Many patients with spinal cord injury (SCI) need mechanical ventilatory support. One type of support is diaphragm pacing, which stimulates the diaphragm, helping the person breathe. A minimally invasive form of diaphragm pacing via laparoscopically placed intramuscular diaphragm electrodes has “liberated thousands of patients from mechanical ventilation,” says Anthony DiMarco, MD. He and VA colleague Krzysztof Kowalski, PhD, have found a way to completely restore respiratory muscle function in patients with SCI safely and effectively.

In mid-thoracic and higher level SCIs, the expiratory muscles are paralyzed, putting patients at risk for respiratory tract infections and atelectasis, a major cause of morbidity and mortality in that population. The research team, led by DiMarco and Kowalski, combined diaphragm pacing with a minimally invasive system that allows the patient—simply with the press of a button—to cough effectively, reducing the risk of aspiration and infections. It is the first method in the world, says Dr. Kowalski, that activates abdominal and lower rib cage muscles to produce an effective cough.

An interventional clinical trial in 3 patients demonstrated that using the 2 systems in tandem was safe. The new system was implanted surgically, with disc electrodes placed on the dorsal surface of the spinal cord via laminectomy. Participants in the study used a stimulator to produce several different cough efforts from light to strong.

Mean peak expiratory airflow and airway pressure generation during spontaneous efforts were 1.7 ± 0.2 L/s and 31 ± 7 cmH₂O, respectively. After the spinal cord stimulation was applied, peak expiratory airflow was 9.0 ± 1.9 L/s and airway pressure generation was 90 ± 6 cmH₂O. In other words, results “characteristic of a normal cough,” the researchers concluded. Moreover, each patient raised secretions much more easily.

The research is being done at the Cleveland Functional Electrical Stimulation Center, a consortium of MetroHealth Medical Center, Case Western Reserve University, and Louis Stokes Cleveland VA Medical Center.

Army veteran David Powers, one of the study participants, in an interview with the VAntage Point blog, says, “Being a part of this research trial has made me feel great. For not only my own health but helping to improve the lives of others as well.”

Many patients with spinal cord injury (SCI) need mechanical ventilatory support. One type of support is diaphragm pacing, which stimulates the diaphragm, helping the person breathe. A minimally invasive form of diaphragm pacing via laparoscopically placed intramuscular diaphragm electrodes has “liberated thousands of patients from mechanical ventilation,” says Anthony DiMarco, MD. He and VA colleague Krzysztof Kowalski, PhD, have found a way to completely restore respiratory muscle function in patients with SCI safely and effectively.

In mid-thoracic and higher level SCIs, the expiratory muscles are paralyzed, putting patients at risk for respiratory tract infections and atelectasis, a major cause of morbidity and mortality in that population. The research team, led by DiMarco and Kowalski, combined diaphragm pacing with a minimally invasive system that allows the patient—simply with the press of a button—to cough effectively, reducing the risk of aspiration and infections. It is the first method in the world, says Dr. Kowalski, that activates abdominal and lower rib cage muscles to produce an effective cough.

An interventional clinical trial in 3 patients demonstrated that using the 2 systems in tandem was safe. The new system was implanted surgically, with disc electrodes placed on the dorsal surface of the spinal cord via laminectomy. Participants in the study used a stimulator to produce several different cough efforts from light to strong.

Mean peak expiratory airflow and airway pressure generation during spontaneous efforts were 1.7 ± 0.2 L/s and 31 ± 7 cmH₂O, respectively. After the spinal cord stimulation was applied, peak expiratory airflow was 9.0 ± 1.9 L/s and airway pressure generation was 90 ± 6 cmH₂O. In other words, results “characteristic of a normal cough,” the researchers concluded. Moreover, each patient raised secretions much more easily.

The research is being done at the Cleveland Functional Electrical Stimulation Center, a consortium of MetroHealth Medical Center, Case Western Reserve University, and Louis Stokes Cleveland VA Medical Center.

Army veteran David Powers, one of the study participants, in an interview with the VAntage Point blog, says, “Being a part of this research trial has made me feel great. For not only my own health but helping to improve the lives of others as well.”

Many patients with spinal cord injury (SCI) need mechanical ventilatory support. One type of support is diaphragm pacing, which stimulates the diaphragm, helping the person breathe. A minimally invasive form of diaphragm pacing via laparoscopically placed intramuscular diaphragm electrodes has “liberated thousands of patients from mechanical ventilation,” says Anthony DiMarco, MD. He and VA colleague Krzysztof Kowalski, PhD, have found a way to completely restore respiratory muscle function in patients with SCI safely and effectively.

In mid-thoracic and higher level SCIs, the expiratory muscles are paralyzed, putting patients at risk for respiratory tract infections and atelectasis, a major cause of morbidity and mortality in that population. The research team, led by DiMarco and Kowalski, combined diaphragm pacing with a minimally invasive system that allows the patient—simply with the press of a button—to cough effectively, reducing the risk of aspiration and infections. It is the first method in the world, says Dr. Kowalski, that activates abdominal and lower rib cage muscles to produce an effective cough.

An interventional clinical trial in 3 patients demonstrated that using the 2 systems in tandem was safe. The new system was implanted surgically, with disc electrodes placed on the dorsal surface of the spinal cord via laminectomy. Participants in the study used a stimulator to produce several different cough efforts from light to strong.

Mean peak expiratory airflow and airway pressure generation during spontaneous efforts were 1.7 ± 0.2 L/s and 31 ± 7 cmH₂O, respectively. After the spinal cord stimulation was applied, peak expiratory airflow was 9.0 ± 1.9 L/s and airway pressure generation was 90 ± 6 cmH₂O. In other words, results “characteristic of a normal cough,” the researchers concluded. Moreover, each patient raised secretions much more easily.

The research is being done at the Cleveland Functional Electrical Stimulation Center, a consortium of MetroHealth Medical Center, Case Western Reserve University, and Louis Stokes Cleveland VA Medical Center.

Army veteran David Powers, one of the study participants, in an interview with the VAntage Point blog, says, “Being a part of this research trial has made me feel great. For not only my own health but helping to improve the lives of others as well.”

The Psychosocial Assessment Tool (PAT) is a promising tool for screening psychosocial risk that could potentially facilitate identification of psychosocial treatment needs among youth with recurrent headache at risk for poor outcomes, a new study found. Youth with recurrent migraine or tension-type headache completed the PAT and validated measures of adolescent emotional and behavioral functioning, parent emotional functioning, and family functioning at baseline (n=239) and 6-month follow-up (n=221). Researchers found:

• Internal consistency for the PAT total score was strong (α = .88).
• At baseline, the PAT total score was significantly associated in the expected direction with established measures of child emotional and behavioral functioning, parent anxiety and depressive symptoms, and family functioning.
• Predictive validity was demonstrated by a significant association between the PAT total scores at baseline with child emotional and behavioral functioning, parent anxiety, parent depression, and family functioning at 6-month follow-up.

Law EF, et al. Screening family and psychosocial risk in pediatric migraine and tension-type headache: Validation of the Psychosocial Assessment Tool (PAT). [Published online ahead of print July 18, 2019]. Headache. doi: 10.1111/head.13599.

The Psychosocial Assessment Tool (PAT) is a promising tool for screening psychosocial risk that could potentially facilitate identification of psychosocial treatment needs among youth with recurrent headache at risk for poor outcomes, a new study found. Youth with recurrent migraine or tension-type headache completed the PAT and validated measures of adolescent emotional and behavioral functioning, parent emotional functioning, and family functioning at baseline (n=239) and 6-month follow-up (n=221). Researchers found:

• Internal consistency for the PAT total score was strong (α = .88).
• At baseline, the PAT total score was significantly associated in the expected direction with established measures of child emotional and behavioral functioning, parent anxiety and depressive symptoms, and family functioning.
• Predictive validity was demonstrated by a significant association between the PAT total scores at baseline with child emotional and behavioral functioning, parent anxiety, parent depression, and family functioning at 6-month follow-up.

Law EF, et al. Screening family and psychosocial risk in pediatric migraine and tension-type headache: Validation of the Psychosocial Assessment Tool (PAT). [Published online ahead of print July 18, 2019]. Headache. doi: 10.1111/head.13599.

The Psychosocial Assessment Tool (PAT) is a promising tool for screening psychosocial risk that could potentially facilitate identification of psychosocial treatment needs among youth with recurrent headache at risk for poor outcomes, a new study found. Youth with recurrent migraine or tension-type headache completed the PAT and validated measures of adolescent emotional and behavioral functioning, parent emotional functioning, and family functioning at baseline (n=239) and 6-month follow-up (n=221). Researchers found:

• Internal consistency for the PAT total score was strong (α = .88).
• At baseline, the PAT total score was significantly associated in the expected direction with established measures of child emotional and behavioral functioning, parent anxiety and depressive symptoms, and family functioning.
• Predictive validity was demonstrated by a significant association between the PAT total scores at baseline with child emotional and behavioral functioning, parent anxiety, parent depression, and family functioning at 6-month follow-up.

Law EF, et al. Screening family and psychosocial risk in pediatric migraine and tension-type headache: Validation of the Psychosocial Assessment Tool (PAT). [Published online ahead of print July 18, 2019]. Headache. doi: 10.1111/head.13599.

Hospitalists cannot bill for everything they do, but they can document and code to obtain appropriate reimbursements. It is important for hospitalists to know the factors that influence coding to ensure accuracy and compliance.

The Society of Hospital Medicine developed the Clinical Documentation & Coding for Hospitalists webinar series (formerly known as CODE-H) to provide hospitalists with the latest information on best practices in coding, documentation, and compliance from nationally recognized experts, along with the opportunity to claim CME.

The Hospitalist recently spoke with Carol Pohlig, BSN, RN, CPC, ACS, course director of the webinar series and a coding and documentation expert at the University of Pennsylvania Medical Center in Philadelphia. She was instrumental in developing the content in the series to ensure it was specifically designed to address challenges regularly faced by hospitalists.
 

What inspired the creation of Clinical Documentation & Coding for Hospitalists?

Providers are so busy trying to keep up with regulations for their institution, such as malpractice and quality issues, that the focus isn’t always on the documentation required for reimbursement. The creation of the series rose out of a need for providers to understand key issues related to documentation and billing and some of the hurdles that they need to overcome – or need to be aware of in the first place.

This series brings awareness and solutions to some of these problems. It is available on an ongoing basis, so viewers can move at their own pace. Given the wealth of information in the series, it made sense to create it in this format.
 

What are some common challenges that hospitalists encounter when coding, and how does this webinar series help to address these challenges?

Some common challenges relate to concurrent care or comanagement. Hospitalists are hired to be the gatekeepers – the ones overseeing patient care. When other consultants are on board, they wind up sharing responsibilities, which can muddy the waters at times, especially with billing and coding. It is important for hospitalists to understand their role in comanagement and, in turn, how the payers view their role.

We highlight everything – including requirements for history, exam, and medical decision making – and review each component in depth. We also discuss billing based on these key components or, when it is appropriate, billing based on time. However, when billing time-based services, you have to meet certain qualifications because it is different from the standard way of reporting, which is something we break down in the series.

Related to mitigating risk, EMRs and their copy and paste function is another topic we delve into. It’s easy to copy and paste and pull forward information from a previous note to help save time. However, it is important to understand what the ramifications are. Each of these copied and pasted encounters must be modified to make it applicable to the current day’s patient and ensure care is not being misrepresented.

Those are just a few of the items covered, but we believe that each of the eight modules in the series offers something unique that will help improve documentation and coding practices.
 

How can this webinar series go beyond the hospital medicine care team and more broadly affect the institution as a whole?

