Andrew D. Bowser

BOSTON – A multimodal pain regimen allowed for safe and effective same-day discharge of women undergoing mastectomy procedures, a recent study showed.

Women had little need for stronger oral narcotic use in the single center, retrospective study presented at the annual clinical congress of the American College of Surgeons.

The analysis included 72 consecutive mastectomies performed at a single center from November 2015 to July 2017. Most mastectomies were bilateral (61, or 84.7%) while 11 (15.3%) were unilateral.

Patients received a standardized pain regimen including 1 gram of IV acetaminophen interoperatively, combined with 30 mg of IV ketorolac and a 4-level intercostal nerve block with liposomal bupivacaine.

Liposomal bupivacaine has a longer half-life than other anesthetics, according to lead study author Radbeh Torabi, MD, a fifth-year plastic surgery resident at Louisiana State University (LSU) Health Science Center in New Orleans.

“That allows for prolonged pain control, especially during the time when the patient’s going to have the most amount of pain, which is the first day to two days postoperatively,” Dr. Torabi said in an interview.

All 72 patients were discharged home on the same day with just a 1-week prescription for acetaminophen with codeine.

Only 5 patients presented to the emergency room in the 30-day postoperative period, and of those, only 2 (2.8%) required readmission for reasons other than mastectomy-related pain, investigators said. The remaining 3 patients did present with pain, but did not require hospital admission.

Taken together, these findings suggest that this multimodal strategy offers excellent pain control and has the potential to minimize inpatient admissions while decreasing oral narcotic use, investigators said in an interview following their presentation.

“The main takeaway is reducing the amount of prescriptions we give,” Dr. Torabi said.

Study co-author Cameron T. Ward Coker, MD, a fourth-year general surgery resident at LSU, said the multimodal pain strategy used in this study could represent a step toward eliminating the risks associated with opioid prescribing.

“From the feedback we got from our lecture and the other surgeons in the room, it seems like that’s already becoming a widespread phenomenon,” Dr. Coker said.

Patients in the study had an average age of about 57 years and an average BMI of 30, according to the investigators.

Dr. Coker and Dr. Torabi had no disclosures related to the presentation.

SOURCE: Torabi R, et al. Scientific forum abstract at American College of Surgeons Clinical Congress. 2018 Oct 23.

BOSTON – A multimodal pain regimen allowed for safe and effective same-day discharge of women undergoing mastectomy procedures, a recent study showed.

Women had little need for stronger oral narcotic use in the single center, retrospective study presented at the annual clinical congress of the American College of Surgeons.

The analysis included 72 consecutive mastectomies performed at a single center from November 2015 to July 2017. Most mastectomies were bilateral (61, or 84.7%) while 11 (15.3%) were unilateral.

Patients received a standardized pain regimen including 1 gram of IV acetaminophen interoperatively, combined with 30 mg of IV ketorolac and a 4-level intercostal nerve block with liposomal bupivacaine.

Liposomal bupivacaine has a longer half-life than other anesthetics, according to lead study author Radbeh Torabi, MD, a fifth-year plastic surgery resident at Louisiana State University (LSU) Health Science Center in New Orleans.

“That allows for prolonged pain control, especially during the time when the patient’s going to have the most amount of pain, which is the first day to two days postoperatively,” Dr. Torabi said in an interview.

All 72 patients were discharged home on the same day with just a 1-week prescription for acetaminophen with codeine.

Only 5 patients presented to the emergency room in the 30-day postoperative period, and of those, only 2 (2.8%) required readmission for reasons other than mastectomy-related pain, investigators said. The remaining 3 patients did present with pain, but did not require hospital admission.

Taken together, these findings suggest that this multimodal strategy offers excellent pain control and has the potential to minimize inpatient admissions while decreasing oral narcotic use, investigators said in an interview following their presentation.

“The main takeaway is reducing the amount of prescriptions we give,” Dr. Torabi said.

Study co-author Cameron T. Ward Coker, MD, a fourth-year general surgery resident at LSU, said the multimodal pain strategy used in this study could represent a step toward eliminating the risks associated with opioid prescribing.

“From the feedback we got from our lecture and the other surgeons in the room, it seems like that’s already becoming a widespread phenomenon,” Dr. Coker said.

Patients in the study had an average age of about 57 years and an average BMI of 30, according to the investigators.

