WASHINGTON – After patients with symptomatic peripheral arterial disease (PAD) were treated with a paclitaxel-coated balloon for 1 year, 89.5% remain free of target lesion restenosis (TLR), according to real-world registry data presented as a late-breaker at CRT 2019 sponsored by MedStar Heart & Vascular Institute.

Ted Bosworth/MDedge News

Freedom from TLR is the primary endpoint of this registry, which will continue to accrue data for 2 more years, according to Nicolas W. Shammas, MD, medical director of Midwest Cardiovascular Research Foundation, Davenport, Iowa.

The nearly 90% rate of freedom from TLR at 1 year was achieved “despite the fact that over 50% of the patients had diabetes, 29% had severe calcification, 35% had critical limb ischemia, and 25% had complete total occlusions,” said Dr. Shammas, an interventional cardiologist.

The registry, called SAFE-DCB, was created to evaluate long-term outcomes after treatment with the Lutonix (Bard Medical) paclitaxel-coated balloon catheter, which is employed in percutaneous angioplasty to treat stenotic lesions in the peripheral vasculature. Over an 18-month period, 1,005 patients were enrolled at 74 treatment centers. Dr. Shammas presented data on 766 of these patients, who have completed 12-months of follow-up. There are 835 patients enrolled in the ongoing study.

In a review of characteristics prior to treatment, Dr. Shammas reported that the average target lesion stenosis was 86.7% and the average target lesion length was 75 mm. Endovascular treatments prior to angioplasty were permitted in the registry protocol. Half of the patients underwent directional atherectomy.

After treatment, the residual stenosis was 11.54%. Even though the recommended protocol called for balloon inflations of 30 seconds each at a pressure of 7 atmospheres, the mean balloon inflation times were 35 seconds at 8 atmospheres. The mean total time for balloon inflations per patient was 152 seconds against the protocol recommendation of 140 seconds.

The primary safety endpoint was freedom from periprocedural mortality, limb amputation, and TLR at 30 days, which was achieved in 98.2% of patients.

Mortality at 1 year was 7.1%. Cardiovascular deaths, such as those due to myocardial infarction, were the most common, but there were noncardiovascular deaths, including those due to sepsis, respiratory failure, and kidney disease.

Women represented 43% of the study population. When compared with men, women achieved the primary outcome at a numerically lower rate, but the difference was not statistically significant. Dr. Shammas reported similar findings for those without complete total occlusions relative to those with complete total occlusions and those treated within the study protocol relative to those who were not. In each case, the differences in the proportion that achieved the primary outcome did not reach statistical significance.

Following his presentation, Dr. Shammas was asked to respond to the criticism that TLR is a soft endpoint. Since some proportion of patients might have had a return of symptoms due to restenosis but elected not to have a second procedure, TLR at 1 year is not equivalent to patency at 1 year.

While acknowledging the accuracy of this criticism, Dr. Shammas reported that TLR was a practical surrogate in the absence of imaging or another objective method of target lesion assessment. Noting that this endpoint has been employed before for long-term follow-up in trials of percutaneous therapies, he said that the TLR rates in this SAFE-DCB registry “are well within previously reported data” for 1-year outcomes with other treatments of symptomatic PAD.

SOURCE: Shammas N. CRT 2019 Mar 5.

WASHINGTON – After patients with symptomatic peripheral arterial disease (PAD) were treated with a paclitaxel-coated balloon for 1 year, 89.5% remain free of target lesion restenosis (TLR), according to real-world registry data presented as a late-breaker at CRT 2019 sponsored by MedStar Heart & Vascular Institute.

Ted Bosworth/MDedge News

Freedom from TLR is the primary endpoint of this registry, which will continue to accrue data for 2 more years, according to Nicolas W. Shammas, MD, medical director of Midwest Cardiovascular Research Foundation, Davenport, Iowa.

The nearly 90% rate of freedom from TLR at 1 year was achieved “despite the fact that over 50% of the patients had diabetes, 29% had severe calcification, 35% had critical limb ischemia, and 25% had complete total occlusions,” said Dr. Shammas, an interventional cardiologist.

The registry, called SAFE-DCB, was created to evaluate long-term outcomes after treatment with the Lutonix (Bard Medical) paclitaxel-coated balloon catheter, which is employed in percutaneous angioplasty to treat stenotic lesions in the peripheral vasculature. Over an 18-month period, 1,005 patients were enrolled at 74 treatment centers. Dr. Shammas presented data on 766 of these patients, who have completed 12-months of follow-up. There are 835 patients enrolled in the ongoing study.

In a review of characteristics prior to treatment, Dr. Shammas reported that the average target lesion stenosis was 86.7% and the average target lesion length was 75 mm. Endovascular treatments prior to angioplasty were permitted in the registry protocol. Half of the patients underwent directional atherectomy.

After treatment, the residual stenosis was 11.54%. Even though the recommended protocol called for balloon inflations of 30 seconds each at a pressure of 7 atmospheres, the mean balloon inflation times were 35 seconds at 8 atmospheres. The mean total time for balloon inflations per patient was 152 seconds against the protocol recommendation of 140 seconds.

The primary safety endpoint was freedom from periprocedural mortality, limb amputation, and TLR at 30 days, which was achieved in 98.2% of patients.

Mortality at 1 year was 7.1%. Cardiovascular deaths, such as those due to myocardial infarction, were the most common, but there were noncardiovascular deaths, including those due to sepsis, respiratory failure, and kidney disease.

Women represented 43% of the study population. When compared with men, women achieved the primary outcome at a numerically lower rate, but the difference was not statistically significant. Dr. Shammas reported similar findings for those without complete total occlusions relative to those with complete total occlusions and those treated within the study protocol relative to those who were not. In each case, the differences in the proportion that achieved the primary outcome did not reach statistical significance.

Following his presentation, Dr. Shammas was asked to respond to the criticism that TLR is a soft endpoint. Since some proportion of patients might have had a return of symptoms due to restenosis but elected not to have a second procedure, TLR at 1 year is not equivalent to patency at 1 year.

While acknowledging the accuracy of this criticism, Dr. Shammas reported that TLR was a practical surrogate in the absence of imaging or another objective method of target lesion assessment. Noting that this endpoint has been employed before for long-term follow-up in trials of percutaneous therapies, he said that the TLR rates in this SAFE-DCB registry “are well within previously reported data” for 1-year outcomes with other treatments of symptomatic PAD.

SOURCE: Shammas N. CRT 2019 Mar 5.

WASHINGTON – After patients with symptomatic peripheral arterial disease (PAD) were treated with a paclitaxel-coated balloon for 1 year, 89.5% remain free of target lesion restenosis (TLR), according to real-world registry data presented as a late-breaker at CRT 2019 sponsored by MedStar Heart & Vascular Institute.

Ted Bosworth/MDedge News

Freedom from TLR is the primary endpoint of this registry, which will continue to accrue data for 2 more years, according to Nicolas W. Shammas, MD, medical director of Midwest Cardiovascular Research Foundation, Davenport, Iowa.

The nearly 90% rate of freedom from TLR at 1 year was achieved “despite the fact that over 50% of the patients had diabetes, 29% had severe calcification, 35% had critical limb ischemia, and 25% had complete total occlusions,” said Dr. Shammas, an interventional cardiologist.

The registry, called SAFE-DCB, was created to evaluate long-term outcomes after treatment with the Lutonix (Bard Medical) paclitaxel-coated balloon catheter, which is employed in percutaneous angioplasty to treat stenotic lesions in the peripheral vasculature. Over an 18-month period, 1,005 patients were enrolled at 74 treatment centers. Dr. Shammas presented data on 766 of these patients, who have completed 12-months of follow-up. There are 835 patients enrolled in the ongoing study.

In a review of characteristics prior to treatment, Dr. Shammas reported that the average target lesion stenosis was 86.7% and the average target lesion length was 75 mm. Endovascular treatments prior to angioplasty were permitted in the registry protocol. Half of the patients underwent directional atherectomy.

After treatment, the residual stenosis was 11.54%. Even though the recommended protocol called for balloon inflations of 30 seconds each at a pressure of 7 atmospheres, the mean balloon inflation times were 35 seconds at 8 atmospheres. The mean total time for balloon inflations per patient was 152 seconds against the protocol recommendation of 140 seconds.

The primary safety endpoint was freedom from periprocedural mortality, limb amputation, and TLR at 30 days, which was achieved in 98.2% of patients.

Mortality at 1 year was 7.1%. Cardiovascular deaths, such as those due to myocardial infarction, were the most common, but there were noncardiovascular deaths, including those due to sepsis, respiratory failure, and kidney disease.

Women represented 43% of the study population. When compared with men, women achieved the primary outcome at a numerically lower rate, but the difference was not statistically significant. Dr. Shammas reported similar findings for those without complete total occlusions relative to those with complete total occlusions and those treated within the study protocol relative to those who were not. In each case, the differences in the proportion that achieved the primary outcome did not reach statistical significance.

Following his presentation, Dr. Shammas was asked to respond to the criticism that TLR is a soft endpoint. Since some proportion of patients might have had a return of symptoms due to restenosis but elected not to have a second procedure, TLR at 1 year is not equivalent to patency at 1 year.

While acknowledging the accuracy of this criticism, Dr. Shammas reported that TLR was a practical surrogate in the absence of imaging or another objective method of target lesion assessment. Noting that this endpoint has been employed before for long-term follow-up in trials of percutaneous therapies, he said that the TLR rates in this SAFE-DCB registry “are well within previously reported data” for 1-year outcomes with other treatments of symptomatic PAD.

