The Diagnosis: Diffuse Dermal Angiomatosis

Diffuse dermal angiomatosis (DDA) is an acquired reactive vascular proliferation in the spectrum of cutaneous reactive angioendotheliomatoses. Clinically, DDA presents as violaceous reticulated plaques, often with secondary ulceration and sometimes necrosis.1-3 Diffuse dermal angiomatosis more commonly presents in patients with a history of severe peripheral vascular disease, coagulopathies, or infection, and it frequently arises on the extremities. Diffuse dermal angiomatosis also has been shown to develop on the breasts, particularly in patients with pendulous breast tissue. Vascular proliferation in DDA is hypothesized to be from ischemia and hypoxia, leading to angiogenesis.^1-3 Diffuse dermal angiomatosis is characterized histologically by the presence of a diffuse proliferation of spindled endothelial cells distributed between the collagen bundles throughout the dermis (quiz image and Figure 1). Spindle-shaped endothelial cells exhibit a vacuolated cytoplasm. On immunohistochemistry, these dermal spindle cells classically stain positive for CD31, CD34, and erythroblast transformation specific–related gene (Erg) and stain negative for both human herpesvirus 8 (HHV-8) and factor XIIIa.

Cutaneous fibrous histiocytoma, more commonly referred to as dermatofibroma, is a common benign lesion that presents clinically as a solitary firm nodule most commonly on the extremities in areas of repetitive trauma or pressure. It classically exhibits dimpling of the overlaying skin with lateral pressure on the lesion, known as the dimple sign.⁴ Histologically, dermatofibromas share similar features to DDA and demonstrate the presence of bland-appearing spindle cells within the dermis between the collagen bundles, resulting in collagen trapping. However, a distinguishing histologic feature of a dermatofibroma in comparison to DDA is the presence of epidermal hyperplasia overlying the dermatofibroma, leading to tabled rete ridges (Figure 2). Spindle cells in dermatofibromas are fibroblasts and have a distinct immunophenotype that includes factor XIIIa positivity and negative staining for CD31, CD34, and Erg.^4,5

Dermatofibrosarcoma protuberans (DFSP) is a rare malignant soft-tissue sarcoma that clinically presents as a firm, flesh-colored, dermal plaque on the trunk, proximal extremities, head, or neck.⁵ Histologically, DFSP can be distinguished from DDA by the high density of spindle cells that are arranged in a storiform pattern, extending and infiltrating the underlying subcutaneous fat in a honeycomblike pattern (Figure 3). Spindle cells in DFSP typically show expression of CD34 but are negative for CD31, Erg, and factor XIIIa.⁵

Kaposi sarcoma (KS) is an endothelial cell–driven angioproliferative neoplasm that is associated with HHV-8 infection.⁶ The clinical presentation of KS can range from isolated pink or purple papules and patches to more extensive ulcerated plaques or nodules. Histopathology exhibits proliferation of monomorphic spindled endothelial cells within the dermis staining positive for HHV-8, Erg, CD31, and CD34, in conjunction with extravasated erythrocytes arranged within slitlike vascular spaces (Figure 4). Additionally, KS classically exhibits aberrant endothelial cell proliferation and vessel formation around preexisting vessels, which is referred to as the promontory sign (Figure 4).

Angiosarcoma is a rare and highly aggressive vascular tumor arising from endothelial cells lining the blood vessels and lymphatics.^7,8 Clinically, angiosarcoma presents as ulcerated violaceous nodules or plaques on the head, neck, or trunk. Histologic evaluation of angiosarcoma reveals a complex and poorly demarcated vascular network dissecting between collagen bundles in the dermis (Figure 5). Multilayering of endothelial cells, papillary projections extending into the vessel lumina, and mitoses frequently are seen. On immunohistochemistry, endothelial cells demonstrate prominent cellular atypia and stain positive with CD31, CD34, and Erg.

The Diagnosis: Diffuse Dermal Angiomatosis

Diffuse dermal angiomatosis (DDA) is an acquired reactive vascular proliferation in the spectrum of cutaneous reactive angioendotheliomatoses. Clinically, DDA presents as violaceous reticulated plaques, often with secondary ulceration and sometimes necrosis.1-3 Diffuse dermal angiomatosis more commonly presents in patients with a history of severe peripheral vascular disease, coagulopathies, or infection, and it frequently arises on the extremities. Diffuse dermal angiomatosis also has been shown to develop on the breasts, particularly in patients with pendulous breast tissue. Vascular proliferation in DDA is hypothesized to be from ischemia and hypoxia, leading to angiogenesis.^1-3 Diffuse dermal angiomatosis is characterized histologically by the presence of a diffuse proliferation of spindled endothelial cells distributed between the collagen bundles throughout the dermis (quiz image and Figure 1). Spindle-shaped endothelial cells exhibit a vacuolated cytoplasm. On immunohistochemistry, these dermal spindle cells classically stain positive for CD31, CD34, and erythroblast transformation specific–related gene (Erg) and stain negative for both human herpesvirus 8 (HHV-8) and factor XIIIa.

Cutaneous fibrous histiocytoma, more commonly referred to as dermatofibroma, is a common benign lesion that presents clinically as a solitary firm nodule most commonly on the extremities in areas of repetitive trauma or pressure. It classically exhibits dimpling of the overlaying skin with lateral pressure on the lesion, known as the dimple sign.⁴ Histologically, dermatofibromas share similar features to DDA and demonstrate the presence of bland-appearing spindle cells within the dermis between the collagen bundles, resulting in collagen trapping. However, a distinguishing histologic feature of a dermatofibroma in comparison to DDA is the presence of epidermal hyperplasia overlying the dermatofibroma, leading to tabled rete ridges (Figure 2). Spindle cells in dermatofibromas are fibroblasts and have a distinct immunophenotype that includes factor XIIIa positivity and negative staining for CD31, CD34, and Erg.^4,5

Dermatofibrosarcoma protuberans (DFSP) is a rare malignant soft-tissue sarcoma that clinically presents as a firm, flesh-colored, dermal plaque on the trunk, proximal extremities, head, or neck.⁵ Histologically, DFSP can be distinguished from DDA by the high density of spindle cells that are arranged in a storiform pattern, extending and infiltrating the underlying subcutaneous fat in a honeycomblike pattern (Figure 3). Spindle cells in DFSP typically show expression of CD34 but are negative for CD31, Erg, and factor XIIIa.⁵

Kaposi sarcoma (KS) is an endothelial cell–driven angioproliferative neoplasm that is associated with HHV-8 infection.⁶ The clinical presentation of KS can range from isolated pink or purple papules and patches to more extensive ulcerated plaques or nodules. Histopathology exhibits proliferation of monomorphic spindled endothelial cells within the dermis staining positive for HHV-8, Erg, CD31, and CD34, in conjunction with extravasated erythrocytes arranged within slitlike vascular spaces (Figure 4). Additionally, KS classically exhibits aberrant endothelial cell proliferation and vessel formation around preexisting vessels, which is referred to as the promontory sign (Figure 4).

Angiosarcoma is a rare and highly aggressive vascular tumor arising from endothelial cells lining the blood vessels and lymphatics.^7,8 Clinically, angiosarcoma presents as ulcerated violaceous nodules or plaques on the head, neck, or trunk. Histologic evaluation of angiosarcoma reveals a complex and poorly demarcated vascular network dissecting between collagen bundles in the dermis (Figure 5). Multilayering of endothelial cells, papillary projections extending into the vessel lumina, and mitoses frequently are seen. On immunohistochemistry, endothelial cells demonstrate prominent cellular atypia and stain positive with CD31, CD34, and Erg.

The Diagnosis: Diffuse Dermal Angiomatosis

Diffuse dermal angiomatosis (DDA) is an acquired reactive vascular proliferation in the spectrum of cutaneous reactive angioendotheliomatoses. Clinically, DDA presents as violaceous reticulated plaques, often with secondary ulceration and sometimes necrosis.1-3 Diffuse dermal angiomatosis more commonly presents in patients with a history of severe peripheral vascular disease, coagulopathies, or infection, and it frequently arises on the extremities. Diffuse dermal angiomatosis also has been shown to develop on the breasts, particularly in patients with pendulous breast tissue. Vascular proliferation in DDA is hypothesized to be from ischemia and hypoxia, leading to angiogenesis.^1-3 Diffuse dermal angiomatosis is characterized histologically by the presence of a diffuse proliferation of spindled endothelial cells distributed between the collagen bundles throughout the dermis (quiz image and Figure 1). Spindle-shaped endothelial cells exhibit a vacuolated cytoplasm. On immunohistochemistry, these dermal spindle cells classically stain positive for CD31, CD34, and erythroblast transformation specific–related gene (Erg) and stain negative for both human herpesvirus 8 (HHV-8) and factor XIIIa.

Cutaneous fibrous histiocytoma, more commonly referred to as dermatofibroma, is a common benign lesion that presents clinically as a solitary firm nodule most commonly on the extremities in areas of repetitive trauma or pressure. It classically exhibits dimpling of the overlaying skin with lateral pressure on the lesion, known as the dimple sign.⁴ Histologically, dermatofibromas share similar features to DDA and demonstrate the presence of bland-appearing spindle cells within the dermis between the collagen bundles, resulting in collagen trapping. However, a distinguishing histologic feature of a dermatofibroma in comparison to DDA is the presence of epidermal hyperplasia overlying the dermatofibroma, leading to tabled rete ridges (Figure 2). Spindle cells in dermatofibromas are fibroblasts and have a distinct immunophenotype that includes factor XIIIa positivity and negative staining for CD31, CD34, and Erg.^4,5

Dermatofibrosarcoma protuberans (DFSP) is a rare malignant soft-tissue sarcoma that clinically presents as a firm, flesh-colored, dermal plaque on the trunk, proximal extremities, head, or neck.⁵ Histologically, DFSP can be distinguished from DDA by the high density of spindle cells that are arranged in a storiform pattern, extending and infiltrating the underlying subcutaneous fat in a honeycomblike pattern (Figure 3). Spindle cells in DFSP typically show expression of CD34 but are negative for CD31, Erg, and factor XIIIa.⁵

Kaposi sarcoma (KS) is an endothelial cell–driven angioproliferative neoplasm that is associated with HHV-8 infection.⁶ The clinical presentation of KS can range from isolated pink or purple papules and patches to more extensive ulcerated plaques or nodules. Histopathology exhibits proliferation of monomorphic spindled endothelial cells within the dermis staining positive for HHV-8, Erg, CD31, and CD34, in conjunction with extravasated erythrocytes arranged within slitlike vascular spaces (Figure 4). Additionally, KS classically exhibits aberrant endothelial cell proliferation and vessel formation around preexisting vessels, which is referred to as the promontory sign (Figure 4).

Angiosarcoma is a rare and highly aggressive vascular tumor arising from endothelial cells lining the blood vessels and lymphatics.^7,8 Clinically, angiosarcoma presents as ulcerated violaceous nodules or plaques on the head, neck, or trunk. Histologic evaluation of angiosarcoma reveals a complex and poorly demarcated vascular network dissecting between collagen bundles in the dermis (Figure 5). Multilayering of endothelial cells, papillary projections extending into the vessel lumina, and mitoses frequently are seen. On immunohistochemistry, endothelial cells demonstrate prominent cellular atypia and stain positive with CD31, CD34, and Erg.

Topline

Long-term mortality rates among individuals who have had a pulmonary embolism are significantly higher than rates in the general population.

Methodology

Researchers investigated long-term outcomes of patients with pulmonary embolism in a single-center registry.

They followed 896 patients for up to 14 years.

Data were from consecutive cases treated between May 2005 and December 2017.
 

Takeaway

The total follow-up time was 3,908 patient-years (median, 3.1 years).

One-year and five-year mortality rates were 19.7% (95% confidence interval, 17.2%-22.4%) and 37.1% (95% CI, 33.6%-40.5%), respectively, for patients with pulmonary embolism.

The most frequent causes of death were cancer (28.5%), pulmonary embolism (19.4%), infections (13.9%), and cardiovascular events (11.6%).

Late mortality (>30 days) was more frequent than in the general population for patients with cancer (5-year standardized mortality ratio, 2.77; 95% CI, 2.41-3.16) and for patients without cancer (1.80; 95% CI, 1.50-2.14), compared with expected rates.
 

In practice

“The mortality risk of pulmonary embolism patients remained elevated compared to the general population throughout the follow-up period,” stated Johannes Eckelt, Clinic of Cardiology and Pneumology, University Medical Center Göttingen (Germany).

