydrophilic, appear to influence changes in cognition or affect separate domains of mental performance, such as memory, language ability, or executive function, over the trial’s follow-up, which averaged almost 5 years.

Although such findings aren’t novel – they are consistent with observations from a number of earlier studies – the new analysis included a possible signal for a statin association with new-onset dementia in a subgroup of more than 18,000 patients. Researchers attribute the retrospective finding, from a trial not designed to explore the issue, to confounding or chance.

Still, the adjusted risk for dementia seemed to go up by a third among statin users who at baseline placed in the lowest quartile for cognitive function, based on a composite test score, in the ASPREE trial, a test of primary-prevention low-dose aspirin in patients 65 or older. The better the baseline cognitive score by quartile, the lower the risk for dementia ( interaction P < .001).

The bottom-quartile association of statins with dementia was driven by new diagnoses of Alzheimer’s disease, as opposed to the study’s other “mixed presentation” dementia subtype, wrote the authors of analysis, published June 21, 2021, in the Journal of the American College of Cardiology), led by Zhen Zhou, PhD, Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.

“I wouldn’t overinterpret that,” said senior author Mark R. Nelson, MBBS, PhD, of the same institution. Indeed, it should be “reassuring” for physicians prescribing statins to older patients that there was no overall statin effect on cognition or new-onset dementia, he said in an interview.

“This is a post hoc analysis within a dataset, although a very-high-quality dataset, it must be said.” The patients were prospectively followed for a range of cognition domains, and the results were adjudicated, Dr. Nelson observed. Although the question of statins and dementia risk is thought to be largely settled, the analysis “was just too tempting not to do.”

On the basis of the current analysis and the bulk of preceding evidence, “lipid lowering in the short term does not appear to result in improvement or deterioration of cognition irrespective of baseline LDL cholesterol levels and medication used,” Christie M. Ballantyne, MD, and Vijay Nambi, MD, PhD, both from Baylor College of Medicine, Houston, wrote in an accompanying editorial.

The current study “provides additional information that the lipo- or hydrophilicity of the statin does not affect changes in cognition. However, the potential increased risk for Alzheimer’s disease, especially among patients with baseline cognitive impairment, requires further investigation.”

The current analysis is reassuring that the likelihood of such statin effects on cognition “is vanishingly small,” Neil J. Stone MD, Northwestern University, Chicago, said in an interview. In fact, its primary finding of no such association “best summarizes what we know in 2021 about statin therapy” after exploration of the issue in a number of prospective trials and systematic reviews, said Dr. Stone, who was not a coauthor on the report.

The observed interaction between statin use and baseline neurocognitive ability “is hypothesis raising at best. It should be explored in randomized, controlled trials that can look at this question in an unbiased manner,” he agreed.

If patients believe or suspect that a statin is causing symptoms that suggest cognitive dysfunction, “what they really need to do is to stop it for 3 weeks and check out other causes. And in rechallenging, the guidelines say, if they think that it’s causing a memory problem that occurs anecdotally, then they can be given another statin, usually, which doesn’t cause it.”

ASPREE compared daily low-dose aspirin with placebo in a community-based older population numbering about 19,000 in Australia and the United States. Patients were initially without known CV disease, dementia, or physical disabilities. It did not randomize patients by statin therapy.

Of note, entry to the trial required a score of at least 78 on the Modified Mini-Mental State Examination (3MS), corresponding to normal cognition.

Aspirin showed no significant benefit for disability-free survival, an endpoint that included death and dementia, or CV events over a median of 4.7 years. It was associated with slightly more cases of major hemorrhage, as previously reported.

A subsequent ASPREE analysis suggested that the aspirin had no effect on risks of mild cognitive impairment, cognitive decline, or dementia.

Of the 18,846 patients in the current post hoc analysis, the average age of the patients was 74 years, and 56.4% were women; 31.3% were taking statins at baseline. The incidence of dementia per 1,000 person-years for those taking statins in comparison with those not taking statins was 6.91 and 6.48, respectively. Any cognitive changes were tracked by the 3MS and three other validated tests in different domains of cognition, with results contributing to the composite score.

The corresponding incidence of dementia considered probable Alzheimer’s disease was 2.97 and 2.65 for those receiving versus not receiving statins, respectively. The incidence of dementia with mixed presentation was 3.94 and 3.84, respectively.

There were no significant differences in risk for dementia overall or for either dementia subtype in multivariate analyses. Adjustments included demographics, CV lifestyle risk factors, family medical history, including dementia, ASPREE randomization group, and individual scores on the four tests of cognition.

Results for development of MCI mirrored those for dementia, as did results stratified for baseline lipids and for use of lipophilic statins, such as atorvastatin or simvastatin versus hydrophilic statins, including pravastatin and rosuvastatin.

Significant interactions were observed between composite cognitive scores and statin therapy at baseline; as scores increased, indicating better cognitive performance, the risks for dementia and its subtypes went down. Statins were associated with incident dementia at the lowest cognitive performance quartile.

That association is probably a function of the cohort’s advanced age, Dr. Nelson said. “If you get into old age, and you’ve got high cognitive scores, you’ve probably got protective factors. That’s how I would interpret that.”

Dr. Ballantyne and Dr. Nambi also emphasized the difficulties of controlling for potential biases even with extensive covariate adjustments. The statin dosages at which patients were treated were not part of the analysis, “and achieved LDL [cholesterol levels over the study period were not known,” they wrote.

“Furthermore, patients who were treated with statins were more likely to have diabetes, hypertension, chronic kidney disease, and obesity, all of which are known to increase risk for cognitive decline, and, as might have been predicted, statin users therefore had significantly lower scores for global cognition and episodic memory.”

Dr. Nelson pointed to an ongoing prospective atorvastatin trial that includes dementia in its primary endpoint and should be “the definitive study.” STAREE (Statin Therapy for Reducing Events in the Elderly) is running throughout Australia with a projected enrollment of 18,000 and primary completion by the end of 2022. “We’ve already enrolled 8,000 patients.”

Less far along is the PREVENTABLE (Pragmatic Evaluation of Events and Benefits of Lipid-Lowering in Older Adults) trial, based in the United States and also randomizing to atorvastatin or placebo, that will have an estimated 20,000 older patients and completion in 5 years. The primary endpoint is new dementia or persistent disability.

Both trials “are powered to enable firm conclusions concerning any statin effects,” said Dr. Ballantyne and Dr. Nambi. “In the meantime, practicing clinicians can have confidence and share with their patients that short-term lipid-lowering therapy in older patients, including with statins, is unlikely to have a major impact on cognition.”

ASPREE was supported by grants from the U.S. National Institute on Aging and the National Cancer Institute and the National Health and Medical Research Council of Australia, by Monash University, and by the Victorian Cancer Agency. Dr. Nelson reported receiving honoraria from Sanofi and Amgen; support from Bayer for ASPREE; and grant support for STAREE. Disclosures for the other authors are in the report. Dr. Ballantyne disclosed grant and research support from Abbott Diagnostic, Akcea, Amgen, Esperion, Ionis, Novartis, Regeneron, and Roche Diagnostics; and consulting for Abbott Diagnostics, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Corvidia, Denka Seiken, Esperion, Genentech, Gilead, Matinas BioPharma, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostics, and Sanofi-Synthelabo. Dr. Nambi is a coinvestigator on a provisional patent along with Baylor College of Medicine and Roche on the use of biomarkers to predict heart failure, and a site principal investigator for studies sponsored by Amgen and Merck. Dr. Stone had no disclosures.

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

A novel therapeutic approach using aptamers – short single strands of DNA or RNA designed to selectively bind to a target – shows promise for treating von Willebrand Disease (VWD), and other congenital bleed disorders such as hemophilia A, investigators say.

In a proof-of-concept study using healthy volunteers, the experimental anti–von Willebrand factor (VWF) molecule BT200 appeared to decrease clearance of VWF and resulted in a twofold increase in endogenous levels of VWF and factor VIII at low doses.

BT200 is currently being explored in a phase 2 trial in patients with hemophilia A and VWD type 2B, Katarina Kovacevic, MPharm, from the Medical University of Vienna, reported at the European Hematology Association annual congress.

“We expect to see a half-life increase of 2 to 4 times of factor VIII products, which will allow us to have a longer time between treatments,” she said in an oral abstract presentation (Abstract S302).
 

Lab-made nucleotide strings

Aptamers are sometimes call “chemical antibodies” because of their high affinity and high specificity for extracellular targets, Dr. Kovacevic said. Unlike conventional humanized or human-derived antibodies, however, they are nonimmunogenic and are less costly to manufacture.

In a previous study from her center, a different anti-VWF aptamer labeled ARC1779 increased plasma levels of VWF, factor VIII, and platelet counts in patients with VWD type 2B.

However, the drug was inconvenient to use, requiring 72-hour infusions, she noted.

In a study published in Feb. 4, 2021 in Scientific Reports, Dr. Kovacevic and colleagues reported that BT200 blocks VWF and platelet function in patients with ischemic strokes, even in the presence of high levels of VWF in patients with left carotid artery atherosclerotic strokes.

The ability of the molecule to block VWF platelet binding may explain how the anti-VWF agent actually results in higher circulating levels of VWF, which also carries factor VIII, said Veronica H. Flood, MD, a VWD specialist at Children’s Hospital of Wisconsin and associate professor at the Medical College of Wisconsin in Milwaukee.

“It might inhibit clearance of the von Willebrand factor, so it’s almost like this was an incidental side effect,” she said in an interview. “Incidentally, this happens to also give you higher levels of the von Willebrand factor and the factor VIII, and with a longer half-life than anything we currently have, so it’s a super-creative strategy,” she said.