Dr. Coker and Dr. Torabi had no disclosures related to the presentation.

SOURCE: Torabi R, et al. Scientific forum abstract at American College of Surgeons Clinical Congress. 2018 Oct 23.

BOSTON – A multimodal pain regimen allowed for safe and effective same-day discharge of women undergoing mastectomy procedures, a recent study showed.

Women had little need for stronger oral narcotic use in the single center, retrospective study presented at the annual clinical congress of the American College of Surgeons.

The analysis included 72 consecutive mastectomies performed at a single center from November 2015 to July 2017. Most mastectomies were bilateral (61, or 84.7%) while 11 (15.3%) were unilateral.

Patients received a standardized pain regimen including 1 gram of IV acetaminophen interoperatively, combined with 30 mg of IV ketorolac and a 4-level intercostal nerve block with liposomal bupivacaine.

Liposomal bupivacaine has a longer half-life than other anesthetics, according to lead study author Radbeh Torabi, MD, a fifth-year plastic surgery resident at Louisiana State University (LSU) Health Science Center in New Orleans.

“That allows for prolonged pain control, especially during the time when the patient’s going to have the most amount of pain, which is the first day to two days postoperatively,” Dr. Torabi said in an interview.

All 72 patients were discharged home on the same day with just a 1-week prescription for acetaminophen with codeine.

Only 5 patients presented to the emergency room in the 30-day postoperative period, and of those, only 2 (2.8%) required readmission for reasons other than mastectomy-related pain, investigators said. The remaining 3 patients did present with pain, but did not require hospital admission.

Taken together, these findings suggest that this multimodal strategy offers excellent pain control and has the potential to minimize inpatient admissions while decreasing oral narcotic use, investigators said in an interview following their presentation.

“The main takeaway is reducing the amount of prescriptions we give,” Dr. Torabi said.

Study co-author Cameron T. Ward Coker, MD, a fourth-year general surgery resident at LSU, said the multimodal pain strategy used in this study could represent a step toward eliminating the risks associated with opioid prescribing.

“From the feedback we got from our lecture and the other surgeons in the room, it seems like that’s already becoming a widespread phenomenon,” Dr. Coker said.

Patients in the study had an average age of about 57 years and an average BMI of 30, according to the investigators.

Dr. Coker and Dr. Torabi had no disclosures related to the presentation.

SOURCE: Torabi R, et al. Scientific forum abstract at American College of Surgeons Clinical Congress. 2018 Oct 23.

Obesity and weight gain are linked to increased risk of colorectal cancer in younger women, according to an analysis of a large, prospective U.S. cohort study.

Young women who were obese had a nearly twofold increase in risk of early-onset colorectal cancer, compared with women of normal weight, authors of the study reported in JAMA Oncology.

The findings suggest body weight could be used to “personalize and complement” early cancer screening strategies among adults younger than 50 years, said investigator Po-Hong Liu, MD, of Washington University, St. Louis, and coauthors.

“Given that most of these younger cases are diagnosed symptomatically with more advanced tumors and with a significant influence on years of life lost, our findings reinforce the benefits of maintaining a healthy weight throughout life,” Dr. Liu and coinvestigators said in their report.

Their analysis was based on the ongoing Nurses Health Study II, which began in 1989 and enrolled a total of 116,430 women between the ages of 25 and 42 years in 14 U.S. states. Women completed questionnaires on demographics, medical and health information, and lifestyle factors every 2 years after enrollment.

Dr. Liu and colleagues were able to document 114 cases of colorectal cancer over a median of 13.9 years of follow-up in 85,256 women who had no cancer or inflammatory bowel disease when they were enrolled in the study. The median age at diagnosis for these cancers was 45 years.

Obesity was independently associated with increased risk of these early-onset colorectal cancers, the investigators found in multivariable analysis.

Women with a body mass index of 30 kg/m² or higher had a relative risk of 1.93 (95% confidence interval, 1.15-3.25) versus women with normal BMIs in the 18.5 to 22.9-kg/m² range, according to results of the analysis, they reported.

There was an apparent linear trend between increasing weight and increasing colorectal cancer risk, they added in their report.

They also found links between BMI in early adulthood and risk of early-onset colorectal cancer, including a relative risk of 1.63 for women who reported a BMI of 23 kg/m² or higher at 18 years of age, versus women with a BMI of 18.5-20.9 kg/m² at that age.

