The natural histories of hepatitis B virus (HBV) and hepatitis C virus (HCV) are very different in children, compared with their progress in adults, and depends on age at time of infection, mode of acquisition, ethnicity, and genotype, according to a review in a special pediatric issue of Clinics in Liver Disease.

Courtesy NIH

Most children infected perinatally or vertically continue to be asymptomatic but are at uniquely higher risk of developing chronic viral hepatitis and progressing to liver cirrhosis and hepatocellular carcinoma (HCC), according to Krupa R. Mysore, MD, and Daniel H. Leung, MD, both of the Baylor College of Medicine, Houston. In addition, because the risk of progression to cancer along with such other liver damage is high in children, the reviewers stated that HCV and HBV can be classified as oncoviruses.

Their article assessed overall epidemiology, viral characteristics, and immune responses, as well as prevention, clinical manifestations, and current advances in the treatment of hepatitis B and C in children.

Because of the introduction of universal infant vaccination for HBV in the United States in 1991, the incidence of acute hepatitis B in U.S. children (those aged less than 19 years) has decreased from approximately 13.80/100,000 population (in children aged 10-19 years) in the 1980s to 0.34/100,000 population in 2002, Dr. Mysore and Dr. Leung wrote.

However, they added that those children who have chronic HBV remain at high risk for HCC, with a 100-fold greater incidence, compared with the HBV-negative population.

Similarly, HCV is a significant problem in children, with an estimated prevalence in the United States of 0.2% and 0.4% for children aged 6-11 years and 12-19 years, respectively. Vertical transmission from the mother is responsible for more than 60% of pediatric HCV infection and adds approximately 7,200 new cases in the United States yearly. Older children can acquire the virus through intravenous and intranasal drug use and high-risk sexual activity, they stated.

“Our understanding of the pathobiology and immunology of hepatitis B and C is unprecedented. As new antiviral therapies are being developed for the pediatric population, the differences in management and monitoring between children and adults with HBV and HCV are beginning to narrow but are still important,” the authors wrote.

They pointed out that soon-to-be-available treatments for HCV will be curative in children aged as young as 3 years. “[T]his will change the natural history of HCV and the prevalence of hepatocellular carcinoma over the next several decades for the better,” Dr. Mysore and Dr. Leung concluded.

They reported that they had no conflicts of interest to disclose.

[email protected]

SOURCE: Mysore KR et al. Clin Liver Dis. 2018; 22:703-22.

The natural histories of hepatitis B virus (HBV) and hepatitis C virus (HCV) are very different in children, compared with their progress in adults, and depends on age at time of infection, mode of acquisition, ethnicity, and genotype, according to a review in a special pediatric issue of Clinics in Liver Disease.

Courtesy NIH

Most children infected perinatally or vertically continue to be asymptomatic but are at uniquely higher risk of developing chronic viral hepatitis and progressing to liver cirrhosis and hepatocellular carcinoma (HCC), according to Krupa R. Mysore, MD, and Daniel H. Leung, MD, both of the Baylor College of Medicine, Houston. In addition, because the risk of progression to cancer along with such other liver damage is high in children, the reviewers stated that HCV and HBV can be classified as oncoviruses.

Their article assessed overall epidemiology, viral characteristics, and immune responses, as well as prevention, clinical manifestations, and current advances in the treatment of hepatitis B and C in children.

Because of the introduction of universal infant vaccination for HBV in the United States in 1991, the incidence of acute hepatitis B in U.S. children (those aged less than 19 years) has decreased from approximately 13.80/100,000 population (in children aged 10-19 years) in the 1980s to 0.34/100,000 population in 2002, Dr. Mysore and Dr. Leung wrote.

However, they added that those children who have chronic HBV remain at high risk for HCC, with a 100-fold greater incidence, compared with the HBV-negative population.

Similarly, HCV is a significant problem in children, with an estimated prevalence in the United States of 0.2% and 0.4% for children aged 6-11 years and 12-19 years, respectively. Vertical transmission from the mother is responsible for more than 60% of pediatric HCV infection and adds approximately 7,200 new cases in the United States yearly. Older children can acquire the virus through intravenous and intranasal drug use and high-risk sexual activity, they stated.

“Our understanding of the pathobiology and immunology of hepatitis B and C is unprecedented. As new antiviral therapies are being developed for the pediatric population, the differences in management and monitoring between children and adults with HBV and HCV are beginning to narrow but are still important,” the authors wrote.

They pointed out that soon-to-be-available treatments for HCV will be curative in children aged as young as 3 years. “[T]his will change the natural history of HCV and the prevalence of hepatocellular carcinoma over the next several decades for the better,” Dr. Mysore and Dr. Leung concluded.

They reported that they had no conflicts of interest to disclose.

[email protected]

SOURCE: Mysore KR et al. Clin Liver Dis. 2018; 22:703-22.

The natural histories of hepatitis B virus (HBV) and hepatitis C virus (HCV) are very different in children, compared with their progress in adults, and depends on age at time of infection, mode of acquisition, ethnicity, and genotype, according to a review in a special pediatric issue of Clinics in Liver Disease.

Courtesy NIH

Most children infected perinatally or vertically continue to be asymptomatic but are at uniquely higher risk of developing chronic viral hepatitis and progressing to liver cirrhosis and hepatocellular carcinoma (HCC), according to Krupa R. Mysore, MD, and Daniel H. Leung, MD, both of the Baylor College of Medicine, Houston. In addition, because the risk of progression to cancer along with such other liver damage is high in children, the reviewers stated that HCV and HBV can be classified as oncoviruses.

Their article assessed overall epidemiology, viral characteristics, and immune responses, as well as prevention, clinical manifestations, and current advances in the treatment of hepatitis B and C in children.

Because of the introduction of universal infant vaccination for HBV in the United States in 1991, the incidence of acute hepatitis B in U.S. children (those aged less than 19 years) has decreased from approximately 13.80/100,000 population (in children aged 10-19 years) in the 1980s to 0.34/100,000 population in 2002, Dr. Mysore and Dr. Leung wrote.

However, they added that those children who have chronic HBV remain at high risk for HCC, with a 100-fold greater incidence, compared with the HBV-negative population.

Similarly, HCV is a significant problem in children, with an estimated prevalence in the United States of 0.2% and 0.4% for children aged 6-11 years and 12-19 years, respectively. Vertical transmission from the mother is responsible for more than 60% of pediatric HCV infection and adds approximately 7,200 new cases in the United States yearly. Older children can acquire the virus through intravenous and intranasal drug use and high-risk sexual activity, they stated.

“Our understanding of the pathobiology and immunology of hepatitis B and C is unprecedented. As new antiviral therapies are being developed for the pediatric population, the differences in management and monitoring between children and adults with HBV and HCV are beginning to narrow but are still important,” the authors wrote.

They pointed out that soon-to-be-available treatments for HCV will be curative in children aged as young as 3 years. “[T]his will change the natural history of HCV and the prevalence of hepatocellular carcinoma over the next several decades for the better,” Dr. Mysore and Dr. Leung concluded.

They reported that they had no conflicts of interest to disclose.

[email protected]

SOURCE: Mysore KR et al. Clin Liver Dis. 2018; 22:703-22.

CHICAGO – Newer isn’t necessarily better – especially when it comes to the plethora of SLE classification criteria, according to Michelle A. Petri, MD, professor of medicine and director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore.

Bruce Jancin/MDedge News

“We have an embarrassment of criteria for lupus right now, and everyone wants to know if one is better than the others,” the rheumatologist said at the annual meeting of the American College of Rheumatology.

She and several coinvestigators who are members of the Systemic Lupus International Collaborating Clinics (SLICC) set out to learn the answer. They developed a new, modified, weighted version of the 2012 SLICC criteria and compared its sensitivity and specificity for SLE diagnosis by 690 physicians with three other major classification systems: the 1997 update to ACR-11 criteria, the nonweighted SLICC 2012 criteria, and the proposed EULAR/ACR criteria, which uses a differentially weighted approach in which the various possible disease manifestations are each assigned a different point score. In contrast, the revised ACR-11 and SLICC 2012 criteria count each SLE manifestation equally.

Long story short: “The two newly derived weighted classification rules did not perform better than the existing list-based rules in terms of overall agreement,” according to Dr. Petri.

“We don’t think that weighting all the criteria, which is what the EULAR/ACR and weighted SLICC 2012 rules do, adds to the performance of the criteria set, and in fact it makes it much more difficult for clinicians to use when there’s a complicated weighting system, unless it’s web-based or there’s an app for it. And to be honest, clinicians are so busy that they’re probably not going to take time out in a clinic visit to go use the web or an app. Our criteria need to be user friendly,” she continued.

So which of the four classification systems is most user friendly? The EULAR/ACR criteria can be dismissed on that score because they are supposed to be used only for research, according to the rheumatologist.

“I think the SLICC 2012 criteria are very useful for clinicians because they have the highest sensitivity. And what a clinician wants is not to miss a diagnosis and to start treatment early,” Dr. Petri said.

To develop the weighted SLICC criteria, whose future at this point doesn’t look bright, she and her coinvestigators redeployed the same physician-rated patient scenarios used to develop the nonweighted 2012 SLICC classification criteria and assigned each of the potential manifestations of SLE a specific point score. For example, acute cutaneous manifestations received 16 points, serositis 9, oral ulcers 16, thrombocytopenia 15, and so forth. Under this system, a patient with a score of at least 56 points, or lupus nephritis, or least one clinical and one immunologic component of SLE was classified as having the disease.

Dr. Petri reported having no financial conflicts regarding her study, supported by the National Institutes of Health.

[email protected]

SOURCE: Petri MA et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1712.