SOURCE: Shammas N. CRT 2019 Mar 5.

Microcystic lymphatic malformations, also known as lymphangioma circumscriptum, are rare hamar­tomatous lesions comprised of dilated lymphatic channels that can be both congenital and acquired.¹ They often present as translucent or hemorrhagic ves­icles of varying sizes that may contain lymphatic fluid and often can cluster together and appear verrucous (Figure 1). The differential diagnosis for microcystic lym­phatic malformations commonly includes molluscum contagiosum, squamous cell carcinoma, verruca vulgaris, or condylomas, as well as atypical vascular lesions. They most often are found in children as congenital lesions but also may be acquired. Most acquired cases are due to chronic inflammatory and scarring processes that damage lymphatic structures, including surgery, radiation, infec­tions, and even Crohn disease.^2,3 Because the differential diagnosis is so broad and the disease can clinically mimic other common disease processes, biopsies often are per­formed to determine the diagnosis. On biopsy, pathologic examination revealed well-circumscribed nodular lesions with large lymphatic channels often in a background of connective tissue stroma. Increased eosinophilic mate­rial, including mast cells, also was seen (Figure 2A). On immunohistochemistry, staining showed D2-40 posi­tivity (Figure 2B). 

Damage to lymphatics from radiation and postsurgi­cal excision of tumors are well-described causes of micro­cystic lymphatic malformations, as in our patient, with most instances in the literature occurring secondary to treatment of breast or cervical cancer.^4-6 In these acquired cases, the pathogenesis is thought to be due to destruc­tion and fibrosis at the layer of the reticular dermis, which causes lymphatic obstruction and subsequent dilation of superficial lymphatic channels.⁶ 

Microcystic lymphatic malformations can be difficult to distinguish from atypical vascular lesions, another common postradiation lesion. Both are benign well-circumscribed lesions that histologically do not extend into surrounding subcutaneous tissues and do not have multilayering of cells, mitosis, or hemorrhage.⁷ Although lymphatic lesions tend to form vesicles, atypical vas­cular lesions arising after radiation treatment present as erythematous or flesh-colored patches or papules. They also tend to be fairly superficial and often only involve the superficial to mid dermis. On histology they show thin-walled channels without erythrocytes that are lined by typical endothelial cells.⁷ Despite these differ­ences, both clinically and histopathologically these lesions can appear similar to acquired microcystic lymphatic malformations. It is important to differentiate between these two entities, as atypical vascular lesions have a slightly higher rate of transformation into malignant tumors such as angiosarcomas. 

Although angiosarcomas clinically may present as ery­thematous patches, plaques, or nodules similar to benign postradiation lesions, they tend to be more edematous than their benign counterparts.^7,8 Two other clinical fac­tors that can help determine if a postradiation lesion is benign or malignant are the size and time of onset of the lesion. Angiosarcomas tend to be much larger than benign postradiation lesions (median size, 7.5 cm) and tend to be more multifocal in nature.^8,9 They also tend to arise on average 5 to 7 years after the initial radiation treatment, while benign lesions arise sooner.⁹ 

Small, asymptomatic, acquired microcystic lymphatic malformations can be followed clinically without treat­ment, but these lesions do not commonly regress spon­taneously. Even when asymptomatic, many clinicians will opt for treatment to prevent secondary complications such as infections, drainage, and pain. Moreover, these lesions can have notable psychosocial impacts on patients due to poor cosmetic appearance. Unfortunately, there is no gold standard of treatment, and recurrence is com­mon, even after treatment. Historically, surgical excision was the treatment of choice, but this option carries a high risk for scarring, invasiveness, and recurrence. Recurrence rates of up to 23.1% have been reported with decreased effectiveness of resection, particularly in areas of deeper involvement.¹⁰ For these deeper lesions, CO2 laser therapy is a promising evolving therapy. It can penetrate up to the mid dermis and seems to destroy the lymphatic chan­nels between deep and surface lymphatics, preventing the cutaneous manifestations of the disease. It has the added benefit of minimal invasiveness and fewer side effects than complete excision, with most studies report­ing hyperpigmentation and scarring as the most common side effects.¹¹ Additional emerging therapies including sclerotherapy and isotretinoin have shown benefits in case studies. Sclerotherapy causes local tissue destruction and thrombosis leading to destruction of vessel lumens and fibrosis that halts disease progression and clears existing lesions.¹² Oral therapy with isotretinoin appears to work by inhibiting certain cytokines and acting as an antiangiogenic factor.¹³ Given the rarity of microcystic lymphatic malformations, further research must be done to determine definitive treatment. 

Acquired microcystic lymphatic malformation is an important sequela of radiation therapy and surgical exci­sion of malignancy. Despite its striking clinical appear­ance, it is sometimes difficult to diagnose given its rarity. It is important that clinicians are able to recognize it clini­cally and understand common treatment options to pre­vent both the mental stigma and complications, including secondary infections, drainage, and pain. 

Microcystic lymphatic malformations, also known as lymphangioma circumscriptum, are rare hamar­tomatous lesions comprised of dilated lymphatic channels that can be both congenital and acquired.¹ They often present as translucent or hemorrhagic ves­icles of varying sizes that may contain lymphatic fluid and often can cluster together and appear verrucous (Figure 1). The differential diagnosis for microcystic lym­phatic malformations commonly includes molluscum contagiosum, squamous cell carcinoma, verruca vulgaris, or condylomas, as well as atypical vascular lesions. They most often are found in children as congenital lesions but also may be acquired. Most acquired cases are due to chronic inflammatory and scarring processes that damage lymphatic structures, including surgery, radiation, infec­tions, and even Crohn disease.^2,3 Because the differential diagnosis is so broad and the disease can clinically mimic other common disease processes, biopsies often are per­formed to determine the diagnosis. On biopsy, pathologic examination revealed well-circumscribed nodular lesions with large lymphatic channels often in a background of connective tissue stroma. Increased eosinophilic mate­rial, including mast cells, also was seen (Figure 2A). On immunohistochemistry, staining showed D2-40 posi­tivity (Figure 2B). 

Damage to lymphatics from radiation and postsurgi­cal excision of tumors are well-described causes of micro­cystic lymphatic malformations, as in our patient, with most instances in the literature occurring secondary to treatment of breast or cervical cancer.^4-6 In these acquired cases, the pathogenesis is thought to be due to destruc­tion and fibrosis at the layer of the reticular dermis, which causes lymphatic obstruction and subsequent dilation of superficial lymphatic channels.⁶ 

Microcystic lymphatic malformations can be difficult to distinguish from atypical vascular lesions, another common postradiation lesion. Both are benign well-circumscribed lesions that histologically do not extend into surrounding subcutaneous tissues and do not have multilayering of cells, mitosis, or hemorrhage.⁷ Although lymphatic lesions tend to form vesicles, atypical vas­cular lesions arising after radiation treatment present as erythematous or flesh-colored patches or papules. They also tend to be fairly superficial and often only involve the superficial to mid dermis. On histology they show thin-walled channels without erythrocytes that are lined by typical endothelial cells.⁷ Despite these differ­ences, both clinically and histopathologically these lesions can appear similar to acquired microcystic lymphatic malformations. It is important to differentiate between these two entities, as atypical vascular lesions have a slightly higher rate of transformation into malignant tumors such as angiosarcomas. 

Although angiosarcomas clinically may present as ery­thematous patches, plaques, or nodules similar to benign postradiation lesions, they tend to be more edematous than their benign counterparts.^7,8 Two other clinical fac­tors that can help determine if a postradiation lesion is benign or malignant are the size and time of onset of the lesion. Angiosarcomas tend to be much larger than benign postradiation lesions (median size, 7.5 cm) and tend to be more multifocal in nature.^8,9 They also tend to arise on average 5 to 7 years after the initial radiation treatment, while benign lesions arise sooner.⁹ 

Small, asymptomatic, acquired microcystic lymphatic malformations can be followed clinically without treat­ment, but these lesions do not commonly regress spon­taneously. Even when asymptomatic, many clinicians will opt for treatment to prevent secondary complications such as infections, drainage, and pain. Moreover, these lesions can have notable psychosocial impacts on patients due to poor cosmetic appearance. Unfortunately, there is no gold standard of treatment, and recurrence is com­mon, even after treatment. Historically, surgical excision was the treatment of choice, but this option carries a high risk for scarring, invasiveness, and recurrence. Recurrence rates of up to 23.1% have been reported with decreased effectiveness of resection, particularly in areas of deeper involvement.¹⁰ For these deeper lesions, CO2 laser therapy is a promising evolving therapy. It can penetrate up to the mid dermis and seems to destroy the lymphatic chan­nels between deep and surface lymphatics, preventing the cutaneous manifestations of the disease. It has the added benefit of minimal invasiveness and fewer side effects than complete excision, with most studies report­ing hyperpigmentation and scarring as the most common side effects.¹¹ Additional emerging therapies including sclerotherapy and isotretinoin have shown benefits in case studies. Sclerotherapy causes local tissue destruction and thrombosis leading to destruction of vessel lumens and fibrosis that halts disease progression and clears existing lesions.¹² Oral therapy with isotretinoin appears to work by inhibiting certain cytokines and acting as an antiangiogenic factor.¹³ Given the rarity of microcystic lymphatic malformations, further research must be done to determine definitive treatment. 

