NATIONAL HARBOR, MD. – Maintenance therapy with the first-in-class PARP inhibitor olaparib was associated with a striking improvement in progression-free survival in patients with platinum-sensitive relapsed ovarian cancer and BRCA 1/2 mutation in the randomized, placebo-controlled phase III SOLO2 trial.

Compared with placebo, the tablet formulation of olaparib was associated with investigator-assessed PFS of 19.1 months in 196 patients, compared with 5.5 months in 99 patients who received placebo (hazard ratio, 0.30), Dr. Eric Pujade-Lauraine reported at the annual meeting of the Society of Gynecologic Oncology.

The SOLO2 results were both clinically meaningful and highly statistically significant, said Dr. Pujade-Lauraine of Hopital Hotel-Dieu, Paris.

Active treatment, which involved a twice-daily 300-mg oral dose of olaparib, was well tolerated; 75% of patients completed the study without dose reduction, he noted.

In this video interview, Dr. Pujade-Lauraine discussed the SOLO2 study and findings, which confirmed those of the phase II Study 19. Study 19 looked at olaparib in all-comers with platinum-sensitive relapsed ovarian cancer and involved a different formulation of the drug, which required that patients take 16 capsules each day to achieve a twice-daily dose of 400 mg. Patients with BRCA mutations were found in that study to derive the most benefit from olaparib.

The current findings are practice changing, Dr. Pujade-Lauraine said, concluding that “it is important to test BRCA, and if this test is positive, to offer olaparib in patients who are platinum sensitive.”

[email protected]

NATIONAL HARBOR, MD. – Maintenance therapy with the first-in-class PARP inhibitor olaparib was associated with a striking improvement in progression-free survival in patients with platinum-sensitive relapsed ovarian cancer and BRCA 1/2 mutation in the randomized, placebo-controlled phase III SOLO2 trial.

Compared with placebo, the tablet formulation of olaparib was associated with investigator-assessed PFS of 19.1 months in 196 patients, compared with 5.5 months in 99 patients who received placebo (hazard ratio, 0.30), Dr. Eric Pujade-Lauraine reported at the annual meeting of the Society of Gynecologic Oncology.

The SOLO2 results were both clinically meaningful and highly statistically significant, said Dr. Pujade-Lauraine of Hopital Hotel-Dieu, Paris.

Active treatment, which involved a twice-daily 300-mg oral dose of olaparib, was well tolerated; 75% of patients completed the study without dose reduction, he noted.

In this video interview, Dr. Pujade-Lauraine discussed the SOLO2 study and findings, which confirmed those of the phase II Study 19. Study 19 looked at olaparib in all-comers with platinum-sensitive relapsed ovarian cancer and involved a different formulation of the drug, which required that patients take 16 capsules each day to achieve a twice-daily dose of 400 mg. Patients with BRCA mutations were found in that study to derive the most benefit from olaparib.

The current findings are practice changing, Dr. Pujade-Lauraine said, concluding that “it is important to test BRCA, and if this test is positive, to offer olaparib in patients who are platinum sensitive.”

[email protected]

NATIONAL HARBOR, MD. – Maintenance therapy with the first-in-class PARP inhibitor olaparib was associated with a striking improvement in progression-free survival in patients with platinum-sensitive relapsed ovarian cancer and BRCA 1/2 mutation in the randomized, placebo-controlled phase III SOLO2 trial.

Compared with placebo, the tablet formulation of olaparib was associated with investigator-assessed PFS of 19.1 months in 196 patients, compared with 5.5 months in 99 patients who received placebo (hazard ratio, 0.30), Dr. Eric Pujade-Lauraine reported at the annual meeting of the Society of Gynecologic Oncology.

The SOLO2 results were both clinically meaningful and highly statistically significant, said Dr. Pujade-Lauraine of Hopital Hotel-Dieu, Paris.

Active treatment, which involved a twice-daily 300-mg oral dose of olaparib, was well tolerated; 75% of patients completed the study without dose reduction, he noted.

In this video interview, Dr. Pujade-Lauraine discussed the SOLO2 study and findings, which confirmed those of the phase II Study 19. Study 19 looked at olaparib in all-comers with platinum-sensitive relapsed ovarian cancer and involved a different formulation of the drug, which required that patients take 16 capsules each day to achieve a twice-daily dose of 400 mg. Patients with BRCA mutations were found in that study to derive the most benefit from olaparib.

The current findings are practice changing, Dr. Pujade-Lauraine said, concluding that “it is important to test BRCA, and if this test is positive, to offer olaparib in patients who are platinum sensitive.”

[email protected]

NATIONAL HARBOR, MD. – A large retrospective database study linked the use of vaginal brachytherapy and chemotherapy with improved survival among patients with early-stage uterine papillary serous carcinoma.

The findings offer a degree of clinical guidance on the adjuvant treatment of this relatively rare, aggressive histologic cancer subtype, Stephanie Cham, MD, said during a video interview at the annual meeting of the Society of Gynecologic Oncology.

Large dataset analyses can be especially helpful for exploring the treatment of rare diseases for which clinical trials can be infeasible, said Dr. Cham of Columbia University College of Physicians and Surgeons in New York. To evaluate chemotherapy, vaginal brachytherapy, and whole beam pelvic radiation therapy in stage I and stage II uterine papillary serous carcinoma, she and her associates analyzed the National Cancer Database.

Among 7,325 patients treated between 1998 and 2012, 38% of patients had received chemotherapy, 18% had received external beam radiation, and 20% received brachytherapy, Dr. Cham said. The use of chemotherapy rose significantly over time, regardless of stage (P less than .0001), as did the use of brachytherapy, while the use of external beam radiation decreased.

After the researchers controlled for numerous demographic and clinical variables, chemotherapy was associated with a statistically significant decrease in the risk of death overall (hazard ratio, 0.78; 95% confidence interval, 0.69 to 0.88) and in patients with stage IB (HR, 0.58; 95% CI, 0.44-0.77) or stage II cancer (HR, 0.74; 95% CI, 0.60-0.90). The use of brachytherapy also was associated with significantly improved survival overall (HR, 0.67), in stage IA cancer (HR, 0.67), and in stage II cancer (HR, 0.64).

The survival effect of brachytherapy held up in additional subgroup analyses, Dr. Cham explained. In contrast, external beam radiation therapy was not associated with improved survival overall or in any subgroup, she said. The results highlight the potential use of vaginal brachytherapy in early-stage uterine papillary serous carcinoma, she emphasized.

Dr. Cham cited no funding sources and reported having no conflicts of interest.

NATIONAL HARBOR, MD. – A large retrospective database study linked the use of vaginal brachytherapy and chemotherapy with improved survival among patients with early-stage uterine papillary serous carcinoma.

The findings offer a degree of clinical guidance on the adjuvant treatment of this relatively rare, aggressive histologic cancer subtype, Stephanie Cham, MD, said during a video interview at the annual meeting of the Society of Gynecologic Oncology.

Large dataset analyses can be especially helpful for exploring the treatment of rare diseases for which clinical trials can be infeasible, said Dr. Cham of Columbia University College of Physicians and Surgeons in New York. To evaluate chemotherapy, vaginal brachytherapy, and whole beam pelvic radiation therapy in stage I and stage II uterine papillary serous carcinoma, she and her associates analyzed the National Cancer Database.

Among 7,325 patients treated between 1998 and 2012, 38% of patients had received chemotherapy, 18% had received external beam radiation, and 20% received brachytherapy, Dr. Cham said. The use of chemotherapy rose significantly over time, regardless of stage (P less than .0001), as did the use of brachytherapy, while the use of external beam radiation decreased.

After the researchers controlled for numerous demographic and clinical variables, chemotherapy was associated with a statistically significant decrease in the risk of death overall (hazard ratio, 0.78; 95% confidence interval, 0.69 to 0.88) and in patients with stage IB (HR, 0.58; 95% CI, 0.44-0.77) or stage II cancer (HR, 0.74; 95% CI, 0.60-0.90). The use of brachytherapy also was associated with significantly improved survival overall (HR, 0.67), in stage IA cancer (HR, 0.67), and in stage II cancer (HR, 0.64).