Hospitalists are often involved in a number of different categories of services, including observation and same-day admission/discharge. The series reviews rules and challenges specific to those sites of service, which on a broader scale, impact not only providers in other service lines but also those who work in the revenue cycle at the parent institution. How each of these parties understands the nuances explained in the series can directly affect the successful processing of the submitted claims.

In addition, interpretation of rules when it comes to coding and documentation can vary at a local level. We raise awareness of local interpretations to ensure everyone involved in the documentation and coding process knows things to look out for when reading rules. You might think it means one thing when, in reality, it could mean another. With this series, everyone involved with billing and coding can reflect on the implications that incorrect or inaccurate coding may have on their hospital.

Who would benefit from viewing this webinar series?

Although we primarily had hospitalists of all types – including physicians, nurse practitioners, and physician assistants – in mind during the development of course content, anyone who works as a practice manager, biller, coder, or internal auditor has the potential to benefit from the series. If they understand broader challenges in coding, it could help them proactively prevent issues throughout the process with more accurate documentation that could reduce claims denials.

Let SHM’s Clinical Documentation & Coding for Hospitalists webinar series bolster your and your team’s accuracy and compliance. Individual and group subscriptions are available. For more information, visit hospitalmedicine.org/coding.

Hospitalists cannot bill for everything they do, but they can document and code to obtain appropriate reimbursements. It is important for hospitalists to know the factors that influence coding to ensure accuracy and compliance.

The Society of Hospital Medicine developed the Clinical Documentation & Coding for Hospitalists webinar series (formerly known as CODE-H) to provide hospitalists with the latest information on best practices in coding, documentation, and compliance from nationally recognized experts, along with the opportunity to claim CME.

The Hospitalist recently spoke with Carol Pohlig, BSN, RN, CPC, ACS, course director of the webinar series and a coding and documentation expert at the University of Pennsylvania Medical Center in Philadelphia. She was instrumental in developing the content in the series to ensure it was specifically designed to address challenges regularly faced by hospitalists.
 

What inspired the creation of Clinical Documentation & Coding for Hospitalists?

Providers are so busy trying to keep up with regulations for their institution, such as malpractice and quality issues, that the focus isn’t always on the documentation required for reimbursement. The creation of the series rose out of a need for providers to understand key issues related to documentation and billing and some of the hurdles that they need to overcome – or need to be aware of in the first place.

This series brings awareness and solutions to some of these problems. It is available on an ongoing basis, so viewers can move at their own pace. Given the wealth of information in the series, it made sense to create it in this format.
 

What are some common challenges that hospitalists encounter when coding, and how does this webinar series help to address these challenges?

Some common challenges relate to concurrent care or comanagement. Hospitalists are hired to be the gatekeepers – the ones overseeing patient care. When other consultants are on board, they wind up sharing responsibilities, which can muddy the waters at times, especially with billing and coding. It is important for hospitalists to understand their role in comanagement and, in turn, how the payers view their role.

We highlight everything – including requirements for history, exam, and medical decision making – and review each component in depth. We also discuss billing based on these key components or, when it is appropriate, billing based on time. However, when billing time-based services, you have to meet certain qualifications because it is different from the standard way of reporting, which is something we break down in the series.

Related to mitigating risk, EMRs and their copy and paste function is another topic we delve into. It’s easy to copy and paste and pull forward information from a previous note to help save time. However, it is important to understand what the ramifications are. Each of these copied and pasted encounters must be modified to make it applicable to the current day’s patient and ensure care is not being misrepresented.

Those are just a few of the items covered, but we believe that each of the eight modules in the series offers something unique that will help improve documentation and coding practices.
 

How can this webinar series go beyond the hospital medicine care team and more broadly affect the institution as a whole?

Hospitalists are often involved in a number of different categories of services, including observation and same-day admission/discharge. The series reviews rules and challenges specific to those sites of service, which on a broader scale, impact not only providers in other service lines but also those who work in the revenue cycle at the parent institution. How each of these parties understands the nuances explained in the series can directly affect the successful processing of the submitted claims.

In addition, interpretation of rules when it comes to coding and documentation can vary at a local level. We raise awareness of local interpretations to ensure everyone involved in the documentation and coding process knows things to look out for when reading rules. You might think it means one thing when, in reality, it could mean another. With this series, everyone involved with billing and coding can reflect on the implications that incorrect or inaccurate coding may have on their hospital.

Who would benefit from viewing this webinar series?

Although we primarily had hospitalists of all types – including physicians, nurse practitioners, and physician assistants – in mind during the development of course content, anyone who works as a practice manager, biller, coder, or internal auditor has the potential to benefit from the series. If they understand broader challenges in coding, it could help them proactively prevent issues throughout the process with more accurate documentation that could reduce claims denials.

Let SHM’s Clinical Documentation & Coding for Hospitalists webinar series bolster your and your team’s accuracy and compliance. Individual and group subscriptions are available. For more information, visit hospitalmedicine.org/coding.

Hospitalists cannot bill for everything they do, but they can document and code to obtain appropriate reimbursements. It is important for hospitalists to know the factors that influence coding to ensure accuracy and compliance.

The Society of Hospital Medicine developed the Clinical Documentation & Coding for Hospitalists webinar series (formerly known as CODE-H) to provide hospitalists with the latest information on best practices in coding, documentation, and compliance from nationally recognized experts, along with the opportunity to claim CME.

The Hospitalist recently spoke with Carol Pohlig, BSN, RN, CPC, ACS, course director of the webinar series and a coding and documentation expert at the University of Pennsylvania Medical Center in Philadelphia. She was instrumental in developing the content in the series to ensure it was specifically designed to address challenges regularly faced by hospitalists.
 

What inspired the creation of Clinical Documentation & Coding for Hospitalists?

Providers are so busy trying to keep up with regulations for their institution, such as malpractice and quality issues, that the focus isn’t always on the documentation required for reimbursement. The creation of the series rose out of a need for providers to understand key issues related to documentation and billing and some of the hurdles that they need to overcome – or need to be aware of in the first place.

This series brings awareness and solutions to some of these problems. It is available on an ongoing basis, so viewers can move at their own pace. Given the wealth of information in the series, it made sense to create it in this format.
 

What are some common challenges that hospitalists encounter when coding, and how does this webinar series help to address these challenges?

Some common challenges relate to concurrent care or comanagement. Hospitalists are hired to be the gatekeepers – the ones overseeing patient care. When other consultants are on board, they wind up sharing responsibilities, which can muddy the waters at times, especially with billing and coding. It is important for hospitalists to understand their role in comanagement and, in turn, how the payers view their role.

We highlight everything – including requirements for history, exam, and medical decision making – and review each component in depth. We also discuss billing based on these key components or, when it is appropriate, billing based on time. However, when billing time-based services, you have to meet certain qualifications because it is different from the standard way of reporting, which is something we break down in the series.

Related to mitigating risk, EMRs and their copy and paste function is another topic we delve into. It’s easy to copy and paste and pull forward information from a previous note to help save time. However, it is important to understand what the ramifications are. Each of these copied and pasted encounters must be modified to make it applicable to the current day’s patient and ensure care is not being misrepresented.

Those are just a few of the items covered, but we believe that each of the eight modules in the series offers something unique that will help improve documentation and coding practices.
 

How can this webinar series go beyond the hospital medicine care team and more broadly affect the institution as a whole?

Hospitalists are often involved in a number of different categories of services, including observation and same-day admission/discharge. The series reviews rules and challenges specific to those sites of service, which on a broader scale, impact not only providers in other service lines but also those who work in the revenue cycle at the parent institution. How each of these parties understands the nuances explained in the series can directly affect the successful processing of the submitted claims.

In addition, interpretation of rules when it comes to coding and documentation can vary at a local level. We raise awareness of local interpretations to ensure everyone involved in the documentation and coding process knows things to look out for when reading rules. You might think it means one thing when, in reality, it could mean another. With this series, everyone involved with billing and coding can reflect on the implications that incorrect or inaccurate coding may have on their hospital.

Who would benefit from viewing this webinar series?

Although we primarily had hospitalists of all types – including physicians, nurse practitioners, and physician assistants – in mind during the development of course content, anyone who works as a practice manager, biller, coder, or internal auditor has the potential to benefit from the series. If they understand broader challenges in coding, it could help them proactively prevent issues throughout the process with more accurate documentation that could reduce claims denials.

Let SHM’s Clinical Documentation & Coding for Hospitalists webinar series bolster your and your team’s accuracy and compliance. Individual and group subscriptions are available. For more information, visit hospitalmedicine.org/coding.

CHICAGO – Dietary therapies can form a beneficial part of personalized treatment for gastroesophageal reflux disease (GERD), according to an overview presented at the meeting, sponsored by the American Gastroenterological Association. Modifying diet may reduce lower esophageal sphincter (LES) pressure and decrease the number of reflux events. Prescribing an overly restrictive diet, however, can promote hypervigilance and overwhelm patients. Successful dietary therapy requires balancing expectations and maintaining cognitive flexibility, said John E. Pandolfino, MD, Hans Popper Professor of Medicine at Northwestern University in Chicago.

When a patient presents with GERD and does not have warning signs such as dysphagia or odynophagia, the initial treatment typically is a proton pump inhibitor (PPI). This therapy effectively reduces the acidity of the gastric juice and improves acid clearance. It does not, however, change the number of reflux events or affect tissue permeability, said Dr. Pandolfino. Dietary therapy has the potential to address these outcomes.
 

Diets can facilitate weight loss

The first mechanism by which dietary therapies reduce GERD is by facilitating weight loss. “Obesity is associated with reflux. If you reduce that gastroesophageal pressure gradient that is generated by truncal obesity, you will improve reflux,” said Dr. Pandolfino. Second, reducing the intake of alcohol, coffee, or carbohydrates can decrease the acidity of the gastric juice. Certain foods can reduce the number of reflux events, and others can strengthen the LES.

The increasing incidence of obesity is associated with increasing incidence of GERD. Exacerbations of GERD increase the number of transient LES relaxations (TLESRs), increase the amount of liquid refluxate, and promote the formation of a hiatus hernia, said Dr. Pandolfino. One study found that moderate weight gain can cause or worsen reflux symptoms among patients of normal weight (N Engl J Med. 2006;354[22]:2340-8.). Weight loss was associated with a decreased risk of GERD symptoms. Another analysis found that reducing body mass index by 3.5 points is associated with “a dramatic reduction in overall symptoms,” said Dr. Pandolfino (Am J Gastroenterol. 2013;108[3]:376-82). Weight loss enhanced the effects of medication and reduced the gastroesophageal pressure gradient.

Dr. Pandolfino and colleagues developed and studied the Reflux Improvement and Monitoring (TRIM) program as a treatment for GERD. In this program, patients with GERD who had a BMI above 30 and were taking a PPI were referred to health coaches for weight loss treatment. Participants’ GERD Q scores decreased from 8.7 at baseline to 7.5 at 3 months and 7.4 at 6 months. Furthermore, percentage of excess body weight continued to decline for 12 months among patients who participated in TRIM, compared with controls (Am J Gastroenterol. 2018;113[1]:23-30.).

“These patients learn healthier habits [such as] walking a little bit more and watching the overall volume of food that they’re taking in,” said Dr. Pandolfino. “This was a simple thing to focus on, diet and exercise, that dramatically reduced overall severity of reflux. The interesting thing here is that we got 30% of people off their PPI therapy.”
 