Acquired microcystic lymphatic malformation is an important sequela of radiation therapy and surgical exci­sion of malignancy. Despite its striking clinical appear­ance, it is sometimes difficult to diagnose given its rarity. It is important that clinicians are able to recognize it clini­cally and understand common treatment options to pre­vent both the mental stigma and complications, including secondary infections, drainage, and pain. 

Microcystic lymphatic malformations, also known as lymphangioma circumscriptum, are rare hamar­tomatous lesions comprised of dilated lymphatic channels that can be both congenital and acquired.¹ They often present as translucent or hemorrhagic ves­icles of varying sizes that may contain lymphatic fluid and often can cluster together and appear verrucous (Figure 1). The differential diagnosis for microcystic lym­phatic malformations commonly includes molluscum contagiosum, squamous cell carcinoma, verruca vulgaris, or condylomas, as well as atypical vascular lesions. They most often are found in children as congenital lesions but also may be acquired. Most acquired cases are due to chronic inflammatory and scarring processes that damage lymphatic structures, including surgery, radiation, infec­tions, and even Crohn disease.^2,3 Because the differential diagnosis is so broad and the disease can clinically mimic other common disease processes, biopsies often are per­formed to determine the diagnosis. On biopsy, pathologic examination revealed well-circumscribed nodular lesions with large lymphatic channels often in a background of connective tissue stroma. Increased eosinophilic mate­rial, including mast cells, also was seen (Figure 2A). On immunohistochemistry, staining showed D2-40 posi­tivity (Figure 2B). 

Damage to lymphatics from radiation and postsurgi­cal excision of tumors are well-described causes of micro­cystic lymphatic malformations, as in our patient, with most instances in the literature occurring secondary to treatment of breast or cervical cancer.^4-6 In these acquired cases, the pathogenesis is thought to be due to destruc­tion and fibrosis at the layer of the reticular dermis, which causes lymphatic obstruction and subsequent dilation of superficial lymphatic channels.⁶ 

Microcystic lymphatic malformations can be difficult to distinguish from atypical vascular lesions, another common postradiation lesion. Both are benign well-circumscribed lesions that histologically do not extend into surrounding subcutaneous tissues and do not have multilayering of cells, mitosis, or hemorrhage.⁷ Although lymphatic lesions tend to form vesicles, atypical vas­cular lesions arising after radiation treatment present as erythematous or flesh-colored patches or papules. They also tend to be fairly superficial and often only involve the superficial to mid dermis. On histology they show thin-walled channels without erythrocytes that are lined by typical endothelial cells.⁷ Despite these differ­ences, both clinically and histopathologically these lesions can appear similar to acquired microcystic lymphatic malformations. It is important to differentiate between these two entities, as atypical vascular lesions have a slightly higher rate of transformation into malignant tumors such as angiosarcomas. 

Although angiosarcomas clinically may present as ery­thematous patches, plaques, or nodules similar to benign postradiation lesions, they tend to be more edematous than their benign counterparts.^7,8 Two other clinical fac­tors that can help determine if a postradiation lesion is benign or malignant are the size and time of onset of the lesion. Angiosarcomas tend to be much larger than benign postradiation lesions (median size, 7.5 cm) and tend to be more multifocal in nature.^8,9 They also tend to arise on average 5 to 7 years after the initial radiation treatment, while benign lesions arise sooner.⁹ 

Small, asymptomatic, acquired microcystic lymphatic malformations can be followed clinically without treat­ment, but these lesions do not commonly regress spon­taneously. Even when asymptomatic, many clinicians will opt for treatment to prevent secondary complications such as infections, drainage, and pain. Moreover, these lesions can have notable psychosocial impacts on patients due to poor cosmetic appearance. Unfortunately, there is no gold standard of treatment, and recurrence is com­mon, even after treatment. Historically, surgical excision was the treatment of choice, but this option carries a high risk for scarring, invasiveness, and recurrence. Recurrence rates of up to 23.1% have been reported with decreased effectiveness of resection, particularly in areas of deeper involvement.¹⁰ For these deeper lesions, CO2 laser therapy is a promising evolving therapy. It can penetrate up to the mid dermis and seems to destroy the lymphatic chan­nels between deep and surface lymphatics, preventing the cutaneous manifestations of the disease. It has the added benefit of minimal invasiveness and fewer side effects than complete excision, with most studies report­ing hyperpigmentation and scarring as the most common side effects.¹¹ Additional emerging therapies including sclerotherapy and isotretinoin have shown benefits in case studies. Sclerotherapy causes local tissue destruction and thrombosis leading to destruction of vessel lumens and fibrosis that halts disease progression and clears existing lesions.¹² Oral therapy with isotretinoin appears to work by inhibiting certain cytokines and acting as an antiangiogenic factor.¹³ Given the rarity of microcystic lymphatic malformations, further research must be done to determine definitive treatment. 

Acquired microcystic lymphatic malformation is an important sequela of radiation therapy and surgical exci­sion of malignancy. Despite its striking clinical appear­ance, it is sometimes difficult to diagnose given its rarity. It is important that clinicians are able to recognize it clini­cally and understand common treatment options to pre­vent both the mental stigma and complications, including secondary infections, drainage, and pain. 

The number of women being screened for von Willebrand disease (VWD) before undergoing hysterectomy for heavy menstrual bleeding is “very low” and appears not to align with current recommendations, according to a retrospective analysis.

U.S. Air Force photo by Staff Sgt. Ciara Gosier

“One essential reason to identify females with VWD prior to hysterectomy or hysterectomy alternative is to avoid peri‐ and postoperative complications,” Amanda E. Jacobson‐Kelly, MD, of Ohio State University in Columbus and her colleagues wrote in a letter to the editor published in Haemophilia.

Current recommendations from the American College of Obstetricians and Gynecologists and other groups call for consideration of underlying bleeding disorders in women with heavy menstrual bleeding and additional risks factors, such as family history of abnormal bleeding.

In this study, researchers retrospectively analyzed 8,998 women under the age of 40 years who had a hysterectomy for heavy menstrual bleeding without a known bleeding disorder. Patient data was collected from a national insurance claims database representative of the entire U.S. population.

“We hypothesized that the overall frequency of VWD screening would be low, despite [more than] 15 years of expert recommendations,” the team wrote.

Study participants were included if they had a diagnosis of anemia or heavy menstrual bleeding before surgery, while women with certain genital malignancies and fibroids were excluded. Other information, such as age, geographical factors, and insurance-related factors were also included to evaluate whether these parameters affected disease screening.

After analysis, the researchers found that just 0.6% (n = 57) of women were screened for VWD in the 12 months leading up to surgery. Additionally, they reported that 14% (n = 1,276) of women underwent other forms of coagulation testing before surgery, such as partial thromboplastin time and prothrombin time.

“We found that greater distance to a [hemophilia treatment center] was strongly predictive of decreased likelihood of undergoing VWD screening,” Dr. Jacobson‐Kelly and her colleagues wrote.

The authors acknowledged that a key limitation of the study was the inability to account for factors not recorded in the database, including drug use, family history of bleeding disorders, and ethnicity.

“This study brings to light the need for the hematology community to improve education and awareness among women’s health providers,” they wrote.

The study was supported by grant funding from the National Heart, Lung, and Blood Institute. The authors reported having no conflicts of interest.

SOURCE: Jacobson-Kelly AE et al. Haemophilia. 2019 Feb 28. doi: 10.1111/hae.13709.

The number of women being screened for von Willebrand disease (VWD) before undergoing hysterectomy for heavy menstrual bleeding is “very low” and appears not to align with current recommendations, according to a retrospective analysis.

U.S. Air Force photo by Staff Sgt. Ciara Gosier

“One essential reason to identify females with VWD prior to hysterectomy or hysterectomy alternative is to avoid peri‐ and postoperative complications,” Amanda E. Jacobson‐Kelly, MD, of Ohio State University in Columbus and her colleagues wrote in a letter to the editor published in Haemophilia.

Current recommendations from the American College of Obstetricians and Gynecologists and other groups call for consideration of underlying bleeding disorders in women with heavy menstrual bleeding and additional risks factors, such as family history of abnormal bleeding.

In this study, researchers retrospectively analyzed 8,998 women under the age of 40 years who had a hysterectomy for heavy menstrual bleeding without a known bleeding disorder. Patient data was collected from a national insurance claims database representative of the entire U.S. population.

“We hypothesized that the overall frequency of VWD screening would be low, despite [more than] 15 years of expert recommendations,” the team wrote.

Study participants were included if they had a diagnosis of anemia or heavy menstrual bleeding before surgery, while women with certain genital malignancies and fibroids were excluded. Other information, such as age, geographical factors, and insurance-related factors were also included to evaluate whether these parameters affected disease screening.

After analysis, the researchers found that just 0.6% (n = 57) of women were screened for VWD in the 12 months leading up to surgery. Additionally, they reported that 14% (n = 1,276) of women underwent other forms of coagulation testing before surgery, such as partial thromboplastin time and prothrombin time.

“We found that greater distance to a [hemophilia treatment center] was strongly predictive of decreased likelihood of undergoing VWD screening,” Dr. Jacobson‐Kelly and her colleagues wrote.

The authors acknowledged that a key limitation of the study was the inability to account for factors not recorded in the database, including drug use, family history of bleeding disorders, and ethnicity.

“This study brings to light the need for the hematology community to improve education and awareness among women’s health providers,” they wrote.

The study was supported by grant funding from the National Heart, Lung, and Blood Institute. The authors reported having no conflicts of interest.

SOURCE: Jacobson-Kelly AE et al. Haemophilia. 2019 Feb 28. doi: 10.1111/hae.13709.

