To the Editor:

A 32-year-old man presented to our clinic with acute-onset erythroderma associated with severe itching of 1 month’s duration. The patient developed the eruption after receiving the second dose of the Sinopharm BBIBP COVID-19 vaccine (BBIBP-CorV) 2 weeks prior to presentation. His medical history was unremarkable. There was no personal or family history of skin disease and no history of drug intake. Physical examination revealed orange-red erythroderma (Figure 1A) with islands of sparing,keratotic follicular orange-red papules on both legs and feet (Figure 1B), well-defined waxy palmoplantar keratoderma (Figures 1C and 1D), and fine scales on the face and scalp. The clinical and laboratory workup were normal, including a negative test for HIV infection.

Histopathology of two 4-mm punch biopsies of the skin on the trunk and lower limb showed irregular epidermal hyperplasia with thick suprapapillary plates and hypergranulosis (Figure 2A) along with alternating orthokeratosis and parakeratosis in vertical and horizontal directions (checkerboard parakeratosis)(Figure 2B). Follicular plugging with shoulder parakeratosis also was seen. The dermis showed a mild, superficial, perivascular lymphohistiocytic infiltrate. These features were diagnostic of pityriasis rubra pilaris (PRP). The patient received acitretin 25 mg/d and methotrexate 17.5 mg/wk (0.4 mg/kg/wk) and showed marked improvement after 2 months of therapy.

Pityriasis rubra pilaris is a rare papulosquamous skin disease of unknown etiology with several theories including genetic factors, aberrant metabolism of vitamin A, infection, drug reaction, autoimmune disease, and malignancy.¹ Clinically, there are 6 types of PRP: type I (classical adult), type II (atypical adult), type III (classical juvenile), type IV (circumscribed juvenile), type V (atypical juvenile), and type VI (HIV associated). Classic features include orange-red keratotic follicular papules that coalesce into plaques with characteristic islands of sparing.¹

Pityriasis rubra pilaris is a rare sequela following administration of certain vaccines, including diphtheria, pertussis, and tetanus; measles-mumps-rubella; and polio vaccines.^2,3 Among the various skin reactions that have been reported following COVID-19 vaccination, PRP has been reported in 19 patients: 7 (36.8%) after AstraZeneca vaccination, 3 (15.8%) after CoronaVac, 3 (15.8%) after Moderna, 5 (26.3%) after Pfizer-BioNTech,⁴ and 1 (5.3%) after Sinopharm.⁵ Our patient represents an additional case of a reaction after the Sinopharm vaccine. The condition developed after the first dose of vaccine in 11 patients, after the second dose in 6 patients, and after the third dose in 2 patients.

Other papulosquamous skin reactions have been reported after the Sinopharm BBIBP-CorV vaccine including psoriasis, lichen planus, and pityriasis rosea. Skin manifestations occurred sporadically, as some happened after the first or second dose or even after booster doses. The exact pathogenic mechanism(s) underlying the development of these conditions following vaccination still are not understood, though they may be attributed to COVID-19 vaccine–induced immune dysregulation.⁶

Pityriasis rubra pilaris can be self-limited in some cases and may not require treatment. Topical therapies such as keratolytics, emollients, and vitamin D may be utilized, especially for localized disease. Systemic therapy may be needed for refractory cases, including retinoids or immunosuppressive medications such as methotrexate, which is considered a second-line treatment for refractory PRP (after retinoids) and was used in our case. Azathioprine and cyclosporine also may be used. Phototherapy may play a role in PRP treatment, but the response is variable.⁷

Pityriasis rubra pilaris should be added to the list of cutaneous adverse reactions that can occur following vaccination with the Sinopharm BBIBP-CorV vaccine. Dermatologists must be aware of the possibility of vaccine-induced PRP, especially in de novo cases.

To the Editor:

A 32-year-old man presented to our clinic with acute-onset erythroderma associated with severe itching of 1 month’s duration. The patient developed the eruption after receiving the second dose of the Sinopharm BBIBP COVID-19 vaccine (BBIBP-CorV) 2 weeks prior to presentation. His medical history was unremarkable. There was no personal or family history of skin disease and no history of drug intake. Physical examination revealed orange-red erythroderma (Figure 1A) with islands of sparing,keratotic follicular orange-red papules on both legs and feet (Figure 1B), well-defined waxy palmoplantar keratoderma (Figures 1C and 1D), and fine scales on the face and scalp. The clinical and laboratory workup were normal, including a negative test for HIV infection.

Histopathology of two 4-mm punch biopsies of the skin on the trunk and lower limb showed irregular epidermal hyperplasia with thick suprapapillary plates and hypergranulosis (Figure 2A) along with alternating orthokeratosis and parakeratosis in vertical and horizontal directions (checkerboard parakeratosis)(Figure 2B). Follicular plugging with shoulder parakeratosis also was seen. The dermis showed a mild, superficial, perivascular lymphohistiocytic infiltrate. These features were diagnostic of pityriasis rubra pilaris (PRP). The patient received acitretin 25 mg/d and methotrexate 17.5 mg/wk (0.4 mg/kg/wk) and showed marked improvement after 2 months of therapy.

Pityriasis rubra pilaris is a rare papulosquamous skin disease of unknown etiology with several theories including genetic factors, aberrant metabolism of vitamin A, infection, drug reaction, autoimmune disease, and malignancy.¹ Clinically, there are 6 types of PRP: type I (classical adult), type II (atypical adult), type III (classical juvenile), type IV (circumscribed juvenile), type V (atypical juvenile), and type VI (HIV associated). Classic features include orange-red keratotic follicular papules that coalesce into plaques with characteristic islands of sparing.¹

Pityriasis rubra pilaris is a rare sequela following administration of certain vaccines, including diphtheria, pertussis, and tetanus; measles-mumps-rubella; and polio vaccines.^2,3 Among the various skin reactions that have been reported following COVID-19 vaccination, PRP has been reported in 19 patients: 7 (36.8%) after AstraZeneca vaccination, 3 (15.8%) after CoronaVac, 3 (15.8%) after Moderna, 5 (26.3%) after Pfizer-BioNTech,⁴ and 1 (5.3%) after Sinopharm.⁵ Our patient represents an additional case of a reaction after the Sinopharm vaccine. The condition developed after the first dose of vaccine in 11 patients, after the second dose in 6 patients, and after the third dose in 2 patients.

Other papulosquamous skin reactions have been reported after the Sinopharm BBIBP-CorV vaccine including psoriasis, lichen planus, and pityriasis rosea. Skin manifestations occurred sporadically, as some happened after the first or second dose or even after booster doses. The exact pathogenic mechanism(s) underlying the development of these conditions following vaccination still are not understood, though they may be attributed to COVID-19 vaccine–induced immune dysregulation.⁶

Pityriasis rubra pilaris can be self-limited in some cases and may not require treatment. Topical therapies such as keratolytics, emollients, and vitamin D may be utilized, especially for localized disease. Systemic therapy may be needed for refractory cases, including retinoids or immunosuppressive medications such as methotrexate, which is considered a second-line treatment for refractory PRP (after retinoids) and was used in our case. Azathioprine and cyclosporine also may be used. Phototherapy may play a role in PRP treatment, but the response is variable.⁷

Pityriasis rubra pilaris should be added to the list of cutaneous adverse reactions that can occur following vaccination with the Sinopharm BBIBP-CorV vaccine. Dermatologists must be aware of the possibility of vaccine-induced PRP, especially in de novo cases.

To the Editor:

A 32-year-old man presented to our clinic with acute-onset erythroderma associated with severe itching of 1 month’s duration. The patient developed the eruption after receiving the second dose of the Sinopharm BBIBP COVID-19 vaccine (BBIBP-CorV) 2 weeks prior to presentation. His medical history was unremarkable. There was no personal or family history of skin disease and no history of drug intake. Physical examination revealed orange-red erythroderma (Figure 1A) with islands of sparing,keratotic follicular orange-red papules on both legs and feet (Figure 1B), well-defined waxy palmoplantar keratoderma (Figures 1C and 1D), and fine scales on the face and scalp. The clinical and laboratory workup were normal, including a negative test for HIV infection.

Histopathology of two 4-mm punch biopsies of the skin on the trunk and lower limb showed irregular epidermal hyperplasia with thick suprapapillary plates and hypergranulosis (Figure 2A) along with alternating orthokeratosis and parakeratosis in vertical and horizontal directions (checkerboard parakeratosis)(Figure 2B). Follicular plugging with shoulder parakeratosis also was seen. The dermis showed a mild, superficial, perivascular lymphohistiocytic infiltrate. These features were diagnostic of pityriasis rubra pilaris (PRP). The patient received acitretin 25 mg/d and methotrexate 17.5 mg/wk (0.4 mg/kg/wk) and showed marked improvement after 2 months of therapy.

Pityriasis rubra pilaris is a rare papulosquamous skin disease of unknown etiology with several theories including genetic factors, aberrant metabolism of vitamin A, infection, drug reaction, autoimmune disease, and malignancy.¹ Clinically, there are 6 types of PRP: type I (classical adult), type II (atypical adult), type III (classical juvenile), type IV (circumscribed juvenile), type V (atypical juvenile), and type VI (HIV associated). Classic features include orange-red keratotic follicular papules that coalesce into plaques with characteristic islands of sparing.¹

Pityriasis rubra pilaris is a rare sequela following administration of certain vaccines, including diphtheria, pertussis, and tetanus; measles-mumps-rubella; and polio vaccines.^2,3 Among the various skin reactions that have been reported following COVID-19 vaccination, PRP has been reported in 19 patients: 7 (36.8%) after AstraZeneca vaccination, 3 (15.8%) after CoronaVac, 3 (15.8%) after Moderna, 5 (26.3%) after Pfizer-BioNTech,⁴ and 1 (5.3%) after Sinopharm.⁵ Our patient represents an additional case of a reaction after the Sinopharm vaccine. The condition developed after the first dose of vaccine in 11 patients, after the second dose in 6 patients, and after the third dose in 2 patients.

Other papulosquamous skin reactions have been reported after the Sinopharm BBIBP-CorV vaccine including psoriasis, lichen planus, and pityriasis rosea. Skin manifestations occurred sporadically, as some happened after the first or second dose or even after booster doses. The exact pathogenic mechanism(s) underlying the development of these conditions following vaccination still are not understood, though they may be attributed to COVID-19 vaccine–induced immune dysregulation.⁶

Pityriasis rubra pilaris can be self-limited in some cases and may not require treatment. Topical therapies such as keratolytics, emollients, and vitamin D may be utilized, especially for localized disease. Systemic therapy may be needed for refractory cases, including retinoids or immunosuppressive medications such as methotrexate, which is considered a second-line treatment for refractory PRP (after retinoids) and was used in our case. Azathioprine and cyclosporine also may be used. Phototherapy may play a role in PRP treatment, but the response is variable.⁷

Pityriasis rubra pilaris should be added to the list of cutaneous adverse reactions that can occur following vaccination with the Sinopharm BBIBP-CorV vaccine. Dermatologists must be aware of the possibility of vaccine-induced PRP, especially in de novo cases.

LIVERPOOL, ENGLAND — The British Society for Rheumatology (BSR) and the British Association of Dermatologists (BAD) have joined forces for the first time to develop the first British guidelines for the management of people living with Behçet’s disease.

The guidelines will also be the first “living guidelines” produced by either society, which means they will be regularly revised and updated when new evidence emerges that warrants inclusion.

With more than 90 recommendations being made, the new guidelines promise to be the most comprehensive and most up-to-date yet for what is regarded as a rare disease. Robert Moots, MBBS, PhD, provided a “sneak peek” of the guidelines at the annual meeting of the British Society for Rheumatology.

Dr. Moots, professor of rheumatology at the University of Liverpool and a consultant rheumatologist for Liverpool University Hospitals NHS Foundation Trust in England, noted that while the European Alliance of Associations for Rheumatology has produced a guideline for Behçet’s disease, this was last updated in 2018 and is not specific for the population for patients that is seen in the United Kingdom.

The British recommendations will cover all possible manifestations of Behçet’s disease and give practical advice on how to manage everything from the most common presentations such as skin lesions, mouth ulcers, and genital ulcers, as well as the potentially more serious eye, neurological, and vascular involvement.

Sara Freeman/Medscape Medical News

Importance of Raising Awareness

“Joint and musculoskeletal problems are actually one of the least complained of symptoms in people with Behçet’s, and they often can’t understand why a rheumatologist is seeing them,” Dr. Moot said. “But of course, people do get joint problems, they can get enthesitis and arthralgia.”

Dr. Moots has been leading one of the three National Health Service (NHS) Centres of Excellence for Behçet’s Syndrome in England for more than a decade and told this news organization that diagnosing patients could be challenging. It can take up to 10 years from the first symptoms appearing to getting a diagnosis, so part of the job of the NHS Centres of Excellence is to raise awareness among both the healthcare profession and the general public.

“It’s a condition that people learn about at medical school. Most doctors will have come across it, but because it was thought to be really rare in the UK, nobody perhaps really expects to see it,” Dr. Moot said.

“But we all have these patients,” he added. “In Liverpool, we’re commissioned to be looking after an anticipated 150 people with Behçet’s — we’ve got 700. With more awareness, there’s more diagnoses being made, and people are being looked after better.”
 