Lifestyle changes may benefit patients

Several common lifestyle recommendations for patients with GERD relate to diet. Such recommendations include avoiding alcohol; eating smaller, more frequent meals; and avoiding food within 3 hours of bedtime. But data suggest that it is not effective to recommend the avoidance of acidic or irritative foods (e.g., citrus fruits, tomatoes, and carbonated beverages) or refluxogenic foods (e.g., fatty or fried foods, coffee, and chocolate) to all patients. Genetic predispositions may cause these foods to be irritants to certain patients, but “I don’t globally tell people to avoid things unless they irritate them,” said Dr. Pandolfino.

Understanding the mechanism by which certain foods trigger GERD can aid in appropriate therapy. For example, coffee can reduce LES pressure and increase gastric acid production. “If you have someone who already has low LES pressure, reducing coffee consumption might help that patient,” said Dr. Pandolfino. Data suggest that certain elimination diets are ineffective, however. Clinical trials do not suggest that eliminating carbonated beverages affects symptoms, and the data about eliminating alcohol, citrus, spicy foods, and chocolate are conflicting (Curr Gastroenterol Rep. 2017;19[8]:38.).

In a 2018 study, investigators gave patients with GERD 5 g of psyllium t.i.d. They performed physiologic testing on the patients at baseline and after 10 days of the diet. The intervention was associated with a significant increase in LES pressure and a reduction in overall reflux (World J Gastroenterol. 2018;24[21]:2291-9.). “This was one of the first studies that showed a dramatic improvement in physiology,” said Dr. Pandolfino. “Certainly, this is provocative, and I think that this is not an unreasonable thing to do in someone who’s not getting enough fiber.”

In addition to improving cardiovascular disease and diabetes, the Mediterranean diet reduces reflux symptoms and complications. When the researchers controlled for eating habits, the association persisted (Dis Esophagus. 2016;29[7]:794-800.).

Optimal GERD therapy follows from an analysis of patient-centered foci, such as obesity and triggers, and specific functional defects. In the quest for personalized therapy, a clinician should not discount the underlying pathogenesis, because some patients may require medications or surgery, said Dr. Pandolfino.

egreb@mdedge.com

CHICAGO – Dietary therapies can form a beneficial part of personalized treatment for gastroesophageal reflux disease (GERD), according to an overview presented at the meeting, sponsored by the American Gastroenterological Association. Modifying diet may reduce lower esophageal sphincter (LES) pressure and decrease the number of reflux events. Prescribing an overly restrictive diet, however, can promote hypervigilance and overwhelm patients. Successful dietary therapy requires balancing expectations and maintaining cognitive flexibility, said John E. Pandolfino, MD, Hans Popper Professor of Medicine at Northwestern University in Chicago.

When a patient presents with GERD and does not have warning signs such as dysphagia or odynophagia, the initial treatment typically is a proton pump inhibitor (PPI). This therapy effectively reduces the acidity of the gastric juice and improves acid clearance. It does not, however, change the number of reflux events or affect tissue permeability, said Dr. Pandolfino. Dietary therapy has the potential to address these outcomes.
 

Diets can facilitate weight loss

The first mechanism by which dietary therapies reduce GERD is by facilitating weight loss. “Obesity is associated with reflux. If you reduce that gastroesophageal pressure gradient that is generated by truncal obesity, you will improve reflux,” said Dr. Pandolfino. Second, reducing the intake of alcohol, coffee, or carbohydrates can decrease the acidity of the gastric juice. Certain foods can reduce the number of reflux events, and others can strengthen the LES.

The increasing incidence of obesity is associated with increasing incidence of GERD. Exacerbations of GERD increase the number of transient LES relaxations (TLESRs), increase the amount of liquid refluxate, and promote the formation of a hiatus hernia, said Dr. Pandolfino. One study found that moderate weight gain can cause or worsen reflux symptoms among patients of normal weight (N Engl J Med. 2006;354[22]:2340-8.). Weight loss was associated with a decreased risk of GERD symptoms. Another analysis found that reducing body mass index by 3.5 points is associated with “a dramatic reduction in overall symptoms,” said Dr. Pandolfino (Am J Gastroenterol. 2013;108[3]:376-82). Weight loss enhanced the effects of medication and reduced the gastroesophageal pressure gradient.

Dr. Pandolfino and colleagues developed and studied the Reflux Improvement and Monitoring (TRIM) program as a treatment for GERD. In this program, patients with GERD who had a BMI above 30 and were taking a PPI were referred to health coaches for weight loss treatment. Participants’ GERD Q scores decreased from 8.7 at baseline to 7.5 at 3 months and 7.4 at 6 months. Furthermore, percentage of excess body weight continued to decline for 12 months among patients who participated in TRIM, compared with controls (Am J Gastroenterol. 2018;113[1]:23-30.).

“These patients learn healthier habits [such as] walking a little bit more and watching the overall volume of food that they’re taking in,” said Dr. Pandolfino. “This was a simple thing to focus on, diet and exercise, that dramatically reduced overall severity of reflux. The interesting thing here is that we got 30% of people off their PPI therapy.”
 

Lifestyle changes may benefit patients

Several common lifestyle recommendations for patients with GERD relate to diet. Such recommendations include avoiding alcohol; eating smaller, more frequent meals; and avoiding food within 3 hours of bedtime. But data suggest that it is not effective to recommend the avoidance of acidic or irritative foods (e.g., citrus fruits, tomatoes, and carbonated beverages) or refluxogenic foods (e.g., fatty or fried foods, coffee, and chocolate) to all patients. Genetic predispositions may cause these foods to be irritants to certain patients, but “I don’t globally tell people to avoid things unless they irritate them,” said Dr. Pandolfino.

Understanding the mechanism by which certain foods trigger GERD can aid in appropriate therapy. For example, coffee can reduce LES pressure and increase gastric acid production. “If you have someone who already has low LES pressure, reducing coffee consumption might help that patient,” said Dr. Pandolfino. Data suggest that certain elimination diets are ineffective, however. Clinical trials do not suggest that eliminating carbonated beverages affects symptoms, and the data about eliminating alcohol, citrus, spicy foods, and chocolate are conflicting (Curr Gastroenterol Rep. 2017;19[8]:38.).

In a 2018 study, investigators gave patients with GERD 5 g of psyllium t.i.d. They performed physiologic testing on the patients at baseline and after 10 days of the diet. The intervention was associated with a significant increase in LES pressure and a reduction in overall reflux (World J Gastroenterol. 2018;24[21]:2291-9.). “This was one of the first studies that showed a dramatic improvement in physiology,” said Dr. Pandolfino. “Certainly, this is provocative, and I think that this is not an unreasonable thing to do in someone who’s not getting enough fiber.”

In addition to improving cardiovascular disease and diabetes, the Mediterranean diet reduces reflux symptoms and complications. When the researchers controlled for eating habits, the association persisted (Dis Esophagus. 2016;29[7]:794-800.).

Optimal GERD therapy follows from an analysis of patient-centered foci, such as obesity and triggers, and specific functional defects. In the quest for personalized therapy, a clinician should not discount the underlying pathogenesis, because some patients may require medications or surgery, said Dr. Pandolfino.

egreb@mdedge.com

CHICAGO – Dietary therapies can form a beneficial part of personalized treatment for gastroesophageal reflux disease (GERD), according to an overview presented at the meeting, sponsored by the American Gastroenterological Association. Modifying diet may reduce lower esophageal sphincter (LES) pressure and decrease the number of reflux events. Prescribing an overly restrictive diet, however, can promote hypervigilance and overwhelm patients. Successful dietary therapy requires balancing expectations and maintaining cognitive flexibility, said John E. Pandolfino, MD, Hans Popper Professor of Medicine at Northwestern University in Chicago.

When a patient presents with GERD and does not have warning signs such as dysphagia or odynophagia, the initial treatment typically is a proton pump inhibitor (PPI). This therapy effectively reduces the acidity of the gastric juice and improves acid clearance. It does not, however, change the number of reflux events or affect tissue permeability, said Dr. Pandolfino. Dietary therapy has the potential to address these outcomes.
 

Diets can facilitate weight loss

The first mechanism by which dietary therapies reduce GERD is by facilitating weight loss. “Obesity is associated with reflux. If you reduce that gastroesophageal pressure gradient that is generated by truncal obesity, you will improve reflux,” said Dr. Pandolfino. Second, reducing the intake of alcohol, coffee, or carbohydrates can decrease the acidity of the gastric juice. Certain foods can reduce the number of reflux events, and others can strengthen the LES.

The increasing incidence of obesity is associated with increasing incidence of GERD. Exacerbations of GERD increase the number of transient LES relaxations (TLESRs), increase the amount of liquid refluxate, and promote the formation of a hiatus hernia, said Dr. Pandolfino. One study found that moderate weight gain can cause or worsen reflux symptoms among patients of normal weight (N Engl J Med. 2006;354[22]:2340-8.). Weight loss was associated with a decreased risk of GERD symptoms. Another analysis found that reducing body mass index by 3.5 points is associated with “a dramatic reduction in overall symptoms,” said Dr. Pandolfino (Am J Gastroenterol. 2013;108[3]:376-82). Weight loss enhanced the effects of medication and reduced the gastroesophageal pressure gradient.

Dr. Pandolfino and colleagues developed and studied the Reflux Improvement and Monitoring (TRIM) program as a treatment for GERD. In this program, patients with GERD who had a BMI above 30 and were taking a PPI were referred to health coaches for weight loss treatment. Participants’ GERD Q scores decreased from 8.7 at baseline to 7.5 at 3 months and 7.4 at 6 months. Furthermore, percentage of excess body weight continued to decline for 12 months among patients who participated in TRIM, compared with controls (Am J Gastroenterol. 2018;113[1]:23-30.).

“These patients learn healthier habits [such as] walking a little bit more and watching the overall volume of food that they’re taking in,” said Dr. Pandolfino. “This was a simple thing to focus on, diet and exercise, that dramatically reduced overall severity of reflux. The interesting thing here is that we got 30% of people off their PPI therapy.”
 

Lifestyle changes may benefit patients

Several common lifestyle recommendations for patients with GERD relate to diet. Such recommendations include avoiding alcohol; eating smaller, more frequent meals; and avoiding food within 3 hours of bedtime. But data suggest that it is not effective to recommend the avoidance of acidic or irritative foods (e.g., citrus fruits, tomatoes, and carbonated beverages) or refluxogenic foods (e.g., fatty or fried foods, coffee, and chocolate) to all patients. Genetic predispositions may cause these foods to be irritants to certain patients, but “I don’t globally tell people to avoid things unless they irritate them,” said Dr. Pandolfino.

Understanding the mechanism by which certain foods trigger GERD can aid in appropriate therapy. For example, coffee can reduce LES pressure and increase gastric acid production. “If you have someone who already has low LES pressure, reducing coffee consumption might help that patient,” said Dr. Pandolfino. Data suggest that certain elimination diets are ineffective, however. Clinical trials do not suggest that eliminating carbonated beverages affects symptoms, and the data about eliminating alcohol, citrus, spicy foods, and chocolate are conflicting (Curr Gastroenterol Rep. 2017;19[8]:38.).

In a 2018 study, investigators gave patients with GERD 5 g of psyllium t.i.d. They performed physiologic testing on the patients at baseline and after 10 days of the diet. The intervention was associated with a significant increase in LES pressure and a reduction in overall reflux (World J Gastroenterol. 2018;24[21]:2291-9.). “This was one of the first studies that showed a dramatic improvement in physiology,” said Dr. Pandolfino. “Certainly, this is provocative, and I think that this is not an unreasonable thing to do in someone who’s not getting enough fiber.”

In addition to improving cardiovascular disease and diabetes, the Mediterranean diet reduces reflux symptoms and complications. When the researchers controlled for eating habits, the association persisted (Dis Esophagus. 2016;29[7]:794-800.).