The number of women being screened for von Willebrand disease (VWD) before undergoing hysterectomy for heavy menstrual bleeding is “very low” and appears not to align with current recommendations, according to a retrospective analysis.

U.S. Air Force photo by Staff Sgt. Ciara Gosier

“One essential reason to identify females with VWD prior to hysterectomy or hysterectomy alternative is to avoid peri‐ and postoperative complications,” Amanda E. Jacobson‐Kelly, MD, of Ohio State University in Columbus and her colleagues wrote in a letter to the editor published in Haemophilia.

Current recommendations from the American College of Obstetricians and Gynecologists and other groups call for consideration of underlying bleeding disorders in women with heavy menstrual bleeding and additional risks factors, such as family history of abnormal bleeding.

In this study, researchers retrospectively analyzed 8,998 women under the age of 40 years who had a hysterectomy for heavy menstrual bleeding without a known bleeding disorder. Patient data was collected from a national insurance claims database representative of the entire U.S. population.

“We hypothesized that the overall frequency of VWD screening would be low, despite [more than] 15 years of expert recommendations,” the team wrote.

Study participants were included if they had a diagnosis of anemia or heavy menstrual bleeding before surgery, while women with certain genital malignancies and fibroids were excluded. Other information, such as age, geographical factors, and insurance-related factors were also included to evaluate whether these parameters affected disease screening.

After analysis, the researchers found that just 0.6% (n = 57) of women were screened for VWD in the 12 months leading up to surgery. Additionally, they reported that 14% (n = 1,276) of women underwent other forms of coagulation testing before surgery, such as partial thromboplastin time and prothrombin time.

“We found that greater distance to a [hemophilia treatment center] was strongly predictive of decreased likelihood of undergoing VWD screening,” Dr. Jacobson‐Kelly and her colleagues wrote.

The authors acknowledged that a key limitation of the study was the inability to account for factors not recorded in the database, including drug use, family history of bleeding disorders, and ethnicity.

“This study brings to light the need for the hematology community to improve education and awareness among women’s health providers,” they wrote.

The study was supported by grant funding from the National Heart, Lung, and Blood Institute. The authors reported having no conflicts of interest.

SOURCE: Jacobson-Kelly AE et al. Haemophilia. 2019 Feb 28. doi: 10.1111/hae.13709.

We read with interest the review article by Keber and Fiebert, “Diabetes in the elderly: Matching meds to needs” (J Fam Pract. 2018;67:408-410,412-415). The authors have provided a timely overview of antidiabetes medications for elderly people with type 2 diabetes mellitus (T2DM) and their relative risks for hypoglycemia.

We’d like to add to this important conversation.

Aging, per se, modifies the glycemic thresholds for autonomic symptoms and cognitive impairment; in older nondiabetic men (mean + SD: age 65 ± 3 years), autonomic symptoms and cognitive dysfunction commence at identical glycemic thresholds (3 ± 0.2 mmol/L [54 ± 4 mg/dL]). By contrast, in younger men (age 23 ± 2 years), a significant gap is observed between the glycemic threshold for symptom generation (3.6 mmol/L [65 mg/dL]) and the onset of cognitive dysfunction (2.6 mmol/L [47 mg/dL]).^1,2 The simultaneous occurrence of symptoms and cognitive impairment in older people may adversely affect their ability to recognize and treat hypoglycemia promptly.

In addition, hypoglycemia in older T2DM patients often presents with atypical neurologic symptoms, including incoordination and ataxia, slurring of speech, and visual disturbances, which either are not identified as hypoglycemia or are misdiagnosed as other medical disorders (eg, transient ischemic attack).³ Knowledge about hypoglycemia symptoms is poor, in both elderly people with diabetes and their relatives and caregivers, which compromises the ability to identify hypoglycemia and provide effective treatment.⁴ Education about the possible presentations of hypoglycemia and its effective treatment is essential for older patients and their relatives.

Jan Brož, MD
Prague, Czech Republic

We read with interest the review article by Keber and Fiebert, “Diabetes in the elderly: Matching meds to needs” (J Fam Pract. 2018;67:408-410,412-415). The authors have provided a timely overview of antidiabetes medications for elderly people with type 2 diabetes mellitus (T2DM) and their relative risks for hypoglycemia.

We’d like to add to this important conversation.

Aging, per se, modifies the glycemic thresholds for autonomic symptoms and cognitive impairment; in older nondiabetic men (mean + SD: age 65 ± 3 years), autonomic symptoms and cognitive dysfunction commence at identical glycemic thresholds (3 ± 0.2 mmol/L [54 ± 4 mg/dL]). By contrast, in younger men (age 23 ± 2 years), a significant gap is observed between the glycemic threshold for symptom generation (3.6 mmol/L [65 mg/dL]) and the onset of cognitive dysfunction (2.6 mmol/L [47 mg/dL]).^1,2 The simultaneous occurrence of symptoms and cognitive impairment in older people may adversely affect their ability to recognize and treat hypoglycemia promptly.

In addition, hypoglycemia in older T2DM patients often presents with atypical neurologic symptoms, including incoordination and ataxia, slurring of speech, and visual disturbances, which either are not identified as hypoglycemia or are misdiagnosed as other medical disorders (eg, transient ischemic attack).³ Knowledge about hypoglycemia symptoms is poor, in both elderly people with diabetes and their relatives and caregivers, which compromises the ability to identify hypoglycemia and provide effective treatment.⁴ Education about the possible presentations of hypoglycemia and its effective treatment is essential for older patients and their relatives.

Jan Brož, MD
Prague, Czech Republic

We read with interest the review article by Keber and Fiebert, “Diabetes in the elderly: Matching meds to needs” (J Fam Pract. 2018;67:408-410,412-415). The authors have provided a timely overview of antidiabetes medications for elderly people with type 2 diabetes mellitus (T2DM) and their relative risks for hypoglycemia.

We’d like to add to this important conversation.

Aging, per se, modifies the glycemic thresholds for autonomic symptoms and cognitive impairment; in older nondiabetic men (mean + SD: age 65 ± 3 years), autonomic symptoms and cognitive dysfunction commence at identical glycemic thresholds (3 ± 0.2 mmol/L [54 ± 4 mg/dL]). By contrast, in younger men (age 23 ± 2 years), a significant gap is observed between the glycemic threshold for symptom generation (3.6 mmol/L [65 mg/dL]) and the onset of cognitive dysfunction (2.6 mmol/L [47 mg/dL]).^1,2 The simultaneous occurrence of symptoms and cognitive impairment in older people may adversely affect their ability to recognize and treat hypoglycemia promptly.

In addition, hypoglycemia in older T2DM patients often presents with atypical neurologic symptoms, including incoordination and ataxia, slurring of speech, and visual disturbances, which either are not identified as hypoglycemia or are misdiagnosed as other medical disorders (eg, transient ischemic attack).³ Knowledge about hypoglycemia symptoms is poor, in both elderly people with diabetes and their relatives and caregivers, which compromises the ability to identify hypoglycemia and provide effective treatment.⁴ Education about the possible presentations of hypoglycemia and its effective treatment is essential for older patients and their relatives.

Jan Brož, MD
Prague, Czech Republic

It is with much enthusiasm that we read the article “Dialing back opioids for chronic pain one conversation at a time” (J Fam Pract. 2018;67:753-757) about the author’s approach to opioid tapering. We have implemented a similar process in our own medical home practice, based on the continuity relationship and the Ecological Systems Theory.

The use of the human resources within the medical home—care coordinator, pharmacist, community health worker, etc— distributes the responsibility and lessens the burden of care for the family physician. The Ecological Systems Theory provides a structure for understanding the interaction between proximal influencers (eg, the team) and more distal influences (eg, national guidelines and institutional mandates).

Recently, we presented our findings at the 2018 North American Primary Care Research Group (NAPCRG) Annual Meeting. Our results showed a 50% decline in per capita medication use over an almost 14-month period.

We feel that opioid tapering provides both a counterpoint and a complementary method to medication-assisted therapies (MAT). A counterpoint, because MAT involves the diagnosis and treatment of opioid misuse disorder. At the core of that diagnosis is the question of whether all chronic opioid use should be labelled as “misuse.” Tapering involves no such diagnosis and focuses on the safety of minimal opioid use, which, when MAT is used appropriately, is also a primary concern.

We appreciate the approach that the authors took in their project and look forward to seeing further iterations.

Bharat Gopal, MD
Cristina Capannolo, DO
Corvallis, Ore

It is with much enthusiasm that we read the article “Dialing back opioids for chronic pain one conversation at a time” (J Fam Pract. 2018;67:753-757) about the author’s approach to opioid tapering. We have implemented a similar process in our own medical home practice, based on the continuity relationship and the Ecological Systems Theory.

The use of the human resources within the medical home—care coordinator, pharmacist, community health worker, etc— distributes the responsibility and lessens the burden of care for the family physician. The Ecological Systems Theory provides a structure for understanding the interaction between proximal influencers (eg, the team) and more distal influences (eg, national guidelines and institutional mandates).

Recently, we presented our findings at the 2018 North American Primary Care Research Group (NAPCRG) Annual Meeting. Our results showed a 50% decline in per capita medication use over an almost 14-month period.

We feel that opioid tapering provides both a counterpoint and a complementary method to medication-assisted therapies (MAT). A counterpoint, because MAT involves the diagnosis and treatment of opioid misuse disorder. At the core of that diagnosis is the question of whether all chronic opioid use should be labelled as “misuse.” Tapering involves no such diagnosis and focuses on the safety of minimal opioid use, which, when MAT is used appropriately, is also a primary concern.

