Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) appears to be cost effective for use in non–small cell lung cancer (NSCLC) staging if the prevalence of mediastinal lymph node metastasis (MLNM) is greater than or equal to 2.5%, according to the results of single institution modeling study. In addition, the study found that confirmatory mediastinoscopy should be performed in high-risk patients in cases of negative EBUS-TBNA.

Katarzyna Czarnecka-Kujawa, MD, of the University of Toronto and Toronto General Hospital, and her colleagues performed a decision analysis to compare health outcomes and costs of four mediastinal staging strategies. They assessed the following: no invasive staging, endobronchial ultrasound-guided transbronchial need aspiration (EBUS-TBNA), mediastinoscopy, and EBUS-TBNA followed by mediastinoscopy if EBUS-TBNA results were negative. They determined incremental cost-effectiveness ratios (ICER) for all strategies and performed comprehensive sensitivity analyses using a willingness to pay threshold of $80,000 [Canadian]/quality adjusted life-year (QALY).

They used data obtained for staging, outcomes, and costs from the patients in the lung cancer program at the Toronto General Hospital from Jan. 1, 2005 to Dec. 31, 2014, as detailed in a report published in the June issue of the Journal of Thoracic and Cardiovascular Surgery (2017. doi: 10.1016/j.jtcvs.2016.12.048).

After exclusions, they utilized a final case count of 499 cases for developing their surgical and procedure cost analysis, and a total of 750 cases in their endoscopy database for endoscopy analysis. For the base-case analysis, they assumed a prevalence of mediastinal metastasis of 9%, and obtained the prevalence of a pathologic lymph nodal stage disease following EBUS-TBNA from their institutional data.

Their results showed that EBUS-TBNA followed by mediastinoscopy was the strategy that resulted in the highest QALYs, but that it had a prohibitive ICER of greater than $1.4 million/QALY. Accordingly, it may not be justifiable to use mediastinoscopy after negative EBUS-TBNA in all patients, the researchers noted. However, the researchers’ data suggest that invasive screening may be justified in a very-low-risk population (MLNM above 2.5%).

In addition, the researchers stated that “[the] benefit conveyed by detecting mediastinal metastatic disease becomes more apparent as the prevalence of MLNM increases, with confirmatory mediastinoscopy becoming cost effective in cases of negative EBUS-TBNA in patients with moderate to high probability of MLNM” (greater than 57%).

Our model points out that there is a well-defined role for the use of different modalities, including mediastinoscopy. This stresses the need for ongoing focus on maintenance of competency and skill acquisition in mediastinoscopy and EBUS-TBNA by currently practicing and future thoracic surgeons respectively,” the researchers concluded.

Dr. Czarnecka-Kujawa disclosed that she is a research consultant with Olympus America. The study was funded in part by agencies of the Austrian government.

[email protected]

Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) appears to be cost effective for use in non–small cell lung cancer (NSCLC) staging if the prevalence of mediastinal lymph node metastasis (MLNM) is greater than or equal to 2.5%, according to the results of single institution modeling study. In addition, the study found that confirmatory mediastinoscopy should be performed in high-risk patients in cases of negative EBUS-TBNA.

Katarzyna Czarnecka-Kujawa, MD, of the University of Toronto and Toronto General Hospital, and her colleagues performed a decision analysis to compare health outcomes and costs of four mediastinal staging strategies. They assessed the following: no invasive staging, endobronchial ultrasound-guided transbronchial need aspiration (EBUS-TBNA), mediastinoscopy, and EBUS-TBNA followed by mediastinoscopy if EBUS-TBNA results were negative. They determined incremental cost-effectiveness ratios (ICER) for all strategies and performed comprehensive sensitivity analyses using a willingness to pay threshold of $80,000 [Canadian]/quality adjusted life-year (QALY).

They used data obtained for staging, outcomes, and costs from the patients in the lung cancer program at the Toronto General Hospital from Jan. 1, 2005 to Dec. 31, 2014, as detailed in a report published in the June issue of the Journal of Thoracic and Cardiovascular Surgery (2017. doi: 10.1016/j.jtcvs.2016.12.048).

After exclusions, they utilized a final case count of 499 cases for developing their surgical and procedure cost analysis, and a total of 750 cases in their endoscopy database for endoscopy analysis. For the base-case analysis, they assumed a prevalence of mediastinal metastasis of 9%, and obtained the prevalence of a pathologic lymph nodal stage disease following EBUS-TBNA from their institutional data.

Their results showed that EBUS-TBNA followed by mediastinoscopy was the strategy that resulted in the highest QALYs, but that it had a prohibitive ICER of greater than $1.4 million/QALY. Accordingly, it may not be justifiable to use mediastinoscopy after negative EBUS-TBNA in all patients, the researchers noted. However, the researchers’ data suggest that invasive screening may be justified in a very-low-risk population (MLNM above 2.5%).

In addition, the researchers stated that “[the] benefit conveyed by detecting mediastinal metastatic disease becomes more apparent as the prevalence of MLNM increases, with confirmatory mediastinoscopy becoming cost effective in cases of negative EBUS-TBNA in patients with moderate to high probability of MLNM” (greater than 57%).

Our model points out that there is a well-defined role for the use of different modalities, including mediastinoscopy. This stresses the need for ongoing focus on maintenance of competency and skill acquisition in mediastinoscopy and EBUS-TBNA by currently practicing and future thoracic surgeons respectively,” the researchers concluded.

Dr. Czarnecka-Kujawa disclosed that she is a research consultant with Olympus America. The study was funded in part by agencies of the Austrian government.

[email protected]

Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) appears to be cost effective for use in non–small cell lung cancer (NSCLC) staging if the prevalence of mediastinal lymph node metastasis (MLNM) is greater than or equal to 2.5%, according to the results of single institution modeling study. In addition, the study found that confirmatory mediastinoscopy should be performed in high-risk patients in cases of negative EBUS-TBNA.

Katarzyna Czarnecka-Kujawa, MD, of the University of Toronto and Toronto General Hospital, and her colleagues performed a decision analysis to compare health outcomes and costs of four mediastinal staging strategies. They assessed the following: no invasive staging, endobronchial ultrasound-guided transbronchial need aspiration (EBUS-TBNA), mediastinoscopy, and EBUS-TBNA followed by mediastinoscopy if EBUS-TBNA results were negative. They determined incremental cost-effectiveness ratios (ICER) for all strategies and performed comprehensive sensitivity analyses using a willingness to pay threshold of $80,000 [Canadian]/quality adjusted life-year (QALY).

They used data obtained for staging, outcomes, and costs from the patients in the lung cancer program at the Toronto General Hospital from Jan. 1, 2005 to Dec. 31, 2014, as detailed in a report published in the June issue of the Journal of Thoracic and Cardiovascular Surgery (2017. doi: 10.1016/j.jtcvs.2016.12.048).

After exclusions, they utilized a final case count of 499 cases for developing their surgical and procedure cost analysis, and a total of 750 cases in their endoscopy database for endoscopy analysis. For the base-case analysis, they assumed a prevalence of mediastinal metastasis of 9%, and obtained the prevalence of a pathologic lymph nodal stage disease following EBUS-TBNA from their institutional data.

Their results showed that EBUS-TBNA followed by mediastinoscopy was the strategy that resulted in the highest QALYs, but that it had a prohibitive ICER of greater than $1.4 million/QALY. Accordingly, it may not be justifiable to use mediastinoscopy after negative EBUS-TBNA in all patients, the researchers noted. However, the researchers’ data suggest that invasive screening may be justified in a very-low-risk population (MLNM above 2.5%).

In addition, the researchers stated that “[the] benefit conveyed by detecting mediastinal metastatic disease becomes more apparent as the prevalence of MLNM increases, with confirmatory mediastinoscopy becoming cost effective in cases of negative EBUS-TBNA in patients with moderate to high probability of MLNM” (greater than 57%).

Our model points out that there is a well-defined role for the use of different modalities, including mediastinoscopy. This stresses the need for ongoing focus on maintenance of competency and skill acquisition in mediastinoscopy and EBUS-TBNA by currently practicing and future thoracic surgeons respectively,” the researchers concluded.

Dr. Czarnecka-Kujawa disclosed that she is a research consultant with Olympus America. The study was funded in part by agencies of the Austrian government.

[email protected]

Monica Saini, MD, a radiologist in Santa Fe, New Mexico, and JoAnn Pushkin, executive director of the nonprofit educational website DenseBreast-info.org, engaged ObGyn attendees on “Breast density: Why it matters and what to do” at the American College of Obstetricians and Gynecologists (ACOG) 2017 Annual Clinical and Scientific Meeting (May 6–9, 2017) in San Diego, California. The program was sponsored by GE Healthcare.

DENSE BREASTS ARE A RISK FACTOR FOR CANCER

Breast density is the second largest risk factor for breast cancer after radiation treatment to the chest, so it is important to identify patients with dense breasts, according to Dr. Saini. The American College of Radiology’s Breast Imaging Reporting and Data System (BI-RADS) classifies breast density into 4 groups: 1) almost entirely fatty, 2) scattered fibroglandular densities, 3) heterogeneously dense, and 4) extremely dense. A woman whose mammograms show heterogeneously dense or extremely dense breasts is considered to have “dense breasts.”

Cancer is often difficult to identify with mammography in dense breasts because masses or lumps appear as white on a white (dense tissue) background; by contrast, a tumor in a nondense (fatty) breast would appear as white on a dark, fatty tissue background. Approximately one-third of cancers in dense breasts have a delayed diagnosis on mammography, and 70% of cancers occur in dense breasts, said Dr. Saini.

Having dense breasts is not an abnormal condition, however, and is actually common—about 40% of women aged 40 or older have dense breasts.

Supplement mammography with other screening modalities

While screening mammograms can save lives, mammography should not be viewed as a one-size-fits-all modality. Screening for breast cancer should be personalized, based on, among other factors, a woman’s personal and family history, age, genetic risk, lifestyle factors, and breast density.

Key point. Women with dense breasts should continue to have screening mammograms. In addition, mammography for these patients should be supplemented with other technologies, such as 3D mammography (digital tomosynthesis), handheld ultrasound, or automated breast ultrasound (ABUS). In women at higher risk (presence of BRCA1 or BRCA2 gene mutation, strong family history of breast cancer, or radiation treatment to the chest) magnetic resonance imaging (MRI) may be considered.