Optimal GERD therapy follows from an analysis of patient-centered foci, such as obesity and triggers, and specific functional defects. In the quest for personalized therapy, a clinician should not discount the underlying pathogenesis, because some patients may require medications or surgery, said Dr. Pandolfino.

egreb@mdedge.com

Sodium divalproate (SD) in low alternating doses appears to be effective as with higher doses, but may induce modest weight gain, a new study found. Consecutive migraineurs to whom SD was prescribed as monotherapy were studied retrospectively. The doses were 250 mg alternated with 500 mg. Headache frequency compared to baseline, adherence expressed by returning to a visit after 2 and 4 months, and side effects reported by patients were evaluated. The study included 68 patients (53 women, 15 men) aged 18 to 58 years.
 

Researchers found:

• The average headache frequency (HF) during baseline was decreased from 8.2 to 5.1 headache days/month among the 50 out of 68 patients returning at 2 months, with adherence rate at 73.5%.
• Weight gain was reported in 30% of patients.
• At 4 months, HF was reduced to 4.2 days/month, with adherence rate at 61.8%, and weight gain reported by 42.8% of patients.

Krymchantowski AV, et al. Sodium divalproate in low alternating daily doses for migraine prevention: A retrospective study. [Published online ahead of print July 1, 2019]. Headache. doi:  10.1111/head.13579.

Sodium divalproate (SD) in low alternating doses appears to be effective as with higher doses, but may induce modest weight gain, a new study found. Consecutive migraineurs to whom SD was prescribed as monotherapy were studied retrospectively. The doses were 250 mg alternated with 500 mg. Headache frequency compared to baseline, adherence expressed by returning to a visit after 2 and 4 months, and side effects reported by patients were evaluated. The study included 68 patients (53 women, 15 men) aged 18 to 58 years.
 

Researchers found:

• The average headache frequency (HF) during baseline was decreased from 8.2 to 5.1 headache days/month among the 50 out of 68 patients returning at 2 months, with adherence rate at 73.5%.
• Weight gain was reported in 30% of patients.
• At 4 months, HF was reduced to 4.2 days/month, with adherence rate at 61.8%, and weight gain reported by 42.8% of patients.

Krymchantowski AV, et al. Sodium divalproate in low alternating daily doses for migraine prevention: A retrospective study. [Published online ahead of print July 1, 2019]. Headache. doi:  10.1111/head.13579.

Sodium divalproate (SD) in low alternating doses appears to be effective as with higher doses, but may induce modest weight gain, a new study found. Consecutive migraineurs to whom SD was prescribed as monotherapy were studied retrospectively. The doses were 250 mg alternated with 500 mg. Headache frequency compared to baseline, adherence expressed by returning to a visit after 2 and 4 months, and side effects reported by patients were evaluated. The study included 68 patients (53 women, 15 men) aged 18 to 58 years.
 

Researchers found:

• The average headache frequency (HF) during baseline was decreased from 8.2 to 5.1 headache days/month among the 50 out of 68 patients returning at 2 months, with adherence rate at 73.5%.
• Weight gain was reported in 30% of patients.
• At 4 months, HF was reduced to 4.2 days/month, with adherence rate at 61.8%, and weight gain reported by 42.8% of patients.

Krymchantowski AV, et al. Sodium divalproate in low alternating daily doses for migraine prevention: A retrospective study. [Published online ahead of print July 1, 2019]. Headache. doi:  10.1111/head.13579.

Migraine-associated vertigo and motion sickness may involve distinct susceptibility genes, according to a new study. Researchers identified a large American family of 29 individuals of which 17 members suffered from at least 1 of the following disorders: migraine, vertigo, or motion sickness. Many suffered from several simultaneously. Family members were phenotyped for each condition and analyzed separately. Among the findings:

• A novel locus for migraine, 9q13-q22 was identified.
• Suggestive LOD scores localized to different chromosomes for each phenotype; vertigo (chromosome 18, LOD score 1.82) and motion sickness (chromosome 4, LOD score 2.09).

Peddareddygari LR, et al. Genetic analysis of a large family with migraine, vertigo, and motion sickness. [Published online ahead of print July 1, 2019]. Can J Neuro Sci. doi: 10.1017/cjn.2019.64.

Migraine-associated vertigo and motion sickness may involve distinct susceptibility genes, according to a new study. Researchers identified a large American family of 29 individuals of which 17 members suffered from at least 1 of the following disorders: migraine, vertigo, or motion sickness. Many suffered from several simultaneously. Family members were phenotyped for each condition and analyzed separately. Among the findings:

• A novel locus for migraine, 9q13-q22 was identified.
• Suggestive LOD scores localized to different chromosomes for each phenotype; vertigo (chromosome 18, LOD score 1.82) and motion sickness (chromosome 4, LOD score 2.09).

Peddareddygari LR, et al. Genetic analysis of a large family with migraine, vertigo, and motion sickness. [Published online ahead of print July 1, 2019]. Can J Neuro Sci. doi: 10.1017/cjn.2019.64.

Migraine-associated vertigo and motion sickness may involve distinct susceptibility genes, according to a new study. Researchers identified a large American family of 29 individuals of which 17 members suffered from at least 1 of the following disorders: migraine, vertigo, or motion sickness. Many suffered from several simultaneously. Family members were phenotyped for each condition and analyzed separately. Among the findings:

• A novel locus for migraine, 9q13-q22 was identified.
• Suggestive LOD scores localized to different chromosomes for each phenotype; vertigo (chromosome 18, LOD score 1.82) and motion sickness (chromosome 4, LOD score 2.09).

Peddareddygari LR, et al. Genetic analysis of a large family with migraine, vertigo, and motion sickness. [Published online ahead of print July 1, 2019]. Can J Neuro Sci. doi: 10.1017/cjn.2019.64.

LJUBLJANA, SLOVENIA – The 4CMenB vaccine didn’t affect carriage of disease-causing genogroups of Neisseria meningitidis in adolescents in the landmark Australian cluster-randomized trial of herd immunity known as the “B Part of It” study, Helen S. Marshall, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

This was the largest-ever randomized trial of adolescents vaccinated against meningococcal disease, and the message, albeit somewhat disappointing, is clear: “MenB [Meningococcal serogroup B] vaccine programs should be designed to provide direct protection for those at highest risk of disease,” declared Dr. Marshall, professor of vaccinology and deputy director of the Robinson Research Institute at the University of Adelaide.

In other words, a protein antigen–based MenB vaccine doesn’t provide indirect protection to unvaccinated adolescents through herd immunity. Youths in the age groups at highest risk of disease – infants and adolescents – need to routinely receive the vaccine.

The B Part of It study, whose sheer scope and rigor drew the attention of infectious disease clinical trialists the world over, randomized nearly 35,000 students at all high schools in the state of South Australia – whether urban, rural, or remote – to two doses of the 4CMenB vaccine known as Bexsero or to a nonvaccinated control group. This massive trial entailed training more than 250 nurses in the study procedures and involved 3,100 miles of travel to transport oropharyngeal swab samples obtained from students in outlying areas for centralized laboratory analysis using real-time polymerase chain reaction with meningococcal genotyping, culture for N. meningitidis, and whole-genome sequencing. Samples were obtained on day 1 of the study and 12 months later.

The investigators created widespread regional enthusiasm for this project through adept use of social media and other methods. As a result, 99.5% of students randomized to the intervention arm received one dose, while 97% got two doses. A gratifying unintended consequence of the study was that parents who’d never previously vaccinated their children enrolled them in B Part of It, Dr. Marshall noted.

The impetus for B Part of It was that, while the Australian national health insurance program covers a single dose of meningococcal conjugate MenACWY vaccine given at age 12 months and 14-19 years, MenB vaccine isn’t covered because of uncertainties about cost effectiveness and the vaccine’s impact on meningococcal carriage and herd immunity. B Part of It was designed to resolve those uncertainties.

South Australia has the highest rate of invasive meningococcal disease in the country, and more than 80% of cases there are caused by meningococcal serogroup B. Moreover, 75% of group B cases in South Australia involve the nasty hypervirulent New Zealand strain known as CC 41/44.

The primary outcome in B Part of It was the difference in carriage of the major disease-causing serotypes – groups A, B, C, W, X, and Y – between vaccinated and unvaccinated students at the 1-year follow-up mark. The carriage prevalence of all N. meningitidis in the vaccinated students went from 2.8% at baseline to 4.0% at 12 months, and similarly from 2.6% to 4.7% in unvaccinated controls. More importantly, the prevalence of disease-causing genotypes rose from 1.3% at baseline to 2.4% at follow-up in the vaccinated subjects, with a near-identical pattern seen in controls, where the prevalence rose from 1.4% to 2.4%. In an as-treated analysis, the rate of acquisition of carriage of disease-causing genotypes was identical at 2.0% in both study arms.

The 4CMenB vaccine proved reassuringly safe and effective in preventing meningococcal disease in vaccinated teens. With more than 58,000 doses of the vaccine given in the study, no new safety concerns or signals emerged. And the observed number of cases of invasive meningococcal disease in South Australian adolescent vaccine recipients to date has been significantly lower than expected.

Secondary and exploratory outcomes

Independent risk factors associated with N. meningitidis carriage in the study participants at the 1-year mark included smoking cigarettes or hookah, intimate kissing within the last week, and being in grades 11-12, as opposed to grade 10.

The vaccine had no significant impact on the carriage rate of the hypervirulent New Zealand serogroup B strain. Nor was there a vaccine impact on carriage density, as Mark McMillan, MD, reported elsewhere at ESPID 2019. But while the 4CMenB vaccine had minimal impact upon N. meningitidis carriage density, it was associated with a significant 41% increase in the likelihood of cleared carriage of disease-causing strains at 12 months, added Dr. McMillan, Dr. Marshall’s coinvestigator at University of Adelaide.

What’s next

The ongoing B Part of It School Leaver study is assessing carriage prevalence in vaccinated versus unvaccinated high schoolers in their first year after graduating.

In addition, the B Part of It investigators plan to prospectively study the impact of the 4CMen B vaccine on N. gonorrhoeae disease in an effort to confirm the intriguing findings of an earlier large, retrospective New Zealand case-control study. The Kiwis found that recipients of an outer membrane vesicle MenB vaccine had an adjusted 31% reduction in the risk of gonorrhea. This was the first-ever report of any vaccine effectiveness against this major global public health problem, in which antibiotic resistance is a growing concern (Lancet. 2017 Sep 30;390[10102]:1603-10). Dr. Marshall reported receiving research funding from GlaxoSmithKline, which markets Bexsero and was the major financial supporter of the B Part of It study.

But wait a minute...

Following Dr. Marshall’s report on the B Part of It study, outgoing ESPID president Adam Finn, MD, PhD, presented longitudinal data that he believes raise the possibility that protein-antigen vaccines such as Bexsero, which promote naturally acquired mucosal immunity, may impact on transmission population wide without reliably preventing acquisition. This would stand in stark contrast to conjugate meningococcus vaccines, which have a well-established massive impact on carriage and acquisition of N. meningitidis.

Bruce Jancin/MDedge News

It may be that in studying throat carriage rates once in individuals immunized 12 months earlier, as in the B Part of It study, investigators are not asking the right question, proposed Dr. Finn, professor of pediatrics at the University of Bristol (England).

His research team has been obtaining throat swabs at monthly intervals in a population of 917 high schoolers aged 16-17 years. In 416 of the students, they also have collected saliva samples weekly both before and after immunization with 4CMenB vaccine, analyzing the samples for N. meningitidis by polymerase chain reaction. This is a novel method of studying meningococcal carriage they have found to be both reliable and far more acceptable to patients than oropharyngeal swabbing, which adolescents balk at if asked to do with any frequency (PLoS One. 2019 Feb 11;14[2]:e0209905).