We appreciate the approach that the authors took in their project and look forward to seeing further iterations.

Bharat Gopal, MD
Cristina Capannolo, DO
Corvallis, Ore

It is with much enthusiasm that we read the article “Dialing back opioids for chronic pain one conversation at a time” (J Fam Pract. 2018;67:753-757) about the author’s approach to opioid tapering. We have implemented a similar process in our own medical home practice, based on the continuity relationship and the Ecological Systems Theory.

The use of the human resources within the medical home—care coordinator, pharmacist, community health worker, etc— distributes the responsibility and lessens the burden of care for the family physician. The Ecological Systems Theory provides a structure for understanding the interaction between proximal influencers (eg, the team) and more distal influences (eg, national guidelines and institutional mandates).

Recently, we presented our findings at the 2018 North American Primary Care Research Group (NAPCRG) Annual Meeting. Our results showed a 50% decline in per capita medication use over an almost 14-month period.

We feel that opioid tapering provides both a counterpoint and a complementary method to medication-assisted therapies (MAT). A counterpoint, because MAT involves the diagnosis and treatment of opioid misuse disorder. At the core of that diagnosis is the question of whether all chronic opioid use should be labelled as “misuse.” Tapering involves no such diagnosis and focuses on the safety of minimal opioid use, which, when MAT is used appropriately, is also a primary concern.

We appreciate the approach that the authors took in their project and look forward to seeing further iterations.

Bharat Gopal, MD
Cristina Capannolo, DO
Corvallis, Ore

In response to a medication shortage, the Food and Drug Administration has approved a new generic of valsartan (Diovan), produced by Alkem Laboratories, for the treatment of high blood pressure and heart failure, the regulatory agency announced in a statement.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA conducted an investigation into generic angiotensin II receptor blocker (ARB) products following reports of N-nitrosodimethylamine impurities being found in a separate valsartan product in the summer of 2018. Since that time, nitrosamine impurities have been detected in multiple ARBs, and as of March 1, 2019, hundreds of lots of ARBs produced by several companies have been recalled. The FDA has implemented new rules to prevent further contamination, but the ongoing recalls have caused a significant shortage.

“[To] address the public health consequences of these shortages, we’ve prioritized the review of generic applications for these valsartan products,” FDA commissioner Scott Gottlieb, MD, said in the statement.

For the new generic’s approval, the FDA assessed Alkem Laboratories’ manufacturing process and ensured that the company used proper testing methods to rule out the presence of nitrosamine impurities.

“We hope that today’s approval of this new generic will help reduce the valsartan shortage, and we remain committed to implementing measures to prevent the formation of these impurities during drug manufacturing processes for existing and future products,” Dr. Gottlieb said.

lfranki@mdedge.com

In response to a medication shortage, the Food and Drug Administration has approved a new generic of valsartan (Diovan), produced by Alkem Laboratories, for the treatment of high blood pressure and heart failure, the regulatory agency announced in a statement.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA conducted an investigation into generic angiotensin II receptor blocker (ARB) products following reports of N-nitrosodimethylamine impurities being found in a separate valsartan product in the summer of 2018. Since that time, nitrosamine impurities have been detected in multiple ARBs, and as of March 1, 2019, hundreds of lots of ARBs produced by several companies have been recalled. The FDA has implemented new rules to prevent further contamination, but the ongoing recalls have caused a significant shortage.

“[To] address the public health consequences of these shortages, we’ve prioritized the review of generic applications for these valsartan products,” FDA commissioner Scott Gottlieb, MD, said in the statement.

For the new generic’s approval, the FDA assessed Alkem Laboratories’ manufacturing process and ensured that the company used proper testing methods to rule out the presence of nitrosamine impurities.

“We hope that today’s approval of this new generic will help reduce the valsartan shortage, and we remain committed to implementing measures to prevent the formation of these impurities during drug manufacturing processes for existing and future products,” Dr. Gottlieb said.

lfranki@mdedge.com

In response to a medication shortage, the Food and Drug Administration has approved a new generic of valsartan (Diovan), produced by Alkem Laboratories, for the treatment of high blood pressure and heart failure, the regulatory agency announced in a statement.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA conducted an investigation into generic angiotensin II receptor blocker (ARB) products following reports of N-nitrosodimethylamine impurities being found in a separate valsartan product in the summer of 2018. Since that time, nitrosamine impurities have been detected in multiple ARBs, and as of March 1, 2019, hundreds of lots of ARBs produced by several companies have been recalled. The FDA has implemented new rules to prevent further contamination, but the ongoing recalls have caused a significant shortage.

“[To] address the public health consequences of these shortages, we’ve prioritized the review of generic applications for these valsartan products,” FDA commissioner Scott Gottlieb, MD, said in the statement.

For the new generic’s approval, the FDA assessed Alkem Laboratories’ manufacturing process and ensured that the company used proper testing methods to rule out the presence of nitrosamine impurities.

“We hope that today’s approval of this new generic will help reduce the valsartan shortage, and we remain committed to implementing measures to prevent the formation of these impurities during drug manufacturing processes for existing and future products,” Dr. Gottlieb said.

lfranki@mdedge.com

SEATTLE – In HIV-positive pregnant women, an antiretroviral therapy (ART) regimen that included the integrase inhibitor raltegravir (RAL-ART) led to faster viral load (VL) reduction and a greater proportion of women with a VL of less than 200 copies/mL at delivery, compared with patients treated with an efavirenz-based ART (EFV-ART). There were no statistically significant differences between the two arms with respect to percentage of stillbirths, preterm delivery, or rates of HIV infection in the newborn.

MattZ90/Thinkstock.com

“There are lots of advantages of these [integrase inhibitor] drugs, and we’d like to have pregnant women take advantage of them. The problem is, there’s no requirement of drug manufacturers to study the drugs in pregnancy. So these studies are put off until after the drug is licensed, and we’re playing catch-up,” Mark Mirochnick, MD, professor of pediatrics at Boston University, said in an interview. Dr. Mirochnick presented the results at the Conference on Retroviruses and Opportunistic Infections.

Another integrase inhibitor, dolutegravir, has a better resistance profile than that of raltegravir, but concerns over neural tube defects observed during a study in Botswana led both the Food and Drug Administration and the European Medicines Agency to issue safety warnings for that drug. The current study did not raise concern, since it began at 20 weeks’ gestation, well after the period when neural tube defects might occur. “I think it just demonstrates that [integrase inhibitors] are safe in mid- to late-pregnancy,” said Dr. Mirochnick.

It remains to be seen whether a potential link to neural tube defects, if it is a real effect, is due to a specific drug or the mechanism of action of integrase inhibitors more generally. “It’s a question we don’t have an answer to. So you have to balance the potential benefits and potential risks, and that’s probably a decision best made by an individual woman and her care provider. Some women do very well on a particular regimen and they don’t want to change, and you run the risk when you change that you’ll get a viral rebound. What do you tell women who are on dolutegravir and are thinking about becoming pregnant? That’s a controversial question. There are risks with both courses,” said Dr. Mirochnick.

The study comprised 408 patients recruited from centers in Brazil, Tanzania, South Africa, Thailand, Argentina, and the United States. The patients were between 20 and 37 weeks’ gestation and had not previously received ART. They were randomized to RAL-ART or EFV-ART. About 12% of patients were Asian, 36% were black, 52% were Hispanic, and 1% were white.

Overall, 94% of patients on RAL-ART had a VL less than 200 copies/mL at delivery, compared to 84% of EFV-ART patients (P = .001). The effect appeared to be driven by patients who enrolled later in pregnancy: There was no significant difference in those enrolled in weeks 20-28, but suppression occurred in 93% of the RAL-ART group versus 71% of the EFV-ART group among those enrolled in weeks 29-37 (P = .04).

Tolerability was slightly better in the RAL-ART group, with 99% versus 97% of patients staying on their assigned therapy (P = .05). In both groups, 30% of women experienced an adverse event of grade 3 or higher, as did 25% of live-born infants in both groups.

A total of 92% of women in the RAL-ART group had a sustained VL response through delivery, compared with 64% in the EFV-ART group (P less than .001). The median time to achieving a VL less than 200 copies/mL was 8 days in the RAL-ART group and 15 days in the EFV-ART group (generalized log-rank test P less than .001).

There was one stillbirth in the EFV-ART arm and three in the RAL-ART arm, with 11% in the EFV-ART group having preterm delivery compared with 12% in the RAL-ART group. In addition, the proportion of HIV-infected infants was lower in the RAL-ART arm (1% versus 3%). These differences were not significant.

The National Institutes of Health funded the study. Glaxo/ViiV, Merck, and Bristol-Myers Squibb supplied study drugs. Dr. Mirochnick has received research funding from those companies.

SOURCE: Mark Mirochnick et al. CROI 2019, Abstract 39 LB.

SEATTLE – In HIV-positive pregnant women, an antiretroviral therapy (ART) regimen that included the integrase inhibitor raltegravir (RAL-ART) led to faster viral load (VL) reduction and a greater proportion of women with a VL of less than 200 copies/mL at delivery, compared with patients treated with an efavirenz-based ART (EFV-ART). There were no statistically significant differences between the two arms with respect to percentage of stillbirths, preterm delivery, or rates of HIV infection in the newborn.