Data on adjunct screening modalities. Dr. Saini discussed the results of the ASTOUND trial, a prospective multicenter study that compared ultrasound and tomosynthesis for the detection of breast cancer in mammography-negative dense breasts.¹ Among the 3,231 asymptomatic women included in the trial, 13 breast cancers were detected with tomosynthesis (incremental cancer detection rate [CDR], 4 per 1,000 screens; 95% confidence interval [CI], 1.8–6.2) and 23 were detected with ultrasound (incremental CDR, 7.1 per 1,000 screens; 95% CI, 4.4–10.0), P = .006. There were 107 false-positive results: 53 with tomosynthesis and 65 with ultrasound, a difference that was not statistically significant. The study authors noted that while ultrasound had better incremental breast cancer detection than tomosynthesis, and at a similar false-positive recall rate, tomosynthesis did detect more than half of the additional breast cancers in these women.¹

Make screening easier for the patient

Dr. Saini noted that for women with dense breasts, performing mammography and adjunctive screening at the same visit is convenient for the patient. Physicians can also write prescriptions for follow-up based on density findings, for example, “3D mammography if available, if dense, order ultrasound.”

Read how to answer patient questions about breast density

ARE YOU READY TO ANSWER PATIENT QUESTIONS ABOUT BREAST DENSITY?

That is the question JoAnn Pushkin, executive director of DenseBreast-info.org, asked in her presentation. You should discuss with patients exactly what it means to have dense breasts, breast density as an independent risk factor for cancer, the breast imaging technologies available for screening (mammography, tomosynthesis, ultrasound, contrast-enhanced MRI), the risks and benefits of each screening modality, and surveillance intervals for women with dense breasts. Good communication with the patient’s radiology team assists in formulating an individualized screening strategy.

Patients may have concerns about the information provided—or not provided—in their state’s breast density notification letter after a mammogram. Currently, 31 states mandate some type of breast density notification, while 4 states have efforts for density reporting or education that do not require notification. The information given to patients and how they will be informed varies by state. Some states, for example, require that patients who have heterogeneously or extremely dense breasts be informed of this by letter, while other states require that all patients receive the same notification with information about dense breasts but does not tell them whether or not they have dense breasts.

A go-to resource for ObGyns and patients

The website of the nonprofit DenseBreast-Info.org (http://densebreast-info.org/), co-founded by Wendie Berg, MD, PhD, who serves as Chief Scientific Advisor to the organization and is Professor of Radiology at the University of Pittsburgh School of Medicine/Magee-Women’s Hospital of UPMC, provides an interactive US map that features state-by-state breast density reporting guidelines so you can stay up-to-date on notification legislation in your area.

Sections for patients offer comprehensive and clearly written information on categories of breast density, a patient risk checklist, screening test descriptions, frequently asked questions, educational videos, and a patient brochure in English and Spanish.

For health care providers, resources include:

• a screening decision support tool flowchart to help assess which patients need more screening
• a table summarizing the cancer detection rates for mammography alone and mammography plus another screening modality (tomosynthesis, ultrasound, MRI)
• a comparison of breast cancer screening guidelines from various medical societies, including the American College of Radiology/Society of Breast Imaging, the American Cancer Society, the American College of Obstetricians and Gynecologists, and the US Preventive Services Task Force.

A special section covers screening technology, and each page includes descriptions, benefits, and considerations for use. Photos of the equipment and images of breast scans with explanatory captions enhance understanding.

Screening for high-risk women

Ms. Pushkin noted that for high-risk patients with dense breasts, mammography plus MRI annually would be an appropriate option.

Monica Saini, MD, a radiologist in Santa Fe, New Mexico, and JoAnn Pushkin, executive director of the nonprofit educational website DenseBreast-info.org, engaged ObGyn attendees on “Breast density: Why it matters and what to do” at the American College of Obstetricians and Gynecologists (ACOG) 2017 Annual Clinical and Scientific Meeting (May 6–9, 2017) in San Diego, California. The program was sponsored by GE Healthcare.

DENSE BREASTS ARE A RISK FACTOR FOR CANCER

Breast density is the second largest risk factor for breast cancer after radiation treatment to the chest, so it is important to identify patients with dense breasts, according to Dr. Saini. The American College of Radiology’s Breast Imaging Reporting and Data System (BI-RADS) classifies breast density into 4 groups: 1) almost entirely fatty, 2) scattered fibroglandular densities, 3) heterogeneously dense, and 4) extremely dense. A woman whose mammograms show heterogeneously dense or extremely dense breasts is considered to have “dense breasts.”

Cancer is often difficult to identify with mammography in dense breasts because masses or lumps appear as white on a white (dense tissue) background; by contrast, a tumor in a nondense (fatty) breast would appear as white on a dark, fatty tissue background. Approximately one-third of cancers in dense breasts have a delayed diagnosis on mammography, and 70% of cancers occur in dense breasts, said Dr. Saini.

Having dense breasts is not an abnormal condition, however, and is actually common—about 40% of women aged 40 or older have dense breasts.

Supplement mammography with other screening modalities

While screening mammograms can save lives, mammography should not be viewed as a one-size-fits-all modality. Screening for breast cancer should be personalized, based on, among other factors, a woman’s personal and family history, age, genetic risk, lifestyle factors, and breast density.

Key point. Women with dense breasts should continue to have screening mammograms. In addition, mammography for these patients should be supplemented with other technologies, such as 3D mammography (digital tomosynthesis), handheld ultrasound, or automated breast ultrasound (ABUS). In women at higher risk (presence of BRCA1 or BRCA2 gene mutation, strong family history of breast cancer, or radiation treatment to the chest) magnetic resonance imaging (MRI) may be considered.

Data on adjunct screening modalities. Dr. Saini discussed the results of the ASTOUND trial, a prospective multicenter study that compared ultrasound and tomosynthesis for the detection of breast cancer in mammography-negative dense breasts.¹ Among the 3,231 asymptomatic women included in the trial, 13 breast cancers were detected with tomosynthesis (incremental cancer detection rate [CDR], 4 per 1,000 screens; 95% confidence interval [CI], 1.8–6.2) and 23 were detected with ultrasound (incremental CDR, 7.1 per 1,000 screens; 95% CI, 4.4–10.0), P = .006. There were 107 false-positive results: 53 with tomosynthesis and 65 with ultrasound, a difference that was not statistically significant. The study authors noted that while ultrasound had better incremental breast cancer detection than tomosynthesis, and at a similar false-positive recall rate, tomosynthesis did detect more than half of the additional breast cancers in these women.¹

Make screening easier for the patient

Dr. Saini noted that for women with dense breasts, performing mammography and adjunctive screening at the same visit is convenient for the patient. Physicians can also write prescriptions for follow-up based on density findings, for example, “3D mammography if available, if dense, order ultrasound.”

Read how to answer patient questions about breast density

ARE YOU READY TO ANSWER PATIENT QUESTIONS ABOUT BREAST DENSITY?

That is the question JoAnn Pushkin, executive director of DenseBreast-info.org, asked in her presentation. You should discuss with patients exactly what it means to have dense breasts, breast density as an independent risk factor for cancer, the breast imaging technologies available for screening (mammography, tomosynthesis, ultrasound, contrast-enhanced MRI), the risks and benefits of each screening modality, and surveillance intervals for women with dense breasts. Good communication with the patient’s radiology team assists in formulating an individualized screening strategy.

Patients may have concerns about the information provided—or not provided—in their state’s breast density notification letter after a mammogram. Currently, 31 states mandate some type of breast density notification, while 4 states have efforts for density reporting or education that do not require notification. The information given to patients and how they will be informed varies by state. Some states, for example, require that patients who have heterogeneously or extremely dense breasts be informed of this by letter, while other states require that all patients receive the same notification with information about dense breasts but does not tell them whether or not they have dense breasts.

A go-to resource for ObGyns and patients

The website of the nonprofit DenseBreast-Info.org (http://densebreast-info.org/), co-founded by Wendie Berg, MD, PhD, who serves as Chief Scientific Advisor to the organization and is Professor of Radiology at the University of Pittsburgh School of Medicine/Magee-Women’s Hospital of UPMC, provides an interactive US map that features state-by-state breast density reporting guidelines so you can stay up-to-date on notification legislation in your area.

Sections for patients offer comprehensive and clearly written information on categories of breast density, a patient risk checklist, screening test descriptions, frequently asked questions, educational videos, and a patient brochure in English and Spanish.

For health care providers, resources include:

• a screening decision support tool flowchart to help assess which patients need more screening
• a table summarizing the cancer detection rates for mammography alone and mammography plus another screening modality (tomosynthesis, ultrasound, MRI)
• a comparison of breast cancer screening guidelines from various medical societies, including the American College of Radiology/Society of Breast Imaging, the American Cancer Society, the American College of Obstetricians and Gynecologists, and the US Preventive Services Task Force.

A special section covers screening technology, and each page includes descriptions, benefits, and considerations for use. Photos of the equipment and images of breast scans with explanatory captions enhance understanding.

Screening for high-risk women

Ms. Pushkin noted that for high-risk patients with dense breasts, mammography plus MRI annually would be an appropriate option.

Monica Saini, MD, a radiologist in Santa Fe, New Mexico, and JoAnn Pushkin, executive director of the nonprofit educational website DenseBreast-info.org, engaged ObGyn attendees on “Breast density: Why it matters and what to do” at the American College of Obstetricians and Gynecologists (ACOG) 2017 Annual Clinical and Scientific Meeting (May 6–9, 2017) in San Diego, California. The program was sponsored by GE Healthcare.

DENSE BREASTS ARE A RISK FACTOR FOR CANCER

Breast density is the second largest risk factor for breast cancer after radiation treatment to the chest, so it is important to identify patients with dense breasts, according to Dr. Saini. The American College of Radiology’s Breast Imaging Reporting and Data System (BI-RADS) classifies breast density into 4 groups: 1) almost entirely fatty, 2) scattered fibroglandular densities, 3) heterogeneously dense, and 4) extremely dense. A woman whose mammograms show heterogeneously dense or extremely dense breasts is considered to have “dense breasts.”

Cancer is often difficult to identify with mammography in dense breasts because masses or lumps appear as white on a white (dense tissue) background; by contrast, a tumor in a nondense (fatty) breast would appear as white on a dark, fatty tissue background. Approximately one-third of cancers in dense breasts have a delayed diagnosis on mammography, and 70% of cancers occur in dense breasts, said Dr. Saini.

Having dense breasts is not an abnormal condition, however, and is actually common—about 40% of women aged 40 or older have dense breasts.