CHICAGO – Newer isn’t necessarily better – especially when it comes to the plethora of SLE classification criteria, according to Michelle A. Petri, MD, professor of medicine and director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore.

Bruce Jancin/MDedge News

“We have an embarrassment of criteria for lupus right now, and everyone wants to know if one is better than the others,” the rheumatologist said at the annual meeting of the American College of Rheumatology.

She and several coinvestigators who are members of the Systemic Lupus International Collaborating Clinics (SLICC) set out to learn the answer. They developed a new, modified, weighted version of the 2012 SLICC criteria and compared its sensitivity and specificity for SLE diagnosis by 690 physicians with three other major classification systems: the 1997 update to ACR-11 criteria, the nonweighted SLICC 2012 criteria, and the proposed EULAR/ACR criteria, which uses a differentially weighted approach in which the various possible disease manifestations are each assigned a different point score. In contrast, the revised ACR-11 and SLICC 2012 criteria count each SLE manifestation equally.

Long story short: “The two newly derived weighted classification rules did not perform better than the existing list-based rules in terms of overall agreement,” according to Dr. Petri.

“We don’t think that weighting all the criteria, which is what the EULAR/ACR and weighted SLICC 2012 rules do, adds to the performance of the criteria set, and in fact it makes it much more difficult for clinicians to use when there’s a complicated weighting system, unless it’s web-based or there’s an app for it. And to be honest, clinicians are so busy that they’re probably not going to take time out in a clinic visit to go use the web or an app. Our criteria need to be user friendly,” she continued.

So which of the four classification systems is most user friendly? The EULAR/ACR criteria can be dismissed on that score because they are supposed to be used only for research, according to the rheumatologist.

“I think the SLICC 2012 criteria are very useful for clinicians because they have the highest sensitivity. And what a clinician wants is not to miss a diagnosis and to start treatment early,” Dr. Petri said.

To develop the weighted SLICC criteria, whose future at this point doesn’t look bright, she and her coinvestigators redeployed the same physician-rated patient scenarios used to develop the nonweighted 2012 SLICC classification criteria and assigned each of the potential manifestations of SLE a specific point score. For example, acute cutaneous manifestations received 16 points, serositis 9, oral ulcers 16, thrombocytopenia 15, and so forth. Under this system, a patient with a score of at least 56 points, or lupus nephritis, or least one clinical and one immunologic component of SLE was classified as having the disease.

Dr. Petri reported having no financial conflicts regarding her study, supported by the National Institutes of Health.

[email protected]

SOURCE: Petri MA et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1712.

CHICAGO – Newer isn’t necessarily better – especially when it comes to the plethora of SLE classification criteria, according to Michelle A. Petri, MD, professor of medicine and director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore.

Bruce Jancin/MDedge News

“We have an embarrassment of criteria for lupus right now, and everyone wants to know if one is better than the others,” the rheumatologist said at the annual meeting of the American College of Rheumatology.

She and several coinvestigators who are members of the Systemic Lupus International Collaborating Clinics (SLICC) set out to learn the answer. They developed a new, modified, weighted version of the 2012 SLICC criteria and compared its sensitivity and specificity for SLE diagnosis by 690 physicians with three other major classification systems: the 1997 update to ACR-11 criteria, the nonweighted SLICC 2012 criteria, and the proposed EULAR/ACR criteria, which uses a differentially weighted approach in which the various possible disease manifestations are each assigned a different point score. In contrast, the revised ACR-11 and SLICC 2012 criteria count each SLE manifestation equally.

Long story short: “The two newly derived weighted classification rules did not perform better than the existing list-based rules in terms of overall agreement,” according to Dr. Petri.

“We don’t think that weighting all the criteria, which is what the EULAR/ACR and weighted SLICC 2012 rules do, adds to the performance of the criteria set, and in fact it makes it much more difficult for clinicians to use when there’s a complicated weighting system, unless it’s web-based or there’s an app for it. And to be honest, clinicians are so busy that they’re probably not going to take time out in a clinic visit to go use the web or an app. Our criteria need to be user friendly,” she continued.

So which of the four classification systems is most user friendly? The EULAR/ACR criteria can be dismissed on that score because they are supposed to be used only for research, according to the rheumatologist.

“I think the SLICC 2012 criteria are very useful for clinicians because they have the highest sensitivity. And what a clinician wants is not to miss a diagnosis and to start treatment early,” Dr. Petri said.

To develop the weighted SLICC criteria, whose future at this point doesn’t look bright, she and her coinvestigators redeployed the same physician-rated patient scenarios used to develop the nonweighted 2012 SLICC classification criteria and assigned each of the potential manifestations of SLE a specific point score. For example, acute cutaneous manifestations received 16 points, serositis 9, oral ulcers 16, thrombocytopenia 15, and so forth. Under this system, a patient with a score of at least 56 points, or lupus nephritis, or least one clinical and one immunologic component of SLE was classified as having the disease.

Dr. Petri reported having no financial conflicts regarding her study, supported by the National Institutes of Health.

[email protected]

SOURCE: Petri MA et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1712.

Various disease parameters can help clinicians make treatment decisions for patients with metastatic renal cell carcinoma (mRCC) undergoing active surveillance, but the change in tumor burden may be the best, suggests an Italian cohort study.

Investigators led by Davide Bimbatti, MD, of Azienda Ospedaliera Universitaria Integrata in Verona, Italy, retrospectively studied 52 patients with mRCC who started active surveillance as their initial strategy for disease management. They assessed three predictors of outcomes: International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk class, number of metastatic sites, and tumor burden.

Patients remained on active surveillance for a median of 18.3 months and had a median total overall survival of 80.1 months, according to study results published in Urologic Oncology. Fully 69.2% started first-line systemic therapy during a median follow-up of 38.5 months.

The only baseline factor predicting time on active surveillance was IMDC class (hazard ratio, 2.15; P = .011).

An increasing number of metastatic sites during active surveillance was associated with poorer total overall survival (HR, 2.86; P = .010) and a trend toward poorer postsurveillance overall survival (HR, 2.37; P = .060).

Increasing tumor burden, measured as the sum in millimeters of the longest tumor diameter of each measurable lesion, during active surveillance was associated with both poorer total overall survival (HR, 1.16; P = .024) and poorer postsurveillance overall survival (HR, 1.21; P = .004).

Finally, an IMDC class of good or intermediate versus poor at the start of systemic therapy was a favorable predictor (HR, 0.07; P = .010; and HR, 0.12; P = .044, respectively) and an increase in tumor burden was an unfavorable predictor (HR, 1.26; P = .005) of postsurveillance overall survival.

“Our study confirms that active surveillance is a safe option for certain patients, with a median time on surveillance of 1.5 years delaying the beginning of systemic therapies and avoiding drug-related toxicities, with a median overall survival greater than 6.5 years,” wrote Dr. Bimbatti and coinvestigators.

“During active surveillance, patients rarely show any deterioration of the IMDC prognostic class. Meanwhile, the tumor burden changes, more than the increase of metastatic sites, account for the heterogeneity of the disease and may help physicians to make decisions about the early termination of active surveillance and the start of systemic therapy,” they concluded.

SOURCE: Bimbatti D et al. Urol Oncol. 2018 Oct 6. doi: 10.1016/j.urolonc.2018.08.018.

Various disease parameters can help clinicians make treatment decisions for patients with metastatic renal cell carcinoma (mRCC) undergoing active surveillance, but the change in tumor burden may be the best, suggests an Italian cohort study.

Investigators led by Davide Bimbatti, MD, of Azienda Ospedaliera Universitaria Integrata in Verona, Italy, retrospectively studied 52 patients with mRCC who started active surveillance as their initial strategy for disease management. They assessed three predictors of outcomes: International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk class, number of metastatic sites, and tumor burden.

Patients remained on active surveillance for a median of 18.3 months and had a median total overall survival of 80.1 months, according to study results published in Urologic Oncology. Fully 69.2% started first-line systemic therapy during a median follow-up of 38.5 months.

The only baseline factor predicting time on active surveillance was IMDC class (hazard ratio, 2.15; P = .011).

An increasing number of metastatic sites during active surveillance was associated with poorer total overall survival (HR, 2.86; P = .010) and a trend toward poorer postsurveillance overall survival (HR, 2.37; P = .060).

Increasing tumor burden, measured as the sum in millimeters of the longest tumor diameter of each measurable lesion, during active surveillance was associated with both poorer total overall survival (HR, 1.16; P = .024) and poorer postsurveillance overall survival (HR, 1.21; P = .004).

Finally, an IMDC class of good or intermediate versus poor at the start of systemic therapy was a favorable predictor (HR, 0.07; P = .010; and HR, 0.12; P = .044, respectively) and an increase in tumor burden was an unfavorable predictor (HR, 1.26; P = .005) of postsurveillance overall survival.

“Our study confirms that active surveillance is a safe option for certain patients, with a median time on surveillance of 1.5 years delaying the beginning of systemic therapies and avoiding drug-related toxicities, with a median overall survival greater than 6.5 years,” wrote Dr. Bimbatti and coinvestigators.

“During active surveillance, patients rarely show any deterioration of the IMDC prognostic class. Meanwhile, the tumor burden changes, more than the increase of metastatic sites, account for the heterogeneity of the disease and may help physicians to make decisions about the early termination of active surveillance and the start of systemic therapy,” they concluded.

SOURCE: Bimbatti D et al. Urol Oncol. 2018 Oct 6. doi: 10.1016/j.urolonc.2018.08.018.

Various disease parameters can help clinicians make treatment decisions for patients with metastatic renal cell carcinoma (mRCC) undergoing active surveillance, but the change in tumor burden may be the best, suggests an Italian cohort study.