Dr. Flood was not involved in the study.
 

Long half-life

BT200 is a third-generation peglyated anti-VWF aptamer that has been shown in preclinical studies to have a long half-life in nonhuman primates. It inhibits the A1 domain of VWF to prevent it from binding to platelet glycoprotein 1b (GP1b).

In the randomized, double-blind, placebo-controlled trial reported at the EHA congress, 88 healthy volunteers received single doses of BT200 ranging from 0.l8 mg to 48 mg by subcutaneous injection or intravenous infusion, 8 received multiple doses, 8 were evaluated for possible interactions with desmopressin, and 8 were evaluated for bioavailability of the aptamer.

The investigators observed a dose-related increase in BT200 concentrations, with a mean plasma terminal elimination half life of between 118 and 284 hours (about 5-12 days). There was also a dose-dependent increase in bioavailability of the agents, reaching 90% at the highest dose level.

The ability of BT200 to inhibit the A1 domains of VWF also was dose dependent, with the largest effect seen with doses of 12 mg and higher. The molecule decreased VWF activity and ristocetin-induced platelet aggregation, and prolonged collagen adenosine diphosphate closure time.

At the highest doses, BT200 caused complete inhibition of VWF (P < .001), and volunteers developed clinical signs of mild mucosal bleeding.

But the aptamer also increased in a dose-dependent fashion VWF antigen levels and factor VIII clotting activity more than fourfold (P <.001).

“This resulted in increased thrombogenicity as measured by thrombin generation and enhanced clotting. In the absence of an increase in VWF propeptide levels, this effect is considered due to decreased clearance of VWF,” the investigators wrote in the study abstract.

They noted that they saw a clinically meaningful twofold increase in both VWF and factor VIII at doses lower than 6 mg.
 

‘Super-exciting strategy’

“This trial identified a novel mechanism of action for BT200: It decreases the clearance of VWF/FVIII, which can be exploited for congenital bleeding disorders. This built a solid foundation for an ongoing basket trial in patients with von Willebrand disease or hemophilia A, which already confirms the expected effect sizes,” Dr. Kovacevic and colleagues wrote.

“I will be interested to see what the clinical side effects are, because there may be some off-target effects, but in reality it is a super-exciting strategy, and there is really a dire need for longer half-life products for these patients,” Dr. Flood said.

The study was sponsored by Band Therapeutics, a division of Guardian Therapeutics. Dr. Kovacevic and Dr. Flood reported having no conflicts of interest to disclose.

A novel therapeutic approach using aptamers – short single strands of DNA or RNA designed to selectively bind to a target – shows promise for treating von Willebrand Disease (VWD), and other congenital bleed disorders such as hemophilia A, investigators say.

In a proof-of-concept study using healthy volunteers, the experimental anti–von Willebrand factor (VWF) molecule BT200 appeared to decrease clearance of VWF and resulted in a twofold increase in endogenous levels of VWF and factor VIII at low doses.

BT200 is currently being explored in a phase 2 trial in patients with hemophilia A and VWD type 2B, Katarina Kovacevic, MPharm, from the Medical University of Vienna, reported at the European Hematology Association annual congress.

“We expect to see a half-life increase of 2 to 4 times of factor VIII products, which will allow us to have a longer time between treatments,” she said in an oral abstract presentation (Abstract S302).
 

Lab-made nucleotide strings

Aptamers are sometimes call “chemical antibodies” because of their high affinity and high specificity for extracellular targets, Dr. Kovacevic said. Unlike conventional humanized or human-derived antibodies, however, they are nonimmunogenic and are less costly to manufacture.

In a previous study from her center, a different anti-VWF aptamer labeled ARC1779 increased plasma levels of VWF, factor VIII, and platelet counts in patients with VWD type 2B.

However, the drug was inconvenient to use, requiring 72-hour infusions, she noted.

In a study published in Feb. 4, 2021 in Scientific Reports, Dr. Kovacevic and colleagues reported that BT200 blocks VWF and platelet function in patients with ischemic strokes, even in the presence of high levels of VWF in patients with left carotid artery atherosclerotic strokes.

The ability of the molecule to block VWF platelet binding may explain how the anti-VWF agent actually results in higher circulating levels of VWF, which also carries factor VIII, said Veronica H. Flood, MD, a VWD specialist at Children’s Hospital of Wisconsin and associate professor at the Medical College of Wisconsin in Milwaukee.

“It might inhibit clearance of the von Willebrand factor, so it’s almost like this was an incidental side effect,” she said in an interview. “Incidentally, this happens to also give you higher levels of the von Willebrand factor and the factor VIII, and with a longer half-life than anything we currently have, so it’s a super-creative strategy,” she said.

Dr. Flood was not involved in the study.
 

Long half-life

BT200 is a third-generation peglyated anti-VWF aptamer that has been shown in preclinical studies to have a long half-life in nonhuman primates. It inhibits the A1 domain of VWF to prevent it from binding to platelet glycoprotein 1b (GP1b).

In the randomized, double-blind, placebo-controlled trial reported at the EHA congress, 88 healthy volunteers received single doses of BT200 ranging from 0.l8 mg to 48 mg by subcutaneous injection or intravenous infusion, 8 received multiple doses, 8 were evaluated for possible interactions with desmopressin, and 8 were evaluated for bioavailability of the aptamer.

The investigators observed a dose-related increase in BT200 concentrations, with a mean plasma terminal elimination half life of between 118 and 284 hours (about 5-12 days). There was also a dose-dependent increase in bioavailability of the agents, reaching 90% at the highest dose level.

The ability of BT200 to inhibit the A1 domains of VWF also was dose dependent, with the largest effect seen with doses of 12 mg and higher. The molecule decreased VWF activity and ristocetin-induced platelet aggregation, and prolonged collagen adenosine diphosphate closure time.

At the highest doses, BT200 caused complete inhibition of VWF (P < .001), and volunteers developed clinical signs of mild mucosal bleeding.

But the aptamer also increased in a dose-dependent fashion VWF antigen levels and factor VIII clotting activity more than fourfold (P <.001).

“This resulted in increased thrombogenicity as measured by thrombin generation and enhanced clotting. In the absence of an increase in VWF propeptide levels, this effect is considered due to decreased clearance of VWF,” the investigators wrote in the study abstract.

They noted that they saw a clinically meaningful twofold increase in both VWF and factor VIII at doses lower than 6 mg.
 

‘Super-exciting strategy’

“This trial identified a novel mechanism of action for BT200: It decreases the clearance of VWF/FVIII, which can be exploited for congenital bleeding disorders. This built a solid foundation for an ongoing basket trial in patients with von Willebrand disease or hemophilia A, which already confirms the expected effect sizes,” Dr. Kovacevic and colleagues wrote.

“I will be interested to see what the clinical side effects are, because there may be some off-target effects, but in reality it is a super-exciting strategy, and there is really a dire need for longer half-life products for these patients,” Dr. Flood said.

The study was sponsored by Band Therapeutics, a division of Guardian Therapeutics. Dr. Kovacevic and Dr. Flood reported having no conflicts of interest to disclose.

A novel therapeutic approach using aptamers – short single strands of DNA or RNA designed to selectively bind to a target – shows promise for treating von Willebrand Disease (VWD), and other congenital bleed disorders such as hemophilia A, investigators say.

In a proof-of-concept study using healthy volunteers, the experimental anti–von Willebrand factor (VWF) molecule BT200 appeared to decrease clearance of VWF and resulted in a twofold increase in endogenous levels of VWF and factor VIII at low doses.

BT200 is currently being explored in a phase 2 trial in patients with hemophilia A and VWD type 2B, Katarina Kovacevic, MPharm, from the Medical University of Vienna, reported at the European Hematology Association annual congress.

“We expect to see a half-life increase of 2 to 4 times of factor VIII products, which will allow us to have a longer time between treatments,” she said in an oral abstract presentation (Abstract S302).
 

Lab-made nucleotide strings

Aptamers are sometimes call “chemical antibodies” because of their high affinity and high specificity for extracellular targets, Dr. Kovacevic said. Unlike conventional humanized or human-derived antibodies, however, they are nonimmunogenic and are less costly to manufacture.

In a previous study from her center, a different anti-VWF aptamer labeled ARC1779 increased plasma levels of VWF, factor VIII, and platelet counts in patients with VWD type 2B.

However, the drug was inconvenient to use, requiring 72-hour infusions, she noted.

In a study published in Feb. 4, 2021 in Scientific Reports, Dr. Kovacevic and colleagues reported that BT200 blocks VWF and platelet function in patients with ischemic strokes, even in the presence of high levels of VWF in patients with left carotid artery atherosclerotic strokes.

The ability of the molecule to block VWF platelet binding may explain how the anti-VWF agent actually results in higher circulating levels of VWF, which also carries factor VIII, said Veronica H. Flood, MD, a VWD specialist at Children’s Hospital of Wisconsin and associate professor at the Medical College of Wisconsin in Milwaukee.

“It might inhibit clearance of the von Willebrand factor, so it’s almost like this was an incidental side effect,” she said in an interview. “Incidentally, this happens to also give you higher levels of the von Willebrand factor and the factor VIII, and with a longer half-life than anything we currently have, so it’s a super-creative strategy,” she said.

Dr. Flood was not involved in the study.
 

Long half-life

BT200 is a third-generation peglyated anti-VWF aptamer that has been shown in preclinical studies to have a long half-life in nonhuman primates. It inhibits the A1 domain of VWF to prevent it from binding to platelet glycoprotein 1b (GP1b).

