A new series of cases of cerebral venous sinus thrombosis (CVST) linked to the adenoviral vector COVID-19 vaccines has been reported, confirming the severity of the reaction and the associated high mortality rate.

The new series comes from an international registry of consecutive patients who experienced CVST within 28 days of COVID-19 vaccination between March 29 and June 18, 2021, from 81 hospitals in 19 countries.

The cases are described in an article published online on Sept. 28. in JAMA Neurology.

“This is a reliable description on the clinical condition of these patients with CVST associated with COVID-19 vaccination. It is striking that this a much worse condition than CVST not associated with COVID-19 vaccination, with a much higher rate of intracerebral hemorrhage and coma and a much higher mortality rate,” senior author Jonathan M. Coutinho, MD, Amsterdam University Medical Centers, told this news organization.

These data confirm the observations from an earlier U.K. cohort in which cases of cerebral venous thrombosis linked to COVID-19 vaccination occurred.

“This is the biggest series, and as an international series, it gives a broader perspective from a larger range of countries,” Dr. Coutinho said. “All the data together show that, although this side effect is rare, the consequences are very severe,” he added.

In the current study, the researchers regarded CVST as being linked to the vaccine if it was accompanied by thrombosis with thrombocytopenia syndrome (TTS), as evidenced by thrombosis and new-onset thrombocytopenia.

In the cohort of 116 patients with CVST after COVID-19 vaccination, 78 (67.2%) had thrombosis with TTS and were thus classified as having had a vaccine-related adverse event. These patients were frequently comatose at presentation (24%) and often had intracerebral hemorrhage (68%) and concomitant thromboembolism (36%); 47% died during hospitalization.

These patients were compared with the 38 patients in the same cohort who had CVST but in whom there was no indication of concomitant thrombosis and thrombocytopenia. The case patients were also compared with a control group of 207 patients with CVST who were included in a separate international registry before the COVID-19 pandemic.

Mortality rates were much higher among the patients deemed to have had a vaccine-related CVST. The in-hospital mortality rate was 47%, compared with 5% among the patients in the same cohort who did not have TTS and 3.9% among the prepandemic control group.

The mortality rate was even higher (61%) among patients in the TTS group for whom the diagnosis was made before the condition garnered attention in the scientific community. The mortality rate was 42% among patients diagnosed later.

Of the 78 patients in whom CVST and TTS occurred after COVID-19 vaccination in this cohort, 76 had received the AstraZeneca vaccine (in 75 patients, CVST and TTS occurred after the first vaccination; in one patient, they occurred after the second vaccination). One patient had received the Johnson & Johnson vaccine, and one had received the Pfizer vaccine.

“After more analysis, the case after the Pfizer vaccination is not believed to be caused by the vaccine,” Dr. Coutinho said. “In that case, the patient had a platelet count just below the lower limit and was taking an immunomodulator drug that is known to be associated with thrombocytopenia.”

For two patients who received the AstraZeneca vaccine, there was also an alternative explanation for the thrombocytopenia.

Dr. Coutinho also pointed out that the Johnson & Johnson vaccine has been used mainly in the United States, and these data were largely from other countries.

The median time from vaccination to CVST symptom onset was 9 days in the TTS group. The median platelet count at hospital admission among patients with postvaccination CVST-TTS was 45. Three patients presented with a normal platelet count and developed thrombocytopenia during admission; two patients presented with mild thrombocytopenia, 30 presented with moderate thrombocytopenia, and 43 presented with severe thrombocytopenia.

Antibodies against platelet factor 4 (PF4) were measured in 69 patients with TTS, of whom 63 (91%) tested positive (the one patient in whom TTS occurred after the patient received the Pfizer vaccine did not test positive). However, the researchers note that sensitivity varies among different PF4 ELISA tests. Findings of platelet activation assays were positive in all 36 tested patients.

In the TTS group, 52 patients (67%) received immunomodulation therapy, most often intravenous immunoglobulins (IVIG). Among patients treated with IVIG, the mortality rate was lower (28%).
 

Different from CVST linked to natural COVID-19 infection

Dr. Coutinho noted that CVST can occur in natural SARS-CoV-2 infection but that vaccine-associated CVST is very different.

“In natural COVID-19 infection, there is an increased risk of thrombosis, and some patients can get CVST as a part of this, but in these cases, this is not accompanied by thrombocytopenia. While the CVST in natural COVID-19 infection is also associated with a bad prognosis, this is more to do with the underlying disease. It is normally the very sick COVID patients who develop CVST, and these patients usually die from the underlying disease rather than the CVST itself,” he explained.

“Clinicians need to be aware of vaccine-related CVST, as it requires very specific and rapid treatment,” Dr. Coutinho stressed.

“Patients presenting with an extremely severe headache (unlike any headache they’ve had before) or with seizures or a focal deficit (weakness in arm or problems with speaking or vision) within 4 weeks of an adenovirus COVID-19 vaccination should ring alarm bells. It is important to do diagnostics quickly, with a platelet count the most important first step, and a rapid CT/MRI scan,” he said.

Other tests that should be conducted are D-dimer for thrombosis and the PF4 antibody test. But results for the PF4 antibody test can take days to come back, and clinicians shouldn’t wait for that, Dr. Coutinho notes.

“Specific treatment needs to be given immediately – with anticoagulation (preferably nonheparin) and immunomodulation with IVIG to stop the immune reaction. Platelets should not be given – that may seem counterintuitive in patients with a low platelet count, but giving platelets makes it worse,” he said.
 

Is there a geographic difference?

Dr. Coutinho pointed out that fewer cases of this vaccine-related CVST are being reported at the current time.

“We are not sure why this is the case. These adenovirus vaccines are not being used much now in Western countries, but our collaboration covers many less developed countries in South America and Asia, which are relying heavily on these vaccines. We are now shifting focus to these countries, but so far we have only seen a handful of cases from these areas,” he said.

He suggested that this may be because these countries started their vaccination programs later and are vaccinating their elderly (who are not so susceptible to this side effect) first, or it may be because of some environmental or genetic factor that has not yet been discovered.

“This is now an important research question – is the risk of vaccine-induced CVST the same in different countries or ethnicities? This could influence decisions on future vaccine strategies,” Dr. Coutinho said.

“So far, female sex is the strongest risk factor for vaccine-induced CVST. In our cohort, 81% of cases were in women. In addition, 95% were White, but that doesn’t allow us to conclude that this is a risk factor, as the majority of people who have been vaccinated are White. So, we have no clear insight into that yet,” he said.

In a comment for this news organization, the lead author of the previous U.K. report of a series of 70 cases of cerebral venous thrombosis linked to COVID-19 vaccination, Richard Perry, PhD, University College Hospital, London, described this new report as “an excellent study, with many of the same strengths and weaknesses as our study and has very similar results.”

Dr. Perry noted that the two studies used slightly different definitions of vaccine-induced thrombotic thrombocytopenia, but the cases reported appear to be very similar overall. “It is reassuring and gratifying to see that they have made such similar observations,” he said.

“And as they have drawn their cases from a broad range of countries whereas ours were all from the U.K., this provides evidence that the observations from both studies are reasonably generalizable,” he added.

Dr. Perry pointed out that this new report states that TTS occurred in one patient after the patient had received a second dose of the AstraZeneca vaccine. “I would like to know more about this case, because we didn’t see any cases after a second dose in our cohort,” he said.

Dr. Coutinho responded that he didn’t believe this was the first reported case after the second dose.

The study did not receive any specific funding. Dr. Coutinho has received grants paid to his institution from Boehringer Ingelheim and Bayer and payments paid to his institution for data safety monitoring board participation by Bayer.

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

A new series of cases of cerebral venous sinus thrombosis (CVST) linked to the adenoviral vector COVID-19 vaccines has been reported, confirming the severity of the reaction and the associated high mortality rate.

The new series comes from an international registry of consecutive patients who experienced CVST within 28 days of COVID-19 vaccination between March 29 and June 18, 2021, from 81 hospitals in 19 countries.

The cases are described in an article published online on Sept. 28. in JAMA Neurology.

“This is a reliable description on the clinical condition of these patients with CVST associated with COVID-19 vaccination. It is striking that this a much worse condition than CVST not associated with COVID-19 vaccination, with a much higher rate of intracerebral hemorrhage and coma and a much higher mortality rate,” senior author Jonathan M. Coutinho, MD, Amsterdam University Medical Centers, told this news organization.

These data confirm the observations from an earlier U.K. cohort in which cases of cerebral venous thrombosis linked to COVID-19 vaccination occurred.

“This is the biggest series, and as an international series, it gives a broader perspective from a larger range of countries,” Dr. Coutinho said. “All the data together show that, although this side effect is rare, the consequences are very severe,” he added.

In the current study, the researchers regarded CVST as being linked to the vaccine if it was accompanied by thrombosis with thrombocytopenia syndrome (TTS), as evidenced by thrombosis and new-onset thrombocytopenia.

In the cohort of 116 patients with CVST after COVID-19 vaccination, 78 (67.2%) had thrombosis with TTS and were thus classified as having had a vaccine-related adverse event. These patients were frequently comatose at presentation (24%) and often had intracerebral hemorrhage (68%) and concomitant thromboembolism (36%); 47% died during hospitalization.

These patients were compared with the 38 patients in the same cohort who had CVST but in whom there was no indication of concomitant thrombosis and thrombocytopenia. The case patients were also compared with a control group of 207 patients with CVST who were included in a separate international registry before the COVID-19 pandemic.

Mortality rates were much higher among the patients deemed to have had a vaccine-related CVST. The in-hospital mortality rate was 47%, compared with 5% among the patients in the same cohort who did not have TTS and 3.9% among the prepandemic control group.

The mortality rate was even higher (61%) among patients in the TTS group for whom the diagnosis was made before the condition garnered attention in the scientific community. The mortality rate was 42% among patients diagnosed later.

Of the 78 patients in whom CVST and TTS occurred after COVID-19 vaccination in this cohort, 76 had received the AstraZeneca vaccine (in 75 patients, CVST and TTS occurred after the first vaccination; in one patient, they occurred after the second vaccination). One patient had received the Johnson & Johnson vaccine, and one had received the Pfizer vaccine.

“After more analysis, the case after the Pfizer vaccination is not believed to be caused by the vaccine,” Dr. Coutinho said. “In that case, the patient had a platelet count just below the lower limit and was taking an immunomodulator drug that is known to be associated with thrombocytopenia.”

For two patients who received the AstraZeneca vaccine, there was also an alternative explanation for the thrombocytopenia.

Dr. Coutinho also pointed out that the Johnson & Johnson vaccine has been used mainly in the United States, and these data were largely from other countries.

The median time from vaccination to CVST symptom onset was 9 days in the TTS group. The median platelet count at hospital admission among patients with postvaccination CVST-TTS was 45. Three patients presented with a normal platelet count and developed thrombocytopenia during admission; two patients presented with mild thrombocytopenia, 30 presented with moderate thrombocytopenia, and 43 presented with severe thrombocytopenia.

Antibodies against platelet factor 4 (PF4) were measured in 69 patients with TTS, of whom 63 (91%) tested positive (the one patient in whom TTS occurred after the patient received the Pfizer vaccine did not test positive). However, the researchers note that sensitivity varies among different PF4 ELISA tests. Findings of platelet activation assays were positive in all 36 tested patients.

In the TTS group, 52 patients (67%) received immunomodulation therapy, most often intravenous immunoglobulins (IVIG). Among patients treated with IVIG, the mortality rate was lower (28%).
 

Different from CVST linked to natural COVID-19 infection

Dr. Coutinho noted that CVST can occur in natural SARS-CoV-2 infection but that vaccine-associated CVST is very different.

“In natural COVID-19 infection, there is an increased risk of thrombosis, and some patients can get CVST as a part of this, but in these cases, this is not accompanied by thrombocytopenia. While the CVST in natural COVID-19 infection is also associated with a bad prognosis, this is more to do with the underlying disease. It is normally the very sick COVID patients who develop CVST, and these patients usually die from the underlying disease rather than the CVST itself,” he explained.

“Clinicians need to be aware of vaccine-related CVST, as it requires very specific and rapid treatment,” Dr. Coutinho stressed.

“Patients presenting with an extremely severe headache (unlike any headache they’ve had before) or with seizures or a focal deficit (weakness in arm or problems with speaking or vision) within 4 weeks of an adenovirus COVID-19 vaccination should ring alarm bells. It is important to do diagnostics quickly, with a platelet count the most important first step, and a rapid CT/MRI scan,” he said.

Other tests that should be conducted are D-dimer for thrombosis and the PF4 antibody test. But results for the PF4 antibody test can take days to come back, and clinicians shouldn’t wait for that, Dr. Coutinho notes.

“Specific treatment needs to be given immediately – with anticoagulation (preferably nonheparin) and immunomodulation with IVIG to stop the immune reaction. Platelets should not be given – that may seem counterintuitive in patients with a low platelet count, but giving platelets makes it worse,” he said.
 

Is there a geographic difference?

Dr. Coutinho pointed out that fewer cases of this vaccine-related CVST are being reported at the current time.

“We are not sure why this is the case. These adenovirus vaccines are not being used much now in Western countries, but our collaboration covers many less developed countries in South America and Asia, which are relying heavily on these vaccines. We are now shifting focus to these countries, but so far we have only seen a handful of cases from these areas,” he said.

He suggested that this may be because these countries started their vaccination programs later and are vaccinating their elderly (who are not so susceptible to this side effect) first, or it may be because of some environmental or genetic factor that has not yet been discovered.

“This is now an important research question – is the risk of vaccine-induced CVST the same in different countries or ethnicities? This could influence decisions on future vaccine strategies,” Dr. Coutinho said.

“So far, female sex is the strongest risk factor for vaccine-induced CVST. In our cohort, 81% of cases were in women. In addition, 95% were White, but that doesn’t allow us to conclude that this is a risk factor, as the majority of people who have been vaccinated are White. So, we have no clear insight into that yet,” he said.

In a comment for this news organization, the lead author of the previous U.K. report of a series of 70 cases of cerebral venous thrombosis linked to COVID-19 vaccination, Richard Perry, PhD, University College Hospital, London, described this new report as “an excellent study, with many of the same strengths and weaknesses as our study and has very similar results.”

Dr. Perry noted that the two studies used slightly different definitions of vaccine-induced thrombotic thrombocytopenia, but the cases reported appear to be very similar overall. “It is reassuring and gratifying to see that they have made such similar observations,” he said.