Dr. Finn said that their findings, which need confirmation, suggest that N. meningitidis carriage is usually brief and dynamic. They also have found that carriage density varies markedly from month to month.

“We see much higher-density carriage in the adolescent population in the early months of the year in conjunction, we think, with viral infection with influenza and so forth,” he said, adding that this could have clinical implications. “It feels sort of intuitive that someone walking around with 1,000 or 10,000 times as many meningococci in their throat is more likely to be more infectious to people around them with a very small number, although this hasn’t been formally proven.”

He hopes that the Be on the TEAM (Teenagers Against Meningitis) study will help provide answers. The study is randomizing 24,000 U.K. high school students to vaccination with the meningococcal B protein–antigen vaccines Bexsero or Trumenba or to no vaccine in order to learn if there are significant herd immunity effects.

Dr. Finn’s meningococcal carriage research is funded by the Meningitis Research Foundation and the National Institute for Health Research. Dr. Marshall reported receiving research funding from GlaxoSmithKline, the major sponsor of the B Part of It study.

bjancin@mdedge.com

LJUBLJANA, SLOVENIA – The 4CMenB vaccine didn’t affect carriage of disease-causing genogroups of Neisseria meningitidis in adolescents in the landmark Australian cluster-randomized trial of herd immunity known as the “B Part of It” study, Helen S. Marshall, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

This was the largest-ever randomized trial of adolescents vaccinated against meningococcal disease, and the message, albeit somewhat disappointing, is clear: “MenB [Meningococcal serogroup B] vaccine programs should be designed to provide direct protection for those at highest risk of disease,” declared Dr. Marshall, professor of vaccinology and deputy director of the Robinson Research Institute at the University of Adelaide.

In other words, a protein antigen–based MenB vaccine doesn’t provide indirect protection to unvaccinated adolescents through herd immunity. Youths in the age groups at highest risk of disease – infants and adolescents – need to routinely receive the vaccine.

The B Part of It study, whose sheer scope and rigor drew the attention of infectious disease clinical trialists the world over, randomized nearly 35,000 students at all high schools in the state of South Australia – whether urban, rural, or remote – to two doses of the 4CMenB vaccine known as Bexsero or to a nonvaccinated control group. This massive trial entailed training more than 250 nurses in the study procedures and involved 3,100 miles of travel to transport oropharyngeal swab samples obtained from students in outlying areas for centralized laboratory analysis using real-time polymerase chain reaction with meningococcal genotyping, culture for N. meningitidis, and whole-genome sequencing. Samples were obtained on day 1 of the study and 12 months later.

The investigators created widespread regional enthusiasm for this project through adept use of social media and other methods. As a result, 99.5% of students randomized to the intervention arm received one dose, while 97% got two doses. A gratifying unintended consequence of the study was that parents who’d never previously vaccinated their children enrolled them in B Part of It, Dr. Marshall noted.

The impetus for B Part of It was that, while the Australian national health insurance program covers a single dose of meningococcal conjugate MenACWY vaccine given at age 12 months and 14-19 years, MenB vaccine isn’t covered because of uncertainties about cost effectiveness and the vaccine’s impact on meningococcal carriage and herd immunity. B Part of It was designed to resolve those uncertainties.

South Australia has the highest rate of invasive meningococcal disease in the country, and more than 80% of cases there are caused by meningococcal serogroup B. Moreover, 75% of group B cases in South Australia involve the nasty hypervirulent New Zealand strain known as CC 41/44.

The primary outcome in B Part of It was the difference in carriage of the major disease-causing serotypes – groups A, B, C, W, X, and Y – between vaccinated and unvaccinated students at the 1-year follow-up mark. The carriage prevalence of all N. meningitidis in the vaccinated students went from 2.8% at baseline to 4.0% at 12 months, and similarly from 2.6% to 4.7% in unvaccinated controls. More importantly, the prevalence of disease-causing genotypes rose from 1.3% at baseline to 2.4% at follow-up in the vaccinated subjects, with a near-identical pattern seen in controls, where the prevalence rose from 1.4% to 2.4%. In an as-treated analysis, the rate of acquisition of carriage of disease-causing genotypes was identical at 2.0% in both study arms.

The 4CMenB vaccine proved reassuringly safe and effective in preventing meningococcal disease in vaccinated teens. With more than 58,000 doses of the vaccine given in the study, no new safety concerns or signals emerged. And the observed number of cases of invasive meningococcal disease in South Australian adolescent vaccine recipients to date has been significantly lower than expected.

Secondary and exploratory outcomes

Independent risk factors associated with N. meningitidis carriage in the study participants at the 1-year mark included smoking cigarettes or hookah, intimate kissing within the last week, and being in grades 11-12, as opposed to grade 10.

The vaccine had no significant impact on the carriage rate of the hypervirulent New Zealand serogroup B strain. Nor was there a vaccine impact on carriage density, as Mark McMillan, MD, reported elsewhere at ESPID 2019. But while the 4CMenB vaccine had minimal impact upon N. meningitidis carriage density, it was associated with a significant 41% increase in the likelihood of cleared carriage of disease-causing strains at 12 months, added Dr. McMillan, Dr. Marshall’s coinvestigator at University of Adelaide.

What’s next

The ongoing B Part of It School Leaver study is assessing carriage prevalence in vaccinated versus unvaccinated high schoolers in their first year after graduating.

In addition, the B Part of It investigators plan to prospectively study the impact of the 4CMen B vaccine on N. gonorrhoeae disease in an effort to confirm the intriguing findings of an earlier large, retrospective New Zealand case-control study. The Kiwis found that recipients of an outer membrane vesicle MenB vaccine had an adjusted 31% reduction in the risk of gonorrhea. This was the first-ever report of any vaccine effectiveness against this major global public health problem, in which antibiotic resistance is a growing concern (Lancet. 2017 Sep 30;390[10102]:1603-10). Dr. Marshall reported receiving research funding from GlaxoSmithKline, which markets Bexsero and was the major financial supporter of the B Part of It study.

But wait a minute...

Following Dr. Marshall’s report on the B Part of It study, outgoing ESPID president Adam Finn, MD, PhD, presented longitudinal data that he believes raise the possibility that protein-antigen vaccines such as Bexsero, which promote naturally acquired mucosal immunity, may impact on transmission population wide without reliably preventing acquisition. This would stand in stark contrast to conjugate meningococcus vaccines, which have a well-established massive impact on carriage and acquisition of N. meningitidis.

Bruce Jancin/MDedge News

It may be that in studying throat carriage rates once in individuals immunized 12 months earlier, as in the B Part of It study, investigators are not asking the right question, proposed Dr. Finn, professor of pediatrics at the University of Bristol (England).

His research team has been obtaining throat swabs at monthly intervals in a population of 917 high schoolers aged 16-17 years. In 416 of the students, they also have collected saliva samples weekly both before and after immunization with 4CMenB vaccine, analyzing the samples for N. meningitidis by polymerase chain reaction. This is a novel method of studying meningococcal carriage they have found to be both reliable and far more acceptable to patients than oropharyngeal swabbing, which adolescents balk at if asked to do with any frequency (PLoS One. 2019 Feb 11;14[2]:e0209905).

Dr. Finn said that their findings, which need confirmation, suggest that N. meningitidis carriage is usually brief and dynamic. They also have found that carriage density varies markedly from month to month.

“We see much higher-density carriage in the adolescent population in the early months of the year in conjunction, we think, with viral infection with influenza and so forth,” he said, adding that this could have clinical implications. “It feels sort of intuitive that someone walking around with 1,000 or 10,000 times as many meningococci in their throat is more likely to be more infectious to people around them with a very small number, although this hasn’t been formally proven.”

He hopes that the Be on the TEAM (Teenagers Against Meningitis) study will help provide answers. The study is randomizing 24,000 U.K. high school students to vaccination with the meningococcal B protein–antigen vaccines Bexsero or Trumenba or to no vaccine in order to learn if there are significant herd immunity effects.

Dr. Finn’s meningococcal carriage research is funded by the Meningitis Research Foundation and the National Institute for Health Research. Dr. Marshall reported receiving research funding from GlaxoSmithKline, the major sponsor of the B Part of It study.

bjancin@mdedge.com

LJUBLJANA, SLOVENIA – The 4CMenB vaccine didn’t affect carriage of disease-causing genogroups of Neisseria meningitidis in adolescents in the landmark Australian cluster-randomized trial of herd immunity known as the “B Part of It” study, Helen S. Marshall, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

This was the largest-ever randomized trial of adolescents vaccinated against meningococcal disease, and the message, albeit somewhat disappointing, is clear: “MenB [Meningococcal serogroup B] vaccine programs should be designed to provide direct protection for those at highest risk of disease,” declared Dr. Marshall, professor of vaccinology and deputy director of the Robinson Research Institute at the University of Adelaide.

In other words, a protein antigen–based MenB vaccine doesn’t provide indirect protection to unvaccinated adolescents through herd immunity. Youths in the age groups at highest risk of disease – infants and adolescents – need to routinely receive the vaccine.

The B Part of It study, whose sheer scope and rigor drew the attention of infectious disease clinical trialists the world over, randomized nearly 35,000 students at all high schools in the state of South Australia – whether urban, rural, or remote – to two doses of the 4CMenB vaccine known as Bexsero or to a nonvaccinated control group. This massive trial entailed training more than 250 nurses in the study procedures and involved 3,100 miles of travel to transport oropharyngeal swab samples obtained from students in outlying areas for centralized laboratory analysis using real-time polymerase chain reaction with meningococcal genotyping, culture for N. meningitidis, and whole-genome sequencing. Samples were obtained on day 1 of the study and 12 months later.

The investigators created widespread regional enthusiasm for this project through adept use of social media and other methods. As a result, 99.5% of students randomized to the intervention arm received one dose, while 97% got two doses. A gratifying unintended consequence of the study was that parents who’d never previously vaccinated their children enrolled them in B Part of It, Dr. Marshall noted.

The impetus for B Part of It was that, while the Australian national health insurance program covers a single dose of meningococcal conjugate MenACWY vaccine given at age 12 months and 14-19 years, MenB vaccine isn’t covered because of uncertainties about cost effectiveness and the vaccine’s impact on meningococcal carriage and herd immunity. B Part of It was designed to resolve those uncertainties.

South Australia has the highest rate of invasive meningococcal disease in the country, and more than 80% of cases there are caused by meningococcal serogroup B. Moreover, 75% of group B cases in South Australia involve the nasty hypervirulent New Zealand strain known as CC 41/44.

The primary outcome in B Part of It was the difference in carriage of the major disease-causing serotypes – groups A, B, C, W, X, and Y – between vaccinated and unvaccinated students at the 1-year follow-up mark. The carriage prevalence of all N. meningitidis in the vaccinated students went from 2.8% at baseline to 4.0% at 12 months, and similarly from 2.6% to 4.7% in unvaccinated controls. More importantly, the prevalence of disease-causing genotypes rose from 1.3% at baseline to 2.4% at follow-up in the vaccinated subjects, with a near-identical pattern seen in controls, where the prevalence rose from 1.4% to 2.4%. In an as-treated analysis, the rate of acquisition of carriage of disease-causing genotypes was identical at 2.0% in both study arms.

The 4CMenB vaccine proved reassuringly safe and effective in preventing meningococcal disease in vaccinated teens. With more than 58,000 doses of the vaccine given in the study, no new safety concerns or signals emerged. And the observed number of cases of invasive meningococcal disease in South Australian adolescent vaccine recipients to date has been significantly lower than expected.