In the randomized, double-blind, placebo-controlled trial reported at the EHA congress, 88 healthy volunteers received single doses of BT200 ranging from 0.l8 mg to 48 mg by subcutaneous injection or intravenous infusion, 8 received multiple doses, 8 were evaluated for possible interactions with desmopressin, and 8 were evaluated for bioavailability of the aptamer.

The investigators observed a dose-related increase in BT200 concentrations, with a mean plasma terminal elimination half life of between 118 and 284 hours (about 5-12 days). There was also a dose-dependent increase in bioavailability of the agents, reaching 90% at the highest dose level.

The ability of BT200 to inhibit the A1 domains of VWF also was dose dependent, with the largest effect seen with doses of 12 mg and higher. The molecule decreased VWF activity and ristocetin-induced platelet aggregation, and prolonged collagen adenosine diphosphate closure time.

At the highest doses, BT200 caused complete inhibition of VWF (P < .001), and volunteers developed clinical signs of mild mucosal bleeding.

But the aptamer also increased in a dose-dependent fashion VWF antigen levels and factor VIII clotting activity more than fourfold (P <.001).

“This resulted in increased thrombogenicity as measured by thrombin generation and enhanced clotting. In the absence of an increase in VWF propeptide levels, this effect is considered due to decreased clearance of VWF,” the investigators wrote in the study abstract.

They noted that they saw a clinically meaningful twofold increase in both VWF and factor VIII at doses lower than 6 mg.
 

‘Super-exciting strategy’

“This trial identified a novel mechanism of action for BT200: It decreases the clearance of VWF/FVIII, which can be exploited for congenital bleeding disorders. This built a solid foundation for an ongoing basket trial in patients with von Willebrand disease or hemophilia A, which already confirms the expected effect sizes,” Dr. Kovacevic and colleagues wrote.

“I will be interested to see what the clinical side effects are, because there may be some off-target effects, but in reality it is a super-exciting strategy, and there is really a dire need for longer half-life products for these patients,” Dr. Flood said.

The study was sponsored by Band Therapeutics, a division of Guardian Therapeutics. Dr. Kovacevic and Dr. Flood reported having no conflicts of interest to disclose.

When it comes to measuring gut transit time, blue dye could be a cost-effective and simple alternative to other, more burdensome methods.

James Griffiths PhotographyiStock/Getty Images Plus

The approach, which only requires fasting followed by eating dyed food, revealed an association between microbiome composition and transit time in healthy individuals, according to authors led by Francisco Asnicar, PhD, of the University of Trento (Italy). The researchers chose the blue food coloring over carmine red dye partly because of its vegetable origin and because the blue color makes it unlikely the recipient would mistake the coloring in stool as originating from some other food, such as beetroot.

Gut motility is connected to digestion, the immune system, the endocrine system, and gut microbiota, according to the authors. For example, some have suggested that transit time may affect postprandial glycemia and lipemia through a potential effect on nutrient absorption and gut microbiome composition. “[This blue dye’s] use therefore has the potential to provide another piece of the puzzle to advance precision medicine,” the authors wrote.

Validated methods to measure transit time include scintigraphy, wireless motility capsule, radio-opaque markers and breath testing, but they require specialized equipment and staff, participants must make at least one in-person visit, and they can be expensive.
 

Transit time’s position in research

Those limitations may explain why the effect of transit time has been understudied, though it has gained momentum in recent years, according to Henrik Roager, PhD, who was asked to comment on the study. “I think it has become clear that it is probably one of the most important factors that explain the [microbiota] differences that we see from individual to individual,” said Dr. Roager, of the department of nutrition, exercise, and sports at the University of Copenhagen.

The relationship is complex, since gut microbes may be releasing metabolites that can affect motility, which in turn would affect the microbes. “The speed by which nutrients pass through a fermenter in the lab will have a huge impact on microbial physiology and metabolism. It’s basically the same principle in humans,” added Dr. Roager, who is engaged in research to identify such microbial metabolites.

To better understand those relationships will require epidemiological studies in healthy populations. Blue dye is one approach. Another is sweet corn, which individuals can obtain even more easily. Dye has one advantage in that it’s unlikely to impact transit time, while the quantity of sweet corn eaten could have an effect. “I definitely think that either this or sweet corn would be standard in many studies in the future,” said Dr. Roager.

Epidemiological studies made easier by dye or sweet corn could also reveal how diet interacts with the microbiome by including transit time as a variable. Transit time can vary from day to day, and Dr. Roager believes those variations may be linked to changes in the gut microbiome. With simpler techniques for measuring transit time, “I think we might be able to better identify effects of diets or drugs or lifestyle on the microbiome.”
 

How the blue dye fared

The researchers analyzed data from 866 twins and unrelated adults from the United States and the United Kingdom who were enrolled in the PREDICT 1 study, which quantified metabolic responses to standardized meals. Participants underwent fasting and then ate two blue muffins, along with a glass of chocolate milk, then logged the first sign of blue coloring in their stool using an app. Participants also answered a questionnaire detailing the frequency and consistency of bowel movements. The researchers also conducted sequencing of stool samples to determine microbiome profile.

There was a strong correlation between stool consistency and frequency, as well as microbial diversity and the composition of the gut microbiome. The dye measurement identified different fast and slow transit time clusters (area under the receiver operating characteristic curve, 0.82), which were associated with the composition of the gut microbiome, including species like Akkermansia muciniphila, Bacteroides species, and Alistipes species (false discovery rate–adjusted P values < .01). Transit times measured with the blue dye was a better predictor of gut function than either stool consistency and stool frequency, suggesting that the dye may be a more useful method for large cohorts of healthy individuals.

Although associations with diet and cardiometabolic factors were more modest, longer transit times appear predictive of greater visceral fat and higher postprandial responses, “which are key measures of health.”

The authors cited some limitations, including the fact that the blue-dye method has not yet been compared with other transit methodologies. However, the gut transit time in this study was found to be strongly correlated with stool consistency and frequency.

“To conclude, our findings indicate that the blue dye method is a novel, inexpensive and scalable method of gut transit assessment providing valuable gut health and metabolic insights,” they wrote. “Its wide use in both research and clinical settings could facilitate the advancement of our understanding of gut function and its determinants, as well as the complex interactions between gut physiology and health outcomes.”

The study authors received funding from a wide range of nonindustry sources. Dr. Roager had no relevant financial disclosures.

When it comes to measuring gut transit time, blue dye could be a cost-effective and simple alternative to other, more burdensome methods.

James Griffiths PhotographyiStock/Getty Images Plus

The approach, which only requires fasting followed by eating dyed food, revealed an association between microbiome composition and transit time in healthy individuals, according to authors led by Francisco Asnicar, PhD, of the University of Trento (Italy). The researchers chose the blue food coloring over carmine red dye partly because of its vegetable origin and because the blue color makes it unlikely the recipient would mistake the coloring in stool as originating from some other food, such as beetroot.

Gut motility is connected to digestion, the immune system, the endocrine system, and gut microbiota, according to the authors. For example, some have suggested that transit time may affect postprandial glycemia and lipemia through a potential effect on nutrient absorption and gut microbiome composition. “[This blue dye’s] use therefore has the potential to provide another piece of the puzzle to advance precision medicine,” the authors wrote.

Validated methods to measure transit time include scintigraphy, wireless motility capsule, radio-opaque markers and breath testing, but they require specialized equipment and staff, participants must make at least one in-person visit, and they can be expensive.
 

Transit time’s position in research

Those limitations may explain why the effect of transit time has been understudied, though it has gained momentum in recent years, according to Henrik Roager, PhD, who was asked to comment on the study. “I think it has become clear that it is probably one of the most important factors that explain the [microbiota] differences that we see from individual to individual,” said Dr. Roager, of the department of nutrition, exercise, and sports at the University of Copenhagen.

The relationship is complex, since gut microbes may be releasing metabolites that can affect motility, which in turn would affect the microbes. “The speed by which nutrients pass through a fermenter in the lab will have a huge impact on microbial physiology and metabolism. It’s basically the same principle in humans,” added Dr. Roager, who is engaged in research to identify such microbial metabolites.

To better understand those relationships will require epidemiological studies in healthy populations. Blue dye is one approach. Another is sweet corn, which individuals can obtain even more easily. Dye has one advantage in that it’s unlikely to impact transit time, while the quantity of sweet corn eaten could have an effect. “I definitely think that either this or sweet corn would be standard in many studies in the future,” said Dr. Roager.

Epidemiological studies made easier by dye or sweet corn could also reveal how diet interacts with the microbiome by including transit time as a variable. Transit time can vary from day to day, and Dr. Roager believes those variations may be linked to changes in the gut microbiome. With simpler techniques for measuring transit time, “I think we might be able to better identify effects of diets or drugs or lifestyle on the microbiome.”
 

How the blue dye fared

The researchers analyzed data from 866 twins and unrelated adults from the United States and the United Kingdom who were enrolled in the PREDICT 1 study, which quantified metabolic responses to standardized meals. Participants underwent fasting and then ate two blue muffins, along with a glass of chocolate milk, then logged the first sign of blue coloring in their stool using an app. Participants also answered a questionnaire detailing the frequency and consistency of bowel movements. The researchers also conducted sequencing of stool samples to determine microbiome profile.

There was a strong correlation between stool consistency and frequency, as well as microbial diversity and the composition of the gut microbiome. The dye measurement identified different fast and slow transit time clusters (area under the receiver operating characteristic curve, 0.82), which were associated with the composition of the gut microbiome, including species like Akkermansia muciniphila, Bacteroides species, and Alistipes species (false discovery rate–adjusted P values < .01). Transit times measured with the blue dye was a better predictor of gut function than either stool consistency and stool frequency, suggesting that the dye may be a more useful method for large cohorts of healthy individuals.