“And as they have drawn their cases from a broad range of countries whereas ours were all from the U.K., this provides evidence that the observations from both studies are reasonably generalizable,” he added.

Dr. Perry pointed out that this new report states that TTS occurred in one patient after the patient had received a second dose of the AstraZeneca vaccine. “I would like to know more about this case, because we didn’t see any cases after a second dose in our cohort,” he said.

Dr. Coutinho responded that he didn’t believe this was the first reported case after the second dose.

The study did not receive any specific funding. Dr. Coutinho has received grants paid to his institution from Boehringer Ingelheim and Bayer and payments paid to his institution for data safety monitoring board participation by Bayer.

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

A new series of cases of cerebral venous sinus thrombosis (CVST) linked to the adenoviral vector COVID-19 vaccines has been reported, confirming the severity of the reaction and the associated high mortality rate.

The new series comes from an international registry of consecutive patients who experienced CVST within 28 days of COVID-19 vaccination between March 29 and June 18, 2021, from 81 hospitals in 19 countries.

The cases are described in an article published online on Sept. 28. in JAMA Neurology.

“This is a reliable description on the clinical condition of these patients with CVST associated with COVID-19 vaccination. It is striking that this a much worse condition than CVST not associated with COVID-19 vaccination, with a much higher rate of intracerebral hemorrhage and coma and a much higher mortality rate,” senior author Jonathan M. Coutinho, MD, Amsterdam University Medical Centers, told this news organization.

These data confirm the observations from an earlier U.K. cohort in which cases of cerebral venous thrombosis linked to COVID-19 vaccination occurred.

“This is the biggest series, and as an international series, it gives a broader perspective from a larger range of countries,” Dr. Coutinho said. “All the data together show that, although this side effect is rare, the consequences are very severe,” he added.

In the current study, the researchers regarded CVST as being linked to the vaccine if it was accompanied by thrombosis with thrombocytopenia syndrome (TTS), as evidenced by thrombosis and new-onset thrombocytopenia.

In the cohort of 116 patients with CVST after COVID-19 vaccination, 78 (67.2%) had thrombosis with TTS and were thus classified as having had a vaccine-related adverse event. These patients were frequently comatose at presentation (24%) and often had intracerebral hemorrhage (68%) and concomitant thromboembolism (36%); 47% died during hospitalization.

These patients were compared with the 38 patients in the same cohort who had CVST but in whom there was no indication of concomitant thrombosis and thrombocytopenia. The case patients were also compared with a control group of 207 patients with CVST who were included in a separate international registry before the COVID-19 pandemic.

Mortality rates were much higher among the patients deemed to have had a vaccine-related CVST. The in-hospital mortality rate was 47%, compared with 5% among the patients in the same cohort who did not have TTS and 3.9% among the prepandemic control group.

The mortality rate was even higher (61%) among patients in the TTS group for whom the diagnosis was made before the condition garnered attention in the scientific community. The mortality rate was 42% among patients diagnosed later.

Of the 78 patients in whom CVST and TTS occurred after COVID-19 vaccination in this cohort, 76 had received the AstraZeneca vaccine (in 75 patients, CVST and TTS occurred after the first vaccination; in one patient, they occurred after the second vaccination). One patient had received the Johnson & Johnson vaccine, and one had received the Pfizer vaccine.

“After more analysis, the case after the Pfizer vaccination is not believed to be caused by the vaccine,” Dr. Coutinho said. “In that case, the patient had a platelet count just below the lower limit and was taking an immunomodulator drug that is known to be associated with thrombocytopenia.”

For two patients who received the AstraZeneca vaccine, there was also an alternative explanation for the thrombocytopenia.

Dr. Coutinho also pointed out that the Johnson & Johnson vaccine has been used mainly in the United States, and these data were largely from other countries.

The median time from vaccination to CVST symptom onset was 9 days in the TTS group. The median platelet count at hospital admission among patients with postvaccination CVST-TTS was 45. Three patients presented with a normal platelet count and developed thrombocytopenia during admission; two patients presented with mild thrombocytopenia, 30 presented with moderate thrombocytopenia, and 43 presented with severe thrombocytopenia.

Antibodies against platelet factor 4 (PF4) were measured in 69 patients with TTS, of whom 63 (91%) tested positive (the one patient in whom TTS occurred after the patient received the Pfizer vaccine did not test positive). However, the researchers note that sensitivity varies among different PF4 ELISA tests. Findings of platelet activation assays were positive in all 36 tested patients.

In the TTS group, 52 patients (67%) received immunomodulation therapy, most often intravenous immunoglobulins (IVIG). Among patients treated with IVIG, the mortality rate was lower (28%).
 

Different from CVST linked to natural COVID-19 infection

Dr. Coutinho noted that CVST can occur in natural SARS-CoV-2 infection but that vaccine-associated CVST is very different.

“In natural COVID-19 infection, there is an increased risk of thrombosis, and some patients can get CVST as a part of this, but in these cases, this is not accompanied by thrombocytopenia. While the CVST in natural COVID-19 infection is also associated with a bad prognosis, this is more to do with the underlying disease. It is normally the very sick COVID patients who develop CVST, and these patients usually die from the underlying disease rather than the CVST itself,” he explained.

“Clinicians need to be aware of vaccine-related CVST, as it requires very specific and rapid treatment,” Dr. Coutinho stressed.

“Patients presenting with an extremely severe headache (unlike any headache they’ve had before) or with seizures or a focal deficit (weakness in arm or problems with speaking or vision) within 4 weeks of an adenovirus COVID-19 vaccination should ring alarm bells. It is important to do diagnostics quickly, with a platelet count the most important first step, and a rapid CT/MRI scan,” he said.

Other tests that should be conducted are D-dimer for thrombosis and the PF4 antibody test. But results for the PF4 antibody test can take days to come back, and clinicians shouldn’t wait for that, Dr. Coutinho notes.

“Specific treatment needs to be given immediately – with anticoagulation (preferably nonheparin) and immunomodulation with IVIG to stop the immune reaction. Platelets should not be given – that may seem counterintuitive in patients with a low platelet count, but giving platelets makes it worse,” he said.
 

Is there a geographic difference?

Dr. Coutinho pointed out that fewer cases of this vaccine-related CVST are being reported at the current time.

“We are not sure why this is the case. These adenovirus vaccines are not being used much now in Western countries, but our collaboration covers many less developed countries in South America and Asia, which are relying heavily on these vaccines. We are now shifting focus to these countries, but so far we have only seen a handful of cases from these areas,” he said.

He suggested that this may be because these countries started their vaccination programs later and are vaccinating their elderly (who are not so susceptible to this side effect) first, or it may be because of some environmental or genetic factor that has not yet been discovered.

“This is now an important research question – is the risk of vaccine-induced CVST the same in different countries or ethnicities? This could influence decisions on future vaccine strategies,” Dr. Coutinho said.

“So far, female sex is the strongest risk factor for vaccine-induced CVST. In our cohort, 81% of cases were in women. In addition, 95% were White, but that doesn’t allow us to conclude that this is a risk factor, as the majority of people who have been vaccinated are White. So, we have no clear insight into that yet,” he said.

In a comment for this news organization, the lead author of the previous U.K. report of a series of 70 cases of cerebral venous thrombosis linked to COVID-19 vaccination, Richard Perry, PhD, University College Hospital, London, described this new report as “an excellent study, with many of the same strengths and weaknesses as our study and has very similar results.”

Dr. Perry noted that the two studies used slightly different definitions of vaccine-induced thrombotic thrombocytopenia, but the cases reported appear to be very similar overall. “It is reassuring and gratifying to see that they have made such similar observations,” he said.

“And as they have drawn their cases from a broad range of countries whereas ours were all from the U.K., this provides evidence that the observations from both studies are reasonably generalizable,” he added.

Dr. Perry pointed out that this new report states that TTS occurred in one patient after the patient had received a second dose of the AstraZeneca vaccine. “I would like to know more about this case, because we didn’t see any cases after a second dose in our cohort,” he said.

Dr. Coutinho responded that he didn’t believe this was the first reported case after the second dose.

The study did not receive any specific funding. Dr. Coutinho has received grants paid to his institution from Boehringer Ingelheim and Bayer and payments paid to his institution for data safety monitoring board participation by Bayer.

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

This young patient is probably presenting with pediatric multiple sclerosis (MS). It is estimated that MS onset before the age of 18 years accounts for 3%-5% of the general population of patients with this autoimmune disease. The condition represents the most common nontraumatic, disabling neurologic disorder among young adults. Disease prevalence is highest between the ages of 13 and 16. In children older than 10, a female predominance is seen, suggesting a hormonal role in pathogenesis. The vast majority (up to 98%) of children and adolescents with MS have a relapsing-remitting course. Overall, pediatric MS has a milder course than adult MS but can lead to significant disability at an early age. Although pediatric patients may experience more frequent relapses, data also suggest that children seem to recover more quickly from episodes than adults.

In children and adolescents, MS most typically manifests with sensory disturbances and impaired coordination. The most commonly reported symptoms in pediatric MS are sensory, motor, and brainstem dysfunction, though cognitive and emotional disorders can emerge over time.

Younger children will often show multifocal symptoms but with the onset of adolescence may begin to present with only a single focal symptom, as is often the case with adult patients.

Diagnosis of pediatric MS goes hand-in-hand with a diagnosis of clinically isolated syndrome (CIS) or sporadic acute disseminated encephalomyelitis (ADEM). CIS is diagnosed when symptoms last for over 24 hours with possible inflammatory demyelination but without encephalopathy. To confirm an MS diagnosis, two or more clinical episodes must occur at least 30 days apart. MRI can both confirm diagnosis and offer great value in monitoring disease progression in the brain and spinal cord. Of note, differentiating the first episode of juvenile MS from ADEM is a significant clinical challenge.

When it comes to treating relapses, the approach in children is similar to that of adults. Therapy may consist of an intravenous pulse of methylprednisolone (20-30 mg/kg/day for 3-5 days). In 2018, the FDA approved the use of the oral MS therapy Gilenya (fingolimod) for the treatment of patients 10 years of age or older with relapsing forms of MS. Providers can also adapt treatments approved for adults for pediatric patients. 

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme

This young patient is probably presenting with pediatric multiple sclerosis (MS). It is estimated that MS onset before the age of 18 years accounts for 3%-5% of the general population of patients with this autoimmune disease. The condition represents the most common nontraumatic, disabling neurologic disorder among young adults. Disease prevalence is highest between the ages of 13 and 16. In children older than 10, a female predominance is seen, suggesting a hormonal role in pathogenesis. The vast majority (up to 98%) of children and adolescents with MS have a relapsing-remitting course. Overall, pediatric MS has a milder course than adult MS but can lead to significant disability at an early age. Although pediatric patients may experience more frequent relapses, data also suggest that children seem to recover more quickly from episodes than adults.

In children and adolescents, MS most typically manifests with sensory disturbances and impaired coordination. The most commonly reported symptoms in pediatric MS are sensory, motor, and brainstem dysfunction, though cognitive and emotional disorders can emerge over time.

Younger children will often show multifocal symptoms but with the onset of adolescence may begin to present with only a single focal symptom, as is often the case with adult patients.

Diagnosis of pediatric MS goes hand-in-hand with a diagnosis of clinically isolated syndrome (CIS) or sporadic acute disseminated encephalomyelitis (ADEM). CIS is diagnosed when symptoms last for over 24 hours with possible inflammatory demyelination but without encephalopathy. To confirm an MS diagnosis, two or more clinical episodes must occur at least 30 days apart. MRI can both confirm diagnosis and offer great value in monitoring disease progression in the brain and spinal cord. Of note, differentiating the first episode of juvenile MS from ADEM is a significant clinical challenge.

When it comes to treating relapses, the approach in children is similar to that of adults. Therapy may consist of an intravenous pulse of methylprednisolone (20-30 mg/kg/day for 3-5 days). In 2018, the FDA approved the use of the oral MS therapy Gilenya (fingolimod) for the treatment of patients 10 years of age or older with relapsing forms of MS. Providers can also adapt treatments approved for adults for pediatric patients. 

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme

This young patient is probably presenting with pediatric multiple sclerosis (MS). It is estimated that MS onset before the age of 18 years accounts for 3%-5% of the general population of patients with this autoimmune disease. The condition represents the most common nontraumatic, disabling neurologic disorder among young adults. Disease prevalence is highest between the ages of 13 and 16. In children older than 10, a female predominance is seen, suggesting a hormonal role in pathogenesis. The vast majority (up to 98%) of children and adolescents with MS have a relapsing-remitting course. Overall, pediatric MS has a milder course than adult MS but can lead to significant disability at an early age. Although pediatric patients may experience more frequent relapses, data also suggest that children seem to recover more quickly from episodes than adults.

In children and adolescents, MS most typically manifests with sensory disturbances and impaired coordination. The most commonly reported symptoms in pediatric MS are sensory, motor, and brainstem dysfunction, though cognitive and emotional disorders can emerge over time.

Younger children will often show multifocal symptoms but with the onset of adolescence may begin to present with only a single focal symptom, as is often the case with adult patients.

Diagnosis of pediatric MS goes hand-in-hand with a diagnosis of clinically isolated syndrome (CIS) or sporadic acute disseminated encephalomyelitis (ADEM). CIS is diagnosed when symptoms last for over 24 hours with possible inflammatory demyelination but without encephalopathy. To confirm an MS diagnosis, two or more clinical episodes must occur at least 30 days apart. MRI can both confirm diagnosis and offer great value in monitoring disease progression in the brain and spinal cord. Of note, differentiating the first episode of juvenile MS from ADEM is a significant clinical challenge.

When it comes to treating relapses, the approach in children is similar to that of adults. Therapy may consist of an intravenous pulse of methylprednisolone (20-30 mg/kg/day for 3-5 days). In 2018, the FDA approved the use of the oral MS therapy Gilenya (fingolimod) for the treatment of patients 10 years of age or older with relapsing forms of MS. Providers can also adapt treatments approved for adults for pediatric patients. 

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme

Two registered nurses in Colorado were charged with fraud and deception for stealing controlled substances from hospital patients, according to the US Attorney’s Office in Denver.