The survival effect of brachytherapy held up in additional subgroup analyses, Dr. Cham explained. In contrast, external beam radiation therapy was not associated with improved survival overall or in any subgroup, she said. The results highlight the potential use of vaginal brachytherapy in early-stage uterine papillary serous carcinoma, she emphasized.

Dr. Cham cited no funding sources and reported having no conflicts of interest.

NATIONAL HARBOR, MD. – A large retrospective database study linked the use of vaginal brachytherapy and chemotherapy with improved survival among patients with early-stage uterine papillary serous carcinoma.

The findings offer a degree of clinical guidance on the adjuvant treatment of this relatively rare, aggressive histologic cancer subtype, Stephanie Cham, MD, said during a video interview at the annual meeting of the Society of Gynecologic Oncology.

Large dataset analyses can be especially helpful for exploring the treatment of rare diseases for which clinical trials can be infeasible, said Dr. Cham of Columbia University College of Physicians and Surgeons in New York. To evaluate chemotherapy, vaginal brachytherapy, and whole beam pelvic radiation therapy in stage I and stage II uterine papillary serous carcinoma, she and her associates analyzed the National Cancer Database.

Among 7,325 patients treated between 1998 and 2012, 38% of patients had received chemotherapy, 18% had received external beam radiation, and 20% received brachytherapy, Dr. Cham said. The use of chemotherapy rose significantly over time, regardless of stage (P less than .0001), as did the use of brachytherapy, while the use of external beam radiation decreased.

After the researchers controlled for numerous demographic and clinical variables, chemotherapy was associated with a statistically significant decrease in the risk of death overall (hazard ratio, 0.78; 95% confidence interval, 0.69 to 0.88) and in patients with stage IB (HR, 0.58; 95% CI, 0.44-0.77) or stage II cancer (HR, 0.74; 95% CI, 0.60-0.90). The use of brachytherapy also was associated with significantly improved survival overall (HR, 0.67), in stage IA cancer (HR, 0.67), and in stage II cancer (HR, 0.64).

The survival effect of brachytherapy held up in additional subgroup analyses, Dr. Cham explained. In contrast, external beam radiation therapy was not associated with improved survival overall or in any subgroup, she said. The results highlight the potential use of vaginal brachytherapy in early-stage uterine papillary serous carcinoma, she emphasized.

Dr. Cham cited no funding sources and reported having no conflicts of interest.

ORLANDO – Vascular inflammation was no different in patients with moderate to severe psoriasis after 16 weeks of treatment with adalimumab than in untreated controls, according to a study that evaluated the impact of blocking tumor necrosis factor–alpha on vascular inflammation.

Further, there was a modest increase in vascular inflammation in carotid arteries after 52 weeks of treatment with the tumor necrosis factor (TNF) alpha-antagonist adalimumab, Robert Bissonnette, MD, president of Innovaderm Research, Montreal, reported in a late-breaking session at the annual meeting of the American Academy of Dermatology.

Whitney McKnight/FrontlineMedicalNews

Several previous studies have suggested that reducing inflammation in psoriasis can also reduce the risk of some cardiovascular events. As to why this study did not demonstrate a correlation between vascular inflammation and treatment, Dr. Bissonnette said during the question and answer portion of the presentation that “either the dose of adalimumab that is used for psoriasis has no impact on vascular inflammation or it may be possible that levels of interleukin-6, a key cytokine correlated with vascular inflammation, were very low in our study.”

Interleukin-6 typically is increased in patients with psoriatic arthritis, he explained, noting that in this study, only 7.5% of patients in the treatment group and about 10% of those in the control group had a history of psoriatic arthritis.

Additionally, at baseline, high-sensitivity C-reactive protein levels were significantly higher in controls: 5.32, compared with 2.72 in the treatment arm (P = .003).

Another possible reason for the results could be the molecule size of adalimumab, session comoderator Joel Gelfand, MD, noted in an interview. “The drug may not penetrate the aorta. These are large molecules. It also might be that [TNF–alpha] is not the main driver of aortic inflammation in people with psoriasis. Increasingly, we think of people with psoriasis as an IL-23 and IL-17 disease, so maybe that is part of it,” said Dr. Gelfand, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia. He also directs the psoriasis and phototherapy treatment center at the university.

In addition to being presented at the meeting, the results were published in the Journal of Investigative Dermatology (2017 Feb 7. doi: 10.1016/j.jid.2017.02.977).

Adalimumab is marketed as Humira by Abbvie; a biosimilar version, adalimumab-atto (Amjevita), was approved in the United States in 2016.

Dr. Bissonnette’s disclosures included serving as an adviser and consultant to Abbvie, which sponsored the study, as well as relationships with other companies, including Amgen, Celgene, Janssen, and Novartis. Dr. Gelfand’s disclosures included serving as a consultant and investigator for Abbvie, and serving as an investigator, speaker, and/or consultant for other companies, including Eli Lilly, Janssen, and Novartis.

[email protected]

On Twitter @whitneymcknight

ORLANDO – Vascular inflammation was no different in patients with moderate to severe psoriasis after 16 weeks of treatment with adalimumab than in untreated controls, according to a study that evaluated the impact of blocking tumor necrosis factor–alpha on vascular inflammation.

Further, there was a modest increase in vascular inflammation in carotid arteries after 52 weeks of treatment with the tumor necrosis factor (TNF) alpha-antagonist adalimumab, Robert Bissonnette, MD, president of Innovaderm Research, Montreal, reported in a late-breaking session at the annual meeting of the American Academy of Dermatology.

Whitney McKnight/FrontlineMedicalNews

Several previous studies have suggested that reducing inflammation in psoriasis can also reduce the risk of some cardiovascular events. As to why this study did not demonstrate a correlation between vascular inflammation and treatment, Dr. Bissonnette said during the question and answer portion of the presentation that “either the dose of adalimumab that is used for psoriasis has no impact on vascular inflammation or it may be possible that levels of interleukin-6, a key cytokine correlated with vascular inflammation, were very low in our study.”

Interleukin-6 typically is increased in patients with psoriatic arthritis, he explained, noting that in this study, only 7.5% of patients in the treatment group and about 10% of those in the control group had a history of psoriatic arthritis.

Additionally, at baseline, high-sensitivity C-reactive protein levels were significantly higher in controls: 5.32, compared with 2.72 in the treatment arm (P = .003).

Another possible reason for the results could be the molecule size of adalimumab, session comoderator Joel Gelfand, MD, noted in an interview. “The drug may not penetrate the aorta. These are large molecules. It also might be that [TNF–alpha] is not the main driver of aortic inflammation in people with psoriasis. Increasingly, we think of people with psoriasis as an IL-23 and IL-17 disease, so maybe that is part of it,” said Dr. Gelfand, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia. He also directs the psoriasis and phototherapy treatment center at the university.

In addition to being presented at the meeting, the results were published in the Journal of Investigative Dermatology (2017 Feb 7. doi: 10.1016/j.jid.2017.02.977).

Adalimumab is marketed as Humira by Abbvie; a biosimilar version, adalimumab-atto (Amjevita), was approved in the United States in 2016.

Dr. Bissonnette’s disclosures included serving as an adviser and consultant to Abbvie, which sponsored the study, as well as relationships with other companies, including Amgen, Celgene, Janssen, and Novartis. Dr. Gelfand’s disclosures included serving as a consultant and investigator for Abbvie, and serving as an investigator, speaker, and/or consultant for other companies, including Eli Lilly, Janssen, and Novartis.

[email protected]

On Twitter @whitneymcknight

ORLANDO – Vascular inflammation was no different in patients with moderate to severe psoriasis after 16 weeks of treatment with adalimumab than in untreated controls, according to a study that evaluated the impact of blocking tumor necrosis factor–alpha on vascular inflammation.

Further, there was a modest increase in vascular inflammation in carotid arteries after 52 weeks of treatment with the tumor necrosis factor (TNF) alpha-antagonist adalimumab, Robert Bissonnette, MD, president of Innovaderm Research, Montreal, reported in a late-breaking session at the annual meeting of the American Academy of Dermatology.