Although associations with diet and cardiometabolic factors were more modest, longer transit times appear predictive of greater visceral fat and higher postprandial responses, “which are key measures of health.”

The authors cited some limitations, including the fact that the blue-dye method has not yet been compared with other transit methodologies. However, the gut transit time in this study was found to be strongly correlated with stool consistency and frequency.

“To conclude, our findings indicate that the blue dye method is a novel, inexpensive and scalable method of gut transit assessment providing valuable gut health and metabolic insights,” they wrote. “Its wide use in both research and clinical settings could facilitate the advancement of our understanding of gut function and its determinants, as well as the complex interactions between gut physiology and health outcomes.”

The study authors received funding from a wide range of nonindustry sources. Dr. Roager had no relevant financial disclosures.

When it comes to measuring gut transit time, blue dye could be a cost-effective and simple alternative to other, more burdensome methods.

James Griffiths PhotographyiStock/Getty Images Plus

The approach, which only requires fasting followed by eating dyed food, revealed an association between microbiome composition and transit time in healthy individuals, according to authors led by Francisco Asnicar, PhD, of the University of Trento (Italy). The researchers chose the blue food coloring over carmine red dye partly because of its vegetable origin and because the blue color makes it unlikely the recipient would mistake the coloring in stool as originating from some other food, such as beetroot.

Gut motility is connected to digestion, the immune system, the endocrine system, and gut microbiota, according to the authors. For example, some have suggested that transit time may affect postprandial glycemia and lipemia through a potential effect on nutrient absorption and gut microbiome composition. “[This blue dye’s] use therefore has the potential to provide another piece of the puzzle to advance precision medicine,” the authors wrote.

Validated methods to measure transit time include scintigraphy, wireless motility capsule, radio-opaque markers and breath testing, but they require specialized equipment and staff, participants must make at least one in-person visit, and they can be expensive.
 

Transit time’s position in research

Those limitations may explain why the effect of transit time has been understudied, though it has gained momentum in recent years, according to Henrik Roager, PhD, who was asked to comment on the study. “I think it has become clear that it is probably one of the most important factors that explain the [microbiota] differences that we see from individual to individual,” said Dr. Roager, of the department of nutrition, exercise, and sports at the University of Copenhagen.

The relationship is complex, since gut microbes may be releasing metabolites that can affect motility, which in turn would affect the microbes. “The speed by which nutrients pass through a fermenter in the lab will have a huge impact on microbial physiology and metabolism. It’s basically the same principle in humans,” added Dr. Roager, who is engaged in research to identify such microbial metabolites.

To better understand those relationships will require epidemiological studies in healthy populations. Blue dye is one approach. Another is sweet corn, which individuals can obtain even more easily. Dye has one advantage in that it’s unlikely to impact transit time, while the quantity of sweet corn eaten could have an effect. “I definitely think that either this or sweet corn would be standard in many studies in the future,” said Dr. Roager.

Epidemiological studies made easier by dye or sweet corn could also reveal how diet interacts with the microbiome by including transit time as a variable. Transit time can vary from day to day, and Dr. Roager believes those variations may be linked to changes in the gut microbiome. With simpler techniques for measuring transit time, “I think we might be able to better identify effects of diets or drugs or lifestyle on the microbiome.”
 

How the blue dye fared

The researchers analyzed data from 866 twins and unrelated adults from the United States and the United Kingdom who were enrolled in the PREDICT 1 study, which quantified metabolic responses to standardized meals. Participants underwent fasting and then ate two blue muffins, along with a glass of chocolate milk, then logged the first sign of blue coloring in their stool using an app. Participants also answered a questionnaire detailing the frequency and consistency of bowel movements. The researchers also conducted sequencing of stool samples to determine microbiome profile.

There was a strong correlation between stool consistency and frequency, as well as microbial diversity and the composition of the gut microbiome. The dye measurement identified different fast and slow transit time clusters (area under the receiver operating characteristic curve, 0.82), which were associated with the composition of the gut microbiome, including species like Akkermansia muciniphila, Bacteroides species, and Alistipes species (false discovery rate–adjusted P values < .01). Transit times measured with the blue dye was a better predictor of gut function than either stool consistency and stool frequency, suggesting that the dye may be a more useful method for large cohorts of healthy individuals.

Although associations with diet and cardiometabolic factors were more modest, longer transit times appear predictive of greater visceral fat and higher postprandial responses, “which are key measures of health.”

The authors cited some limitations, including the fact that the blue-dye method has not yet been compared with other transit methodologies. However, the gut transit time in this study was found to be strongly correlated with stool consistency and frequency.

“To conclude, our findings indicate that the blue dye method is a novel, inexpensive and scalable method of gut transit assessment providing valuable gut health and metabolic insights,” they wrote. “Its wide use in both research and clinical settings could facilitate the advancement of our understanding of gut function and its determinants, as well as the complex interactions between gut physiology and health outcomes.”

The study authors received funding from a wide range of nonindustry sources. Dr. Roager had no relevant financial disclosures.

To the Editor:

Annular leukoderma, or the halo phenomenon, is a circular reaction of hypopigmentation that most commonly is observed alongside congenital nevi, acquired melanocytic nevi, blue nevi, Spitz nevi, vitiligo, and rarely melanoma.¹ There is limited literature on the mechanism of the halo phenomenon. Most of the literature proposes a T cell–mediated immune response to antigens, which causes not only surrounding pigment loss but also heralds the regression of central lesions.² Others have suggested a vascular mechanism, with blood shunted away from the lesions.³ Because guidelines discourage biopsy of typical halo nevi, it becomes important to evaluate lesions for worrisome features such as ulceration or asymmetry, especially in older patients. We present a case of a pigmented basal cell carcinoma (BCC) that exhibited the halo phenomenon. Four other cases have been described in the literature.^3-6

A 53-year-old man presented for evaluation of an asymptomatic lesion on the left side of the abdomen of approximately 8 months’ duration. He had no personal or family history of skin cancer. Physical examination revealed a central 1-cm, pink, verrucous papule surrounded by a 2×1.2-cm, depigmented, circular patch on the left side of the inferior abdomen (Figure 1). Upon questioning, the patient produced cell phone photographs of the trunk from 3 years prior, which did not show any lesions present. Full-body skin examination did not reveal any other concerning pigmented lesions. Excisional biopsy was performed due to concern for amelanotic melanoma, and histopathology revealed a superficial and pigmented BCC (Figure 2). Immunohistochemistry with Melan-A was negative for atypical melanocytes, with no uptake in the leukoderma areas.

Our patient’s final histologic diagnosis was pigmented BCC, which comprises only 6% of all BCCs.³ The proposed mechanism is that melanocytes colonize the tumor in the surrounding stroma and produce excess melanin. Basal cell carcinoma with halo phenomenon is a rare presentation. As in our case, 2 prior BCC reports also involved patients older than 50 years,^3,5 with the 2 other cases describing women in their late twenties and early thirties.^4,6 Additionally, 2 of 4 reports described patients with a history of multiple BCCs.^3,5

In summary, the seemingly benign halo phenomenon may accompany malignant processes such as nonmelanoma skin cancer. Careful consideration of lesion time course and atypia is imperative for proper clinical suspicion in such cases.

To the Editor:

Annular leukoderma, or the halo phenomenon, is a circular reaction of hypopigmentation that most commonly is observed alongside congenital nevi, acquired melanocytic nevi, blue nevi, Spitz nevi, vitiligo, and rarely melanoma.¹ There is limited literature on the mechanism of the halo phenomenon. Most of the literature proposes a T cell–mediated immune response to antigens, which causes not only surrounding pigment loss but also heralds the regression of central lesions.² Others have suggested a vascular mechanism, with blood shunted away from the lesions.³ Because guidelines discourage biopsy of typical halo nevi, it becomes important to evaluate lesions for worrisome features such as ulceration or asymmetry, especially in older patients. We present a case of a pigmented basal cell carcinoma (BCC) that exhibited the halo phenomenon. Four other cases have been described in the literature.^3-6

A 53-year-old man presented for evaluation of an asymptomatic lesion on the left side of the abdomen of approximately 8 months’ duration. He had no personal or family history of skin cancer. Physical examination revealed a central 1-cm, pink, verrucous papule surrounded by a 2×1.2-cm, depigmented, circular patch on the left side of the inferior abdomen (Figure 1). Upon questioning, the patient produced cell phone photographs of the trunk from 3 years prior, which did not show any lesions present. Full-body skin examination did not reveal any other concerning pigmented lesions. Excisional biopsy was performed due to concern for amelanotic melanoma, and histopathology revealed a superficial and pigmented BCC (Figure 2). Immunohistochemistry with Melan-A was negative for atypical melanocytes, with no uptake in the leukoderma areas.

Our patient’s final histologic diagnosis was pigmented BCC, which comprises only 6% of all BCCs.³ The proposed mechanism is that melanocytes colonize the tumor in the surrounding stroma and produce excess melanin. Basal cell carcinoma with halo phenomenon is a rare presentation. As in our case, 2 prior BCC reports also involved patients older than 50 years,^3,5 with the 2 other cases describing women in their late twenties and early thirties.^4,6 Additionally, 2 of 4 reports described patients with a history of multiple BCCs.^3,5

In summary, the seemingly benign halo phenomenon may accompany malignant processes such as nonmelanoma skin cancer. Careful consideration of lesion time course and atypia is imperative for proper clinical suspicion in such cases.