Investigators led by Davide Bimbatti, MD, of Azienda Ospedaliera Universitaria Integrata in Verona, Italy, retrospectively studied 52 patients with mRCC who started active surveillance as their initial strategy for disease management. They assessed three predictors of outcomes: International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk class, number of metastatic sites, and tumor burden.

Patients remained on active surveillance for a median of 18.3 months and had a median total overall survival of 80.1 months, according to study results published in Urologic Oncology. Fully 69.2% started first-line systemic therapy during a median follow-up of 38.5 months.

The only baseline factor predicting time on active surveillance was IMDC class (hazard ratio, 2.15; P = .011).

An increasing number of metastatic sites during active surveillance was associated with poorer total overall survival (HR, 2.86; P = .010) and a trend toward poorer postsurveillance overall survival (HR, 2.37; P = .060).

Increasing tumor burden, measured as the sum in millimeters of the longest tumor diameter of each measurable lesion, during active surveillance was associated with both poorer total overall survival (HR, 1.16; P = .024) and poorer postsurveillance overall survival (HR, 1.21; P = .004).

Finally, an IMDC class of good or intermediate versus poor at the start of systemic therapy was a favorable predictor (HR, 0.07; P = .010; and HR, 0.12; P = .044, respectively) and an increase in tumor burden was an unfavorable predictor (HR, 1.26; P = .005) of postsurveillance overall survival.

“Our study confirms that active surveillance is a safe option for certain patients, with a median time on surveillance of 1.5 years delaying the beginning of systemic therapies and avoiding drug-related toxicities, with a median overall survival greater than 6.5 years,” wrote Dr. Bimbatti and coinvestigators.

“During active surveillance, patients rarely show any deterioration of the IMDC prognostic class. Meanwhile, the tumor burden changes, more than the increase of metastatic sites, account for the heterogeneity of the disease and may help physicians to make decisions about the early termination of active surveillance and the start of systemic therapy,” they concluded.

SOURCE: Bimbatti D et al. Urol Oncol. 2018 Oct 6. doi: 10.1016/j.urolonc.2018.08.018.

A new clinical practice guideline on the management of bradycardia and cardiac conduction system disorders in adults emphasizes the importance of patient-centered care and “shared decision-making” between patient and clinician, particularly with regard to patients who have indications for pacemaker implantation.

Shared decision-making extends to the end-of-life setting where “complex” informed consent and refusal of care decisions need to be patient-specific, and must involve all stakeholders, according to the new 2018 guidelines from the American College of Cardiology (ACC), American Heart Association (AHA), and Heart Rhythm Society (HRS).

“Patients with decision-making capacity or his/her legally defined surrogate has the right to refuse or request withdrawal of pacemaker therapy, even if the patient is pacemaker dependent, which should be considered palliative, end-of-life care, and not physician-assisted suicide,” the guidelines read.

The guidelines additionally update the evaluation and treatment of sinus node dysfunction, atrioventricular block, and conduction disorders, based in part on a comprehensive evidence review conducted from January to September 2017. They supersede a 2008 guideline from the three societies on device-based therapy of cardiac rhythm abnormalities, and the focused update to that guideline published in 2012.

These guidelines will be useful not only to arrhythmia specialists, but also to internists and family physicians, cardiologists, surgeons, emergency physicians, and anesthesiologists, according to the guideline writing committee, which included representativens of ACC, AHA, HRS, and several other national organizations. The committee included cardiac electrophysiologists, cardiologists, surgeons, an anesthesiologist, and other clinicians, as well as a patient/lay representative, and was chaired by Fred M. Kusumoto, MD, of Mayo Clinic Florida in Jacksonville.

For sinus node dysfunction, no minimum heart rate or pause duration has been determined for which permanent pacing would be recommended, the guidelines state. To determine whether permanent pacing is necessary in those patients, clinicians should work to establish a temporal correlation bewteen bradycardia and symptoms, according to the guideline authors.

Left bundle branch block, when found on echocardiogram, greatly increases the chances of underlying structural heart disease and of a left ventricular systolic dysfunction diagnosis, according to the guidelines, which state that echocardiography is the most appropriate initial screening test for left ventricular systolic dysfunction and other structural heart disease.

Permanent pacing is recommended for certain types of atrioventricular (AV) block, according to the guidelines, which include high-grade AV block, acquired second-degree Mobitz type II AV block, and third-degree AV block not related to reversible or physiologic causes.

Treatment of sleep apnea can reduce frequency of nocturnal bradycardia and may provide a cardiovascular benefit, the guideline authors state. Patients with nocturnal bradycardias should be screened for sleep apnea, though authors cautioned that these arrhythmias are not, in and of themselves, an indication for permanent pacing.

“Treatment decisions are based not only on the best available evidence, but also on the patient’s goals of care and preferences,” Dr. Kusumoto said in a press release jointly issued by the ACC, AHA, and HRS. Toward that end, patients should receive “trusted material” to help them understand the consequences and risks of any proposed management decision.

Emerging pacing technologies such as His bundle pacing and transcatheter leadless pacing systems need more study to determine which patient populations will benefit most from them, the guidelines state.

“Regardless of technology, for the foreseeable future, pacing therapy requires implantation of a medical device,” Dr. Kusumoto said in the release. “Future studies are warranted to focus on the long-term implications associated with lifelong therapy.”

The 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay is now published in the Journal of the American College of Cardiology, and simultaneously in the journals Circulation and HeartRhythm.

Dr. Kusumoto reported no relationships with industry or other entities. Guideline co-authors provided disclosures related to Boston Scientific, Janssen Pharmaceuticals, Medtronic, Daiichi-Sankyo, Sanofi-Aventis, St. Jude Medical, and Abbott, among others.
 

SOURCE: Kusumoto FM, et al. J Am Coll Cardiol. 2018 Nov 6.

A new clinical practice guideline on the management of bradycardia and cardiac conduction system disorders in adults emphasizes the importance of patient-centered care and “shared decision-making” between patient and clinician, particularly with regard to patients who have indications for pacemaker implantation.

Shared decision-making extends to the end-of-life setting where “complex” informed consent and refusal of care decisions need to be patient-specific, and must involve all stakeholders, according to the new 2018 guidelines from the American College of Cardiology (ACC), American Heart Association (AHA), and Heart Rhythm Society (HRS).

“Patients with decision-making capacity or his/her legally defined surrogate has the right to refuse or request withdrawal of pacemaker therapy, even if the patient is pacemaker dependent, which should be considered palliative, end-of-life care, and not physician-assisted suicide,” the guidelines read.

The guidelines additionally update the evaluation and treatment of sinus node dysfunction, atrioventricular block, and conduction disorders, based in part on a comprehensive evidence review conducted from January to September 2017. They supersede a 2008 guideline from the three societies on device-based therapy of cardiac rhythm abnormalities, and the focused update to that guideline published in 2012.

These guidelines will be useful not only to arrhythmia specialists, but also to internists and family physicians, cardiologists, surgeons, emergency physicians, and anesthesiologists, according to the guideline writing committee, which included representativens of ACC, AHA, HRS, and several other national organizations. The committee included cardiac electrophysiologists, cardiologists, surgeons, an anesthesiologist, and other clinicians, as well as a patient/lay representative, and was chaired by Fred M. Kusumoto, MD, of Mayo Clinic Florida in Jacksonville.

For sinus node dysfunction, no minimum heart rate or pause duration has been determined for which permanent pacing would be recommended, the guidelines state. To determine whether permanent pacing is necessary in those patients, clinicians should work to establish a temporal correlation bewteen bradycardia and symptoms, according to the guideline authors.

Left bundle branch block, when found on echocardiogram, greatly increases the chances of underlying structural heart disease and of a left ventricular systolic dysfunction diagnosis, according to the guidelines, which state that echocardiography is the most appropriate initial screening test for left ventricular systolic dysfunction and other structural heart disease.

Permanent pacing is recommended for certain types of atrioventricular (AV) block, according to the guidelines, which include high-grade AV block, acquired second-degree Mobitz type II AV block, and third-degree AV block not related to reversible or physiologic causes.

Treatment of sleep apnea can reduce frequency of nocturnal bradycardia and may provide a cardiovascular benefit, the guideline authors state. Patients with nocturnal bradycardias should be screened for sleep apnea, though authors cautioned that these arrhythmias are not, in and of themselves, an indication for permanent pacing.

“Treatment decisions are based not only on the best available evidence, but also on the patient’s goals of care and preferences,” Dr. Kusumoto said in a press release jointly issued by the ACC, AHA, and HRS. Toward that end, patients should receive “trusted material” to help them understand the consequences and risks of any proposed management decision.

Emerging pacing technologies such as His bundle pacing and transcatheter leadless pacing systems need more study to determine which patient populations will benefit most from them, the guidelines state.

“Regardless of technology, for the foreseeable future, pacing therapy requires implantation of a medical device,” Dr. Kusumoto said in the release. “Future studies are warranted to focus on the long-term implications associated with lifelong therapy.”

The 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay is now published in the Journal of the American College of Cardiology, and simultaneously in the journals Circulation and HeartRhythm.

Dr. Kusumoto reported no relationships with industry or other entities. Guideline co-authors provided disclosures related to Boston Scientific, Janssen Pharmaceuticals, Medtronic, Daiichi-Sankyo, Sanofi-Aventis, St. Jude Medical, and Abbott, among others.
 

SOURCE: Kusumoto FM, et al. J Am Coll Cardiol. 2018 Nov 6.

A new clinical practice guideline on the management of bradycardia and cardiac conduction system disorders in adults emphasizes the importance of patient-centered care and “shared decision-making” between patient and clinician, particularly with regard to patients who have indications for pacemaker implantation.