Supplement mammography with other screening modalities

While screening mammograms can save lives, mammography should not be viewed as a one-size-fits-all modality. Screening for breast cancer should be personalized, based on, among other factors, a woman’s personal and family history, age, genetic risk, lifestyle factors, and breast density.

Key point. Women with dense breasts should continue to have screening mammograms. In addition, mammography for these patients should be supplemented with other technologies, such as 3D mammography (digital tomosynthesis), handheld ultrasound, or automated breast ultrasound (ABUS). In women at higher risk (presence of BRCA1 or BRCA2 gene mutation, strong family history of breast cancer, or radiation treatment to the chest) magnetic resonance imaging (MRI) may be considered.

Data on adjunct screening modalities. Dr. Saini discussed the results of the ASTOUND trial, a prospective multicenter study that compared ultrasound and tomosynthesis for the detection of breast cancer in mammography-negative dense breasts.¹ Among the 3,231 asymptomatic women included in the trial, 13 breast cancers were detected with tomosynthesis (incremental cancer detection rate [CDR], 4 per 1,000 screens; 95% confidence interval [CI], 1.8–6.2) and 23 were detected with ultrasound (incremental CDR, 7.1 per 1,000 screens; 95% CI, 4.4–10.0), P = .006. There were 107 false-positive results: 53 with tomosynthesis and 65 with ultrasound, a difference that was not statistically significant. The study authors noted that while ultrasound had better incremental breast cancer detection than tomosynthesis, and at a similar false-positive recall rate, tomosynthesis did detect more than half of the additional breast cancers in these women.¹

Make screening easier for the patient

Dr. Saini noted that for women with dense breasts, performing mammography and adjunctive screening at the same visit is convenient for the patient. Physicians can also write prescriptions for follow-up based on density findings, for example, “3D mammography if available, if dense, order ultrasound.”

Read how to answer patient questions about breast density

ARE YOU READY TO ANSWER PATIENT QUESTIONS ABOUT BREAST DENSITY?

That is the question JoAnn Pushkin, executive director of DenseBreast-info.org, asked in her presentation. You should discuss with patients exactly what it means to have dense breasts, breast density as an independent risk factor for cancer, the breast imaging technologies available for screening (mammography, tomosynthesis, ultrasound, contrast-enhanced MRI), the risks and benefits of each screening modality, and surveillance intervals for women with dense breasts. Good communication with the patient’s radiology team assists in formulating an individualized screening strategy.

Patients may have concerns about the information provided—or not provided—in their state’s breast density notification letter after a mammogram. Currently, 31 states mandate some type of breast density notification, while 4 states have efforts for density reporting or education that do not require notification. The information given to patients and how they will be informed varies by state. Some states, for example, require that patients who have heterogeneously or extremely dense breasts be informed of this by letter, while other states require that all patients receive the same notification with information about dense breasts but does not tell them whether or not they have dense breasts.

A go-to resource for ObGyns and patients

The website of the nonprofit DenseBreast-Info.org (http://densebreast-info.org/), co-founded by Wendie Berg, MD, PhD, who serves as Chief Scientific Advisor to the organization and is Professor of Radiology at the University of Pittsburgh School of Medicine/Magee-Women’s Hospital of UPMC, provides an interactive US map that features state-by-state breast density reporting guidelines so you can stay up-to-date on notification legislation in your area.

Sections for patients offer comprehensive and clearly written information on categories of breast density, a patient risk checklist, screening test descriptions, frequently asked questions, educational videos, and a patient brochure in English and Spanish.

For health care providers, resources include:

• a screening decision support tool flowchart to help assess which patients need more screening
• a table summarizing the cancer detection rates for mammography alone and mammography plus another screening modality (tomosynthesis, ultrasound, MRI)
• a comparison of breast cancer screening guidelines from various medical societies, including the American College of Radiology/Society of Breast Imaging, the American Cancer Society, the American College of Obstetricians and Gynecologists, and the US Preventive Services Task Force.

A special section covers screening technology, and each page includes descriptions, benefits, and considerations for use. Photos of the equipment and images of breast scans with explanatory captions enhance understanding.

Screening for high-risk women

Ms. Pushkin noted that for high-risk patients with dense breasts, mammography plus MRI annually would be an appropriate option.

Los Angeles County, California, has been identified as one of 7 areas in the nation with the highest risk of local Zika transmission by the Centers for Disease Control and Prevention (CDC), advise Adriana Ramos and colleagues from Los Angeles County Department of Public Health (DPH), Maternal, Child & Adolescent Health Programs.¹ One factor for this classification is the county’s high birth rate. According to Ramos at el the CDC recommends that, before a Zika outbreak occurs, health departments in areas with Aedes species mosquitos increase access to and use of effective contraception.¹ Long-acting reversible contraceptives (LARCs), including the intrauterine device (IUD) and the implant, are proven most effective methods.¹

In a poster presented at the American College of Obstetricians and Gynecologists (ACOG) Annual Clinical Meeting in San Diego, California, Ramos and colleagues summarized contraceptive use within LA County using data from the Los Angeles Mommy and Baby (LAMB) project, conducted by the Maternal, Child, and Adolescent Health (MCAH) Programs of the LA County DPH, which surveyed mothers who recently delivered a live baby about their preconception and perinatal experiences. In 2012, 6,893 mothers participated. In 2014, MCAH re-interviewed the 2012 LAMB respondents, excluding those with a subsequent pregnancy after the 2012 survey or who had not originally answered questions about family planning, leaving 3,175 respondents. Findings, weighted to the 2012 live-birth cohort, estimated the weighted population at 115,284 live births.¹

The study defined contraception use by efficacy, identifying no contraception use, condoms, withdrawal, and the rhythm method as less effective; oral contraceptive pills and vaginal ring as moderately effective; and LARCs and sterilization as highly effective. Unintended births account for 47% of births in LAC and more than 59% of women report using less effective contraceptive methods.¹

Results of the study

As a result of their study, MCAH researchers Adriana Ramos, Shin Chao, MD, MPH, and Diana E. Ramos, MD, MPH, conclude that educating providers to place LARC contraceptives and educating the public on the most effective contraceptive methods can decrease the neonatal Zika complication rates by preventing unplanned pregnancy. LAC is undertaking these activities to decrease the number of neonatal Zika cases.¹

Los Angeles County, California, has been identified as one of 7 areas in the nation with the highest risk of local Zika transmission by the Centers for Disease Control and Prevention (CDC), advise Adriana Ramos and colleagues from Los Angeles County Department of Public Health (DPH), Maternal, Child & Adolescent Health Programs.¹ One factor for this classification is the county’s high birth rate. According to Ramos at el the CDC recommends that, before a Zika outbreak occurs, health departments in areas with Aedes species mosquitos increase access to and use of effective contraception.¹ Long-acting reversible contraceptives (LARCs), including the intrauterine device (IUD) and the implant, are proven most effective methods.¹

In a poster presented at the American College of Obstetricians and Gynecologists (ACOG) Annual Clinical Meeting in San Diego, California, Ramos and colleagues summarized contraceptive use within LA County using data from the Los Angeles Mommy and Baby (LAMB) project, conducted by the Maternal, Child, and Adolescent Health (MCAH) Programs of the LA County DPH, which surveyed mothers who recently delivered a live baby about their preconception and perinatal experiences. In 2012, 6,893 mothers participated. In 2014, MCAH re-interviewed the 2012 LAMB respondents, excluding those with a subsequent pregnancy after the 2012 survey or who had not originally answered questions about family planning, leaving 3,175 respondents. Findings, weighted to the 2012 live-birth cohort, estimated the weighted population at 115,284 live births.¹

The study defined contraception use by efficacy, identifying no contraception use, condoms, withdrawal, and the rhythm method as less effective; oral contraceptive pills and vaginal ring as moderately effective; and LARCs and sterilization as highly effective. Unintended births account for 47% of births in LAC and more than 59% of women report using less effective contraceptive methods.¹

Results of the study

As a result of their study, MCAH researchers Adriana Ramos, Shin Chao, MD, MPH, and Diana E. Ramos, MD, MPH, conclude that educating providers to place LARC contraceptives and educating the public on the most effective contraceptive methods can decrease the neonatal Zika complication rates by preventing unplanned pregnancy. LAC is undertaking these activities to decrease the number of neonatal Zika cases.¹

Los Angeles County, California, has been identified as one of 7 areas in the nation with the highest risk of local Zika transmission by the Centers for Disease Control and Prevention (CDC), advise Adriana Ramos and colleagues from Los Angeles County Department of Public Health (DPH), Maternal, Child & Adolescent Health Programs.¹ One factor for this classification is the county’s high birth rate. According to Ramos at el the CDC recommends that, before a Zika outbreak occurs, health departments in areas with Aedes species mosquitos increase access to and use of effective contraception.¹ Long-acting reversible contraceptives (LARCs), including the intrauterine device (IUD) and the implant, are proven most effective methods.¹

In a poster presented at the American College of Obstetricians and Gynecologists (ACOG) Annual Clinical Meeting in San Diego, California, Ramos and colleagues summarized contraceptive use within LA County using data from the Los Angeles Mommy and Baby (LAMB) project, conducted by the Maternal, Child, and Adolescent Health (MCAH) Programs of the LA County DPH, which surveyed mothers who recently delivered a live baby about their preconception and perinatal experiences. In 2012, 6,893 mothers participated. In 2014, MCAH re-interviewed the 2012 LAMB respondents, excluding those with a subsequent pregnancy after the 2012 survey or who had not originally answered questions about family planning, leaving 3,175 respondents. Findings, weighted to the 2012 live-birth cohort, estimated the weighted population at 115,284 live births.¹

The study defined contraception use by efficacy, identifying no contraception use, condoms, withdrawal, and the rhythm method as less effective; oral contraceptive pills and vaginal ring as moderately effective; and LARCs and sterilization as highly effective. Unintended births account for 47% of births in LAC and more than 59% of women report using less effective contraceptive methods.¹

Results of the study

As a result of their study, MCAH researchers Adriana Ramos, Shin Chao, MD, MPH, and Diana E. Ramos, MD, MPH, conclude that educating providers to place LARC contraceptives and educating the public on the most effective contraceptive methods can decrease the neonatal Zika complication rates by preventing unplanned pregnancy. LAC is undertaking these activities to decrease the number of neonatal Zika cases.¹

Embolization was the major cause of permanent stroke in patients with moderate or severe carotid or intracranial atherosclerosis who underwent elective open aortic arch surgery at a single institution, according to the results of a retrospective study.