Similarly, increase in weight since early adulthood was associated with increased cancer risk, they reported.

While the link between excess weight and colorectal cancer incidence and mortality is well established in previous studies, this study is one of few reports looking at the association in younger individuals, according to Dr. Liu and colleagues.

This is thought to be the first prospective study looking at the link between obesity and risk of colo-rectal cancer diagnosed before the age of 50, they added.

The study was funded by grants from the National Institutes of Health. Dr. Liu had no conflict of interest disclosures related to the study. One coauthor reported consulting fees from Bayer Pharma AG, Janssen, and Pfizer.

ginews@gastro.org

SOURCE: Liu P-H et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4280.

AGA Resource 

Visit the AGA GI Patient Center for education to share with your patients about obesity, colorectal cancer and other GI disorders at patient.gastro.org.

Obesity and weight gain are linked to increased risk of colorectal cancer in younger women, according to an analysis of a large, prospective U.S. cohort study.

Young women who were obese had a nearly twofold increase in risk of early-onset colorectal cancer, compared with women of normal weight, authors of the study reported in JAMA Oncology.

The findings suggest body weight could be used to “personalize and complement” early cancer screening strategies among adults younger than 50 years, said investigator Po-Hong Liu, MD, of Washington University, St. Louis, and coauthors.

“Given that most of these younger cases are diagnosed symptomatically with more advanced tumors and with a significant influence on years of life lost, our findings reinforce the benefits of maintaining a healthy weight throughout life,” Dr. Liu and coinvestigators said in their report.

Their analysis was based on the ongoing Nurses Health Study II, which began in 1989 and enrolled a total of 116,430 women between the ages of 25 and 42 years in 14 U.S. states. Women completed questionnaires on demographics, medical and health information, and lifestyle factors every 2 years after enrollment.

Dr. Liu and colleagues were able to document 114 cases of colorectal cancer over a median of 13.9 years of follow-up in 85,256 women who had no cancer or inflammatory bowel disease when they were enrolled in the study. The median age at diagnosis for these cancers was 45 years.

Obesity was independently associated with increased risk of these early-onset colorectal cancers, the investigators found in multivariable analysis.

Women with a body mass index of 30 kg/m² or higher had a relative risk of 1.93 (95% confidence interval, 1.15-3.25) versus women with normal BMIs in the 18.5 to 22.9-kg/m² range, according to results of the analysis, they reported.

There was an apparent linear trend between increasing weight and increasing colorectal cancer risk, they added in their report.

They also found links between BMI in early adulthood and risk of early-onset colorectal cancer, including a relative risk of 1.63 for women who reported a BMI of 23 kg/m² or higher at 18 years of age, versus women with a BMI of 18.5-20.9 kg/m² at that age.

Similarly, increase in weight since early adulthood was associated with increased cancer risk, they reported.

While the link between excess weight and colorectal cancer incidence and mortality is well established in previous studies, this study is one of few reports looking at the association in younger individuals, according to Dr. Liu and colleagues.

This is thought to be the first prospective study looking at the link between obesity and risk of colo-rectal cancer diagnosed before the age of 50, they added.

The study was funded by grants from the National Institutes of Health. Dr. Liu had no conflict of interest disclosures related to the study. One coauthor reported consulting fees from Bayer Pharma AG, Janssen, and Pfizer.

ginews@gastro.org

SOURCE: Liu P-H et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4280.

AGA Resource 

Visit the AGA GI Patient Center for education to share with your patients about obesity, colorectal cancer and other GI disorders at patient.gastro.org.

Obesity and weight gain are linked to increased risk of colorectal cancer in younger women, according to an analysis of a large, prospective U.S. cohort study.

Young women who were obese had a nearly twofold increase in risk of early-onset colorectal cancer, compared with women of normal weight, authors of the study reported in JAMA Oncology.

The findings suggest body weight could be used to “personalize and complement” early cancer screening strategies among adults younger than 50 years, said investigator Po-Hong Liu, MD, of Washington University, St. Louis, and coauthors.

“Given that most of these younger cases are diagnosed symptomatically with more advanced tumors and with a significant influence on years of life lost, our findings reinforce the benefits of maintaining a healthy weight throughout life,” Dr. Liu and coinvestigators said in their report.