To the Editor:

Annular leukoderma, or the halo phenomenon, is a circular reaction of hypopigmentation that most commonly is observed alongside congenital nevi, acquired melanocytic nevi, blue nevi, Spitz nevi, vitiligo, and rarely melanoma.¹ There is limited literature on the mechanism of the halo phenomenon. Most of the literature proposes a T cell–mediated immune response to antigens, which causes not only surrounding pigment loss but also heralds the regression of central lesions.² Others have suggested a vascular mechanism, with blood shunted away from the lesions.³ Because guidelines discourage biopsy of typical halo nevi, it becomes important to evaluate lesions for worrisome features such as ulceration or asymmetry, especially in older patients. We present a case of a pigmented basal cell carcinoma (BCC) that exhibited the halo phenomenon. Four other cases have been described in the literature.^3-6

A 53-year-old man presented for evaluation of an asymptomatic lesion on the left side of the abdomen of approximately 8 months’ duration. He had no personal or family history of skin cancer. Physical examination revealed a central 1-cm, pink, verrucous papule surrounded by a 2×1.2-cm, depigmented, circular patch on the left side of the inferior abdomen (Figure 1). Upon questioning, the patient produced cell phone photographs of the trunk from 3 years prior, which did not show any lesions present. Full-body skin examination did not reveal any other concerning pigmented lesions. Excisional biopsy was performed due to concern for amelanotic melanoma, and histopathology revealed a superficial and pigmented BCC (Figure 2). Immunohistochemistry with Melan-A was negative for atypical melanocytes, with no uptake in the leukoderma areas.

Our patient’s final histologic diagnosis was pigmented BCC, which comprises only 6% of all BCCs.³ The proposed mechanism is that melanocytes colonize the tumor in the surrounding stroma and produce excess melanin. Basal cell carcinoma with halo phenomenon is a rare presentation. As in our case, 2 prior BCC reports also involved patients older than 50 years,^3,5 with the 2 other cases describing women in their late twenties and early thirties.^4,6 Additionally, 2 of 4 reports described patients with a history of multiple BCCs.^3,5

In summary, the seemingly benign halo phenomenon may accompany malignant processes such as nonmelanoma skin cancer. Careful consideration of lesion time course and atypia is imperative for proper clinical suspicion in such cases.

As dermatology residents, we have a lot on our plates. With so many diagnoses to learn and treatments to understand, the sheer volume of knowledge we are expected to be familiar with sometimes can be overwhelming. The thought of adding yet another thing to the list of many things we already need to know—least of all a topic such as dermatoethics—may be unappealing. This article will discuss the importance of ethics training in dermatology residency as well as provide helpful resources for how this training can be achieved.

Professionalism as a Core Competency

The Accreditation Council for Graduate Medical Education (ACGME) considers professionalism as 1 of its 6 core competencies.¹ These competencies provide a conceptual framework detailing the domains physicians should be proficient in before they can enter autonomous practice. When it comes to professionalism, residents are expected to demonstrate compassion, integrity, and respect for others; honesty with patients; respect for patient confidentiality and autonomy; appropriate relationships with patients; accountability to patients, society, and the profession; and a sensitivity and responsiveness to diverse patient population.¹

The ACGME milestones are intended to assess resident development within the 6 competencies with more specific parameters for evaluation.² Those pertaining to professionalism evaluate a resident’s ability to demonstrate professional behavior, an understanding of ethical principles, accountability, and conscientiousness, as well as self-awareness and the ability to seek help for personal or professional well-being. The crux of the kinds of activities that constitute acquisition of these professional skills are specialty specific. The ACGME ultimately believes that having a working knowledge of professionalism and ethical principles prepares residents for practicing medicine in the real world. Because of these requirements, residency programs are expected to provide resources for residents to explore ethical problems faced by dermatologists.

Beyond “Passing” Residency

The reality is that learning about medical ethics and practicing professional behavior is not just about ticking boxes to get ACGME accreditation or to “pass” residency. The data suggest that having a strong foundation in these principles is good for overall personal well-being, job satisfaction, and patient care. Studies have shown that unprofessional behavior in medical school is correlated to disciplinary action by state licensing boards against practicing physicians.^3,4 In fact, a study found that in one cohort of physicians (N=68), 95% of disciplinary actions were for lapses in professionalism, which included activities such as sexual misconduct and inappropriate prescribing.⁴ Behaving appropriately protects your license to practice medicine.

Thinking through these problematic ethical scenarios also goes beyond coming up with the right answer. Exploring ethical conundrums is thought to develop analytical skills that can help one navigate future tricky situations that can be morally distressing and can lead to burnout. Introspection and self-awareness coupled with these skills ideally will help physicians think through sensitive and difficult situations with the courage to hold true to their convictions and ultimately uphold the professionalism of the specialty.⁵

Self-awareness has the additional bonus of empowering physicians to acknowledge personal and professional limitations with the goal of seeking help when it is needed before it is too late. It comes as no surprise that how we feel as physicians directly impacts how we treat our patients. One study found that depressed residents were more than 6 times more likely to make medication errors compared to nondepressed colleagues.⁶ Regularly taking stock of our professional and personal reserves can go a long way to improving overall well-being.

Resources for Dermatoethics Training

The best starting point for developing a robust dermatoethics curriculum is the material provided by the American Board of Dermatology, which is available online.⁷ An ad hoc subcommittee of the American Board of Dermatology composed of experts in dermatoethics and resident education reviewed relevant ethics literature and identified 6 core domains considered fundamental to dermatology resident education in ethics and professionalism.⁸ This team also provided a thorough list of relevant background readings for each topic. To cover pertinent material, the subcommittee recommended a 60-minute teaching session every other month with the intent of covering all the material over a 3-year period. If your program directors are not aware of this great resource and you feel your own ethics training may be lacking, bringing this up as a template might be helpful. A detailed description of an innovative dermatoethics curriculum organized at the Department of Dermatology at the Warren Alpert Medical School of Brown University (Providence, Rhode Island) in 2001 also may serve as a guide for programs hoping to design their own approach.⁵

For those interested in self-study, there is an excellent text dedicated to dermatoethics, which is aptly entitled Dermatoethics: Contemporary Ethics and Professionalism in Dermatology.⁹ This book offers superb case-based discussions on a wide range of ethical quandaries that dermatologists may face, ranging from unsolicited dermatologic advice (eg, Is it wrong to tell the person next to you in the grocery store that they might have a melanoma?) to research and publication ethics. This text provides a toolkit for handling tough situations in the clinic and beyond. The Journal of the American Academy of Dermatology publishes an Ethics Journal Club for which contributors can submit real-life practical ethical dilemmas, and the journal solicits a resolution or response from a dermatoethicist.

Additionally, a pilot curriculum project out of the University of Utah (Salt Lake City, Utah), of which I am a team member, currently is designing and testing several dermatoethics PowerPoint modules with the intention of making this material widely available through medical education portals.

The Hidden Curriculum

A formal curriculum can only provide so much when it comes to ethics training. In truth, much of what we learn as ethically minded dermatologists comes from our day-to-day practice.¹⁰ Paying attention to the more informal curriculum that we are immersed in during routine as well as unusual encounters also is important for achieving milestones. Teaching moments for thinking through ethical dilemmas abound, and this approach easily can be incorporated into routine workflow.¹¹ Next time you encounter an ethical situation that gives you pause (eg, Can I biopsy an intubated patient without getting appropriate consent?), talk it through with your supervisor. Gems of autonomous practice often can be mined from these off-the-cuff conversations.

Can Professionalism Be Taught?

Finally, it is worth mentioning that while the number of resources available to dermatology residents for honing their ethics skills is increasing, ways of measuring the impact of this additional training in vivo are not.¹² There are no good tools available to determine how ethics training influences resident behaviors. Similarly, there is no good evidence for what constitutes the most effective method for teaching medical ethics to trainees. It is a growing field with lots of room for more robust research. For now, the overall goal of a dermatoethics curriculum is to provide a mix of curriculum opportunities, ranging from formal lectures and readings to more informal conversations, with the hope of providing residents a toolbox for dealing with ethical dilemmas and a working knowledge of professionalism.

Final Thoughts

There are several resources available for dermatology programs to provide quality dermatoethics training to their residents. These can be mixed and matched to create a tailored formal curriculum alongside the more informal ethics training that happens in the clinic and on the wards. Providing this education is about more than just fulfilling accreditation requirements. Understanding ethical principles and how they can be applied to navigate sensitive situations is ultimately good for both professional and personal well-being.

As dermatology residents, we have a lot on our plates. With so many diagnoses to learn and treatments to understand, the sheer volume of knowledge we are expected to be familiar with sometimes can be overwhelming. The thought of adding yet another thing to the list of many things we already need to know—least of all a topic such as dermatoethics—may be unappealing. This article will discuss the importance of ethics training in dermatology residency as well as provide helpful resources for how this training can be achieved.

Professionalism as a Core Competency

The Accreditation Council for Graduate Medical Education (ACGME) considers professionalism as 1 of its 6 core competencies.¹ These competencies provide a conceptual framework detailing the domains physicians should be proficient in before they can enter autonomous practice. When it comes to professionalism, residents are expected to demonstrate compassion, integrity, and respect for others; honesty with patients; respect for patient confidentiality and autonomy; appropriate relationships with patients; accountability to patients, society, and the profession; and a sensitivity and responsiveness to diverse patient population.¹

The ACGME milestones are intended to assess resident development within the 6 competencies with more specific parameters for evaluation.² Those pertaining to professionalism evaluate a resident’s ability to demonstrate professional behavior, an understanding of ethical principles, accountability, and conscientiousness, as well as self-awareness and the ability to seek help for personal or professional well-being. The crux of the kinds of activities that constitute acquisition of these professional skills are specialty specific. The ACGME ultimately believes that having a working knowledge of professionalism and ethical principles prepares residents for practicing medicine in the real world. Because of these requirements, residency programs are expected to provide resources for residents to explore ethical problems faced by dermatologists.