Source

“Long-term Mortality in Pulmonary Embolism: Results in a Single-Center Registry,” by Mr. Eckelt and colleagues was published in Research and Practice in Thrombosis and Haemostasis.

Limitations

Owing to the single-center study design, selection bias cannot be excluded, limiting the generalizability of the study findings, the authors stated.
 

Disclosures

The authors have disclosed no relevant financial relationships.

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

Topline

Long-term mortality rates among individuals who have had a pulmonary embolism are significantly higher than rates in the general population.

Methodology

Researchers investigated long-term outcomes of patients with pulmonary embolism in a single-center registry.

They followed 896 patients for up to 14 years.

Data were from consecutive cases treated between May 2005 and December 2017.
 

Takeaway

The total follow-up time was 3,908 patient-years (median, 3.1 years).

One-year and five-year mortality rates were 19.7% (95% confidence interval, 17.2%-22.4%) and 37.1% (95% CI, 33.6%-40.5%), respectively, for patients with pulmonary embolism.

The most frequent causes of death were cancer (28.5%), pulmonary embolism (19.4%), infections (13.9%), and cardiovascular events (11.6%).

Late mortality (>30 days) was more frequent than in the general population for patients with cancer (5-year standardized mortality ratio, 2.77; 95% CI, 2.41-3.16) and for patients without cancer (1.80; 95% CI, 1.50-2.14), compared with expected rates.
 

In practice

“The mortality risk of pulmonary embolism patients remained elevated compared to the general population throughout the follow-up period,” stated Johannes Eckelt, Clinic of Cardiology and Pneumology, University Medical Center Göttingen (Germany).

Source

“Long-term Mortality in Pulmonary Embolism: Results in a Single-Center Registry,” by Mr. Eckelt and colleagues was published in Research and Practice in Thrombosis and Haemostasis.

Limitations

Owing to the single-center study design, selection bias cannot be excluded, limiting the generalizability of the study findings, the authors stated.
 

Disclosures

The authors have disclosed no relevant financial relationships.

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

Topline

Long-term mortality rates among individuals who have had a pulmonary embolism are significantly higher than rates in the general population.

Methodology

Researchers investigated long-term outcomes of patients with pulmonary embolism in a single-center registry.

They followed 896 patients for up to 14 years.

Data were from consecutive cases treated between May 2005 and December 2017.
 

Takeaway

The total follow-up time was 3,908 patient-years (median, 3.1 years).

One-year and five-year mortality rates were 19.7% (95% confidence interval, 17.2%-22.4%) and 37.1% (95% CI, 33.6%-40.5%), respectively, for patients with pulmonary embolism.

The most frequent causes of death were cancer (28.5%), pulmonary embolism (19.4%), infections (13.9%), and cardiovascular events (11.6%).

Late mortality (>30 days) was more frequent than in the general population for patients with cancer (5-year standardized mortality ratio, 2.77; 95% CI, 2.41-3.16) and for patients without cancer (1.80; 95% CI, 1.50-2.14), compared with expected rates.
 

In practice

“The mortality risk of pulmonary embolism patients remained elevated compared to the general population throughout the follow-up period,” stated Johannes Eckelt, Clinic of Cardiology and Pneumology, University Medical Center Göttingen (Germany).

Source

“Long-term Mortality in Pulmonary Embolism: Results in a Single-Center Registry,” by Mr. Eckelt and colleagues was published in Research and Practice in Thrombosis and Haemostasis.

Limitations

Owing to the single-center study design, selection bias cannot be excluded, limiting the generalizability of the study findings, the authors stated.
 

Disclosures

The authors have disclosed no relevant financial relationships.

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

Key takeaways

• Small-town physicians mostly love their practices; they are close to their patients and community, have the opportunity to practice very varied medicine, and feel like they make a difference. But they also struggle with many issues.
• Small practices are at a disadvantage when it comes to negotiating reimbursements.
• Resources such as access to specialists, equipment, and specialty meds put small-town docs in more precarious situations.

The challenges are mounting for physicians in small-town practices and rural areas, with private equity buying up many practices, the cost of overhead rising, and increased stress in attracting top talent. In the first of a two-part series, this news organization spoke to physicians in small towns around the country to identify some of the pain points squeezing small-town practices’ profits and making patient care more difficult.

Here are how physicians are working to offset the challenges and to make their small-town practices more rewarding.
 

Low reimbursements remain challenging

Jennifer Bacani McKenney, MD, owner of Fredonia Family Care, a private family medicine practice in Fredonia, Kan. (population 2,132), loves having close relationships with her patients and being an integral part of the community. However, she said that owning the only clinic in her town, which is 90 miles from Wichita, limits her power when negotiating for reimbursements.

“We don’t have bargaining power, so we often will end up getting terribly low reimbursements, especially for Medicaid,” she said. “We pay the price for not being part of a big health system.”

To bolster her ability to get reimbursement price concessions, her practice – which was initially started by her father and now includes four physicians – joined an accountable care organization in 2016.

“By joining other private practices around the state, we made some gains,” said Dr. McKenney, who was born in the hospital where she now works. “It enabled us to sit at the table with Blue Cross/Blue Shield of Kansas, for example, and have conversations that they listen to.”
 

Talent recruitment is an ongoing issue

For Ann Lima, MD, a family physician who came to Orofino, Idaho (population 3,000), 8 years ago after her residency in Ventura, Calif., practicing small-town medicine and seeing patients with a myriad of medical issues is a fulfilling challenge, but finding trained providers to join her practice remains problematic.

That’s because the physicians in her practice need to be nimble and to be able to routinely pivot from primary care to obstetrics to emergency medicine, owing to the nature of small-town practicing.

“It’s challenging in terms of finding people who are able to stay on top of all facets of hospital and acute care emergency care as well as OB and primary care,” she said. She noted that, for patients who require additional care, the nearest cities are Spokane, Wash., and Coeur D’Alene, Idaho, both approximately 3 hours away.

“It’s a challenge to find well-trained family physicians who want to do this diverse type of medicine.”

When it comes to staffing at her clinic, Dr. McKenney said it’s been more efficient to train employees from the ground up than try to find health care workers who already have significant experience.

“Right now, I have two 19-year-olds, a 21-year-old, and a 24-year-old working for me,” Dr. McKenney said of her clinic staff, which currently includes four doctors, a nurse practitioner, and 14 employees. “I hired the 19-year-old at age 17 and taught her to be a medical assistant.”

In addition to difficulty in recruiting physicians, nurses, and staff to a small-town practice, trying to find affordable housing makes it difficult to attract staffing in certain locations, said Frank Batcha, MD, a family physician in Hailey, Idaho (population 9,463), and chief of staff at St. Luke’s Wood River Regional Hospital in Ketchum, Idaho, where he has worked since the 1990s.

“We’re a resort community, so housing is unaffordable for somebody with an entry-level job,” he said. The region, a valley that includes Sun Valley, a popular ski resort with about 22,000 residents, is home to a handful of celebrities. It’s a popular destination spot and makes for a beautiful back country to call home.

“But it’s difficult to recruit physicians out of residency for this reason,” said Dr. Batcha. “We call it the scenery tax. It comes with a price.” Idaho is 49th out of 50th in physicians per capita for the entire United States.
 

Resources can be scarce

Another stressor for rural and small-town physicians is access to specialists, resources, and, in some cases, vital equipment.

“We have a general surgeon but no other specialty care,” Dr. Lima said. “This means that we can do acute appendicitis, we can take out gall bladders and do hernia repairs locally, but for significant trauma care and for patients who are very sick with ICU needs, we have to transfer them.”

Weather is also a huge factor that can affect ground ambulance or helicopter travel to a larger hospital.

“If there’s a storm, instead of a 45-minute transfer via helicopter, it’s a 3½ hour drive along mountain and river roads,” said Dr. Lima.

Ultimately, Dr. McKenney wished colleagues better understood the challenges facing rural physicians.

“When I transfer a patient from my hospital to a bigger facility, it’s because I don’t have certain medications on hand or an MRI ready to go,” she said. “It’s not that I don’t know what I’m doing.”

In addition, when she calls for a consult or sends a patient to a larger facility, it’s always because of a lack of resources.

“As rural physicians, we are really well educated and well trained,” she said “Our issue is that we’re practicing in a place with fewer things. But, when we call upon you, just know that we’ve tried everything we can first.”

Dr. McKenney lives and works happily in the town she grew up in and said no place could have given her a warmer welcome. In fact, while she was still finishing school, the townspeople campaigned to get her to come back and practice there – hard to come by that in a big city.

Small-town physicians offered five tactics for making a small-town practice work successfully:

• Develop relationships with specialists in your nearest large facility for referrals.
• Consider joining an ACO to improve work flow, diversify revenue streams, and maintain independence.
• Create a culture that’s welcoming to all incoming young professionals.
• Host medical students and residents as part of their education. “If they learn about your community, your practice, and rural healthcare early on, they will be more likely to be interested in coming back to serve that same community,” said Dr. McKenney.
• Recruit more than one physician if possible. “It’s really scary for new physicians to go out and practice on their own right out of training. Most rural communities need more than one more doctor anyway, and this gives them a built-in support system from the beginning,” said Dr. McKenney.

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

Key takeaways

• Small-town physicians mostly love their practices; they are close to their patients and community, have the opportunity to practice very varied medicine, and feel like they make a difference. But they also struggle with many issues.
• Small practices are at a disadvantage when it comes to negotiating reimbursements.
• Resources such as access to specialists, equipment, and specialty meds put small-town docs in more precarious situations.

The challenges are mounting for physicians in small-town practices and rural areas, with private equity buying up many practices, the cost of overhead rising, and increased stress in attracting top talent. In the first of a two-part series, this news organization spoke to physicians in small towns around the country to identify some of the pain points squeezing small-town practices’ profits and making patient care more difficult.

Here are how physicians are working to offset the challenges and to make their small-town practices more rewarding.
 

Low reimbursements remain challenging

Jennifer Bacani McKenney, MD, owner of Fredonia Family Care, a private family medicine practice in Fredonia, Kan. (population 2,132), loves having close relationships with her patients and being an integral part of the community. However, she said that owning the only clinic in her town, which is 90 miles from Wichita, limits her power when negotiating for reimbursements.

“We don’t have bargaining power, so we often will end up getting terribly low reimbursements, especially for Medicaid,” she said. “We pay the price for not being part of a big health system.”

To bolster her ability to get reimbursement price concessions, her practice – which was initially started by her father and now includes four physicians – joined an accountable care organization in 2016.

“By joining other private practices around the state, we made some gains,” said Dr. McKenney, who was born in the hospital where she now works. “It enabled us to sit at the table with Blue Cross/Blue Shield of Kansas, for example, and have conversations that they listen to.”
 

Talent recruitment is an ongoing issue

For Ann Lima, MD, a family physician who came to Orofino, Idaho (population 3,000), 8 years ago after her residency in Ventura, Calif., practicing small-town medicine and seeing patients with a myriad of medical issues is a fulfilling challenge, but finding trained providers to join her practice remains problematic.

That’s because the physicians in her practice need to be nimble and to be able to routinely pivot from primary care to obstetrics to emergency medicine, owing to the nature of small-town practicing.

“It’s challenging in terms of finding people who are able to stay on top of all facets of hospital and acute care emergency care as well as OB and primary care,” she said. She noted that, for patients who require additional care, the nearest cities are Spokane, Wash., and Coeur D’Alene, Idaho, both approximately 3 hours away.

“It’s a challenge to find well-trained family physicians who want to do this diverse type of medicine.”

When it comes to staffing at her clinic, Dr. McKenney said it’s been more efficient to train employees from the ground up than try to find health care workers who already have significant experience.

“Right now, I have two 19-year-olds, a 21-year-old, and a 24-year-old working for me,” Dr. McKenney said of her clinic staff, which currently includes four doctors, a nurse practitioner, and 14 employees. “I hired the 19-year-old at age 17 and taught her to be a medical assistant.”

In addition to difficulty in recruiting physicians, nurses, and staff to a small-town practice, trying to find affordable housing makes it difficult to attract staffing in certain locations, said Frank Batcha, MD, a family physician in Hailey, Idaho (population 9,463), and chief of staff at St. Luke’s Wood River Regional Hospital in Ketchum, Idaho, where he has worked since the 1990s.

“We’re a resort community, so housing is unaffordable for somebody with an entry-level job,” he said. The region, a valley that includes Sun Valley, a popular ski resort with about 22,000 residents, is home to a handful of celebrities. It’s a popular destination spot and makes for a beautiful back country to call home.

“But it’s difficult to recruit physicians out of residency for this reason,” said Dr. Batcha. “We call it the scenery tax. It comes with a price.” Idaho is 49th out of 50th in physicians per capita for the entire United States.
 