Secondary and exploratory outcomes

Independent risk factors associated with N. meningitidis carriage in the study participants at the 1-year mark included smoking cigarettes or hookah, intimate kissing within the last week, and being in grades 11-12, as opposed to grade 10.

The vaccine had no significant impact on the carriage rate of the hypervirulent New Zealand serogroup B strain. Nor was there a vaccine impact on carriage density, as Mark McMillan, MD, reported elsewhere at ESPID 2019. But while the 4CMenB vaccine had minimal impact upon N. meningitidis carriage density, it was associated with a significant 41% increase in the likelihood of cleared carriage of disease-causing strains at 12 months, added Dr. McMillan, Dr. Marshall’s coinvestigator at University of Adelaide.

What’s next

The ongoing B Part of It School Leaver study is assessing carriage prevalence in vaccinated versus unvaccinated high schoolers in their first year after graduating.

In addition, the B Part of It investigators plan to prospectively study the impact of the 4CMen B vaccine on N. gonorrhoeae disease in an effort to confirm the intriguing findings of an earlier large, retrospective New Zealand case-control study. The Kiwis found that recipients of an outer membrane vesicle MenB vaccine had an adjusted 31% reduction in the risk of gonorrhea. This was the first-ever report of any vaccine effectiveness against this major global public health problem, in which antibiotic resistance is a growing concern (Lancet. 2017 Sep 30;390[10102]:1603-10). Dr. Marshall reported receiving research funding from GlaxoSmithKline, which markets Bexsero and was the major financial supporter of the B Part of It study.

But wait a minute...

Following Dr. Marshall’s report on the B Part of It study, outgoing ESPID president Adam Finn, MD, PhD, presented longitudinal data that he believes raise the possibility that protein-antigen vaccines such as Bexsero, which promote naturally acquired mucosal immunity, may impact on transmission population wide without reliably preventing acquisition. This would stand in stark contrast to conjugate meningococcus vaccines, which have a well-established massive impact on carriage and acquisition of N. meningitidis.

Bruce Jancin/MDedge News

It may be that in studying throat carriage rates once in individuals immunized 12 months earlier, as in the B Part of It study, investigators are not asking the right question, proposed Dr. Finn, professor of pediatrics at the University of Bristol (England).

His research team has been obtaining throat swabs at monthly intervals in a population of 917 high schoolers aged 16-17 years. In 416 of the students, they also have collected saliva samples weekly both before and after immunization with 4CMenB vaccine, analyzing the samples for N. meningitidis by polymerase chain reaction. This is a novel method of studying meningococcal carriage they have found to be both reliable and far more acceptable to patients than oropharyngeal swabbing, which adolescents balk at if asked to do with any frequency (PLoS One. 2019 Feb 11;14[2]:e0209905).

Dr. Finn said that their findings, which need confirmation, suggest that N. meningitidis carriage is usually brief and dynamic. They also have found that carriage density varies markedly from month to month.

“We see much higher-density carriage in the adolescent population in the early months of the year in conjunction, we think, with viral infection with influenza and so forth,” he said, adding that this could have clinical implications. “It feels sort of intuitive that someone walking around with 1,000 or 10,000 times as many meningococci in their throat is more likely to be more infectious to people around them with a very small number, although this hasn’t been formally proven.”

He hopes that the Be on the TEAM (Teenagers Against Meningitis) study will help provide answers. The study is randomizing 24,000 U.K. high school students to vaccination with the meningococcal B protein–antigen vaccines Bexsero or Trumenba or to no vaccine in order to learn if there are significant herd immunity effects.

Dr. Finn’s meningococcal carriage research is funded by the Meningitis Research Foundation and the National Institute for Health Research. Dr. Marshall reported receiving research funding from GlaxoSmithKline, the major sponsor of the B Part of It study.

bjancin@mdedge.com

The SGLT2 inhibitor dapagliflozin (Farxiga) successfully met the primary endpoint of the phase 3 DAPA-HF trial in patients with heart failure, according to a press release from AstraZeneca.

DAPA-HF is an international, multicenter, parallel group, randomized, double-blind trial in patients with heart failure and reduced ejection fraction with or without type 2 diabetes. Patients in the study received either 10 mg dapagliflozin or placebo, and the primary outcome was time to a worsening heart failure event or to cardiovascular death. Patients who received dapagliflozin had a statistically significant reduction in incidence of cardiovascular death and an increase in time to a heart failure event.

The adverse events reported for dapagliflozin in DAPA-HF matched the established safety profile for the drug, AstraZeneca noted in the press release.

“The benefits of dapagliflozin in DAPA-HF are very impressive, with a substantial reduction in the primary composite outcome of cardiovascular death or hospital admission. We hope these exciting new findings will ultimately help reduce the terrible burden of disease caused by heart failure and help improve outcomes for our patients,” said John McMurray, MD, of the Institute of Cardiovascular and Medical Sciences at the University of Glasgow.

Another dapagliflozin trial, called DELIVER, is focused on 4,700 patients with heart failure with preserved ejection fraction randomized to dapagliflozin (Farxiga) or placebo. That is due to be completed next year.

The full results from DAPA-HF will be presented at a later date.

lfranki@mdedge.com

The SGLT2 inhibitor dapagliflozin (Farxiga) successfully met the primary endpoint of the phase 3 DAPA-HF trial in patients with heart failure, according to a press release from AstraZeneca.

DAPA-HF is an international, multicenter, parallel group, randomized, double-blind trial in patients with heart failure and reduced ejection fraction with or without type 2 diabetes. Patients in the study received either 10 mg dapagliflozin or placebo, and the primary outcome was time to a worsening heart failure event or to cardiovascular death. Patients who received dapagliflozin had a statistically significant reduction in incidence of cardiovascular death and an increase in time to a heart failure event.

The adverse events reported for dapagliflozin in DAPA-HF matched the established safety profile for the drug, AstraZeneca noted in the press release.

“The benefits of dapagliflozin in DAPA-HF are very impressive, with a substantial reduction in the primary composite outcome of cardiovascular death or hospital admission. We hope these exciting new findings will ultimately help reduce the terrible burden of disease caused by heart failure and help improve outcomes for our patients,” said John McMurray, MD, of the Institute of Cardiovascular and Medical Sciences at the University of Glasgow.

Another dapagliflozin trial, called DELIVER, is focused on 4,700 patients with heart failure with preserved ejection fraction randomized to dapagliflozin (Farxiga) or placebo. That is due to be completed next year.

The full results from DAPA-HF will be presented at a later date.

lfranki@mdedge.com

The SGLT2 inhibitor dapagliflozin (Farxiga) successfully met the primary endpoint of the phase 3 DAPA-HF trial in patients with heart failure, according to a press release from AstraZeneca.

DAPA-HF is an international, multicenter, parallel group, randomized, double-blind trial in patients with heart failure and reduced ejection fraction with or without type 2 diabetes. Patients in the study received either 10 mg dapagliflozin or placebo, and the primary outcome was time to a worsening heart failure event or to cardiovascular death. Patients who received dapagliflozin had a statistically significant reduction in incidence of cardiovascular death and an increase in time to a heart failure event.

The adverse events reported for dapagliflozin in DAPA-HF matched the established safety profile for the drug, AstraZeneca noted in the press release.

“The benefits of dapagliflozin in DAPA-HF are very impressive, with a substantial reduction in the primary composite outcome of cardiovascular death or hospital admission. We hope these exciting new findings will ultimately help reduce the terrible burden of disease caused by heart failure and help improve outcomes for our patients,” said John McMurray, MD, of the Institute of Cardiovascular and Medical Sciences at the University of Glasgow.

Another dapagliflozin trial, called DELIVER, is focused on 4,700 patients with heart failure with preserved ejection fraction randomized to dapagliflozin (Farxiga) or placebo. That is due to be completed next year.

The full results from DAPA-HF will be presented at a later date.

lfranki@mdedge.com

For patients with EGFR-mutated, advanced non–small cell lung cancer (NSCLC), adding pemetrexed and carboplatin to standard gefitinib therapy markedly extends progression free survival, but at the cost of twice as many serious toxicities, in a recent phase 3 trial.

Two previous phase 2 trials (J Clin Oncol. 2016 Sep 20;34[27]:3258-66 and Ann Oncol. 2015 Feb 10;26[5]:888-94) suggested that adding chemotherapy could improve outcomes over gefitinib alone, but this is the first study to clearly demonstrate better overall survival, reported lead author Vanita Noronha, MD, of Tata Memorial Hospital in Mumbai, India, and colleagues. They noted that this is the second regimen to demonstrate better overall survival than standard gefitinib for EGFR-mutated lung cancer, with dacomitinib being the first, as shown by the ARCHER 1050 trial.

The present study involved 350 patients with advanced, EGFR-mutated NSCLC who had an Eastern Cooperative Oncology (ECOG) performance status of 0-2 and were candidates for first-line palliative therapy. Approximately one-fifth of patients (21%) had a performance status of 2, and almost as many (18%) had brain metastases. After stratification for performance status and mutation type, patients were randomized in a 1:1 ratio to receive either gefitinib monotherapy (250 mg once daily) or gefitinib plus a chemotherapy combination of pemetrexed (500 mg/m²) and carboplatin (area under the curve of 5 with Calvert formula) on day 1 of four 21-day cycles. Subsequently, nonprogressing patients in the chemotherapy group received maintenance therapy with pemetrexed at the same dose and frequency. Treatment was continued until progression, toxicity, or withdrawal of consent. The primary endpoint was progression-free survival (PFS). Secondary outcomes included overall survival (OS), response rate, quality of life, and toxicity.

After a median follow-up of 17 months, the investigators found that adding chemotherapy to gefitinib resulted in a clear benefit, with estimated median PFS increasing from 8 months to 16 months (P less than .001). Estimated median overall survival also increased, with a figure not reached in the chemotherapy/gefitinib group, compared with 17 months among those who received gefitinib alone. Response rates echoed these findings, with more patients in the chemotherapy/gefitinib group achieving complete (2.9% vs. 0.6%) and partial remission (72.4% vs. 61.9%).

“[T]he PFS attained in our study is noteworthy, considering that 21% of our study patients had a [performance status] of 2, whereas the FLAURA study, [which demonstrated a PFS of 18.9 months with osimertinib], only included patients with a [performance status] of 1 or lower,” the investigators wrote. Their report is in Journal of Clinical Oncology.

Still, introducing chemotherapy was not without negative consequences. Compared with the gefitinib monotherapy group, patients who also received chemotherapy more often had grade 3 or higher adverse events (75% vs. 49.4%), and twice as many had clinically significant, serious toxicities (50.6% vs. 25.3%). The additional toxicities were predominantly due to myelosuppression and nephrotoxicity.

Despite these drawbacks, the investigators concluded that combination therapy was superior to gefitinib alone. “The combination of gefitinib, pemetrexed, and carboplatin represents a new standard first-line therapy for EGFR-mutant NSCLC,” the investigators concluded.

The study was funded by Tata Memorial Center Research Administration Council, Fresenius Kabi India, Lung Cancer Consortium India, and others. The investigators reported relationships with Roche, Biocon, Amgen, and others.

SOURCE: Noronha et al. Journal of Clinical Oncology. 2019 Aug 14. doi: 10.1200/JCO.19.01154.

For patients with EGFR-mutated, advanced non–small cell lung cancer (NSCLC), adding pemetrexed and carboplatin to standard gefitinib therapy markedly extends progression free survival, but at the cost of twice as many serious toxicities, in a recent phase 3 trial.