Preoperative craniocervical and aortic screening may aid in modifying the operative strategy to reduce the incidence of stroke in these patients, according to a report published in the May issue of the Journal of Thoracic and Cardiovascular Surgery.

Preventing stroke in this patient population is an important consideration, because perioperative stroke is approximately 4 times more common in open aortic arch surgery (OAAS) than in coronary artery bypass grafting or valve surgery, according to Ken-ichi Imasaka, MD, and his colleagues at the National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.

The study population comprised 200 consecutive patients undergoing elective OAAS at the institution between October 2008 and October 2015, including 34% women and with a mean patient age of 71 years (J Thorac Cardiovasc Surg. 2017;153:1045-53).

After preoperative screening, 21% of patients were diagnosed with carotid or intracranial artery disease (CIAD). None of these patients were diagnosed with impaired cerebral perfusion reserve on brain SPECT (single-photon emission computed tomography). A total of 92% of patients underwent ascending aorta or aortic arch replacement through a median sternotomy, while the remaining 8% underwent extended aortic arch replacement via L-incision (15 patients) or combined median sternotomy and left posterior lateral thoracotomy (1 patient). Among the patients, 16% underwent ascending aorta replacement; 8% had partial arch replacement; and the remaining 76% had total arch replacement.

Shaggy aorta was present in 19% of the patients, with 51% of these showing CIAD (P less than .0001). A total of 30% of the patients with shaggy aorta had the total arch replacement through an L-incision or combined median sternotomy and left posterior lateral thoracotomy, a significant difference (P less than .0001).

Dr. Ourania Preventza of the Baylor College of Medicine, Houston

[email protected]

Embolization was the major cause of permanent stroke in patients with moderate or severe carotid or intracranial atherosclerosis who underwent elective open aortic arch surgery at a single institution, according to the results of a retrospective study.

Preoperative craniocervical and aortic screening may aid in modifying the operative strategy to reduce the incidence of stroke in these patients, according to a report published in the May issue of the Journal of Thoracic and Cardiovascular Surgery.

Preventing stroke in this patient population is an important consideration, because perioperative stroke is approximately 4 times more common in open aortic arch surgery (OAAS) than in coronary artery bypass grafting or valve surgery, according to Ken-ichi Imasaka, MD, and his colleagues at the National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.

The study population comprised 200 consecutive patients undergoing elective OAAS at the institution between October 2008 and October 2015, including 34% women and with a mean patient age of 71 years (J Thorac Cardiovasc Surg. 2017;153:1045-53).

After preoperative screening, 21% of patients were diagnosed with carotid or intracranial artery disease (CIAD). None of these patients were diagnosed with impaired cerebral perfusion reserve on brain SPECT (single-photon emission computed tomography). A total of 92% of patients underwent ascending aorta or aortic arch replacement through a median sternotomy, while the remaining 8% underwent extended aortic arch replacement via L-incision (15 patients) or combined median sternotomy and left posterior lateral thoracotomy (1 patient). Among the patients, 16% underwent ascending aorta replacement; 8% had partial arch replacement; and the remaining 76% had total arch replacement.

Shaggy aorta was present in 19% of the patients, with 51% of these showing CIAD (P less than .0001). A total of 30% of the patients with shaggy aorta had the total arch replacement through an L-incision or combined median sternotomy and left posterior lateral thoracotomy, a significant difference (P less than .0001).

Dr. Ourania Preventza of the Baylor College of Medicine, Houston

[email protected]

Embolization was the major cause of permanent stroke in patients with moderate or severe carotid or intracranial atherosclerosis who underwent elective open aortic arch surgery at a single institution, according to the results of a retrospective study.

Preoperative craniocervical and aortic screening may aid in modifying the operative strategy to reduce the incidence of stroke in these patients, according to a report published in the May issue of the Journal of Thoracic and Cardiovascular Surgery.

Preventing stroke in this patient population is an important consideration, because perioperative stroke is approximately 4 times more common in open aortic arch surgery (OAAS) than in coronary artery bypass grafting or valve surgery, according to Ken-ichi Imasaka, MD, and his colleagues at the National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.

The study population comprised 200 consecutive patients undergoing elective OAAS at the institution between October 2008 and October 2015, including 34% women and with a mean patient age of 71 years (J Thorac Cardiovasc Surg. 2017;153:1045-53).

After preoperative screening, 21% of patients were diagnosed with carotid or intracranial artery disease (CIAD). None of these patients were diagnosed with impaired cerebral perfusion reserve on brain SPECT (single-photon emission computed tomography). A total of 92% of patients underwent ascending aorta or aortic arch replacement through a median sternotomy, while the remaining 8% underwent extended aortic arch replacement via L-incision (15 patients) or combined median sternotomy and left posterior lateral thoracotomy (1 patient). Among the patients, 16% underwent ascending aorta replacement; 8% had partial arch replacement; and the remaining 76% had total arch replacement.

Shaggy aorta was present in 19% of the patients, with 51% of these showing CIAD (P less than .0001). A total of 30% of the patients with shaggy aorta had the total arch replacement through an L-incision or combined median sternotomy and left posterior lateral thoracotomy, a significant difference (P less than .0001).

Dr. Ourania Preventza of the Baylor College of Medicine, Houston

[email protected]

BIRMINGHAM, ENGLAND – Improvements in physical health with response to treatment of rheumatoid arthritis (RA) don’t necessarily translate into improvements in patients’ mental health, based on results of a systematic review presented at the British Society for Rheumatology annual conference.

Reducing levels of joint pain and inflammation did not appreciably improve mental well-being, said Faith Matcham, PhD, of the Institute of Psychiatry, Psychology, and Neuroscience, King’s College London. The standardized mean difference between biologics and disease-modifying antirheumatic drugs (DMARDs) in improving the physical and mental components of the 36-item Short Form survey were a respective 0.47 and 0.25.

Sara Freeman/Frontline Medical News

Dr. Matcham reported having no financial disclosures.

BIRMINGHAM, ENGLAND – Improvements in physical health with response to treatment of rheumatoid arthritis (RA) don’t necessarily translate into improvements in patients’ mental health, based on results of a systematic review presented at the British Society for Rheumatology annual conference.

Reducing levels of joint pain and inflammation did not appreciably improve mental well-being, said Faith Matcham, PhD, of the Institute of Psychiatry, Psychology, and Neuroscience, King’s College London. The standardized mean difference between biologics and disease-modifying antirheumatic drugs (DMARDs) in improving the physical and mental components of the 36-item Short Form survey were a respective 0.47 and 0.25.

Sara Freeman/Frontline Medical News

Dr. Matcham reported having no financial disclosures.

BIRMINGHAM, ENGLAND – Improvements in physical health with response to treatment of rheumatoid arthritis (RA) don’t necessarily translate into improvements in patients’ mental health, based on results of a systematic review presented at the British Society for Rheumatology annual conference.

Reducing levels of joint pain and inflammation did not appreciably improve mental well-being, said Faith Matcham, PhD, of the Institute of Psychiatry, Psychology, and Neuroscience, King’s College London. The standardized mean difference between biologics and disease-modifying antirheumatic drugs (DMARDs) in improving the physical and mental components of the 36-item Short Form survey were a respective 0.47 and 0.25.

Sara Freeman/Frontline Medical News

Dr. Matcham reported having no financial disclosures.

PORTLAND – The investigational agent CC-220 showed some efficacy but important safety signals in a 12-week, phase II, dose-escalation study of 42 patients with systemic lupus erythematosus (SLE).

In all, 14% of patients stopped treatment because of adverse effects, including five patients who were receiving CC-220 and one patient on placebo, Victoria Werth, MD, of the University of Pennsylvania, Philadelphia, said during a poster presentation at the annual meeting of the Society for Investigative Dermatology. Higher doses of CC-220 were associated with neutropenia, pneumonia, and dermatitis, she reported.

PORTLAND – The investigational agent CC-220 showed some efficacy but important safety signals in a 12-week, phase II, dose-escalation study of 42 patients with systemic lupus erythematosus (SLE).

In all, 14% of patients stopped treatment because of adverse effects, including five patients who were receiving CC-220 and one patient on placebo, Victoria Werth, MD, of the University of Pennsylvania, Philadelphia, said during a poster presentation at the annual meeting of the Society for Investigative Dermatology. Higher doses of CC-220 were associated with neutropenia, pneumonia, and dermatitis, she reported.

PORTLAND – The investigational agent CC-220 showed some efficacy but important safety signals in a 12-week, phase II, dose-escalation study of 42 patients with systemic lupus erythematosus (SLE).

In all, 14% of patients stopped treatment because of adverse effects, including five patients who were receiving CC-220 and one patient on placebo, Victoria Werth, MD, of the University of Pennsylvania, Philadelphia, said during a poster presentation at the annual meeting of the Society for Investigative Dermatology. Higher doses of CC-220 were associated with neutropenia, pneumonia, and dermatitis, she reported.

AMSTERDAM – There is a “very, very rich pipeline” of drugs being developed for the treatment of nonalcoholic steatohepatitis (NASH), Jean-François Dufour, MD, the head of hepatology and director of the University Clinic for Visceral Surgery and Medicine at the University of Berne (Switzerland) said at the International Liver Congress.

“We have many therapeutic options [under investigation],” Dr. Dufour noted at the Congress, which is sponsored by the European Association for the Study of the Liver (EASL). These include drugs that target metabolic homeostasis, insulin resistance, inflammation, oxidative stress, or fibrosis (Liver Int. 2017 May;37:634-47).

In fact, there is such a range of options that target different pathways, from fatty acid and bile acid synthesis to the early and late stages of fibrosis, that it is very likely that these drugs will be used in combination, Dr. Dufour observed as he gave an overview of the current trials that are underway in NASH.

There are currently five ongoing multicenter phase III trials being undertaken with four drugs. First, there is the REGENERATE trial with Intercept’s farnesoid X receptor obeticholic acid(Ocaliva). This is a placebo-controlled trial comparing two daily doses of obeticholic acid (10 and 25 mg) on top of the standard of care. The trial will recruit just over 2,000 patients with biopsy-proven stage 2-3 NASH fibrosis, and the primary endpoint is the resolution of NASH without fibrosis worsening or improvement in fibrosis without worsening of NASH at week 72.

Second there is the RESOLVE-IT trial with Genfit’s peroxisome proliferator-activated receptor alpha/delta agonist elafibranor. This randomized, double-blind trial hopes to recruit 2,000 patients with biopsy-proven NASH stage 1-3 fibrosis and will compare elafibranor 120 mg given once a day with placebo. The primary endpoint is the resolution of NASH without worsening of fibrosis at week 72.