Patient Perspective

Tony Thornburn, OBE, chair of the patient advocacy group Behçet’s UK, agreed in a separate interview that raising awareness of the syndrome was key to improving its management.

“Patients have said that it is a bit like having arthritis, lupus, MS [multiple sclerosis], and Crohn’s [disease] all at once,” Mr. Thorburn said. “So what we need is a guideline to ensure that people know what they’re looking at.”

Mr. Thorburn added, “Guidelines are important for raising awareness but also providing the detailed information that clinicians and GPs [general practitioners] need to have to treat a patient when they come in with this multifaceted condition.”
 

Multifaceted Means Multidisciplinary Management

Because there can be so many different aspects to managing someone with Behçet’s disease, a multispecialty team that was convened to develop the guidelines agreed that multidisciplinary management should be an overarching theme.

“The guideline development group consisted of all the specialties that you would need for a complex multisystem disease like Behçet’s,” Dr. Moot said. He highlighted that working alongside the consultants in adult and pediatric rheumatology were specialists in dermatology, gastroenterology, neurology, ophthalmology, obstetrics and gynecology, and psychology.

“We’re actually looking at psychological interactions and their impact for the first time,” Dr. Moot said, noting that clinicians needed to “take it seriously, and ask about it.”
 

Management of Manifestations

One of the general principles of the guidelines is to assess the involvement of each organ system and target treatment accordingly.

“One of the problems is that the evidence base to tell us what to do is pretty low,” Dr. Moots acknowledged. There have been few good quality randomized trials, so “treatment tends to be eminence-based rather than evidence-based.”

The recommendation wording bears this in mind, stating whether a treatment should or should not be offered, or just considered if there is no strong evidence to back up its use.

With regard to musculoskeletal manifestations, the recommendations say that colchicine should be offered, perhaps as a first-line option, or an intraarticular steroid injection in the case of monoarthritis. An intramuscular depot steroid may also be appropriate to offer, and there was good evidence to offer azathioprine or, as an alternative in refractory cases, a tumor necrosis factor (TNF) inhibitor. Nonsteroidal anti-inflammatory drugs, methotrexate, apremilast, secukinumab, and referral to a physiotherapist could only be considered, however, based on weaker levels of evidence for their use.

To treat mucocutaneous disease, the guidelines advise offering topical steroids in the form of ointment for genital ulcers or mouthwash or ointment for oral ulcers. For skin lesions, it is recommended to offer colchicine, azathioprine, mycophenolate mofetil, or TNF inhibitor and to consider the use of apremilast, secukinumab, or dapsone.
 

Future Work and Revision

“One of the key things we would like to see developing is a national registry,” Dr. Moots said. This would include biobanking samples for future research and possible genomic and phenotyping studies.

More work needs to be done in conducting clinical trials in children and young people with Behçet’s disease, studies to find prognostic factors for neurological disease, and clinical trials of potential new drug approaches such as Janus kinase inhibitors. Importantly, an auditing process needs to be set up to see what effect, if any, the guidelines will actually have onpatient management.

“It’s taken 5 years to today” to develop the guidelines, Dr. Moot said. What form the process of updating them will take still has to be decided, he said in the interview. It is likely that the necessary literature searches will be performed every 6 months or so, but it will be a compromise between the ideal situation and having the staffing time to do it.

“It’s a big ask,” Dr. Moot acknowledged, adding that even if updates were only once a year, it would still be much faster than the 5- or 6-year cycle that it traditionally takes for most guidelines to be updated.

The BSR and BAD’s processes for developing guidelines are accredited by the National Institute for Health and Care Excellence in England. Dr. Moots is the chief investigator for the Secukinumab in Behçet’s trial, which is sponsored by the Liverpool University Hospitals NHS Foundation Trust via grant funding from Novartis.
 

A version of this article appeared on Medscape.com.

LIVERPOOL, ENGLAND — The British Society for Rheumatology (BSR) and the British Association of Dermatologists (BAD) have joined forces for the first time to develop the first British guidelines for the management of people living with Behçet’s disease.

The guidelines will also be the first “living guidelines” produced by either society, which means they will be regularly revised and updated when new evidence emerges that warrants inclusion.

With more than 90 recommendations being made, the new guidelines promise to be the most comprehensive and most up-to-date yet for what is regarded as a rare disease. Robert Moots, MBBS, PhD, provided a “sneak peek” of the guidelines at the annual meeting of the British Society for Rheumatology.

Dr. Moots, professor of rheumatology at the University of Liverpool and a consultant rheumatologist for Liverpool University Hospitals NHS Foundation Trust in England, noted that while the European Alliance of Associations for Rheumatology has produced a guideline for Behçet’s disease, this was last updated in 2018 and is not specific for the population for patients that is seen in the United Kingdom.

The British recommendations will cover all possible manifestations of Behçet’s disease and give practical advice on how to manage everything from the most common presentations such as skin lesions, mouth ulcers, and genital ulcers, as well as the potentially more serious eye, neurological, and vascular involvement.

Sara Freeman/Medscape Medical News

Importance of Raising Awareness

“Joint and musculoskeletal problems are actually one of the least complained of symptoms in people with Behçet’s, and they often can’t understand why a rheumatologist is seeing them,” Dr. Moot said. “But of course, people do get joint problems, they can get enthesitis and arthralgia.”

Dr. Moots has been leading one of the three National Health Service (NHS) Centres of Excellence for Behçet’s Syndrome in England for more than a decade and told this news organization that diagnosing patients could be challenging. It can take up to 10 years from the first symptoms appearing to getting a diagnosis, so part of the job of the NHS Centres of Excellence is to raise awareness among both the healthcare profession and the general public.

“It’s a condition that people learn about at medical school. Most doctors will have come across it, but because it was thought to be really rare in the UK, nobody perhaps really expects to see it,” Dr. Moot said.

“But we all have these patients,” he added. “In Liverpool, we’re commissioned to be looking after an anticipated 150 people with Behçet’s — we’ve got 700. With more awareness, there’s more diagnoses being made, and people are being looked after better.”
 

Patient Perspective

Tony Thornburn, OBE, chair of the patient advocacy group Behçet’s UK, agreed in a separate interview that raising awareness of the syndrome was key to improving its management.

“Patients have said that it is a bit like having arthritis, lupus, MS [multiple sclerosis], and Crohn’s [disease] all at once,” Mr. Thorburn said. “So what we need is a guideline to ensure that people know what they’re looking at.”

Mr. Thorburn added, “Guidelines are important for raising awareness but also providing the detailed information that clinicians and GPs [general practitioners] need to have to treat a patient when they come in with this multifaceted condition.”
 

Multifaceted Means Multidisciplinary Management

Because there can be so many different aspects to managing someone with Behçet’s disease, a multispecialty team that was convened to develop the guidelines agreed that multidisciplinary management should be an overarching theme.

“The guideline development group consisted of all the specialties that you would need for a complex multisystem disease like Behçet’s,” Dr. Moot said. He highlighted that working alongside the consultants in adult and pediatric rheumatology were specialists in dermatology, gastroenterology, neurology, ophthalmology, obstetrics and gynecology, and psychology.

“We’re actually looking at psychological interactions and their impact for the first time,” Dr. Moot said, noting that clinicians needed to “take it seriously, and ask about it.”
 

Management of Manifestations

One of the general principles of the guidelines is to assess the involvement of each organ system and target treatment accordingly.

“One of the problems is that the evidence base to tell us what to do is pretty low,” Dr. Moots acknowledged. There have been few good quality randomized trials, so “treatment tends to be eminence-based rather than evidence-based.”

The recommendation wording bears this in mind, stating whether a treatment should or should not be offered, or just considered if there is no strong evidence to back up its use.

With regard to musculoskeletal manifestations, the recommendations say that colchicine should be offered, perhaps as a first-line option, or an intraarticular steroid injection in the case of monoarthritis. An intramuscular depot steroid may also be appropriate to offer, and there was good evidence to offer azathioprine or, as an alternative in refractory cases, a tumor necrosis factor (TNF) inhibitor. Nonsteroidal anti-inflammatory drugs, methotrexate, apremilast, secukinumab, and referral to a physiotherapist could only be considered, however, based on weaker levels of evidence for their use.

To treat mucocutaneous disease, the guidelines advise offering topical steroids in the form of ointment for genital ulcers or mouthwash or ointment for oral ulcers. For skin lesions, it is recommended to offer colchicine, azathioprine, mycophenolate mofetil, or TNF inhibitor and to consider the use of apremilast, secukinumab, or dapsone.
 

Future Work and Revision

“One of the key things we would like to see developing is a national registry,” Dr. Moots said. This would include biobanking samples for future research and possible genomic and phenotyping studies.

More work needs to be done in conducting clinical trials in children and young people with Behçet’s disease, studies to find prognostic factors for neurological disease, and clinical trials of potential new drug approaches such as Janus kinase inhibitors. Importantly, an auditing process needs to be set up to see what effect, if any, the guidelines will actually have onpatient management.

“It’s taken 5 years to today” to develop the guidelines, Dr. Moot said. What form the process of updating them will take still has to be decided, he said in the interview. It is likely that the necessary literature searches will be performed every 6 months or so, but it will be a compromise between the ideal situation and having the staffing time to do it.

“It’s a big ask,” Dr. Moot acknowledged, adding that even if updates were only once a year, it would still be much faster than the 5- or 6-year cycle that it traditionally takes for most guidelines to be updated.

The BSR and BAD’s processes for developing guidelines are accredited by the National Institute for Health and Care Excellence in England. Dr. Moots is the chief investigator for the Secukinumab in Behçet’s trial, which is sponsored by the Liverpool University Hospitals NHS Foundation Trust via grant funding from Novartis.
 

A version of this article appeared on Medscape.com.

LIVERPOOL, ENGLAND — The British Society for Rheumatology (BSR) and the British Association of Dermatologists (BAD) have joined forces for the first time to develop the first British guidelines for the management of people living with Behçet’s disease.

The guidelines will also be the first “living guidelines” produced by either society, which means they will be regularly revised and updated when new evidence emerges that warrants inclusion.

With more than 90 recommendations being made, the new guidelines promise to be the most comprehensive and most up-to-date yet for what is regarded as a rare disease. Robert Moots, MBBS, PhD, provided a “sneak peek” of the guidelines at the annual meeting of the British Society for Rheumatology.

Dr. Moots, professor of rheumatology at the University of Liverpool and a consultant rheumatologist for Liverpool University Hospitals NHS Foundation Trust in England, noted that while the European Alliance of Associations for Rheumatology has produced a guideline for Behçet’s disease, this was last updated in 2018 and is not specific for the population for patients that is seen in the United Kingdom.

The British recommendations will cover all possible manifestations of Behçet’s disease and give practical advice on how to manage everything from the most common presentations such as skin lesions, mouth ulcers, and genital ulcers, as well as the potentially more serious eye, neurological, and vascular involvement.

Sara Freeman/Medscape Medical News

Importance of Raising Awareness

“Joint and musculoskeletal problems are actually one of the least complained of symptoms in people with Behçet’s, and they often can’t understand why a rheumatologist is seeing them,” Dr. Moot said. “But of course, people do get joint problems, they can get enthesitis and arthralgia.”

Dr. Moots has been leading one of the three National Health Service (NHS) Centres of Excellence for Behçet’s Syndrome in England for more than a decade and told this news organization that diagnosing patients could be challenging. It can take up to 10 years from the first symptoms appearing to getting a diagnosis, so part of the job of the NHS Centres of Excellence is to raise awareness among both the healthcare profession and the general public.

“It’s a condition that people learn about at medical school. Most doctors will have come across it, but because it was thought to be really rare in the UK, nobody perhaps really expects to see it,” Dr. Moot said.

“But we all have these patients,” he added. “In Liverpool, we’re commissioned to be looking after an anticipated 150 people with Behçet’s — we’ve got 700. With more awareness, there’s more diagnoses being made, and people are being looked after better.”
 

Patient Perspective

Tony Thornburn, OBE, chair of the patient advocacy group Behçet’s UK, agreed in a separate interview that raising awareness of the syndrome was key to improving its management.

“Patients have said that it is a bit like having arthritis, lupus, MS [multiple sclerosis], and Crohn’s [disease] all at once,” Mr. Thorburn said. “So what we need is a guideline to ensure that people know what they’re looking at.”

Mr. Thorburn added, “Guidelines are important for raising awareness but also providing the detailed information that clinicians and GPs [general practitioners] need to have to treat a patient when they come in with this multifaceted condition.”
 

Multifaceted Means Multidisciplinary Management

Because there can be so many different aspects to managing someone with Behçet’s disease, a multispecialty team that was convened to develop the guidelines agreed that multidisciplinary management should be an overarching theme.

“The guideline development group consisted of all the specialties that you would need for a complex multisystem disease like Behçet’s,” Dr. Moot said. He highlighted that working alongside the consultants in adult and pediatric rheumatology were specialists in dermatology, gastroenterology, neurology, ophthalmology, obstetrics and gynecology, and psychology.

“We’re actually looking at psychological interactions and their impact for the first time,” Dr. Moot said, noting that clinicians needed to “take it seriously, and ask about it.”
 