Their analysis was based on the ongoing Nurses Health Study II, which began in 1989 and enrolled a total of 116,430 women between the ages of 25 and 42 years in 14 U.S. states. Women completed questionnaires on demographics, medical and health information, and lifestyle factors every 2 years after enrollment.

Dr. Liu and colleagues were able to document 114 cases of colorectal cancer over a median of 13.9 years of follow-up in 85,256 women who had no cancer or inflammatory bowel disease when they were enrolled in the study. The median age at diagnosis for these cancers was 45 years.

Obesity was independently associated with increased risk of these early-onset colorectal cancers, the investigators found in multivariable analysis.

Women with a body mass index of 30 kg/m² or higher had a relative risk of 1.93 (95% confidence interval, 1.15-3.25) versus women with normal BMIs in the 18.5 to 22.9-kg/m² range, according to results of the analysis, they reported.

There was an apparent linear trend between increasing weight and increasing colorectal cancer risk, they added in their report.

They also found links between BMI in early adulthood and risk of early-onset colorectal cancer, including a relative risk of 1.63 for women who reported a BMI of 23 kg/m² or higher at 18 years of age, versus women with a BMI of 18.5-20.9 kg/m² at that age.

Similarly, increase in weight since early adulthood was associated with increased cancer risk, they reported.

While the link between excess weight and colorectal cancer incidence and mortality is well established in previous studies, this study is one of few reports looking at the association in younger individuals, according to Dr. Liu and colleagues.

This is thought to be the first prospective study looking at the link between obesity and risk of colo-rectal cancer diagnosed before the age of 50, they added.

The study was funded by grants from the National Institutes of Health. Dr. Liu had no conflict of interest disclosures related to the study. One coauthor reported consulting fees from Bayer Pharma AG, Janssen, and Pfizer.

ginews@gastro.org

SOURCE: Liu P-H et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4280.

AGA Resource 

Visit the AGA GI Patient Center for education to share with your patients about obesity, colorectal cancer and other GI disorders at patient.gastro.org.

Warfarin tablets

Researchers say they have identified single-nucleotide polymorphisms (SNPs) that are associated with increased bleeding risk in African-American patients on warfarin.

A retrospective study revealed four SNPs associated with increased bleeding risk in African Americans with an international normalized ratio (INR) of less than 4.

One of these SNPs was seen in more than a third of bleeding cases and less than 5% of controls.

These preliminary findings could have implications for patients of African descent, but independent validation of the study results are needed, according to Minoli A. Perera, PharmD, PhD, of Northwestern University in Chicago, and her coauthors.

The researchers reported their findings in JAMA.

The report covered findings in a discovery cohort of African-American patients from a genome-wide study conducted at the University of Chicago and a replication cohort of patients who self-identified as African American and had routinely received care at University of Chicago hospitals.

The discovery cohort included 31 patients with major bleeding that occurred at an INR less than 4 and 184 controls with no documented history of bleeding related to warfarin.

In that cohort, Dr. Perera and her colleagues found four SNPs in linkage disequilibrium on chromosome 6 associated with warfarin-related bleeding:

• rs115112393
• rs16871327
• rs78132896
• rs114504854.

In particular, rs78132896 was found in 35.5% of cases (11/31) and 4.9% of controls (9/184), with an odds ratio of 8.31 (95% confidence interval [CI], 3.2-21.5).

The replication cohort, including 40 cases and 148 warfarin-treated controls, was genotyped specifically for rs78132896. The SNP was similarly found in 35.0% of cases (14/40) and 4.8% of controls (7/148), with an odds ratio of 8.24 (95% CI, 3.1-25.3).

“Genome-wide significance of this cohort was achieved when the cohorts were combined via meta-analysis,” the researchers wrote. They reported an odds ratio of 8.27 for that analysis (95% CI, 4.18-16.38).

Further analysis showed that, compared with wild-type alleles, the rs16871327 and rs78132896 risk alleles increased EPHA7 gene transcription.

Expression of the EPHA7 gene on vascular endothelial cells and peripheral lymphocytes is increased during inflammation, according to Dr. Perera and her coauthors. Increased EPHA7 expression might lead to bleeding in patients who are taking warfarin.

“This haplotype might also have potential implications for bleeding risk with direct oral anticoagulants,” the researchers wrote.