Beyond “Passing” Residency

The reality is that learning about medical ethics and practicing professional behavior is not just about ticking boxes to get ACGME accreditation or to “pass” residency. The data suggest that having a strong foundation in these principles is good for overall personal well-being, job satisfaction, and patient care. Studies have shown that unprofessional behavior in medical school is correlated to disciplinary action by state licensing boards against practicing physicians.^3,4 In fact, a study found that in one cohort of physicians (N=68), 95% of disciplinary actions were for lapses in professionalism, which included activities such as sexual misconduct and inappropriate prescribing.⁴ Behaving appropriately protects your license to practice medicine.

Thinking through these problematic ethical scenarios also goes beyond coming up with the right answer. Exploring ethical conundrums is thought to develop analytical skills that can help one navigate future tricky situations that can be morally distressing and can lead to burnout. Introspection and self-awareness coupled with these skills ideally will help physicians think through sensitive and difficult situations with the courage to hold true to their convictions and ultimately uphold the professionalism of the specialty.⁵

Self-awareness has the additional bonus of empowering physicians to acknowledge personal and professional limitations with the goal of seeking help when it is needed before it is too late. It comes as no surprise that how we feel as physicians directly impacts how we treat our patients. One study found that depressed residents were more than 6 times more likely to make medication errors compared to nondepressed colleagues.⁶ Regularly taking stock of our professional and personal reserves can go a long way to improving overall well-being.

Resources for Dermatoethics Training

The best starting point for developing a robust dermatoethics curriculum is the material provided by the American Board of Dermatology, which is available online.⁷ An ad hoc subcommittee of the American Board of Dermatology composed of experts in dermatoethics and resident education reviewed relevant ethics literature and identified 6 core domains considered fundamental to dermatology resident education in ethics and professionalism.⁸ This team also provided a thorough list of relevant background readings for each topic. To cover pertinent material, the subcommittee recommended a 60-minute teaching session every other month with the intent of covering all the material over a 3-year period. If your program directors are not aware of this great resource and you feel your own ethics training may be lacking, bringing this up as a template might be helpful. A detailed description of an innovative dermatoethics curriculum organized at the Department of Dermatology at the Warren Alpert Medical School of Brown University (Providence, Rhode Island) in 2001 also may serve as a guide for programs hoping to design their own approach.⁵

For those interested in self-study, there is an excellent text dedicated to dermatoethics, which is aptly entitled Dermatoethics: Contemporary Ethics and Professionalism in Dermatology.⁹ This book offers superb case-based discussions on a wide range of ethical quandaries that dermatologists may face, ranging from unsolicited dermatologic advice (eg, Is it wrong to tell the person next to you in the grocery store that they might have a melanoma?) to research and publication ethics. This text provides a toolkit for handling tough situations in the clinic and beyond. The Journal of the American Academy of Dermatology publishes an Ethics Journal Club for which contributors can submit real-life practical ethical dilemmas, and the journal solicits a resolution or response from a dermatoethicist.

Additionally, a pilot curriculum project out of the University of Utah (Salt Lake City, Utah), of which I am a team member, currently is designing and testing several dermatoethics PowerPoint modules with the intention of making this material widely available through medical education portals.

The Hidden Curriculum

A formal curriculum can only provide so much when it comes to ethics training. In truth, much of what we learn as ethically minded dermatologists comes from our day-to-day practice.¹⁰ Paying attention to the more informal curriculum that we are immersed in during routine as well as unusual encounters also is important for achieving milestones. Teaching moments for thinking through ethical dilemmas abound, and this approach easily can be incorporated into routine workflow.¹¹ Next time you encounter an ethical situation that gives you pause (eg, Can I biopsy an intubated patient without getting appropriate consent?), talk it through with your supervisor. Gems of autonomous practice often can be mined from these off-the-cuff conversations.

Can Professionalism Be Taught?

Finally, it is worth mentioning that while the number of resources available to dermatology residents for honing their ethics skills is increasing, ways of measuring the impact of this additional training in vivo are not.¹² There are no good tools available to determine how ethics training influences resident behaviors. Similarly, there is no good evidence for what constitutes the most effective method for teaching medical ethics to trainees. It is a growing field with lots of room for more robust research. For now, the overall goal of a dermatoethics curriculum is to provide a mix of curriculum opportunities, ranging from formal lectures and readings to more informal conversations, with the hope of providing residents a toolbox for dealing with ethical dilemmas and a working knowledge of professionalism.

Final Thoughts

There are several resources available for dermatology programs to provide quality dermatoethics training to their residents. These can be mixed and matched to create a tailored formal curriculum alongside the more informal ethics training that happens in the clinic and on the wards. Providing this education is about more than just fulfilling accreditation requirements. Understanding ethical principles and how they can be applied to navigate sensitive situations is ultimately good for both professional and personal well-being.

As dermatology residents, we have a lot on our plates. With so many diagnoses to learn and treatments to understand, the sheer volume of knowledge we are expected to be familiar with sometimes can be overwhelming. The thought of adding yet another thing to the list of many things we already need to know—least of all a topic such as dermatoethics—may be unappealing. This article will discuss the importance of ethics training in dermatology residency as well as provide helpful resources for how this training can be achieved.

Professionalism as a Core Competency

The Accreditation Council for Graduate Medical Education (ACGME) considers professionalism as 1 of its 6 core competencies.¹ These competencies provide a conceptual framework detailing the domains physicians should be proficient in before they can enter autonomous practice. When it comes to professionalism, residents are expected to demonstrate compassion, integrity, and respect for others; honesty with patients; respect for patient confidentiality and autonomy; appropriate relationships with patients; accountability to patients, society, and the profession; and a sensitivity and responsiveness to diverse patient population.¹

The ACGME milestones are intended to assess resident development within the 6 competencies with more specific parameters for evaluation.² Those pertaining to professionalism evaluate a resident’s ability to demonstrate professional behavior, an understanding of ethical principles, accountability, and conscientiousness, as well as self-awareness and the ability to seek help for personal or professional well-being. The crux of the kinds of activities that constitute acquisition of these professional skills are specialty specific. The ACGME ultimately believes that having a working knowledge of professionalism and ethical principles prepares residents for practicing medicine in the real world. Because of these requirements, residency programs are expected to provide resources for residents to explore ethical problems faced by dermatologists.

Beyond “Passing” Residency

The reality is that learning about medical ethics and practicing professional behavior is not just about ticking boxes to get ACGME accreditation or to “pass” residency. The data suggest that having a strong foundation in these principles is good for overall personal well-being, job satisfaction, and patient care. Studies have shown that unprofessional behavior in medical school is correlated to disciplinary action by state licensing boards against practicing physicians.^3,4 In fact, a study found that in one cohort of physicians (N=68), 95% of disciplinary actions were for lapses in professionalism, which included activities such as sexual misconduct and inappropriate prescribing.⁴ Behaving appropriately protects your license to practice medicine.

Thinking through these problematic ethical scenarios also goes beyond coming up with the right answer. Exploring ethical conundrums is thought to develop analytical skills that can help one navigate future tricky situations that can be morally distressing and can lead to burnout. Introspection and self-awareness coupled with these skills ideally will help physicians think through sensitive and difficult situations with the courage to hold true to their convictions and ultimately uphold the professionalism of the specialty.⁵

Self-awareness has the additional bonus of empowering physicians to acknowledge personal and professional limitations with the goal of seeking help when it is needed before it is too late. It comes as no surprise that how we feel as physicians directly impacts how we treat our patients. One study found that depressed residents were more than 6 times more likely to make medication errors compared to nondepressed colleagues.⁶ Regularly taking stock of our professional and personal reserves can go a long way to improving overall well-being.

Resources for Dermatoethics Training

The best starting point for developing a robust dermatoethics curriculum is the material provided by the American Board of Dermatology, which is available online.⁷ An ad hoc subcommittee of the American Board of Dermatology composed of experts in dermatoethics and resident education reviewed relevant ethics literature and identified 6 core domains considered fundamental to dermatology resident education in ethics and professionalism.⁸ This team also provided a thorough list of relevant background readings for each topic. To cover pertinent material, the subcommittee recommended a 60-minute teaching session every other month with the intent of covering all the material over a 3-year period. If your program directors are not aware of this great resource and you feel your own ethics training may be lacking, bringing this up as a template might be helpful. A detailed description of an innovative dermatoethics curriculum organized at the Department of Dermatology at the Warren Alpert Medical School of Brown University (Providence, Rhode Island) in 2001 also may serve as a guide for programs hoping to design their own approach.⁵

For those interested in self-study, there is an excellent text dedicated to dermatoethics, which is aptly entitled Dermatoethics: Contemporary Ethics and Professionalism in Dermatology.⁹ This book offers superb case-based discussions on a wide range of ethical quandaries that dermatologists may face, ranging from unsolicited dermatologic advice (eg, Is it wrong to tell the person next to you in the grocery store that they might have a melanoma?) to research and publication ethics. This text provides a toolkit for handling tough situations in the clinic and beyond. The Journal of the American Academy of Dermatology publishes an Ethics Journal Club for which contributors can submit real-life practical ethical dilemmas, and the journal solicits a resolution or response from a dermatoethicist.