Resources can be scarce

Another stressor for rural and small-town physicians is access to specialists, resources, and, in some cases, vital equipment.

“We have a general surgeon but no other specialty care,” Dr. Lima said. “This means that we can do acute appendicitis, we can take out gall bladders and do hernia repairs locally, but for significant trauma care and for patients who are very sick with ICU needs, we have to transfer them.”

Weather is also a huge factor that can affect ground ambulance or helicopter travel to a larger hospital.

“If there’s a storm, instead of a 45-minute transfer via helicopter, it’s a 3½ hour drive along mountain and river roads,” said Dr. Lima.

Ultimately, Dr. McKenney wished colleagues better understood the challenges facing rural physicians.

“When I transfer a patient from my hospital to a bigger facility, it’s because I don’t have certain medications on hand or an MRI ready to go,” she said. “It’s not that I don’t know what I’m doing.”

In addition, when she calls for a consult or sends a patient to a larger facility, it’s always because of a lack of resources.

“As rural physicians, we are really well educated and well trained,” she said “Our issue is that we’re practicing in a place with fewer things. But, when we call upon you, just know that we’ve tried everything we can first.”

Dr. McKenney lives and works happily in the town she grew up in and said no place could have given her a warmer welcome. In fact, while she was still finishing school, the townspeople campaigned to get her to come back and practice there – hard to come by that in a big city.

Small-town physicians offered five tactics for making a small-town practice work successfully:

• Develop relationships with specialists in your nearest large facility for referrals.
• Consider joining an ACO to improve work flow, diversify revenue streams, and maintain independence.
• Create a culture that’s welcoming to all incoming young professionals.
• Host medical students and residents as part of their education. “If they learn about your community, your practice, and rural healthcare early on, they will be more likely to be interested in coming back to serve that same community,” said Dr. McKenney.
• Recruit more than one physician if possible. “It’s really scary for new physicians to go out and practice on their own right out of training. Most rural communities need more than one more doctor anyway, and this gives them a built-in support system from the beginning,” said Dr. McKenney.

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

Key takeaways

• Small-town physicians mostly love their practices; they are close to their patients and community, have the opportunity to practice very varied medicine, and feel like they make a difference. But they also struggle with many issues.
• Small practices are at a disadvantage when it comes to negotiating reimbursements.
• Resources such as access to specialists, equipment, and specialty meds put small-town docs in more precarious situations.

The challenges are mounting for physicians in small-town practices and rural areas, with private equity buying up many practices, the cost of overhead rising, and increased stress in attracting top talent. In the first of a two-part series, this news organization spoke to physicians in small towns around the country to identify some of the pain points squeezing small-town practices’ profits and making patient care more difficult.

Here are how physicians are working to offset the challenges and to make their small-town practices more rewarding.
 

Low reimbursements remain challenging

Jennifer Bacani McKenney, MD, owner of Fredonia Family Care, a private family medicine practice in Fredonia, Kan. (population 2,132), loves having close relationships with her patients and being an integral part of the community. However, she said that owning the only clinic in her town, which is 90 miles from Wichita, limits her power when negotiating for reimbursements.

“We don’t have bargaining power, so we often will end up getting terribly low reimbursements, especially for Medicaid,” she said. “We pay the price for not being part of a big health system.”

To bolster her ability to get reimbursement price concessions, her practice – which was initially started by her father and now includes four physicians – joined an accountable care organization in 2016.

“By joining other private practices around the state, we made some gains,” said Dr. McKenney, who was born in the hospital where she now works. “It enabled us to sit at the table with Blue Cross/Blue Shield of Kansas, for example, and have conversations that they listen to.”
 

Talent recruitment is an ongoing issue

For Ann Lima, MD, a family physician who came to Orofino, Idaho (population 3,000), 8 years ago after her residency in Ventura, Calif., practicing small-town medicine and seeing patients with a myriad of medical issues is a fulfilling challenge, but finding trained providers to join her practice remains problematic.

That’s because the physicians in her practice need to be nimble and to be able to routinely pivot from primary care to obstetrics to emergency medicine, owing to the nature of small-town practicing.

“It’s challenging in terms of finding people who are able to stay on top of all facets of hospital and acute care emergency care as well as OB and primary care,” she said. She noted that, for patients who require additional care, the nearest cities are Spokane, Wash., and Coeur D’Alene, Idaho, both approximately 3 hours away.

“It’s a challenge to find well-trained family physicians who want to do this diverse type of medicine.”

When it comes to staffing at her clinic, Dr. McKenney said it’s been more efficient to train employees from the ground up than try to find health care workers who already have significant experience.

“Right now, I have two 19-year-olds, a 21-year-old, and a 24-year-old working for me,” Dr. McKenney said of her clinic staff, which currently includes four doctors, a nurse practitioner, and 14 employees. “I hired the 19-year-old at age 17 and taught her to be a medical assistant.”

In addition to difficulty in recruiting physicians, nurses, and staff to a small-town practice, trying to find affordable housing makes it difficult to attract staffing in certain locations, said Frank Batcha, MD, a family physician in Hailey, Idaho (population 9,463), and chief of staff at St. Luke’s Wood River Regional Hospital in Ketchum, Idaho, where he has worked since the 1990s.

“We’re a resort community, so housing is unaffordable for somebody with an entry-level job,” he said. The region, a valley that includes Sun Valley, a popular ski resort with about 22,000 residents, is home to a handful of celebrities. It’s a popular destination spot and makes for a beautiful back country to call home.

“But it’s difficult to recruit physicians out of residency for this reason,” said Dr. Batcha. “We call it the scenery tax. It comes with a price.” Idaho is 49th out of 50th in physicians per capita for the entire United States.
 

Resources can be scarce

Another stressor for rural and small-town physicians is access to specialists, resources, and, in some cases, vital equipment.

“We have a general surgeon but no other specialty care,” Dr. Lima said. “This means that we can do acute appendicitis, we can take out gall bladders and do hernia repairs locally, but for significant trauma care and for patients who are very sick with ICU needs, we have to transfer them.”

Weather is also a huge factor that can affect ground ambulance or helicopter travel to a larger hospital.

“If there’s a storm, instead of a 45-minute transfer via helicopter, it’s a 3½ hour drive along mountain and river roads,” said Dr. Lima.

Ultimately, Dr. McKenney wished colleagues better understood the challenges facing rural physicians.

“When I transfer a patient from my hospital to a bigger facility, it’s because I don’t have certain medications on hand or an MRI ready to go,” she said. “It’s not that I don’t know what I’m doing.”

In addition, when she calls for a consult or sends a patient to a larger facility, it’s always because of a lack of resources.

“As rural physicians, we are really well educated and well trained,” she said “Our issue is that we’re practicing in a place with fewer things. But, when we call upon you, just know that we’ve tried everything we can first.”

Dr. McKenney lives and works happily in the town she grew up in and said no place could have given her a warmer welcome. In fact, while she was still finishing school, the townspeople campaigned to get her to come back and practice there – hard to come by that in a big city.

Small-town physicians offered five tactics for making a small-town practice work successfully:

• Develop relationships with specialists in your nearest large facility for referrals.
• Consider joining an ACO to improve work flow, diversify revenue streams, and maintain independence.
• Create a culture that’s welcoming to all incoming young professionals.
• Host medical students and residents as part of their education. “If they learn about your community, your practice, and rural healthcare early on, they will be more likely to be interested in coming back to serve that same community,” said Dr. McKenney.
• Recruit more than one physician if possible. “It’s really scary for new physicians to go out and practice on their own right out of training. Most rural communities need more than one more doctor anyway, and this gives them a built-in support system from the beginning,” said Dr. McKenney.

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

When the nails peel off from the proximal nail folds, the clinical term is onychomadesis and it is important to ask about recent infections or severe metabolic stressors. In children and adults, onychomadesis on multiple fingers may occur after infections and has been associated with hand-foot-mouth disease caused by common viral infections—especially strains of coxsackievirus.¹

Because shed nails show evidence of viral infection, one hypothesis for their peeling off is that the tissue of the nail matrix is infected, leading to metabolic changes. As the nail matrix returns to normal function, a new nail is made and ultimately will replace the nail that has come off. In healthy US adults, fingernails grow 3.47 mm per month on average while toenails grow 1.62 mm per month on average.²

Sometimes it’s hard to elicit a history of a very mild viral illness weeks or months after it has resolved. Asking specifically about mouth ulcers may help. If there is a history of a viral illness, no specific work-up or treatment is necessary. Patients may be reassured that nails will improve over several months without lasting effects.

In this case, the patient and her family were given reassurance and the nails returned to normal within a few months.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

When the nails peel off from the proximal nail folds, the clinical term is onychomadesis and it is important to ask about recent infections or severe metabolic stressors. In children and adults, onychomadesis on multiple fingers may occur after infections and has been associated with hand-foot-mouth disease caused by common viral infections—especially strains of coxsackievirus.¹

Because shed nails show evidence of viral infection, one hypothesis for their peeling off is that the tissue of the nail matrix is infected, leading to metabolic changes. As the nail matrix returns to normal function, a new nail is made and ultimately will replace the nail that has come off. In healthy US adults, fingernails grow 3.47 mm per month on average while toenails grow 1.62 mm per month on average.²

Sometimes it’s hard to elicit a history of a very mild viral illness weeks or months after it has resolved. Asking specifically about mouth ulcers may help. If there is a history of a viral illness, no specific work-up or treatment is necessary. Patients may be reassured that nails will improve over several months without lasting effects.

In this case, the patient and her family were given reassurance and the nails returned to normal within a few months.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

When the nails peel off from the proximal nail folds, the clinical term is onychomadesis and it is important to ask about recent infections or severe metabolic stressors. In children and adults, onychomadesis on multiple fingers may occur after infections and has been associated with hand-foot-mouth disease caused by common viral infections—especially strains of coxsackievirus.¹

Because shed nails show evidence of viral infection, one hypothesis for their peeling off is that the tissue of the nail matrix is infected, leading to metabolic changes. As the nail matrix returns to normal function, a new nail is made and ultimately will replace the nail that has come off. In healthy US adults, fingernails grow 3.47 mm per month on average while toenails grow 1.62 mm per month on average.²

Sometimes it’s hard to elicit a history of a very mild viral illness weeks or months after it has resolved. Asking specifically about mouth ulcers may help. If there is a history of a viral illness, no specific work-up or treatment is necessary. Patients may be reassured that nails will improve over several months without lasting effects.

In this case, the patient and her family were given reassurance and the nails returned to normal within a few months.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.

The percentage of time spent in the pregnancy-specific target blood glucose range of 63-140 mg/dL (3.5-7.8 mmol/L) from 16 weeks’ gestation to delivery was significantly higher in women in the AID group.

Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.

The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.

CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”

The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.

Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”  

However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
 

Two experts weigh in

Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.

“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.

USC Westside Center for Diabetes

Study rationale, method, and findings

Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.

“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.

Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin. 

As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.

Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.

They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.

A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).

Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.

The effect was consistent across clinical sites and maternal age and A1c categories.
 

Ongoing studies, off-label use

Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”

There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.

The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.

“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.

“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.

The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.

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

In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.

The percentage of time spent in the pregnancy-specific target blood glucose range of 63-140 mg/dL (3.5-7.8 mmol/L) from 16 weeks’ gestation to delivery was significantly higher in women in the AID group.

Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.

The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.

CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”

The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.

Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”  

However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
 

Two experts weigh in

Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.

“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.

USC Westside Center for Diabetes

Study rationale, method, and findings

Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.

“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.

Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin. 

As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.

Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.

They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.

A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).

Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.

The effect was consistent across clinical sites and maternal age and A1c categories.
 

Ongoing studies, off-label use

Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”

There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.

The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.

“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.

“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.

The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.

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

In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.

The percentage of time spent in the pregnancy-specific target blood glucose range of 63-140 mg/dL (3.5-7.8 mmol/L) from 16 weeks’ gestation to delivery was significantly higher in women in the AID group.

Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.

The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.

CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”

The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.

Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”  

However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
 

Two experts weigh in

Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.

“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.

USC Westside Center for Diabetes

Study rationale, method, and findings

Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.

“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.

Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin. 

As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.

Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.

They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.

A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).

Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.

The effect was consistent across clinical sites and maternal age and A1c categories.
 

Ongoing studies, off-label use

Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”

There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.

The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.

“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.

“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.

The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.

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

As we all face remarkable challenges in giving great care to our patients and maintaining great care for ourselves, I wanted to share a few thoughts I have had regarding difficult things I have seen in the past few months.