Management of Manifestations

One of the general principles of the guidelines is to assess the involvement of each organ system and target treatment accordingly.

“One of the problems is that the evidence base to tell us what to do is pretty low,” Dr. Moots acknowledged. There have been few good quality randomized trials, so “treatment tends to be eminence-based rather than evidence-based.”

The recommendation wording bears this in mind, stating whether a treatment should or should not be offered, or just considered if there is no strong evidence to back up its use.

With regard to musculoskeletal manifestations, the recommendations say that colchicine should be offered, perhaps as a first-line option, or an intraarticular steroid injection in the case of monoarthritis. An intramuscular depot steroid may also be appropriate to offer, and there was good evidence to offer azathioprine or, as an alternative in refractory cases, a tumor necrosis factor (TNF) inhibitor. Nonsteroidal anti-inflammatory drugs, methotrexate, apremilast, secukinumab, and referral to a physiotherapist could only be considered, however, based on weaker levels of evidence for their use.

To treat mucocutaneous disease, the guidelines advise offering topical steroids in the form of ointment for genital ulcers or mouthwash or ointment for oral ulcers. For skin lesions, it is recommended to offer colchicine, azathioprine, mycophenolate mofetil, or TNF inhibitor and to consider the use of apremilast, secukinumab, or dapsone.
 

Future Work and Revision

“One of the key things we would like to see developing is a national registry,” Dr. Moots said. This would include biobanking samples for future research and possible genomic and phenotyping studies.

More work needs to be done in conducting clinical trials in children and young people with Behçet’s disease, studies to find prognostic factors for neurological disease, and clinical trials of potential new drug approaches such as Janus kinase inhibitors. Importantly, an auditing process needs to be set up to see what effect, if any, the guidelines will actually have onpatient management.

“It’s taken 5 years to today” to develop the guidelines, Dr. Moot said. What form the process of updating them will take still has to be decided, he said in the interview. It is likely that the necessary literature searches will be performed every 6 months or so, but it will be a compromise between the ideal situation and having the staffing time to do it.

“It’s a big ask,” Dr. Moot acknowledged, adding that even if updates were only once a year, it would still be much faster than the 5- or 6-year cycle that it traditionally takes for most guidelines to be updated.

The BSR and BAD’s processes for developing guidelines are accredited by the National Institute for Health and Care Excellence in England. Dr. Moots is the chief investigator for the Secukinumab in Behçet’s trial, which is sponsored by the Liverpool University Hospitals NHS Foundation Trust via grant funding from Novartis.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the gene therapy fidanacogene elaparvovec (Beqvez) for adults with hemophilia B, a rare bleeding disorder that affects almost 4 in 100,000 US men.

Patients are eligible for a one-time infusion of Pfizer’s gene therapy if they are currently using clotting factor IX prophylaxis therapy; have current or historical life-threatening hemorrhages; or have repeated, serious spontaneous bleeding episodes. 

Beqvez is the second gene therapy the agency has approved for hemophilia B, a deficiency in clotting factor IX because of a faulty gene that occurs mostly in males. The FDA approved the first gene therapy, etranacogene dezaparvovec (Hemgenix), in November 2022. 

Both therapies deliver a functional copy of the factor IX gene to liver cells via a viral vector. 

Pfizer said the list price of Beqvez will be $3.5 million — the same price as Hemgenix. The argument for this hefty price tag is that these gene therapies offer the possibility of a cure whereas ongoing factor IX infusions can cost more than $20 million over a patient’s lifetime. Uptake of Hemgenix, however, has been slow, given the cost and concerns about the therapy’s durability and safety.

Beqvez was approved on the basis of the phase 3 BENEGENE-2 trial in 45 men with moderate to severe hemophilia B. These men had been on factor IX prophylaxis for at least 6 months and had tested negative for antibodies against the viral delivery vector. 

The annualized bleeding rate fell from a mean of 4.5 events during the pretreatment period of at least 6 months to a mean of 2.5 events between week 12 and data cutoff (median, 1.8 years of follow-up), according to Pfizer’s press release. Overall, bleeding events were eliminated in 60% of patients who received the one-time infusion vs 29% of patients on factor IX prophylaxis therapy.

Overall, Pfizer reported that the gene therapy was “generally well-tolerated,” with an increase in transaminases reported as the most common adverse event. No deaths, serious infusion reactions, thrombotic events, or development of factor IX antibodies occurred. 

Pfizer has said it will continue to monitor patients to assess the therapy’s long-term durability and safety over a 15-year period.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the gene therapy fidanacogene elaparvovec (Beqvez) for adults with hemophilia B, a rare bleeding disorder that affects almost 4 in 100,000 US men.

Patients are eligible for a one-time infusion of Pfizer’s gene therapy if they are currently using clotting factor IX prophylaxis therapy; have current or historical life-threatening hemorrhages; or have repeated, serious spontaneous bleeding episodes. 

Beqvez is the second gene therapy the agency has approved for hemophilia B, a deficiency in clotting factor IX because of a faulty gene that occurs mostly in males. The FDA approved the first gene therapy, etranacogene dezaparvovec (Hemgenix), in November 2022. 

Both therapies deliver a functional copy of the factor IX gene to liver cells via a viral vector. 

Pfizer said the list price of Beqvez will be $3.5 million — the same price as Hemgenix. The argument for this hefty price tag is that these gene therapies offer the possibility of a cure whereas ongoing factor IX infusions can cost more than $20 million over a patient’s lifetime. Uptake of Hemgenix, however, has been slow, given the cost and concerns about the therapy’s durability and safety.

Beqvez was approved on the basis of the phase 3 BENEGENE-2 trial in 45 men with moderate to severe hemophilia B. These men had been on factor IX prophylaxis for at least 6 months and had tested negative for antibodies against the viral delivery vector. 

The annualized bleeding rate fell from a mean of 4.5 events during the pretreatment period of at least 6 months to a mean of 2.5 events between week 12 and data cutoff (median, 1.8 years of follow-up), according to Pfizer’s press release. Overall, bleeding events were eliminated in 60% of patients who received the one-time infusion vs 29% of patients on factor IX prophylaxis therapy.

Overall, Pfizer reported that the gene therapy was “generally well-tolerated,” with an increase in transaminases reported as the most common adverse event. No deaths, serious infusion reactions, thrombotic events, or development of factor IX antibodies occurred. 

Pfizer has said it will continue to monitor patients to assess the therapy’s long-term durability and safety over a 15-year period.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the gene therapy fidanacogene elaparvovec (Beqvez) for adults with hemophilia B, a rare bleeding disorder that affects almost 4 in 100,000 US men.

Patients are eligible for a one-time infusion of Pfizer’s gene therapy if they are currently using clotting factor IX prophylaxis therapy; have current or historical life-threatening hemorrhages; or have repeated, serious spontaneous bleeding episodes. 

Beqvez is the second gene therapy the agency has approved for hemophilia B, a deficiency in clotting factor IX because of a faulty gene that occurs mostly in males. The FDA approved the first gene therapy, etranacogene dezaparvovec (Hemgenix), in November 2022. 

Both therapies deliver a functional copy of the factor IX gene to liver cells via a viral vector. 

Pfizer said the list price of Beqvez will be $3.5 million — the same price as Hemgenix. The argument for this hefty price tag is that these gene therapies offer the possibility of a cure whereas ongoing factor IX infusions can cost more than $20 million over a patient’s lifetime. Uptake of Hemgenix, however, has been slow, given the cost and concerns about the therapy’s durability and safety.

Beqvez was approved on the basis of the phase 3 BENEGENE-2 trial in 45 men with moderate to severe hemophilia B. These men had been on factor IX prophylaxis for at least 6 months and had tested negative for antibodies against the viral delivery vector. 

The annualized bleeding rate fell from a mean of 4.5 events during the pretreatment period of at least 6 months to a mean of 2.5 events between week 12 and data cutoff (median, 1.8 years of follow-up), according to Pfizer’s press release. Overall, bleeding events were eliminated in 60% of patients who received the one-time infusion vs 29% of patients on factor IX prophylaxis therapy.

Overall, Pfizer reported that the gene therapy was “generally well-tolerated,” with an increase in transaminases reported as the most common adverse event. No deaths, serious infusion reactions, thrombotic events, or development of factor IX antibodies occurred. 

Pfizer has said it will continue to monitor patients to assess the therapy’s long-term durability and safety over a 15-year period.

A version of this article appeared on Medscape.com.

Inflammatory arthritis codes increased 30-fold in the transition from the ninth to the 10th revision of the International Classification of Diseases (ICD-9 and -10), yet few were used in clinical practice, according to new research.

Most of the new codes for inflammatory arthritis in ICD-10 were rarely used, if at all, from 2015 to 2021.

“About 10-20 codes were comprising the majority of usage for inflammatory arthritis patients in ICD-10,” first author Justin Zhu, a researcher and medical student at Yale University in New Haven, Connecticut, told this news organization. “The other 380 or 400 codes just weren’t seeing a lot of use.”

Yale University

The findings show the difficulties of transitioning to a new system, he added, and emphasize the need for additional training to improve adoption of ICD-11. The new coding system launched globally in January 2022, but it is not clear when it will be implemented in the United States.

ICD-10 was launched in the United States in 2015, with the goal of enabling greater specificity in identifying health conditions. For example, the new coding system allowed users to include information on laterality and anatomic location for the first time. The total number of codes increased from 14,500 with ICD-9 to 70,000 with ICD-10, with the number of inflammatory arthritis diagnosis codes growing from 14 to 425.

To see how these ICD-10 codes were utilized compared with ICD-9, Zhu and colleagues used national multi-insurance administrative claims data to find inflammatory arthritis diagnostic codes for over 5.1 million patients. About half were coded in ICD-9, while the remaining half were coded in ICD-10. Mr. Zhu and colleagues defined “higher-usage codes” as those that were used more than 1% of the time.

The findings were published in a research letter in JAMA Network Open on April 18.

For ICD-9, four of the available 14 codes (28.6%) were higher-usage codes. In contrast, only nine of the 425 ICD-10 codes (2.1%) were frequently used. Though ICD-10 allowed for increased granularity in diagnosis, data showed that nonspecific codes were most popular. Of the 20 most used ICD-10 arthritis codes, 65% contained “unspecified or other specified” in its wording.

The researchers also found that there was no significant change in these higher-usage codes throughout the study period from 2015 to 2021, suggesting there was not a detectable learning curve in ICD-10 usage among physicians and coders. They also found that clinician specialty did not change code usage patterns.

“The percentage of codes used was not better for rheumatologists (who might be expected to be more refined users of such codes) than primary care clinicians,” Mr. Zhu and colleagues wrote.
 

Moving to ICD-11 Brings Challenges as Well as Opportunities

Mr. Zhu noted that the study highlights the challenges of adopting new technological systems into daily practice, which can inform the eventual transition to ICD-11.

“There is this need to emphasize training as well as just invest more in improving adoption of ICD-11,” he said.

Michael Pine, MD, MBA, of MJP Healthcare Innovations, LLC in Evanston, Illinois, added that ICD-11 needs to be more user-friendly to be useful in practice. While ICD-10 allowed for greater granularity in coding, it did not result in “usable granularity, in terms of the things doctors really want to communicate,” he told this news organization.

And the transition to ICD-11 could pose greater challenges; rather than ICD-10’s taxonomy system, ICD-11 is formatted as an ontology.

A version of this article appeared on Medscape.com.

Inflammatory arthritis codes increased 30-fold in the transition from the ninth to the 10th revision of the International Classification of Diseases (ICD-9 and -10), yet few were used in clinical practice, according to new research.

Most of the new codes for inflammatory arthritis in ICD-10 were rarely used, if at all, from 2015 to 2021.

“About 10-20 codes were comprising the majority of usage for inflammatory arthritis patients in ICD-10,” first author Justin Zhu, a researcher and medical student at Yale University in New Haven, Connecticut, told this news organization. “The other 380 or 400 codes just weren’t seeing a lot of use.”

Yale University

The findings show the difficulties of transitioning to a new system, he added, and emphasize the need for additional training to improve adoption of ICD-11. The new coding system launched globally in January 2022, but it is not clear when it will be implemented in the United States.

ICD-10 was launched in the United States in 2015, with the goal of enabling greater specificity in identifying health conditions. For example, the new coding system allowed users to include information on laterality and anatomic location for the first time. The total number of codes increased from 14,500 with ICD-9 to 70,000 with ICD-10, with the number of inflammatory arthritis diagnosis codes growing from 14 to 425.

To see how these ICD-10 codes were utilized compared with ICD-9, Zhu and colleagues used national multi-insurance administrative claims data to find inflammatory arthritis diagnostic codes for over 5.1 million patients. About half were coded in ICD-9, while the remaining half were coded in ICD-10. Mr. Zhu and colleagues defined “higher-usage codes” as those that were used more than 1% of the time.

The findings were published in a research letter in JAMA Network Open on April 18.

For ICD-9, four of the available 14 codes (28.6%) were higher-usage codes. In contrast, only nine of the 425 ICD-10 codes (2.1%) were frequently used. Though ICD-10 allowed for increased granularity in diagnosis, data showed that nonspecific codes were most popular. Of the 20 most used ICD-10 arthritis codes, 65% contained “unspecified or other specified” in its wording.