Alicia Nickel-Tangeman, 44, formerly of Woodland Park, Colo., pled guilty to four counts of obtaining controlled substances using fraud and deception. She gained access to rooms of patients who weren’t assigned to her and diverted drugs from their pain-on-demand devices, according to federal officials.

The defendant told patients she was conducting a study on the pumps that deliver drugs to relieve pain when the patient pushes a button, the officials stated. She would open the machine and would remove a portion of the drug with a syringe. She obtained drugs in this way from three patients on four occasions, a press release stated.

When questioned by law enforcement, Ms. Nickel-Tangeman continued to lie about her conduct and produced a false email address to substantiate her claims, the Department of Justice reported. She is scheduled to be sentenced November 30.

Ms. Nickel-Tangeman’s LinkedIn profile shows that she was a nurse with UCHealth in Colorado for 17 years, ending in May 2019.

Katie Muhs, 34, of Littleton, Colo., was convicted of a felony for using fraud and deception to divert fentanyl for her personal use while serving as an intensive care nurse.

The defendant admitted that between June and September 2019 she stole fentanyl by removing it from the IV bags of patients using a syringe. She also admitted to stealing fentanyl that remained in vials after fentanyl had been administered to patients. She would replace the stolen drug with saline and would “then have a fellow nurse witness her ‘waste,’ or dispose of the saline.”

U.S. District Judge Raymond Moore sentenced Ms. Muhs to 3 months of probation as a result of “the defendant’s confession and her cooperation in disclosing full information on her diversion, which is a matter potentially affecting the public health and the integrity of the health care system. The felony offense is punishable by up to four years of imprisonment and a fine of $250,000, per count.”

In pleading guilty to the single count in the case, Ms. Muhs admitted that on September 8, 2019, “she removed a bag of fentanyl from the automated medication control machine at the hospital under a different nurse’s login credentials. She then removed fentanyl from the IV bag for personal use.”

In April, the Colorado Court of Appeals denied her request for unemployment benefits. Court documents reveal that Ms. Muhs lost her job at St. Anthony Hospital after it was discovered that she stole and self-injected fentanyl while working as a registered nurse there.

The investigations in these cases were conducted by the U.S. Food and Drug Administration, the Office of Criminal Investigations, and the Drug Enforcement Administration (DEA).

“We want it to be known that healthcare professionals who take advantage of patients in need by stealing their medications will be held accountable to the law,” said Deanne Reuter, DEA Denver Field Division special agent in charge.

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

Two registered nurses in Colorado were charged with fraud and deception for stealing controlled substances from hospital patients, according to the US Attorney’s Office in Denver.

Alicia Nickel-Tangeman, 44, formerly of Woodland Park, Colo., pled guilty to four counts of obtaining controlled substances using fraud and deception. She gained access to rooms of patients who weren’t assigned to her and diverted drugs from their pain-on-demand devices, according to federal officials.

The defendant told patients she was conducting a study on the pumps that deliver drugs to relieve pain when the patient pushes a button, the officials stated. She would open the machine and would remove a portion of the drug with a syringe. She obtained drugs in this way from three patients on four occasions, a press release stated.

When questioned by law enforcement, Ms. Nickel-Tangeman continued to lie about her conduct and produced a false email address to substantiate her claims, the Department of Justice reported. She is scheduled to be sentenced November 30.

Ms. Nickel-Tangeman’s LinkedIn profile shows that she was a nurse with UCHealth in Colorado for 17 years, ending in May 2019.

Katie Muhs, 34, of Littleton, Colo., was convicted of a felony for using fraud and deception to divert fentanyl for her personal use while serving as an intensive care nurse.

The defendant admitted that between June and September 2019 she stole fentanyl by removing it from the IV bags of patients using a syringe. She also admitted to stealing fentanyl that remained in vials after fentanyl had been administered to patients. She would replace the stolen drug with saline and would “then have a fellow nurse witness her ‘waste,’ or dispose of the saline.”

U.S. District Judge Raymond Moore sentenced Ms. Muhs to 3 months of probation as a result of “the defendant’s confession and her cooperation in disclosing full information on her diversion, which is a matter potentially affecting the public health and the integrity of the health care system. The felony offense is punishable by up to four years of imprisonment and a fine of $250,000, per count.”

In pleading guilty to the single count in the case, Ms. Muhs admitted that on September 8, 2019, “she removed a bag of fentanyl from the automated medication control machine at the hospital under a different nurse’s login credentials. She then removed fentanyl from the IV bag for personal use.”

In April, the Colorado Court of Appeals denied her request for unemployment benefits. Court documents reveal that Ms. Muhs lost her job at St. Anthony Hospital after it was discovered that she stole and self-injected fentanyl while working as a registered nurse there.

The investigations in these cases were conducted by the U.S. Food and Drug Administration, the Office of Criminal Investigations, and the Drug Enforcement Administration (DEA).

“We want it to be known that healthcare professionals who take advantage of patients in need by stealing their medications will be held accountable to the law,” said Deanne Reuter, DEA Denver Field Division special agent in charge.

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

Two registered nurses in Colorado were charged with fraud and deception for stealing controlled substances from hospital patients, according to the US Attorney’s Office in Denver.

Alicia Nickel-Tangeman, 44, formerly of Woodland Park, Colo., pled guilty to four counts of obtaining controlled substances using fraud and deception. She gained access to rooms of patients who weren’t assigned to her and diverted drugs from their pain-on-demand devices, according to federal officials.

The defendant told patients she was conducting a study on the pumps that deliver drugs to relieve pain when the patient pushes a button, the officials stated. She would open the machine and would remove a portion of the drug with a syringe. She obtained drugs in this way from three patients on four occasions, a press release stated.

When questioned by law enforcement, Ms. Nickel-Tangeman continued to lie about her conduct and produced a false email address to substantiate her claims, the Department of Justice reported. She is scheduled to be sentenced November 30.

Ms. Nickel-Tangeman’s LinkedIn profile shows that she was a nurse with UCHealth in Colorado for 17 years, ending in May 2019.

Katie Muhs, 34, of Littleton, Colo., was convicted of a felony for using fraud and deception to divert fentanyl for her personal use while serving as an intensive care nurse.

The defendant admitted that between June and September 2019 she stole fentanyl by removing it from the IV bags of patients using a syringe. She also admitted to stealing fentanyl that remained in vials after fentanyl had been administered to patients. She would replace the stolen drug with saline and would “then have a fellow nurse witness her ‘waste,’ or dispose of the saline.”

U.S. District Judge Raymond Moore sentenced Ms. Muhs to 3 months of probation as a result of “the defendant’s confession and her cooperation in disclosing full information on her diversion, which is a matter potentially affecting the public health and the integrity of the health care system. The felony offense is punishable by up to four years of imprisonment and a fine of $250,000, per count.”

In pleading guilty to the single count in the case, Ms. Muhs admitted that on September 8, 2019, “she removed a bag of fentanyl from the automated medication control machine at the hospital under a different nurse’s login credentials. She then removed fentanyl from the IV bag for personal use.”

In April, the Colorado Court of Appeals denied her request for unemployment benefits. Court documents reveal that Ms. Muhs lost her job at St. Anthony Hospital after it was discovered that she stole and self-injected fentanyl while working as a registered nurse there.

The investigations in these cases were conducted by the U.S. Food and Drug Administration, the Office of Criminal Investigations, and the Drug Enforcement Administration (DEA).

“We want it to be known that healthcare professionals who take advantage of patients in need by stealing their medications will be held accountable to the law,” said Deanne Reuter, DEA Denver Field Division special agent in charge.

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

Physician and advanced practice provider (APP) (collectively, “provider”) onboarding into health care delivery settings requires careful planning and systematic integration. Assimilation into health care settings and cultures necessitates more than a 1- or 2-day orientation. Rather, an intentional, longitudinal onboarding program (starting with orientation) needs to be designed to assimilate providers into the unique culture of a medical practice.

Establishing mutual expectations

Communication concerning mutual expectations is a vital component of the agreement between provider and practice. Items that should be included in provider onboarding (likely addressed in either the practice visit or amplified in a contract) include the following:

• Committees: Committee orientation should include a discussion of provider preferences/expectations and why getting the new provider involved in the business of the practice is a priority of the group.
• Operations: Key clinical operations details should be reviewed with the incoming provider and reinforced through follow-up discussions with a physician mentor/coach (for example, call distribution; role of the senior nonclinical leadership team/accountants, fellow practice/group partners, and IT support; role definitions and expectations for duties, transitioning call, and EHR charting; revenue-sharing; supplies/preferences/adaptability to scope type).
• Interests: Specific provider interests (for example, clinical research, infusion, hemorrhoidal banding, weight loss/nutrition, inflammatory bowel disease, irritable bowel disease, pathology) and productivity expectations (for example, number of procedures, number of new and return patient visits per day) should be communicated.
• Miscellaneous: Discussion about marketing the practice, importance of growing satellite programs and nuance of major referral groups to the practice are also key components of the assimilation process.

Leadership self-awareness and cultural alignment

Leadership self-awareness is a key element of provider onboarding. Physicians and APPs are trained to think independently and may be challenged to share decision-making and rely on others. The following are some no-cost self-assessment and awareness resources:

• Myers-Briggs Personality Profile Preferences:
• VIA Strengths:
• VARK Analysis:

Cultural alignment is also a critical consideration to ensure orderly assimilation into the practice/health care setting and with stakeholders. A shared commitment to embed a culture with shared values has relevance to merging cultures – not only when organizations come together – but with individuals as well. Time spent developing a better understanding of the customs, culture and traditions of the practice will be helpful if a practice must change its trajectory based on meeting an unmovable obstruction (for example, market forces requiring practice consolidation).

Improved quality

Transitioning a new provider into an existing practice culture can have a ripple effect on support staff and patient satisfaction and is, therefore, an important consideration in provider onboarding. Written standards, procedures, expectations, and practices are always advisable when possible. Attention to the demographics of the recruited physician is also important with shifts in interests and priorities from a practice. Millennials will constitute most of the workforce by 2025 and arrive with a mindset that the tenure in a role will be shorter than providers before them. Accordingly, the intentionality of the relationship is critical for successful bonding.

If current physician leaders want to achieve simultaneous succession planning and maintain the legacy of a patient-centric and resilient practice, these leaders must consider bridging the “cultural knowledge acumen gap.” James S. Hernandez, MD, MS, FCAP, and colleagues suggest a “connector” role between new and experienced providers. Reverse mentoring/distance/reciprocal mentoring is also mentioned as a two-way learning process between mentor and mentee.
 

Process structure considerations

Each new hire affects the culture of the practice. Best practices for the onboarding and orientation process should be followed. A written project master list with a timeline for completion of onboarding tasks with responsible and accountable persons, target dates for completion, and measurement should be established. Establishing mutual expectations up front can help practices tailor committee roles and clinical responsibilities to maximize provider engagement and longevity. A robust onboarding process may take up to 2 years depending on the size of the practice and the complexity of its structure and associated duties.

Desired outcomes

The desired outcome of the onboarding process is a satisfied provider whose passion and enthusiasm for quality patient care is demonstrated objectively through excellent performance on clinical quality measures and metrics of patient and referral source satisfaction.

Periodic reviews of how the onboarding process is progressing should be undertaken. These reviews can be modeled after the After-Action Review (AAR) process used in the military for measuring progress. Simply stated, what items went well with onboarding and why? What items did not go well with onboarding and why not? (Consider something like the Center for Medicare & Medicaid Services’ “5 Whys” assessment to determine root cause for items that need correction.) What elements of the onboarding process could be further improved? Using a Delphi method during the AAR session is an excellent way for the group to hear from all participants ranging from senior partners to recently recruited providers.
 

Conclusion

Medical practices must recognize that assimilating a new provider into the practice through a robust onboarding process is not lost effort but rather a force multiplier. Effective provider onboarding gives the incoming provider a sense of purpose and resolve, which results in optimized clinical productivity and engagement because the new provider is invested in the future of the practice. Once successfully onboarded and integrated into the practice, new providers need to understand that the work effort invested in their onboarding comes with a “pay it forward” obligation for the next provider recruited by the group. Group members also need to realize that the baseline is always changing–the provider onboarding process needs to continually evolve and adapt as the practice changes and new providers are hired.

Mr. Rudnick is a visiting professor and program director healthcare quality, innovation, and strategy at St Thomas University, Miami. Mr. Turner is regional vice president for the Midatlantic market of Covenant Physician Partners.

References

“Best practices for onboarding physicians.” The Rheumatologist. 2019 Sep 17. Accessed 2021 Sep 6. https://www.the-rheumatologist.org/article/best-practices-for-onboarding-new-physicians/

Centers for Medicare & Medicaid Services. Five Whys Tool for Root Cause Analysis: QAPI. 2021. Accessed 2021 Sep 6. https://www.cms.gov/medicare/provider-enrollment-and-certification/qapi/downloads/fivewhys.pdf.

DeIuliis ET, Saylor E. Open J Occup Ther. 2021;9(1):1-13. 

Hernandez JS et al. “Discussion: Mentoring millennials for future leadership.” Physician Leadership Journal. 2018 May 14. Accessed 2021 Sep 6. https://www.physicianleaders.org/news/discussion-mentoring-millennials-future-leadership

Moore L et al. J Trauma Acute Care Surg. 2015 Jun;78(6):1168-75..

Klein CJ et al. West J Nurs Res. 2021 Feb;43(2):105-114.

Weinburger T, Gordon J. Health Prog. Nov-Dec 2013;94(6):76-9.

Wentlandt K et al. Healthc Q. 2016;18(4):36-41.
 

Physician and advanced practice provider (APP) (collectively, “provider”) onboarding into health care delivery settings requires careful planning and systematic integration. Assimilation into health care settings and cultures necessitates more than a 1- or 2-day orientation. Rather, an intentional, longitudinal onboarding program (starting with orientation) needs to be designed to assimilate providers into the unique culture of a medical practice.

Establishing mutual expectations

Communication concerning mutual expectations is a vital component of the agreement between provider and practice. Items that should be included in provider onboarding (likely addressed in either the practice visit or amplified in a contract) include the following:

• Committees: Committee orientation should include a discussion of provider preferences/expectations and why getting the new provider involved in the business of the practice is a priority of the group.
• Operations: Key clinical operations details should be reviewed with the incoming provider and reinforced through follow-up discussions with a physician mentor/coach (for example, call distribution; role of the senior nonclinical leadership team/accountants, fellow practice/group partners, and IT support; role definitions and expectations for duties, transitioning call, and EHR charting; revenue-sharing; supplies/preferences/adaptability to scope type).
• Interests: Specific provider interests (for example, clinical research, infusion, hemorrhoidal banding, weight loss/nutrition, inflammatory bowel disease, irritable bowel disease, pathology) and productivity expectations (for example, number of procedures, number of new and return patient visits per day) should be communicated.
• Miscellaneous: Discussion about marketing the practice, importance of growing satellite programs and nuance of major referral groups to the practice are also key components of the assimilation process.