Whitney McKnight/FrontlineMedicalNews

Several previous studies have suggested that reducing inflammation in psoriasis can also reduce the risk of some cardiovascular events. As to why this study did not demonstrate a correlation between vascular inflammation and treatment, Dr. Bissonnette said during the question and answer portion of the presentation that “either the dose of adalimumab that is used for psoriasis has no impact on vascular inflammation or it may be possible that levels of interleukin-6, a key cytokine correlated with vascular inflammation, were very low in our study.”

Interleukin-6 typically is increased in patients with psoriatic arthritis, he explained, noting that in this study, only 7.5% of patients in the treatment group and about 10% of those in the control group had a history of psoriatic arthritis.

Additionally, at baseline, high-sensitivity C-reactive protein levels were significantly higher in controls: 5.32, compared with 2.72 in the treatment arm (P = .003).

Another possible reason for the results could be the molecule size of adalimumab, session comoderator Joel Gelfand, MD, noted in an interview. “The drug may not penetrate the aorta. These are large molecules. It also might be that [TNF–alpha] is not the main driver of aortic inflammation in people with psoriasis. Increasingly, we think of people with psoriasis as an IL-23 and IL-17 disease, so maybe that is part of it,” said Dr. Gelfand, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia. He also directs the psoriasis and phototherapy treatment center at the university.

In addition to being presented at the meeting, the results were published in the Journal of Investigative Dermatology (2017 Feb 7. doi: 10.1016/j.jid.2017.02.977).

Adalimumab is marketed as Humira by Abbvie; a biosimilar version, adalimumab-atto (Amjevita), was approved in the United States in 2016.

Dr. Bissonnette’s disclosures included serving as an adviser and consultant to Abbvie, which sponsored the study, as well as relationships with other companies, including Amgen, Celgene, Janssen, and Novartis. Dr. Gelfand’s disclosures included serving as a consultant and investigator for Abbvie, and serving as an investigator, speaker, and/or consultant for other companies, including Eli Lilly, Janssen, and Novartis.

[email protected]

On Twitter @whitneymcknight

A few weeks ago I received an email from a pediatrician thanking me for supporting her decision to quit work so that she could be home when her teenage son came home from school. She felt that by being home during her son’s adolescence, not only had she provided him a secure base but she also had helped protect him from a drug-dominated culture that permeated the community where they lived. While I hadn’t touched on it in my column, “Perfect Attendance” (Pediatric News, March 2017), this pediatrician’s experience highlights another benefit of a parental presence during those potentially stormy adolescent years.

In a recent article in the New York Times (“Teenagers Do Dumb Things, but There Are Ways to Limit Recklessness,” by Lisa Damour, March 8, 2017), Dr. Laurence Steinberg, a psychology professor at Temple University, is quoted as saying that “the context in which kids grow up must matter a great deal, and that recklessness isn’t the inevitable byproduct of the period’s biology.”

rez-art/Thinkstock

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

A few weeks ago I received an email from a pediatrician thanking me for supporting her decision to quit work so that she could be home when her teenage son came home from school. She felt that by being home during her son’s adolescence, not only had she provided him a secure base but she also had helped protect him from a drug-dominated culture that permeated the community where they lived. While I hadn’t touched on it in my column, “Perfect Attendance” (Pediatric News, March 2017), this pediatrician’s experience highlights another benefit of a parental presence during those potentially stormy adolescent years.

In a recent article in the New York Times (“Teenagers Do Dumb Things, but There Are Ways to Limit Recklessness,” by Lisa Damour, March 8, 2017), Dr. Laurence Steinberg, a psychology professor at Temple University, is quoted as saying that “the context in which kids grow up must matter a great deal, and that recklessness isn’t the inevitable byproduct of the period’s biology.”

rez-art/Thinkstock

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

A few weeks ago I received an email from a pediatrician thanking me for supporting her decision to quit work so that she could be home when her teenage son came home from school. She felt that by being home during her son’s adolescence, not only had she provided him a secure base but she also had helped protect him from a drug-dominated culture that permeated the community where they lived. While I hadn’t touched on it in my column, “Perfect Attendance” (Pediatric News, March 2017), this pediatrician’s experience highlights another benefit of a parental presence during those potentially stormy adolescent years.

In a recent article in the New York Times (“Teenagers Do Dumb Things, but There Are Ways to Limit Recklessness,” by Lisa Damour, March 8, 2017), Dr. Laurence Steinberg, a psychology professor at Temple University, is quoted as saying that “the context in which kids grow up must matter a great deal, and that recklessness isn’t the inevitable byproduct of the period’s biology.”

rez-art/Thinkstock

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

The knowledge about Loeys-Dietz syndrome has evolved quickly since Hal Dietz, MD, and Bart Loeys, MD, at Johns Hopkins University, Baltimore, first reported on it in 2005.

Now, another team of Johns Hopkins investigators have reported that an aggressive approach with aortic root replacement coupled with valve-sparing whenever possible produces favorable results, but that clinicians must follow these patients closely with cardiovascular imaging.

“Growing experience with Loeys-Dietz syndrome has confirmed early impressions of its aggressive nature and proclivity toward aortic catastrophe,” Nishant D. Patel, MD, and his coauthors said in the February issue of the Journal of Thoracic and Cardiovascular Surgery (2017;153:406-12). They reported on results of all 79 patients with Loeys-Dietz syndrome (LDS) who had cardiovascular surgery at Johns Hopkins. There were two (3%) deaths during surgery and eight (10%) late deaths. Patients with LDS are at risk for dissection early when the aortic root reaches 4 cm. Despite what they termed “favorable” outcomes of surgery, Dr. Patel and his coauthors acknowledged that reintervention rates for this population are high – 19 patients (24%) had subsequent operations. That suggests cardiac surgeons must closely monitor these patients. “Meticulous follow-up with cardiovascular surveillance imaging remains important for management, particularly as clinical LDS subtypes are characterized and more tailored treatment is developed,” Dr. Patel and his coauthors reported.

They advise echocardiography every 3 to 6 months for the first year after surgery and then every 6 to 12 months afterward. Full-body imaging should occur at least every 2 years. “In particular, patients with type B dissections should be monitored aggressively for aneurysm growth,” Dr. Patel and his coauthors said. They recommend imaging at seven to 14 days after dissection, then repeat imaging at 1, 3, 6, and 12 months, and then yearly thereafter.

They noted that four LDS subtypes have been identified. Although those with LDS1 and 2 subtypes are prone to aortic rupture at an earlier age and at smaller aortic diameters than other connective tissue disorders, the medical and surgical management for all subtypes are similar, Dr. Patel and his coauthors indicated.

“Certain congenital heart defects are more common among patients with LDS, compared with the normal population, including patent ductus arteriosus and mitral valve prolapse/insufficiency,” they said. Genotype is one factor that determines the need for surgery in LDS patients, Dr. Patel and his coauthors said. Others are growth rate, aortic valve function, family history, and severity of noncardiac phenotype.

The 79 patients in the study were divided almost evenly between gender, and the average age at first operation was 24.9 years; 38 were children younger than 18 years and 20 had a previous sternotomy. Aortic root replacement represented the predominant operation in the group, accounting for 65 operations (82.3%), of which 52 (80%) were valve-sparing procedures and the remainder were composite valve-graft procedures. The other procedures the researchers performed were nine aortic arch replacements (11.4%), three open thoracoabdominal repairs (3.8%) and two ascending aorta replacements (2.5%).

“Valve-sparing root replacement has become a safe and reliable option for appropriately selected younger patients with LDS,” Dr. Patel and his coauthors wrote. Five patients needed a second operation on the aortic valve or root; three of them had a Florida sleeve procedure. “Based on these initial outcomes with the Florida sleeve at our institution, we have abandoned this procedure in favor of conventional valve-sparing root replacement,” Dr. Patel and his coauthors stated.

Dr. Patel and his coauthors had no financial relationships to disclose.