The researchers also found that there was no significant change in these higher-usage codes throughout the study period from 2015 to 2021, suggesting there was not a detectable learning curve in ICD-10 usage among physicians and coders. They also found that clinician specialty did not change code usage patterns.

“The percentage of codes used was not better for rheumatologists (who might be expected to be more refined users of such codes) than primary care clinicians,” Mr. Zhu and colleagues wrote.
 

Moving to ICD-11 Brings Challenges as Well as Opportunities

Mr. Zhu noted that the study highlights the challenges of adopting new technological systems into daily practice, which can inform the eventual transition to ICD-11.

“There is this need to emphasize training as well as just invest more in improving adoption of ICD-11,” he said.

Michael Pine, MD, MBA, of MJP Healthcare Innovations, LLC in Evanston, Illinois, added that ICD-11 needs to be more user-friendly to be useful in practice. While ICD-10 allowed for greater granularity in coding, it did not result in “usable granularity, in terms of the things doctors really want to communicate,” he told this news organization.

And the transition to ICD-11 could pose greater challenges; rather than ICD-10’s taxonomy system, ICD-11 is formatted as an ontology.

A version of this article appeared on Medscape.com.

Inflammatory arthritis codes increased 30-fold in the transition from the ninth to the 10th revision of the International Classification of Diseases (ICD-9 and -10), yet few were used in clinical practice, according to new research.

Most of the new codes for inflammatory arthritis in ICD-10 were rarely used, if at all, from 2015 to 2021.

“About 10-20 codes were comprising the majority of usage for inflammatory arthritis patients in ICD-10,” first author Justin Zhu, a researcher and medical student at Yale University in New Haven, Connecticut, told this news organization. “The other 380 or 400 codes just weren’t seeing a lot of use.”

Yale University

The findings show the difficulties of transitioning to a new system, he added, and emphasize the need for additional training to improve adoption of ICD-11. The new coding system launched globally in January 2022, but it is not clear when it will be implemented in the United States.

ICD-10 was launched in the United States in 2015, with the goal of enabling greater specificity in identifying health conditions. For example, the new coding system allowed users to include information on laterality and anatomic location for the first time. The total number of codes increased from 14,500 with ICD-9 to 70,000 with ICD-10, with the number of inflammatory arthritis diagnosis codes growing from 14 to 425.

To see how these ICD-10 codes were utilized compared with ICD-9, Zhu and colleagues used national multi-insurance administrative claims data to find inflammatory arthritis diagnostic codes for over 5.1 million patients. About half were coded in ICD-9, while the remaining half were coded in ICD-10. Mr. Zhu and colleagues defined “higher-usage codes” as those that were used more than 1% of the time.

The findings were published in a research letter in JAMA Network Open on April 18.

For ICD-9, four of the available 14 codes (28.6%) were higher-usage codes. In contrast, only nine of the 425 ICD-10 codes (2.1%) were frequently used. Though ICD-10 allowed for increased granularity in diagnosis, data showed that nonspecific codes were most popular. Of the 20 most used ICD-10 arthritis codes, 65% contained “unspecified or other specified” in its wording.

The researchers also found that there was no significant change in these higher-usage codes throughout the study period from 2015 to 2021, suggesting there was not a detectable learning curve in ICD-10 usage among physicians and coders. They also found that clinician specialty did not change code usage patterns.

“The percentage of codes used was not better for rheumatologists (who might be expected to be more refined users of such codes) than primary care clinicians,” Mr. Zhu and colleagues wrote.
 

Moving to ICD-11 Brings Challenges as Well as Opportunities

Mr. Zhu noted that the study highlights the challenges of adopting new technological systems into daily practice, which can inform the eventual transition to ICD-11.

“There is this need to emphasize training as well as just invest more in improving adoption of ICD-11,” he said.

Michael Pine, MD, MBA, of MJP Healthcare Innovations, LLC in Evanston, Illinois, added that ICD-11 needs to be more user-friendly to be useful in practice. While ICD-10 allowed for greater granularity in coding, it did not result in “usable granularity, in terms of the things doctors really want to communicate,” he told this news organization.

And the transition to ICD-11 could pose greater challenges; rather than ICD-10’s taxonomy system, ICD-11 is formatted as an ontology.

A version of this article appeared on Medscape.com.

I recently read an op-ed piece in which the author wondered if any young people entering the practice of medicine felt that they were answering a “calling.” I suspect that there will continue to be, and will always be, idealists whose primary motivation for choosing medicine is that they will be healing the sick or at least providing comfort to the suffering. I occasionally hear that about a former patient who has been inspired by a personal or familial experience with a serious illness.

Unfortunately, I suspect those who feel called are the providers most likely to feel discouraged and frustrated by the current state of primary care. Luckily, I never felt a calling. For me, primary care pediatrics was a job. One that l felt obligated to perform to the best of my ability. Mine was not a calling but an inherited philosophy that work in itself was virtuous. A work ethic, if you will. Pediatrics offered the additional reward that, if well done, it might help some parents and their children feel a little better.

Fifty years ago I was not alone in treating medicine as a job. Most physicians were self-employed. Although there were exceptions like Albert Schweitzer, even those of us with a calling had to obey the basic rules of business as it applied to medicine. We were employer and employee and had to understand the critical factors of overhead, profit, and loss.

I have burdened you with this little history recitation not to suggest that things were better in the good old days, but to provide a stepping stone into the murky and uncomfortable topic of primary care physician (PCP) compensation. Because almost three quarters of you work for a hospital, health system, or corporate entity, I am going to illuminate our journey by leaning on the advice of an international company with 7000 employees and revenue of 2.5 billion dollars that considers itself a “global leader” in management consulting. Your employer is listening to some management consultant and it may help us to view your compensation from someone on their side of the table.

First, you should be aware that “most health systems lose money on their primary care operations — up to $200,000 or more per primary care physician.” This may help explain why despite being in short supply, you and most PCPs feel undervalued. However, if we are such losers, we must provide something(s) that the systems are seeking. It is likely that the system is looking to tout its ability to provide comprehensive care and demonstrate that it has a patient base broad enough to warrant attention and provide bargaining leverage on volume discounts.

The system also may want to minimize competition by absorbing the remaining PCPs in the community into their system. With you outside of the system, it had less control over your compensation than it does when you are under its umbrella.

Your employer may want to grow and feed its specialty care network, and it sees PCPs as having the fuel stored in their patient volume to do just that. In simplest and most cynical terms, the systems are willing to take a loss on us less profitable high-volume grunts in order to reap the profits of the lower-volume high-profitability specialties and subspecialties.

So that’s why you as a PCP have any value at all to a large healthcare system. But, it means that to maintain your value to the system you must continue to provide the volume it anticipates and needs. While the system may have been willing to accept some degrees of unprofitability when it hired you, there are limits. And, we shouldn’t be surprised if they continue to urge or demand that we narrow the gap between the revenue we generate and the costs that we incur, ie, our overhead.

In Part 2 of this series, I’m going to discuss the collateral damage that occurs when volume and overhead collide in an environment that claims to be committed to patient care.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

I recently read an op-ed piece in which the author wondered if any young people entering the practice of medicine felt that they were answering a “calling.” I suspect that there will continue to be, and will always be, idealists whose primary motivation for choosing medicine is that they will be healing the sick or at least providing comfort to the suffering. I occasionally hear that about a former patient who has been inspired by a personal or familial experience with a serious illness.

Unfortunately, I suspect those who feel called are the providers most likely to feel discouraged and frustrated by the current state of primary care. Luckily, I never felt a calling. For me, primary care pediatrics was a job. One that l felt obligated to perform to the best of my ability. Mine was not a calling but an inherited philosophy that work in itself was virtuous. A work ethic, if you will. Pediatrics offered the additional reward that, if well done, it might help some parents and their children feel a little better.

Fifty years ago I was not alone in treating medicine as a job. Most physicians were self-employed. Although there were exceptions like Albert Schweitzer, even those of us with a calling had to obey the basic rules of business as it applied to medicine. We were employer and employee and had to understand the critical factors of overhead, profit, and loss.

I have burdened you with this little history recitation not to suggest that things were better in the good old days, but to provide a stepping stone into the murky and uncomfortable topic of primary care physician (PCP) compensation. Because almost three quarters of you work for a hospital, health system, or corporate entity, I am going to illuminate our journey by leaning on the advice of an international company with 7000 employees and revenue of 2.5 billion dollars that considers itself a “global leader” in management consulting. Your employer is listening to some management consultant and it may help us to view your compensation from someone on their side of the table.

First, you should be aware that “most health systems lose money on their primary care operations — up to $200,000 or more per primary care physician.” This may help explain why despite being in short supply, you and most PCPs feel undervalued. However, if we are such losers, we must provide something(s) that the systems are seeking. It is likely that the system is looking to tout its ability to provide comprehensive care and demonstrate that it has a patient base broad enough to warrant attention and provide bargaining leverage on volume discounts.

The system also may want to minimize competition by absorbing the remaining PCPs in the community into their system. With you outside of the system, it had less control over your compensation than it does when you are under its umbrella.

Your employer may want to grow and feed its specialty care network, and it sees PCPs as having the fuel stored in their patient volume to do just that. In simplest and most cynical terms, the systems are willing to take a loss on us less profitable high-volume grunts in order to reap the profits of the lower-volume high-profitability specialties and subspecialties.

So that’s why you as a PCP have any value at all to a large healthcare system. But, it means that to maintain your value to the system you must continue to provide the volume it anticipates and needs. While the system may have been willing to accept some degrees of unprofitability when it hired you, there are limits. And, we shouldn’t be surprised if they continue to urge or demand that we narrow the gap between the revenue we generate and the costs that we incur, ie, our overhead.

In Part 2 of this series, I’m going to discuss the collateral damage that occurs when volume and overhead collide in an environment that claims to be committed to patient care.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

I recently read an op-ed piece in which the author wondered if any young people entering the practice of medicine felt that they were answering a “calling.” I suspect that there will continue to be, and will always be, idealists whose primary motivation for choosing medicine is that they will be healing the sick or at least providing comfort to the suffering. I occasionally hear that about a former patient who has been inspired by a personal or familial experience with a serious illness.

Unfortunately, I suspect those who feel called are the providers most likely to feel discouraged and frustrated by the current state of primary care. Luckily, I never felt a calling. For me, primary care pediatrics was a job. One that l felt obligated to perform to the best of my ability. Mine was not a calling but an inherited philosophy that work in itself was virtuous. A work ethic, if you will. Pediatrics offered the additional reward that, if well done, it might help some parents and their children feel a little better.

Fifty years ago I was not alone in treating medicine as a job. Most physicians were self-employed. Although there were exceptions like Albert Schweitzer, even those of us with a calling had to obey the basic rules of business as it applied to medicine. We were employer and employee and had to understand the critical factors of overhead, profit, and loss.

I have burdened you with this little history recitation not to suggest that things were better in the good old days, but to provide a stepping stone into the murky and uncomfortable topic of primary care physician (PCP) compensation. Because almost three quarters of you work for a hospital, health system, or corporate entity, I am going to illuminate our journey by leaning on the advice of an international company with 7000 employees and revenue of 2.5 billion dollars that considers itself a “global leader” in management consulting. Your employer is listening to some management consultant and it may help us to view your compensation from someone on their side of the table.

First, you should be aware that “most health systems lose money on their primary care operations — up to $200,000 or more per primary care physician.” This may help explain why despite being in short supply, you and most PCPs feel undervalued. However, if we are such losers, we must provide something(s) that the systems are seeking. It is likely that the system is looking to tout its ability to provide comprehensive care and demonstrate that it has a patient base broad enough to warrant attention and provide bargaining leverage on volume discounts.

The system also may want to minimize competition by absorbing the remaining PCPs in the community into their system. With you outside of the system, it had less control over your compensation than it does when you are under its umbrella.

Your employer may want to grow and feed its specialty care network, and it sees PCPs as having the fuel stored in their patient volume to do just that. In simplest and most cynical terms, the systems are willing to take a loss on us less profitable high-volume grunts in order to reap the profits of the lower-volume high-profitability specialties and subspecialties.

So that’s why you as a PCP have any value at all to a large healthcare system. But, it means that to maintain your value to the system you must continue to provide the volume it anticipates and needs. While the system may have been willing to accept some degrees of unprofitability when it hired you, there are limits. And, we shouldn’t be surprised if they continue to urge or demand that we narrow the gap between the revenue we generate and the costs that we incur, ie, our overhead.

In Part 2 of this series, I’m going to discuss the collateral damage that occurs when volume and overhead collide in an environment that claims to be committed to patient care.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

On April 4, Oregon’s Governor Tina Kotek signed a bill into law that officially changed the title of “physician assistants” to “physician associates” in the state. The switch is the first of its kind in the United States and comes on the heels of a decision from 2021 by the American Academy of Physician Associates (AAPA) to change the meaning of “PA” to “physician associate” from “physician assistant.”

In the Medscape Physician Assistant Career Satisfaction Report 2023, a diverse range of opinions on the title switch was reflected. Only 40% of PAs favored the name change at the time, 45% neither opposed nor favored it, and 15% opposed the name change, reflecting the complexity of the issue.