Next, Tobira Therapeutics’ C-C chemokine receptor type 2 and 5 antagonist cenicriviroc is being studied in the AURORA trial. Again, recruiting around 2,000 patients is the target, but this time with stage 2-3 biopsy-proven NASH fibrosis. Cenicriviroc will be given daily at a dose of 150 mg and will be compared against placebo. The primary endpoint is the improvement of fibrosis by one or more stage with no worsening of steatohepatitis at 1 year.

Finally, there are the STELLA 3 and STELLA 4 trials with Gilead’s apoptosis signal-regulated kinase-1 inhibitor selonsertib. Target accrual in both studies is 800 patients with STELLA 3 recruiting patients with stage-3 NASH fibrosis and STELLA 4 recruiting those with compensated cirrhosis from NASH. Both trials will compared two daily doses of selonsertib (6 mg and 18 mg) versus placebo. The primary endpoints are the improvement of at least one or more fibrosis stage with no worsening of steatohepatitis at 48 weeks and event-free survival at week 240.

In addition, there are at least 20 phase 2b and 2a studies looking at a variety of other novel drugs with different therapeutic targets, Dr. Dufour said, and during separate presentations at the congress, results of several early trials with novel drugs being tested for NASH were given.

Eric J. Lawitz, MD, reported the promising results of a “proof of concept” open-label study in which the safety and efficacy of 12 weeks’ treatment with the oral acetyl-CoA carboxylase (ACC) inhibitor, GS-0976, was examined in 10 patients with a clinical diagnosis of nonalcoholic fatty liver disease (NAFLD).

“ACC catalyzes the rate-limiting step in de novo hepatic lipogenesis (DNL),” which is an underlying pathologic process in NASH, Dr. Lawitz, who is vice president of scientific and research development at the Texas Liver Institute, San Antonio, observed.

He reported that 12 weeks’ treatment with the ACC inhibitor GS-0976 suppressed DNL by 29%, compared with baseline (P = .022). There was also a 43% decrease in hepatic steatosis from baseline to 12 weeks (P = .006), as measured by the magnetic resonance imaging–proton-density fat fraction (MRI-PDFF), and a nonsignificant 9% reduction in liver stiffness measured using magnetic resonance elastography (MRE).

Two markers of fibrosis and cell death (TIMP-1 and CK18) were also improved, he said, noting that overall, the drug was well tolerated, bar a trend to an increase in triglycerides and reduction in high-density lipoprotein cholesterol that needs further follow up.

“There is a placebo-controlled phase II trial of GS-0976 in patients with NASH that is ongoing,” Dr. Lawitz said. Results of two phase II studies presented during the late-breaking abstracts session at the meeting showed similar promising results could be achieved with drugs mimicking the activity of different fibroblast growth factors.

“Fibroblast growth factor 21 (FGF21) is a nonmitogenic hormone produced in the liver that is an important regulator of energy metabolism,” said Arun J. Sanyal, MD, who presented the findings of a study with the FGF21 inhibitor BMS-986036.

”From a NASH perspective, it improves insulin sensitivity and by doing that, decreases lipogenesis, and it also has been shown to have some antifibrotic effects,” Dr. Sanyal of Virginia Commonwealth University in Richmond, added.

FGF21 has a short half-life, however, and BMS-986036 is a recombinant human analog of this hormone that could potentially allow it to be given up to once weekly.

The study involved 74 patients with stage 1-3 biopsy-proven NASH fibrosis and a hepatic fat fraction of 10% or greater measured by MRI-PDFF. Patients were randomized to treatment with BMS-986036 at subcutaneously administered doses of 10 mg given once daily or 20 mg given once weekly or to placebo for 16 weeks.

A significant reduction in the hepatic fat fraction was seen in patients treated with both the once-daily and once-weekly regimen of the active treatment relative to placebo, with absolute changes from baseline of –6.8% (P = .008) and –5.2% (P = .0004), respectively, and just –1.3% for placebo.

“Results suggest that BMS-986036 had beneficial effects on steatosis, liver injury, and fibrosis in NASH,” said Dr. Sanyal, who also noted that there were no deaths and no signal that there could be any safety concerns.

NGM282 is another recombinant human analog mimicking the action of an FGF, this time FGF19, and early data also suggest that it also reduces hepatic steatosis and key biomarkers of NASH. Dr. Stephen Harrison, MD, the medical director of Pinnacle Clinical Research in Live Oak, reported data on 82 patients with stage 1-3 NASH fibrosis who had been treated with NGM-282 3 mg or 6 mg subcutaneously once a day or placebo for 12 weeks.

“The primary endpoint [decrease in absolute liver fat content greater than or equal to 5%] was met in 79% of NGM-282-treated subjects, with over one-third of subjects achieving normalization of liver fat content with 12 weeks of therapy,” Dr. Harrison reported.

“There were significant and rapid reductions in multiple markers that are relevant to the resolution of NASH and improvement in fibrosis,” Dr. Harrison added.

One serious adverse event of acute pancreatitis occurred in a patient treated with FGF19, which was possibly thought to be treatment related, but otherwise adverse events were generally mild and included gastrointestinal effects such as diarrhea and nausea, and injection site reactions.

“These data strongly support the continued development of NGM282 in NASH,” Dr. Harrison said.

During his presentation at a symposium session on current and future approaches to NAFLD and NASH, Dr. Dufour was keen to point out that a combination of diet and exercise remains central to managing patients with NASH.

“We should not forget, that the first line of discussion with these patients should be about changing their lifestyles.” Improving diet and exercise is something that everybody can do, he said, it is widely available and inexpensive, associated with few side effects and can produce good results.

However, convincing some patients can be difficult and those with a low acceptance to lifestyle changes often prefer to take medication. That is likely to come at a cost, not just in terms of money but there are likely to be some side effects, and, of course, efficacy in NASH is yet to be proven in many cases, Dr. Dufour said.

Dr. Dufour disclosed he had been part of a number of advisory committees or received speaking and teaching fees from a host of pharmaceutical companies, many of whom have an interest in the development of treatments for NASH.

Gilead Sciences supported the study reported by Dr. Lawitz and he disclosed receiving research grants or other support from the company, as well as several other pharmaceutical companies.

The study presented by Dr. Sanyal was financed by Bristol-Myers Squibb and he disclosed research funding was provided to his institution. Dr. Sanyal also disclosed receiving research support and consulting fees from multiple other pharmaceutical companies.

Dr. Harrison acknowledged receiving research funding from and acting as a consultant to NGM Bio, who sponsored the study he presented. He also disclosed acting as an adviser or speaker, and receiving grants from other pharmaceutical companies in the past 12 months.

AMSTERDAM – There is a “very, very rich pipeline” of drugs being developed for the treatment of nonalcoholic steatohepatitis (NASH), Jean-François Dufour, MD, the head of hepatology and director of the University Clinic for Visceral Surgery and Medicine at the University of Berne (Switzerland) said at the International Liver Congress.

“We have many therapeutic options [under investigation],” Dr. Dufour noted at the Congress, which is sponsored by the European Association for the Study of the Liver (EASL). These include drugs that target metabolic homeostasis, insulin resistance, inflammation, oxidative stress, or fibrosis (Liver Int. 2017 May;37:634-47).

In fact, there is such a range of options that target different pathways, from fatty acid and bile acid synthesis to the early and late stages of fibrosis, that it is very likely that these drugs will be used in combination, Dr. Dufour observed as he gave an overview of the current trials that are underway in NASH.

There are currently five ongoing multicenter phase III trials being undertaken with four drugs. First, there is the REGENERATE trial with Intercept’s farnesoid X receptor obeticholic acid(Ocaliva). This is a placebo-controlled trial comparing two daily doses of obeticholic acid (10 and 25 mg) on top of the standard of care. The trial will recruit just over 2,000 patients with biopsy-proven stage 2-3 NASH fibrosis, and the primary endpoint is the resolution of NASH without fibrosis worsening or improvement in fibrosis without worsening of NASH at week 72.

Second there is the RESOLVE-IT trial with Genfit’s peroxisome proliferator-activated receptor alpha/delta agonist elafibranor. This randomized, double-blind trial hopes to recruit 2,000 patients with biopsy-proven NASH stage 1-3 fibrosis and will compare elafibranor 120 mg given once a day with placebo. The primary endpoint is the resolution of NASH without worsening of fibrosis at week 72.

Next, Tobira Therapeutics’ C-C chemokine receptor type 2 and 5 antagonist cenicriviroc is being studied in the AURORA trial. Again, recruiting around 2,000 patients is the target, but this time with stage 2-3 biopsy-proven NASH fibrosis. Cenicriviroc will be given daily at a dose of 150 mg and will be compared against placebo. The primary endpoint is the improvement of fibrosis by one or more stage with no worsening of steatohepatitis at 1 year.

Finally, there are the STELLA 3 and STELLA 4 trials with Gilead’s apoptosis signal-regulated kinase-1 inhibitor selonsertib. Target accrual in both studies is 800 patients with STELLA 3 recruiting patients with stage-3 NASH fibrosis and STELLA 4 recruiting those with compensated cirrhosis from NASH. Both trials will compared two daily doses of selonsertib (6 mg and 18 mg) versus placebo. The primary endpoints are the improvement of at least one or more fibrosis stage with no worsening of steatohepatitis at 48 weeks and event-free survival at week 240.

In addition, there are at least 20 phase 2b and 2a studies looking at a variety of other novel drugs with different therapeutic targets, Dr. Dufour said, and during separate presentations at the congress, results of several early trials with novel drugs being tested for NASH were given.

Eric J. Lawitz, MD, reported the promising results of a “proof of concept” open-label study in which the safety and efficacy of 12 weeks’ treatment with the oral acetyl-CoA carboxylase (ACC) inhibitor, GS-0976, was examined in 10 patients with a clinical diagnosis of nonalcoholic fatty liver disease (NAFLD).

“ACC catalyzes the rate-limiting step in de novo hepatic lipogenesis (DNL),” which is an underlying pathologic process in NASH, Dr. Lawitz, who is vice president of scientific and research development at the Texas Liver Institute, San Antonio, observed.

He reported that 12 weeks’ treatment with the ACC inhibitor GS-0976 suppressed DNL by 29%, compared with baseline (P = .022). There was also a 43% decrease in hepatic steatosis from baseline to 12 weeks (P = .006), as measured by the magnetic resonance imaging–proton-density fat fraction (MRI-PDFF), and a nonsignificant 9% reduction in liver stiffness measured using magnetic resonance elastography (MRE).