Shared decision-making extends to the end-of-life setting where “complex” informed consent and refusal of care decisions need to be patient-specific, and must involve all stakeholders, according to the new 2018 guidelines from the American College of Cardiology (ACC), American Heart Association (AHA), and Heart Rhythm Society (HRS).

“Patients with decision-making capacity or his/her legally defined surrogate has the right to refuse or request withdrawal of pacemaker therapy, even if the patient is pacemaker dependent, which should be considered palliative, end-of-life care, and not physician-assisted suicide,” the guidelines read.

The guidelines additionally update the evaluation and treatment of sinus node dysfunction, atrioventricular block, and conduction disorders, based in part on a comprehensive evidence review conducted from January to September 2017. They supersede a 2008 guideline from the three societies on device-based therapy of cardiac rhythm abnormalities, and the focused update to that guideline published in 2012.

These guidelines will be useful not only to arrhythmia specialists, but also to internists and family physicians, cardiologists, surgeons, emergency physicians, and anesthesiologists, according to the guideline writing committee, which included representativens of ACC, AHA, HRS, and several other national organizations. The committee included cardiac electrophysiologists, cardiologists, surgeons, an anesthesiologist, and other clinicians, as well as a patient/lay representative, and was chaired by Fred M. Kusumoto, MD, of Mayo Clinic Florida in Jacksonville.

For sinus node dysfunction, no minimum heart rate or pause duration has been determined for which permanent pacing would be recommended, the guidelines state. To determine whether permanent pacing is necessary in those patients, clinicians should work to establish a temporal correlation bewteen bradycardia and symptoms, according to the guideline authors.

Left bundle branch block, when found on echocardiogram, greatly increases the chances of underlying structural heart disease and of a left ventricular systolic dysfunction diagnosis, according to the guidelines, which state that echocardiography is the most appropriate initial screening test for left ventricular systolic dysfunction and other structural heart disease.

Permanent pacing is recommended for certain types of atrioventricular (AV) block, according to the guidelines, which include high-grade AV block, acquired second-degree Mobitz type II AV block, and third-degree AV block not related to reversible or physiologic causes.

Treatment of sleep apnea can reduce frequency of nocturnal bradycardia and may provide a cardiovascular benefit, the guideline authors state. Patients with nocturnal bradycardias should be screened for sleep apnea, though authors cautioned that these arrhythmias are not, in and of themselves, an indication for permanent pacing.

“Treatment decisions are based not only on the best available evidence, but also on the patient’s goals of care and preferences,” Dr. Kusumoto said in a press release jointly issued by the ACC, AHA, and HRS. Toward that end, patients should receive “trusted material” to help them understand the consequences and risks of any proposed management decision.

Emerging pacing technologies such as His bundle pacing and transcatheter leadless pacing systems need more study to determine which patient populations will benefit most from them, the guidelines state.

“Regardless of technology, for the foreseeable future, pacing therapy requires implantation of a medical device,” Dr. Kusumoto said in the release. “Future studies are warranted to focus on the long-term implications associated with lifelong therapy.”

The 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay is now published in the Journal of the American College of Cardiology, and simultaneously in the journals Circulation and HeartRhythm.

Dr. Kusumoto reported no relationships with industry or other entities. Guideline co-authors provided disclosures related to Boston Scientific, Janssen Pharmaceuticals, Medtronic, Daiichi-Sankyo, Sanofi-Aventis, St. Jude Medical, and Abbott, among others.
 

SOURCE: Kusumoto FM, et al. J Am Coll Cardiol. 2018 Nov 6.

ORLANDO – Flavoring and lack of Food and Drug Administration regulation of e-cigarettes has led to more children and adolescents using these devices, according to American Academy of Pediatrics President Colleen A. Kraft, MD.

In an interview, Dr. Kraft said the FDA should regulate these products and limit their purchase to adults who are at least 21 years old. E-cigarettes were initially intended as an aid for adults to reduce their cigarette use, but the addition of flavoring has attracted children and adolescents to the devices, Dr. Kraft noted.

“When you have these devices that have flavors like gummy bear and cotton candy and bubblegum, you are marketing to children, and we are calling out the FDA because they could actually stop this today,” she said. In fact, Dr. Kraft added, many children and adolescents don’t even realize that e-cigarettes contain nicotine.

Dr. Kraft reported no relevant conflicts of interest.

ORLANDO – Flavoring and lack of Food and Drug Administration regulation of e-cigarettes has led to more children and adolescents using these devices, according to American Academy of Pediatrics President Colleen A. Kraft, MD.

In an interview, Dr. Kraft said the FDA should regulate these products and limit their purchase to adults who are at least 21 years old. E-cigarettes were initially intended as an aid for adults to reduce their cigarette use, but the addition of flavoring has attracted children and adolescents to the devices, Dr. Kraft noted.

“When you have these devices that have flavors like gummy bear and cotton candy and bubblegum, you are marketing to children, and we are calling out the FDA because they could actually stop this today,” she said. In fact, Dr. Kraft added, many children and adolescents don’t even realize that e-cigarettes contain nicotine.

Dr. Kraft reported no relevant conflicts of interest.

ORLANDO – Flavoring and lack of Food and Drug Administration regulation of e-cigarettes has led to more children and adolescents using these devices, according to American Academy of Pediatrics President Colleen A. Kraft, MD.

In an interview, Dr. Kraft said the FDA should regulate these products and limit their purchase to adults who are at least 21 years old. E-cigarettes were initially intended as an aid for adults to reduce their cigarette use, but the addition of flavoring has attracted children and adolescents to the devices, Dr. Kraft noted.

“When you have these devices that have flavors like gummy bear and cotton candy and bubblegum, you are marketing to children, and we are calling out the FDA because they could actually stop this today,” she said. In fact, Dr. Kraft added, many children and adolescents don’t even realize that e-cigarettes contain nicotine.

Dr. Kraft reported no relevant conflicts of interest.

ORLANDO – Pediatricians can learn from how Millennials use services and purchase products from popular companies, such as Amazon Alexa, Warby Parker, Instagram, and Snapchat, and use that information to connect with Millennial parents and children in their practice, Kristopher Jones, JD, MS, said.

In a video interview, Mr. Jones explained how Amazon Alexa uses structured data as recommendations when users make queries of the service; for example, a Millennial might make a choice to book an appointment with a pediatrician based on the results Amazon Alexa displays, such as an office’s available hours. An office that is not optimized to appear in those results would be missed by those potential patients.

Warby Parker has a digital-first strategy focused on convenience, ease of use, and an emphasis on mission; one opportunity for pediatricians in this area is to be more overt about which causes they are supporting, Mr. Jones said. In the case of Instagram and Snapchat, pediatricians should consider creating a presence on these platforms and focusing on less text-heavy content to appeal to Millennials.

“It’s a really, really important opportunity to be able to meet the Millennials where they want to be met, and that means developing strategies to leveraging pictures and videos and other forms of Millennial content to communicate with them,” he said.

Mr. Jones reported no relevant conflicts of interest.

ORLANDO – Pediatricians can learn from how Millennials use services and purchase products from popular companies, such as Amazon Alexa, Warby Parker, Instagram, and Snapchat, and use that information to connect with Millennial parents and children in their practice, Kristopher Jones, JD, MS, said.

In a video interview, Mr. Jones explained how Amazon Alexa uses structured data as recommendations when users make queries of the service; for example, a Millennial might make a choice to book an appointment with a pediatrician based on the results Amazon Alexa displays, such as an office’s available hours. An office that is not optimized to appear in those results would be missed by those potential patients.

Warby Parker has a digital-first strategy focused on convenience, ease of use, and an emphasis on mission; one opportunity for pediatricians in this area is to be more overt about which causes they are supporting, Mr. Jones said. In the case of Instagram and Snapchat, pediatricians should consider creating a presence on these platforms and focusing on less text-heavy content to appeal to Millennials.

“It’s a really, really important opportunity to be able to meet the Millennials where they want to be met, and that means developing strategies to leveraging pictures and videos and other forms of Millennial content to communicate with them,” he said.

Mr. Jones reported no relevant conflicts of interest.

ORLANDO – Pediatricians can learn from how Millennials use services and purchase products from popular companies, such as Amazon Alexa, Warby Parker, Instagram, and Snapchat, and use that information to connect with Millennial parents and children in their practice, Kristopher Jones, JD, MS, said.

In a video interview, Mr. Jones explained how Amazon Alexa uses structured data as recommendations when users make queries of the service; for example, a Millennial might make a choice to book an appointment with a pediatrician based on the results Amazon Alexa displays, such as an office’s available hours. An office that is not optimized to appear in those results would be missed by those potential patients.

Warby Parker has a digital-first strategy focused on convenience, ease of use, and an emphasis on mission; one opportunity for pediatricians in this area is to be more overt about which causes they are supporting, Mr. Jones said. In the case of Instagram and Snapchat, pediatricians should consider creating a presence on these platforms and focusing on less text-heavy content to appeal to Millennials.

“It’s a really, really important opportunity to be able to meet the Millennials where they want to be met, and that means developing strategies to leveraging pictures and videos and other forms of Millennial content to communicate with them,” he said.

Mr. Jones reported no relevant conflicts of interest.

ORLANDO – The American Academy of Pediatrics has issued a new policy statement taking a stronger stance against corporal punishment, including spanking, 20 years after releasing its last position statement on effective discipline.

The 1998 policy statement discouraged the use of corporal punishment and encouraged parents to seek other ways to discipline their children, while the latest statement goes further, citing the latest research showing corporal punishment’s harmful effects on children and encouraging pediatricians to counsel parents about the harms of corporal punishment and offer alternative forms of discipline. The 2018 policy statement will be published in the December issue of Pediatrics.