The knowledge about Loeys-Dietz syndrome has evolved quickly since Hal Dietz, MD, and Bart Loeys, MD, at Johns Hopkins University, Baltimore, first reported on it in 2005.

Now, another team of Johns Hopkins investigators have reported that an aggressive approach with aortic root replacement coupled with valve-sparing whenever possible produces favorable results, but that clinicians must follow these patients closely with cardiovascular imaging.

“Growing experience with Loeys-Dietz syndrome has confirmed early impressions of its aggressive nature and proclivity toward aortic catastrophe,” Nishant D. Patel, MD, and his coauthors said in the February issue of the Journal of Thoracic and Cardiovascular Surgery (2017;153:406-12). They reported on results of all 79 patients with Loeys-Dietz syndrome (LDS) who had cardiovascular surgery at Johns Hopkins. There were two (3%) deaths during surgery and eight (10%) late deaths. Patients with LDS are at risk for dissection early when the aortic root reaches 4 cm. Despite what they termed “favorable” outcomes of surgery, Dr. Patel and his coauthors acknowledged that reintervention rates for this population are high – 19 patients (24%) had subsequent operations. That suggests cardiac surgeons must closely monitor these patients. “Meticulous follow-up with cardiovascular surveillance imaging remains important for management, particularly as clinical LDS subtypes are characterized and more tailored treatment is developed,” Dr. Patel and his coauthors reported.

They advise echocardiography every 3 to 6 months for the first year after surgery and then every 6 to 12 months afterward. Full-body imaging should occur at least every 2 years. “In particular, patients with type B dissections should be monitored aggressively for aneurysm growth,” Dr. Patel and his coauthors said. They recommend imaging at seven to 14 days after dissection, then repeat imaging at 1, 3, 6, and 12 months, and then yearly thereafter.

They noted that four LDS subtypes have been identified. Although those with LDS1 and 2 subtypes are prone to aortic rupture at an earlier age and at smaller aortic diameters than other connective tissue disorders, the medical and surgical management for all subtypes are similar, Dr. Patel and his coauthors indicated.

“Certain congenital heart defects are more common among patients with LDS, compared with the normal population, including patent ductus arteriosus and mitral valve prolapse/insufficiency,” they said. Genotype is one factor that determines the need for surgery in LDS patients, Dr. Patel and his coauthors said. Others are growth rate, aortic valve function, family history, and severity of noncardiac phenotype.

The 79 patients in the study were divided almost evenly between gender, and the average age at first operation was 24.9 years; 38 were children younger than 18 years and 20 had a previous sternotomy. Aortic root replacement represented the predominant operation in the group, accounting for 65 operations (82.3%), of which 52 (80%) were valve-sparing procedures and the remainder were composite valve-graft procedures. The other procedures the researchers performed were nine aortic arch replacements (11.4%), three open thoracoabdominal repairs (3.8%) and two ascending aorta replacements (2.5%).

“Valve-sparing root replacement has become a safe and reliable option for appropriately selected younger patients with LDS,” Dr. Patel and his coauthors wrote. Five patients needed a second operation on the aortic valve or root; three of them had a Florida sleeve procedure. “Based on these initial outcomes with the Florida sleeve at our institution, we have abandoned this procedure in favor of conventional valve-sparing root replacement,” Dr. Patel and his coauthors stated.

Dr. Patel and his coauthors had no financial relationships to disclose.

The knowledge about Loeys-Dietz syndrome has evolved quickly since Hal Dietz, MD, and Bart Loeys, MD, at Johns Hopkins University, Baltimore, first reported on it in 2005.

Now, another team of Johns Hopkins investigators have reported that an aggressive approach with aortic root replacement coupled with valve-sparing whenever possible produces favorable results, but that clinicians must follow these patients closely with cardiovascular imaging.

“Growing experience with Loeys-Dietz syndrome has confirmed early impressions of its aggressive nature and proclivity toward aortic catastrophe,” Nishant D. Patel, MD, and his coauthors said in the February issue of the Journal of Thoracic and Cardiovascular Surgery (2017;153:406-12). They reported on results of all 79 patients with Loeys-Dietz syndrome (LDS) who had cardiovascular surgery at Johns Hopkins. There were two (3%) deaths during surgery and eight (10%) late deaths. Patients with LDS are at risk for dissection early when the aortic root reaches 4 cm. Despite what they termed “favorable” outcomes of surgery, Dr. Patel and his coauthors acknowledged that reintervention rates for this population are high – 19 patients (24%) had subsequent operations. That suggests cardiac surgeons must closely monitor these patients. “Meticulous follow-up with cardiovascular surveillance imaging remains important for management, particularly as clinical LDS subtypes are characterized and more tailored treatment is developed,” Dr. Patel and his coauthors reported.

They advise echocardiography every 3 to 6 months for the first year after surgery and then every 6 to 12 months afterward. Full-body imaging should occur at least every 2 years. “In particular, patients with type B dissections should be monitored aggressively for aneurysm growth,” Dr. Patel and his coauthors said. They recommend imaging at seven to 14 days after dissection, then repeat imaging at 1, 3, 6, and 12 months, and then yearly thereafter.

They noted that four LDS subtypes have been identified. Although those with LDS1 and 2 subtypes are prone to aortic rupture at an earlier age and at smaller aortic diameters than other connective tissue disorders, the medical and surgical management for all subtypes are similar, Dr. Patel and his coauthors indicated.

“Certain congenital heart defects are more common among patients with LDS, compared with the normal population, including patent ductus arteriosus and mitral valve prolapse/insufficiency,” they said. Genotype is one factor that determines the need for surgery in LDS patients, Dr. Patel and his coauthors said. Others are growth rate, aortic valve function, family history, and severity of noncardiac phenotype.

The 79 patients in the study were divided almost evenly between gender, and the average age at first operation was 24.9 years; 38 were children younger than 18 years and 20 had a previous sternotomy. Aortic root replacement represented the predominant operation in the group, accounting for 65 operations (82.3%), of which 52 (80%) were valve-sparing procedures and the remainder were composite valve-graft procedures. The other procedures the researchers performed were nine aortic arch replacements (11.4%), three open thoracoabdominal repairs (3.8%) and two ascending aorta replacements (2.5%).

“Valve-sparing root replacement has become a safe and reliable option for appropriately selected younger patients with LDS,” Dr. Patel and his coauthors wrote. Five patients needed a second operation on the aortic valve or root; three of them had a Florida sleeve procedure. “Based on these initial outcomes with the Florida sleeve at our institution, we have abandoned this procedure in favor of conventional valve-sparing root replacement,” Dr. Patel and his coauthors stated.

Dr. Patel and his coauthors had no financial relationships to disclose.

Secretary of Veterans Affairs David J. Shulkin, MD, testified before the House Committee on Veterans’ Affairs, promising to tackle the epidemic of suicide and to continue the process to improve the Veterans Choice Act. Dr. Shulkin pledged to begin providing some mental health care service to veterans with other than honorable (OTH) discharges. “We know the rate of death by suicide among veterans who do not use VA care is increasing at a greater rate than veterans who use VA care,” Shulkin told the panel. “This is a national emergency that requires bold action. We must and we will do all that we can to help former service members who may be at risk. When we say even 1 veteran suicide is 1 too many, we mean it.”

Related: Senate, VA Agree—Veterans Choice Act Needs Fixing

The VA estimates that there are more than 500,000 former service members with OTH discharges. Previously, these veterans were not eligible for VA health benefits. As part of the proposal, former OTH service members would be able to seek treatment at a VA emergency department, Vet Center, or Veterans Crisis Line.

“I appreciate Secretary Shulkin taking steps to ensure veterans in crisis with OTH discharges have access to mental health services,” Phil Roe, MD (R-Tenn), chairman of the House Committee on Veterans’ Affairs, said in a written response. “With that said, this must be done in a fair, transparent way that ensures no veteran, especially those who have honorably served, are being skipped over for the care they need. I look forward to continuing this conversation with Secretary Shulkin.”