Two markers of fibrosis and cell death (TIMP-1 and CK18) were also improved, he said, noting that overall, the drug was well tolerated, bar a trend to an increase in triglycerides and reduction in high-density lipoprotein cholesterol that needs further follow up.

“There is a placebo-controlled phase II trial of GS-0976 in patients with NASH that is ongoing,” Dr. Lawitz said. Results of two phase II studies presented during the late-breaking abstracts session at the meeting showed similar promising results could be achieved with drugs mimicking the activity of different fibroblast growth factors.

“Fibroblast growth factor 21 (FGF21) is a nonmitogenic hormone produced in the liver that is an important regulator of energy metabolism,” said Arun J. Sanyal, MD, who presented the findings of a study with the FGF21 inhibitor BMS-986036.

”From a NASH perspective, it improves insulin sensitivity and by doing that, decreases lipogenesis, and it also has been shown to have some antifibrotic effects,” Dr. Sanyal of Virginia Commonwealth University in Richmond, added.

FGF21 has a short half-life, however, and BMS-986036 is a recombinant human analog of this hormone that could potentially allow it to be given up to once weekly.

The study involved 74 patients with stage 1-3 biopsy-proven NASH fibrosis and a hepatic fat fraction of 10% or greater measured by MRI-PDFF. Patients were randomized to treatment with BMS-986036 at subcutaneously administered doses of 10 mg given once daily or 20 mg given once weekly or to placebo for 16 weeks.

A significant reduction in the hepatic fat fraction was seen in patients treated with both the once-daily and once-weekly regimen of the active treatment relative to placebo, with absolute changes from baseline of –6.8% (P = .008) and –5.2% (P = .0004), respectively, and just –1.3% for placebo.

“Results suggest that BMS-986036 had beneficial effects on steatosis, liver injury, and fibrosis in NASH,” said Dr. Sanyal, who also noted that there were no deaths and no signal that there could be any safety concerns.

NGM282 is another recombinant human analog mimicking the action of an FGF, this time FGF19, and early data also suggest that it also reduces hepatic steatosis and key biomarkers of NASH. Dr. Stephen Harrison, MD, the medical director of Pinnacle Clinical Research in Live Oak, reported data on 82 patients with stage 1-3 NASH fibrosis who had been treated with NGM-282 3 mg or 6 mg subcutaneously once a day or placebo for 12 weeks.

“The primary endpoint [decrease in absolute liver fat content greater than or equal to 5%] was met in 79% of NGM-282-treated subjects, with over one-third of subjects achieving normalization of liver fat content with 12 weeks of therapy,” Dr. Harrison reported.

“There were significant and rapid reductions in multiple markers that are relevant to the resolution of NASH and improvement in fibrosis,” Dr. Harrison added.

One serious adverse event of acute pancreatitis occurred in a patient treated with FGF19, which was possibly thought to be treatment related, but otherwise adverse events were generally mild and included gastrointestinal effects such as diarrhea and nausea, and injection site reactions.

“These data strongly support the continued development of NGM282 in NASH,” Dr. Harrison said.

During his presentation at a symposium session on current and future approaches to NAFLD and NASH, Dr. Dufour was keen to point out that a combination of diet and exercise remains central to managing patients with NASH.

“We should not forget, that the first line of discussion with these patients should be about changing their lifestyles.” Improving diet and exercise is something that everybody can do, he said, it is widely available and inexpensive, associated with few side effects and can produce good results.

However, convincing some patients can be difficult and those with a low acceptance to lifestyle changes often prefer to take medication. That is likely to come at a cost, not just in terms of money but there are likely to be some side effects, and, of course, efficacy in NASH is yet to be proven in many cases, Dr. Dufour said.

Dr. Dufour disclosed he had been part of a number of advisory committees or received speaking and teaching fees from a host of pharmaceutical companies, many of whom have an interest in the development of treatments for NASH.

Gilead Sciences supported the study reported by Dr. Lawitz and he disclosed receiving research grants or other support from the company, as well as several other pharmaceutical companies.

The study presented by Dr. Sanyal was financed by Bristol-Myers Squibb and he disclosed research funding was provided to his institution. Dr. Sanyal also disclosed receiving research support and consulting fees from multiple other pharmaceutical companies.

Dr. Harrison acknowledged receiving research funding from and acting as a consultant to NGM Bio, who sponsored the study he presented. He also disclosed acting as an adviser or speaker, and receiving grants from other pharmaceutical companies in the past 12 months.

AMSTERDAM – There is a “very, very rich pipeline” of drugs being developed for the treatment of nonalcoholic steatohepatitis (NASH), Jean-François Dufour, MD, the head of hepatology and director of the University Clinic for Visceral Surgery and Medicine at the University of Berne (Switzerland) said at the International Liver Congress.

“We have many therapeutic options [under investigation],” Dr. Dufour noted at the Congress, which is sponsored by the European Association for the Study of the Liver (EASL). These include drugs that target metabolic homeostasis, insulin resistance, inflammation, oxidative stress, or fibrosis (Liver Int. 2017 May;37:634-47).

In fact, there is such a range of options that target different pathways, from fatty acid and bile acid synthesis to the early and late stages of fibrosis, that it is very likely that these drugs will be used in combination, Dr. Dufour observed as he gave an overview of the current trials that are underway in NASH.

There are currently five ongoing multicenter phase III trials being undertaken with four drugs. First, there is the REGENERATE trial with Intercept’s farnesoid X receptor obeticholic acid(Ocaliva). This is a placebo-controlled trial comparing two daily doses of obeticholic acid (10 and 25 mg) on top of the standard of care. The trial will recruit just over 2,000 patients with biopsy-proven stage 2-3 NASH fibrosis, and the primary endpoint is the resolution of NASH without fibrosis worsening or improvement in fibrosis without worsening of NASH at week 72.

Second there is the RESOLVE-IT trial with Genfit’s peroxisome proliferator-activated receptor alpha/delta agonist elafibranor. This randomized, double-blind trial hopes to recruit 2,000 patients with biopsy-proven NASH stage 1-3 fibrosis and will compare elafibranor 120 mg given once a day with placebo. The primary endpoint is the resolution of NASH without worsening of fibrosis at week 72.

Next, Tobira Therapeutics’ C-C chemokine receptor type 2 and 5 antagonist cenicriviroc is being studied in the AURORA trial. Again, recruiting around 2,000 patients is the target, but this time with stage 2-3 biopsy-proven NASH fibrosis. Cenicriviroc will be given daily at a dose of 150 mg and will be compared against placebo. The primary endpoint is the improvement of fibrosis by one or more stage with no worsening of steatohepatitis at 1 year.

Finally, there are the STELLA 3 and STELLA 4 trials with Gilead’s apoptosis signal-regulated kinase-1 inhibitor selonsertib. Target accrual in both studies is 800 patients with STELLA 3 recruiting patients with stage-3 NASH fibrosis and STELLA 4 recruiting those with compensated cirrhosis from NASH. Both trials will compared two daily doses of selonsertib (6 mg and 18 mg) versus placebo. The primary endpoints are the improvement of at least one or more fibrosis stage with no worsening of steatohepatitis at 48 weeks and event-free survival at week 240.

In addition, there are at least 20 phase 2b and 2a studies looking at a variety of other novel drugs with different therapeutic targets, Dr. Dufour said, and during separate presentations at the congress, results of several early trials with novel drugs being tested for NASH were given.

Eric J. Lawitz, MD, reported the promising results of a “proof of concept” open-label study in which the safety and efficacy of 12 weeks’ treatment with the oral acetyl-CoA carboxylase (ACC) inhibitor, GS-0976, was examined in 10 patients with a clinical diagnosis of nonalcoholic fatty liver disease (NAFLD).

“ACC catalyzes the rate-limiting step in de novo hepatic lipogenesis (DNL),” which is an underlying pathologic process in NASH, Dr. Lawitz, who is vice president of scientific and research development at the Texas Liver Institute, San Antonio, observed.

He reported that 12 weeks’ treatment with the ACC inhibitor GS-0976 suppressed DNL by 29%, compared with baseline (P = .022). There was also a 43% decrease in hepatic steatosis from baseline to 12 weeks (P = .006), as measured by the magnetic resonance imaging–proton-density fat fraction (MRI-PDFF), and a nonsignificant 9% reduction in liver stiffness measured using magnetic resonance elastography (MRE).

Two markers of fibrosis and cell death (TIMP-1 and CK18) were also improved, he said, noting that overall, the drug was well tolerated, bar a trend to an increase in triglycerides and reduction in high-density lipoprotein cholesterol that needs further follow up.

“There is a placebo-controlled phase II trial of GS-0976 in patients with NASH that is ongoing,” Dr. Lawitz said. Results of two phase II studies presented during the late-breaking abstracts session at the meeting showed similar promising results could be achieved with drugs mimicking the activity of different fibroblast growth factors.

“Fibroblast growth factor 21 (FGF21) is a nonmitogenic hormone produced in the liver that is an important regulator of energy metabolism,” said Arun J. Sanyal, MD, who presented the findings of a study with the FGF21 inhibitor BMS-986036.

”From a NASH perspective, it improves insulin sensitivity and by doing that, decreases lipogenesis, and it also has been shown to have some antifibrotic effects,” Dr. Sanyal of Virginia Commonwealth University in Richmond, added.

FGF21 has a short half-life, however, and BMS-986036 is a recombinant human analog of this hormone that could potentially allow it to be given up to once weekly.

The study involved 74 patients with stage 1-3 biopsy-proven NASH fibrosis and a hepatic fat fraction of 10% or greater measured by MRI-PDFF. Patients were randomized to treatment with BMS-986036 at subcutaneously administered doses of 10 mg given once daily or 20 mg given once weekly or to placebo for 16 weeks.

A significant reduction in the hepatic fat fraction was seen in patients treated with both the once-daily and once-weekly regimen of the active treatment relative to placebo, with absolute changes from baseline of –6.8% (P = .008) and –5.2% (P = .0004), respectively, and just –1.3% for placebo.

“Results suggest that BMS-986036 had beneficial effects on steatosis, liver injury, and fibrosis in NASH,” said Dr. Sanyal, who also noted that there were no deaths and no signal that there could be any safety concerns.