• Call centers: Yikes! I think this is an overlooked stress on the primary care system. In a cost-cutting effort, organizations have gone to call centers to handle incoming calls, and hold times can be enormous. My own organization often has wait times longer than 30 minutes. I recently called another organization and had a wait time more than 30 minutes. Patients become frustrated and will message their primary care team to intervene for scheduling issues then will arrive at their appointments frustrated by all the hassles.
• Difficult encounters: We all have visits that we know will be challenging. I think it is even more difficult when we enter the visit stressed and tired. I have always found that, when I am in a calm place, even the most difficult visits go much better. Our patients arrive at clinic visits more stressed and tired too, as they face the challenge of a stretched and overwhelmed primary care system.
• Limited availability of specialists: My organization has had a sharp increase in wait times for specialty care over the past few years. Waits for some specialties can be almost a year. A study by Reddy and colleagues found a wait time of 3 months for patients referred to gastroenterologists.¹ The lack of timely access to specialists adds to the stress and burden of primary care professionals. Managing problems deemed in need of subspecialty care as patients wait for appointments is difficult.
• Patient portals: Some practices are starting to figure this out this problem, others aren’t. Budd reviewed all the factors with the EHR that contribute to physician burnout.² Portals have added another source of patient care outside face-to-face visits that adds to physician work load; for many practices is not appropriately accounted for in effort or productivity measures. Some practices are now starting to charge for patient messaging, but this may require even more physician time in documentation and billing. Unless this directly helps the physician reduce work hours or improve compensation, then it may make the problem worse.

There is little mystery why it seems so hard ... it is! Many things have been added to the plate of primary care professionals (increased messaging, calming patients frustrated with the medical system, and increased need for bridging care while patients wait for specialty appointments). Our patients need us now more than ever to give excellent, compassionate care in a poorly functioning system. We need to be emotionally and physically healthy enough to be there for our patients. Prioritize your own needs.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Reddy K et al. Health Equity. 2018 Jun 1;2(1):103-8.

2. Budd J. J Prim Care Community Health. 2023 Apr 19.

As we all face remarkable challenges in giving great care to our patients and maintaining great care for ourselves, I wanted to share a few thoughts I have had regarding difficult things I have seen in the past few months.

• Call centers: Yikes! I think this is an overlooked stress on the primary care system. In a cost-cutting effort, organizations have gone to call centers to handle incoming calls, and hold times can be enormous. My own organization often has wait times longer than 30 minutes. I recently called another organization and had a wait time more than 30 minutes. Patients become frustrated and will message their primary care team to intervene for scheduling issues then will arrive at their appointments frustrated by all the hassles.
• Difficult encounters: We all have visits that we know will be challenging. I think it is even more difficult when we enter the visit stressed and tired. I have always found that, when I am in a calm place, even the most difficult visits go much better. Our patients arrive at clinic visits more stressed and tired too, as they face the challenge of a stretched and overwhelmed primary care system.
• Limited availability of specialists: My organization has had a sharp increase in wait times for specialty care over the past few years. Waits for some specialties can be almost a year. A study by Reddy and colleagues found a wait time of 3 months for patients referred to gastroenterologists.¹ The lack of timely access to specialists adds to the stress and burden of primary care professionals. Managing problems deemed in need of subspecialty care as patients wait for appointments is difficult.
• Patient portals: Some practices are starting to figure this out this problem, others aren’t. Budd reviewed all the factors with the EHR that contribute to physician burnout.² Portals have added another source of patient care outside face-to-face visits that adds to physician work load; for many practices is not appropriately accounted for in effort or productivity measures. Some practices are now starting to charge for patient messaging, but this may require even more physician time in documentation and billing. Unless this directly helps the physician reduce work hours or improve compensation, then it may make the problem worse.

There is little mystery why it seems so hard ... it is! Many things have been added to the plate of primary care professionals (increased messaging, calming patients frustrated with the medical system, and increased need for bridging care while patients wait for specialty appointments). Our patients need us now more than ever to give excellent, compassionate care in a poorly functioning system. We need to be emotionally and physically healthy enough to be there for our patients. Prioritize your own needs.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Reddy K et al. Health Equity. 2018 Jun 1;2(1):103-8.

2. Budd J. J Prim Care Community Health. 2023 Apr 19.

As we all face remarkable challenges in giving great care to our patients and maintaining great care for ourselves, I wanted to share a few thoughts I have had regarding difficult things I have seen in the past few months.

• Call centers: Yikes! I think this is an overlooked stress on the primary care system. In a cost-cutting effort, organizations have gone to call centers to handle incoming calls, and hold times can be enormous. My own organization often has wait times longer than 30 minutes. I recently called another organization and had a wait time more than 30 minutes. Patients become frustrated and will message their primary care team to intervene for scheduling issues then will arrive at their appointments frustrated by all the hassles.
• Difficult encounters: We all have visits that we know will be challenging. I think it is even more difficult when we enter the visit stressed and tired. I have always found that, when I am in a calm place, even the most difficult visits go much better. Our patients arrive at clinic visits more stressed and tired too, as they face the challenge of a stretched and overwhelmed primary care system.
• Limited availability of specialists: My organization has had a sharp increase in wait times for specialty care over the past few years. Waits for some specialties can be almost a year. A study by Reddy and colleagues found a wait time of 3 months for patients referred to gastroenterologists.¹ The lack of timely access to specialists adds to the stress and burden of primary care professionals. Managing problems deemed in need of subspecialty care as patients wait for appointments is difficult.
• Patient portals: Some practices are starting to figure this out this problem, others aren’t. Budd reviewed all the factors with the EHR that contribute to physician burnout.² Portals have added another source of patient care outside face-to-face visits that adds to physician work load; for many practices is not appropriately accounted for in effort or productivity measures. Some practices are now starting to charge for patient messaging, but this may require even more physician time in documentation and billing. Unless this directly helps the physician reduce work hours or improve compensation, then it may make the problem worse.

There is little mystery why it seems so hard ... it is! Many things have been added to the plate of primary care professionals (increased messaging, calming patients frustrated with the medical system, and increased need for bridging care while patients wait for specialty appointments). Our patients need us now more than ever to give excellent, compassionate care in a poorly functioning system. We need to be emotionally and physically healthy enough to be there for our patients. Prioritize your own needs.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Reddy K et al. Health Equity. 2018 Jun 1;2(1):103-8.

2. Budd J. J Prim Care Community Health. 2023 Apr 19.

AUSTIN, TEX – Treatment with ubrogepant (Ubrelvy, Abbvie) during the prodromal phase of a migraine led to a reduction in both prodromal symptoms and ensuing migraine frequency, according to results from a new randomized, crossover study. Researchers took pains to identify migraineurs who could predict an ensuing headache 75% of the time based on prodromal symptoms. Those who could make such predictions were allowed into the randomized study.

Patients are quite good at predicting ensuing headaches when encouraged to do so, according to Peter J. Goadsby, MBBS, MD, PhD, who presented the study findings at the annual meeting of the American Headache Society.

“I find it quite useful to ask patients about these [symptoms]: Have you got cognitive clouding? Do you pass more urine? Have you got mood change? Do you feel fatigue? Associated with the attack, is how I phrase it. Get them first into the idea of thinking about the symptoms, and then get them to think about when they’re occurring. Certainly with things like brain fog, many patients will tell you that it happens. If you ask them whether they’re 100% [certain] when that’s happening, they will tell you [they’re] not. This is part of taking a history and building a relationship with the patient,” Dr. Goadsby, professor of neurology at the University of California, Los Angeles, said during the Q&A after his presentation.
 

‘Significant’ finding

“This is a significant finding because what patients really want is not to develop their headache and no medication has been shown to prevent a headache during the prodrome,” said Alan M. Rapoport, MD, a board certified neurologist and headache expert, as well as clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews. Successful treatment during the prodrome treatment could eliminate the need for use of preventive medication, which might decrease the patient’s adverse effects, he said.

Session comoderator Jason J. Sico, MD, took note of the patient experience during the prodrome period. “One of many noteworthy things is the large percentage of people that reported disability during prodrome before the headache. I just find that staggering, though not surprising to many of us,” he said during the session. Dr. Sico is associate professor of neurology and internal medicine at Yale University, New Haven, Conn.

Dr. Rapoport and Dr. Sico were not involved in the study.
 

Probing the prodrome

The study included a 60-day screening period, which had to include between 3 and 16 recorded prodrome events. Headaches had to occur within 1-6 hours in at least 75% of prodrome events. Study subjects were then randomized to 100 mg ubrogepant or placebo for up to 60 days. After their first prodrome event, they entered a 7-day washout period, and then crossed over to the other group until they experienced a second prodrome event.

During the screening period, 81.5% of prodromal events identified by patients were followed by a headache within 1-6 hours of onset. Nearly 10% of the time headache occurred in 1 hour or less, 81.5% between 1 and 6 hours, and 4.5% between 6 and 24 hours after prodrome. Commonly reported prodromal symptoms included sensitivity to light (57.2%), fatigue (50.1%), neck pain (41.9%), sensitivity to sound (33.9%), and dizziness (27.8%).

The study included 247 patients in the first sequence, and 233 in the second sequence. Patient characteristics were similar in both. Ubrogepant treatment led to a greater absence of moderate- or severe-intensity headache within 24 hours of the dose (45.5% vs. 28.6% headache-free; odds ratio [OR], 2.09; P < .0001). They were also more likely to report normal functioning over 24 hours (OR, 1.66; P < .0001) and to have absence of headache within 24 hours (23.7% vs. 13.9%; OR, 1.93; P < .0001).

Between 73% and 75% of participants reported at least mild functional disability before taking medication. Two hours after a dose, ubrogepant led to a higher rate of normal functioning (37.0% vs. 26.1%; P < .001). Ubrogepant had a similar positive effect on sensitivity to light, fatigue, neck pain, sensitivity to sound, and dizziness. Adverse events were higher during ubrogepant treatment (13.2% vs. 9.1%), and included nausea, dizziness, fatigue, and somnolence, all of which were mild. “One is really scraping the barrel [to identify adverse events]. There were no serious adverse events,” said Dr. Goadsby.
 

A unique result?

One questioner asked if other medications used during the prodrome might yield similar results. Dr. Goadsby expressed doubt. “I think the evidence for other treatments is not terribly good. The triptan evidence is really poor. There is no randomized, placebo-controlled trial of a triptan explicitly in promontory symptomatology. There are randomized placebo controlled trials of triptans during the aura phase. The best one was the injected sumatriptan study, and it failed. So, as far as I can see from the randomized-controlled data, triptans don’t do this, and we don’t have good data for nonsteroidals and other therapies,” said Dr. Goadsby.

The researchers showed that you could treat a patient in advance of the headache to actually prevent the headache a significant number of times; it also reduced the prodromal events and it got patients back to normal functioning to a greater extent.

Dr. Goadsby was asked how many patients are typically able to identify prodrome periods on their own. He estimated that about one in three can do it initially. “I think if you teach people how to do this, it becomes very common. I would say four out of five people in my practice are able to talk about this, but you have to introduce the topic. They’ve had [prodrome symptoms], but they haven’t thought about it for a while. This is one of the things where headache doctors can offer real benefit in helping educate patients,” said Dr. Goadsby.

Dr. Sico did not disclose any conflicts of interest. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. He is editor-in-chief of Neurology Reviews and on the Editorial Board of CNS Drugs. Dr. Goadsby has financial ties to Amgen, Eli Lilly, Alder Biopharmaceuticals, Allergan, Autonomic Technologies Inc., Biohaven Pharmaceuticals Inc., Dr. Reddy’s Laboratories, Electrocore, eNeura, Massachusetts Medical Society, MedicoLegal work, Novartis, Oxford University Press, Teva Pharmaceuticals, Trigemina, Up-to-Date, and Wolters Kluwer. He has a patent for headache assigned to eNeura without fee.

AUSTIN, TEX – Treatment with ubrogepant (Ubrelvy, Abbvie) during the prodromal phase of a migraine led to a reduction in both prodromal symptoms and ensuing migraine frequency, according to results from a new randomized, crossover study. Researchers took pains to identify migraineurs who could predict an ensuing headache 75% of the time based on prodromal symptoms. Those who could make such predictions were allowed into the randomized study.

Patients are quite good at predicting ensuing headaches when encouraged to do so, according to Peter J. Goadsby, MBBS, MD, PhD, who presented the study findings at the annual meeting of the American Headache Society.