Support for corporal punishment, such as spanking, is declining. According to the Child Trends data bank, 76% of men and 66% of women supported spanking in some cases, compared with 84% of men and 82% of women in 1986. In its latest statement, the AAP noted that 6% of pediatricians (92% in primary care) supported spanking in a 2016 survey of 787 pediatricians.

In a presentation at the annual meeting of the American Academy of Pediatrics, Ryan D. Brown, MD, of the University of Oklahoma, Oklahoma City, noted that studies have shown children who are spanked are more likely to exhibit mental health problems, antisocial behavior, aggression, negative relationships with a parent, low self-esteem, externalizing behavior such as acting out, substance abuse, low moral internalization, and are more likely to be victims of physical abuse. He cited a study showing that children who were spanked one time per month had a 14%-19% reduction in the decision making area of their brains (Neuroimage. 2009 Aug;47 Suppl 2:T66-T71) and another study showing that children spanked aged between 2 and 9 years had 2.8-5.0 fewer IQ points than children who were not spanked (J Aggress Maltreat Trauma. 2009 Jul 22;18[5]:459-83).

Science has shown that there are more effective ways of disciplining children, and pediatricians are the experts who can explain the difference between discipline and punishment. Parents can use discipline as a teaching opportunity while corporal punishment inflicts physical pain on children with the intent to modify behavior. However, this does not train children to learn. “We want to teach our children to grow,” Dr. Brown said.

He pointed out the AAP’s policy on ipecac syrup and erythromycin/sulfafurazole for otitis media as examples of recommendations changing when more scientific data becomes available.

“[W]hen we get parents that say, ‘You know what? I was spanked as a kid and I turned out okay,’ I said, ‘You know, I rode in a car without a seat belt, but science has shown seat belts are effective,’ ” Dr. Brown said.

Instead of spanking and other forms of corporal punishment, parents should practice positive parenting, such as telling a child when they are being “good,” so children understand what good behavior looks like to build up self-esteem. Parents also should play with their children daily and provide simple, easy-to-understand commands. “Interact with the kids so they can see what is good behavior,” he said.

Disciplining children should be swift, age appropriate relative to mental rather than chronological age, and the discipline should “fit the crime,” Dr. Brown said. Parents also should not discipline a child in accidental situations, such as dropping a glass when helping clean up the dinner table, he added.

“The only time I kind of say that [discipline] should be delayed is in kids [who] understand the delay,” such as teenagers, Dr. Brown added. Rather than embarrassing or shaming a teenager in public for their behavior, parents should address the issue in private.

Pediatricians can implement the new guidelines in their practices by providing resources to parents about alternative forms of discipline, such as the AAP sites HealthyChildren.org and Connected Kids, training office staff in diffusing stressful situations between a caregiver and a child, and making their office a “no hit zone” for caregivers and children.

Dr. Brown reported no relevant conflicts of interest.

ORLANDO – The American Academy of Pediatrics has issued a new policy statement taking a stronger stance against corporal punishment, including spanking, 20 years after releasing its last position statement on effective discipline.

The 1998 policy statement discouraged the use of corporal punishment and encouraged parents to seek other ways to discipline their children, while the latest statement goes further, citing the latest research showing corporal punishment’s harmful effects on children and encouraging pediatricians to counsel parents about the harms of corporal punishment and offer alternative forms of discipline. The 2018 policy statement will be published in the December issue of Pediatrics.

Support for corporal punishment, such as spanking, is declining. According to the Child Trends data bank, 76% of men and 66% of women supported spanking in some cases, compared with 84% of men and 82% of women in 1986. In its latest statement, the AAP noted that 6% of pediatricians (92% in primary care) supported spanking in a 2016 survey of 787 pediatricians.

In a presentation at the annual meeting of the American Academy of Pediatrics, Ryan D. Brown, MD, of the University of Oklahoma, Oklahoma City, noted that studies have shown children who are spanked are more likely to exhibit mental health problems, antisocial behavior, aggression, negative relationships with a parent, low self-esteem, externalizing behavior such as acting out, substance abuse, low moral internalization, and are more likely to be victims of physical abuse. He cited a study showing that children who were spanked one time per month had a 14%-19% reduction in the decision making area of their brains (Neuroimage. 2009 Aug;47 Suppl 2:T66-T71) and another study showing that children spanked aged between 2 and 9 years had 2.8-5.0 fewer IQ points than children who were not spanked (J Aggress Maltreat Trauma. 2009 Jul 22;18[5]:459-83).

Science has shown that there are more effective ways of disciplining children, and pediatricians are the experts who can explain the difference between discipline and punishment. Parents can use discipline as a teaching opportunity while corporal punishment inflicts physical pain on children with the intent to modify behavior. However, this does not train children to learn. “We want to teach our children to grow,” Dr. Brown said.

He pointed out the AAP’s policy on ipecac syrup and erythromycin/sulfafurazole for otitis media as examples of recommendations changing when more scientific data becomes available.

“[W]hen we get parents that say, ‘You know what? I was spanked as a kid and I turned out okay,’ I said, ‘You know, I rode in a car without a seat belt, but science has shown seat belts are effective,’ ” Dr. Brown said.

Instead of spanking and other forms of corporal punishment, parents should practice positive parenting, such as telling a child when they are being “good,” so children understand what good behavior looks like to build up self-esteem. Parents also should play with their children daily and provide simple, easy-to-understand commands. “Interact with the kids so they can see what is good behavior,” he said.

Disciplining children should be swift, age appropriate relative to mental rather than chronological age, and the discipline should “fit the crime,” Dr. Brown said. Parents also should not discipline a child in accidental situations, such as dropping a glass when helping clean up the dinner table, he added.

“The only time I kind of say that [discipline] should be delayed is in kids [who] understand the delay,” such as teenagers, Dr. Brown added. Rather than embarrassing or shaming a teenager in public for their behavior, parents should address the issue in private.

Pediatricians can implement the new guidelines in their practices by providing resources to parents about alternative forms of discipline, such as the AAP sites HealthyChildren.org and Connected Kids, training office staff in diffusing stressful situations between a caregiver and a child, and making their office a “no hit zone” for caregivers and children.

Dr. Brown reported no relevant conflicts of interest.

ORLANDO – The American Academy of Pediatrics has issued a new policy statement taking a stronger stance against corporal punishment, including spanking, 20 years after releasing its last position statement on effective discipline.

The 1998 policy statement discouraged the use of corporal punishment and encouraged parents to seek other ways to discipline their children, while the latest statement goes further, citing the latest research showing corporal punishment’s harmful effects on children and encouraging pediatricians to counsel parents about the harms of corporal punishment and offer alternative forms of discipline. The 2018 policy statement will be published in the December issue of Pediatrics.

Support for corporal punishment, such as spanking, is declining. According to the Child Trends data bank, 76% of men and 66% of women supported spanking in some cases, compared with 84% of men and 82% of women in 1986. In its latest statement, the AAP noted that 6% of pediatricians (92% in primary care) supported spanking in a 2016 survey of 787 pediatricians.

In a presentation at the annual meeting of the American Academy of Pediatrics, Ryan D. Brown, MD, of the University of Oklahoma, Oklahoma City, noted that studies have shown children who are spanked are more likely to exhibit mental health problems, antisocial behavior, aggression, negative relationships with a parent, low self-esteem, externalizing behavior such as acting out, substance abuse, low moral internalization, and are more likely to be victims of physical abuse. He cited a study showing that children who were spanked one time per month had a 14%-19% reduction in the decision making area of their brains (Neuroimage. 2009 Aug;47 Suppl 2:T66-T71) and another study showing that children spanked aged between 2 and 9 years had 2.8-5.0 fewer IQ points than children who were not spanked (J Aggress Maltreat Trauma. 2009 Jul 22;18[5]:459-83).

Science has shown that there are more effective ways of disciplining children, and pediatricians are the experts who can explain the difference between discipline and punishment. Parents can use discipline as a teaching opportunity while corporal punishment inflicts physical pain on children with the intent to modify behavior. However, this does not train children to learn. “We want to teach our children to grow,” Dr. Brown said.

He pointed out the AAP’s policy on ipecac syrup and erythromycin/sulfafurazole for otitis media as examples of recommendations changing when more scientific data becomes available.

“[W]hen we get parents that say, ‘You know what? I was spanked as a kid and I turned out okay,’ I said, ‘You know, I rode in a car without a seat belt, but science has shown seat belts are effective,’ ” Dr. Brown said.

Instead of spanking and other forms of corporal punishment, parents should practice positive parenting, such as telling a child when they are being “good,” so children understand what good behavior looks like to build up self-esteem. Parents also should play with their children daily and provide simple, easy-to-understand commands. “Interact with the kids so they can see what is good behavior,” he said.

Disciplining children should be swift, age appropriate relative to mental rather than chronological age, and the discipline should “fit the crime,” Dr. Brown said. Parents also should not discipline a child in accidental situations, such as dropping a glass when helping clean up the dinner table, he added.

“The only time I kind of say that [discipline] should be delayed is in kids [who] understand the delay,” such as teenagers, Dr. Brown added. Rather than embarrassing or shaming a teenager in public for their behavior, parents should address the issue in private.

Pediatricians can implement the new guidelines in their practices by providing resources to parents about alternative forms of discipline, such as the AAP sites HealthyChildren.org and Connected Kids, training office staff in diffusing stressful situations between a caregiver and a child, and making their office a “no hit zone” for caregivers and children.

Dr. Brown reported no relevant conflicts of interest.

Two new guidelines are set to be presented at the American Heart Association scientific sessions in Chicago.

First up will be the first update to the controversial 2013 cholesterol guidelines, which will be presented on Saturday, Nov. 10, in two sessions.

Second, the U.S. Department of Health and Human Services will unveil its new national guidelines for physical activity on Monday, Nov. 12.