Two previous phase 2 trials (J Clin Oncol. 2016 Sep 20;34[27]:3258-66 and Ann Oncol. 2015 Feb 10;26[5]:888-94) suggested that adding chemotherapy could improve outcomes over gefitinib alone, but this is the first study to clearly demonstrate better overall survival, reported lead author Vanita Noronha, MD, of Tata Memorial Hospital in Mumbai, India, and colleagues. They noted that this is the second regimen to demonstrate better overall survival than standard gefitinib for EGFR-mutated lung cancer, with dacomitinib being the first, as shown by the ARCHER 1050 trial.

The present study involved 350 patients with advanced, EGFR-mutated NSCLC who had an Eastern Cooperative Oncology (ECOG) performance status of 0-2 and were candidates for first-line palliative therapy. Approximately one-fifth of patients (21%) had a performance status of 2, and almost as many (18%) had brain metastases. After stratification for performance status and mutation type, patients were randomized in a 1:1 ratio to receive either gefitinib monotherapy (250 mg once daily) or gefitinib plus a chemotherapy combination of pemetrexed (500 mg/m²) and carboplatin (area under the curve of 5 with Calvert formula) on day 1 of four 21-day cycles. Subsequently, nonprogressing patients in the chemotherapy group received maintenance therapy with pemetrexed at the same dose and frequency. Treatment was continued until progression, toxicity, or withdrawal of consent. The primary endpoint was progression-free survival (PFS). Secondary outcomes included overall survival (OS), response rate, quality of life, and toxicity.

After a median follow-up of 17 months, the investigators found that adding chemotherapy to gefitinib resulted in a clear benefit, with estimated median PFS increasing from 8 months to 16 months (P less than .001). Estimated median overall survival also increased, with a figure not reached in the chemotherapy/gefitinib group, compared with 17 months among those who received gefitinib alone. Response rates echoed these findings, with more patients in the chemotherapy/gefitinib group achieving complete (2.9% vs. 0.6%) and partial remission (72.4% vs. 61.9%).

“[T]he PFS attained in our study is noteworthy, considering that 21% of our study patients had a [performance status] of 2, whereas the FLAURA study, [which demonstrated a PFS of 18.9 months with osimertinib], only included patients with a [performance status] of 1 or lower,” the investigators wrote. Their report is in Journal of Clinical Oncology.

Still, introducing chemotherapy was not without negative consequences. Compared with the gefitinib monotherapy group, patients who also received chemotherapy more often had grade 3 or higher adverse events (75% vs. 49.4%), and twice as many had clinically significant, serious toxicities (50.6% vs. 25.3%). The additional toxicities were predominantly due to myelosuppression and nephrotoxicity.

Despite these drawbacks, the investigators concluded that combination therapy was superior to gefitinib alone. “The combination of gefitinib, pemetrexed, and carboplatin represents a new standard first-line therapy for EGFR-mutant NSCLC,” the investigators concluded.

The study was funded by Tata Memorial Center Research Administration Council, Fresenius Kabi India, Lung Cancer Consortium India, and others. The investigators reported relationships with Roche, Biocon, Amgen, and others.

SOURCE: Noronha et al. Journal of Clinical Oncology. 2019 Aug 14. doi: 10.1200/JCO.19.01154.

For patients with EGFR-mutated, advanced non–small cell lung cancer (NSCLC), adding pemetrexed and carboplatin to standard gefitinib therapy markedly extends progression free survival, but at the cost of twice as many serious toxicities, in a recent phase 3 trial.

Two previous phase 2 trials (J Clin Oncol. 2016 Sep 20;34[27]:3258-66 and Ann Oncol. 2015 Feb 10;26[5]:888-94) suggested that adding chemotherapy could improve outcomes over gefitinib alone, but this is the first study to clearly demonstrate better overall survival, reported lead author Vanita Noronha, MD, of Tata Memorial Hospital in Mumbai, India, and colleagues. They noted that this is the second regimen to demonstrate better overall survival than standard gefitinib for EGFR-mutated lung cancer, with dacomitinib being the first, as shown by the ARCHER 1050 trial.

The present study involved 350 patients with advanced, EGFR-mutated NSCLC who had an Eastern Cooperative Oncology (ECOG) performance status of 0-2 and were candidates for first-line palliative therapy. Approximately one-fifth of patients (21%) had a performance status of 2, and almost as many (18%) had brain metastases. After stratification for performance status and mutation type, patients were randomized in a 1:1 ratio to receive either gefitinib monotherapy (250 mg once daily) or gefitinib plus a chemotherapy combination of pemetrexed (500 mg/m²) and carboplatin (area under the curve of 5 with Calvert formula) on day 1 of four 21-day cycles. Subsequently, nonprogressing patients in the chemotherapy group received maintenance therapy with pemetrexed at the same dose and frequency. Treatment was continued until progression, toxicity, or withdrawal of consent. The primary endpoint was progression-free survival (PFS). Secondary outcomes included overall survival (OS), response rate, quality of life, and toxicity.

After a median follow-up of 17 months, the investigators found that adding chemotherapy to gefitinib resulted in a clear benefit, with estimated median PFS increasing from 8 months to 16 months (P less than .001). Estimated median overall survival also increased, with a figure not reached in the chemotherapy/gefitinib group, compared with 17 months among those who received gefitinib alone. Response rates echoed these findings, with more patients in the chemotherapy/gefitinib group achieving complete (2.9% vs. 0.6%) and partial remission (72.4% vs. 61.9%).

“[T]he PFS attained in our study is noteworthy, considering that 21% of our study patients had a [performance status] of 2, whereas the FLAURA study, [which demonstrated a PFS of 18.9 months with osimertinib], only included patients with a [performance status] of 1 or lower,” the investigators wrote. Their report is in Journal of Clinical Oncology.

Still, introducing chemotherapy was not without negative consequences. Compared with the gefitinib monotherapy group, patients who also received chemotherapy more often had grade 3 or higher adverse events (75% vs. 49.4%), and twice as many had clinically significant, serious toxicities (50.6% vs. 25.3%). The additional toxicities were predominantly due to myelosuppression and nephrotoxicity.

Despite these drawbacks, the investigators concluded that combination therapy was superior to gefitinib alone. “The combination of gefitinib, pemetrexed, and carboplatin represents a new standard first-line therapy for EGFR-mutant NSCLC,” the investigators concluded.

The study was funded by Tata Memorial Center Research Administration Council, Fresenius Kabi India, Lung Cancer Consortium India, and others. The investigators reported relationships with Roche, Biocon, Amgen, and others.

SOURCE: Noronha et al. Journal of Clinical Oncology. 2019 Aug 14. doi: 10.1200/JCO.19.01154.

Dermatology patients experience a high burden of mental health disturbance. Psychiatric disease is seen in an estimated 30% to 60% of our patients.¹ It can be secondary to or comorbid with dermatologic disorders, or it can be the primary condition that is driving cutaneous disease. Patients with secondary or comorbid psychiatric disorders often are amenable to referral to a mental health provider or are already participating in some form of mental health treatment; however, patients with primary psychiatric disease who present to dermatology generally do not accept these referrals.² Therefore, if these patients are to receive care anywhere in the health care system, it often must be in the department of dermatology.

What primary psychiatric conditions do we see in dermatology?

Common primary psychiatric conditions seen in dermatology include delusional infestation, obsessive-compulsive disorder and related disorders, and dermatitis artefacta.

Delusional Infestation
Also known as delusions of parasitosis or delusional parasitosis, delusional infestation presents as a fixed false belief that there is an organism or other foreign entity that is present in the skin and is the cause of cutaneous disruption. It often is an isolated delusion but can have a notable psychosocial impact. The term delusional infestation is sometimes preferred, as it is inclusive of delusions focused on any type of organism, not just parasites. It also encompasses delusions of infestation with nonliving matter such as fibers, also known as Morgellons disease.³

Obsessive-Compulsive Disorder and Related Disorders
This broad category includes several conditions encountered in dermatology. Body dysmorphic disorder (BDD), olfactory reference syndrome (ORS), excoriation disorder, and trichotillomania are some of the most common variants. In patients with BDD, skin and hair are the 2 most common preoccupations. It has been estimated that 12% of dermatology patients experience BDD. Unsurprisingly, it is more common in patients presenting to cosmetic dermatology, but general dermatology patients also are affected at a rate of 7%.² Patients with ORS falsely believe they have body odor and/or halitosis. Excoriation disorder manifests as repetitive skin picking, either of normal skin or of lesions such as pimples and scabs. Trichotillomania presents as repeated hair pulling, and trichophagia (eating the pulled hair) also may be present.

Dermatitis Artefacta
Almost 1 in 4 patients who seek dermatologic evaluation for primarily psychiatric disorders have dermatitis artefacta, the presence of deliberately self-inflicted skin lesions.² Patients with dermatitis artefacta have unconscious motives for their behavior and should be distinguished from malingering patients who have a conscious goal of secondary gain.

What treatments are available?

Antidepressants
Selective serotonin reuptake inhibitors are one of the first-line treatments for BDD and may be useful in ORS. In excoriation disorder and trichotillomania, selective serotonin reuptake inhibitors are the most commonly prescribed pharmacotherapy, but they have limited efficacy.²

Antipsychotics
The recommended treatment of delusional infestation is antipsychotic pharmacotherapy. Treatment with risperidone and olanzapine has been reported to achieve full or partial remission in more than two-thirds of cases.⁴ Aripiprazole, a newer antipsychotic, has fewer side effects and has been successful in several case reports.^5-7

Cognitive Behavioral Therapy
Psychotherapy, most often in the form of cognitive behavioral therapy, has been reported as effective treatment of several psychocutaneous diseases. Cognitive behavioral therapy is considered first-line treatment of body-focused repetitive behavior disorders such as excoriation disorder and trichotillomania.² It addresses maladaptive thought patterns to modify behavior.

Who treats patients with neurodermatoses?

If a patient presents to dermatology with a rash found to be related to an underlying thyroid disorder, the treatment plan likely would include referral to an endocrinologist. Similarly, patients with primary psychiatric conditions presenting to dermatology should ideally be referred to psychiatrists or psychotherapists, the providers most thoroughly trained and best equipped to treat them. The challenge in psychodermatology is that patients often are resistant to the assessment that the primary pathology is psychiatric. Patients may deny that they are “crazy” and see numerous providers in search of a dermatologist who “believes” them.⁸

Referral to mental health professionals almost always is refused by patients with primarily psychiatric neurodermatoses, which presents dermatologists with a dilemma. As the authors of the “Psychotropic Agents” chapter of Comprehensive Dermatologic Drug Therapy put it: “A dermatologist has two choices. The first is to try to ‘look the other way’ and pacify the patient by providing relatively benign, but minimally effective treatments. The other option is to try to directly address the psychological/psychiatric problems.” The chapter then provides a thorough guide for the use of psychotropic medications in the dermatology population, advocating for option 2: treatment by dermatologists.⁹

Should a dermatologist prescribe psychotropic drugs?

In Dermatology, the principle reference textbook in many dermatology training programs, it is stated that “[a]lthough less comprehensive than treatment delivered in collaboration with a psychiatrist, in the authors’ opinion, management of these issues by a dermatologist is better than no treatment at all.”¹⁰ Recent reviews in the dermatologic literature of psychiatric diseases and drugs in dermatology agree that dermatologists should feel comfortable with prescribing pharmacologic treatment.^2,8,11 Performance of psychotherapy by dermatologists, on the other hand, is not recommended based on time constraints and lack of training.