Leadership self-awareness and cultural alignment

Leadership self-awareness is a key element of provider onboarding. Physicians and APPs are trained to think independently and may be challenged to share decision-making and rely on others. The following are some no-cost self-assessment and awareness resources:

• Myers-Briggs Personality Profile Preferences:
• VIA Strengths:
• VARK Analysis:

Cultural alignment is also a critical consideration to ensure orderly assimilation into the practice/health care setting and with stakeholders. A shared commitment to embed a culture with shared values has relevance to merging cultures – not only when organizations come together – but with individuals as well. Time spent developing a better understanding of the customs, culture and traditions of the practice will be helpful if a practice must change its trajectory based on meeting an unmovable obstruction (for example, market forces requiring practice consolidation).

Improved quality

Transitioning a new provider into an existing practice culture can have a ripple effect on support staff and patient satisfaction and is, therefore, an important consideration in provider onboarding. Written standards, procedures, expectations, and practices are always advisable when possible. Attention to the demographics of the recruited physician is also important with shifts in interests and priorities from a practice. Millennials will constitute most of the workforce by 2025 and arrive with a mindset that the tenure in a role will be shorter than providers before them. Accordingly, the intentionality of the relationship is critical for successful bonding.

If current physician leaders want to achieve simultaneous succession planning and maintain the legacy of a patient-centric and resilient practice, these leaders must consider bridging the “cultural knowledge acumen gap.” James S. Hernandez, MD, MS, FCAP, and colleagues suggest a “connector” role between new and experienced providers. Reverse mentoring/distance/reciprocal mentoring is also mentioned as a two-way learning process between mentor and mentee.
 

Process structure considerations

Each new hire affects the culture of the practice. Best practices for the onboarding and orientation process should be followed. A written project master list with a timeline for completion of onboarding tasks with responsible and accountable persons, target dates for completion, and measurement should be established. Establishing mutual expectations up front can help practices tailor committee roles and clinical responsibilities to maximize provider engagement and longevity. A robust onboarding process may take up to 2 years depending on the size of the practice and the complexity of its structure and associated duties.

Desired outcomes

The desired outcome of the onboarding process is a satisfied provider whose passion and enthusiasm for quality patient care is demonstrated objectively through excellent performance on clinical quality measures and metrics of patient and referral source satisfaction.

Periodic reviews of how the onboarding process is progressing should be undertaken. These reviews can be modeled after the After-Action Review (AAR) process used in the military for measuring progress. Simply stated, what items went well with onboarding and why? What items did not go well with onboarding and why not? (Consider something like the Center for Medicare & Medicaid Services’ “5 Whys” assessment to determine root cause for items that need correction.) What elements of the onboarding process could be further improved? Using a Delphi method during the AAR session is an excellent way for the group to hear from all participants ranging from senior partners to recently recruited providers.
 

Conclusion

Medical practices must recognize that assimilating a new provider into the practice through a robust onboarding process is not lost effort but rather a force multiplier. Effective provider onboarding gives the incoming provider a sense of purpose and resolve, which results in optimized clinical productivity and engagement because the new provider is invested in the future of the practice. Once successfully onboarded and integrated into the practice, new providers need to understand that the work effort invested in their onboarding comes with a “pay it forward” obligation for the next provider recruited by the group. Group members also need to realize that the baseline is always changing–the provider onboarding process needs to continually evolve and adapt as the practice changes and new providers are hired.

Mr. Rudnick is a visiting professor and program director healthcare quality, innovation, and strategy at St Thomas University, Miami. Mr. Turner is regional vice president for the Midatlantic market of Covenant Physician Partners.

References

“Best practices for onboarding physicians.” The Rheumatologist. 2019 Sep 17. Accessed 2021 Sep 6. https://www.the-rheumatologist.org/article/best-practices-for-onboarding-new-physicians/

Centers for Medicare & Medicaid Services. Five Whys Tool for Root Cause Analysis: QAPI. 2021. Accessed 2021 Sep 6. https://www.cms.gov/medicare/provider-enrollment-and-certification/qapi/downloads/fivewhys.pdf.

DeIuliis ET, Saylor E. Open J Occup Ther. 2021;9(1):1-13. 

Hernandez JS et al. “Discussion: Mentoring millennials for future leadership.” Physician Leadership Journal. 2018 May 14. Accessed 2021 Sep 6. https://www.physicianleaders.org/news/discussion-mentoring-millennials-future-leadership

Moore L et al. J Trauma Acute Care Surg. 2015 Jun;78(6):1168-75..

Klein CJ et al. West J Nurs Res. 2021 Feb;43(2):105-114.

Weinburger T, Gordon J. Health Prog. Nov-Dec 2013;94(6):76-9.

Wentlandt K et al. Healthc Q. 2016;18(4):36-41.
 

Physician and advanced practice provider (APP) (collectively, “provider”) onboarding into health care delivery settings requires careful planning and systematic integration. Assimilation into health care settings and cultures necessitates more than a 1- or 2-day orientation. Rather, an intentional, longitudinal onboarding program (starting with orientation) needs to be designed to assimilate providers into the unique culture of a medical practice.

Establishing mutual expectations

Communication concerning mutual expectations is a vital component of the agreement between provider and practice. Items that should be included in provider onboarding (likely addressed in either the practice visit or amplified in a contract) include the following:

• Committees: Committee orientation should include a discussion of provider preferences/expectations and why getting the new provider involved in the business of the practice is a priority of the group.
• Operations: Key clinical operations details should be reviewed with the incoming provider and reinforced through follow-up discussions with a physician mentor/coach (for example, call distribution; role of the senior nonclinical leadership team/accountants, fellow practice/group partners, and IT support; role definitions and expectations for duties, transitioning call, and EHR charting; revenue-sharing; supplies/preferences/adaptability to scope type).
• Interests: Specific provider interests (for example, clinical research, infusion, hemorrhoidal banding, weight loss/nutrition, inflammatory bowel disease, irritable bowel disease, pathology) and productivity expectations (for example, number of procedures, number of new and return patient visits per day) should be communicated.
• Miscellaneous: Discussion about marketing the practice, importance of growing satellite programs and nuance of major referral groups to the practice are also key components of the assimilation process.

Leadership self-awareness and cultural alignment

Leadership self-awareness is a key element of provider onboarding. Physicians and APPs are trained to think independently and may be challenged to share decision-making and rely on others. The following are some no-cost self-assessment and awareness resources:

• Myers-Briggs Personality Profile Preferences:
• VIA Strengths:
• VARK Analysis:

Cultural alignment is also a critical consideration to ensure orderly assimilation into the practice/health care setting and with stakeholders. A shared commitment to embed a culture with shared values has relevance to merging cultures – not only when organizations come together – but with individuals as well. Time spent developing a better understanding of the customs, culture and traditions of the practice will be helpful if a practice must change its trajectory based on meeting an unmovable obstruction (for example, market forces requiring practice consolidation).

Improved quality

Transitioning a new provider into an existing practice culture can have a ripple effect on support staff and patient satisfaction and is, therefore, an important consideration in provider onboarding. Written standards, procedures, expectations, and practices are always advisable when possible. Attention to the demographics of the recruited physician is also important with shifts in interests and priorities from a practice. Millennials will constitute most of the workforce by 2025 and arrive with a mindset that the tenure in a role will be shorter than providers before them. Accordingly, the intentionality of the relationship is critical for successful bonding.

If current physician leaders want to achieve simultaneous succession planning and maintain the legacy of a patient-centric and resilient practice, these leaders must consider bridging the “cultural knowledge acumen gap.” James S. Hernandez, MD, MS, FCAP, and colleagues suggest a “connector” role between new and experienced providers. Reverse mentoring/distance/reciprocal mentoring is also mentioned as a two-way learning process between mentor and mentee.
 

Process structure considerations

Each new hire affects the culture of the practice. Best practices for the onboarding and orientation process should be followed. A written project master list with a timeline for completion of onboarding tasks with responsible and accountable persons, target dates for completion, and measurement should be established. Establishing mutual expectations up front can help practices tailor committee roles and clinical responsibilities to maximize provider engagement and longevity. A robust onboarding process may take up to 2 years depending on the size of the practice and the complexity of its structure and associated duties.

Desired outcomes

The desired outcome of the onboarding process is a satisfied provider whose passion and enthusiasm for quality patient care is demonstrated objectively through excellent performance on clinical quality measures and metrics of patient and referral source satisfaction.

Periodic reviews of how the onboarding process is progressing should be undertaken. These reviews can be modeled after the After-Action Review (AAR) process used in the military for measuring progress. Simply stated, what items went well with onboarding and why? What items did not go well with onboarding and why not? (Consider something like the Center for Medicare & Medicaid Services’ “5 Whys” assessment to determine root cause for items that need correction.) What elements of the onboarding process could be further improved? Using a Delphi method during the AAR session is an excellent way for the group to hear from all participants ranging from senior partners to recently recruited providers.
 

Conclusion

Medical practices must recognize that assimilating a new provider into the practice through a robust onboarding process is not lost effort but rather a force multiplier. Effective provider onboarding gives the incoming provider a sense of purpose and resolve, which results in optimized clinical productivity and engagement because the new provider is invested in the future of the practice. Once successfully onboarded and integrated into the practice, new providers need to understand that the work effort invested in their onboarding comes with a “pay it forward” obligation for the next provider recruited by the group. Group members also need to realize that the baseline is always changing–the provider onboarding process needs to continually evolve and adapt as the practice changes and new providers are hired.

Mr. Rudnick is a visiting professor and program director healthcare quality, innovation, and strategy at St Thomas University, Miami. Mr. Turner is regional vice president for the Midatlantic market of Covenant Physician Partners.

References

“Best practices for onboarding physicians.” The Rheumatologist. 2019 Sep 17. Accessed 2021 Sep 6. https://www.the-rheumatologist.org/article/best-practices-for-onboarding-new-physicians/

Centers for Medicare & Medicaid Services. Five Whys Tool for Root Cause Analysis: QAPI. 2021. Accessed 2021 Sep 6. https://www.cms.gov/medicare/provider-enrollment-and-certification/qapi/downloads/fivewhys.pdf.

DeIuliis ET, Saylor E. Open J Occup Ther. 2021;9(1):1-13. 

Hernandez JS et al. “Discussion: Mentoring millennials for future leadership.” Physician Leadership Journal. 2018 May 14. Accessed 2021 Sep 6. https://www.physicianleaders.org/news/discussion-mentoring-millennials-future-leadership

Moore L et al. J Trauma Acute Care Surg. 2015 Jun;78(6):1168-75..

Klein CJ et al. West J Nurs Res. 2021 Feb;43(2):105-114.

Weinburger T, Gordon J. Health Prog. Nov-Dec 2013;94(6):76-9.

Wentlandt K et al. Healthc Q. 2016;18(4):36-41.
 

Many people are confused — patients and healthcare providers alike — in the wake of the U.S. Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) announcements about who is authorized to get a third or ‘booster’ shot of the Pfizer/BioNTech COVID-19 vaccine.

The official word on boosters from the CDC in the early morning hours of September 24 sparked a jump in people calling about or coming in for a third shot, healthcare providers report. At the same time, the uncertainty from changing federal messages about boosters is causing some chaos, especially in the form of vaccine misinformation.

The confusion started, in part, with the August 13 announcement that immunocompromised Americans were eligible for a booster shot. Next came the initial Biden administration intention to provide most U.S. adults with a third shot starting September 20 — an announcement later rolled back — followed by the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) limiting boosters to select groups last week.

“It was only 3% of the population that was going to be getting a third dose, then it was back to everyone being able to get the booster, and then it’s back to a select crew,” Louito Edje, MD, a family physician in private practice in Cincinnati, said in an interview with this news organization.

This kind of mixed messaging is generating more questions than answers.  

“Even though that is following the science, translating the science into policy, it’s really fraught with confusion for patients, especially,” added Dr. Edje, professor educator in the departments of medical education and family and community medicine at UC Health and a fellow of the American Academy of Family Physicians.

When asked if he’s seeing more uncertainty about boosters, community pharmacist Brian Caswell, RPh, said: “I’m going to have to say yes because I’ve been confused myself at times.”

“Yes, there is a lot of confusion,” added Mr. Caswell, owner or co-owner of four pharmacies in Kansas and Missouri and president of the National Community Pharmacists Association. 
 

Boosting misinformation?

“Unfortunately, confusion leads to an acceleration of misinformation,” Mr. Caswell said.

Dr. Edje shared an example. “The folks who have been hesitant to even get the first vaccine appear now a little less likely to want to go ahead and get vaccinated.”

These patients point to breakthrough COVID-19 cases of the Delta variant, which “reinforces that they don’t need to get vaccinated in the first place,” Dr. Edje said.

“That’s unfortunate because it’s a complete fallacy.”

Clearer communication from the federal government could help alleviate confusion, Mr. Caswell said. “I would like to see an official CDC chart that states who is eligible as of a certain date. Something that is accessible through their webpage or a social media source that can be updated. That would help all of us.”

“For myself, I’ve got patients from Kansas, Oklahoma, and Missouri that might be operating under different guidelines. That makes it even more confusing,” he said.

More clarity is needed for individuals seeking boosters as well. “It would help to be very clear with the general public, who are becoming very knowledgeable within this vaccine realm,” Mr. Caswell said.
 

‘Gaming the system’

Although most people seeking a booster shot at one of Caswell’s pharmacies are following official recommendations, there are some who remain ineligible but nonetheless come in for an additional vaccine.

“Even before this announcement last Friday, in the latter part of August when the CDC talked about a booster for immunocompromised, we had interest from people who did not meet the criteria,” Mr. Caswell said.

To the ineligible, he and his staff explain the approval process, why certain decisions are made, and point out that the number of eligible Americans is likely to expand in the future.

“The vast majority of them are understanding,” Mr. Caswell said. “But we’ve had some people who really didn’t want to accept the information, and I don’t know what they’ve done.”