Dr. Perera and her coauthors reported no conflicts of interest related to their work on this study, which was funded by grants from the National Heart, Lung, and Blood Institute; the National Institute of General Medicine; the National Institutes of Health; and the American Heart Association Midwest Affiliate; as well as a research award from the University of Illinois at Chicago College of Pharmacy.

Warfarin tablets

Researchers say they have identified single-nucleotide polymorphisms (SNPs) that are associated with increased bleeding risk in African-American patients on warfarin.

A retrospective study revealed four SNPs associated with increased bleeding risk in African Americans with an international normalized ratio (INR) of less than 4.

One of these SNPs was seen in more than a third of bleeding cases and less than 5% of controls.

These preliminary findings could have implications for patients of African descent, but independent validation of the study results are needed, according to Minoli A. Perera, PharmD, PhD, of Northwestern University in Chicago, and her coauthors.

The researchers reported their findings in JAMA.

The report covered findings in a discovery cohort of African-American patients from a genome-wide study conducted at the University of Chicago and a replication cohort of patients who self-identified as African American and had routinely received care at University of Chicago hospitals.

The discovery cohort included 31 patients with major bleeding that occurred at an INR less than 4 and 184 controls with no documented history of bleeding related to warfarin.

In that cohort, Dr. Perera and her colleagues found four SNPs in linkage disequilibrium on chromosome 6 associated with warfarin-related bleeding:

• rs115112393
• rs16871327
• rs78132896
• rs114504854.

In particular, rs78132896 was found in 35.5% of cases (11/31) and 4.9% of controls (9/184), with an odds ratio of 8.31 (95% confidence interval [CI], 3.2-21.5).

The replication cohort, including 40 cases and 148 warfarin-treated controls, was genotyped specifically for rs78132896. The SNP was similarly found in 35.0% of cases (14/40) and 4.8% of controls (7/148), with an odds ratio of 8.24 (95% CI, 3.1-25.3).

“Genome-wide significance of this cohort was achieved when the cohorts were combined via meta-analysis,” the researchers wrote. They reported an odds ratio of 8.27 for that analysis (95% CI, 4.18-16.38).

Further analysis showed that, compared with wild-type alleles, the rs16871327 and rs78132896 risk alleles increased EPHA7 gene transcription.

Expression of the EPHA7 gene on vascular endothelial cells and peripheral lymphocytes is increased during inflammation, according to Dr. Perera and her coauthors. Increased EPHA7 expression might lead to bleeding in patients who are taking warfarin.

“This haplotype might also have potential implications for bleeding risk with direct oral anticoagulants,” the researchers wrote.

Dr. Perera and her coauthors reported no conflicts of interest related to their work on this study, which was funded by grants from the National Heart, Lung, and Blood Institute; the National Institute of General Medicine; the National Institutes of Health; and the American Heart Association Midwest Affiliate; as well as a research award from the University of Illinois at Chicago College of Pharmacy.

Warfarin tablets

Researchers say they have identified single-nucleotide polymorphisms (SNPs) that are associated with increased bleeding risk in African-American patients on warfarin.

A retrospective study revealed four SNPs associated with increased bleeding risk in African Americans with an international normalized ratio (INR) of less than 4.

One of these SNPs was seen in more than a third of bleeding cases and less than 5% of controls.

These preliminary findings could have implications for patients of African descent, but independent validation of the study results are needed, according to Minoli A. Perera, PharmD, PhD, of Northwestern University in Chicago, and her coauthors.

The researchers reported their findings in JAMA.

The report covered findings in a discovery cohort of African-American patients from a genome-wide study conducted at the University of Chicago and a replication cohort of patients who self-identified as African American and had routinely received care at University of Chicago hospitals.

The discovery cohort included 31 patients with major bleeding that occurred at an INR less than 4 and 184 controls with no documented history of bleeding related to warfarin.

In that cohort, Dr. Perera and her colleagues found four SNPs in linkage disequilibrium on chromosome 6 associated with warfarin-related bleeding:

• rs115112393
• rs16871327
• rs78132896
• rs114504854.

In particular, rs78132896 was found in 35.5% of cases (11/31) and 4.9% of controls (9/184), with an odds ratio of 8.31 (95% confidence interval [CI], 3.2-21.5).