“I find it quite useful to ask patients about these [symptoms]: Have you got cognitive clouding? Do you pass more urine? Have you got mood change? Do you feel fatigue? Associated with the attack, is how I phrase it. Get them first into the idea of thinking about the symptoms, and then get them to think about when they’re occurring. Certainly with things like brain fog, many patients will tell you that it happens. If you ask them whether they’re 100% [certain] when that’s happening, they will tell you [they’re] not. This is part of taking a history and building a relationship with the patient,” Dr. Goadsby, professor of neurology at the University of California, Los Angeles, said during the Q&A after his presentation.
 

‘Significant’ finding

“This is a significant finding because what patients really want is not to develop their headache and no medication has been shown to prevent a headache during the prodrome,” said Alan M. Rapoport, MD, a board certified neurologist and headache expert, as well as clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews. Successful treatment during the prodrome treatment could eliminate the need for use of preventive medication, which might decrease the patient’s adverse effects, he said.

Session comoderator Jason J. Sico, MD, took note of the patient experience during the prodrome period. “One of many noteworthy things is the large percentage of people that reported disability during prodrome before the headache. I just find that staggering, though not surprising to many of us,” he said during the session. Dr. Sico is associate professor of neurology and internal medicine at Yale University, New Haven, Conn.

Dr. Rapoport and Dr. Sico were not involved in the study.
 

Probing the prodrome

The study included a 60-day screening period, which had to include between 3 and 16 recorded prodrome events. Headaches had to occur within 1-6 hours in at least 75% of prodrome events. Study subjects were then randomized to 100 mg ubrogepant or placebo for up to 60 days. After their first prodrome event, they entered a 7-day washout period, and then crossed over to the other group until they experienced a second prodrome event.

During the screening period, 81.5% of prodromal events identified by patients were followed by a headache within 1-6 hours of onset. Nearly 10% of the time headache occurred in 1 hour or less, 81.5% between 1 and 6 hours, and 4.5% between 6 and 24 hours after prodrome. Commonly reported prodromal symptoms included sensitivity to light (57.2%), fatigue (50.1%), neck pain (41.9%), sensitivity to sound (33.9%), and dizziness (27.8%).

The study included 247 patients in the first sequence, and 233 in the second sequence. Patient characteristics were similar in both. Ubrogepant treatment led to a greater absence of moderate- or severe-intensity headache within 24 hours of the dose (45.5% vs. 28.6% headache-free; odds ratio [OR], 2.09; P < .0001). They were also more likely to report normal functioning over 24 hours (OR, 1.66; P < .0001) and to have absence of headache within 24 hours (23.7% vs. 13.9%; OR, 1.93; P < .0001).

Between 73% and 75% of participants reported at least mild functional disability before taking medication. Two hours after a dose, ubrogepant led to a higher rate of normal functioning (37.0% vs. 26.1%; P < .001). Ubrogepant had a similar positive effect on sensitivity to light, fatigue, neck pain, sensitivity to sound, and dizziness. Adverse events were higher during ubrogepant treatment (13.2% vs. 9.1%), and included nausea, dizziness, fatigue, and somnolence, all of which were mild. “One is really scraping the barrel [to identify adverse events]. There were no serious adverse events,” said Dr. Goadsby.
 

A unique result?

One questioner asked if other medications used during the prodrome might yield similar results. Dr. Goadsby expressed doubt. “I think the evidence for other treatments is not terribly good. The triptan evidence is really poor. There is no randomized, placebo-controlled trial of a triptan explicitly in promontory symptomatology. There are randomized placebo controlled trials of triptans during the aura phase. The best one was the injected sumatriptan study, and it failed. So, as far as I can see from the randomized-controlled data, triptans don’t do this, and we don’t have good data for nonsteroidals and other therapies,” said Dr. Goadsby.

The researchers showed that you could treat a patient in advance of the headache to actually prevent the headache a significant number of times; it also reduced the prodromal events and it got patients back to normal functioning to a greater extent.

Dr. Goadsby was asked how many patients are typically able to identify prodrome periods on their own. He estimated that about one in three can do it initially. “I think if you teach people how to do this, it becomes very common. I would say four out of five people in my practice are able to talk about this, but you have to introduce the topic. They’ve had [prodrome symptoms], but they haven’t thought about it for a while. This is one of the things where headache doctors can offer real benefit in helping educate patients,” said Dr. Goadsby.

Dr. Sico did not disclose any conflicts of interest. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. He is editor-in-chief of Neurology Reviews and on the Editorial Board of CNS Drugs. Dr. Goadsby has financial ties to Amgen, Eli Lilly, Alder Biopharmaceuticals, Allergan, Autonomic Technologies Inc., Biohaven Pharmaceuticals Inc., Dr. Reddy’s Laboratories, Electrocore, eNeura, Massachusetts Medical Society, MedicoLegal work, Novartis, Oxford University Press, Teva Pharmaceuticals, Trigemina, Up-to-Date, and Wolters Kluwer. He has a patent for headache assigned to eNeura without fee.

AUSTIN, TEX – Treatment with ubrogepant (Ubrelvy, Abbvie) during the prodromal phase of a migraine led to a reduction in both prodromal symptoms and ensuing migraine frequency, according to results from a new randomized, crossover study. Researchers took pains to identify migraineurs who could predict an ensuing headache 75% of the time based on prodromal symptoms. Those who could make such predictions were allowed into the randomized study.

Patients are quite good at predicting ensuing headaches when encouraged to do so, according to Peter J. Goadsby, MBBS, MD, PhD, who presented the study findings at the annual meeting of the American Headache Society.

“I find it quite useful to ask patients about these [symptoms]: Have you got cognitive clouding? Do you pass more urine? Have you got mood change? Do you feel fatigue? Associated with the attack, is how I phrase it. Get them first into the idea of thinking about the symptoms, and then get them to think about when they’re occurring. Certainly with things like brain fog, many patients will tell you that it happens. If you ask them whether they’re 100% [certain] when that’s happening, they will tell you [they’re] not. This is part of taking a history and building a relationship with the patient,” Dr. Goadsby, professor of neurology at the University of California, Los Angeles, said during the Q&A after his presentation.
 

‘Significant’ finding

“This is a significant finding because what patients really want is not to develop their headache and no medication has been shown to prevent a headache during the prodrome,” said Alan M. Rapoport, MD, a board certified neurologist and headache expert, as well as clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews. Successful treatment during the prodrome treatment could eliminate the need for use of preventive medication, which might decrease the patient’s adverse effects, he said.

Session comoderator Jason J. Sico, MD, took note of the patient experience during the prodrome period. “One of many noteworthy things is the large percentage of people that reported disability during prodrome before the headache. I just find that staggering, though not surprising to many of us,” he said during the session. Dr. Sico is associate professor of neurology and internal medicine at Yale University, New Haven, Conn.

Dr. Rapoport and Dr. Sico were not involved in the study.
 

Probing the prodrome

The study included a 60-day screening period, which had to include between 3 and 16 recorded prodrome events. Headaches had to occur within 1-6 hours in at least 75% of prodrome events. Study subjects were then randomized to 100 mg ubrogepant or placebo for up to 60 days. After their first prodrome event, they entered a 7-day washout period, and then crossed over to the other group until they experienced a second prodrome event.

During the screening period, 81.5% of prodromal events identified by patients were followed by a headache within 1-6 hours of onset. Nearly 10% of the time headache occurred in 1 hour or less, 81.5% between 1 and 6 hours, and 4.5% between 6 and 24 hours after prodrome. Commonly reported prodromal symptoms included sensitivity to light (57.2%), fatigue (50.1%), neck pain (41.9%), sensitivity to sound (33.9%), and dizziness (27.8%).

The study included 247 patients in the first sequence, and 233 in the second sequence. Patient characteristics were similar in both. Ubrogepant treatment led to a greater absence of moderate- or severe-intensity headache within 24 hours of the dose (45.5% vs. 28.6% headache-free; odds ratio [OR], 2.09; P < .0001). They were also more likely to report normal functioning over 24 hours (OR, 1.66; P < .0001) and to have absence of headache within 24 hours (23.7% vs. 13.9%; OR, 1.93; P < .0001).

Between 73% and 75% of participants reported at least mild functional disability before taking medication. Two hours after a dose, ubrogepant led to a higher rate of normal functioning (37.0% vs. 26.1%; P < .001). Ubrogepant had a similar positive effect on sensitivity to light, fatigue, neck pain, sensitivity to sound, and dizziness. Adverse events were higher during ubrogepant treatment (13.2% vs. 9.1%), and included nausea, dizziness, fatigue, and somnolence, all of which were mild. “One is really scraping the barrel [to identify adverse events]. There were no serious adverse events,” said Dr. Goadsby.
 

A unique result?

One questioner asked if other medications used during the prodrome might yield similar results. Dr. Goadsby expressed doubt. “I think the evidence for other treatments is not terribly good. The triptan evidence is really poor. There is no randomized, placebo-controlled trial of a triptan explicitly in promontory symptomatology. There are randomized placebo controlled trials of triptans during the aura phase. The best one was the injected sumatriptan study, and it failed. So, as far as I can see from the randomized-controlled data, triptans don’t do this, and we don’t have good data for nonsteroidals and other therapies,” said Dr. Goadsby.

The researchers showed that you could treat a patient in advance of the headache to actually prevent the headache a significant number of times; it also reduced the prodromal events and it got patients back to normal functioning to a greater extent.

Dr. Goadsby was asked how many patients are typically able to identify prodrome periods on their own. He estimated that about one in three can do it initially. “I think if you teach people how to do this, it becomes very common. I would say four out of five people in my practice are able to talk about this, but you have to introduce the topic. They’ve had [prodrome symptoms], but they haven’t thought about it for a while. This is one of the things where headache doctors can offer real benefit in helping educate patients,” said Dr. Goadsby.

Dr. Sico did not disclose any conflicts of interest. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. He is editor-in-chief of Neurology Reviews and on the Editorial Board of CNS Drugs. Dr. Goadsby has financial ties to Amgen, Eli Lilly, Alder Biopharmaceuticals, Allergan, Autonomic Technologies Inc., Biohaven Pharmaceuticals Inc., Dr. Reddy’s Laboratories, Electrocore, eNeura, Massachusetts Medical Society, MedicoLegal work, Novartis, Oxford University Press, Teva Pharmaceuticals, Trigemina, Up-to-Date, and Wolters Kluwer. He has a patent for headache assigned to eNeura without fee.

Family physicians are the only providers of care for most patients with several chronic diseases, according to new research.

A population-based retrospective cohort study examined data from nearly 1 million patients with common chronic conditions in Alberta, Canada. Family doctors were the sole providers of care for 85.7% of patients with hypertension and 70.9% of those with diabetes.

The study is part of efforts to encourage more research “by primary care, for primary care,” study author Jessica Kirkwood, MD, family physician and assistant professor of family medicine at the University of Alberta, Edmonton, said in an interview. The prevalence of primary care involvement demonstrates the importance of involving family physicians in creating guidelines for management and developing clinical trials, Dr. Kirkwood said.

The study was published in Canadian Family Physician.
 

Who provides care?

The study focused on care provided from 2013 to 2017 for seven chronic conditions. The information collected consisted of data from administrative health databases, which track medical services provided by Alberta’s government-funded universal health care system.

Most patients’ care was managed by family physicians alone in four of the conditions studied: hypertension (85.7%), diabetes (70.9%), chronic obstructive pulmonary disease (59.8%), and asthma (65.5%).

Specialists were more involved in the remaining three diseases. They provided the sole management in 49.1% of patients with ischemic heart disease, 42.2% of those with chronic kidney disease, and 35.6% of those with heart failure. For these conditions, family physicians remained involved in the care for a large proportion of patients. Specialist involvement may be more common with these diseases because they sometimes involve interventions that only specialists offer, like angiography and dialysis, said Dr. Kirkwood.

The study also found that nurse practitioners were involved in care for very few patients (less than 1%), in accordance with the small number of nurse practitioners working in primary care settings.

Dr. Kirkwood acknowledged that the data come with certain limitations because they were not intended for research purposes. One limitation is that some conditions may not have been recorded because of “shadow billing.” Salaried physicians and practitioners do not have an incentive to include all diagnostic codes in their records. By comparison, clinicians operating under a fee-for-service model would be likely to indicate all diagnoses.
 

Developing guidelines

Despite the widespread management of chronic conditions by family physicians, these doctors represented about 17% of the experts who contribute to guidelines and recommendations, according to a 2015 study that the investigators cited.

“Frankly, that’s concerning,” said Dr. Kirkwood, regarding the disconnect between the people creating the recommendations and the people using them. The guidelines should include the perspective of clinicians who regularly work with patients, she said. Providing that perspective would also make the design of clinical trials on interventions more informative, the researchers concluded.