According to the AAPA, the change came about to better reflect the work PAs do in not just “assisting” physicians but in working independently with patients. Some also felt that the word “assistant” implies dependence. However, despite associate’s more accurate reflection of the job, PAs mostly remain split on whether they want the new moniker.

Many say that the name change will be confusing for the public and their patients, while others say that physician assistant was already not well understood, as patients often thought of the profession as a doctor’s helper or an assistant, like a medical assistant.

Yet many long-time PAs say that they prefer the title they’ve always had and that explaining to patients the new associate title will be equally confusing. Some mentioned patients may think they’re a business associate of the physician.

Oregon PAs won’t immediately switch to the new name. The new law takes effect on June 6, 2024. The Oregon Medical Board will establish regulations and guidance before PAs adopt the new name in their practices.

The law only changes the name of PAs in Oregon, not in other states. In fact, prematurely using the title of physician associate could subject a PA to regulatory challenges or disciplinary actions.

A version of this article appeared on Medscape.com.

On April 4, Oregon’s Governor Tina Kotek signed a bill into law that officially changed the title of “physician assistants” to “physician associates” in the state. The switch is the first of its kind in the United States and comes on the heels of a decision from 2021 by the American Academy of Physician Associates (AAPA) to change the meaning of “PA” to “physician associate” from “physician assistant.”

In the Medscape Physician Assistant Career Satisfaction Report 2023, a diverse range of opinions on the title switch was reflected. Only 40% of PAs favored the name change at the time, 45% neither opposed nor favored it, and 15% opposed the name change, reflecting the complexity of the issue.

According to the AAPA, the change came about to better reflect the work PAs do in not just “assisting” physicians but in working independently with patients. Some also felt that the word “assistant” implies dependence. However, despite associate’s more accurate reflection of the job, PAs mostly remain split on whether they want the new moniker.

Many say that the name change will be confusing for the public and their patients, while others say that physician assistant was already not well understood, as patients often thought of the profession as a doctor’s helper or an assistant, like a medical assistant.

Yet many long-time PAs say that they prefer the title they’ve always had and that explaining to patients the new associate title will be equally confusing. Some mentioned patients may think they’re a business associate of the physician.

Oregon PAs won’t immediately switch to the new name. The new law takes effect on June 6, 2024. The Oregon Medical Board will establish regulations and guidance before PAs adopt the new name in their practices.

The law only changes the name of PAs in Oregon, not in other states. In fact, prematurely using the title of physician associate could subject a PA to regulatory challenges or disciplinary actions.

A version of this article appeared on Medscape.com.

On April 4, Oregon’s Governor Tina Kotek signed a bill into law that officially changed the title of “physician assistants” to “physician associates” in the state. The switch is the first of its kind in the United States and comes on the heels of a decision from 2021 by the American Academy of Physician Associates (AAPA) to change the meaning of “PA” to “physician associate” from “physician assistant.”

In the Medscape Physician Assistant Career Satisfaction Report 2023, a diverse range of opinions on the title switch was reflected. Only 40% of PAs favored the name change at the time, 45% neither opposed nor favored it, and 15% opposed the name change, reflecting the complexity of the issue.

According to the AAPA, the change came about to better reflect the work PAs do in not just “assisting” physicians but in working independently with patients. Some also felt that the word “assistant” implies dependence. However, despite associate’s more accurate reflection of the job, PAs mostly remain split on whether they want the new moniker.

Many say that the name change will be confusing for the public and their patients, while others say that physician assistant was already not well understood, as patients often thought of the profession as a doctor’s helper or an assistant, like a medical assistant.

Yet many long-time PAs say that they prefer the title they’ve always had and that explaining to patients the new associate title will be equally confusing. Some mentioned patients may think they’re a business associate of the physician.

Oregon PAs won’t immediately switch to the new name. The new law takes effect on June 6, 2024. The Oregon Medical Board will establish regulations and guidance before PAs adopt the new name in their practices.

The law only changes the name of PAs in Oregon, not in other states. In fact, prematurely using the title of physician associate could subject a PA to regulatory challenges or disciplinary actions.

A version of this article appeared on Medscape.com.

As the pendulum has swung against recommending aspirin for the primary prevention of heart attacks and strokes, clinicians should focus on other ways to help patients avoid cardiovascular events.

A landmark study published in 1988 in The New England Journal of Medicine reported an astonishing 44% drop in the number of heart attacks among US male physicians aged 40-84 years who took aspirin.

Aspirin subsequently became a daily habit for millions of Americans. In 2017, nearly a quarter of Americans over age 40 who did not have cardiovascular disease (CVD) took the drug, and over 20% of those were doing so without a physician’s recommendation.

But in 2018, three studies (ASCEND, ARRIVE, and ASPREE) showed a stunning reversal in the purported benefit, according to John Wong, MD, vice-chair of the US Preventive Services Task Force (USPSTF).

The calculus for taking aspirin appeared to have changed dramatically: The drug decreased the risk for myocardial infarction by only 11% among study subjects, while its potential harms were much more pronounced.

According to Dr. Wong, who is also a professor of medicine and a primary care physician at Tufts University School of Medicine in Boston, Massachusetts, patients taking low-dose aspirin had a 58% increase in their risk for gastrointestinal bleeding compared with those not on aspirin, as well as a 31% increased risk for intracranial bleeding.

Did aspirin suddenly lose its magic powers in preventing heart attacks? Dr. Wong attributed the decline in effectiveness of aspirin in preventing heart attacks to other “primary care interventions that help reduce the cardiovascular disease risk in patients who haven’t had a heart attack or stroke.”

Fewer Americans smoke cigarettes, more realize the benefits of a healthy diet and physical activity, and the medical community better recognizes and treats hypertension. New classes of medications such as statins for high cholesterol are also moving the needle.

But a newer class of drugs may provide a safer replacement for aspirin, according to Muhammad Maqsood, MD, a cardiology fellow at DeBakey Heart and Vascular Center at Methodist Hospital in Houston, Texas. P2Y purinoceptor 12 (P2Y12) inhibitors are effective in lowering the risk for heart attack and stroke in patients with acute coronary syndrome or those undergoing elective percutaneous coronary interventions.

“They have shown a better bleeding profile, especially clopidogrel compared to aspirin,” Dr. Maqsood said.

However, the findings come from trials of patients who already had CVD, so results cannot yet be extrapolated to primary prevention. Dr. Maqsood said the gap highlights the need for clinical trials that evaluate P2Y12 inhibitors for primary prevention, but no such study is registered on clinicaltrials.gov.
 

Benefits Persist for Some Patients

The new evidence led the USPSTF to publish new guidelines in 2022, downgrading the recommendation for low-dose aspirin use for primary prevention. Previously, the organization stated that clinicians “should” initiate daily low-dose aspirin in adults aged 50-59 years and “consider” its use in adults aged 60-69 years whose 10-year risk for CVD was higher than 10%.

The updated guidelines stated that the decision to initiate low-dose aspirin in adults aged 40-59 years with a greater than 10% risk for CVD “should be an individual one,” based on professional judgment and individual patient preferences. The USPSTF also recommended against the use of aspirin in anyone over the age of 60.

Meanwhile, the American College of Cardiology and American Heart Association also dialed down previously strong recommendations on low-dose aspirin to a more nuanced recommendation stating, “low-dose aspirin might be considered for primary prevention of ASCVD among select adults 40-70 years of age.”

With a varying age limit for recommending aspirin, clinicians may take into consideration several variables.

“Is there a magic age? I don’t think there is,” said Douglas Lloyd-Jones, the former president of the American Heart Association and current chair of the Department of Preventive Medicine and a practicing cardiologist at Northwestern University Feinberg School of Medicine in Chicago, Illinois.

For a patient over age 60 who is at a high risk for adverse cardiovascular outcomes, is unable to quit smoking, and is not likely to experience problematic bleeding, a clinician might recommend aspirin, Dr. Lloyd-Jones said. He said he sometimes also assesses coronary artery calcium to guide his clinical decisions: If elevated (an Agatston score above 100), he might recommend low-dose aspirin.

Dr. Lloyd-Jones also reiterated that patients should continue taking low-dose aspirin if they have already experienced a heart attack, stroke, episode of atrial fibrillation, or required a vascular stent.

Unless a patient with established CVD has intractable bleeding, “the aspirin is really for life,” Dr. Lloyd-Jones said. Patients who have a stent or who are at high risk for recurrence of stroke are more likely to experience thrombosis, and aspirin can decrease the risk.

“In our cardiology community, we don’t just strictly use the age of 70; the decision is always individualized,” Dr. Maqsood said.

Dr. Wong said primary care providers should focus on the USPSTF’s other recommendations that address CVD (Table), such as smoking cessation and screening for hypertension.

“I think our challenge is that we have so many of those A and B recommendations,” Dr. Wong said. “And I think part of the challenge for us is working with the patient to find out what’s most important to them.”

Discussing heart attacks and strokes often will strike a chord with patients because someone they know has been affected.

Dr. Maqsood emphasized the importance of behavioral interventions, such as helping patients decrease their body mass index and control their hyperlipidemia.

“The behavioral interventions are those which are the most cost-effective without any side effects,” he said.

His other piece of advice is to inquire with younger patients about a family history of heart attacks. Familial hypercholesteremia is unlikely to be controlled by diet and exercise and will need medical therapy.

Dr. Lloyd-Jones described the discussions he has with patients about preventing heart attacks as “the most important conversations we can have: Remember that cardiovascular disease is still the leading cause of death and disability in the world and in the United States.”

Dr. Wong, Dr. Lloyd-Jones, and Dr. Maqsood reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

As the pendulum has swung against recommending aspirin for the primary prevention of heart attacks and strokes, clinicians should focus on other ways to help patients avoid cardiovascular events.

A landmark study published in 1988 in The New England Journal of Medicine reported an astonishing 44% drop in the number of heart attacks among US male physicians aged 40-84 years who took aspirin.

Aspirin subsequently became a daily habit for millions of Americans. In 2017, nearly a quarter of Americans over age 40 who did not have cardiovascular disease (CVD) took the drug, and over 20% of those were doing so without a physician’s recommendation.

But in 2018, three studies (ASCEND, ARRIVE, and ASPREE) showed a stunning reversal in the purported benefit, according to John Wong, MD, vice-chair of the US Preventive Services Task Force (USPSTF).

The calculus for taking aspirin appeared to have changed dramatically: The drug decreased the risk for myocardial infarction by only 11% among study subjects, while its potential harms were much more pronounced.

According to Dr. Wong, who is also a professor of medicine and a primary care physician at Tufts University School of Medicine in Boston, Massachusetts, patients taking low-dose aspirin had a 58% increase in their risk for gastrointestinal bleeding compared with those not on aspirin, as well as a 31% increased risk for intracranial bleeding.

Did aspirin suddenly lose its magic powers in preventing heart attacks? Dr. Wong attributed the decline in effectiveness of aspirin in preventing heart attacks to other “primary care interventions that help reduce the cardiovascular disease risk in patients who haven’t had a heart attack or stroke.”

Fewer Americans smoke cigarettes, more realize the benefits of a healthy diet and physical activity, and the medical community better recognizes and treats hypertension. New classes of medications such as statins for high cholesterol are also moving the needle.

But a newer class of drugs may provide a safer replacement for aspirin, according to Muhammad Maqsood, MD, a cardiology fellow at DeBakey Heart and Vascular Center at Methodist Hospital in Houston, Texas. P2Y purinoceptor 12 (P2Y12) inhibitors are effective in lowering the risk for heart attack and stroke in patients with acute coronary syndrome or those undergoing elective percutaneous coronary interventions.

“They have shown a better bleeding profile, especially clopidogrel compared to aspirin,” Dr. Maqsood said.

However, the findings come from trials of patients who already had CVD, so results cannot yet be extrapolated to primary prevention. Dr. Maqsood said the gap highlights the need for clinical trials that evaluate P2Y12 inhibitors for primary prevention, but no such study is registered on clinicaltrials.gov.
 

Benefits Persist for Some Patients

The new evidence led the USPSTF to publish new guidelines in 2022, downgrading the recommendation for low-dose aspirin use for primary prevention. Previously, the organization stated that clinicians “should” initiate daily low-dose aspirin in adults aged 50-59 years and “consider” its use in adults aged 60-69 years whose 10-year risk for CVD was higher than 10%.

The updated guidelines stated that the decision to initiate low-dose aspirin in adults aged 40-59 years with a greater than 10% risk for CVD “should be an individual one,” based on professional judgment and individual patient preferences. The USPSTF also recommended against the use of aspirin in anyone over the age of 60.

Meanwhile, the American College of Cardiology and American Heart Association also dialed down previously strong recommendations on low-dose aspirin to a more nuanced recommendation stating, “low-dose aspirin might be considered for primary prevention of ASCVD among select adults 40-70 years of age.”

With a varying age limit for recommending aspirin, clinicians may take into consideration several variables.

“Is there a magic age? I don’t think there is,” said Douglas Lloyd-Jones, the former president of the American Heart Association and current chair of the Department of Preventive Medicine and a practicing cardiologist at Northwestern University Feinberg School of Medicine in Chicago, Illinois.