Based on new information that has become available since previous versions, both are expected to include substantial changes.
 

Cholesterol guidelines

For the cholesterol guidelines, the most important messages for clinical practice will be presented in a session beginning at 10:45 a.m. A second session, beginning at 5:30 p.m. on Saturday, can be considered more of a “deep dive” into the details and rationale, Donald M. Lloyd-Jones, MD, cochair of this year’s Committee on Scientific Sessions Program, said in a teleconference with reporters.

“In the 10:45 session, we plan to cover the most important take-home messages and top-line issues,” explained Dr. Lloyd-Jones, a professor of cardiology at Northwestern University, Chicago, as well as one of the authors of both the 2013 cholesterol guidelines and these updated ones.

This will include the key changes since the AHA/American College of Cardiology Guideline on the Assessment of Cardiovascular Risk guidelines were released 2013. One major update will be the inclusion of the role of PCSK9 inhibitors, which were introduced after the 2013 guidelines were written. Moreover, the new guidelines will devote attention to personalizing treatment choices, according to Dr. Lloyd-Jones.

“The deep-dive session later that day will cover such issues as risk assessment and cost effectiveness of drug treatments for specific populations,” said Dr. Lloyd-Jones, who added that case studies will be presented to illustrate how the new recommendations should affect practice.

Because of changes in risk assessment, the 2013 guidelines, which greatly expanded the candidates for lipid-lowering therapies, were labeled “controversial” in numerous critiques published in peer-reviewed journals and elsewhere. The authors of the new guidelines hope to avoid these problems.

“Since 2013, I think there have been questions about when we should use risk scores, whether there are risk scores that might be better than others, or if there are strategies of risk assessment we should be employing beyond just risk scores,” Dr. Lloyd-Jones acknowledged. “This was a big part of the discussion in developing these guidelines, and I think you will see some pretty significant advances in how we think about which patients are appropriate for treatment and which patients in whom we might think of withholding statin therapy when benefit is unlikely.”

Despite the large number of changes, Dr. Lloyd-Jones emphasized that the document will be more concise and easier to use than the guidelines from 2013.

“The organization is modular, meaning that if you have a question about a certain aspect of management, you can go straight to the recommendation, which is accompanied by very brief text to explain the rationale,” Dr. Lloyd-Jones reported. “The presentation has been very much streamlined.”
 

HHS Guidelines on Physical Activity

The HHS guidelines on physical activity will be presented at 9 a.m. on Monday, Nov. 12. The 2018 version will be the first update since the original guidelines were made available in 2008.

“It has been 10 years since the last set of guidelines, and I think we are all looking forward to what these new recommendations will offer,” Dr. Lloyd-Jones said. He believes that the science has progressed significantly over the past decade.

“In addition to our longstanding understanding that doing something is better than doing nothing and doing more is better than doing something, I think we have seen some really interesting data in the last 10 years on intensity and duration of exercise and how those can be considered when trying to improve health-related outcomes,” said Dr. Lloyd-Jones.

The specifics of these guidelines will not be known until they are presented on Monday, but there is abundant evidence that a healthy lifestyle is the first defense against illness in general and against cardiovascular disease in particular. Dr. Lloyd-Jones indicated that authoritative and evidence-based guidelines could prove to a useful tool for empowering patients to make changes that reduce an array of health risks not just those related to vascular disease.












 

Two new guidelines are set to be presented at the American Heart Association scientific sessions in Chicago.

First up will be the first update to the controversial 2013 cholesterol guidelines, which will be presented on Saturday, Nov. 10, in two sessions.

Second, the U.S. Department of Health and Human Services will unveil its new national guidelines for physical activity on Monday, Nov. 12.

Based on new information that has become available since previous versions, both are expected to include substantial changes.
 

Cholesterol guidelines

For the cholesterol guidelines, the most important messages for clinical practice will be presented in a session beginning at 10:45 a.m. A second session, beginning at 5:30 p.m. on Saturday, can be considered more of a “deep dive” into the details and rationale, Donald M. Lloyd-Jones, MD, cochair of this year’s Committee on Scientific Sessions Program, said in a teleconference with reporters.

“In the 10:45 session, we plan to cover the most important take-home messages and top-line issues,” explained Dr. Lloyd-Jones, a professor of cardiology at Northwestern University, Chicago, as well as one of the authors of both the 2013 cholesterol guidelines and these updated ones.

This will include the key changes since the AHA/American College of Cardiology Guideline on the Assessment of Cardiovascular Risk guidelines were released 2013. One major update will be the inclusion of the role of PCSK9 inhibitors, which were introduced after the 2013 guidelines were written. Moreover, the new guidelines will devote attention to personalizing treatment choices, according to Dr. Lloyd-Jones.

“The deep-dive session later that day will cover such issues as risk assessment and cost effectiveness of drug treatments for specific populations,” said Dr. Lloyd-Jones, who added that case studies will be presented to illustrate how the new recommendations should affect practice.

Because of changes in risk assessment, the 2013 guidelines, which greatly expanded the candidates for lipid-lowering therapies, were labeled “controversial” in numerous critiques published in peer-reviewed journals and elsewhere. The authors of the new guidelines hope to avoid these problems.

“Since 2013, I think there have been questions about when we should use risk scores, whether there are risk scores that might be better than others, or if there are strategies of risk assessment we should be employing beyond just risk scores,” Dr. Lloyd-Jones acknowledged. “This was a big part of the discussion in developing these guidelines, and I think you will see some pretty significant advances in how we think about which patients are appropriate for treatment and which patients in whom we might think of withholding statin therapy when benefit is unlikely.”

Despite the large number of changes, Dr. Lloyd-Jones emphasized that the document will be more concise and easier to use than the guidelines from 2013.

“The organization is modular, meaning that if you have a question about a certain aspect of management, you can go straight to the recommendation, which is accompanied by very brief text to explain the rationale,” Dr. Lloyd-Jones reported. “The presentation has been very much streamlined.”
 

HHS Guidelines on Physical Activity

The HHS guidelines on physical activity will be presented at 9 a.m. on Monday, Nov. 12. The 2018 version will be the first update since the original guidelines were made available in 2008.

“It has been 10 years since the last set of guidelines, and I think we are all looking forward to what these new recommendations will offer,” Dr. Lloyd-Jones said. He believes that the science has progressed significantly over the past decade.

“In addition to our longstanding understanding that doing something is better than doing nothing and doing more is better than doing something, I think we have seen some really interesting data in the last 10 years on intensity and duration of exercise and how those can be considered when trying to improve health-related outcomes,” said Dr. Lloyd-Jones.

The specifics of these guidelines will not be known until they are presented on Monday, but there is abundant evidence that a healthy lifestyle is the first defense against illness in general and against cardiovascular disease in particular. Dr. Lloyd-Jones indicated that authoritative and evidence-based guidelines could prove to a useful tool for empowering patients to make changes that reduce an array of health risks not just those related to vascular disease.












 

Two new guidelines are set to be presented at the American Heart Association scientific sessions in Chicago.

First up will be the first update to the controversial 2013 cholesterol guidelines, which will be presented on Saturday, Nov. 10, in two sessions.

Second, the U.S. Department of Health and Human Services will unveil its new national guidelines for physical activity on Monday, Nov. 12.

Based on new information that has become available since previous versions, both are expected to include substantial changes.
 

Cholesterol guidelines

For the cholesterol guidelines, the most important messages for clinical practice will be presented in a session beginning at 10:45 a.m. A second session, beginning at 5:30 p.m. on Saturday, can be considered more of a “deep dive” into the details and rationale, Donald M. Lloyd-Jones, MD, cochair of this year’s Committee on Scientific Sessions Program, said in a teleconference with reporters.

“In the 10:45 session, we plan to cover the most important take-home messages and top-line issues,” explained Dr. Lloyd-Jones, a professor of cardiology at Northwestern University, Chicago, as well as one of the authors of both the 2013 cholesterol guidelines and these updated ones.

This will include the key changes since the AHA/American College of Cardiology Guideline on the Assessment of Cardiovascular Risk guidelines were released 2013. One major update will be the inclusion of the role of PCSK9 inhibitors, which were introduced after the 2013 guidelines were written. Moreover, the new guidelines will devote attention to personalizing treatment choices, according to Dr. Lloyd-Jones.

“The deep-dive session later that day will cover such issues as risk assessment and cost effectiveness of drug treatments for specific populations,” said Dr. Lloyd-Jones, who added that case studies will be presented to illustrate how the new recommendations should affect practice.

Because of changes in risk assessment, the 2013 guidelines, which greatly expanded the candidates for lipid-lowering therapies, were labeled “controversial” in numerous critiques published in peer-reviewed journals and elsewhere. The authors of the new guidelines hope to avoid these problems.

“Since 2013, I think there have been questions about when we should use risk scores, whether there are risk scores that might be better than others, or if there are strategies of risk assessment we should be employing beyond just risk scores,” Dr. Lloyd-Jones acknowledged. “This was a big part of the discussion in developing these guidelines, and I think you will see some pretty significant advances in how we think about which patients are appropriate for treatment and which patients in whom we might think of withholding statin therapy when benefit is unlikely.”

Despite the large number of changes, Dr. Lloyd-Jones emphasized that the document will be more concise and easier to use than the guidelines from 2013.

“The organization is modular, meaning that if you have a question about a certain aspect of management, you can go straight to the recommendation, which is accompanied by very brief text to explain the rationale,” Dr. Lloyd-Jones reported. “The presentation has been very much streamlined.”
 

HHS Guidelines on Physical Activity

The HHS guidelines on physical activity will be presented at 9 a.m. on Monday, Nov. 12. The 2018 version will be the first update since the original guidelines were made available in 2008.