Related: "Call to Action" on Veteran Suicide Yields Policy Shifts

In addition, Dr. Shulkin revealed that 5.5 million appointments have been made through the  Veterans Choice Act and only 5,000 use community care exclusively. The bulk of veterans access both Veterans Choice and VA health care services. The Choice Act is set to expire in less than 6 months on August 7, 2017, if it does not receive congressional reapproval.

To modernize and consolidating the community care portion of the Veterans Choice Act, Shulkin outlined 7 steps:

1. High performance integrated network, including VA, other federal health care, and community providers;
2. Increase choice for all veterans, starting with those with service-connected health needs;
3. Help veterans get care closer to their homes;
4. Optimize and coordinate veterans’ care with other insurance providers;
5. Maintain affordability for lowest income veterans;
6. Assist in care coordination for veterans with multiple care providers; and
7. Apply industry standards for quality and affordability to the program.

Related: Veteran Suicide Rate Up 32% Since 2001

Secretary of Veterans Affairs David J. Shulkin, MD, testified before the House Committee on Veterans’ Affairs, promising to tackle the epidemic of suicide and to continue the process to improve the Veterans Choice Act. Dr. Shulkin pledged to begin providing some mental health care service to veterans with other than honorable (OTH) discharges. “We know the rate of death by suicide among veterans who do not use VA care is increasing at a greater rate than veterans who use VA care,” Shulkin told the panel. “This is a national emergency that requires bold action. We must and we will do all that we can to help former service members who may be at risk. When we say even 1 veteran suicide is 1 too many, we mean it.”

Related: Senate, VA Agree—Veterans Choice Act Needs Fixing

The VA estimates that there are more than 500,000 former service members with OTH discharges. Previously, these veterans were not eligible for VA health benefits. As part of the proposal, former OTH service members would be able to seek treatment at a VA emergency department, Vet Center, or Veterans Crisis Line.

“I appreciate Secretary Shulkin taking steps to ensure veterans in crisis with OTH discharges have access to mental health services,” Phil Roe, MD (R-Tenn), chairman of the House Committee on Veterans’ Affairs, said in a written response. “With that said, this must be done in a fair, transparent way that ensures no veteran, especially those who have honorably served, are being skipped over for the care they need. I look forward to continuing this conversation with Secretary Shulkin.”

Related: "Call to Action" on Veteran Suicide Yields Policy Shifts

In addition, Dr. Shulkin revealed that 5.5 million appointments have been made through the  Veterans Choice Act and only 5,000 use community care exclusively. The bulk of veterans access both Veterans Choice and VA health care services. The Choice Act is set to expire in less than 6 months on August 7, 2017, if it does not receive congressional reapproval.

To modernize and consolidating the community care portion of the Veterans Choice Act, Shulkin outlined 7 steps:

1. High performance integrated network, including VA, other federal health care, and community providers;
2. Increase choice for all veterans, starting with those with service-connected health needs;
3. Help veterans get care closer to their homes;
4. Optimize and coordinate veterans’ care with other insurance providers;
5. Maintain affordability for lowest income veterans;
6. Assist in care coordination for veterans with multiple care providers; and
7. Apply industry standards for quality and affordability to the program.

Related: Veteran Suicide Rate Up 32% Since 2001

Secretary of Veterans Affairs David J. Shulkin, MD, testified before the House Committee on Veterans’ Affairs, promising to tackle the epidemic of suicide and to continue the process to improve the Veterans Choice Act. Dr. Shulkin pledged to begin providing some mental health care service to veterans with other than honorable (OTH) discharges. “We know the rate of death by suicide among veterans who do not use VA care is increasing at a greater rate than veterans who use VA care,” Shulkin told the panel. “This is a national emergency that requires bold action. We must and we will do all that we can to help former service members who may be at risk. When we say even 1 veteran suicide is 1 too many, we mean it.”

Related: Senate, VA Agree—Veterans Choice Act Needs Fixing

The VA estimates that there are more than 500,000 former service members with OTH discharges. Previously, these veterans were not eligible for VA health benefits. As part of the proposal, former OTH service members would be able to seek treatment at a VA emergency department, Vet Center, or Veterans Crisis Line.

“I appreciate Secretary Shulkin taking steps to ensure veterans in crisis with OTH discharges have access to mental health services,” Phil Roe, MD (R-Tenn), chairman of the House Committee on Veterans’ Affairs, said in a written response. “With that said, this must be done in a fair, transparent way that ensures no veteran, especially those who have honorably served, are being skipped over for the care they need. I look forward to continuing this conversation with Secretary Shulkin.”

Related: "Call to Action" on Veteran Suicide Yields Policy Shifts

In addition, Dr. Shulkin revealed that 5.5 million appointments have been made through the  Veterans Choice Act and only 5,000 use community care exclusively. The bulk of veterans access both Veterans Choice and VA health care services. The Choice Act is set to expire in less than 6 months on August 7, 2017, if it does not receive congressional reapproval.

To modernize and consolidating the community care portion of the Veterans Choice Act, Shulkin outlined 7 steps:

1. High performance integrated network, including VA, other federal health care, and community providers;
2. Increase choice for all veterans, starting with those with service-connected health needs;
3. Help veterans get care closer to their homes;
4. Optimize and coordinate veterans’ care with other insurance providers;
5. Maintain affordability for lowest income veterans;
6. Assist in care coordination for veterans with multiple care providers; and
7. Apply industry standards for quality and affordability to the program.

Related: Veteran Suicide Rate Up 32% Since 2001

Some patients who experience long-term grief may be slipping through the health care net. With data collected in 2 National Institute of Mental Health-funded treatment studies, researchers used proposed criteria from DSM-5 to identify patients with a stress-response syndrome of “persistent impairing grief”—that is, persistent complex bereavement disorder (PCBD), prolonged grief disorder (BGD) and complicated grief (CG). They studied 2 groups of patients in university-based psychiatric research clinics: 240 grief-treatment seeking participants scored ≥ 30 on the Inventory of Complicated Grief (ICG), and 86 bereaved adults scored < 20 on the ICG.

The PCBD criteria diagnosed 70% of the first group, PGD criteria identified 59.6%, and CG criteria identified 99.6%. None of the 3 proposed criteria identified cases in the bereaved comparison group. Only the CG criteria produced rates of case identification sufficient to be of clinical utility, the researchers say.

Their findings are “virtually identical” with those of the community-based National Military Family Bereavement Study, the researchers say, in which all 3 criteria sets identified < 2% of the bereaved military family survey population that scored < 20 on the ICG.

There are treatments specific to grief, the researchers note. But as of yet there is no gold standard for diagnosing persistent impairing grief. The researchers say the solution could lie in using the CG criteria set and modifying decision rules for CBD or PGD criteria or developing a new group of symptoms and decision rules. However it’s done, the researchers conclude, they see a “pressing need” to establish criteria that can lead to correct diagnosis and targeted treatment.

Some patients who experience long-term grief may be slipping through the health care net. With data collected in 2 National Institute of Mental Health-funded treatment studies, researchers used proposed criteria from DSM-5 to identify patients with a stress-response syndrome of “persistent impairing grief”—that is, persistent complex bereavement disorder (PCBD), prolonged grief disorder (BGD) and complicated grief (CG). They studied 2 groups of patients in university-based psychiatric research clinics: 240 grief-treatment seeking participants scored ≥ 30 on the Inventory of Complicated Grief (ICG), and 86 bereaved adults scored < 20 on the ICG.

The PCBD criteria diagnosed 70% of the first group, PGD criteria identified 59.6%, and CG criteria identified 99.6%. None of the 3 proposed criteria identified cases in the bereaved comparison group. Only the CG criteria produced rates of case identification sufficient to be of clinical utility, the researchers say.

Their findings are “virtually identical” with those of the community-based National Military Family Bereavement Study, the researchers say, in which all 3 criteria sets identified < 2% of the bereaved military family survey population that scored < 20 on the ICG.

There are treatments specific to grief, the researchers note. But as of yet there is no gold standard for diagnosing persistent impairing grief. The researchers say the solution could lie in using the CG criteria set and modifying decision rules for CBD or PGD criteria or developing a new group of symptoms and decision rules. However it’s done, the researchers conclude, they see a “pressing need” to establish criteria that can lead to correct diagnosis and targeted treatment.