“I know as a family doctor myself that some recommendations are completely overwhelming,” especially given the range of issues that primary care clinicians see, said Dr. Kirkwood. Including primary care representatives who are familiar with the demands of the position “hopefully will make the recommendations much more applicable to the people that they will affect,” she said.

Dr. Kirkwood also noted the need for sufficient support for family doctors to contribute to guideline creation and research, especially for doctors in rural communities who are not already affiliated with a university.

The involvement of primary care providers in research settings is a primary goal of Patients, Experience, Evidence and Research (PEER), a primary care-led group that collaborates with the College of Family Physicians of Canada. The current investigators are members of PEER.
 

Additional conditions

Commenting on the study, Martin Fortin, MD, clinical teaching professor at the University of Sherbrooke, Quebec, said, “This is a good opportunity to advocate for more studies to be done in the primary care context, where the majority of chronic disease management is done.”

However, Dr. Fortin wishes that more diagnoses had been included in the study, such as mental health and musculoskeletal conditions like back pain and osteoarthritis. These conditions are also commonly seen by primary care clinicians, according to Dr. Fortin.

Because the number of conditions studied is limited, the data may not reflect the true prevalence of multimorbidity, Dr. Fortin added.

Primary care doctors provide a broad perspective on the overall health of patients, compared with specialists who focus on particular conditions. Similarly, during drug trials, pharmaceutical companies aim to reduce complicating factors, even though the medications are prescribed for conditions where multimorbidity is common. “Medication should be tested in the real environment,” said Dr. Fortin.

Ultimately, he added, the study cannot address the complexity of the patients, but it nevertheless sheds light on who is providing care and where the research on these conditions should be done.

The study was conducted without outside funding. Dr. Kirkwood and Dr. Fortin reported no relevant financial relationships.

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

Family physicians are the only providers of care for most patients with several chronic diseases, according to new research.

A population-based retrospective cohort study examined data from nearly 1 million patients with common chronic conditions in Alberta, Canada. Family doctors were the sole providers of care for 85.7% of patients with hypertension and 70.9% of those with diabetes.

The study is part of efforts to encourage more research “by primary care, for primary care,” study author Jessica Kirkwood, MD, family physician and assistant professor of family medicine at the University of Alberta, Edmonton, said in an interview. The prevalence of primary care involvement demonstrates the importance of involving family physicians in creating guidelines for management and developing clinical trials, Dr. Kirkwood said.

The study was published in Canadian Family Physician.
 

Who provides care?

The study focused on care provided from 2013 to 2017 for seven chronic conditions. The information collected consisted of data from administrative health databases, which track medical services provided by Alberta’s government-funded universal health care system.

Most patients’ care was managed by family physicians alone in four of the conditions studied: hypertension (85.7%), diabetes (70.9%), chronic obstructive pulmonary disease (59.8%), and asthma (65.5%).

Specialists were more involved in the remaining three diseases. They provided the sole management in 49.1% of patients with ischemic heart disease, 42.2% of those with chronic kidney disease, and 35.6% of those with heart failure. For these conditions, family physicians remained involved in the care for a large proportion of patients. Specialist involvement may be more common with these diseases because they sometimes involve interventions that only specialists offer, like angiography and dialysis, said Dr. Kirkwood.

The study also found that nurse practitioners were involved in care for very few patients (less than 1%), in accordance with the small number of nurse practitioners working in primary care settings.

Dr. Kirkwood acknowledged that the data come with certain limitations because they were not intended for research purposes. One limitation is that some conditions may not have been recorded because of “shadow billing.” Salaried physicians and practitioners do not have an incentive to include all diagnostic codes in their records. By comparison, clinicians operating under a fee-for-service model would be likely to indicate all diagnoses.
 

Developing guidelines

Despite the widespread management of chronic conditions by family physicians, these doctors represented about 17% of the experts who contribute to guidelines and recommendations, according to a 2015 study that the investigators cited.

“Frankly, that’s concerning,” said Dr. Kirkwood, regarding the disconnect between the people creating the recommendations and the people using them. The guidelines should include the perspective of clinicians who regularly work with patients, she said. Providing that perspective would also make the design of clinical trials on interventions more informative, the researchers concluded.

“I know as a family doctor myself that some recommendations are completely overwhelming,” especially given the range of issues that primary care clinicians see, said Dr. Kirkwood. Including primary care representatives who are familiar with the demands of the position “hopefully will make the recommendations much more applicable to the people that they will affect,” she said.

Dr. Kirkwood also noted the need for sufficient support for family doctors to contribute to guideline creation and research, especially for doctors in rural communities who are not already affiliated with a university.

The involvement of primary care providers in research settings is a primary goal of Patients, Experience, Evidence and Research (PEER), a primary care-led group that collaborates with the College of Family Physicians of Canada. The current investigators are members of PEER.
 

Additional conditions

Commenting on the study, Martin Fortin, MD, clinical teaching professor at the University of Sherbrooke, Quebec, said, “This is a good opportunity to advocate for more studies to be done in the primary care context, where the majority of chronic disease management is done.”

However, Dr. Fortin wishes that more diagnoses had been included in the study, such as mental health and musculoskeletal conditions like back pain and osteoarthritis. These conditions are also commonly seen by primary care clinicians, according to Dr. Fortin.

Because the number of conditions studied is limited, the data may not reflect the true prevalence of multimorbidity, Dr. Fortin added.

Primary care doctors provide a broad perspective on the overall health of patients, compared with specialists who focus on particular conditions. Similarly, during drug trials, pharmaceutical companies aim to reduce complicating factors, even though the medications are prescribed for conditions where multimorbidity is common. “Medication should be tested in the real environment,” said Dr. Fortin.

Ultimately, he added, the study cannot address the complexity of the patients, but it nevertheless sheds light on who is providing care and where the research on these conditions should be done.

The study was conducted without outside funding. Dr. Kirkwood and Dr. Fortin reported no relevant financial relationships.

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

Family physicians are the only providers of care for most patients with several chronic diseases, according to new research.

A population-based retrospective cohort study examined data from nearly 1 million patients with common chronic conditions in Alberta, Canada. Family doctors were the sole providers of care for 85.7% of patients with hypertension and 70.9% of those with diabetes.

The study is part of efforts to encourage more research “by primary care, for primary care,” study author Jessica Kirkwood, MD, family physician and assistant professor of family medicine at the University of Alberta, Edmonton, said in an interview. The prevalence of primary care involvement demonstrates the importance of involving family physicians in creating guidelines for management and developing clinical trials, Dr. Kirkwood said.

The study was published in Canadian Family Physician.
 

Who provides care?

The study focused on care provided from 2013 to 2017 for seven chronic conditions. The information collected consisted of data from administrative health databases, which track medical services provided by Alberta’s government-funded universal health care system.

Most patients’ care was managed by family physicians alone in four of the conditions studied: hypertension (85.7%), diabetes (70.9%), chronic obstructive pulmonary disease (59.8%), and asthma (65.5%).

Specialists were more involved in the remaining three diseases. They provided the sole management in 49.1% of patients with ischemic heart disease, 42.2% of those with chronic kidney disease, and 35.6% of those with heart failure. For these conditions, family physicians remained involved in the care for a large proportion of patients. Specialist involvement may be more common with these diseases because they sometimes involve interventions that only specialists offer, like angiography and dialysis, said Dr. Kirkwood.

The study also found that nurse practitioners were involved in care for very few patients (less than 1%), in accordance with the small number of nurse practitioners working in primary care settings.

Dr. Kirkwood acknowledged that the data come with certain limitations because they were not intended for research purposes. One limitation is that some conditions may not have been recorded because of “shadow billing.” Salaried physicians and practitioners do not have an incentive to include all diagnostic codes in their records. By comparison, clinicians operating under a fee-for-service model would be likely to indicate all diagnoses.
 

Developing guidelines

Despite the widespread management of chronic conditions by family physicians, these doctors represented about 17% of the experts who contribute to guidelines and recommendations, according to a 2015 study that the investigators cited.

“Frankly, that’s concerning,” said Dr. Kirkwood, regarding the disconnect between the people creating the recommendations and the people using them. The guidelines should include the perspective of clinicians who regularly work with patients, she said. Providing that perspective would also make the design of clinical trials on interventions more informative, the researchers concluded.

“I know as a family doctor myself that some recommendations are completely overwhelming,” especially given the range of issues that primary care clinicians see, said Dr. Kirkwood. Including primary care representatives who are familiar with the demands of the position “hopefully will make the recommendations much more applicable to the people that they will affect,” she said.

Dr. Kirkwood also noted the need for sufficient support for family doctors to contribute to guideline creation and research, especially for doctors in rural communities who are not already affiliated with a university.

The involvement of primary care providers in research settings is a primary goal of Patients, Experience, Evidence and Research (PEER), a primary care-led group that collaborates with the College of Family Physicians of Canada. The current investigators are members of PEER.
 

Additional conditions

Commenting on the study, Martin Fortin, MD, clinical teaching professor at the University of Sherbrooke, Quebec, said, “This is a good opportunity to advocate for more studies to be done in the primary care context, where the majority of chronic disease management is done.”

However, Dr. Fortin wishes that more diagnoses had been included in the study, such as mental health and musculoskeletal conditions like back pain and osteoarthritis. These conditions are also commonly seen by primary care clinicians, according to Dr. Fortin.

Because the number of conditions studied is limited, the data may not reflect the true prevalence of multimorbidity, Dr. Fortin added.

Primary care doctors provide a broad perspective on the overall health of patients, compared with specialists who focus on particular conditions. Similarly, during drug trials, pharmaceutical companies aim to reduce complicating factors, even though the medications are prescribed for conditions where multimorbidity is common. “Medication should be tested in the real environment,” said Dr. Fortin.

Ultimately, he added, the study cannot address the complexity of the patients, but it nevertheless sheds light on who is providing care and where the research on these conditions should be done.

The study was conducted without outside funding. Dr. Kirkwood and Dr. Fortin reported no relevant financial relationships.

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

Adults aged 60 or older who took high monthly doses of vitamin D for 5 years failed to show a significant drop in risk for cardiovascular (CV) events in general but may have benefited for other CV outcomes in an analysis from a large prospective randomized trial.

Risk reductions on vitamin D in the mixed primary- and secondary-prevention population were slight in absolute terms but reached a significant 19% in the case of myocardial infarction (MI).

Over 5 years, 6.6% of those in placebo group experienced major CV events, the primary endpoint, compared with 6% in the vitamin D group. The difference, which corresponded to 5.8 fewer events per 1,000 participants, was short of significance in adjusted analysis.

Benefits minimal

The 21,302 patients in the D-Health trial, conducted in Australia from 2014 to 2020, were randomly assigned double-blind to receive either placebo or vitamin D3 supplements for a planned 5 years. They were instructed to take one placebo or vitamin D capsule per month, each active capsule containing 60,000 IU of the vitamin.

People with self-reported hypercalcemia, hyperparathyroidism, kidney stones, osteomalacia, or sarcoidosis, and those taking greater than 500 IU/day vitamin D supplements were excluded from enrollment. Participants ranged in age from 60 to 84 at randomization and 46% were women.

With 80% of the 10,658 participants assigned to vitamin D and 78% of the 10,644 control subjects completing the 5-year intervention, 6% and 6.6%, respectively, met the primary endpoint of a major CV event, defined as MI, stroke, or coronary revascularization.

The hazard ratio for a vitamin-D effect on the primary endpoint was 0.91 (95% confidence interval, 0.81-1.01). The number needed to treat to avoid one major CV event was 172.

The HR for MI was 0.81 (95% CI, 0.67-0.98), for coronary intervention was 0.89 (0.78-1.01), and for stroke was 0.99 (0.80-1.23).

Adverse event rates were similar at about 16% in both groups and included hypercalcemia, kidney stones, gastrointestinal issues, and skin rash.

Vitamin D at moderate dosages has low toxicity, Dr. Neale said, “so I think it would be reasonable for clinicians to consider supplementing elderly people who do not have contraindications, particularly those who have underlying risk factors for CV disease,” Dr. Neale said. But patients should be told that the evidence for such a recommendation is not strong, so they can make an informed decision, she added.

Also, in general “we would be cautious about extrapolating to formulations other than those used in the study,” Dr. Neale said. “However, in this case, I think it would be reasonable to extrapolate to the use of 2,000 IU per day taken orally, provided that the same adherence can be maintained for a lengthy period.”
 

Chance findings?

Based on the current study and in light of prior research, “it is premature to recommend vitamin D supplementation for cardiovascular disease prevention specifically,” Nour Makarem, PhD, of the Mailman School of Public Health, Columbia University, New York, said in an interview.