MattZ90/Thinkstock.com

“There are lots of advantages of these [integrase inhibitor] drugs, and we’d like to have pregnant women take advantage of them. The problem is, there’s no requirement of drug manufacturers to study the drugs in pregnancy. So these studies are put off until after the drug is licensed, and we’re playing catch-up,” Mark Mirochnick, MD, professor of pediatrics at Boston University, said in an interview. Dr. Mirochnick presented the results at the Conference on Retroviruses and Opportunistic Infections.

Another integrase inhibitor, dolutegravir, has a better resistance profile than that of raltegravir, but concerns over neural tube defects observed during a study in Botswana led both the Food and Drug Administration and the European Medicines Agency to issue safety warnings for that drug. The current study did not raise concern, since it began at 20 weeks’ gestation, well after the period when neural tube defects might occur. “I think it just demonstrates that [integrase inhibitors] are safe in mid- to late-pregnancy,” said Dr. Mirochnick.

It remains to be seen whether a potential link to neural tube defects, if it is a real effect, is due to a specific drug or the mechanism of action of integrase inhibitors more generally. “It’s a question we don’t have an answer to. So you have to balance the potential benefits and potential risks, and that’s probably a decision best made by an individual woman and her care provider. Some women do very well on a particular regimen and they don’t want to change, and you run the risk when you change that you’ll get a viral rebound. What do you tell women who are on dolutegravir and are thinking about becoming pregnant? That’s a controversial question. There are risks with both courses,” said Dr. Mirochnick.

The study comprised 408 patients recruited from centers in Brazil, Tanzania, South Africa, Thailand, Argentina, and the United States. The patients were between 20 and 37 weeks’ gestation and had not previously received ART. They were randomized to RAL-ART or EFV-ART. About 12% of patients were Asian, 36% were black, 52% were Hispanic, and 1% were white.

Overall, 94% of patients on RAL-ART had a VL less than 200 copies/mL at delivery, compared to 84% of EFV-ART patients (P = .001). The effect appeared to be driven by patients who enrolled later in pregnancy: There was no significant difference in those enrolled in weeks 20-28, but suppression occurred in 93% of the RAL-ART group versus 71% of the EFV-ART group among those enrolled in weeks 29-37 (P = .04).

Tolerability was slightly better in the RAL-ART group, with 99% versus 97% of patients staying on their assigned therapy (P = .05). In both groups, 30% of women experienced an adverse event of grade 3 or higher, as did 25% of live-born infants in both groups.

A total of 92% of women in the RAL-ART group had a sustained VL response through delivery, compared with 64% in the EFV-ART group (P less than .001). The median time to achieving a VL less than 200 copies/mL was 8 days in the RAL-ART group and 15 days in the EFV-ART group (generalized log-rank test P less than .001).

There was one stillbirth in the EFV-ART arm and three in the RAL-ART arm, with 11% in the EFV-ART group having preterm delivery compared with 12% in the RAL-ART group. In addition, the proportion of HIV-infected infants was lower in the RAL-ART arm (1% versus 3%). These differences were not significant.

The National Institutes of Health funded the study. Glaxo/ViiV, Merck, and Bristol-Myers Squibb supplied study drugs. Dr. Mirochnick has received research funding from those companies.

SOURCE: Mark Mirochnick et al. CROI 2019, Abstract 39 LB.

SEATTLE – In HIV-positive pregnant women, an antiretroviral therapy (ART) regimen that included the integrase inhibitor raltegravir (RAL-ART) led to faster viral load (VL) reduction and a greater proportion of women with a VL of less than 200 copies/mL at delivery, compared with patients treated with an efavirenz-based ART (EFV-ART). There were no statistically significant differences between the two arms with respect to percentage of stillbirths, preterm delivery, or rates of HIV infection in the newborn.

MattZ90/Thinkstock.com

“There are lots of advantages of these [integrase inhibitor] drugs, and we’d like to have pregnant women take advantage of them. The problem is, there’s no requirement of drug manufacturers to study the drugs in pregnancy. So these studies are put off until after the drug is licensed, and we’re playing catch-up,” Mark Mirochnick, MD, professor of pediatrics at Boston University, said in an interview. Dr. Mirochnick presented the results at the Conference on Retroviruses and Opportunistic Infections.

Another integrase inhibitor, dolutegravir, has a better resistance profile than that of raltegravir, but concerns over neural tube defects observed during a study in Botswana led both the Food and Drug Administration and the European Medicines Agency to issue safety warnings for that drug. The current study did not raise concern, since it began at 20 weeks’ gestation, well after the period when neural tube defects might occur. “I think it just demonstrates that [integrase inhibitors] are safe in mid- to late-pregnancy,” said Dr. Mirochnick.

It remains to be seen whether a potential link to neural tube defects, if it is a real effect, is due to a specific drug or the mechanism of action of integrase inhibitors more generally. “It’s a question we don’t have an answer to. So you have to balance the potential benefits and potential risks, and that’s probably a decision best made by an individual woman and her care provider. Some women do very well on a particular regimen and they don’t want to change, and you run the risk when you change that you’ll get a viral rebound. What do you tell women who are on dolutegravir and are thinking about becoming pregnant? That’s a controversial question. There are risks with both courses,” said Dr. Mirochnick.

The study comprised 408 patients recruited from centers in Brazil, Tanzania, South Africa, Thailand, Argentina, and the United States. The patients were between 20 and 37 weeks’ gestation and had not previously received ART. They were randomized to RAL-ART or EFV-ART. About 12% of patients were Asian, 36% were black, 52% were Hispanic, and 1% were white.

Overall, 94% of patients on RAL-ART had a VL less than 200 copies/mL at delivery, compared to 84% of EFV-ART patients (P = .001). The effect appeared to be driven by patients who enrolled later in pregnancy: There was no significant difference in those enrolled in weeks 20-28, but suppression occurred in 93% of the RAL-ART group versus 71% of the EFV-ART group among those enrolled in weeks 29-37 (P = .04).

Tolerability was slightly better in the RAL-ART group, with 99% versus 97% of patients staying on their assigned therapy (P = .05). In both groups, 30% of women experienced an adverse event of grade 3 or higher, as did 25% of live-born infants in both groups.

A total of 92% of women in the RAL-ART group had a sustained VL response through delivery, compared with 64% in the EFV-ART group (P less than .001). The median time to achieving a VL less than 200 copies/mL was 8 days in the RAL-ART group and 15 days in the EFV-ART group (generalized log-rank test P less than .001).

There was one stillbirth in the EFV-ART arm and three in the RAL-ART arm, with 11% in the EFV-ART group having preterm delivery compared with 12% in the RAL-ART group. In addition, the proportion of HIV-infected infants was lower in the RAL-ART arm (1% versus 3%). These differences were not significant.

The National Institutes of Health funded the study. Glaxo/ViiV, Merck, and Bristol-Myers Squibb supplied study drugs. Dr. Mirochnick has received research funding from those companies.

SOURCE: Mark Mirochnick et al. CROI 2019, Abstract 39 LB.

In his guest editorial, “Upending this country’s approach to health care” (J Fam Pract. 2018;67:744-745), T. R. Reid makes a number of good points. However, I disagree with his opinion that “This disgraceful state of affairs is not the fault of the nation’s physicians. Rather, the problems with health care in the United States stem from the system that American providers have to work in.”

Through our choices, we have helped create this current system. I started as a family practice attending physician in 1994 and worked in 2 community hospitals. One of these hospitals closed its doors in 2012 and the other merged with a large health care system in 2015. During my 25 years of practice, I watched all of my outstanding primary care colleagues (family medicine, internal medicine, and pediatrics; 25 to 30 in total) stop their practice of combined outpatient and inpatient work. I currently do not see any primary care physicians (who do outpatient work) during my hospital patient care. Yes, it’s lonely.

I believe this significant change in practice across the United States has led to unintended consequences. First, the administrative burdens (and likely costs) for hospitals and health care systems have risen. Newborn, pediatric, and adult hospitalist services had to be built or bolstered, and then maintained, and the growing number of employed physicians had to be managed. Second, primary care’s attractiveness to some medical students has declined. Should students want a practice where they will likely never take care of their patients in the office and the hospital?

I agree we have a “disgraceful state of affairs,” and we need to work together for the tough solutions. However, as health care leaders, we must take responsibility for our roles in creating the current system. We must acknowledge these roles and learn from them.  

Chris Noah, MD
Middleville, Mich

As a longtime family medicine practitioner, I can’t agree more with Mr. Reid’s assessments of the state of our health care system. I have experienced health care from my practice as part of an HMO in Wisconsin, and in a hospital system in Raleigh, NC. Our “system” has done such a poor job of allocating its resources and has sacrificed so much to generate profit for the insurance and pharmaceutical corporations. The question is: How do we develop the political will to overcome these deep pockets to change the system? Victor Fuch’s article in the November issue of JAMA makes a very compelling case for a national health plan.¹

Jeff Keil, MD
Cary, NC

In his guest editorial, “Upending this country’s approach to health care” (J Fam Pract. 2018;67:744-745), T. R. Reid makes a number of good points. However, I disagree with his opinion that “This disgraceful state of affairs is not the fault of the nation’s physicians. Rather, the problems with health care in the United States stem from the system that American providers have to work in.”

Through our choices, we have helped create this current system. I started as a family practice attending physician in 1994 and worked in 2 community hospitals. One of these hospitals closed its doors in 2012 and the other merged with a large health care system in 2015. During my 25 years of practice, I watched all of my outstanding primary care colleagues (family medicine, internal medicine, and pediatrics; 25 to 30 in total) stop their practice of combined outpatient and inpatient work. I currently do not see any primary care physicians (who do outpatient work) during my hospital patient care. Yes, it’s lonely.