“Some people are gaming the system to get their booster or second shot of J&J,” he said.

For example, Mr. Caswell had a patient who crossed over state lines from Missouri seeking a vaccine booster at Wolkar Drug, a pharmacy in Baxter Springs, Kan. “We found out later he had a J&J shot at a facility or provider in Missouri. He came over to Kansas, signed up for it and got a booster with Moderna.”

“We called and asked him if he was aware of it. He said, ‘yes.’ When we questioned him more about it, he hung up.”

Dr. Edje is likewise seeing interest from some ineligible patients, she said.
 

Crossing a liability line?

Mr. Caswell has asked for advice from lawyers and the State Board of Pharmacy on potential liability if a pharmacist gives a booster to a patient not eligible under the official FDA and CDC guidance.

“We ask patients direct questions about whether they’ve had the COVID vaccine, COVID, and a whole litany of questions they must answer. And we’re assuming they are going to be honest and forthright,” he said. “The pharmacist needs to make sure they make every effort to get that information from the patient.”

Normally, healthcare providers like Mr. Caswell report each COVID-19 vaccination to the state registry after administration. “We have not gone through a police action and checked the registry first,” he said.

But, if people continue to try ‘gaming the system,’ he said, he might have to start checking the state registry before giving someone a booster.

The American Academy of Family Physicians offers advice from the CDC about legal protections for providers.

“As outlined by CDC, any off-label use of the Comirnaty/Pfizer-BioNTech COVID-19 vaccine is not authorized at this time and may not be covered under the PREP Act or the PREP Act declaration. This means that clinicians providing the vaccine outside of the authorized/approved use may not have immunity from claims,” the AAFP website states.

“Per CDC, individuals who receive a third dose may not be eligible for compensation after a possible adverse event. Such use would be in violation of the CDC COVID-19 vaccination program provider agreement and therefore may not be reimbursable and may impact the ability of a provider to remain in the CDC program, in addition to other potential sanctions. Administration fees for off-label doses may not be reimbursed by payers.”
 

Despite confusion, demand is up

Even amid all the uncertainty, there appears to be a jump in enthusiasm for the booster shots.

“The requests have gone up quite a bit. We’ve seen a number of requests from people in person and over the phone looking to get a booster,” Mr. Caswell said. “Since the discussion at the federal level...there has been a lot of interest in the third shot booster, itself, as well as about a booster for J&J.”

“There is quite a bit of excitement out there,” he said.

Dr. Edje agreed: “I take care of a fair number of folks...including the elderly and healthcare professionals. They are already asking for the booster.”

Interestingly, Dr. Edje would like to get a booster herself but is not eligible for the Pfizer third shot. She is a participant in a Moderna vaccine trial and can only receive additional immunization as part of the study.
 

‘Walk, don’t run’

To quell any potential early rush to get a third shot, U.S. health officials are reminding booster-ineligible people that they still have some protection against COVID-19.

“If you’re a person who ultimately might get a booster that will make you optimally protected, you don’t necessarily need to get it tomorrow,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases told CNN.

CDC Director Rochelle Walensky, MD, also weighed in. She told ABC that boosters for people who received a Moderna or Johnson & Johnson vaccine will be addressed with urgency.

“I want to reiterate that this is a very slow wane. There is no urgency here to go and get your booster immediately. You know, walk don’t run to your booster appointment,” she said.

“We will come and look at the data for Moderna and J&J in very short order.”

Dr. Edje and Mr. Caswell have reported no relevant financial relationships.

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

Many people are confused — patients and healthcare providers alike — in the wake of the U.S. Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) announcements about who is authorized to get a third or ‘booster’ shot of the Pfizer/BioNTech COVID-19 vaccine.

The official word on boosters from the CDC in the early morning hours of September 24 sparked a jump in people calling about or coming in for a third shot, healthcare providers report. At the same time, the uncertainty from changing federal messages about boosters is causing some chaos, especially in the form of vaccine misinformation.

The confusion started, in part, with the August 13 announcement that immunocompromised Americans were eligible for a booster shot. Next came the initial Biden administration intention to provide most U.S. adults with a third shot starting September 20 — an announcement later rolled back — followed by the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) limiting boosters to select groups last week.

“It was only 3% of the population that was going to be getting a third dose, then it was back to everyone being able to get the booster, and then it’s back to a select crew,” Louito Edje, MD, a family physician in private practice in Cincinnati, said in an interview with this news organization.

This kind of mixed messaging is generating more questions than answers.  

“Even though that is following the science, translating the science into policy, it’s really fraught with confusion for patients, especially,” added Dr. Edje, professor educator in the departments of medical education and family and community medicine at UC Health and a fellow of the American Academy of Family Physicians.

When asked if he’s seeing more uncertainty about boosters, community pharmacist Brian Caswell, RPh, said: “I’m going to have to say yes because I’ve been confused myself at times.”

“Yes, there is a lot of confusion,” added Mr. Caswell, owner or co-owner of four pharmacies in Kansas and Missouri and president of the National Community Pharmacists Association. 
 

Boosting misinformation?

“Unfortunately, confusion leads to an acceleration of misinformation,” Mr. Caswell said.

Dr. Edje shared an example. “The folks who have been hesitant to even get the first vaccine appear now a little less likely to want to go ahead and get vaccinated.”

These patients point to breakthrough COVID-19 cases of the Delta variant, which “reinforces that they don’t need to get vaccinated in the first place,” Dr. Edje said.

“That’s unfortunate because it’s a complete fallacy.”

Clearer communication from the federal government could help alleviate confusion, Mr. Caswell said. “I would like to see an official CDC chart that states who is eligible as of a certain date. Something that is accessible through their webpage or a social media source that can be updated. That would help all of us.”

“For myself, I’ve got patients from Kansas, Oklahoma, and Missouri that might be operating under different guidelines. That makes it even more confusing,” he said.

More clarity is needed for individuals seeking boosters as well. “It would help to be very clear with the general public, who are becoming very knowledgeable within this vaccine realm,” Mr. Caswell said.
 

‘Gaming the system’

Although most people seeking a booster shot at one of Caswell’s pharmacies are following official recommendations, there are some who remain ineligible but nonetheless come in for an additional vaccine.

“Even before this announcement last Friday, in the latter part of August when the CDC talked about a booster for immunocompromised, we had interest from people who did not meet the criteria,” Mr. Caswell said.

To the ineligible, he and his staff explain the approval process, why certain decisions are made, and point out that the number of eligible Americans is likely to expand in the future.

“The vast majority of them are understanding,” Mr. Caswell said. “But we’ve had some people who really didn’t want to accept the information, and I don’t know what they’ve done.”

“Some people are gaming the system to get their booster or second shot of J&J,” he said.

For example, Mr. Caswell had a patient who crossed over state lines from Missouri seeking a vaccine booster at Wolkar Drug, a pharmacy in Baxter Springs, Kan. “We found out later he had a J&J shot at a facility or provider in Missouri. He came over to Kansas, signed up for it and got a booster with Moderna.”

“We called and asked him if he was aware of it. He said, ‘yes.’ When we questioned him more about it, he hung up.”

Dr. Edje is likewise seeing interest from some ineligible patients, she said.
 

Crossing a liability line?

Mr. Caswell has asked for advice from lawyers and the State Board of Pharmacy on potential liability if a pharmacist gives a booster to a patient not eligible under the official FDA and CDC guidance.

“We ask patients direct questions about whether they’ve had the COVID vaccine, COVID, and a whole litany of questions they must answer. And we’re assuming they are going to be honest and forthright,” he said. “The pharmacist needs to make sure they make every effort to get that information from the patient.”

Normally, healthcare providers like Mr. Caswell report each COVID-19 vaccination to the state registry after administration. “We have not gone through a police action and checked the registry first,” he said.

But, if people continue to try ‘gaming the system,’ he said, he might have to start checking the state registry before giving someone a booster.

The American Academy of Family Physicians offers advice from the CDC about legal protections for providers.

“As outlined by CDC, any off-label use of the Comirnaty/Pfizer-BioNTech COVID-19 vaccine is not authorized at this time and may not be covered under the PREP Act or the PREP Act declaration. This means that clinicians providing the vaccine outside of the authorized/approved use may not have immunity from claims,” the AAFP website states.

“Per CDC, individuals who receive a third dose may not be eligible for compensation after a possible adverse event. Such use would be in violation of the CDC COVID-19 vaccination program provider agreement and therefore may not be reimbursable and may impact the ability of a provider to remain in the CDC program, in addition to other potential sanctions. Administration fees for off-label doses may not be reimbursed by payers.”
 

Despite confusion, demand is up

Even amid all the uncertainty, there appears to be a jump in enthusiasm for the booster shots.

“The requests have gone up quite a bit. We’ve seen a number of requests from people in person and over the phone looking to get a booster,” Mr. Caswell said. “Since the discussion at the federal level...there has been a lot of interest in the third shot booster, itself, as well as about a booster for J&J.”

“There is quite a bit of excitement out there,” he said.

Dr. Edje agreed: “I take care of a fair number of folks...including the elderly and healthcare professionals. They are already asking for the booster.”

Interestingly, Dr. Edje would like to get a booster herself but is not eligible for the Pfizer third shot. She is a participant in a Moderna vaccine trial and can only receive additional immunization as part of the study.
 

‘Walk, don’t run’

To quell any potential early rush to get a third shot, U.S. health officials are reminding booster-ineligible people that they still have some protection against COVID-19.

“If you’re a person who ultimately might get a booster that will make you optimally protected, you don’t necessarily need to get it tomorrow,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases told CNN.

CDC Director Rochelle Walensky, MD, also weighed in. She told ABC that boosters for people who received a Moderna or Johnson & Johnson vaccine will be addressed with urgency.

“I want to reiterate that this is a very slow wane. There is no urgency here to go and get your booster immediately. You know, walk don’t run to your booster appointment,” she said.

“We will come and look at the data for Moderna and J&J in very short order.”

Dr. Edje and Mr. Caswell have reported no relevant financial relationships.

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

Many people are confused — patients and healthcare providers alike — in the wake of the U.S. Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) announcements about who is authorized to get a third or ‘booster’ shot of the Pfizer/BioNTech COVID-19 vaccine.

The official word on boosters from the CDC in the early morning hours of September 24 sparked a jump in people calling about or coming in for a third shot, healthcare providers report. At the same time, the uncertainty from changing federal messages about boosters is causing some chaos, especially in the form of vaccine misinformation.

The confusion started, in part, with the August 13 announcement that immunocompromised Americans were eligible for a booster shot. Next came the initial Biden administration intention to provide most U.S. adults with a third shot starting September 20 — an announcement later rolled back — followed by the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) limiting boosters to select groups last week.

“It was only 3% of the population that was going to be getting a third dose, then it was back to everyone being able to get the booster, and then it’s back to a select crew,” Louito Edje, MD, a family physician in private practice in Cincinnati, said in an interview with this news organization.

This kind of mixed messaging is generating more questions than answers.  

“Even though that is following the science, translating the science into policy, it’s really fraught with confusion for patients, especially,” added Dr. Edje, professor educator in the departments of medical education and family and community medicine at UC Health and a fellow of the American Academy of Family Physicians.

When asked if he’s seeing more uncertainty about boosters, community pharmacist Brian Caswell, RPh, said: “I’m going to have to say yes because I’ve been confused myself at times.”

“Yes, there is a lot of confusion,” added Mr. Caswell, owner or co-owner of four pharmacies in Kansas and Missouri and president of the National Community Pharmacists Association. 
 

Boosting misinformation?

“Unfortunately, confusion leads to an acceleration of misinformation,” Mr. Caswell said.

Dr. Edje shared an example. “The folks who have been hesitant to even get the first vaccine appear now a little less likely to want to go ahead and get vaccinated.”

These patients point to breakthrough COVID-19 cases of the Delta variant, which “reinforces that they don’t need to get vaccinated in the first place,” Dr. Edje said.

“That’s unfortunate because it’s a complete fallacy.”

Clearer communication from the federal government could help alleviate confusion, Mr. Caswell said. “I would like to see an official CDC chart that states who is eligible as of a certain date. Something that is accessible through their webpage or a social media source that can be updated. That would help all of us.”

“For myself, I’ve got patients from Kansas, Oklahoma, and Missouri that might be operating under different guidelines. That makes it even more confusing,” he said.

More clarity is needed for individuals seeking boosters as well. “It would help to be very clear with the general public, who are becoming very knowledgeable within this vaccine realm,” Mr. Caswell said.
 

‘Gaming the system’

Although most people seeking a booster shot at one of Caswell’s pharmacies are following official recommendations, there are some who remain ineligible but nonetheless come in for an additional vaccine.

“Even before this announcement last Friday, in the latter part of August when the CDC talked about a booster for immunocompromised, we had interest from people who did not meet the criteria,” Mr. Caswell said.

To the ineligible, he and his staff explain the approval process, why certain decisions are made, and point out that the number of eligible Americans is likely to expand in the future.

“The vast majority of them are understanding,” Mr. Caswell said. “But we’ve had some people who really didn’t want to accept the information, and I don’t know what they’ve done.”

“Some people are gaming the system to get their booster or second shot of J&J,” he said.

For example, Mr. Caswell had a patient who crossed over state lines from Missouri seeking a vaccine booster at Wolkar Drug, a pharmacy in Baxter Springs, Kan. “We found out later he had a J&J shot at a facility or provider in Missouri. He came over to Kansas, signed up for it and got a booster with Moderna.”

“We called and asked him if he was aware of it. He said, ‘yes.’ When we questioned him more about it, he hung up.”

Dr. Edje is likewise seeing interest from some ineligible patients, she said.
 

Crossing a liability line?

Mr. Caswell has asked for advice from lawyers and the State Board of Pharmacy on potential liability if a pharmacist gives a booster to a patient not eligible under the official FDA and CDC guidance.

“We ask patients direct questions about whether they’ve had the COVID vaccine, COVID, and a whole litany of questions they must answer. And we’re assuming they are going to be honest and forthright,” he said. “The pharmacist needs to make sure they make every effort to get that information from the patient.”

Normally, healthcare providers like Mr. Caswell report each COVID-19 vaccination to the state registry after administration. “We have not gone through a police action and checked the registry first,” he said.

But, if people continue to try ‘gaming the system,’ he said, he might have to start checking the state registry before giving someone a booster.