For a patient over age 60 who is at a high risk for adverse cardiovascular outcomes, is unable to quit smoking, and is not likely to experience problematic bleeding, a clinician might recommend aspirin, Dr. Lloyd-Jones said. He said he sometimes also assesses coronary artery calcium to guide his clinical decisions: If elevated (an Agatston score above 100), he might recommend low-dose aspirin.

Dr. Lloyd-Jones also reiterated that patients should continue taking low-dose aspirin if they have already experienced a heart attack, stroke, episode of atrial fibrillation, or required a vascular stent.

Unless a patient with established CVD has intractable bleeding, “the aspirin is really for life,” Dr. Lloyd-Jones said. Patients who have a stent or who are at high risk for recurrence of stroke are more likely to experience thrombosis, and aspirin can decrease the risk.

“In our cardiology community, we don’t just strictly use the age of 70; the decision is always individualized,” Dr. Maqsood said.

Dr. Wong said primary care providers should focus on the USPSTF’s other recommendations that address CVD (Table), such as smoking cessation and screening for hypertension.

“I think our challenge is that we have so many of those A and B recommendations,” Dr. Wong said. “And I think part of the challenge for us is working with the patient to find out what’s most important to them.”

Discussing heart attacks and strokes often will strike a chord with patients because someone they know has been affected.

Dr. Maqsood emphasized the importance of behavioral interventions, such as helping patients decrease their body mass index and control their hyperlipidemia.

“The behavioral interventions are those which are the most cost-effective without any side effects,” he said.

His other piece of advice is to inquire with younger patients about a family history of heart attacks. Familial hypercholesteremia is unlikely to be controlled by diet and exercise and will need medical therapy.

Dr. Lloyd-Jones described the discussions he has with patients about preventing heart attacks as “the most important conversations we can have: Remember that cardiovascular disease is still the leading cause of death and disability in the world and in the United States.”

Dr. Wong, Dr. Lloyd-Jones, and Dr. Maqsood reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

As the pendulum has swung against recommending aspirin for the primary prevention of heart attacks and strokes, clinicians should focus on other ways to help patients avoid cardiovascular events.

A landmark study published in 1988 in The New England Journal of Medicine reported an astonishing 44% drop in the number of heart attacks among US male physicians aged 40-84 years who took aspirin.

Aspirin subsequently became a daily habit for millions of Americans. In 2017, nearly a quarter of Americans over age 40 who did not have cardiovascular disease (CVD) took the drug, and over 20% of those were doing so without a physician’s recommendation.

But in 2018, three studies (ASCEND, ARRIVE, and ASPREE) showed a stunning reversal in the purported benefit, according to John Wong, MD, vice-chair of the US Preventive Services Task Force (USPSTF).

The calculus for taking aspirin appeared to have changed dramatically: The drug decreased the risk for myocardial infarction by only 11% among study subjects, while its potential harms were much more pronounced.

According to Dr. Wong, who is also a professor of medicine and a primary care physician at Tufts University School of Medicine in Boston, Massachusetts, patients taking low-dose aspirin had a 58% increase in their risk for gastrointestinal bleeding compared with those not on aspirin, as well as a 31% increased risk for intracranial bleeding.

Did aspirin suddenly lose its magic powers in preventing heart attacks? Dr. Wong attributed the decline in effectiveness of aspirin in preventing heart attacks to other “primary care interventions that help reduce the cardiovascular disease risk in patients who haven’t had a heart attack or stroke.”

Fewer Americans smoke cigarettes, more realize the benefits of a healthy diet and physical activity, and the medical community better recognizes and treats hypertension. New classes of medications such as statins for high cholesterol are also moving the needle.

But a newer class of drugs may provide a safer replacement for aspirin, according to Muhammad Maqsood, MD, a cardiology fellow at DeBakey Heart and Vascular Center at Methodist Hospital in Houston, Texas. P2Y purinoceptor 12 (P2Y12) inhibitors are effective in lowering the risk for heart attack and stroke in patients with acute coronary syndrome or those undergoing elective percutaneous coronary interventions.

“They have shown a better bleeding profile, especially clopidogrel compared to aspirin,” Dr. Maqsood said.

However, the findings come from trials of patients who already had CVD, so results cannot yet be extrapolated to primary prevention. Dr. Maqsood said the gap highlights the need for clinical trials that evaluate P2Y12 inhibitors for primary prevention, but no such study is registered on clinicaltrials.gov.
 

Benefits Persist for Some Patients

The new evidence led the USPSTF to publish new guidelines in 2022, downgrading the recommendation for low-dose aspirin use for primary prevention. Previously, the organization stated that clinicians “should” initiate daily low-dose aspirin in adults aged 50-59 years and “consider” its use in adults aged 60-69 years whose 10-year risk for CVD was higher than 10%.

The updated guidelines stated that the decision to initiate low-dose aspirin in adults aged 40-59 years with a greater than 10% risk for CVD “should be an individual one,” based on professional judgment and individual patient preferences. The USPSTF also recommended against the use of aspirin in anyone over the age of 60.

Meanwhile, the American College of Cardiology and American Heart Association also dialed down previously strong recommendations on low-dose aspirin to a more nuanced recommendation stating, “low-dose aspirin might be considered for primary prevention of ASCVD among select adults 40-70 years of age.”

With a varying age limit for recommending aspirin, clinicians may take into consideration several variables.

“Is there a magic age? I don’t think there is,” said Douglas Lloyd-Jones, the former president of the American Heart Association and current chair of the Department of Preventive Medicine and a practicing cardiologist at Northwestern University Feinberg School of Medicine in Chicago, Illinois.

For a patient over age 60 who is at a high risk for adverse cardiovascular outcomes, is unable to quit smoking, and is not likely to experience problematic bleeding, a clinician might recommend aspirin, Dr. Lloyd-Jones said. He said he sometimes also assesses coronary artery calcium to guide his clinical decisions: If elevated (an Agatston score above 100), he might recommend low-dose aspirin.

Dr. Lloyd-Jones also reiterated that patients should continue taking low-dose aspirin if they have already experienced a heart attack, stroke, episode of atrial fibrillation, or required a vascular stent.

Unless a patient with established CVD has intractable bleeding, “the aspirin is really for life,” Dr. Lloyd-Jones said. Patients who have a stent or who are at high risk for recurrence of stroke are more likely to experience thrombosis, and aspirin can decrease the risk.

“In our cardiology community, we don’t just strictly use the age of 70; the decision is always individualized,” Dr. Maqsood said.

Dr. Wong said primary care providers should focus on the USPSTF’s other recommendations that address CVD (Table), such as smoking cessation and screening for hypertension.

“I think our challenge is that we have so many of those A and B recommendations,” Dr. Wong said. “And I think part of the challenge for us is working with the patient to find out what’s most important to them.”

Discussing heart attacks and strokes often will strike a chord with patients because someone they know has been affected.

Dr. Maqsood emphasized the importance of behavioral interventions, such as helping patients decrease their body mass index and control their hyperlipidemia.

“The behavioral interventions are those which are the most cost-effective without any side effects,” he said.

His other piece of advice is to inquire with younger patients about a family history of heart attacks. Familial hypercholesteremia is unlikely to be controlled by diet and exercise and will need medical therapy.

Dr. Lloyd-Jones described the discussions he has with patients about preventing heart attacks as “the most important conversations we can have: Remember that cardiovascular disease is still the leading cause of death and disability in the world and in the United States.”

Dr. Wong, Dr. Lloyd-Jones, and Dr. Maqsood reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Immunization with inactivated vaccines while receiving the natalizumab for highly active multiple sclerosis (MS) is safe and immunogenic, with no increased risk for disease progression, new research shows. 

The study, the first to examine vaccine safety and immunogenicity in highly active MS, revealed high seroprotection rates following receipt of vaccines for COVID-19 and hepatitis A and B, regardless of the duration of treatment with natalizumab.

On the basis of these findings, investigators created an algorithm that clinicians can use to map an immunization schedule in patients who might otherwise delay initiation of disease-modifying therapy until they are fully vaccinated.

“We observed seroprotection rates exceeding 90% for hepatitis A and B, and mRNA COVID-19 vaccines, and all vaccines demonstrated a favorable safety profile, with no exacerbation of disease activity detected,” said lead author René Carvajal, MD, of the Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. “This points to potential benefits for patients with highly active MS who require both immunization and high-efficacy therapies that may impact vaccine responses.” 

The study was published online in JAMA Network Open.
 

A Controversial Issue

Today’s high-efficacy therapies for MS may increase the risk of acquiring new infections, reactivate latent pathogens, or worsen ongoing infectious conditions, and immunogenicity of vaccination can be compromised by immunosuppressive agents, particularly CD20 therapies, researchers noted.

As a result, many clinicians opt to delay initiation of such therapies until vaccination schedules are complete to avoid exposure to vaccine-preventable infections. But delaying treatment can potentially affect disease progression. 

Reports of disease worsening following vaccination “have raised controversy around vaccine safety,” the authors wrote. The issue is especially relevant to those with highly active MS due to the scarcity of available data in this population.

The motivation for the study “stemmed from the complex balance clinicians face between initiating highly effective therapies promptly in patients with highly active MS and ensuring adequate protection against preventable infections through vaccination,” Dr. Carvajal said.
 

High Seroprotection Rate

Researchers analyzed data on 60 patients (mean age, 43 years; 44 female; mean disease duration, 17 years) participating in one of two prospectively followed cohorts: The Barcelona Clinically Isolated Syndromes Inception Cohort and the Barcelona Treatment Cohort. Data included demographic, clinical, radiologic, and biological data as well as regular clinical assessments, evaluations of the Expanded Disability Status Scale (EDSS), and MRI scans.

Patients enrolled in the current study had received at least one of these vaccines between September 2016 and February 2022: hepatitis A virus (HAV), hepatitis B virus (HBV; enhanced immunity high load or adjuvanted), or COVID-19 (BNT162b2 [Pfizer-BioNTech], mRAN-1273 [Moderna], or ChAdOx1-S [recombinant; AstraZeneca]).

The researchers conducted a retrospective, self-controlled analysis to compare the annualized relapse rate, EDSS score, and new T2 lesions counts during the 12 months before and after vaccination in patients with short- and long-term treatment duration.

They also compared John Cunningham virus serostatus between the two periods, as well as immunoglobulin G titers for each vaccine.

The global seroprotection rate was 93% (95% CI, 86%-98%). Individual vaccine rates were 92% for HAV, 93% for HBV, and 100% for COVID-19.

There was a significant reduction between the pre- and postvaccination periods in mean relapse rates (P = .004) and median number of new T2 lesions (P  = .01).

There were no changes in EDSS scores before and after vaccinations and duration of natalizumab treatment had no impact on safety and immunogenicity.
 

‘Viable Option’

The researchers used their findings to create a proposed algorithm to inform immunization decisions in patients with highly active MS who require prompt initiation of high-efficacy disease-modifying therapy.

The algorithm is “integrated into a risk-minimization strategy tailored for patients with highly active MS, emphasizing in this case the pivotal role of natalizumab in averting treatment delays and providing adequate protection against potentially severe infections,” Dr. Carvajal said.

Participants who initiated or continued treatment with natalizumab completed their vaccination regimen without any incidents of progressive multifocal leukoencephalopathy (PML) or disease activity rebound following natalizumab discontinuation.

This suggests that using natalizumab for a brief duration might be a “viable option to contemplate,” the authors noted.

Commenting on the findings, Grace Gombolay, MD, assistant professor of pediatrics in the Division of Pediatric Neurology and director of the Pediatric Neuroimmunology and Multiple Sclerosis Clinic, Emory University, Atlanta, Georgia, said the study “demonstrates that vaccines are safe and do not trigger attacks in patients with MS on natalizumab, and that immunity — as measured by antibodies — is preserved in MS patients who receive natalizumab.”

This “contrasts with other treatments, as decreased antibody responses in COVID-19 are noted in certain treatments,” said Dr. Gombolay, who was not part of the study. “If both disease control and immunity against infection are the goals for the patient, then natalizumab is a reasonable option.” 

“However, this must be balanced with other considerations,” she added, including the risk for PML and pregnancy. 

This study was supported by grants from the European Committee for Treatment and Research in Multiple Sclerosis, Instituto de Salud Carlos III, and the European Union. Dr. Carvajal reported receiving grants from Vall d’Hebron Institut de Recerca and the European Committee for Treatment and Research in Multiple Sclerosis and honoraria from Roche, Novartis, BIIB-Colombia, Merck, and Sanofi outside the submitted work. Dr. Gombolay serves as media editor for Pediatric Neurology and as associate editor of the Annals of the Child Neurology Society. She is also a part-time CDC consultant for acute flaccid myelitis and received an honorarium as a speaker at the Georgia Neurological Society meeting, sponsored by Academic CME and TG Therapeutics.

A version of this article appeared on Medscape.com.

Immunization with inactivated vaccines while receiving the natalizumab for highly active multiple sclerosis (MS) is safe and immunogenic, with no increased risk for disease progression, new research shows. 

The study, the first to examine vaccine safety and immunogenicity in highly active MS, revealed high seroprotection rates following receipt of vaccines for COVID-19 and hepatitis A and B, regardless of the duration of treatment with natalizumab.