NGM282 is another recombinant human analog mimicking the action of an FGF, this time FGF19, and early data also suggest that it also reduces hepatic steatosis and key biomarkers of NASH. Dr. Stephen Harrison, MD, the medical director of Pinnacle Clinical Research in Live Oak, reported data on 82 patients with stage 1-3 NASH fibrosis who had been treated with NGM-282 3 mg or 6 mg subcutaneously once a day or placebo for 12 weeks.

“The primary endpoint [decrease in absolute liver fat content greater than or equal to 5%] was met in 79% of NGM-282-treated subjects, with over one-third of subjects achieving normalization of liver fat content with 12 weeks of therapy,” Dr. Harrison reported.

“There were significant and rapid reductions in multiple markers that are relevant to the resolution of NASH and improvement in fibrosis,” Dr. Harrison added.

One serious adverse event of acute pancreatitis occurred in a patient treated with FGF19, which was possibly thought to be treatment related, but otherwise adverse events were generally mild and included gastrointestinal effects such as diarrhea and nausea, and injection site reactions.

“These data strongly support the continued development of NGM282 in NASH,” Dr. Harrison said.

During his presentation at a symposium session on current and future approaches to NAFLD and NASH, Dr. Dufour was keen to point out that a combination of diet and exercise remains central to managing patients with NASH.

“We should not forget, that the first line of discussion with these patients should be about changing their lifestyles.” Improving diet and exercise is something that everybody can do, he said, it is widely available and inexpensive, associated with few side effects and can produce good results.

However, convincing some patients can be difficult and those with a low acceptance to lifestyle changes often prefer to take medication. That is likely to come at a cost, not just in terms of money but there are likely to be some side effects, and, of course, efficacy in NASH is yet to be proven in many cases, Dr. Dufour said.

Dr. Dufour disclosed he had been part of a number of advisory committees or received speaking and teaching fees from a host of pharmaceutical companies, many of whom have an interest in the development of treatments for NASH.

Gilead Sciences supported the study reported by Dr. Lawitz and he disclosed receiving research grants or other support from the company, as well as several other pharmaceutical companies.

The study presented by Dr. Sanyal was financed by Bristol-Myers Squibb and he disclosed research funding was provided to his institution. Dr. Sanyal also disclosed receiving research support and consulting fees from multiple other pharmaceutical companies.

Dr. Harrison acknowledged receiving research funding from and acting as a consultant to NGM Bio, who sponsored the study he presented. He also disclosed acting as an adviser or speaker, and receiving grants from other pharmaceutical companies in the past 12 months.

GENEVA – Patients with stage IV non–small cell lung cancer (NSCLC) who have disease progression following treatment with an immune checkpoint inhibitor have a 30% better chance of achieving at least a partial response with salvage chemotherapy compared with patients who had received prior chemotherapy but not immunotherapy, according to Swiss and U.S. investigators.

In a study of 82 patients with advanced NSCLC, 18 of 67 patients (27%) who had progressed on an inhibitor of programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) had a partial response to combination chemotherapy, compared with just 1 of 15 (7%) of patients who had not received a checkpoint inhibitor, reported Sacha Rothschild, MD, PhD, of University Hospital Basel, Switzerland, and colleagues.

“The odds of achieving a partial response to salvage chemotherapy were significantly higher in patients with prior exposure to PD-1/PD-L1 inhibitors. This observed difference, however, warrants confirmation in larger cohorts. Ongoing investigations include the duration of response as well as evaluation of toxicity,” the researchers wrote in a scientific poster presented at the European Lung Cancer Conference.

Immune checkpoint inhibitors have been shown to be active in patients with late-stage NSCLC who have experienced disease progression following chemotherapy. To see whether salvage chemotherapy could offer any additional benefit to patients who had disease progression on immunotherapy, the investigators conducted a retrospective case-control study. They reviewed 355 patient records, and identified 82 patients – 46 men and 36 women – who met the study criteria.

Of this group, 67 patients had received a PD-1/PD-L1 checkpoint inhibitor, either nivolumab (Opdivo, 56 patients), pembrolizumab (Keytruda, 7), or atezolizumab (Tecentriq, 4). These patients were designated as cases. The remaining 15 patients, who had received prior chemotherapy or chemoradiotherapy only, were designated as controls.

Of all 82 patients, 63 (77%) had adenocarcinomas, 18 (22%) had squamous cell carcinomas, and 1 (1%) had a large-cell carcinoma.

Cases had a mean of 2.37 chemotherapy regimens prior to salvage chemotherapy, and controls had a mean of 1.93. Drugs used in the salvage regimens were docetaxel in 62% of patients, pemetrexed in 20%, gemcitabine in 12%, and paclitaxel in 6%.

GENEVA – Patients with stage IV non–small cell lung cancer (NSCLC) who have disease progression following treatment with an immune checkpoint inhibitor have a 30% better chance of achieving at least a partial response with salvage chemotherapy compared with patients who had received prior chemotherapy but not immunotherapy, according to Swiss and U.S. investigators.

In a study of 82 patients with advanced NSCLC, 18 of 67 patients (27%) who had progressed on an inhibitor of programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) had a partial response to combination chemotherapy, compared with just 1 of 15 (7%) of patients who had not received a checkpoint inhibitor, reported Sacha Rothschild, MD, PhD, of University Hospital Basel, Switzerland, and colleagues.

“The odds of achieving a partial response to salvage chemotherapy were significantly higher in patients with prior exposure to PD-1/PD-L1 inhibitors. This observed difference, however, warrants confirmation in larger cohorts. Ongoing investigations include the duration of response as well as evaluation of toxicity,” the researchers wrote in a scientific poster presented at the European Lung Cancer Conference.

Immune checkpoint inhibitors have been shown to be active in patients with late-stage NSCLC who have experienced disease progression following chemotherapy. To see whether salvage chemotherapy could offer any additional benefit to patients who had disease progression on immunotherapy, the investigators conducted a retrospective case-control study. They reviewed 355 patient records, and identified 82 patients – 46 men and 36 women – who met the study criteria.

Of this group, 67 patients had received a PD-1/PD-L1 checkpoint inhibitor, either nivolumab (Opdivo, 56 patients), pembrolizumab (Keytruda, 7), or atezolizumab (Tecentriq, 4). These patients were designated as cases. The remaining 15 patients, who had received prior chemotherapy or chemoradiotherapy only, were designated as controls.

Of all 82 patients, 63 (77%) had adenocarcinomas, 18 (22%) had squamous cell carcinomas, and 1 (1%) had a large-cell carcinoma.

Cases had a mean of 2.37 chemotherapy regimens prior to salvage chemotherapy, and controls had a mean of 1.93. Drugs used in the salvage regimens were docetaxel in 62% of patients, pemetrexed in 20%, gemcitabine in 12%, and paclitaxel in 6%.

GENEVA – Patients with stage IV non–small cell lung cancer (NSCLC) who have disease progression following treatment with an immune checkpoint inhibitor have a 30% better chance of achieving at least a partial response with salvage chemotherapy compared with patients who had received prior chemotherapy but not immunotherapy, according to Swiss and U.S. investigators.

In a study of 82 patients with advanced NSCLC, 18 of 67 patients (27%) who had progressed on an inhibitor of programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) had a partial response to combination chemotherapy, compared with just 1 of 15 (7%) of patients who had not received a checkpoint inhibitor, reported Sacha Rothschild, MD, PhD, of University Hospital Basel, Switzerland, and colleagues.

“The odds of achieving a partial response to salvage chemotherapy were significantly higher in patients with prior exposure to PD-1/PD-L1 inhibitors. This observed difference, however, warrants confirmation in larger cohorts. Ongoing investigations include the duration of response as well as evaluation of toxicity,” the researchers wrote in a scientific poster presented at the European Lung Cancer Conference.

Immune checkpoint inhibitors have been shown to be active in patients with late-stage NSCLC who have experienced disease progression following chemotherapy. To see whether salvage chemotherapy could offer any additional benefit to patients who had disease progression on immunotherapy, the investigators conducted a retrospective case-control study. They reviewed 355 patient records, and identified 82 patients – 46 men and 36 women – who met the study criteria.

Of this group, 67 patients had received a PD-1/PD-L1 checkpoint inhibitor, either nivolumab (Opdivo, 56 patients), pembrolizumab (Keytruda, 7), or atezolizumab (Tecentriq, 4). These patients were designated as cases. The remaining 15 patients, who had received prior chemotherapy or chemoradiotherapy only, were designated as controls.

Of all 82 patients, 63 (77%) had adenocarcinomas, 18 (22%) had squamous cell carcinomas, and 1 (1%) had a large-cell carcinoma.

Cases had a mean of 2.37 chemotherapy regimens prior to salvage chemotherapy, and controls had a mean of 1.93. Drugs used in the salvage regimens were docetaxel in 62% of patients, pemetrexed in 20%, gemcitabine in 12%, and paclitaxel in 6%.

Cognitive behavioral therapy administered online can effectively treat symptoms of depression in older people with knee osteoarthritis, according to results from the first randomized trial of its kind.

The benefits of the 10-week program extended to improving pain, stiffness, physical functioning, and self-efficacy, reported Kathleen A. O’Moore, PsyD, of St. Vincent’s Hospital, Sydney, Australia, and her colleagues (Arthritis Care Res. 2017 April 20. doi: 10.1002/acr.23257).

The investigators became motivated to conduct the trial by the fact that about one in five older people with osteoarthritis (OA) experience depression, yet many do not seek treatment, and depression in this population has been associated with an increased use of pain medication, reduced adherence to treatment recommendations, and, when recommendations are followed, reduced treatment benefits.

Pixelheadphoto/Thinkstock

Cognitive behavioral therapy administered online can effectively treat symptoms of depression in older people with knee osteoarthritis, according to results from the first randomized trial of its kind.

The benefits of the 10-week program extended to improving pain, stiffness, physical functioning, and self-efficacy, reported Kathleen A. O’Moore, PsyD, of St. Vincent’s Hospital, Sydney, Australia, and her colleagues (Arthritis Care Res. 2017 April 20. doi: 10.1002/acr.23257).

The investigators became motivated to conduct the trial by the fact that about one in five older people with osteoarthritis (OA) experience depression, yet many do not seek treatment, and depression in this population has been associated with an increased use of pain medication, reduced adherence to treatment recommendations, and, when recommendations are followed, reduced treatment benefits.

Pixelheadphoto/Thinkstock

Cognitive behavioral therapy administered online can effectively treat symptoms of depression in older people with knee osteoarthritis, according to results from the first randomized trial of its kind.