“It has been 10 years since the last set of guidelines, and I think we are all looking forward to what these new recommendations will offer,” Dr. Lloyd-Jones said. He believes that the science has progressed significantly over the past decade.

“In addition to our longstanding understanding that doing something is better than doing nothing and doing more is better than doing something, I think we have seen some really interesting data in the last 10 years on intensity and duration of exercise and how those can be considered when trying to improve health-related outcomes,” said Dr. Lloyd-Jones.

The specifics of these guidelines will not be known until they are presented on Monday, but there is abundant evidence that a healthy lifestyle is the first defense against illness in general and against cardiovascular disease in particular. Dr. Lloyd-Jones indicated that authoritative and evidence-based guidelines could prove to a useful tool for empowering patients to make changes that reduce an array of health risks not just those related to vascular disease.












 

Although a day shorter than meetings over recent years, more than 4,000 abstracts, keynote addresses, special sessions, and education programs have been squeezed into 800 sessions divided into 26 tracks of interest at the American Heart Association Scientific Sessions.

“We think that, for both for the presenters as well as for the attendees, this new format is going to be quite lively, exciting, and consistent with where scientific meetings should be going in the future,” explained Eric Peterson, MD, chair of this year’s Committee on Scientific Sessions Program in a teleconference with reporters.

The shorter program is just one of many substantive changes made by the program committee to enhance the value of attendance, according to Dr. Peterson, professor of medicine, Duke University, Durham, N.C. In particular, the committee worked to make the sessions more interactive.

“There will be much less of someone just standing up and delivering slides,” he said. Through phone apps that will allow the audience to pose questions and comments to speakers in every major session, “there will be more opportunities for the audience to give their impression of the science being delivered.”

From the beginning, it was the intention of the program committee “to do things differently,” according to Dr. Peterson as well as his cochair Donald M. Lloyd-Jones, MD, professor of cardiology at Northwestern University, Chicago.

“The 3-day format means full days, but I think that we have packed in some really exciting science,” said Dr. Lloyd-Jones, who described a diverse slate of programming goals. In addition to the traditional emphasis on new science, he said there will be more attention on “new management and new practice opportunities for clinicians to really hone their skills.”

Those coming to the Scientific Sessions will see a difference on the first day. In place of an awards ceremony and presidential address, which have long been staples of the opening sessions, this year’s meeting will begin with a series of simultaneous programs delving into key issues in cardiology and medical practice.

“We are starting things off with a bang with TED-like lectures given in multiple locations addressing the cutting edge of where we are with the hottest things in science,” Dr. Peterson said. “These will cover everything from how your microbiome might be affecting your risk for cardiovascular events to progress toward vaccines that might some day prevent cardiovascular disease.”

Innovative and forward-thinking programs unfold from there, according to Dr. Lloyd-Jones.

Health technology will be a common thread across all 3 days of the Scientific Sessions, according to Dr. Peterson. One of the 26 tracks of this year’s meeting, health technology is imposing fundamental shifts in medical practice and how health care is delivered.

“This is a topic that covers electronic medical records, your cell phone, and mobile wearable devices that can help us as clinicians better understand what is going on with cardiovascular disease as well as help ourselves as individuals modify our risks,” said Dr. Peterson. Within this track, session programs range from how-to instruction to a technology forum organized like the “Shark Tank” television program.

“Health technology is moving rapidly,” Dr. Peterson pointed out. He suggested that the AHA Scientific Sessions provide a unique opportunity for cardiologists to stay current with evolving strategies for efficient care.

Within the effort to update the meeting format, traditional forms of late-breaking science, particularly late-breaking trials with potentially practice changing data, will not be lost. However, Dr. Peterson indicated that he expects this year’s meeting to have a somewhat different pace and sensibility.

“We believe that what we have been doing will not work any longer, and we needed to do things differently,” Dr. Peterson said. While the shorter more concentrated program is one example, Dr. Peterson also believes that the effort to diminish the distance between those who are speaking and those who are listening will lead to a richer experience for everyone.
 

Although a day shorter than meetings over recent years, more than 4,000 abstracts, keynote addresses, special sessions, and education programs have been squeezed into 800 sessions divided into 26 tracks of interest at the American Heart Association Scientific Sessions.

“We think that, for both for the presenters as well as for the attendees, this new format is going to be quite lively, exciting, and consistent with where scientific meetings should be going in the future,” explained Eric Peterson, MD, chair of this year’s Committee on Scientific Sessions Program in a teleconference with reporters.

The shorter program is just one of many substantive changes made by the program committee to enhance the value of attendance, according to Dr. Peterson, professor of medicine, Duke University, Durham, N.C. In particular, the committee worked to make the sessions more interactive.

“There will be much less of someone just standing up and delivering slides,” he said. Through phone apps that will allow the audience to pose questions and comments to speakers in every major session, “there will be more opportunities for the audience to give their impression of the science being delivered.”

From the beginning, it was the intention of the program committee “to do things differently,” according to Dr. Peterson as well as his cochair Donald M. Lloyd-Jones, MD, professor of cardiology at Northwestern University, Chicago.

“The 3-day format means full days, but I think that we have packed in some really exciting science,” said Dr. Lloyd-Jones, who described a diverse slate of programming goals. In addition to the traditional emphasis on new science, he said there will be more attention on “new management and new practice opportunities for clinicians to really hone their skills.”

Those coming to the Scientific Sessions will see a difference on the first day. In place of an awards ceremony and presidential address, which have long been staples of the opening sessions, this year’s meeting will begin with a series of simultaneous programs delving into key issues in cardiology and medical practice.

“We are starting things off with a bang with TED-like lectures given in multiple locations addressing the cutting edge of where we are with the hottest things in science,” Dr. Peterson said. “These will cover everything from how your microbiome might be affecting your risk for cardiovascular events to progress toward vaccines that might some day prevent cardiovascular disease.”

Innovative and forward-thinking programs unfold from there, according to Dr. Lloyd-Jones.

Health technology will be a common thread across all 3 days of the Scientific Sessions, according to Dr. Peterson. One of the 26 tracks of this year’s meeting, health technology is imposing fundamental shifts in medical practice and how health care is delivered.

“This is a topic that covers electronic medical records, your cell phone, and mobile wearable devices that can help us as clinicians better understand what is going on with cardiovascular disease as well as help ourselves as individuals modify our risks,” said Dr. Peterson. Within this track, session programs range from how-to instruction to a technology forum organized like the “Shark Tank” television program.

“Health technology is moving rapidly,” Dr. Peterson pointed out. He suggested that the AHA Scientific Sessions provide a unique opportunity for cardiologists to stay current with evolving strategies for efficient care.

Within the effort to update the meeting format, traditional forms of late-breaking science, particularly late-breaking trials with potentially practice changing data, will not be lost. However, Dr. Peterson indicated that he expects this year’s meeting to have a somewhat different pace and sensibility.

“We believe that what we have been doing will not work any longer, and we needed to do things differently,” Dr. Peterson said. While the shorter more concentrated program is one example, Dr. Peterson also believes that the effort to diminish the distance between those who are speaking and those who are listening will lead to a richer experience for everyone.
 

Although a day shorter than meetings over recent years, more than 4,000 abstracts, keynote addresses, special sessions, and education programs have been squeezed into 800 sessions divided into 26 tracks of interest at the American Heart Association Scientific Sessions.

“We think that, for both for the presenters as well as for the attendees, this new format is going to be quite lively, exciting, and consistent with where scientific meetings should be going in the future,” explained Eric Peterson, MD, chair of this year’s Committee on Scientific Sessions Program in a teleconference with reporters.

The shorter program is just one of many substantive changes made by the program committee to enhance the value of attendance, according to Dr. Peterson, professor of medicine, Duke University, Durham, N.C. In particular, the committee worked to make the sessions more interactive.

“There will be much less of someone just standing up and delivering slides,” he said. Through phone apps that will allow the audience to pose questions and comments to speakers in every major session, “there will be more opportunities for the audience to give their impression of the science being delivered.”

From the beginning, it was the intention of the program committee “to do things differently,” according to Dr. Peterson as well as his cochair Donald M. Lloyd-Jones, MD, professor of cardiology at Northwestern University, Chicago.

“The 3-day format means full days, but I think that we have packed in some really exciting science,” said Dr. Lloyd-Jones, who described a diverse slate of programming goals. In addition to the traditional emphasis on new science, he said there will be more attention on “new management and new practice opportunities for clinicians to really hone their skills.”

Those coming to the Scientific Sessions will see a difference on the first day. In place of an awards ceremony and presidential address, which have long been staples of the opening sessions, this year’s meeting will begin with a series of simultaneous programs delving into key issues in cardiology and medical practice.

“We are starting things off with a bang with TED-like lectures given in multiple locations addressing the cutting edge of where we are with the hottest things in science,” Dr. Peterson said. “These will cover everything from how your microbiome might be affecting your risk for cardiovascular events to progress toward vaccines that might some day prevent cardiovascular disease.”

Innovative and forward-thinking programs unfold from there, according to Dr. Lloyd-Jones.

Health technology will be a common thread across all 3 days of the Scientific Sessions, according to Dr. Peterson. One of the 26 tracks of this year’s meeting, health technology is imposing fundamental shifts in medical practice and how health care is delivered.

“This is a topic that covers electronic medical records, your cell phone, and mobile wearable devices that can help us as clinicians better understand what is going on with cardiovascular disease as well as help ourselves as individuals modify our risks,” said Dr. Peterson. Within this track, session programs range from how-to instruction to a technology forum organized like the “Shark Tank” television program.

“Health technology is moving rapidly,” Dr. Peterson pointed out. He suggested that the AHA Scientific Sessions provide a unique opportunity for cardiologists to stay current with evolving strategies for efficient care.