The American Academy of Family Physicians offers advice from the CDC about legal protections for providers.

“As outlined by CDC, any off-label use of the Comirnaty/Pfizer-BioNTech COVID-19 vaccine is not authorized at this time and may not be covered under the PREP Act or the PREP Act declaration. This means that clinicians providing the vaccine outside of the authorized/approved use may not have immunity from claims,” the AAFP website states.

“Per CDC, individuals who receive a third dose may not be eligible for compensation after a possible adverse event. Such use would be in violation of the CDC COVID-19 vaccination program provider agreement and therefore may not be reimbursable and may impact the ability of a provider to remain in the CDC program, in addition to other potential sanctions. Administration fees for off-label doses may not be reimbursed by payers.”
 

Despite confusion, demand is up

Even amid all the uncertainty, there appears to be a jump in enthusiasm for the booster shots.

“The requests have gone up quite a bit. We’ve seen a number of requests from people in person and over the phone looking to get a booster,” Mr. Caswell said. “Since the discussion at the federal level...there has been a lot of interest in the third shot booster, itself, as well as about a booster for J&J.”

“There is quite a bit of excitement out there,” he said.

Dr. Edje agreed: “I take care of a fair number of folks...including the elderly and healthcare professionals. They are already asking for the booster.”

Interestingly, Dr. Edje would like to get a booster herself but is not eligible for the Pfizer third shot. She is a participant in a Moderna vaccine trial and can only receive additional immunization as part of the study.
 

‘Walk, don’t run’

To quell any potential early rush to get a third shot, U.S. health officials are reminding booster-ineligible people that they still have some protection against COVID-19.

“If you’re a person who ultimately might get a booster that will make you optimally protected, you don’t necessarily need to get it tomorrow,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases told CNN.

CDC Director Rochelle Walensky, MD, also weighed in. She told ABC that boosters for people who received a Moderna or Johnson & Johnson vaccine will be addressed with urgency.

“I want to reiterate that this is a very slow wane. There is no urgency here to go and get your booster immediately. You know, walk don’t run to your booster appointment,” she said.

“We will come and look at the data for Moderna and J&J in very short order.”

Dr. Edje and Mr. Caswell have reported no relevant financial relationships.

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

REFERENCES

1. US Preventive Services Task Force. Screening for prediabetes and type 2 diabetes. JAMA. 2021;326:736-743. doi: 10.1001/jama.2021.12531
2. American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2021. Diabetes Care. 2021;44(suppl 1):S15-S33. https://doi.org/10.2337/dc21-S002

REFERENCES

1. US Preventive Services Task Force. Screening for prediabetes and type 2 diabetes. JAMA. 2021;326:736-743. doi: 10.1001/jama.2021.12531
2. American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2021. Diabetes Care. 2021;44(suppl 1):S15-S33. https://doi.org/10.2337/dc21-S002

REFERENCES

1. US Preventive Services Task Force. Screening for prediabetes and type 2 diabetes. JAMA. 2021;326:736-743. doi: 10.1001/jama.2021.12531
2. American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2021. Diabetes Care. 2021;44(suppl 1):S15-S33. https://doi.org/10.2337/dc21-S002

Key clinical point: Infection with the SARS-CoV-2 Delta (B.1.617.2) variant carries a significantly higher risk for hospitalization and attending hospital for emergency care than the Alpha (B.1.1.7) variant.

Major finding: The Delta variant was associated with more than twice the risk of being admitted to hospital (adjusted hazard ratio [aHR], 2·26; 95% confidence interval [CI], 1·32-3·89) and nearly 1.5 times the risk of seeking emergency care (aHR, 1·45; 95% CI, 1·08-1·95) compared with the Alpha variant.

Study details: A cohort study included 43,338 COVID-19-positive cases in England who were found to be infected with either the Alpha or Delta SARS-CoV-2 variant through whole-genome sequencing.

Disclosures: The study was funded by Medical Research Council, UK Research and Innovation, Department of Health and Social Care, and National Institute for Health Research. GD's employer, Public Health England was funded by GlaxoSmithKline for a research project related to seasonal influenza and antiviral treatment but had no relation to COVID-19. The remaining authors declared no conflict of interests.

Source: Twohig KA et al. Lancet Infect Dis. 2021 Aug 27. doi: 10.1016/S1473-3099(21)00475-8.

Key clinical point: Infection with the SARS-CoV-2 Delta (B.1.617.2) variant carries a significantly higher risk for hospitalization and attending hospital for emergency care than the Alpha (B.1.1.7) variant.

Major finding: The Delta variant was associated with more than twice the risk of being admitted to hospital (adjusted hazard ratio [aHR], 2·26; 95% confidence interval [CI], 1·32-3·89) and nearly 1.5 times the risk of seeking emergency care (aHR, 1·45; 95% CI, 1·08-1·95) compared with the Alpha variant.

Study details: A cohort study included 43,338 COVID-19-positive cases in England who were found to be infected with either the Alpha or Delta SARS-CoV-2 variant through whole-genome sequencing.

Disclosures: The study was funded by Medical Research Council, UK Research and Innovation, Department of Health and Social Care, and National Institute for Health Research. GD's employer, Public Health England was funded by GlaxoSmithKline for a research project related to seasonal influenza and antiviral treatment but had no relation to COVID-19. The remaining authors declared no conflict of interests.

Source: Twohig KA et al. Lancet Infect Dis. 2021 Aug 27. doi: 10.1016/S1473-3099(21)00475-8.

Key clinical point: Infection with the SARS-CoV-2 Delta (B.1.617.2) variant carries a significantly higher risk for hospitalization and attending hospital for emergency care than the Alpha (B.1.1.7) variant.

Major finding: The Delta variant was associated with more than twice the risk of being admitted to hospital (adjusted hazard ratio [aHR], 2·26; 95% confidence interval [CI], 1·32-3·89) and nearly 1.5 times the risk of seeking emergency care (aHR, 1·45; 95% CI, 1·08-1·95) compared with the Alpha variant.

Study details: A cohort study included 43,338 COVID-19-positive cases in England who were found to be infected with either the Alpha or Delta SARS-CoV-2 variant through whole-genome sequencing.

Disclosures: The study was funded by Medical Research Council, UK Research and Innovation, Department of Health and Social Care, and National Institute for Health Research. GD's employer, Public Health England was funded by GlaxoSmithKline for a research project related to seasonal influenza and antiviral treatment but had no relation to COVID-19. The remaining authors declared no conflict of interests.

Source: Twohig KA et al. Lancet Infect Dis. 2021 Aug 27. doi: 10.1016/S1473-3099(21)00475-8.

Based on significant progression-free survival (PFS) benefits shown in the phase 3 TULIP trial, trastuzumab duocarmazine (SYD985) may provide a new treatment option among HER2-positive metastatic breast cancer patients, according to Cristina Saura, MD, head of the breast cancer program at Vall d’Hebron University Hospital, Barcelona. Dr. Saura presented the results of the TULIP trial (abstract LBA15) on Sept. 19 at the 2021 European Society for Medical Oncology Congress.

Trastuzumab duocarmazine is a novel HER2-targeting antibody-drug conjugate that consists of trastuzumab and a drug containing duocarmycin. Its three-way mechanism of action includes uptake of the antibody-drug conjugate by internalization and intracellular release of duocarmycin with two bystander effects: proteolytic cleavage and subsequent release of payload in the tumor microenvironment and diffusion of active payload to neighboring tumor cells.

While one physician described the results as encouraging, another said the treatment is not nearly ready for primetime.

“It is encouraging to observe clinically meaningful and potentially practice changing progression-free survival improvements in patients receiving treatment in the third line and beyond,” said Aditya Bardia, MD, Massachusetts General Hospital, Boston. “Several agents have been approved as treatments for HER2-positive metastatic breast cancer in recent years including T-DXd, neratinib, tucatinib, and margetuximab. Trastuzumab duocarmazine could eventually be another option.”

Fatima Cardoso, MD, director of the breast cancer unit at the Breast Cancer Research Foundation, New York, said: “At this time there is only a minor 2-month difference in progression-free survival and a nonsignificant overall difference. With the high incidence of ocular toxicity and four toxic deaths, we cannot recommend this drug for clinical practice, in my opinion.”
 

Two or more prior therapies for metastatic breast cancer

TULIP investigators enrolled 437 patients from 83 sites in 11 countries with HER2-positive locally advanced or metastatic breast cancer who had received two or more therapies for metastatic disease (treatment for brain metastases allowed). They were randomized 2:1 to trastuzumab duocarmazine (1.2 mg/kg every 21 days, 291 patients) or physician’s choice (146 patients) of one of three trastuzumab-containing combinations or lapatinib plus capecitabine. Treatment was continued until progression or unacceptable toxicity. The primary endpoint was centrally assessed PFS.

Longer PFS with trastuzumab duocarmazine

Median age was 57 years, and the median number of prior metastatic breast cancer regimens was 4.7. Centrally reviewed PFS was significantly longer in the trastuzumab duocarmazine group at 7.0 months versus 4.9 months for physicians choice treatment (hazard ratio, 0.64; 95% confidence interval, 0.49-0.84; P = .002). Subgroup analysis, also centrally reviewed, revealed numerical advantage for trastuzumab duocarmazine over physician’s choice across all categories (except for Eastern Cooperative Oncology Group status 2). Analysis of PFS by investigators showed a similar benefit for trastuzumab duocarmazine (6.9 months vs. 4.6 months; HR, 0.60; P < .001).

A first look at median overall survival showed a nonsignificant advantage for trastuzumab duocarmazine (20.4 months vs. 16.3 months (HR, 0.83; 95% CI, 0.62-1.09, P = .153). The overall response rate (partial or complete response) was similar between groups at 27.8% for trastuzumab duocarmazine and 29.5% for physician’s choice with reductions in target lesion measurement at 70.2% and 32.2% for trastuzumab duocarmazine and physician’s choice, respectively. The clinical benefit rates were 38.5% for trastuzumab duocarmazine and 32.2% for physician’s choice.
 

Ocular toxicity

Most patients had at least one treatment-related adverse event (96.5% SD985, 96.4% PC), and grade 3 or higher event rates were similar between groups (52.8% SYD985, 48.2% PC). The most frequently reported adverse events for trastuzumab duocarmazine were ocular toxicity, with conjunctivitis reported in 38.2%, and keratitis in 38.2%, with fatigue at 33.3%; for physician’s choice these were diarrhea (35.8%), nausea (31.4%) and fatigue (29.9%). Interstitial lung disease pneumonitis was reported for 7.6% (5.2% grade 1-2) of patients treated with trastuzumab duocarmazine, including two grade 5 events.

Eye toxicity led to discontinuations in 20.8% of trastuzumab duocarmazine patients, dose modifications in 22.9%, with dose modifications for interstitial lung disease/pneumonitis in 5.2% of trastuzumab duocarmazine patients. Six fatalities (2.1%) were reported in the trastuzumab duocarmazine group, with four attributed to treatment. Assessment of health-related quality of life showed no significant difference between groups.

Dr. Manich outlined risk mitigation strategies. Patients with prior keratitis were excluded and patients were given prophylactic lubricating eye drops and regular eye exams by ophthalmologists. Treatment was discontinued if grade 3 or higher keratitis developed, and was delayed if grade 3 conjunctivitis developed until it reduced to grade 2. Also, patients with prior pneumonitis were excluded and CT lung scans were evaluated for lung changes. New or worsening respiratory symptoms triggered a full diagnostic workup. Treatment was discontinued for grade 2 or higher pneumonitis and delayed until resolution for grade 1 pneumonitis.

TULIP was funded by Byondis. Dr. Saura disclosed numerous financial interests including support from AstraZeneca and Daiichi Sankyo.

Based on significant progression-free survival (PFS) benefits shown in the phase 3 TULIP trial, trastuzumab duocarmazine (SYD985) may provide a new treatment option among HER2-positive metastatic breast cancer patients, according to Cristina Saura, MD, head of the breast cancer program at Vall d’Hebron University Hospital, Barcelona. Dr. Saura presented the results of the TULIP trial (abstract LBA15) on Sept. 19 at the 2021 European Society for Medical Oncology Congress.

Trastuzumab duocarmazine is a novel HER2-targeting antibody-drug conjugate that consists of trastuzumab and a drug containing duocarmycin. Its three-way mechanism of action includes uptake of the antibody-drug conjugate by internalization and intracellular release of duocarmycin with two bystander effects: proteolytic cleavage and subsequent release of payload in the tumor microenvironment and diffusion of active payload to neighboring tumor cells.

While one physician described the results as encouraging, another said the treatment is not nearly ready for primetime.

“It is encouraging to observe clinically meaningful and potentially practice changing progression-free survival improvements in patients receiving treatment in the third line and beyond,” said Aditya Bardia, MD, Massachusetts General Hospital, Boston. “Several agents have been approved as treatments for HER2-positive metastatic breast cancer in recent years including T-DXd, neratinib, tucatinib, and margetuximab. Trastuzumab duocarmazine could eventually be another option.”

Fatima Cardoso, MD, director of the breast cancer unit at the Breast Cancer Research Foundation, New York, said: “At this time there is only a minor 2-month difference in progression-free survival and a nonsignificant overall difference. With the high incidence of ocular toxicity and four toxic deaths, we cannot recommend this drug for clinical practice, in my opinion.”
 

Two or more prior therapies for metastatic breast cancer

TULIP investigators enrolled 437 patients from 83 sites in 11 countries with HER2-positive locally advanced or metastatic breast cancer who had received two or more therapies for metastatic disease (treatment for brain metastases allowed). They were randomized 2:1 to trastuzumab duocarmazine (1.2 mg/kg every 21 days, 291 patients) or physician’s choice (146 patients) of one of three trastuzumab-containing combinations or lapatinib plus capecitabine. Treatment was continued until progression or unacceptable toxicity. The primary endpoint was centrally assessed PFS.

Longer PFS with trastuzumab duocarmazine

Median age was 57 years, and the median number of prior metastatic breast cancer regimens was 4.7. Centrally reviewed PFS was significantly longer in the trastuzumab duocarmazine group at 7.0 months versus 4.9 months for physicians choice treatment (hazard ratio, 0.64; 95% confidence interval, 0.49-0.84; P = .002). Subgroup analysis, also centrally reviewed, revealed numerical advantage for trastuzumab duocarmazine over physician’s choice across all categories (except for Eastern Cooperative Oncology Group status 2). Analysis of PFS by investigators showed a similar benefit for trastuzumab duocarmazine (6.9 months vs. 4.6 months; HR, 0.60; P < .001).