The benefits of the 10-week program extended to improving pain, stiffness, physical functioning, and self-efficacy, reported Kathleen A. O’Moore, PsyD, of St. Vincent’s Hospital, Sydney, Australia, and her colleagues (Arthritis Care Res. 2017 April 20. doi: 10.1002/acr.23257).

The investigators became motivated to conduct the trial by the fact that about one in five older people with osteoarthritis (OA) experience depression, yet many do not seek treatment, and depression in this population has been associated with an increased use of pain medication, reduced adherence to treatment recommendations, and, when recommendations are followed, reduced treatment benefits.

Pixelheadphoto/Thinkstock

LAS VEGAS – Young people who sustain an intra-articular knee injury while participating in youth sports are not only at increased risk for early posttraumatic osteoarthritis 3-10 years later as young adults, but they also are more prone to develop obesity and other modifiable risk factors for osteoarthritis, according to Jackie Whittaker, PhD.

“It appears that some of these young active individuals, after sustaining an injury which is itself a risk factor for osteoarthritis, are going down a pathway where they’re developing a second risk factor for the disease. This may accelerate the rate at which they get the disease and may very well also accelerate the rate at which the disease progresses after its onset,” Dr. Whittaker of the University of Alberta, Edmonton, said at the World Congress on Osteoarthritis.

Dr. Jackie L. Whittaker of the University of Alberta in Edmonton, Canada.

“In Canada, we know that injury during sport and recreation is the No. 1 reason that youth between the ages of 11 and 18 seek medical attention, with an alarming one in three doing so. Knee injuries are among the most common of those injuries,” she said.

At follow-up, 29% of the group with a history of knee injury and 4% of controls already had OA as defined by MRI. The likelihood of MRI evidence of OA was 13.5-fold greater in patients who underwent knee surgery for their injury, compared with controls.

“We saw the highest risk, as expected, in patients with ACL [anterior cruciate ligament] and/or meniscal tears, but we also saw a twofold increased risk of OA in those with seemingly less severe injuries, like grade 1-3 medial and collateral ligament injuries,” said Dr. Whittaker.

“I don’t think we were really shocked that knee injury can lead to structural changes that can be associated with future symptomatic OA, but we were surprised to be seeing that as early as 3-10 years post injury. And we were also seeing greater adiposity, a higher rate of being overweight or obese, reduced physical activity, weaker knee muscular strength, and poorer performance on balance and physical function tests,” she continued.

Indeed, at follow-up the subjects with a history of a youth sports knee injury were 4.4-fold more likely to be in the top quartile of fat mass index, compared with uninjured controls, 5.7-fold more likely to be in the highest quartile for abdominal fat, 2.1 times more likely to be in the lowest quartile for total weekly physical activity, and 2.4-fold more likely to be overweight or obese by body mass index (BMI). They were significantly less aerobically fit as reflected in their performance on the 20-meter shuttle run. And they scored significantly worse on the validated Knee Injury and Osteoarthritis Outcome Score (KOOS), particularly on the knee-related quality of life, pain, and symptom subscales.

“The study is ongoing, but it has already contributed to identification of who we’re probably going to need to target for secondary prevention strategies: obviously, individuals who have torn their ACL and/or their meniscus, as was already well known, but perhaps also individuals that have had less severe injuries, those who have a high BMI or some other indicator of adiposity, and those at risk of becoming physically inactive,” Dr. Whittaker said.

She added that a key take-away message from the study, for which she is coprincipal investigator, is that reduced physical activity on the part of someone with a history of a youth sports knee injury is a big red flag. These patients need to address their modifiable risk factors for OA via physical therapy and rehabilitation, along with receiving education reinforcing the importance of lifelong musculoskeletal health.

“Reduced physical activity is a warning sign. Don’t wait for knee pain,” she emphasized.

The Alberta Youth Prevention in Early OA study is funded by the Canadian Institutes of Health Research and nonprofit organizations. Dr. Whittaker reported having no financial conflicts.

[email protected]

LAS VEGAS – Young people who sustain an intra-articular knee injury while participating in youth sports are not only at increased risk for early posttraumatic osteoarthritis 3-10 years later as young adults, but they also are more prone to develop obesity and other modifiable risk factors for osteoarthritis, according to Jackie Whittaker, PhD.

“It appears that some of these young active individuals, after sustaining an injury which is itself a risk factor for osteoarthritis, are going down a pathway where they’re developing a second risk factor for the disease. This may accelerate the rate at which they get the disease and may very well also accelerate the rate at which the disease progresses after its onset,” Dr. Whittaker of the University of Alberta, Edmonton, said at the World Congress on Osteoarthritis.

Dr. Jackie L. Whittaker of the University of Alberta in Edmonton, Canada.

“In Canada, we know that injury during sport and recreation is the No. 1 reason that youth between the ages of 11 and 18 seek medical attention, with an alarming one in three doing so. Knee injuries are among the most common of those injuries,” she said.

At follow-up, 29% of the group with a history of knee injury and 4% of controls already had OA as defined by MRI. The likelihood of MRI evidence of OA was 13.5-fold greater in patients who underwent knee surgery for their injury, compared with controls.

“We saw the highest risk, as expected, in patients with ACL [anterior cruciate ligament] and/or meniscal tears, but we also saw a twofold increased risk of OA in those with seemingly less severe injuries, like grade 1-3 medial and collateral ligament injuries,” said Dr. Whittaker.

“I don’t think we were really shocked that knee injury can lead to structural changes that can be associated with future symptomatic OA, but we were surprised to be seeing that as early as 3-10 years post injury. And we were also seeing greater adiposity, a higher rate of being overweight or obese, reduced physical activity, weaker knee muscular strength, and poorer performance on balance and physical function tests,” she continued.

Indeed, at follow-up the subjects with a history of a youth sports knee injury were 4.4-fold more likely to be in the top quartile of fat mass index, compared with uninjured controls, 5.7-fold more likely to be in the highest quartile for abdominal fat, 2.1 times more likely to be in the lowest quartile for total weekly physical activity, and 2.4-fold more likely to be overweight or obese by body mass index (BMI). They were significantly less aerobically fit as reflected in their performance on the 20-meter shuttle run. And they scored significantly worse on the validated Knee Injury and Osteoarthritis Outcome Score (KOOS), particularly on the knee-related quality of life, pain, and symptom subscales.

“The study is ongoing, but it has already contributed to identification of who we’re probably going to need to target for secondary prevention strategies: obviously, individuals who have torn their ACL and/or their meniscus, as was already well known, but perhaps also individuals that have had less severe injuries, those who have a high BMI or some other indicator of adiposity, and those at risk of becoming physically inactive,” Dr. Whittaker said.

She added that a key take-away message from the study, for which she is coprincipal investigator, is that reduced physical activity on the part of someone with a history of a youth sports knee injury is a big red flag. These patients need to address their modifiable risk factors for OA via physical therapy and rehabilitation, along with receiving education reinforcing the importance of lifelong musculoskeletal health.

“Reduced physical activity is a warning sign. Don’t wait for knee pain,” she emphasized.

The Alberta Youth Prevention in Early OA study is funded by the Canadian Institutes of Health Research and nonprofit organizations. Dr. Whittaker reported having no financial conflicts.

[email protected]

LAS VEGAS – Young people who sustain an intra-articular knee injury while participating in youth sports are not only at increased risk for early posttraumatic osteoarthritis 3-10 years later as young adults, but they also are more prone to develop obesity and other modifiable risk factors for osteoarthritis, according to Jackie Whittaker, PhD.

“It appears that some of these young active individuals, after sustaining an injury which is itself a risk factor for osteoarthritis, are going down a pathway where they’re developing a second risk factor for the disease. This may accelerate the rate at which they get the disease and may very well also accelerate the rate at which the disease progresses after its onset,” Dr. Whittaker of the University of Alberta, Edmonton, said at the World Congress on Osteoarthritis.

Dr. Jackie L. Whittaker of the University of Alberta in Edmonton, Canada.

“In Canada, we know that injury during sport and recreation is the No. 1 reason that youth between the ages of 11 and 18 seek medical attention, with an alarming one in three doing so. Knee injuries are among the most common of those injuries,” she said.

At follow-up, 29% of the group with a history of knee injury and 4% of controls already had OA as defined by MRI. The likelihood of MRI evidence of OA was 13.5-fold greater in patients who underwent knee surgery for their injury, compared with controls.

“We saw the highest risk, as expected, in patients with ACL [anterior cruciate ligament] and/or meniscal tears, but we also saw a twofold increased risk of OA in those with seemingly less severe injuries, like grade 1-3 medial and collateral ligament injuries,” said Dr. Whittaker.

“I don’t think we were really shocked that knee injury can lead to structural changes that can be associated with future symptomatic OA, but we were surprised to be seeing that as early as 3-10 years post injury. And we were also seeing greater adiposity, a higher rate of being overweight or obese, reduced physical activity, weaker knee muscular strength, and poorer performance on balance and physical function tests,” she continued.

Indeed, at follow-up the subjects with a history of a youth sports knee injury were 4.4-fold more likely to be in the top quartile of fat mass index, compared with uninjured controls, 5.7-fold more likely to be in the highest quartile for abdominal fat, 2.1 times more likely to be in the lowest quartile for total weekly physical activity, and 2.4-fold more likely to be overweight or obese by body mass index (BMI). They were significantly less aerobically fit as reflected in their performance on the 20-meter shuttle run. And they scored significantly worse on the validated Knee Injury and Osteoarthritis Outcome Score (KOOS), particularly on the knee-related quality of life, pain, and symptom subscales.

“The study is ongoing, but it has already contributed to identification of who we’re probably going to need to target for secondary prevention strategies: obviously, individuals who have torn their ACL and/or their meniscus, as was already well known, but perhaps also individuals that have had less severe injuries, those who have a high BMI or some other indicator of adiposity, and those at risk of becoming physically inactive,” Dr. Whittaker said.

She added that a key take-away message from the study, for which she is coprincipal investigator, is that reduced physical activity on the part of someone with a history of a youth sports knee injury is a big red flag. These patients need to address their modifiable risk factors for OA via physical therapy and rehabilitation, along with receiving education reinforcing the importance of lifelong musculoskeletal health.

“Reduced physical activity is a warning sign. Don’t wait for knee pain,” she emphasized.

The Alberta Youth Prevention in Early OA study is funded by the Canadian Institutes of Health Research and nonprofit organizations. Dr. Whittaker reported having no financial conflicts.

[email protected]