Some patients who experience long-term grief may be slipping through the health care net. With data collected in 2 National Institute of Mental Health-funded treatment studies, researchers used proposed criteria from DSM-5 to identify patients with a stress-response syndrome of “persistent impairing grief”—that is, persistent complex bereavement disorder (PCBD), prolonged grief disorder (BGD) and complicated grief (CG). They studied 2 groups of patients in university-based psychiatric research clinics: 240 grief-treatment seeking participants scored ≥ 30 on the Inventory of Complicated Grief (ICG), and 86 bereaved adults scored < 20 on the ICG.

The PCBD criteria diagnosed 70% of the first group, PGD criteria identified 59.6%, and CG criteria identified 99.6%. None of the 3 proposed criteria identified cases in the bereaved comparison group. Only the CG criteria produced rates of case identification sufficient to be of clinical utility, the researchers say.

Their findings are “virtually identical” with those of the community-based National Military Family Bereavement Study, the researchers say, in which all 3 criteria sets identified < 2% of the bereaved military family survey population that scored < 20 on the ICG.

There are treatments specific to grief, the researchers note. But as of yet there is no gold standard for diagnosing persistent impairing grief. The researchers say the solution could lie in using the CG criteria set and modifying decision rules for CBD or PGD criteria or developing a new group of symptoms and decision rules. However it’s done, the researchers conclude, they see a “pressing need” to establish criteria that can lead to correct diagnosis and targeted treatment.

Cpl Si Longworth RLC

People who have served in the Armed Forces do not have an increased risk of leukemia or lymphoma, according to research published in Cancer Epidemiology.

Researchers analyzed the long-term risks of developing leukemia, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) in veterans living in Scotland.

At a mean 30 years of follow-up, there were no significant differences in the risk of the aforementioned malignancies between veterans and non-veterans in Scotland.

This retrospective study included 56,205 veterans and 172,741 non-veterans.

The veterans’ earliest date of entering service was January 1960, and the latest date of leaving service was December 2012.

At a mean follow-up of 29.3 years, 294 (0.52%) veterans and 974 (0.56%) non-veterans were diagnosed with leukemia, HL, or NHL.

There were 125 (0.22%) cases of leukemia in veterans and 365 (0.21%) in non-veterans. There were 59 (0.10%) cases of HL in veterans and 182 (0.11%) in non-veterans. And there were 144 (0.26%) cases of NHL in veterans and 538 (0.31%) in non-veterans.

There was no significant difference in the risk of all 3 cancer types between the veterans and non-veterans. The unadjusted hazard ratio (HR) was 0.96 (P=0.541).

There were no significant differences in an adjusted analysis either. (The analysis was adjusted for regional deprivation, which takes into account information on income, employment, health, education, housing, crime, and access to services.)

The adjusted HR was 1.03 (P=0.773) for leukemias, 1.19 (P=0.272) for HL, and 0.86 (P=0.110) for NHL.

“This is an important study which provides reassurance that military service in the last 50 years does not increase people’s risk of leukemia overall,” said study author Beverly Bergman, PhD, of the University of Glasgow in the UK.

“The Armed Forces comply with all relevant health and safety legislation and regulations, and we can now see that their risk is no different from the general population.”

Cpl Si Longworth RLC

People who have served in the Armed Forces do not have an increased risk of leukemia or lymphoma, according to research published in Cancer Epidemiology.

Researchers analyzed the long-term risks of developing leukemia, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) in veterans living in Scotland.

At a mean 30 years of follow-up, there were no significant differences in the risk of the aforementioned malignancies between veterans and non-veterans in Scotland.

This retrospective study included 56,205 veterans and 172,741 non-veterans.

The veterans’ earliest date of entering service was January 1960, and the latest date of leaving service was December 2012.

At a mean follow-up of 29.3 years, 294 (0.52%) veterans and 974 (0.56%) non-veterans were diagnosed with leukemia, HL, or NHL.

There were 125 (0.22%) cases of leukemia in veterans and 365 (0.21%) in non-veterans. There were 59 (0.10%) cases of HL in veterans and 182 (0.11%) in non-veterans. And there were 144 (0.26%) cases of NHL in veterans and 538 (0.31%) in non-veterans.

There was no significant difference in the risk of all 3 cancer types between the veterans and non-veterans. The unadjusted hazard ratio (HR) was 0.96 (P=0.541).

There were no significant differences in an adjusted analysis either. (The analysis was adjusted for regional deprivation, which takes into account information on income, employment, health, education, housing, crime, and access to services.)

The adjusted HR was 1.03 (P=0.773) for leukemias, 1.19 (P=0.272) for HL, and 0.86 (P=0.110) for NHL.

“This is an important study which provides reassurance that military service in the last 50 years does not increase people’s risk of leukemia overall,” said study author Beverly Bergman, PhD, of the University of Glasgow in the UK.

“The Armed Forces comply with all relevant health and safety legislation and regulations, and we can now see that their risk is no different from the general population.”

Cpl Si Longworth RLC

People who have served in the Armed Forces do not have an increased risk of leukemia or lymphoma, according to research published in Cancer Epidemiology.

Researchers analyzed the long-term risks of developing leukemia, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) in veterans living in Scotland.

At a mean 30 years of follow-up, there were no significant differences in the risk of the aforementioned malignancies between veterans and non-veterans in Scotland.

This retrospective study included 56,205 veterans and 172,741 non-veterans.

The veterans’ earliest date of entering service was January 1960, and the latest date of leaving service was December 2012.

At a mean follow-up of 29.3 years, 294 (0.52%) veterans and 974 (0.56%) non-veterans were diagnosed with leukemia, HL, or NHL.

There were 125 (0.22%) cases of leukemia in veterans and 365 (0.21%) in non-veterans. There were 59 (0.10%) cases of HL in veterans and 182 (0.11%) in non-veterans. And there were 144 (0.26%) cases of NHL in veterans and 538 (0.31%) in non-veterans.

There was no significant difference in the risk of all 3 cancer types between the veterans and non-veterans. The unadjusted hazard ratio (HR) was 0.96 (P=0.541).

There were no significant differences in an adjusted analysis either. (The analysis was adjusted for regional deprivation, which takes into account information on income, employment, health, education, housing, crime, and access to services.)

The adjusted HR was 1.03 (P=0.773) for leukemias, 1.19 (P=0.272) for HL, and 0.86 (P=0.110) for NHL.

“This is an important study which provides reassurance that military service in the last 50 years does not increase people’s risk of leukemia overall,” said study author Beverly Bergman, PhD, of the University of Glasgow in the UK.

“The Armed Forces comply with all relevant health and safety legislation and regulations, and we can now see that their risk is no different from the general population.”

Warfarin tablets

A large study has revealed an association between stroke and “inadequate” anticoagulation among patients with atrial fibrillation.

More than 80% of the patients studied did not receive guideline-recommended anticoagulant therapy prior to having a stroke.

The study also showed that when patients did receive recommended anticoagulants, they had less severe stroke outcomes and a lower risk of death.

These findings were published in JAMA.

“Atrial fibrillation is very common, and people with the condition are at a much higher risk of having stroke,” said study author Ying Xian, MD, PhD, of the Duke University Medical Center in Durham, North Carolina.

“Treatment guidelines call for these patients to receive an anticoagulant such as warfarin at a therapeutic dose or a non-vitamin K antagonist oral anticoagulant (NOAC), so it’s surprising that this is not occurring in the vast majority of cases that occur in community settings.”

The study included 94,474 patients who had an acute ischemic stroke and known history of atrial fibrillation.

The patients were admitted from October 2012 through March 2015 to 1622 hospitals participating in the “Get with the Guidelines-Stroke” program, a national stroke registry sponsored by the American Heart Association and American Stroke Association.

In analyzing data from these patients, the researchers found the following:

• 83.6% of patients were not receiving therapeutic anticoagulation prior to stroke
• 30.3% were not receiving any antithrombotic treatment
• 39.9% were receiving antiplatelet therapy only
• 13.5% were receiving sub-therapeutic warfarin
• 7.6% were receiving therapeutic warfarin
• 8.8% were receiving NOACs.