Additionally, a pilot curriculum project out of the University of Utah (Salt Lake City, Utah), of which I am a team member, currently is designing and testing several dermatoethics PowerPoint modules with the intention of making this material widely available through medical education portals.

The Hidden Curriculum

A formal curriculum can only provide so much when it comes to ethics training. In truth, much of what we learn as ethically minded dermatologists comes from our day-to-day practice.¹⁰ Paying attention to the more informal curriculum that we are immersed in during routine as well as unusual encounters also is important for achieving milestones. Teaching moments for thinking through ethical dilemmas abound, and this approach easily can be incorporated into routine workflow.¹¹ Next time you encounter an ethical situation that gives you pause (eg, Can I biopsy an intubated patient without getting appropriate consent?), talk it through with your supervisor. Gems of autonomous practice often can be mined from these off-the-cuff conversations.

Can Professionalism Be Taught?

Finally, it is worth mentioning that while the number of resources available to dermatology residents for honing their ethics skills is increasing, ways of measuring the impact of this additional training in vivo are not.¹² There are no good tools available to determine how ethics training influences resident behaviors. Similarly, there is no good evidence for what constitutes the most effective method for teaching medical ethics to trainees. It is a growing field with lots of room for more robust research. For now, the overall goal of a dermatoethics curriculum is to provide a mix of curriculum opportunities, ranging from formal lectures and readings to more informal conversations, with the hope of providing residents a toolbox for dealing with ethical dilemmas and a working knowledge of professionalism.

Final Thoughts

There are several resources available for dermatology programs to provide quality dermatoethics training to their residents. These can be mixed and matched to create a tailored formal curriculum alongside the more informal ethics training that happens in the clinic and on the wards. Providing this education is about more than just fulfilling accreditation requirements. Understanding ethical principles and how they can be applied to navigate sensitive situations is ultimately good for both professional and personal well-being.

Type 2 diabetes patients hospitalized for worsening heart failure who took sotagliflozin remained alive and out of the hospital for more days after discharge than ones who took placebo, according to a new analysis.

The outcome measure –days alive and out of the hospital – may be a meaningful, patient-centered way of capturing disease burden, the researchers wrote in their paper, published in Annals of Internal Medicine.

“The question was: Can we keep patients alive and out of the hospital for any reason, accounting for the duration of each hospitalization?” author Michael Szarek, PhD, a visiting professor in the division of cardiology at the University of Colorado at Denver, Aurora, said in an interview.

“For every 100 days of follow-up, patients in the sotagliflozin group were alive and out of the hospital 3% more days in relative terms or 2.9 days in absolute terms than those in the placebo group (91.8 vs. 88.9 days),” the researchers reported in their analysis of data from the SOLOIST-WHF trial.

“If you translate that to over the course of a year, that’s more than 10 days,” said Dr. Szarek, who is also a faculty member of CPC Clinical Research, an academic research organization affiliated with the University of Colorado.

Most patients in both groups survived to the end of the study without hospitalization, according to the paper.

Sotagliflozin, a sodium-glucose cotransporter 1 and SGLT2 inhibitor, is not approved in the United States. In 2019, the Food and Drug Administration rejected sotagliflozin as an adjunct to insulin for the treatment of type 1 diabetes after members of an advisory committee expressed concerns about an increased risk for diabetic ketoacidosis with the drug.
 

Methods and results

To examine whether sotagliflozin increased days alive and out of the hospital in the SOLOIST-WHF trial, Dr. Szarek and colleagues analyzed data from this randomized, double-blind, placebo-controlled study. The trial’s primary results were published in the New England Journal of Medicine in January 2021. Researchers conducted SOLOIST-WHF at more than 300 sites in 32 countries. The trial included 1,222 patients with type 2 diabetes and reduced or preserved ejection fraction who were recently hospitalized for worsening heart failure.

In the new analysis the researchers looked at hospitalizations for any reason and the duration of hospital admissions after randomization. They analyzed days alive and out of the hospital using prespecified models.

Similar proportions of patients who received sotagliflozin and placebo were hospitalized at least once (38.5% vs. 41.4%) during a median follow-up of 9 months. Fewer patients who received sotagliflozin were hospitalized more than once (16.3% vs. 22.1%). In all, 64 patients in the sotagliflozin group and 76 patients in the placebo group died.

The reason for each hospitalization was unspecified, except for cases of heart failure, the authors noted. About 62% of hospitalizations during the trial were for reasons other than heart failure.
 

Outside expert cites similarities to initial trial

The results for days alive and out of the hospital are “not particularly surprising given the previous publication” of the trial’s primary results, but the new analysis provides a “different view of outcomes that might be clinically meaningful for patients,” commented Frank Brosius, MD, a professor of medicine at the University of Arizona, Tucson.

The SOLOIST-WHF trial indicated that doctors may be able to effectively treat patients with relatively new heart failure with sotagliflozin as long as patients are relatively stable, said Dr. Brosius, who coauthored an editorial in the New England Journal of Medicine that accompanied the initial results from the SOLOIST-WHF trial. It appears that previously reported benefits with regard to heart failure outcomes “showed up in these other indicators” in the secondary analysis.

Still, the effect sizes in the new analysis were relatively small and “probably more studies will be necessary” to examine these end points, he added.

SOLOIST-WHF was funded by Sanofi at initiation and by Lexicon Pharmaceuticals at completion. Dr. Szarek disclosed grants from Lexicon and grants and personal fees from Sanofi, as well as personal fees from other companies. His coauthors included employees of Lexicon and other researchers with financial ties to Lexicon and other pharmaceutical companies. Dr. Brosius disclosed personal fees from the American Diabetes Association and is a member of the Diabetic Kidney Disease Collaborative task force for the American Society of Nephrology that is broadly advocating the use of SGLT2 inhibitors by patients with diabetic kidney diseases. He also has participated in an advisory group for treatment of diabetic kidney disease for Gilead.

[email protected]

Type 2 diabetes patients hospitalized for worsening heart failure who took sotagliflozin remained alive and out of the hospital for more days after discharge than ones who took placebo, according to a new analysis.

The outcome measure –days alive and out of the hospital – may be a meaningful, patient-centered way of capturing disease burden, the researchers wrote in their paper, published in Annals of Internal Medicine.

“The question was: Can we keep patients alive and out of the hospital for any reason, accounting for the duration of each hospitalization?” author Michael Szarek, PhD, a visiting professor in the division of cardiology at the University of Colorado at Denver, Aurora, said in an interview.

“For every 100 days of follow-up, patients in the sotagliflozin group were alive and out of the hospital 3% more days in relative terms or 2.9 days in absolute terms than those in the placebo group (91.8 vs. 88.9 days),” the researchers reported in their analysis of data from the SOLOIST-WHF trial.

“If you translate that to over the course of a year, that’s more than 10 days,” said Dr. Szarek, who is also a faculty member of CPC Clinical Research, an academic research organization affiliated with the University of Colorado.

Most patients in both groups survived to the end of the study without hospitalization, according to the paper.

Sotagliflozin, a sodium-glucose cotransporter 1 and SGLT2 inhibitor, is not approved in the United States. In 2019, the Food and Drug Administration rejected sotagliflozin as an adjunct to insulin for the treatment of type 1 diabetes after members of an advisory committee expressed concerns about an increased risk for diabetic ketoacidosis with the drug.
 

Methods and results

To examine whether sotagliflozin increased days alive and out of the hospital in the SOLOIST-WHF trial, Dr. Szarek and colleagues analyzed data from this randomized, double-blind, placebo-controlled study. The trial’s primary results were published in the New England Journal of Medicine in January 2021. Researchers conducted SOLOIST-WHF at more than 300 sites in 32 countries. The trial included 1,222 patients with type 2 diabetes and reduced or preserved ejection fraction who were recently hospitalized for worsening heart failure.

In the new analysis the researchers looked at hospitalizations for any reason and the duration of hospital admissions after randomization. They analyzed days alive and out of the hospital using prespecified models.

Similar proportions of patients who received sotagliflozin and placebo were hospitalized at least once (38.5% vs. 41.4%) during a median follow-up of 9 months. Fewer patients who received sotagliflozin were hospitalized more than once (16.3% vs. 22.1%). In all, 64 patients in the sotagliflozin group and 76 patients in the placebo group died.

The reason for each hospitalization was unspecified, except for cases of heart failure, the authors noted. About 62% of hospitalizations during the trial were for reasons other than heart failure.
 

Outside expert cites similarities to initial trial

The results for days alive and out of the hospital are “not particularly surprising given the previous publication” of the trial’s primary results, but the new analysis provides a “different view of outcomes that might be clinically meaningful for patients,” commented Frank Brosius, MD, a professor of medicine at the University of Arizona, Tucson.

The SOLOIST-WHF trial indicated that doctors may be able to effectively treat patients with relatively new heart failure with sotagliflozin as long as patients are relatively stable, said Dr. Brosius, who coauthored an editorial in the New England Journal of Medicine that accompanied the initial results from the SOLOIST-WHF trial. It appears that previously reported benefits with regard to heart failure outcomes “showed up in these other indicators” in the secondary analysis.

Still, the effect sizes in the new analysis were relatively small and “probably more studies will be necessary” to examine these end points, he added.

SOLOIST-WHF was funded by Sanofi at initiation and by Lexicon Pharmaceuticals at completion. Dr. Szarek disclosed grants from Lexicon and grants and personal fees from Sanofi, as well as personal fees from other companies. His coauthors included employees of Lexicon and other researchers with financial ties to Lexicon and other pharmaceutical companies. Dr. Brosius disclosed personal fees from the American Diabetes Association and is a member of the Diabetic Kidney Disease Collaborative task force for the American Society of Nephrology that is broadly advocating the use of SGLT2 inhibitors by patients with diabetic kidney diseases. He also has participated in an advisory group for treatment of diabetic kidney disease for Gilead.