On the basis of these findings, investigators created an algorithm that clinicians can use to map an immunization schedule in patients who might otherwise delay initiation of disease-modifying therapy until they are fully vaccinated.

“We observed seroprotection rates exceeding 90% for hepatitis A and B, and mRNA COVID-19 vaccines, and all vaccines demonstrated a favorable safety profile, with no exacerbation of disease activity detected,” said lead author René Carvajal, MD, of the Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. “This points to potential benefits for patients with highly active MS who require both immunization and high-efficacy therapies that may impact vaccine responses.” 

The study was published online in JAMA Network Open.
 

A Controversial Issue

Today’s high-efficacy therapies for MS may increase the risk of acquiring new infections, reactivate latent pathogens, or worsen ongoing infectious conditions, and immunogenicity of vaccination can be compromised by immunosuppressive agents, particularly CD20 therapies, researchers noted.

As a result, many clinicians opt to delay initiation of such therapies until vaccination schedules are complete to avoid exposure to vaccine-preventable infections. But delaying treatment can potentially affect disease progression. 

Reports of disease worsening following vaccination “have raised controversy around vaccine safety,” the authors wrote. The issue is especially relevant to those with highly active MS due to the scarcity of available data in this population.

The motivation for the study “stemmed from the complex balance clinicians face between initiating highly effective therapies promptly in patients with highly active MS and ensuring adequate protection against preventable infections through vaccination,” Dr. Carvajal said.
 

High Seroprotection Rate

Researchers analyzed data on 60 patients (mean age, 43 years; 44 female; mean disease duration, 17 years) participating in one of two prospectively followed cohorts: The Barcelona Clinically Isolated Syndromes Inception Cohort and the Barcelona Treatment Cohort. Data included demographic, clinical, radiologic, and biological data as well as regular clinical assessments, evaluations of the Expanded Disability Status Scale (EDSS), and MRI scans.

Patients enrolled in the current study had received at least one of these vaccines between September 2016 and February 2022: hepatitis A virus (HAV), hepatitis B virus (HBV; enhanced immunity high load or adjuvanted), or COVID-19 (BNT162b2 [Pfizer-BioNTech], mRAN-1273 [Moderna], or ChAdOx1-S [recombinant; AstraZeneca]).

The researchers conducted a retrospective, self-controlled analysis to compare the annualized relapse rate, EDSS score, and new T2 lesions counts during the 12 months before and after vaccination in patients with short- and long-term treatment duration.

They also compared John Cunningham virus serostatus between the two periods, as well as immunoglobulin G titers for each vaccine.

The global seroprotection rate was 93% (95% CI, 86%-98%). Individual vaccine rates were 92% for HAV, 93% for HBV, and 100% for COVID-19.

There was a significant reduction between the pre- and postvaccination periods in mean relapse rates (P = .004) and median number of new T2 lesions (P  = .01).

There were no changes in EDSS scores before and after vaccinations and duration of natalizumab treatment had no impact on safety and immunogenicity.
 

‘Viable Option’

The researchers used their findings to create a proposed algorithm to inform immunization decisions in patients with highly active MS who require prompt initiation of high-efficacy disease-modifying therapy.

The algorithm is “integrated into a risk-minimization strategy tailored for patients with highly active MS, emphasizing in this case the pivotal role of natalizumab in averting treatment delays and providing adequate protection against potentially severe infections,” Dr. Carvajal said.

Participants who initiated or continued treatment with natalizumab completed their vaccination regimen without any incidents of progressive multifocal leukoencephalopathy (PML) or disease activity rebound following natalizumab discontinuation.

This suggests that using natalizumab for a brief duration might be a “viable option to contemplate,” the authors noted.

Commenting on the findings, Grace Gombolay, MD, assistant professor of pediatrics in the Division of Pediatric Neurology and director of the Pediatric Neuroimmunology and Multiple Sclerosis Clinic, Emory University, Atlanta, Georgia, said the study “demonstrates that vaccines are safe and do not trigger attacks in patients with MS on natalizumab, and that immunity — as measured by antibodies — is preserved in MS patients who receive natalizumab.”

This “contrasts with other treatments, as decreased antibody responses in COVID-19 are noted in certain treatments,” said Dr. Gombolay, who was not part of the study. “If both disease control and immunity against infection are the goals for the patient, then natalizumab is a reasonable option.” 

“However, this must be balanced with other considerations,” she added, including the risk for PML and pregnancy. 

This study was supported by grants from the European Committee for Treatment and Research in Multiple Sclerosis, Instituto de Salud Carlos III, and the European Union. Dr. Carvajal reported receiving grants from Vall d’Hebron Institut de Recerca and the European Committee for Treatment and Research in Multiple Sclerosis and honoraria from Roche, Novartis, BIIB-Colombia, Merck, and Sanofi outside the submitted work. Dr. Gombolay serves as media editor for Pediatric Neurology and as associate editor of the Annals of the Child Neurology Society. She is also a part-time CDC consultant for acute flaccid myelitis and received an honorarium as a speaker at the Georgia Neurological Society meeting, sponsored by Academic CME and TG Therapeutics.

A version of this article appeared on Medscape.com.

Immunization with inactivated vaccines while receiving the natalizumab for highly active multiple sclerosis (MS) is safe and immunogenic, with no increased risk for disease progression, new research shows. 

The study, the first to examine vaccine safety and immunogenicity in highly active MS, revealed high seroprotection rates following receipt of vaccines for COVID-19 and hepatitis A and B, regardless of the duration of treatment with natalizumab.

On the basis of these findings, investigators created an algorithm that clinicians can use to map an immunization schedule in patients who might otherwise delay initiation of disease-modifying therapy until they are fully vaccinated.

“We observed seroprotection rates exceeding 90% for hepatitis A and B, and mRNA COVID-19 vaccines, and all vaccines demonstrated a favorable safety profile, with no exacerbation of disease activity detected,” said lead author René Carvajal, MD, of the Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. “This points to potential benefits for patients with highly active MS who require both immunization and high-efficacy therapies that may impact vaccine responses.” 

The study was published online in JAMA Network Open.
 

A Controversial Issue

Today’s high-efficacy therapies for MS may increase the risk of acquiring new infections, reactivate latent pathogens, or worsen ongoing infectious conditions, and immunogenicity of vaccination can be compromised by immunosuppressive agents, particularly CD20 therapies, researchers noted.

As a result, many clinicians opt to delay initiation of such therapies until vaccination schedules are complete to avoid exposure to vaccine-preventable infections. But delaying treatment can potentially affect disease progression. 

Reports of disease worsening following vaccination “have raised controversy around vaccine safety,” the authors wrote. The issue is especially relevant to those with highly active MS due to the scarcity of available data in this population.

The motivation for the study “stemmed from the complex balance clinicians face between initiating highly effective therapies promptly in patients with highly active MS and ensuring adequate protection against preventable infections through vaccination,” Dr. Carvajal said.
 

High Seroprotection Rate

Researchers analyzed data on 60 patients (mean age, 43 years; 44 female; mean disease duration, 17 years) participating in one of two prospectively followed cohorts: The Barcelona Clinically Isolated Syndromes Inception Cohort and the Barcelona Treatment Cohort. Data included demographic, clinical, radiologic, and biological data as well as regular clinical assessments, evaluations of the Expanded Disability Status Scale (EDSS), and MRI scans.

Patients enrolled in the current study had received at least one of these vaccines between September 2016 and February 2022: hepatitis A virus (HAV), hepatitis B virus (HBV; enhanced immunity high load or adjuvanted), or COVID-19 (BNT162b2 [Pfizer-BioNTech], mRAN-1273 [Moderna], or ChAdOx1-S [recombinant; AstraZeneca]).

The researchers conducted a retrospective, self-controlled analysis to compare the annualized relapse rate, EDSS score, and new T2 lesions counts during the 12 months before and after vaccination in patients with short- and long-term treatment duration.

They also compared John Cunningham virus serostatus between the two periods, as well as immunoglobulin G titers for each vaccine.

The global seroprotection rate was 93% (95% CI, 86%-98%). Individual vaccine rates were 92% for HAV, 93% for HBV, and 100% for COVID-19.

There was a significant reduction between the pre- and postvaccination periods in mean relapse rates (P = .004) and median number of new T2 lesions (P  = .01).

There were no changes in EDSS scores before and after vaccinations and duration of natalizumab treatment had no impact on safety and immunogenicity.
 

‘Viable Option’

The researchers used their findings to create a proposed algorithm to inform immunization decisions in patients with highly active MS who require prompt initiation of high-efficacy disease-modifying therapy.

The algorithm is “integrated into a risk-minimization strategy tailored for patients with highly active MS, emphasizing in this case the pivotal role of natalizumab in averting treatment delays and providing adequate protection against potentially severe infections,” Dr. Carvajal said.

Participants who initiated or continued treatment with natalizumab completed their vaccination regimen without any incidents of progressive multifocal leukoencephalopathy (PML) or disease activity rebound following natalizumab discontinuation.

This suggests that using natalizumab for a brief duration might be a “viable option to contemplate,” the authors noted.

Commenting on the findings, Grace Gombolay, MD, assistant professor of pediatrics in the Division of Pediatric Neurology and director of the Pediatric Neuroimmunology and Multiple Sclerosis Clinic, Emory University, Atlanta, Georgia, said the study “demonstrates that vaccines are safe and do not trigger attacks in patients with MS on natalizumab, and that immunity — as measured by antibodies — is preserved in MS patients who receive natalizumab.”

This “contrasts with other treatments, as decreased antibody responses in COVID-19 are noted in certain treatments,” said Dr. Gombolay, who was not part of the study. “If both disease control and immunity against infection are the goals for the patient, then natalizumab is a reasonable option.” 

“However, this must be balanced with other considerations,” she added, including the risk for PML and pregnancy. 

This study was supported by grants from the European Committee for Treatment and Research in Multiple Sclerosis, Instituto de Salud Carlos III, and the European Union. Dr. Carvajal reported receiving grants from Vall d’Hebron Institut de Recerca and the European Committee for Treatment and Research in Multiple Sclerosis and honoraria from Roche, Novartis, BIIB-Colombia, Merck, and Sanofi outside the submitted work. Dr. Gombolay serves as media editor for Pediatric Neurology and as associate editor of the Annals of the Child Neurology Society. She is also a part-time CDC consultant for acute flaccid myelitis and received an honorarium as a speaker at the Georgia Neurological Society meeting, sponsored by Academic CME and TG Therapeutics.

A version of this article appeared on Medscape.com.

TOPLINE:

Decreased total sleep time (TST) and increased resting heart rate (RHR), heart rate variability (HRV), and average nightly respiratory rate (ARR) as measured by a multisensor device worn during sleep accurately correlated with self-reported stress levels in college students, a new study suggests. Investigators say the findings support the potential utility of wearable devices to collect data that identify young adults at greatest risk for stress. 

METHODOLOGY:

• First-semester college students (n = 525; aged 18-24 years) enrolled in the Lived Experiences measured Using Rings Study (LEMURS) provided continuous biometric data via a wearable device (Oura Ring; Oura Health) and answered weekly surveys regarding stress levels.
• The researchers used mixed-effects regression models to identify associations between perceived stress scores and average nightly TST, RHR, HRV, and ARR.

TAKEAWAY:

• Consistent associations were found between perceived stress scores and TST, RHR, HRV, and ARR, which persisted even after controlling for gender and week of the semester.
• Risk for moderate to high stress decreased by 38% with every additional hour of TST (P < .01) and by 1.2% with each millisecond increase in HRV (P < .05).
• Moderate to high stress risk increased by 3.6% with each beat-per-minute-increase in RHR (P < .01) and by 23% with each additional breath-per-minute increase in ARR (P < .01).
• Participants who identified as female, nonbinary, or transgender reported significantly higher stress throughout the study.

IN PRACTICE:

“The present work highlights the potential utility of monitoring sleep, suggesting that these measures may identify within individual changes that are concerning for stress. As the demand for mental health services grows, determining which wearable-derived sleep estimates provide information about well-being and can predict worsening mental health in young adults is an important area of study,” study authors wrote.

SOURCE:

The study, led by Laura S.P. Bloomfield, University of Vermont, Burlington, Vermont, was published online in PLOS Digital Health.

LIMITATIONS:

The study focused on raw sleep measures; the researchers suggest that future studies evaluate additional sleep variables (eg, daytime naps), which have been associated with mental health in college students. In addition, the researchers did not have stress or sleep data before participants started college, so they could not assess the impact of starting college on participants’ sleep.

DISCLOSURES:

Bloomfield was supported by the Gund Fellowship and received a partial salary from the Mass Mutual Insurance Wellness Initiative. Other authors’ funding is reported in the original article.

A version of this article appeared on Medscape.com.

TOPLINE:

Decreased total sleep time (TST) and increased resting heart rate (RHR), heart rate variability (HRV), and average nightly respiratory rate (ARR) as measured by a multisensor device worn during sleep accurately correlated with self-reported stress levels in college students, a new study suggests. Investigators say the findings support the potential utility of wearable devices to collect data that identify young adults at greatest risk for stress. 