“While some of these patients may have had reasons for not being anticoagulated, such as high bleeding or fall risk, more than two-thirds had no documented reason for receiving inadequate stroke prevention therapy,” Dr Xian said.

Dr Xian added that, in those cases where anticoagulation failed to prevent a stroke, patients who were on anticoagulant therapy tended to have less severe strokes, with less disability and death.

The researchers said the unadjusted rates of moderate or severe stroke were lower among patients receiving therapeutic warfarin (15.8%) or NOACs (17.5%) than among patients receiving no antithrombotic therapy (27.1%), antiplatelet therapy alone (24.8%), or sub-therapeutic warfarin (25.8%).

The same was true for the unadjusted rates of in-hospital mortality. Patients receiving therapeutic warfarin (6.4%) or NOACs (6.3%) had lower rates than patients receiving no antithrombotic therapy (9.3%), antiplatelet therapy alone (8.1%), or sub-therapeutic warfarin (8.8%).

In an adjusted analysis, the use of therapeutic warfarin, NOACs, or antiplatelet therapy was associated with lower odds of moderate or severe stroke (adjusted odds ratio=0.56, 0.65, and 0.88, respectively) and in-hospital mortality (adjusted odds ratio=0.75, 0.79, and 0.83, respectively), when compared to no antithrombotic treatment.

“These findings highlight the human costs of atrial fibrillation and the importance of appropriate anticoagulation,” Dr Xian said. “Broader adherence to these atrial fibrillation treatment guidelines could substantially reduce both the number and severity of strokes in the US. We estimate that between 58,000 to 88,000 strokes might be preventable per year if the treatment guidelines are followed appropriately.” 

Warfarin tablets

A large study has revealed an association between stroke and “inadequate” anticoagulation among patients with atrial fibrillation.

More than 80% of the patients studied did not receive guideline-recommended anticoagulant therapy prior to having a stroke.

The study also showed that when patients did receive recommended anticoagulants, they had less severe stroke outcomes and a lower risk of death.

These findings were published in JAMA.

“Atrial fibrillation is very common, and people with the condition are at a much higher risk of having stroke,” said study author Ying Xian, MD, PhD, of the Duke University Medical Center in Durham, North Carolina.

“Treatment guidelines call for these patients to receive an anticoagulant such as warfarin at a therapeutic dose or a non-vitamin K antagonist oral anticoagulant (NOAC), so it’s surprising that this is not occurring in the vast majority of cases that occur in community settings.”

The study included 94,474 patients who had an acute ischemic stroke and known history of atrial fibrillation.

The patients were admitted from October 2012 through March 2015 to 1622 hospitals participating in the “Get with the Guidelines-Stroke” program, a national stroke registry sponsored by the American Heart Association and American Stroke Association.

In analyzing data from these patients, the researchers found the following:

• 83.6% of patients were not receiving therapeutic anticoagulation prior to stroke
• 30.3% were not receiving any antithrombotic treatment
• 39.9% were receiving antiplatelet therapy only
• 13.5% were receiving sub-therapeutic warfarin
• 7.6% were receiving therapeutic warfarin
• 8.8% were receiving NOACs.

“While some of these patients may have had reasons for not being anticoagulated, such as high bleeding or fall risk, more than two-thirds had no documented reason for receiving inadequate stroke prevention therapy,” Dr Xian said.

Dr Xian added that, in those cases where anticoagulation failed to prevent a stroke, patients who were on anticoagulant therapy tended to have less severe strokes, with less disability and death.

The researchers said the unadjusted rates of moderate or severe stroke were lower among patients receiving therapeutic warfarin (15.8%) or NOACs (17.5%) than among patients receiving no antithrombotic therapy (27.1%), antiplatelet therapy alone (24.8%), or sub-therapeutic warfarin (25.8%).

The same was true for the unadjusted rates of in-hospital mortality. Patients receiving therapeutic warfarin (6.4%) or NOACs (6.3%) had lower rates than patients receiving no antithrombotic therapy (9.3%), antiplatelet therapy alone (8.1%), or sub-therapeutic warfarin (8.8%).

In an adjusted analysis, the use of therapeutic warfarin, NOACs, or antiplatelet therapy was associated with lower odds of moderate or severe stroke (adjusted odds ratio=0.56, 0.65, and 0.88, respectively) and in-hospital mortality (adjusted odds ratio=0.75, 0.79, and 0.83, respectively), when compared to no antithrombotic treatment.

“These findings highlight the human costs of atrial fibrillation and the importance of appropriate anticoagulation,” Dr Xian said. “Broader adherence to these atrial fibrillation treatment guidelines could substantially reduce both the number and severity of strokes in the US. We estimate that between 58,000 to 88,000 strokes might be preventable per year if the treatment guidelines are followed appropriately.” 

Warfarin tablets

A large study has revealed an association between stroke and “inadequate” anticoagulation among patients with atrial fibrillation.

More than 80% of the patients studied did not receive guideline-recommended anticoagulant therapy prior to having a stroke.

The study also showed that when patients did receive recommended anticoagulants, they had less severe stroke outcomes and a lower risk of death.

These findings were published in JAMA.

“Atrial fibrillation is very common, and people with the condition are at a much higher risk of having stroke,” said study author Ying Xian, MD, PhD, of the Duke University Medical Center in Durham, North Carolina.

“Treatment guidelines call for these patients to receive an anticoagulant such as warfarin at a therapeutic dose or a non-vitamin K antagonist oral anticoagulant (NOAC), so it’s surprising that this is not occurring in the vast majority of cases that occur in community settings.”

The study included 94,474 patients who had an acute ischemic stroke and known history of atrial fibrillation.

The patients were admitted from October 2012 through March 2015 to 1622 hospitals participating in the “Get with the Guidelines-Stroke” program, a national stroke registry sponsored by the American Heart Association and American Stroke Association.

In analyzing data from these patients, the researchers found the following:

• 83.6% of patients were not receiving therapeutic anticoagulation prior to stroke
• 30.3% were not receiving any antithrombotic treatment
• 39.9% were receiving antiplatelet therapy only
• 13.5% were receiving sub-therapeutic warfarin
• 7.6% were receiving therapeutic warfarin
• 8.8% were receiving NOACs.

“While some of these patients may have had reasons for not being anticoagulated, such as high bleeding or fall risk, more than two-thirds had no documented reason for receiving inadequate stroke prevention therapy,” Dr Xian said.

Dr Xian added that, in those cases where anticoagulation failed to prevent a stroke, patients who were on anticoagulant therapy tended to have less severe strokes, with less disability and death.

The researchers said the unadjusted rates of moderate or severe stroke were lower among patients receiving therapeutic warfarin (15.8%) or NOACs (17.5%) than among patients receiving no antithrombotic therapy (27.1%), antiplatelet therapy alone (24.8%), or sub-therapeutic warfarin (25.8%).

The same was true for the unadjusted rates of in-hospital mortality. Patients receiving therapeutic warfarin (6.4%) or NOACs (6.3%) had lower rates than patients receiving no antithrombotic therapy (9.3%), antiplatelet therapy alone (8.1%), or sub-therapeutic warfarin (8.8%).

In an adjusted analysis, the use of therapeutic warfarin, NOACs, or antiplatelet therapy was associated with lower odds of moderate or severe stroke (adjusted odds ratio=0.56, 0.65, and 0.88, respectively) and in-hospital mortality (adjusted odds ratio=0.75, 0.79, and 0.83, respectively), when compared to no antithrombotic treatment.

“These findings highlight the human costs of atrial fibrillation and the importance of appropriate anticoagulation,” Dr Xian said. “Broader adherence to these atrial fibrillation treatment guidelines could substantially reduce both the number and severity of strokes in the US. We estimate that between 58,000 to 88,000 strokes might be preventable per year if the treatment guidelines are followed appropriately.” 

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has granted accelerated approval for pembrolizumab (Keytruda) as a treatment for adult and pediatric patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.

The drug, which is being developed by Merck, previously received FDA approval as a treatment for melanoma, lung cancer, and head and neck cancer.