I believe this significant change in practice across the United States has led to unintended consequences. First, the administrative burdens (and likely costs) for hospitals and health care systems have risen. Newborn, pediatric, and adult hospitalist services had to be built or bolstered, and then maintained, and the growing number of employed physicians had to be managed. Second, primary care’s attractiveness to some medical students has declined. Should students want a practice where they will likely never take care of their patients in the office and the hospital?

I agree we have a “disgraceful state of affairs,” and we need to work together for the tough solutions. However, as health care leaders, we must take responsibility for our roles in creating the current system. We must acknowledge these roles and learn from them.  

Chris Noah, MD
Middleville, Mich

As a longtime family medicine practitioner, I can’t agree more with Mr. Reid’s assessments of the state of our health care system. I have experienced health care from my practice as part of an HMO in Wisconsin, and in a hospital system in Raleigh, NC. Our “system” has done such a poor job of allocating its resources and has sacrificed so much to generate profit for the insurance and pharmaceutical corporations. The question is: How do we develop the political will to overcome these deep pockets to change the system? Victor Fuch’s article in the November issue of JAMA makes a very compelling case for a national health plan.¹

Jeff Keil, MD
Cary, NC

In his guest editorial, “Upending this country’s approach to health care” (J Fam Pract. 2018;67:744-745), T. R. Reid makes a number of good points. However, I disagree with his opinion that “This disgraceful state of affairs is not the fault of the nation’s physicians. Rather, the problems with health care in the United States stem from the system that American providers have to work in.”

Through our choices, we have helped create this current system. I started as a family practice attending physician in 1994 and worked in 2 community hospitals. One of these hospitals closed its doors in 2012 and the other merged with a large health care system in 2015. During my 25 years of practice, I watched all of my outstanding primary care colleagues (family medicine, internal medicine, and pediatrics; 25 to 30 in total) stop their practice of combined outpatient and inpatient work. I currently do not see any primary care physicians (who do outpatient work) during my hospital patient care. Yes, it’s lonely.

I believe this significant change in practice across the United States has led to unintended consequences. First, the administrative burdens (and likely costs) for hospitals and health care systems have risen. Newborn, pediatric, and adult hospitalist services had to be built or bolstered, and then maintained, and the growing number of employed physicians had to be managed. Second, primary care’s attractiveness to some medical students has declined. Should students want a practice where they will likely never take care of their patients in the office and the hospital?

I agree we have a “disgraceful state of affairs,” and we need to work together for the tough solutions. However, as health care leaders, we must take responsibility for our roles in creating the current system. We must acknowledge these roles and learn from them.  

Chris Noah, MD
Middleville, Mich

As a longtime family medicine practitioner, I can’t agree more with Mr. Reid’s assessments of the state of our health care system. I have experienced health care from my practice as part of an HMO in Wisconsin, and in a hospital system in Raleigh, NC. Our “system” has done such a poor job of allocating its resources and has sacrificed so much to generate profit for the insurance and pharmaceutical corporations. The question is: How do we develop the political will to overcome these deep pockets to change the system? Victor Fuch’s article in the November issue of JAMA makes a very compelling case for a national health plan.¹

Jeff Keil, MD
Cary, NC

An all-oral, three-drug regimen may be a treatment option for relapsed or refractory multiple myeloma, according to researchers.

Courtesy Wikimedia Commons/KGH/Creative Commons License

The regimen – clarithromycin, pomalidomide, and dexamethasone (ClaPd) – produced an overall response rate (ORR) of 60% in a phase 2 trial of patients with relapsed/refractory multiple myeloma (RRMM). Response rates were similar whether patients were refractory to lenalidomide, bortezomib, or both drugs.

The most common adverse events (AEs) in this trial were hematologic toxicities.

Tomer M. Mark, MD, of the University of Colorado at Denver, Aurora, and his colleagues, reported these results in Blood Advances.

The trial (NCT01159574) included 120 patients with RRMM. They had a median age of 63 years (range, 42-87 years) and were a median of 4.6 years (range, 0.8-21.2 years) from diagnosis at baseline.

The patients had received a median of 5 (range, 3-15) prior lines of therapy. Most patients were refractory to lenalidomide (n = 101), bortezomib (n = 94), or both (n = 81).

The ClaPd regimen consisted of clarithromycin given at 500 mg twice daily, pomalidomide at 4 mg on days 1-21, and dexamethasone at 40 mg on days 1, 8, 15, and 22 of a 28-day cycle. The patients received ClaPd until intolerance or disease progression. In addition to ClaPd, patients received thromboprophylaxis (aspirin at 81 mg daily) and Pneumocystis jiroveci prophylaxis (trimethoprim-sulfamethoxazole or an alternative).

The toxicities were manageable, with low rates of nonhematologic and high-grade events, according to the researchers. The most common grade 3 or higher AEs were lymphopenia (60%), neutropenia (58%), leukopenia (34%), thrombocytopenia (31%), and anemia (28%).

Among all evaluable patients, the ORR was 60% (70/117). One patient had a complete response, 6 had a stringent complete response, 20 had a very good partial response, and 43 had a partial response.

ORRs were similar whether patients were refractory to bortezomib, lenalidomide, or both. The ORR was 58% (n = 59) among lenalidomide-refractory patients, 55% (n = 52) among bortezomib-refractory patients, and 54% (n = 44) among double-refractory patients.

For the entire cohort, the median progression-free survival was 7.7 months and the median overall survival was 19.2 months.

In a multivariate analysis, there were two factors significantly associated with inferior overall survival – having a revised International Staging System score greater than 1 (hazard ratio, 2.75; P = .044) and having at least 5% of CD138 cells positive for Ki67 on immunohistochemistry (hazard ratio, 1.84, P = .030).

“The ClaPd regimen demonstrated high rates of overall response and significant duration of disease control in a heavily pretreated RRMM population while maintaining a toxicity profile similar to Pom-dex [pomalidone-dexamethasone] alone,” Dr. Mark and his colleagues wrote. “The clinical efficacy advantage of adding clarithromycin to Pom-dex should be explored further in a phase 3 clinical trial.”

This research was supported by Celgene; the Myeloma Center at Weill Cornell Medicine, New York; and a grant from the National Institutes of Health. Dr. Mark reported relationships with Amgen, Takeda, Celgene, and Janssen. Other study authors reported relationships with Celgene, Takeda, and Onyx Pharmaceuticals.

jensmith@mdedge.com

SOURCE: Mark TM et al. Blood Adv. 2019 Feb 26;3(4):603-11.

An all-oral, three-drug regimen may be a treatment option for relapsed or refractory multiple myeloma, according to researchers.

Courtesy Wikimedia Commons/KGH/Creative Commons License

The regimen – clarithromycin, pomalidomide, and dexamethasone (ClaPd) – produced an overall response rate (ORR) of 60% in a phase 2 trial of patients with relapsed/refractory multiple myeloma (RRMM). Response rates were similar whether patients were refractory to lenalidomide, bortezomib, or both drugs.

The most common adverse events (AEs) in this trial were hematologic toxicities.

Tomer M. Mark, MD, of the University of Colorado at Denver, Aurora, and his colleagues, reported these results in Blood Advances.

The trial (NCT01159574) included 120 patients with RRMM. They had a median age of 63 years (range, 42-87 years) and were a median of 4.6 years (range, 0.8-21.2 years) from diagnosis at baseline.

The patients had received a median of 5 (range, 3-15) prior lines of therapy. Most patients were refractory to lenalidomide (n = 101), bortezomib (n = 94), or both (n = 81).

The ClaPd regimen consisted of clarithromycin given at 500 mg twice daily, pomalidomide at 4 mg on days 1-21, and dexamethasone at 40 mg on days 1, 8, 15, and 22 of a 28-day cycle. The patients received ClaPd until intolerance or disease progression. In addition to ClaPd, patients received thromboprophylaxis (aspirin at 81 mg daily) and Pneumocystis jiroveci prophylaxis (trimethoprim-sulfamethoxazole or an alternative).

The toxicities were manageable, with low rates of nonhematologic and high-grade events, according to the researchers. The most common grade 3 or higher AEs were lymphopenia (60%), neutropenia (58%), leukopenia (34%), thrombocytopenia (31%), and anemia (28%).

Among all evaluable patients, the ORR was 60% (70/117). One patient had a complete response, 6 had a stringent complete response, 20 had a very good partial response, and 43 had a partial response.

ORRs were similar whether patients were refractory to bortezomib, lenalidomide, or both. The ORR was 58% (n = 59) among lenalidomide-refractory patients, 55% (n = 52) among bortezomib-refractory patients, and 54% (n = 44) among double-refractory patients.

For the entire cohort, the median progression-free survival was 7.7 months and the median overall survival was 19.2 months.

In a multivariate analysis, there were two factors significantly associated with inferior overall survival – having a revised International Staging System score greater than 1 (hazard ratio, 2.75; P = .044) and having at least 5% of CD138 cells positive for Ki67 on immunohistochemistry (hazard ratio, 1.84, P = .030).

“The ClaPd regimen demonstrated high rates of overall response and significant duration of disease control in a heavily pretreated RRMM population while maintaining a toxicity profile similar to Pom-dex [pomalidone-dexamethasone] alone,” Dr. Mark and his colleagues wrote. “The clinical efficacy advantage of adding clarithromycin to Pom-dex should be explored further in a phase 3 clinical trial.”