Within the effort to update the meeting format, traditional forms of late-breaking science, particularly late-breaking trials with potentially practice changing data, will not be lost. However, Dr. Peterson indicated that he expects this year’s meeting to have a somewhat different pace and sensibility.

“We believe that what we have been doing will not work any longer, and we needed to do things differently,” Dr. Peterson said. While the shorter more concentrated program is one example, Dr. Peterson also believes that the effort to diminish the distance between those who are speaking and those who are listening will lead to a richer experience for everyone.
 

SEATTLE – A novel extrasynaptic gamma-aminobutyric acid (GABA)–receptor agonist called OV-101 was safe and well-tolerated in adult and adolescent Angelman syndrome patients in a 12-week phase 2 trial. In a secondary analysis, the treatment appeared to improve sleep.

Jim Kling/MDedge News

Angelman syndrome is associated with a microdeletion on chromosome 15 encompassing the ubiquitin protein ligase E3a (UBE3A) gene. The resulting loss of expression of the UBE3A protein leads to increases in the uptake of GABA and reduces levels of extrasynaptic GABA. Patients with Angelman syndrome typically have motor dysfunction, often extreme: “These kids are very excitable, very active, and they have lots of trouble with sleep,” said Alex Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, in an interview.

Dr. Kolevzon presented the results at a poster session at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The study was conducted at 12 sites in the United States and 1 in Israel. Ovid Pharmaceuticals plans to apply to the Food and Drug Administration later this year for approval. There is no existing drug for Angelman syndrome, and the study provided good safety reassurance. “There were some side effects, but for the most part we considered them mild, and only four (out of 88 subjects) discontinued because of side effects,” said Dr. Kolevzon.

The researchers used actigraphy to gain a more objective measure of sleep in the study participants. They randomized 88 patients with Angelman syndrome (aged 13-49 years) to receive placebo in the morning and 15 mg of OV-101 at night, 10 mg OVID-101 in the morning and 15 mg OVID-101 at night, or placebo both in the morning and at night.

Pyrexia occurred in 24% of the group who received the active drug only at night, 3% of the group given the twice-daily dose, and 7% of the placebo group. Seizures occurred in 7% of the once-daily group and 10% of the twice-daily group; seizures were not noted in the placebo group.

The main efficacy outcome measure was the Clinical Global Impressions-9 (CGI-9) scale. The once-daily group had a significant benefit in the sleep domain at 12 weeks, compared with placebo (difference, –0.77; P = .0141), but the twice-daily group had only a trend toward improvement in sleep (difference, –0.45; P = .1407).

Both active therapy groups had significant improvement in CGI-9 measures after 12 weeks of treatment compared to placebo – the twice-daily group (P = .0206, Fisher’s Exact Test) and the once-daily group (P = .0006, mixed model repeated measures analysis).

The actigraphy analysis, conducted in the 45% of patients who could tolerate its use, found that, compared to placebo, the once-daily dosing group experienced an 25.7 minute improvement in latency to sleep onset (P = .0147), as well an approximately 50 minute reduction in sleep time during the day, and a 3.65% improvement in sleep efficiency.

OV-101 has the potential to treat other conditions as well. “Obviously there are a lot of neurodevelopmental disorders where you see dysregulation between the GABAergic and glutamergic systems. This is a drug that has a unique effect on the GABAergic system. It’s already being studied in Fragile X syndrome, where we see this same kind of dysregulation and excess excitation,” said Dr. Kolevzon.

Dr. Kolevzon is a consultant for several drug companies including Ovid Therapeutics.
 

SOURCE: AACAP 2018. New Research Poster 3.1.

SEATTLE – A novel extrasynaptic gamma-aminobutyric acid (GABA)–receptor agonist called OV-101 was safe and well-tolerated in adult and adolescent Angelman syndrome patients in a 12-week phase 2 trial. In a secondary analysis, the treatment appeared to improve sleep.

Jim Kling/MDedge News

Angelman syndrome is associated with a microdeletion on chromosome 15 encompassing the ubiquitin protein ligase E3a (UBE3A) gene. The resulting loss of expression of the UBE3A protein leads to increases in the uptake of GABA and reduces levels of extrasynaptic GABA. Patients with Angelman syndrome typically have motor dysfunction, often extreme: “These kids are very excitable, very active, and they have lots of trouble with sleep,” said Alex Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, in an interview.

Dr. Kolevzon presented the results at a poster session at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The study was conducted at 12 sites in the United States and 1 in Israel. Ovid Pharmaceuticals plans to apply to the Food and Drug Administration later this year for approval. There is no existing drug for Angelman syndrome, and the study provided good safety reassurance. “There were some side effects, but for the most part we considered them mild, and only four (out of 88 subjects) discontinued because of side effects,” said Dr. Kolevzon.

The researchers used actigraphy to gain a more objective measure of sleep in the study participants. They randomized 88 patients with Angelman syndrome (aged 13-49 years) to receive placebo in the morning and 15 mg of OV-101 at night, 10 mg OVID-101 in the morning and 15 mg OVID-101 at night, or placebo both in the morning and at night.

Pyrexia occurred in 24% of the group who received the active drug only at night, 3% of the group given the twice-daily dose, and 7% of the placebo group. Seizures occurred in 7% of the once-daily group and 10% of the twice-daily group; seizures were not noted in the placebo group.

The main efficacy outcome measure was the Clinical Global Impressions-9 (CGI-9) scale. The once-daily group had a significant benefit in the sleep domain at 12 weeks, compared with placebo (difference, –0.77; P = .0141), but the twice-daily group had only a trend toward improvement in sleep (difference, –0.45; P = .1407).

Both active therapy groups had significant improvement in CGI-9 measures after 12 weeks of treatment compared to placebo – the twice-daily group (P = .0206, Fisher’s Exact Test) and the once-daily group (P = .0006, mixed model repeated measures analysis).

The actigraphy analysis, conducted in the 45% of patients who could tolerate its use, found that, compared to placebo, the once-daily dosing group experienced an 25.7 minute improvement in latency to sleep onset (P = .0147), as well an approximately 50 minute reduction in sleep time during the day, and a 3.65% improvement in sleep efficiency.

OV-101 has the potential to treat other conditions as well. “Obviously there are a lot of neurodevelopmental disorders where you see dysregulation between the GABAergic and glutamergic systems. This is a drug that has a unique effect on the GABAergic system. It’s already being studied in Fragile X syndrome, where we see this same kind of dysregulation and excess excitation,” said Dr. Kolevzon.

Dr. Kolevzon is a consultant for several drug companies including Ovid Therapeutics.
 

SOURCE: AACAP 2018. New Research Poster 3.1.

SEATTLE – A novel extrasynaptic gamma-aminobutyric acid (GABA)–receptor agonist called OV-101 was safe and well-tolerated in adult and adolescent Angelman syndrome patients in a 12-week phase 2 trial. In a secondary analysis, the treatment appeared to improve sleep.

Jim Kling/MDedge News

Angelman syndrome is associated with a microdeletion on chromosome 15 encompassing the ubiquitin protein ligase E3a (UBE3A) gene. The resulting loss of expression of the UBE3A protein leads to increases in the uptake of GABA and reduces levels of extrasynaptic GABA. Patients with Angelman syndrome typically have motor dysfunction, often extreme: “These kids are very excitable, very active, and they have lots of trouble with sleep,” said Alex Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, in an interview.

Dr. Kolevzon presented the results at a poster session at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The study was conducted at 12 sites in the United States and 1 in Israel. Ovid Pharmaceuticals plans to apply to the Food and Drug Administration later this year for approval. There is no existing drug for Angelman syndrome, and the study provided good safety reassurance. “There were some side effects, but for the most part we considered them mild, and only four (out of 88 subjects) discontinued because of side effects,” said Dr. Kolevzon.

The researchers used actigraphy to gain a more objective measure of sleep in the study participants. They randomized 88 patients with Angelman syndrome (aged 13-49 years) to receive placebo in the morning and 15 mg of OV-101 at night, 10 mg OVID-101 in the morning and 15 mg OVID-101 at night, or placebo both in the morning and at night.

Pyrexia occurred in 24% of the group who received the active drug only at night, 3% of the group given the twice-daily dose, and 7% of the placebo group. Seizures occurred in 7% of the once-daily group and 10% of the twice-daily group; seizures were not noted in the placebo group.

The main efficacy outcome measure was the Clinical Global Impressions-9 (CGI-9) scale. The once-daily group had a significant benefit in the sleep domain at 12 weeks, compared with placebo (difference, –0.77; P = .0141), but the twice-daily group had only a trend toward improvement in sleep (difference, –0.45; P = .1407).

Both active therapy groups had significant improvement in CGI-9 measures after 12 weeks of treatment compared to placebo – the twice-daily group (P = .0206, Fisher’s Exact Test) and the once-daily group (P = .0006, mixed model repeated measures analysis).

The actigraphy analysis, conducted in the 45% of patients who could tolerate its use, found that, compared to placebo, the once-daily dosing group experienced an 25.7 minute improvement in latency to sleep onset (P = .0147), as well an approximately 50 minute reduction in sleep time during the day, and a 3.65% improvement in sleep efficiency.

OV-101 has the potential to treat other conditions as well. “Obviously there are a lot of neurodevelopmental disorders where you see dysregulation between the GABAergic and glutamergic systems. This is a drug that has a unique effect on the GABAergic system. It’s already being studied in Fragile X syndrome, where we see this same kind of dysregulation and excess excitation,” said Dr. Kolevzon.

Dr. Kolevzon is a consultant for several drug companies including Ovid Therapeutics.
 

SOURCE: AACAP 2018. New Research Poster 3.1.