[email protected]

Type 2 diabetes patients hospitalized for worsening heart failure who took sotagliflozin remained alive and out of the hospital for more days after discharge than ones who took placebo, according to a new analysis.

The outcome measure –days alive and out of the hospital – may be a meaningful, patient-centered way of capturing disease burden, the researchers wrote in their paper, published in Annals of Internal Medicine.

“The question was: Can we keep patients alive and out of the hospital for any reason, accounting for the duration of each hospitalization?” author Michael Szarek, PhD, a visiting professor in the division of cardiology at the University of Colorado at Denver, Aurora, said in an interview.

“For every 100 days of follow-up, patients in the sotagliflozin group were alive and out of the hospital 3% more days in relative terms or 2.9 days in absolute terms than those in the placebo group (91.8 vs. 88.9 days),” the researchers reported in their analysis of data from the SOLOIST-WHF trial.

“If you translate that to over the course of a year, that’s more than 10 days,” said Dr. Szarek, who is also a faculty member of CPC Clinical Research, an academic research organization affiliated with the University of Colorado.

Most patients in both groups survived to the end of the study without hospitalization, according to the paper.

Sotagliflozin, a sodium-glucose cotransporter 1 and SGLT2 inhibitor, is not approved in the United States. In 2019, the Food and Drug Administration rejected sotagliflozin as an adjunct to insulin for the treatment of type 1 diabetes after members of an advisory committee expressed concerns about an increased risk for diabetic ketoacidosis with the drug.
 

Methods and results

To examine whether sotagliflozin increased days alive and out of the hospital in the SOLOIST-WHF trial, Dr. Szarek and colleagues analyzed data from this randomized, double-blind, placebo-controlled study. The trial’s primary results were published in the New England Journal of Medicine in January 2021. Researchers conducted SOLOIST-WHF at more than 300 sites in 32 countries. The trial included 1,222 patients with type 2 diabetes and reduced or preserved ejection fraction who were recently hospitalized for worsening heart failure.

In the new analysis the researchers looked at hospitalizations for any reason and the duration of hospital admissions after randomization. They analyzed days alive and out of the hospital using prespecified models.

Similar proportions of patients who received sotagliflozin and placebo were hospitalized at least once (38.5% vs. 41.4%) during a median follow-up of 9 months. Fewer patients who received sotagliflozin were hospitalized more than once (16.3% vs. 22.1%). In all, 64 patients in the sotagliflozin group and 76 patients in the placebo group died.

The reason for each hospitalization was unspecified, except for cases of heart failure, the authors noted. About 62% of hospitalizations during the trial were for reasons other than heart failure.
 

Outside expert cites similarities to initial trial

The results for days alive and out of the hospital are “not particularly surprising given the previous publication” of the trial’s primary results, but the new analysis provides a “different view of outcomes that might be clinically meaningful for patients,” commented Frank Brosius, MD, a professor of medicine at the University of Arizona, Tucson.

The SOLOIST-WHF trial indicated that doctors may be able to effectively treat patients with relatively new heart failure with sotagliflozin as long as patients are relatively stable, said Dr. Brosius, who coauthored an editorial in the New England Journal of Medicine that accompanied the initial results from the SOLOIST-WHF trial. It appears that previously reported benefits with regard to heart failure outcomes “showed up in these other indicators” in the secondary analysis.

Still, the effect sizes in the new analysis were relatively small and “probably more studies will be necessary” to examine these end points, he added.

SOLOIST-WHF was funded by Sanofi at initiation and by Lexicon Pharmaceuticals at completion. Dr. Szarek disclosed grants from Lexicon and grants and personal fees from Sanofi, as well as personal fees from other companies. His coauthors included employees of Lexicon and other researchers with financial ties to Lexicon and other pharmaceutical companies. Dr. Brosius disclosed personal fees from the American Diabetes Association and is a member of the Diabetic Kidney Disease Collaborative task force for the American Society of Nephrology that is broadly advocating the use of SGLT2 inhibitors by patients with diabetic kidney diseases. He also has participated in an advisory group for treatment of diabetic kidney disease for Gilead.

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Tardive dyskinesia is a movement disorder characterized by involuntary and repetitive movements of the tongue, lips, face, trunk, and extremities. It is caused by the use of dopamine receptor-blocking drugs, most often antipsychotics, but has also been associated with treatments for some gastrointestinal disorders. 

Dr. Peter LeWitt, Sastry Foundation Endowed Chair in Neurology at Wayne State University School of Medicine in Detroit, MI, walks through some of the known causes of tardive dyskinesia as well as steps physicians can take in making a differential diagnosis. 

Next, Dr. LeWitt dives into the role of targeted therapy in the management of tardive dyskinesia. VMAT2 (vesicular monoamine transporter type 2) inhibitors are emerging as a treatment class of choice that help suppress tardive dyskinesia symptoms by depleting presynaptic dopamine, while other patients may benefit more from benzodiazepines, botulinum toxin, or deep brain stimulation. 

--

Dr. Peter LeWitt, Sastry Foundation Endowed Chair in Neurology at Wayne State University School of Medicine in Detroit, MI.

Peter A. LeWitt reports advisory roles for: Abide, Acorda Therapeutics, Adamas, Biogen, Cavion, Denali, Intec Pharma, Jazz Pharmaceuticals, Lundbeck, Neurocrine, Mitsubishi NeuroDerm Ltd, Prexton, Revance, Sage, and US WorldMeds.

Lecture fees from: Acorda, American Academy of Neurology, Kyowa Hakko Kirin, and US WorldMeds.

Research grant support from: Abide, Acorda, Amneal, Lundbeck, Michael J. Fox Foundation for Parkinson's Research, Mitsubishi NeuroDerm Ltd, Parkinson Study Group; Pharma 2B, Revance, Hoffmann-La Roche; Sunovion, Sun Pharma, and US WorldMeds.

Tardive dyskinesia is a movement disorder characterized by involuntary and repetitive movements of the tongue, lips, face, trunk, and extremities. It is caused by the use of dopamine receptor-blocking drugs, most often antipsychotics, but has also been associated with treatments for some gastrointestinal disorders. 

Dr. Peter LeWitt, Sastry Foundation Endowed Chair in Neurology at Wayne State University School of Medicine in Detroit, MI, walks through some of the known causes of tardive dyskinesia as well as steps physicians can take in making a differential diagnosis. 

Next, Dr. LeWitt dives into the role of targeted therapy in the management of tardive dyskinesia. VMAT2 (vesicular monoamine transporter type 2) inhibitors are emerging as a treatment class of choice that help suppress tardive dyskinesia symptoms by depleting presynaptic dopamine, while other patients may benefit more from benzodiazepines, botulinum toxin, or deep brain stimulation. 

--

Dr. Peter LeWitt, Sastry Foundation Endowed Chair in Neurology at Wayne State University School of Medicine in Detroit, MI.

Peter A. LeWitt reports advisory roles for: Abide, Acorda Therapeutics, Adamas, Biogen, Cavion, Denali, Intec Pharma, Jazz Pharmaceuticals, Lundbeck, Neurocrine, Mitsubishi NeuroDerm Ltd, Prexton, Revance, Sage, and US WorldMeds.

Lecture fees from: Acorda, American Academy of Neurology, Kyowa Hakko Kirin, and US WorldMeds.

Research grant support from: Abide, Acorda, Amneal, Lundbeck, Michael J. Fox Foundation for Parkinson's Research, Mitsubishi NeuroDerm Ltd, Parkinson Study Group; Pharma 2B, Revance, Hoffmann-La Roche; Sunovion, Sun Pharma, and US WorldMeds.

Tardive dyskinesia is a movement disorder characterized by involuntary and repetitive movements of the tongue, lips, face, trunk, and extremities. It is caused by the use of dopamine receptor-blocking drugs, most often antipsychotics, but has also been associated with treatments for some gastrointestinal disorders. 

Dr. Peter LeWitt, Sastry Foundation Endowed Chair in Neurology at Wayne State University School of Medicine in Detroit, MI, walks through some of the known causes of tardive dyskinesia as well as steps physicians can take in making a differential diagnosis. 

Next, Dr. LeWitt dives into the role of targeted therapy in the management of tardive dyskinesia. VMAT2 (vesicular monoamine transporter type 2) inhibitors are emerging as a treatment class of choice that help suppress tardive dyskinesia symptoms by depleting presynaptic dopamine, while other patients may benefit more from benzodiazepines, botulinum toxin, or deep brain stimulation. 

--

Dr. Peter LeWitt, Sastry Foundation Endowed Chair in Neurology at Wayne State University School of Medicine in Detroit, MI.

Peter A. LeWitt reports advisory roles for: Abide, Acorda Therapeutics, Adamas, Biogen, Cavion, Denali, Intec Pharma, Jazz Pharmaceuticals, Lundbeck, Neurocrine, Mitsubishi NeuroDerm Ltd, Prexton, Revance, Sage, and US WorldMeds.

Lecture fees from: Acorda, American Academy of Neurology, Kyowa Hakko Kirin, and US WorldMeds.

Research grant support from: Abide, Acorda, Amneal, Lundbeck, Michael J. Fox Foundation for Parkinson's Research, Mitsubishi NeuroDerm Ltd, Parkinson Study Group; Pharma 2B, Revance, Hoffmann-La Roche; Sunovion, Sun Pharma, and US WorldMeds.