“Prior clinical trials did not show an association between vitamin D supplementation and cardiovascular events,” observed Dr. Makarem, who is not affiliated with the current study. Also, she agreed, it looked at “multiple outcomes, which increases the likelihood that findings may be due to chance.”

She added that the study’s authors observed a possible vitamin-D protective effect “among people who were vitamin D sufficient at baseline but not among those who were insufficient. It is important to interpret this finding with caution because they used predicted, not measured, vitamin D status for these analyses.”

There’s a need for studies in other populations, including younger persons and “particularly populations with higher rates of vitamin D deficiency,” Dr. Makarem observed. Also, further research should aim to “understand the interactions between vitamin D supplementation and cardiovascular medications, including statins.” 

The D-Health Trial is funded by National Health and Medical Research Council project grants. Dr. Neale was supported by fellowships from the NHMRC. Neither she nor Dr. Makarem reported any relevant financial relationships.

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

Adults aged 60 or older who took high monthly doses of vitamin D for 5 years failed to show a significant drop in risk for cardiovascular (CV) events in general but may have benefited for other CV outcomes in an analysis from a large prospective randomized trial.

Risk reductions on vitamin D in the mixed primary- and secondary-prevention population were slight in absolute terms but reached a significant 19% in the case of myocardial infarction (MI).

Over 5 years, 6.6% of those in placebo group experienced major CV events, the primary endpoint, compared with 6% in the vitamin D group. The difference, which corresponded to 5.8 fewer events per 1,000 participants, was short of significance in adjusted analysis.

Benefits minimal

The 21,302 patients in the D-Health trial, conducted in Australia from 2014 to 2020, were randomly assigned double-blind to receive either placebo or vitamin D3 supplements for a planned 5 years. They were instructed to take one placebo or vitamin D capsule per month, each active capsule containing 60,000 IU of the vitamin.

People with self-reported hypercalcemia, hyperparathyroidism, kidney stones, osteomalacia, or sarcoidosis, and those taking greater than 500 IU/day vitamin D supplements were excluded from enrollment. Participants ranged in age from 60 to 84 at randomization and 46% were women.

With 80% of the 10,658 participants assigned to vitamin D and 78% of the 10,644 control subjects completing the 5-year intervention, 6% and 6.6%, respectively, met the primary endpoint of a major CV event, defined as MI, stroke, or coronary revascularization.

The hazard ratio for a vitamin-D effect on the primary endpoint was 0.91 (95% confidence interval, 0.81-1.01). The number needed to treat to avoid one major CV event was 172.

The HR for MI was 0.81 (95% CI, 0.67-0.98), for coronary intervention was 0.89 (0.78-1.01), and for stroke was 0.99 (0.80-1.23).

Adverse event rates were similar at about 16% in both groups and included hypercalcemia, kidney stones, gastrointestinal issues, and skin rash.

Vitamin D at moderate dosages has low toxicity, Dr. Neale said, “so I think it would be reasonable for clinicians to consider supplementing elderly people who do not have contraindications, particularly those who have underlying risk factors for CV disease,” Dr. Neale said. But patients should be told that the evidence for such a recommendation is not strong, so they can make an informed decision, she added.

Also, in general “we would be cautious about extrapolating to formulations other than those used in the study,” Dr. Neale said. “However, in this case, I think it would be reasonable to extrapolate to the use of 2,000 IU per day taken orally, provided that the same adherence can be maintained for a lengthy period.”
 

Chance findings?

Based on the current study and in light of prior research, “it is premature to recommend vitamin D supplementation for cardiovascular disease prevention specifically,” Nour Makarem, PhD, of the Mailman School of Public Health, Columbia University, New York, said in an interview.

“Prior clinical trials did not show an association between vitamin D supplementation and cardiovascular events,” observed Dr. Makarem, who is not affiliated with the current study. Also, she agreed, it looked at “multiple outcomes, which increases the likelihood that findings may be due to chance.”

She added that the study’s authors observed a possible vitamin-D protective effect “among people who were vitamin D sufficient at baseline but not among those who were insufficient. It is important to interpret this finding with caution because they used predicted, not measured, vitamin D status for these analyses.”

There’s a need for studies in other populations, including younger persons and “particularly populations with higher rates of vitamin D deficiency,” Dr. Makarem observed. Also, further research should aim to “understand the interactions between vitamin D supplementation and cardiovascular medications, including statins.” 

The D-Health Trial is funded by National Health and Medical Research Council project grants. Dr. Neale was supported by fellowships from the NHMRC. Neither she nor Dr. Makarem reported any relevant financial relationships.

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

Adults aged 60 or older who took high monthly doses of vitamin D for 5 years failed to show a significant drop in risk for cardiovascular (CV) events in general but may have benefited for other CV outcomes in an analysis from a large prospective randomized trial.

Risk reductions on vitamin D in the mixed primary- and secondary-prevention population were slight in absolute terms but reached a significant 19% in the case of myocardial infarction (MI).

Over 5 years, 6.6% of those in placebo group experienced major CV events, the primary endpoint, compared with 6% in the vitamin D group. The difference, which corresponded to 5.8 fewer events per 1,000 participants, was short of significance in adjusted analysis.

Benefits minimal

The 21,302 patients in the D-Health trial, conducted in Australia from 2014 to 2020, were randomly assigned double-blind to receive either placebo or vitamin D3 supplements for a planned 5 years. They were instructed to take one placebo or vitamin D capsule per month, each active capsule containing 60,000 IU of the vitamin.

People with self-reported hypercalcemia, hyperparathyroidism, kidney stones, osteomalacia, or sarcoidosis, and those taking greater than 500 IU/day vitamin D supplements were excluded from enrollment. Participants ranged in age from 60 to 84 at randomization and 46% were women.

With 80% of the 10,658 participants assigned to vitamin D and 78% of the 10,644 control subjects completing the 5-year intervention, 6% and 6.6%, respectively, met the primary endpoint of a major CV event, defined as MI, stroke, or coronary revascularization.

The hazard ratio for a vitamin-D effect on the primary endpoint was 0.91 (95% confidence interval, 0.81-1.01). The number needed to treat to avoid one major CV event was 172.

The HR for MI was 0.81 (95% CI, 0.67-0.98), for coronary intervention was 0.89 (0.78-1.01), and for stroke was 0.99 (0.80-1.23).

Adverse event rates were similar at about 16% in both groups and included hypercalcemia, kidney stones, gastrointestinal issues, and skin rash.

Vitamin D at moderate dosages has low toxicity, Dr. Neale said, “so I think it would be reasonable for clinicians to consider supplementing elderly people who do not have contraindications, particularly those who have underlying risk factors for CV disease,” Dr. Neale said. But patients should be told that the evidence for such a recommendation is not strong, so they can make an informed decision, she added.

Also, in general “we would be cautious about extrapolating to formulations other than those used in the study,” Dr. Neale said. “However, in this case, I think it would be reasonable to extrapolate to the use of 2,000 IU per day taken orally, provided that the same adherence can be maintained for a lengthy period.”
 

Chance findings?

Based on the current study and in light of prior research, “it is premature to recommend vitamin D supplementation for cardiovascular disease prevention specifically,” Nour Makarem, PhD, of the Mailman School of Public Health, Columbia University, New York, said in an interview.

“Prior clinical trials did not show an association between vitamin D supplementation and cardiovascular events,” observed Dr. Makarem, who is not affiliated with the current study. Also, she agreed, it looked at “multiple outcomes, which increases the likelihood that findings may be due to chance.”

She added that the study’s authors observed a possible vitamin-D protective effect “among people who were vitamin D sufficient at baseline but not among those who were insufficient. It is important to interpret this finding with caution because they used predicted, not measured, vitamin D status for these analyses.”

There’s a need for studies in other populations, including younger persons and “particularly populations with higher rates of vitamin D deficiency,” Dr. Makarem observed. Also, further research should aim to “understand the interactions between vitamin D supplementation and cardiovascular medications, including statins.” 

The D-Health Trial is funded by National Health and Medical Research Council project grants. Dr. Neale was supported by fellowships from the NHMRC. Neither she nor Dr. Makarem reported any relevant financial relationships.

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

SAN DIEGO – Survodutide, a dual glucagonlike peptide–1 (GLP-1) and glucagon receptor agonist, led to “striking” weight loss in a phase 2 dosing trial in people with overweight/obesity but without type 2 diabetes.

Close to 40% of people who were taking the highest dose lost 20% or more of their starting weight at 46 weeks, Carel Le Roux, MBChB, PhD, reported at the annual scientific sessions of the American Diabetes Association.

Boehringer Ingelheim and Zealand Pharma are developing survodutide (formerly BI 456906) to treat obesity and nonalcoholic fatty liver disease (NAFLD), according to a company press release.

Glucagon receptor agonism increases energy expenditure, and GLP-1 receptor agonism inhibits appetite, both part of the mechanism of action, Dr. Le Roux, a professor at University College in Dublin, explained.

The trial showed a “striking” and clear dose-response in terms of weight loss, with no new unexpected safety signals, he reported.

Invited to comment, session moderator Elisabetta Patorno, MD, DrPH, noted that “Obesity is one of the main risk factors for [type 2] diabetes.”

“It’s very stimulating to see this new medication class make such a big impact on weight loss in such a short amount of time,” Dr. Patorno, associate professor of medicine at Harvard Medical School, Boston, said in an interview. However, whether the weight loss can be maintained over time remains to be determined in further research, she said.

Head-to-head weight-loss studies of the dual agonist survodutide versus the mono GLP-1 agonist semaglutide (Ozempic, Wegovy, Novo Nordisk) have not been conducted, Dr. Le Roux said during a press briefing.

“What we don’t know is if somebody doesn’t respond to [weight-loss drug] product A, will they respond to product B?” he said. Because survodutide acts on two types of receptors, “you could argue that you would not only increase the absolute amount of weight but you might also increase the number of patients who would respond, but that’s theoretical at the moment,” he explained.
 

Close to 400 patients, five doses, 46-week endpoint

The researchers randomized 387 adults aged 18-75 who had a body mass index (BMI) ≥ 27 kg/m² (overweight or obesity) without type 2 diabetes at sites in North America, Europe, Australia/New Zealand, and Asia.

On average, patients were 49 years old with a body weight of 106 kg (234 lb) and a BMI of 37 kg/m², and 68% were women.

They were randomized to receive a planned weekly subcutaneous maintenance survodutide dose of 0.6 mg (76 patients), 2.4 mg (78 patients), 3.6 mg (76 patients), or 4.8 mg (76 patients), or placebo (77 patients).

The dose was escalated rapidly (monthly) during a 20-week dose-escalation phase, followed by a 26-week maintenance phase.

Patients who did not reach the planned dose remained on a lower dose during the maintenance phase.

In terms of actual treatment, during the maintenance phase, 76 patients were taking placebo, 88 patients were taking 0.6 mg survodutide, 92 were taking 2.4 mg survodutide, 71 were taking 3.6 mg survodutide, and 54 were taking 4.8 mg survodutide, all given as weekly subcutaneous injections.

Primary outcome was the percentage change in body weight from baseline to week 46.

Secondary outcomes included the percentage of patients who reached a body weight reduction of ≥ 5%, ≥ 10%, and ≥ 15% from baseline to week 46.

Mean weight loss at 46 weeks in the planned treatment analysis (where some patients in each group were taking a lower than planned dose during maintenance) was 6.2% in the 0.6-mg survodutide group, 12.5% in the 2.4-mg group, 13.2% in the 3.6-mg group, 14.9% in the 4.8-mg group, and 2.8% in the placebo group.

Among participants who did reach and stay on their assigned dose during the maintenance phase, average weight loss was 6.8% in the 0.6-mg survodutide group,13.6% with 2.4 mg survodutide,16.7% with 3.6 mg survodutide, 18.6% with 4.8 mg survodutide, and 2.0% with placebo.

That is, patients reaching and staying on a weekly subcutaneous dose of 4.8 mg survodutide lost 18.6% of their body weight at 46 weeks, Dr. Le Roux emphasized.

In terms of secondary outcomes, in the group of patients with a planned weekly dose of 4.8 mg survodutide, 83%, 69%, and 55% attained weight loss of ≥ 5%, ≥ 10%, and ≥ 15% of their initial weight, respectively, at 46 weeks.

In the group of patients with an actual weekly dose of 4.8 mg survodutide, 98%, 82%, and 67% attained weight loss of ≥ 5%, ≥ 10%, and ≥ 15% of their initial weight, respectively, at 46 weeks.