This research was supported by Celgene; the Myeloma Center at Weill Cornell Medicine, New York; and a grant from the National Institutes of Health. Dr. Mark reported relationships with Amgen, Takeda, Celgene, and Janssen. Other study authors reported relationships with Celgene, Takeda, and Onyx Pharmaceuticals.

jensmith@mdedge.com

SOURCE: Mark TM et al. Blood Adv. 2019 Feb 26;3(4):603-11.

An all-oral, three-drug regimen may be a treatment option for relapsed or refractory multiple myeloma, according to researchers.

Courtesy Wikimedia Commons/KGH/Creative Commons License

The regimen – clarithromycin, pomalidomide, and dexamethasone (ClaPd) – produced an overall response rate (ORR) of 60% in a phase 2 trial of patients with relapsed/refractory multiple myeloma (RRMM). Response rates were similar whether patients were refractory to lenalidomide, bortezomib, or both drugs.

The most common adverse events (AEs) in this trial were hematologic toxicities.

Tomer M. Mark, MD, of the University of Colorado at Denver, Aurora, and his colleagues, reported these results in Blood Advances.

The trial (NCT01159574) included 120 patients with RRMM. They had a median age of 63 years (range, 42-87 years) and were a median of 4.6 years (range, 0.8-21.2 years) from diagnosis at baseline.

The patients had received a median of 5 (range, 3-15) prior lines of therapy. Most patients were refractory to lenalidomide (n = 101), bortezomib (n = 94), or both (n = 81).

The ClaPd regimen consisted of clarithromycin given at 500 mg twice daily, pomalidomide at 4 mg on days 1-21, and dexamethasone at 40 mg on days 1, 8, 15, and 22 of a 28-day cycle. The patients received ClaPd until intolerance or disease progression. In addition to ClaPd, patients received thromboprophylaxis (aspirin at 81 mg daily) and Pneumocystis jiroveci prophylaxis (trimethoprim-sulfamethoxazole or an alternative).

The toxicities were manageable, with low rates of nonhematologic and high-grade events, according to the researchers. The most common grade 3 or higher AEs were lymphopenia (60%), neutropenia (58%), leukopenia (34%), thrombocytopenia (31%), and anemia (28%).

Among all evaluable patients, the ORR was 60% (70/117). One patient had a complete response, 6 had a stringent complete response, 20 had a very good partial response, and 43 had a partial response.

ORRs were similar whether patients were refractory to bortezomib, lenalidomide, or both. The ORR was 58% (n = 59) among lenalidomide-refractory patients, 55% (n = 52) among bortezomib-refractory patients, and 54% (n = 44) among double-refractory patients.

For the entire cohort, the median progression-free survival was 7.7 months and the median overall survival was 19.2 months.

In a multivariate analysis, there were two factors significantly associated with inferior overall survival – having a revised International Staging System score greater than 1 (hazard ratio, 2.75; P = .044) and having at least 5% of CD138 cells positive for Ki67 on immunohistochemistry (hazard ratio, 1.84, P = .030).

“The ClaPd regimen demonstrated high rates of overall response and significant duration of disease control in a heavily pretreated RRMM population while maintaining a toxicity profile similar to Pom-dex [pomalidone-dexamethasone] alone,” Dr. Mark and his colleagues wrote. “The clinical efficacy advantage of adding clarithromycin to Pom-dex should be explored further in a phase 3 clinical trial.”

This research was supported by Celgene; the Myeloma Center at Weill Cornell Medicine, New York; and a grant from the National Institutes of Health. Dr. Mark reported relationships with Amgen, Takeda, Celgene, and Janssen. Other study authors reported relationships with Celgene, Takeda, and Onyx Pharmaceuticals.

jensmith@mdedge.com

SOURCE: Mark TM et al. Blood Adv. 2019 Feb 26;3(4):603-11.

Testosterone therapy can be personalized for transgender men who begin to develop acne during masculinizing hormone treatment, but patient compatibility will depend upon several factors, advised Jason A. Park and his associates in a research letter to the editor of the Journal of the American Academy of Dermatology.

In a multivariate logistic regression analysis, Mr. Park and his colleagues at Boston University sought to determine the timing of onset of acne in female-to-male transgender patients.

A total of 55 patients undergoing hormone therapy at the Center for Transgender Medicine and Surgery at Boston Medical Center between January 1, 2010, and December 31, 2017 were selected following a systematic chart review. Patients were excluded who were under the age of 18 years, who had been receiving testosterone therapy for less than 2 years, who presented with acne before start of treatment, or whose medical records were incomplete.

Given evidence in prior studies reporting on an association between elevated androgen levels and increased incidence of acne in this patient group, a median serum testosterone level of 630 ng/dL “was used to differentiate between higher and lower levels.”

Acne was found to develop in 9% of transgender men after 3 months and in 18% after 6 months; 38% of the subjects were found to have developed acne at some point during the study after 24 months of treatment. The authors found that acne was “significantly associated with serum testosterone levels higher than 630 ng/dL.” Increased body mass index (BMI), especially in those with positive smoking status, also was associated with an increased incidence of acne, the authors said.

According to several existing studies, transgender men undergoing testosterone therapy tend to develop increased sebum production and acne. Because the systemic and dermatologic virilization effects of testosterone are unpredictable once treatment has started, and because individual goals also are varied (from maximum virilization to only suppressing feminine secondary sex characteristics), Mr. Park and his colleagues suggested that customization may be ideal, provided they do not clash with individual patient transition goals, priorities, risk factors, and other comorbidities that may be present.

The study was funded by the Medical Student Summer Research Program at Boston University. The authors had no conflicts of interest to report.

SOURCE: Park JA et al. J Am Acad Dermatol. 2019. doi: 10.1016/j.jaad.2018.12.040.

Testosterone therapy can be personalized for transgender men who begin to develop acne during masculinizing hormone treatment, but patient compatibility will depend upon several factors, advised Jason A. Park and his associates in a research letter to the editor of the Journal of the American Academy of Dermatology.

In a multivariate logistic regression analysis, Mr. Park and his colleagues at Boston University sought to determine the timing of onset of acne in female-to-male transgender patients.

A total of 55 patients undergoing hormone therapy at the Center for Transgender Medicine and Surgery at Boston Medical Center between January 1, 2010, and December 31, 2017 were selected following a systematic chart review. Patients were excluded who were under the age of 18 years, who had been receiving testosterone therapy for less than 2 years, who presented with acne before start of treatment, or whose medical records were incomplete.

Given evidence in prior studies reporting on an association between elevated androgen levels and increased incidence of acne in this patient group, a median serum testosterone level of 630 ng/dL “was used to differentiate between higher and lower levels.”

Acne was found to develop in 9% of transgender men after 3 months and in 18% after 6 months; 38% of the subjects were found to have developed acne at some point during the study after 24 months of treatment. The authors found that acne was “significantly associated with serum testosterone levels higher than 630 ng/dL.” Increased body mass index (BMI), especially in those with positive smoking status, also was associated with an increased incidence of acne, the authors said.

According to several existing studies, transgender men undergoing testosterone therapy tend to develop increased sebum production and acne. Because the systemic and dermatologic virilization effects of testosterone are unpredictable once treatment has started, and because individual goals also are varied (from maximum virilization to only suppressing feminine secondary sex characteristics), Mr. Park and his colleagues suggested that customization may be ideal, provided they do not clash with individual patient transition goals, priorities, risk factors, and other comorbidities that may be present.

The study was funded by the Medical Student Summer Research Program at Boston University. The authors had no conflicts of interest to report.

SOURCE: Park JA et al. J Am Acad Dermatol. 2019. doi: 10.1016/j.jaad.2018.12.040.

Testosterone therapy can be personalized for transgender men who begin to develop acne during masculinizing hormone treatment, but patient compatibility will depend upon several factors, advised Jason A. Park and his associates in a research letter to the editor of the Journal of the American Academy of Dermatology.

In a multivariate logistic regression analysis, Mr. Park and his colleagues at Boston University sought to determine the timing of onset of acne in female-to-male transgender patients.

A total of 55 patients undergoing hormone therapy at the Center for Transgender Medicine and Surgery at Boston Medical Center between January 1, 2010, and December 31, 2017 were selected following a systematic chart review. Patients were excluded who were under the age of 18 years, who had been receiving testosterone therapy for less than 2 years, who presented with acne before start of treatment, or whose medical records were incomplete.

Given evidence in prior studies reporting on an association between elevated androgen levels and increased incidence of acne in this patient group, a median serum testosterone level of 630 ng/dL “was used to differentiate between higher and lower levels.”

Acne was found to develop in 9% of transgender men after 3 months and in 18% after 6 months; 38% of the subjects were found to have developed acne at some point during the study after 24 months of treatment. The authors found that acne was “significantly associated with serum testosterone levels higher than 630 ng/dL.” Increased body mass index (BMI), especially in those with positive smoking status, also was associated with an increased incidence of acne, the authors said.

According to several existing studies, transgender men undergoing testosterone therapy tend to develop increased sebum production and acne. Because the systemic and dermatologic virilization effects of testosterone are unpredictable once treatment has started, and because individual goals also are varied (from maximum virilization to only suppressing feminine secondary sex characteristics), Mr. Park and his colleagues suggested that customization may be ideal, provided they do not clash with individual patient transition goals, priorities, risk factors, and other comorbidities that may be present.

The study was funded by the Medical Student Summer Research Program at Boston University. The authors had no conflicts of interest to report.

SOURCE: Park JA et al. J Am Acad Dermatol. 2019. doi: 10.1016/j.jaad.2018.12.040.