METHODOLOGY:

• First-semester college students (n = 525; aged 18-24 years) enrolled in the Lived Experiences measured Using Rings Study (LEMURS) provided continuous biometric data via a wearable device (Oura Ring; Oura Health) and answered weekly surveys regarding stress levels.
• The researchers used mixed-effects regression models to identify associations between perceived stress scores and average nightly TST, RHR, HRV, and ARR.

TAKEAWAY:

• Consistent associations were found between perceived stress scores and TST, RHR, HRV, and ARR, which persisted even after controlling for gender and week of the semester.
• Risk for moderate to high stress decreased by 38% with every additional hour of TST (P < .01) and by 1.2% with each millisecond increase in HRV (P < .05).
• Moderate to high stress risk increased by 3.6% with each beat-per-minute-increase in RHR (P < .01) and by 23% with each additional breath-per-minute increase in ARR (P < .01).
• Participants who identified as female, nonbinary, or transgender reported significantly higher stress throughout the study.

IN PRACTICE:

“The present work highlights the potential utility of monitoring sleep, suggesting that these measures may identify within individual changes that are concerning for stress. As the demand for mental health services grows, determining which wearable-derived sleep estimates provide information about well-being and can predict worsening mental health in young adults is an important area of study,” study authors wrote.

SOURCE:

The study, led by Laura S.P. Bloomfield, University of Vermont, Burlington, Vermont, was published online in PLOS Digital Health.

LIMITATIONS:

The study focused on raw sleep measures; the researchers suggest that future studies evaluate additional sleep variables (eg, daytime naps), which have been associated with mental health in college students. In addition, the researchers did not have stress or sleep data before participants started college, so they could not assess the impact of starting college on participants’ sleep.

DISCLOSURES:

Bloomfield was supported by the Gund Fellowship and received a partial salary from the Mass Mutual Insurance Wellness Initiative. Other authors’ funding is reported in the original article.

A version of this article appeared on Medscape.com.

TOPLINE:

Decreased total sleep time (TST) and increased resting heart rate (RHR), heart rate variability (HRV), and average nightly respiratory rate (ARR) as measured by a multisensor device worn during sleep accurately correlated with self-reported stress levels in college students, a new study suggests. Investigators say the findings support the potential utility of wearable devices to collect data that identify young adults at greatest risk for stress. 

METHODOLOGY:

• First-semester college students (n = 525; aged 18-24 years) enrolled in the Lived Experiences measured Using Rings Study (LEMURS) provided continuous biometric data via a wearable device (Oura Ring; Oura Health) and answered weekly surveys regarding stress levels.
• The researchers used mixed-effects regression models to identify associations between perceived stress scores and average nightly TST, RHR, HRV, and ARR.

TAKEAWAY:

• Consistent associations were found between perceived stress scores and TST, RHR, HRV, and ARR, which persisted even after controlling for gender and week of the semester.
• Risk for moderate to high stress decreased by 38% with every additional hour of TST (P < .01) and by 1.2% with each millisecond increase in HRV (P < .05).
• Moderate to high stress risk increased by 3.6% with each beat-per-minute-increase in RHR (P < .01) and by 23% with each additional breath-per-minute increase in ARR (P < .01).
• Participants who identified as female, nonbinary, or transgender reported significantly higher stress throughout the study.

IN PRACTICE:

“The present work highlights the potential utility of monitoring sleep, suggesting that these measures may identify within individual changes that are concerning for stress. As the demand for mental health services grows, determining which wearable-derived sleep estimates provide information about well-being and can predict worsening mental health in young adults is an important area of study,” study authors wrote.

SOURCE:

The study, led by Laura S.P. Bloomfield, University of Vermont, Burlington, Vermont, was published online in PLOS Digital Health.

LIMITATIONS:

The study focused on raw sleep measures; the researchers suggest that future studies evaluate additional sleep variables (eg, daytime naps), which have been associated with mental health in college students. In addition, the researchers did not have stress or sleep data before participants started college, so they could not assess the impact of starting college on participants’ sleep.

DISCLOSURES:

Bloomfield was supported by the Gund Fellowship and received a partial salary from the Mass Mutual Insurance Wellness Initiative. Other authors’ funding is reported in the original article.

A version of this article appeared on Medscape.com.

TOPLINE:

Moderate to vigorous aerobic physical activity performed in the evening is associated with the lowest risk for mortality, cardiovascular disease (CVD), and microvascular disease (MVD) in adults with obesity, including those with type 2 diabetes (T2D).

METHODOLOGY:

• Bouts of moderate to vigorous aerobic physical activity are widely recognized to improve cardiometabolic risk factors, but whether morning, afternoon, or evening timing may lead to greater improvements is unclear.
• Researchers analyzed UK Biobank data of 29,836 participants with obesity (body mass index, › 30; mean age, 62.2 years; 53.2% women), including 2995 also diagnosed with T2D, all enrolled in 2006-2010.
• Aerobic activity was defined as bouts lasting ≥ 3 minutes, and the intensity of activity was classified as light, moderate, or vigorous using accelerometer data collected from participants.
• Participants were stratified into the morning (6 a.m. to < 12 p.m.), afternoon (12 p.m. to < 6 p.m.), and evening (6 p.m. to < 12 a.m.) groups based on when > 50% of their total moderate to vigorous activity occurred, and those with no aerobic bouts were considered the reference group.
• The association between the timing of aerobic physical activity and risk for all-cause mortality, CVD (defined as circulatory, such as hypertension), and MVD (neuropathy, nephropathy, or retinopathy) was evaluated over a median follow-up of 7.9 years.

TAKEAWAY:

• Mortality risk was lowest in the evening moderate to vigorous physical activity group (hazard ratio [HR], 0.39; 95% CI, 0.27-0.55) and even lower in the T2D subgroup (HR, 0.24; 95% CI, 0.08-0.76) than in the reference group.
• Mortality risk was lower in the afternoon (HR, 0.60; 95% CI, 0.51-0.71) and morning (HR, 0.67; 95% CI, 0.56-0.79) activity groups than in the reference group, but this association was weaker than that observed in the evening activity group.
• The evening moderate to vigorous activity group had a lower risk for CVD (HR, 0.64; 95% CI, 0.54-0.75) and MVD (HR, 0.76; 95% CI, 0.63-0.92) than the reference group.
• Among participants with obesity and T2D, moderate to vigorous physical activity in the evening was associated with a lower risk for mortality, CVD, and MVD.

IN PRACTICE:

The authors wrote, “The results of this study emphasize that beyond the total volume of MVPA [moderate to vigorous physical activity], its timing, particularly in the evening, was consistently associated with the lowest risk of mortality relative to other timing windows.”

SOURCE:

The study, led by Angelo Sabag, PhD, Charles Perkins Centre, University of Sydney, Australia, was published online in Diabetes Care.

LIMITATIONS:

Because this was an observational study, the possibility of reverse causation from prodromal disease and unaccounted confounding factors could not have been ruled out. There was a lag of a median of 5.5 years between the UK Biobank baseline, when covariate measurements were taken, and the accelerometry study. Moreover, the response rate of the UK Biobank was low.

DISCLOSURES:

The study was funded by an Australian National Health and Medical Research Council Investigator Grant and the National Heart Foundation of Australia Postdoctoral Fellowship. The authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Moderate to vigorous aerobic physical activity performed in the evening is associated with the lowest risk for mortality, cardiovascular disease (CVD), and microvascular disease (MVD) in adults with obesity, including those with type 2 diabetes (T2D).

METHODOLOGY:

• Bouts of moderate to vigorous aerobic physical activity are widely recognized to improve cardiometabolic risk factors, but whether morning, afternoon, or evening timing may lead to greater improvements is unclear.
• Researchers analyzed UK Biobank data of 29,836 participants with obesity (body mass index, › 30; mean age, 62.2 years; 53.2% women), including 2995 also diagnosed with T2D, all enrolled in 2006-2010.
• Aerobic activity was defined as bouts lasting ≥ 3 minutes, and the intensity of activity was classified as light, moderate, or vigorous using accelerometer data collected from participants.
• Participants were stratified into the morning (6 a.m. to < 12 p.m.), afternoon (12 p.m. to < 6 p.m.), and evening (6 p.m. to < 12 a.m.) groups based on when > 50% of their total moderate to vigorous activity occurred, and those with no aerobic bouts were considered the reference group.
• The association between the timing of aerobic physical activity and risk for all-cause mortality, CVD (defined as circulatory, such as hypertension), and MVD (neuropathy, nephropathy, or retinopathy) was evaluated over a median follow-up of 7.9 years.

TAKEAWAY:

• Mortality risk was lowest in the evening moderate to vigorous physical activity group (hazard ratio [HR], 0.39; 95% CI, 0.27-0.55) and even lower in the T2D subgroup (HR, 0.24; 95% CI, 0.08-0.76) than in the reference group.
• Mortality risk was lower in the afternoon (HR, 0.60; 95% CI, 0.51-0.71) and morning (HR, 0.67; 95% CI, 0.56-0.79) activity groups than in the reference group, but this association was weaker than that observed in the evening activity group.
• The evening moderate to vigorous activity group had a lower risk for CVD (HR, 0.64; 95% CI, 0.54-0.75) and MVD (HR, 0.76; 95% CI, 0.63-0.92) than the reference group.
• Among participants with obesity and T2D, moderate to vigorous physical activity in the evening was associated with a lower risk for mortality, CVD, and MVD.

IN PRACTICE:

The authors wrote, “The results of this study emphasize that beyond the total volume of MVPA [moderate to vigorous physical activity], its timing, particularly in the evening, was consistently associated with the lowest risk of mortality relative to other timing windows.”

SOURCE:

The study, led by Angelo Sabag, PhD, Charles Perkins Centre, University of Sydney, Australia, was published online in Diabetes Care.

LIMITATIONS:

Because this was an observational study, the possibility of reverse causation from prodromal disease and unaccounted confounding factors could not have been ruled out. There was a lag of a median of 5.5 years between the UK Biobank baseline, when covariate measurements were taken, and the accelerometry study. Moreover, the response rate of the UK Biobank was low.

DISCLOSURES:

The study was funded by an Australian National Health and Medical Research Council Investigator Grant and the National Heart Foundation of Australia Postdoctoral Fellowship. The authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Moderate to vigorous aerobic physical activity performed in the evening is associated with the lowest risk for mortality, cardiovascular disease (CVD), and microvascular disease (MVD) in adults with obesity, including those with type 2 diabetes (T2D).

METHODOLOGY:

• Bouts of moderate to vigorous aerobic physical activity are widely recognized to improve cardiometabolic risk factors, but whether morning, afternoon, or evening timing may lead to greater improvements is unclear.
• Researchers analyzed UK Biobank data of 29,836 participants with obesity (body mass index, › 30; mean age, 62.2 years; 53.2% women), including 2995 also diagnosed with T2D, all enrolled in 2006-2010.
• Aerobic activity was defined as bouts lasting ≥ 3 minutes, and the intensity of activity was classified as light, moderate, or vigorous using accelerometer data collected from participants.
• Participants were stratified into the morning (6 a.m. to < 12 p.m.), afternoon (12 p.m. to < 6 p.m.), and evening (6 p.m. to < 12 a.m.) groups based on when > 50% of their total moderate to vigorous activity occurred, and those with no aerobic bouts were considered the reference group.
• The association between the timing of aerobic physical activity and risk for all-cause mortality, CVD (defined as circulatory, such as hypertension), and MVD (neuropathy, nephropathy, or retinopathy) was evaluated over a median follow-up of 7.9 years.

TAKEAWAY:

• Mortality risk was lowest in the evening moderate to vigorous physical activity group (hazard ratio [HR], 0.39; 95% CI, 0.27-0.55) and even lower in the T2D subgroup (HR, 0.24; 95% CI, 0.08-0.76) than in the reference group.
• Mortality risk was lower in the afternoon (HR, 0.60; 95% CI, 0.51-0.71) and morning (HR, 0.67; 95% CI, 0.56-0.79) activity groups than in the reference group, but this association was weaker than that observed in the evening activity group.
• The evening moderate to vigorous activity group had a lower risk for CVD (HR, 0.64; 95% CI, 0.54-0.75) and MVD (HR, 0.76; 95% CI, 0.63-0.92) than the reference group.
• Among participants with obesity and T2D, moderate to vigorous physical activity in the evening was associated with a lower risk for mortality, CVD, and MVD.

IN PRACTICE:

The authors wrote, “The results of this study emphasize that beyond the total volume of MVPA [moderate to vigorous physical activity], its timing, particularly in the evening, was consistently associated with the lowest risk of mortality relative to other timing windows.”

SOURCE:

The study, led by Angelo Sabag, PhD, Charles Perkins Centre, University of Sydney, Australia, was published online in Diabetes Care.

LIMITATIONS:

Because this was an observational study, the possibility of reverse causation from prodromal disease and unaccounted confounding factors could not have been ruled out. There was a lag of a median of 5.5 years between the UK Biobank baseline, when covariate measurements were taken, and the accelerometry study. Moreover, the response rate of the UK Biobank was low.

DISCLOSURES:

The study was funded by an Australian National Health and Medical Research Council Investigator Grant and the National Heart Foundation of Australia Postdoctoral Fellowship. The authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.