Moreover, 33% of patients in the group with a planned weekly dose of 4.8 mg survodutide and 38% of patients with an actual weekly dose of 4.8 mg survodutide lost ≥ 20% of their baseline body weight by week 46.

Adverse events occurred in 91% of patients in the survodutide groups and 75% in the placebo group. The most common side effects were nausea, vomiting, diarrhea, and constipation, which were mostly mild to moderate and mainly occurred during dose escalation. These effects may potentially be mitigated by more gradual dose escalation, Dr. Le Roux said.

There were no unexpected safety or tolerability concerns, and no serious drug-related adverse events.

These “encouraging data” support further study of survodutide for weight loss in larger phase 3 trials, Dr. Le Roux and colleagues conclude.
 

Survodutide has FDA fast track designation for NASH

Survodutide has received U.S. Food and Drug Administration Fast Track Designation for adults with NASH. The drug is currently being evaluated in a phase 2 study in adults with NASH and stages F1/F2/F3 liver fibrosis, with trial completion expected in the last quarter of 2023.

The current trial was funded by Boehringer Ingelheim. Dr. Le Roux has reported being on an advisory panel for Boehringer Ingelheim and being on advisory panels and receiving research funding from multiple other pharmaceutical companies. Two study authors are Boehringer Ingelheim employees.

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

SAN DIEGO – Survodutide, a dual glucagonlike peptide–1 (GLP-1) and glucagon receptor agonist, led to “striking” weight loss in a phase 2 dosing trial in people with overweight/obesity but without type 2 diabetes.

Close to 40% of people who were taking the highest dose lost 20% or more of their starting weight at 46 weeks, Carel Le Roux, MBChB, PhD, reported at the annual scientific sessions of the American Diabetes Association.

Boehringer Ingelheim and Zealand Pharma are developing survodutide (formerly BI 456906) to treat obesity and nonalcoholic fatty liver disease (NAFLD), according to a company press release.

Glucagon receptor agonism increases energy expenditure, and GLP-1 receptor agonism inhibits appetite, both part of the mechanism of action, Dr. Le Roux, a professor at University College in Dublin, explained.

The trial showed a “striking” and clear dose-response in terms of weight loss, with no new unexpected safety signals, he reported.

Invited to comment, session moderator Elisabetta Patorno, MD, DrPH, noted that “Obesity is one of the main risk factors for [type 2] diabetes.”

“It’s very stimulating to see this new medication class make such a big impact on weight loss in such a short amount of time,” Dr. Patorno, associate professor of medicine at Harvard Medical School, Boston, said in an interview. However, whether the weight loss can be maintained over time remains to be determined in further research, she said.

Head-to-head weight-loss studies of the dual agonist survodutide versus the mono GLP-1 agonist semaglutide (Ozempic, Wegovy, Novo Nordisk) have not been conducted, Dr. Le Roux said during a press briefing.

“What we don’t know is if somebody doesn’t respond to [weight-loss drug] product A, will they respond to product B?” he said. Because survodutide acts on two types of receptors, “you could argue that you would not only increase the absolute amount of weight but you might also increase the number of patients who would respond, but that’s theoretical at the moment,” he explained.
 

Close to 400 patients, five doses, 46-week endpoint

The researchers randomized 387 adults aged 18-75 who had a body mass index (BMI) ≥ 27 kg/m² (overweight or obesity) without type 2 diabetes at sites in North America, Europe, Australia/New Zealand, and Asia.

On average, patients were 49 years old with a body weight of 106 kg (234 lb) and a BMI of 37 kg/m², and 68% were women.

They were randomized to receive a planned weekly subcutaneous maintenance survodutide dose of 0.6 mg (76 patients), 2.4 mg (78 patients), 3.6 mg (76 patients), or 4.8 mg (76 patients), or placebo (77 patients).

The dose was escalated rapidly (monthly) during a 20-week dose-escalation phase, followed by a 26-week maintenance phase.

Patients who did not reach the planned dose remained on a lower dose during the maintenance phase.

In terms of actual treatment, during the maintenance phase, 76 patients were taking placebo, 88 patients were taking 0.6 mg survodutide, 92 were taking 2.4 mg survodutide, 71 were taking 3.6 mg survodutide, and 54 were taking 4.8 mg survodutide, all given as weekly subcutaneous injections.

Primary outcome was the percentage change in body weight from baseline to week 46.

Secondary outcomes included the percentage of patients who reached a body weight reduction of ≥ 5%, ≥ 10%, and ≥ 15% from baseline to week 46.

Mean weight loss at 46 weeks in the planned treatment analysis (where some patients in each group were taking a lower than planned dose during maintenance) was 6.2% in the 0.6-mg survodutide group, 12.5% in the 2.4-mg group, 13.2% in the 3.6-mg group, 14.9% in the 4.8-mg group, and 2.8% in the placebo group.

Among participants who did reach and stay on their assigned dose during the maintenance phase, average weight loss was 6.8% in the 0.6-mg survodutide group,13.6% with 2.4 mg survodutide,16.7% with 3.6 mg survodutide, 18.6% with 4.8 mg survodutide, and 2.0% with placebo.

That is, patients reaching and staying on a weekly subcutaneous dose of 4.8 mg survodutide lost 18.6% of their body weight at 46 weeks, Dr. Le Roux emphasized.

In terms of secondary outcomes, in the group of patients with a planned weekly dose of 4.8 mg survodutide, 83%, 69%, and 55% attained weight loss of ≥ 5%, ≥ 10%, and ≥ 15% of their initial weight, respectively, at 46 weeks.

In the group of patients with an actual weekly dose of 4.8 mg survodutide, 98%, 82%, and 67% attained weight loss of ≥ 5%, ≥ 10%, and ≥ 15% of their initial weight, respectively, at 46 weeks.

Moreover, 33% of patients in the group with a planned weekly dose of 4.8 mg survodutide and 38% of patients with an actual weekly dose of 4.8 mg survodutide lost ≥ 20% of their baseline body weight by week 46.

Adverse events occurred in 91% of patients in the survodutide groups and 75% in the placebo group. The most common side effects were nausea, vomiting, diarrhea, and constipation, which were mostly mild to moderate and mainly occurred during dose escalation. These effects may potentially be mitigated by more gradual dose escalation, Dr. Le Roux said.

There were no unexpected safety or tolerability concerns, and no serious drug-related adverse events.

These “encouraging data” support further study of survodutide for weight loss in larger phase 3 trials, Dr. Le Roux and colleagues conclude.
 

Survodutide has FDA fast track designation for NASH

Survodutide has received U.S. Food and Drug Administration Fast Track Designation for adults with NASH. The drug is currently being evaluated in a phase 2 study in adults with NASH and stages F1/F2/F3 liver fibrosis, with trial completion expected in the last quarter of 2023.

The current trial was funded by Boehringer Ingelheim. Dr. Le Roux has reported being on an advisory panel for Boehringer Ingelheim and being on advisory panels and receiving research funding from multiple other pharmaceutical companies. Two study authors are Boehringer Ingelheim employees.

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

SAN DIEGO – Survodutide, a dual glucagonlike peptide–1 (GLP-1) and glucagon receptor agonist, led to “striking” weight loss in a phase 2 dosing trial in people with overweight/obesity but without type 2 diabetes.

Close to 40% of people who were taking the highest dose lost 20% or more of their starting weight at 46 weeks, Carel Le Roux, MBChB, PhD, reported at the annual scientific sessions of the American Diabetes Association.

Boehringer Ingelheim and Zealand Pharma are developing survodutide (formerly BI 456906) to treat obesity and nonalcoholic fatty liver disease (NAFLD), according to a company press release.

Glucagon receptor agonism increases energy expenditure, and GLP-1 receptor agonism inhibits appetite, both part of the mechanism of action, Dr. Le Roux, a professor at University College in Dublin, explained.

The trial showed a “striking” and clear dose-response in terms of weight loss, with no new unexpected safety signals, he reported.

Invited to comment, session moderator Elisabetta Patorno, MD, DrPH, noted that “Obesity is one of the main risk factors for [type 2] diabetes.”

“It’s very stimulating to see this new medication class make such a big impact on weight loss in such a short amount of time,” Dr. Patorno, associate professor of medicine at Harvard Medical School, Boston, said in an interview. However, whether the weight loss can be maintained over time remains to be determined in further research, she said.

Head-to-head weight-loss studies of the dual agonist survodutide versus the mono GLP-1 agonist semaglutide (Ozempic, Wegovy, Novo Nordisk) have not been conducted, Dr. Le Roux said during a press briefing.

“What we don’t know is if somebody doesn’t respond to [weight-loss drug] product A, will they respond to product B?” he said. Because survodutide acts on two types of receptors, “you could argue that you would not only increase the absolute amount of weight but you might also increase the number of patients who would respond, but that’s theoretical at the moment,” he explained.
 

Close to 400 patients, five doses, 46-week endpoint

The researchers randomized 387 adults aged 18-75 who had a body mass index (BMI) ≥ 27 kg/m² (overweight or obesity) without type 2 diabetes at sites in North America, Europe, Australia/New Zealand, and Asia.

On average, patients were 49 years old with a body weight of 106 kg (234 lb) and a BMI of 37 kg/m², and 68% were women.

They were randomized to receive a planned weekly subcutaneous maintenance survodutide dose of 0.6 mg (76 patients), 2.4 mg (78 patients), 3.6 mg (76 patients), or 4.8 mg (76 patients), or placebo (77 patients).

The dose was escalated rapidly (monthly) during a 20-week dose-escalation phase, followed by a 26-week maintenance phase.

Patients who did not reach the planned dose remained on a lower dose during the maintenance phase.

In terms of actual treatment, during the maintenance phase, 76 patients were taking placebo, 88 patients were taking 0.6 mg survodutide, 92 were taking 2.4 mg survodutide, 71 were taking 3.6 mg survodutide, and 54 were taking 4.8 mg survodutide, all given as weekly subcutaneous injections.

Primary outcome was the percentage change in body weight from baseline to week 46.

Secondary outcomes included the percentage of patients who reached a body weight reduction of ≥ 5%, ≥ 10%, and ≥ 15% from baseline to week 46.

Mean weight loss at 46 weeks in the planned treatment analysis (where some patients in each group were taking a lower than planned dose during maintenance) was 6.2% in the 0.6-mg survodutide group, 12.5% in the 2.4-mg group, 13.2% in the 3.6-mg group, 14.9% in the 4.8-mg group, and 2.8% in the placebo group.

Among participants who did reach and stay on their assigned dose during the maintenance phase, average weight loss was 6.8% in the 0.6-mg survodutide group,13.6% with 2.4 mg survodutide,16.7% with 3.6 mg survodutide, 18.6% with 4.8 mg survodutide, and 2.0% with placebo.

That is, patients reaching and staying on a weekly subcutaneous dose of 4.8 mg survodutide lost 18.6% of their body weight at 46 weeks, Dr. Le Roux emphasized.

In terms of secondary outcomes, in the group of patients with a planned weekly dose of 4.8 mg survodutide, 83%, 69%, and 55% attained weight loss of ≥ 5%, ≥ 10%, and ≥ 15% of their initial weight, respectively, at 46 weeks.

In the group of patients with an actual weekly dose of 4.8 mg survodutide, 98%, 82%, and 67% attained weight loss of ≥ 5%, ≥ 10%, and ≥ 15% of their initial weight, respectively, at 46 weeks.

Moreover, 33% of patients in the group with a planned weekly dose of 4.8 mg survodutide and 38% of patients with an actual weekly dose of 4.8 mg survodutide lost ≥ 20% of their baseline body weight by week 46.

Adverse events occurred in 91% of patients in the survodutide groups and 75% in the placebo group. The most common side effects were nausea, vomiting, diarrhea, and constipation, which were mostly mild to moderate and mainly occurred during dose escalation. These effects may potentially be mitigated by more gradual dose escalation, Dr. Le Roux said.

There were no unexpected safety or tolerability concerns, and no serious drug-related adverse events.

These “encouraging data” support further study of survodutide for weight loss in larger phase 3 trials, Dr. Le Roux and colleagues conclude.
 

Survodutide has FDA fast track designation for NASH

Survodutide has received U.S. Food and Drug Administration Fast Track Designation for adults with NASH. The drug is currently being evaluated in a phase 2 study in adults with NASH and stages F1/F2/F3 liver fibrosis, with trial completion expected in the last quarter of 2023.

The current trial was funded by Boehringer Ingelheim. Dr. Le Roux has reported being on an advisory panel for Boehringer Ingelheim and being on advisory panels and receiving research funding from multiple other pharmaceutical companies. Two study authors are Boehringer Ingelheim employees.

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