Now, pembrolizumab has received accelerated approval to treat adult and pediatric patients with refractory cHL or those with cHL who have relapsed after 3 or more prior lines of therapy.

The accelerated approval was based on tumor response rate and durability of response. Continued approval of pembrolizumab for cHL patients may be contingent upon the verification and description of clinical benefit in confirmatory trials.

In adults with cHL, pembrolizumab is administered at a fixed dose of 200 mg every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

In pediatric patients with cHL, pembrolizumab is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Pembrolizumab trials

The FDA’s approval of pembrolizumab in adults with cHL is based on data from the phase 2 KEYNOTE-087 trial. (The following data were provided by Merck.)

The trial enrolled 210 patients who received pembrolizumab at a dose of 200 mg every 3 weeks until unacceptable toxicity or documented disease progression, or for up to 24 months in patients who did not progress.

Fifty-eight percent of patients were refractory to their last prior therapy, including 35% with primary refractory disease and 14% whose disease was refractory to all prior regimens.

Sixty-one percent of patients had undergone prior autologous hematopoietic stem cell transplant, 83% had prior brentuximab use, and 36% had prior radiation therapy.

At a median follow-up of 9.4 months, the overall response rate was 69%, and the complete response rate was 22%. The median duration of response was 11.1 months (range, 0.0+ to 11.1 months).

Five percent of patients discontinued pembrolizumab due to adverse events (AEs), and 26% had dose interruptions due to AEs. Fifteen percent of patients had an AE requiring systemic corticosteroid therapy.

The most common AEs (occurring in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

Serious AEs occurred in 16% of patients. The most frequent serious AEs (≥1%) were pneumonia, pneumonitis, pyrexia, dyspnea, graft-vs-host disease, and herpes zoster.

Two patients died from causes other than disease progression. One death was a result of graft-vs-host disease after subsequent allogeneic transplant, and the other was from septic shock.

There is limited experience with pembrolizumab in pediatric patients. The efficacy of the drug for pediatric patients was extrapolated from the results in the adult cHL population.

However, there is safety data on pembrolizumab in pediatric patients enrolled in the phase 1/2 KEYNOTE-051 trial. (These data were also provided by Merck.)

The trial included 40 pediatric patients with advanced melanoma or PD-L1–positive advanced, relapsed, or refractory solid tumors or lymphoma. Patients in this trial received pembrolizumab for a median of 43 days (range, 1-414 days).

The safety profile in these patients was similar to the profile in adults. Toxicities that occurred at a higher rate (≥15% difference) in pediatric patients than in adults under age 65 were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has granted accelerated approval for pembrolizumab (Keytruda) as a treatment for adult and pediatric patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.

The drug, which is being developed by Merck, previously received FDA approval as a treatment for melanoma, lung cancer, and head and neck cancer.

Now, pembrolizumab has received accelerated approval to treat adult and pediatric patients with refractory cHL or those with cHL who have relapsed after 3 or more prior lines of therapy.

The accelerated approval was based on tumor response rate and durability of response. Continued approval of pembrolizumab for cHL patients may be contingent upon the verification and description of clinical benefit in confirmatory trials.

In adults with cHL, pembrolizumab is administered at a fixed dose of 200 mg every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

In pediatric patients with cHL, pembrolizumab is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Pembrolizumab trials

The FDA’s approval of pembrolizumab in adults with cHL is based on data from the phase 2 KEYNOTE-087 trial. (The following data were provided by Merck.)

The trial enrolled 210 patients who received pembrolizumab at a dose of 200 mg every 3 weeks until unacceptable toxicity or documented disease progression, or for up to 24 months in patients who did not progress.

Fifty-eight percent of patients were refractory to their last prior therapy, including 35% with primary refractory disease and 14% whose disease was refractory to all prior regimens.

Sixty-one percent of patients had undergone prior autologous hematopoietic stem cell transplant, 83% had prior brentuximab use, and 36% had prior radiation therapy.

At a median follow-up of 9.4 months, the overall response rate was 69%, and the complete response rate was 22%. The median duration of response was 11.1 months (range, 0.0+ to 11.1 months).

Five percent of patients discontinued pembrolizumab due to adverse events (AEs), and 26% had dose interruptions due to AEs. Fifteen percent of patients had an AE requiring systemic corticosteroid therapy.

The most common AEs (occurring in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

Serious AEs occurred in 16% of patients. The most frequent serious AEs (≥1%) were pneumonia, pneumonitis, pyrexia, dyspnea, graft-vs-host disease, and herpes zoster.

Two patients died from causes other than disease progression. One death was a result of graft-vs-host disease after subsequent allogeneic transplant, and the other was from septic shock.

There is limited experience with pembrolizumab in pediatric patients. The efficacy of the drug for pediatric patients was extrapolated from the results in the adult cHL population.

However, there is safety data on pembrolizumab in pediatric patients enrolled in the phase 1/2 KEYNOTE-051 trial. (These data were also provided by Merck.)

The trial included 40 pediatric patients with advanced melanoma or PD-L1–positive advanced, relapsed, or refractory solid tumors or lymphoma. Patients in this trial received pembrolizumab for a median of 43 days (range, 1-414 days).

The safety profile in these patients was similar to the profile in adults. Toxicities that occurred at a higher rate (≥15% difference) in pediatric patients than in adults under age 65 were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has granted accelerated approval for pembrolizumab (Keytruda) as a treatment for adult and pediatric patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.

The drug, which is being developed by Merck, previously received FDA approval as a treatment for melanoma, lung cancer, and head and neck cancer.

Now, pembrolizumab has received accelerated approval to treat adult and pediatric patients with refractory cHL or those with cHL who have relapsed after 3 or more prior lines of therapy.

The accelerated approval was based on tumor response rate and durability of response. Continued approval of pembrolizumab for cHL patients may be contingent upon the verification and description of clinical benefit in confirmatory trials.

In adults with cHL, pembrolizumab is administered at a fixed dose of 200 mg every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

In pediatric patients with cHL, pembrolizumab is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Pembrolizumab trials

The FDA’s approval of pembrolizumab in adults with cHL is based on data from the phase 2 KEYNOTE-087 trial. (The following data were provided by Merck.)

The trial enrolled 210 patients who received pembrolizumab at a dose of 200 mg every 3 weeks until unacceptable toxicity or documented disease progression, or for up to 24 months in patients who did not progress.

Fifty-eight percent of patients were refractory to their last prior therapy, including 35% with primary refractory disease and 14% whose disease was refractory to all prior regimens.

Sixty-one percent of patients had undergone prior autologous hematopoietic stem cell transplant, 83% had prior brentuximab use, and 36% had prior radiation therapy.

At a median follow-up of 9.4 months, the overall response rate was 69%, and the complete response rate was 22%. The median duration of response was 11.1 months (range, 0.0+ to 11.1 months).

Five percent of patients discontinued pembrolizumab due to adverse events (AEs), and 26% had dose interruptions due to AEs. Fifteen percent of patients had an AE requiring systemic corticosteroid therapy.

The most common AEs (occurring in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

Serious AEs occurred in 16% of patients. The most frequent serious AEs (≥1%) were pneumonia, pneumonitis, pyrexia, dyspnea, graft-vs-host disease, and herpes zoster.

Two patients died from causes other than disease progression. One death was a result of graft-vs-host disease after subsequent allogeneic transplant, and the other was from septic shock.

There is limited experience with pembrolizumab in pediatric patients. The efficacy of the drug for pediatric patients was extrapolated from the results in the adult cHL population.

However, there is safety data on pembrolizumab in pediatric patients enrolled in the phase 1/2 KEYNOTE-051 trial. (These data were also provided by Merck.)

The trial included 40 pediatric patients with advanced melanoma or PD-L1–positive advanced, relapsed, or refractory solid tumors or lymphoma. Patients in this trial received pembrolizumab for a median of 43 days (range, 1-414 days).

The safety profile in these patients was similar to the profile in adults. Toxicities that occurred at a higher rate (≥15% difference) in pediatric patients than in adults under age 65 were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).