A first look at median overall survival showed a nonsignificant advantage for trastuzumab duocarmazine (20.4 months vs. 16.3 months (HR, 0.83; 95% CI, 0.62-1.09, P = .153). The overall response rate (partial or complete response) was similar between groups at 27.8% for trastuzumab duocarmazine and 29.5% for physician’s choice with reductions in target lesion measurement at 70.2% and 32.2% for trastuzumab duocarmazine and physician’s choice, respectively. The clinical benefit rates were 38.5% for trastuzumab duocarmazine and 32.2% for physician’s choice.
 

Ocular toxicity

Most patients had at least one treatment-related adverse event (96.5% SD985, 96.4% PC), and grade 3 or higher event rates were similar between groups (52.8% SYD985, 48.2% PC). The most frequently reported adverse events for trastuzumab duocarmazine were ocular toxicity, with conjunctivitis reported in 38.2%, and keratitis in 38.2%, with fatigue at 33.3%; for physician’s choice these were diarrhea (35.8%), nausea (31.4%) and fatigue (29.9%). Interstitial lung disease pneumonitis was reported for 7.6% (5.2% grade 1-2) of patients treated with trastuzumab duocarmazine, including two grade 5 events.

Eye toxicity led to discontinuations in 20.8% of trastuzumab duocarmazine patients, dose modifications in 22.9%, with dose modifications for interstitial lung disease/pneumonitis in 5.2% of trastuzumab duocarmazine patients. Six fatalities (2.1%) were reported in the trastuzumab duocarmazine group, with four attributed to treatment. Assessment of health-related quality of life showed no significant difference between groups.

Dr. Manich outlined risk mitigation strategies. Patients with prior keratitis were excluded and patients were given prophylactic lubricating eye drops and regular eye exams by ophthalmologists. Treatment was discontinued if grade 3 or higher keratitis developed, and was delayed if grade 3 conjunctivitis developed until it reduced to grade 2. Also, patients with prior pneumonitis were excluded and CT lung scans were evaluated for lung changes. New or worsening respiratory symptoms triggered a full diagnostic workup. Treatment was discontinued for grade 2 or higher pneumonitis and delayed until resolution for grade 1 pneumonitis.

TULIP was funded by Byondis. Dr. Saura disclosed numerous financial interests including support from AstraZeneca and Daiichi Sankyo.

Based on significant progression-free survival (PFS) benefits shown in the phase 3 TULIP trial, trastuzumab duocarmazine (SYD985) may provide a new treatment option among HER2-positive metastatic breast cancer patients, according to Cristina Saura, MD, head of the breast cancer program at Vall d’Hebron University Hospital, Barcelona. Dr. Saura presented the results of the TULIP trial (abstract LBA15) on Sept. 19 at the 2021 European Society for Medical Oncology Congress.

Trastuzumab duocarmazine is a novel HER2-targeting antibody-drug conjugate that consists of trastuzumab and a drug containing duocarmycin. Its three-way mechanism of action includes uptake of the antibody-drug conjugate by internalization and intracellular release of duocarmycin with two bystander effects: proteolytic cleavage and subsequent release of payload in the tumor microenvironment and diffusion of active payload to neighboring tumor cells.

While one physician described the results as encouraging, another said the treatment is not nearly ready for primetime.

“It is encouraging to observe clinically meaningful and potentially practice changing progression-free survival improvements in patients receiving treatment in the third line and beyond,” said Aditya Bardia, MD, Massachusetts General Hospital, Boston. “Several agents have been approved as treatments for HER2-positive metastatic breast cancer in recent years including T-DXd, neratinib, tucatinib, and margetuximab. Trastuzumab duocarmazine could eventually be another option.”

Fatima Cardoso, MD, director of the breast cancer unit at the Breast Cancer Research Foundation, New York, said: “At this time there is only a minor 2-month difference in progression-free survival and a nonsignificant overall difference. With the high incidence of ocular toxicity and four toxic deaths, we cannot recommend this drug for clinical practice, in my opinion.”
 

Two or more prior therapies for metastatic breast cancer

TULIP investigators enrolled 437 patients from 83 sites in 11 countries with HER2-positive locally advanced or metastatic breast cancer who had received two or more therapies for metastatic disease (treatment for brain metastases allowed). They were randomized 2:1 to trastuzumab duocarmazine (1.2 mg/kg every 21 days, 291 patients) or physician’s choice (146 patients) of one of three trastuzumab-containing combinations or lapatinib plus capecitabine. Treatment was continued until progression or unacceptable toxicity. The primary endpoint was centrally assessed PFS.

Longer PFS with trastuzumab duocarmazine

Median age was 57 years, and the median number of prior metastatic breast cancer regimens was 4.7. Centrally reviewed PFS was significantly longer in the trastuzumab duocarmazine group at 7.0 months versus 4.9 months for physicians choice treatment (hazard ratio, 0.64; 95% confidence interval, 0.49-0.84; P = .002). Subgroup analysis, also centrally reviewed, revealed numerical advantage for trastuzumab duocarmazine over physician’s choice across all categories (except for Eastern Cooperative Oncology Group status 2). Analysis of PFS by investigators showed a similar benefit for trastuzumab duocarmazine (6.9 months vs. 4.6 months; HR, 0.60; P < .001).

A first look at median overall survival showed a nonsignificant advantage for trastuzumab duocarmazine (20.4 months vs. 16.3 months (HR, 0.83; 95% CI, 0.62-1.09, P = .153). The overall response rate (partial or complete response) was similar between groups at 27.8% for trastuzumab duocarmazine and 29.5% for physician’s choice with reductions in target lesion measurement at 70.2% and 32.2% for trastuzumab duocarmazine and physician’s choice, respectively. The clinical benefit rates were 38.5% for trastuzumab duocarmazine and 32.2% for physician’s choice.
 

Ocular toxicity

Most patients had at least one treatment-related adverse event (96.5% SD985, 96.4% PC), and grade 3 or higher event rates were similar between groups (52.8% SYD985, 48.2% PC). The most frequently reported adverse events for trastuzumab duocarmazine were ocular toxicity, with conjunctivitis reported in 38.2%, and keratitis in 38.2%, with fatigue at 33.3%; for physician’s choice these were diarrhea (35.8%), nausea (31.4%) and fatigue (29.9%). Interstitial lung disease pneumonitis was reported for 7.6% (5.2% grade 1-2) of patients treated with trastuzumab duocarmazine, including two grade 5 events.

Eye toxicity led to discontinuations in 20.8% of trastuzumab duocarmazine patients, dose modifications in 22.9%, with dose modifications for interstitial lung disease/pneumonitis in 5.2% of trastuzumab duocarmazine patients. Six fatalities (2.1%) were reported in the trastuzumab duocarmazine group, with four attributed to treatment. Assessment of health-related quality of life showed no significant difference between groups.

Dr. Manich outlined risk mitigation strategies. Patients with prior keratitis were excluded and patients were given prophylactic lubricating eye drops and regular eye exams by ophthalmologists. Treatment was discontinued if grade 3 or higher keratitis developed, and was delayed if grade 3 conjunctivitis developed until it reduced to grade 2. Also, patients with prior pneumonitis were excluded and CT lung scans were evaluated for lung changes. New or worsening respiratory symptoms triggered a full diagnostic workup. Treatment was discontinued for grade 2 or higher pneumonitis and delayed until resolution for grade 1 pneumonitis.

TULIP was funded by Byondis. Dr. Saura disclosed numerous financial interests including support from AstraZeneca and Daiichi Sankyo.

Decreased motor function, as well as other adverse outcomes, are linked to post–COVID-19 syndrome in patients with Parkinson’s disease, new research suggests.

Results from a small, international retrospective case study show that about half of participants with Parkinson’s disease who developed post–COVID-19 syndrome experienced a worsening of motor symptoms and that their need for anti-Parkinson’s medication increased.

“In our series of 27 patients with Parkinson’s disease, 85% developed post–COVID-19 symptoms,” said lead investigator Valentina Leta, MD, Parkinson’s Foundation Center of Excellence, Kings College Hospital, London.

The most common long-term effects were worsening of motor function and an increase in the need for daily levodopa. Other adverse effects included fatigue; cognitive disturbances, including brain fog, loss of concentration, and memory deficits; and sleep disturbances, such as insomnia, Dr. Leta said.

The findings were presented at the International Congress of Parkinson’s Disease and Movement Disorders.
 

Long-term sequelae

Previous studies have documented worsening of motor and nonmotor symptoms among patients with Parkinson’s disease in the acute phase of COVID-19. Results of these studies suggest that mortality may be higher among patients with more advanced Parkinson’s disease, comorbidities, and frailty.

Dr. Leta noted that long-term sequelae with so-called long COVID have not been adequately explored, prompting the current study.

The case series included 27 patients with Parkinson’s disease in the United Kingdom, Italy, Romania, and Mexico who were also affected by COVID-19. The investigators defined post–COVID-19 syndrome as “signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks, and are not explained by an alternative diagnosis.”

Because some of the symptoms are also associated with Parkinson’s disease, symptoms were attributed to post–COVID-19 only if they occurred after a confirmed severe acute respiratory infection with SARS-CoV-2 or if patients experienced an acute or subacute worsening of a pre-existing symptom that had previously been stable.

Among the participants, 59.3% were men. The mean age at the time of Parkinson’s disease diagnosis was 59.0 ± 12.7 years, and the mean Parkinson’s disease duration was 9.2 ± 7.8 years. The patients were in Hoehn and Yahr stage 2.0 ± 1.0 at the time of their COVID-19 diagnosis.

Charlson Comorbidity Index score at COVID-19 diagnosis was 2.0 ± 1.5, and the levodopa equivalent daily dose (LEDD) was 1053.5 ± 842.4 mg.
 

Symptom worsening

“Cognitive disturbances” were defined as brain fog, concentration difficulty, or memory problems. “Peripheral neuropathy symptoms” were defined as having feelings of pins and needles or numbness.

By far, the most prevalent sequelae were worsening motor symptoms and increased need for anti-Parkinson’s medications. Each affected about half of the study cohort, the investigators noted.

Dr. Leta added the non-Parkinson’s disease-specific findings are in line with the existing literature on long COVID in the general population. The severity of COVID-19, as indicated by a history of hospitalization, did not seem to correlate with development of post–COVID-19 syndrome in patients with Parkinson’s disease.

In this series, few patients had respiratory, cardiovascular, gastrointestinal, musculoskeletal, or dermatologic symptoms. Interestingly, only four patients reported a loss of taste or smell.

The investigators noted that in addition to viral illness, the stress of prolonged lockdown during the pandemic and reduced access to health care and rehabilitation programs may contribute to the burden of post–COVID-19 syndrome in patients with Parkinson’s disease.

Study limitations cited include the relatively small sample size and the lack of a control group. The researchers noted the need for larger studies to elucidate the natural history of COVID-19 among patients with Parkinson’s disease in order to raise awareness of their needs and to help develop personalized management strategies.
 

Meaningful addition

Commenting on the findings, Kyle Mitchell, MD, movement disorders neurologist, Duke University, Durham, N.C., said he found the study to be a meaningful addition in light of the fact that data on the challenges that patients with Parkinson’s disease may face after having COVID-19 are limited.

“What I liked about this study was there’s data from multiple countries, what looks like a diverse population of study participants, and really just addressing a question that we get asked a lot in clinic and we see a fair amount, but we don’t really know a lot about: how people with Parkinson’s disease will do during and post COVID-19 infection,” said Dr. Mitchell, who was not involved with the research.

He said the worsening of motor symptoms and the need for increased dopaminergic medication brought some questions to mind.

“Is this increase in medications permanent, or is it temporary until post-COVID resolves? Or is it truly something where they stay on a higher dose?” he asked.

Dr. Mitchell said he does not believe the worsening of symptoms is specific to COVID-19 and that he sees individuals with Parkinson’s disease who experience setbacks “from any number of infections.” These include urinary tract infections and influenza, which are associated with worsening mobility, rigidity, tremor, fatigue, and cognition.

“People with Parkinson’s disease seem to get hit harder by infections in general,” he said.

The study had no outside funding. Dr. Leta and Dr. Mitchell have disclosed no relevant financial relationships.

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

Decreased motor function, as well as other adverse outcomes, are linked to post–COVID-19 syndrome in patients with Parkinson’s disease, new research suggests.

Results from a small, international retrospective case study show that about half of participants with Parkinson’s disease who developed post–COVID-19 syndrome experienced a worsening of motor symptoms and that their need for anti-Parkinson’s medication increased.

“In our series of 27 patients with Parkinson’s disease, 85% developed post–COVID-19 symptoms,” said lead investigator Valentina Leta, MD, Parkinson’s Foundation Center of Excellence, Kings College Hospital, London.

The most common long-term effects were worsening of motor function and an increase in the need for daily levodopa. Other adverse effects included fatigue; cognitive disturbances, including brain fog, loss of concentration, and memory deficits; and sleep disturbances, such as insomnia, Dr. Leta said.

The findings were presented at the International Congress of Parkinson’s Disease and Movement Disorders.
 

Long-term sequelae

Previous studies have documented worsening of motor and nonmotor symptoms among patients with Parkinson’s disease in the acute phase of COVID-19. Results of these studies suggest that mortality may be higher among patients with more advanced Parkinson’s disease, comorbidities, and frailty.

Dr. Leta noted that long-term sequelae with so-called long COVID have not been adequately explored, prompting the current study.

The case series included 27 patients with Parkinson’s disease in the United Kingdom, Italy, Romania, and Mexico who were also affected by COVID-19. The investigators defined post–COVID-19 syndrome as “signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks, and are not explained by an alternative diagnosis.”

Because some of the symptoms are also associated with Parkinson’s disease, symptoms were attributed to post–COVID-19 only if they occurred after a confirmed severe acute respiratory infection with SARS-CoV-2 or if patients experienced an acute or subacute worsening of a pre-existing symptom that had previously been stable.

Among the participants, 59.3% were men. The mean age at the time of Parkinson’s disease diagnosis was 59.0 ± 12.7 years, and the mean Parkinson’s disease duration was 9.2 ± 7.8 years. The patients were in Hoehn and Yahr stage 2.0 ± 1.0 at the time of their COVID-19 diagnosis.