Despite the apparent agreement in the texts and literature that pharmacotherapy of psychiatric neurodermatoses is within our scope of practice in dermatology, most dermatologists do not prescribe psychotropic agents. Dermatology residencies generally do not provide thorough training in psychopharmacotherapy.⁹ Unsurprisingly, a survey of 40 dermatologists at one academic institution found that only 11% felt comfortable prescribing an antidepressant and a mere 3% were comfortable prescribing an antipsychotic.¹²

Final Thoughts

The challenges involved in managing patients with primary psychiatric disease in dermatology are great and many patients are undertreated despite the availability of effective, evidence-based treatment options. We need to continue to work toward providing better access to these treatments in a way that maximizes the chance that our patients will accept our care.

Dermatology patients experience a high burden of mental health disturbance. Psychiatric disease is seen in an estimated 30% to 60% of our patients.¹ It can be secondary to or comorbid with dermatologic disorders, or it can be the primary condition that is driving cutaneous disease. Patients with secondary or comorbid psychiatric disorders often are amenable to referral to a mental health provider or are already participating in some form of mental health treatment; however, patients with primary psychiatric disease who present to dermatology generally do not accept these referrals.² Therefore, if these patients are to receive care anywhere in the health care system, it often must be in the department of dermatology.

What primary psychiatric conditions do we see in dermatology?

Common primary psychiatric conditions seen in dermatology include delusional infestation, obsessive-compulsive disorder and related disorders, and dermatitis artefacta.

Delusional Infestation
Also known as delusions of parasitosis or delusional parasitosis, delusional infestation presents as a fixed false belief that there is an organism or other foreign entity that is present in the skin and is the cause of cutaneous disruption. It often is an isolated delusion but can have a notable psychosocial impact. The term delusional infestation is sometimes preferred, as it is inclusive of delusions focused on any type of organism, not just parasites. It also encompasses delusions of infestation with nonliving matter such as fibers, also known as Morgellons disease.³

Obsessive-Compulsive Disorder and Related Disorders
This broad category includes several conditions encountered in dermatology. Body dysmorphic disorder (BDD), olfactory reference syndrome (ORS), excoriation disorder, and trichotillomania are some of the most common variants. In patients with BDD, skin and hair are the 2 most common preoccupations. It has been estimated that 12% of dermatology patients experience BDD. Unsurprisingly, it is more common in patients presenting to cosmetic dermatology, but general dermatology patients also are affected at a rate of 7%.² Patients with ORS falsely believe they have body odor and/or halitosis. Excoriation disorder manifests as repetitive skin picking, either of normal skin or of lesions such as pimples and scabs. Trichotillomania presents as repeated hair pulling, and trichophagia (eating the pulled hair) also may be present.

Dermatitis Artefacta
Almost 1 in 4 patients who seek dermatologic evaluation for primarily psychiatric disorders have dermatitis artefacta, the presence of deliberately self-inflicted skin lesions.² Patients with dermatitis artefacta have unconscious motives for their behavior and should be distinguished from malingering patients who have a conscious goal of secondary gain.

What treatments are available?

Antidepressants
Selective serotonin reuptake inhibitors are one of the first-line treatments for BDD and may be useful in ORS. In excoriation disorder and trichotillomania, selective serotonin reuptake inhibitors are the most commonly prescribed pharmacotherapy, but they have limited efficacy.²

Antipsychotics
The recommended treatment of delusional infestation is antipsychotic pharmacotherapy. Treatment with risperidone and olanzapine has been reported to achieve full or partial remission in more than two-thirds of cases.⁴ Aripiprazole, a newer antipsychotic, has fewer side effects and has been successful in several case reports.^5-7

Cognitive Behavioral Therapy
Psychotherapy, most often in the form of cognitive behavioral therapy, has been reported as effective treatment of several psychocutaneous diseases. Cognitive behavioral therapy is considered first-line treatment of body-focused repetitive behavior disorders such as excoriation disorder and trichotillomania.² It addresses maladaptive thought patterns to modify behavior.

Who treats patients with neurodermatoses?

If a patient presents to dermatology with a rash found to be related to an underlying thyroid disorder, the treatment plan likely would include referral to an endocrinologist. Similarly, patients with primary psychiatric conditions presenting to dermatology should ideally be referred to psychiatrists or psychotherapists, the providers most thoroughly trained and best equipped to treat them. The challenge in psychodermatology is that patients often are resistant to the assessment that the primary pathology is psychiatric. Patients may deny that they are “crazy” and see numerous providers in search of a dermatologist who “believes” them.⁸

Referral to mental health professionals almost always is refused by patients with primarily psychiatric neurodermatoses, which presents dermatologists with a dilemma. As the authors of the “Psychotropic Agents” chapter of Comprehensive Dermatologic Drug Therapy put it: “A dermatologist has two choices. The first is to try to ‘look the other way’ and pacify the patient by providing relatively benign, but minimally effective treatments. The other option is to try to directly address the psychological/psychiatric problems.” The chapter then provides a thorough guide for the use of psychotropic medications in the dermatology population, advocating for option 2: treatment by dermatologists.⁹

Should a dermatologist prescribe psychotropic drugs?

In Dermatology, the principle reference textbook in many dermatology training programs, it is stated that “[a]lthough less comprehensive than treatment delivered in collaboration with a psychiatrist, in the authors’ opinion, management of these issues by a dermatologist is better than no treatment at all.”¹⁰ Recent reviews in the dermatologic literature of psychiatric diseases and drugs in dermatology agree that dermatologists should feel comfortable with prescribing pharmacologic treatment.^2,8,11 Performance of psychotherapy by dermatologists, on the other hand, is not recommended based on time constraints and lack of training.

Despite the apparent agreement in the texts and literature that pharmacotherapy of psychiatric neurodermatoses is within our scope of practice in dermatology, most dermatologists do not prescribe psychotropic agents. Dermatology residencies generally do not provide thorough training in psychopharmacotherapy.⁹ Unsurprisingly, a survey of 40 dermatologists at one academic institution found that only 11% felt comfortable prescribing an antidepressant and a mere 3% were comfortable prescribing an antipsychotic.¹²

Final Thoughts

The challenges involved in managing patients with primary psychiatric disease in dermatology are great and many patients are undertreated despite the availability of effective, evidence-based treatment options. We need to continue to work toward providing better access to these treatments in a way that maximizes the chance that our patients will accept our care.

Dermatology patients experience a high burden of mental health disturbance. Psychiatric disease is seen in an estimated 30% to 60% of our patients.¹ It can be secondary to or comorbid with dermatologic disorders, or it can be the primary condition that is driving cutaneous disease. Patients with secondary or comorbid psychiatric disorders often are amenable to referral to a mental health provider or are already participating in some form of mental health treatment; however, patients with primary psychiatric disease who present to dermatology generally do not accept these referrals.² Therefore, if these patients are to receive care anywhere in the health care system, it often must be in the department of dermatology.

What primary psychiatric conditions do we see in dermatology?

Common primary psychiatric conditions seen in dermatology include delusional infestation, obsessive-compulsive disorder and related disorders, and dermatitis artefacta.

Delusional Infestation
Also known as delusions of parasitosis or delusional parasitosis, delusional infestation presents as a fixed false belief that there is an organism or other foreign entity that is present in the skin and is the cause of cutaneous disruption. It often is an isolated delusion but can have a notable psychosocial impact. The term delusional infestation is sometimes preferred, as it is inclusive of delusions focused on any type of organism, not just parasites. It also encompasses delusions of infestation with nonliving matter such as fibers, also known as Morgellons disease.³

Obsessive-Compulsive Disorder and Related Disorders
This broad category includes several conditions encountered in dermatology. Body dysmorphic disorder (BDD), olfactory reference syndrome (ORS), excoriation disorder, and trichotillomania are some of the most common variants. In patients with BDD, skin and hair are the 2 most common preoccupations. It has been estimated that 12% of dermatology patients experience BDD. Unsurprisingly, it is more common in patients presenting to cosmetic dermatology, but general dermatology patients also are affected at a rate of 7%.² Patients with ORS falsely believe they have body odor and/or halitosis. Excoriation disorder manifests as repetitive skin picking, either of normal skin or of lesions such as pimples and scabs. Trichotillomania presents as repeated hair pulling, and trichophagia (eating the pulled hair) also may be present.

Dermatitis Artefacta
Almost 1 in 4 patients who seek dermatologic evaluation for primarily psychiatric disorders have dermatitis artefacta, the presence of deliberately self-inflicted skin lesions.² Patients with dermatitis artefacta have unconscious motives for their behavior and should be distinguished from malingering patients who have a conscious goal of secondary gain.

What treatments are available?

Antidepressants
Selective serotonin reuptake inhibitors are one of the first-line treatments for BDD and may be useful in ORS. In excoriation disorder and trichotillomania, selective serotonin reuptake inhibitors are the most commonly prescribed pharmacotherapy, but they have limited efficacy.²

Antipsychotics
The recommended treatment of delusional infestation is antipsychotic pharmacotherapy. Treatment with risperidone and olanzapine has been reported to achieve full or partial remission in more than two-thirds of cases.⁴ Aripiprazole, a newer antipsychotic, has fewer side effects and has been successful in several case reports.^5-7

Cognitive Behavioral Therapy
Psychotherapy, most often in the form of cognitive behavioral therapy, has been reported as effective treatment of several psychocutaneous diseases. Cognitive behavioral therapy is considered first-line treatment of body-focused repetitive behavior disorders such as excoriation disorder and trichotillomania.² It addresses maladaptive thought patterns to modify behavior.

Who treats patients with neurodermatoses?

If a patient presents to dermatology with a rash found to be related to an underlying thyroid disorder, the treatment plan likely would include referral to an endocrinologist. Similarly, patients with primary psychiatric conditions presenting to dermatology should ideally be referred to psychiatrists or psychotherapists, the providers most thoroughly trained and best equipped to treat them. The challenge in psychodermatology is that patients often are resistant to the assessment that the primary pathology is psychiatric. Patients may deny that they are “crazy” and see numerous providers in search of a dermatologist who “believes” them.⁸

Referral to mental health professionals almost always is refused by patients with primarily psychiatric neurodermatoses, which presents dermatologists with a dilemma. As the authors of the “Psychotropic Agents” chapter of Comprehensive Dermatologic Drug Therapy put it: “A dermatologist has two choices. The first is to try to ‘look the other way’ and pacify the patient by providing relatively benign, but minimally effective treatments. The other option is to try to directly address the psychological/psychiatric problems.” The chapter then provides a thorough guide for the use of psychotropic medications in the dermatology population, advocating for option 2: treatment by dermatologists.⁹

Should a dermatologist prescribe psychotropic drugs?

In Dermatology, the principle reference textbook in many dermatology training programs, it is stated that “[a]lthough less comprehensive than treatment delivered in collaboration with a psychiatrist, in the authors’ opinion, management of these issues by a dermatologist is better than no treatment at all.”¹⁰ Recent reviews in the dermatologic literature of psychiatric diseases and drugs in dermatology agree that dermatologists should feel comfortable with prescribing pharmacologic treatment.^2,8,11 Performance of psychotherapy by dermatologists, on the other hand, is not recommended based on time constraints and lack of training.

Despite the apparent agreement in the texts and literature that pharmacotherapy of psychiatric neurodermatoses is within our scope of practice in dermatology, most dermatologists do not prescribe psychotropic agents. Dermatology residencies generally do not provide thorough training in psychopharmacotherapy.⁹ Unsurprisingly, a survey of 40 dermatologists at one academic institution found that only 11% felt comfortable prescribing an antidepressant and a mere 3% were comfortable prescribing an antipsychotic.¹²

Final Thoughts

The challenges involved in managing patients with primary psychiatric disease in dermatology are great and many patients are undertreated despite the availability of effective, evidence-based treatment options. We need to continue to work toward providing better access to these treatments in a way that maximizes the chance that our patients will accept our care.