Charlson Comorbidity Index score at COVID-19 diagnosis was 2.0 ± 1.5, and the levodopa equivalent daily dose (LEDD) was 1053.5 ± 842.4 mg.
 

Symptom worsening

“Cognitive disturbances” were defined as brain fog, concentration difficulty, or memory problems. “Peripheral neuropathy symptoms” were defined as having feelings of pins and needles or numbness.

By far, the most prevalent sequelae were worsening motor symptoms and increased need for anti-Parkinson’s medications. Each affected about half of the study cohort, the investigators noted.

Dr. Leta added the non-Parkinson’s disease-specific findings are in line with the existing literature on long COVID in the general population. The severity of COVID-19, as indicated by a history of hospitalization, did not seem to correlate with development of post–COVID-19 syndrome in patients with Parkinson’s disease.

In this series, few patients had respiratory, cardiovascular, gastrointestinal, musculoskeletal, or dermatologic symptoms. Interestingly, only four patients reported a loss of taste or smell.

The investigators noted that in addition to viral illness, the stress of prolonged lockdown during the pandemic and reduced access to health care and rehabilitation programs may contribute to the burden of post–COVID-19 syndrome in patients with Parkinson’s disease.

Study limitations cited include the relatively small sample size and the lack of a control group. The researchers noted the need for larger studies to elucidate the natural history of COVID-19 among patients with Parkinson’s disease in order to raise awareness of their needs and to help develop personalized management strategies.
 

Meaningful addition

Commenting on the findings, Kyle Mitchell, MD, movement disorders neurologist, Duke University, Durham, N.C., said he found the study to be a meaningful addition in light of the fact that data on the challenges that patients with Parkinson’s disease may face after having COVID-19 are limited.

“What I liked about this study was there’s data from multiple countries, what looks like a diverse population of study participants, and really just addressing a question that we get asked a lot in clinic and we see a fair amount, but we don’t really know a lot about: how people with Parkinson’s disease will do during and post COVID-19 infection,” said Dr. Mitchell, who was not involved with the research.

He said the worsening of motor symptoms and the need for increased dopaminergic medication brought some questions to mind.

“Is this increase in medications permanent, or is it temporary until post-COVID resolves? Or is it truly something where they stay on a higher dose?” he asked.

Dr. Mitchell said he does not believe the worsening of symptoms is specific to COVID-19 and that he sees individuals with Parkinson’s disease who experience setbacks “from any number of infections.” These include urinary tract infections and influenza, which are associated with worsening mobility, rigidity, tremor, fatigue, and cognition.

“People with Parkinson’s disease seem to get hit harder by infections in general,” he said.

The study had no outside funding. Dr. Leta and Dr. Mitchell have disclosed no relevant financial relationships.

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

Decreased motor function, as well as other adverse outcomes, are linked to post–COVID-19 syndrome in patients with Parkinson’s disease, new research suggests.

Results from a small, international retrospective case study show that about half of participants with Parkinson’s disease who developed post–COVID-19 syndrome experienced a worsening of motor symptoms and that their need for anti-Parkinson’s medication increased.

“In our series of 27 patients with Parkinson’s disease, 85% developed post–COVID-19 symptoms,” said lead investigator Valentina Leta, MD, Parkinson’s Foundation Center of Excellence, Kings College Hospital, London.

The most common long-term effects were worsening of motor function and an increase in the need for daily levodopa. Other adverse effects included fatigue; cognitive disturbances, including brain fog, loss of concentration, and memory deficits; and sleep disturbances, such as insomnia, Dr. Leta said.

The findings were presented at the International Congress of Parkinson’s Disease and Movement Disorders.
 

Long-term sequelae

Previous studies have documented worsening of motor and nonmotor symptoms among patients with Parkinson’s disease in the acute phase of COVID-19. Results of these studies suggest that mortality may be higher among patients with more advanced Parkinson’s disease, comorbidities, and frailty.

Dr. Leta noted that long-term sequelae with so-called long COVID have not been adequately explored, prompting the current study.

The case series included 27 patients with Parkinson’s disease in the United Kingdom, Italy, Romania, and Mexico who were also affected by COVID-19. The investigators defined post–COVID-19 syndrome as “signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks, and are not explained by an alternative diagnosis.”

Because some of the symptoms are also associated with Parkinson’s disease, symptoms were attributed to post–COVID-19 only if they occurred after a confirmed severe acute respiratory infection with SARS-CoV-2 or if patients experienced an acute or subacute worsening of a pre-existing symptom that had previously been stable.

Among the participants, 59.3% were men. The mean age at the time of Parkinson’s disease diagnosis was 59.0 ± 12.7 years, and the mean Parkinson’s disease duration was 9.2 ± 7.8 years. The patients were in Hoehn and Yahr stage 2.0 ± 1.0 at the time of their COVID-19 diagnosis.

Charlson Comorbidity Index score at COVID-19 diagnosis was 2.0 ± 1.5, and the levodopa equivalent daily dose (LEDD) was 1053.5 ± 842.4 mg.
 

Symptom worsening

“Cognitive disturbances” were defined as brain fog, concentration difficulty, or memory problems. “Peripheral neuropathy symptoms” were defined as having feelings of pins and needles or numbness.

By far, the most prevalent sequelae were worsening motor symptoms and increased need for anti-Parkinson’s medications. Each affected about half of the study cohort, the investigators noted.

Dr. Leta added the non-Parkinson’s disease-specific findings are in line with the existing literature on long COVID in the general population. The severity of COVID-19, as indicated by a history of hospitalization, did not seem to correlate with development of post–COVID-19 syndrome in patients with Parkinson’s disease.

In this series, few patients had respiratory, cardiovascular, gastrointestinal, musculoskeletal, or dermatologic symptoms. Interestingly, only four patients reported a loss of taste or smell.

The investigators noted that in addition to viral illness, the stress of prolonged lockdown during the pandemic and reduced access to health care and rehabilitation programs may contribute to the burden of post–COVID-19 syndrome in patients with Parkinson’s disease.

Study limitations cited include the relatively small sample size and the lack of a control group. The researchers noted the need for larger studies to elucidate the natural history of COVID-19 among patients with Parkinson’s disease in order to raise awareness of their needs and to help develop personalized management strategies.
 

Meaningful addition

Commenting on the findings, Kyle Mitchell, MD, movement disorders neurologist, Duke University, Durham, N.C., said he found the study to be a meaningful addition in light of the fact that data on the challenges that patients with Parkinson’s disease may face after having COVID-19 are limited.

“What I liked about this study was there’s data from multiple countries, what looks like a diverse population of study participants, and really just addressing a question that we get asked a lot in clinic and we see a fair amount, but we don’t really know a lot about: how people with Parkinson’s disease will do during and post COVID-19 infection,” said Dr. Mitchell, who was not involved with the research.

He said the worsening of motor symptoms and the need for increased dopaminergic medication brought some questions to mind.

“Is this increase in medications permanent, or is it temporary until post-COVID resolves? Or is it truly something where they stay on a higher dose?” he asked.

Dr. Mitchell said he does not believe the worsening of symptoms is specific to COVID-19 and that he sees individuals with Parkinson’s disease who experience setbacks “from any number of infections.” These include urinary tract infections and influenza, which are associated with worsening mobility, rigidity, tremor, fatigue, and cognition.

“People with Parkinson’s disease seem to get hit harder by infections in general,” he said.

The study had no outside funding. Dr. Leta and Dr. Mitchell have disclosed no relevant financial relationships.

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

This patient was given a diagnosis of linear IgA bullous dermatosis (LABD) based on biopsy results. (Biopsy is extremely helpful in differentiating bullous disorders.) A shave biopsy of 1 of the mid-chest 3-mm vesicles and a perilesional punch biopsy sent in Michel media showed linear deposition of IgA and IgG along the basement membrane zone and subepidermal blister with neutrophils and eosinophils. The IgA appeared stronger in the direct immunofluorescence study and there were numerous neutrophils on histology, which confirmed the diagnosis.

LABD is one of the less common blistering disorders. It has a bimodal distribution occurring mostly in adults around 60 years of age and a lower peak incidence in young children.¹ It often manifests with an acute onset of tense vesicles and bullae. The lesions can be extremely pruritic and can appear on mucous membranes, normal skin, or inflamed skin. Lesion formation is often sudden and manifests in clusters with an erythematous base on the trunk, extensor extremities, buttocks, and face—especially the area in and around the mouth.¹

LABD is diagnosed by linear deposits of IgA at the dermo-epidermal interface by direct immunofluorescence. The mechanism for lesion formation is still not well known. It can occur spontaneously or can be drug-induced. In many individuals with LABD (such as this one), the precipitating event for the disease is unknown.

It is important to differentiate LABD from other blistering diseases that can also affect the oral mucosa. Bullous pemphigoid has tense vesicles, as well, but often has a prodromal phase before lesions appear in a nonclustered pattern on the skin.² Pemphigus vulgaris, which is also in the differential, is characterized by soft blisters and almost always includes the oral mucosa, which is usually where lesions first develop.

Dapsone is first-line therapy. However, due to the risk of hemolysis with dapsone treatment in patients with glucose-6-phosphate dehydrogenase (G6DP) deficiency, the physician confirmed that the patient had normal levels of G6DP before starting the patient on dapsone 25 mg/d po. After starting dapsone, the patient reported unexplained syncopal episodes and falls and stopped the medication. (This was not an anticipated adverse effect.) The patient was then started on colchicine 0.6 mg orally tid. (Other second-line therapies include sulfapyridine and sulfamethoxypyridazine.¹) Follow-up in 1 month was scheduled.

‌

Image courtesy Daniel Stulberg, MD. Text courtesy of Riley Diehl, MD, Department of Internal Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque. Photo courtesy Daniel Stulberg, MD.

This patient was given a diagnosis of linear IgA bullous dermatosis (LABD) based on biopsy results. (Biopsy is extremely helpful in differentiating bullous disorders.) A shave biopsy of 1 of the mid-chest 3-mm vesicles and a perilesional punch biopsy sent in Michel media showed linear deposition of IgA and IgG along the basement membrane zone and subepidermal blister with neutrophils and eosinophils. The IgA appeared stronger in the direct immunofluorescence study and there were numerous neutrophils on histology, which confirmed the diagnosis.

LABD is one of the less common blistering disorders. It has a bimodal distribution occurring mostly in adults around 60 years of age and a lower peak incidence in young children.¹ It often manifests with an acute onset of tense vesicles and bullae. The lesions can be extremely pruritic and can appear on mucous membranes, normal skin, or inflamed skin. Lesion formation is often sudden and manifests in clusters with an erythematous base on the trunk, extensor extremities, buttocks, and face—especially the area in and around the mouth.¹

LABD is diagnosed by linear deposits of IgA at the dermo-epidermal interface by direct immunofluorescence. The mechanism for lesion formation is still not well known. It can occur spontaneously or can be drug-induced. In many individuals with LABD (such as this one), the precipitating event for the disease is unknown.

It is important to differentiate LABD from other blistering diseases that can also affect the oral mucosa. Bullous pemphigoid has tense vesicles, as well, but often has a prodromal phase before lesions appear in a nonclustered pattern on the skin.² Pemphigus vulgaris, which is also in the differential, is characterized by soft blisters and almost always includes the oral mucosa, which is usually where lesions first develop.

Dapsone is first-line therapy. However, due to the risk of hemolysis with dapsone treatment in patients with glucose-6-phosphate dehydrogenase (G6DP) deficiency, the physician confirmed that the patient had normal levels of G6DP before starting the patient on dapsone 25 mg/d po. After starting dapsone, the patient reported unexplained syncopal episodes and falls and stopped the medication. (This was not an anticipated adverse effect.) The patient was then started on colchicine 0.6 mg orally tid. (Other second-line therapies include sulfapyridine and sulfamethoxypyridazine.¹) Follow-up in 1 month was scheduled.

‌

Image courtesy Daniel Stulberg, MD. Text courtesy of Riley Diehl, MD, Department of Internal Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque. Photo courtesy Daniel Stulberg, MD.

This patient was given a diagnosis of linear IgA bullous dermatosis (LABD) based on biopsy results. (Biopsy is extremely helpful in differentiating bullous disorders.) A shave biopsy of 1 of the mid-chest 3-mm vesicles and a perilesional punch biopsy sent in Michel media showed linear deposition of IgA and IgG along the basement membrane zone and subepidermal blister with neutrophils and eosinophils. The IgA appeared stronger in the direct immunofluorescence study and there were numerous neutrophils on histology, which confirmed the diagnosis.

LABD is one of the less common blistering disorders. It has a bimodal distribution occurring mostly in adults around 60 years of age and a lower peak incidence in young children.¹ It often manifests with an acute onset of tense vesicles and bullae. The lesions can be extremely pruritic and can appear on mucous membranes, normal skin, or inflamed skin. Lesion formation is often sudden and manifests in clusters with an erythematous base on the trunk, extensor extremities, buttocks, and face—especially the area in and around the mouth.¹

LABD is diagnosed by linear deposits of IgA at the dermo-epidermal interface by direct immunofluorescence. The mechanism for lesion formation is still not well known. It can occur spontaneously or can be drug-induced. In many individuals with LABD (such as this one), the precipitating event for the disease is unknown.

It is important to differentiate LABD from other blistering diseases that can also affect the oral mucosa. Bullous pemphigoid has tense vesicles, as well, but often has a prodromal phase before lesions appear in a nonclustered pattern on the skin.² Pemphigus vulgaris, which is also in the differential, is characterized by soft blisters and almost always includes the oral mucosa, which is usually where lesions first develop.

Dapsone is first-line therapy. However, due to the risk of hemolysis with dapsone treatment in patients with glucose-6-phosphate dehydrogenase (G6DP) deficiency, the physician confirmed that the patient had normal levels of G6DP before starting the patient on dapsone 25 mg/d po. After starting dapsone, the patient reported unexplained syncopal episodes and falls and stopped the medication. (This was not an anticipated adverse effect.) The patient was then started on colchicine 0.6 mg orally tid. (Other second-line therapies include sulfapyridine and sulfamethoxypyridazine.¹) Follow-up in 1 month was scheduled.

‌

Image courtesy Daniel Stulberg, MD. Text courtesy of Riley Diehl, MD, Department of Internal Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque. Photo courtesy Daniel Stulberg, MD.