The replication cohort, including 40 cases and 148 warfarin-treated controls, was genotyped specifically for rs78132896. The SNP was similarly found in 35.0% of cases (14/40) and 4.8% of controls (7/148), with an odds ratio of 8.24 (95% CI, 3.1-25.3).

“Genome-wide significance of this cohort was achieved when the cohorts were combined via meta-analysis,” the researchers wrote. They reported an odds ratio of 8.27 for that analysis (95% CI, 4.18-16.38).

Further analysis showed that, compared with wild-type alleles, the rs16871327 and rs78132896 risk alleles increased EPHA7 gene transcription.

Expression of the EPHA7 gene on vascular endothelial cells and peripheral lymphocytes is increased during inflammation, according to Dr. Perera and her coauthors. Increased EPHA7 expression might lead to bleeding in patients who are taking warfarin.

“This haplotype might also have potential implications for bleeding risk with direct oral anticoagulants,” the researchers wrote.

Dr. Perera and her coauthors reported no conflicts of interest related to their work on this study, which was funded by grants from the National Heart, Lung, and Blood Institute; the National Institute of General Medicine; the National Institutes of Health; and the American Heart Association Midwest Affiliate; as well as a research award from the University of Illinois at Chicago College of Pharmacy.

Uterine serous carcinoma patients may have a high risk of venous thromboembolism (VTE), not just in the postoperative period, but throughout the natural history of the disease, results of a retrospective analysis suggest.

Most patients developed VTE either before staging surgery or more than 6 months postoperatively, according to results of the analysis reported in Obstetrics & Gynecology.

Nearly one-third (31%) of the women developed VTE while receiving chemotherapy, reported Gregory M. Gressel, MD, a gynecologic oncology fellow at Montefiore Medical Center, New York, and his coinvestigators.

The risk was highest in women with cardiovascular disease, hypertension, and stage III and IV disease, they said.

“Although this is a retrospective study, it generates the hypothesis that venous thromboembolism prophylaxis may be beneficial in women with active uterine serous carcinoma, at least while receiving treatment such as neoadjuvant or adjuvant chemotherapy,” Dr. Gressel and his coauthors noted.

Historically, clinical practice guidelines have focused on risk stratification in the perioperative period due to the strong association between cancer-related VTE and surgery, the authors wrote.

To better assess the timing and risk factors associated with clot development, Dr. Gressel and his colleagues abstracted clinical data from the medical records of 413 patients with uterine serous carcinoma between 1999 and 2016 at one center in New York, about half of whom identified as black and one-quarter as Hispanic.

Eighty-four percent of the patients were diagnosed with VTE before or after the 6-week postoperative window when thromboprophylaxis typically is recommended, and 31% developed clots during chemotherapy, the investigators reported. The median time to clot development was 7.2 months after diagnosis, and, after excluding patients who developed clots preoperatively or during chemotherapy, the investigators found the median time from surgery to VTE was 13.2 months.

Patients with stage III and IV disease were, respectively, 2.6 and 4 times more likely to develop thrombosis, compared with patients with stage I disease. Conversely, age, body mass index, and race were not associated with VTE diagnosis.

Patients who developed VTE on chemotherapy had a median Khorana score of 1, which corresponds to an intermediate risk of VTE, the investigators said, adding that pharmacologic prophylaxis is recommended only in patients with scores of 3 or higher.

“Ours is not the first report to posit that currently available venous thromboembolism risk stratification tools are of limited utility in gynecologic oncology patients,” said Dr. Gressel and his coauthors.

However, larger prospective studies are needed, not only to look at the utility of Khorana scoring in this high-risk histologic subtype, they said, but also to test their hypothesis that VTE prophylaxis may be beneficial during chemotherapy or other active treatment.

Dr. Gressel and his colleagues reported no conflicts of interest. The study was supported by the National Institutes of Health and a grant from the National Center for Advancing Translational Science.

SOURCE: Gressel GM et al. Obstet Gynecol. 2018 Oct 5;132:1130-6.

Uterine serous carcinoma patients may have a high risk of venous thromboembolism (VTE), not just in the postoperative period, but throughout the natural history of the disease, results of a retrospective analysis suggest.

Most patients developed VTE either before staging surgery or more than 6 months postoperatively, according to results of the analysis reported in Obstetrics & Gynecology.

Nearly one-third (31%) of the women developed VTE while receiving chemotherapy, reported Gregory M. Gressel, MD, a gynecologic oncology fellow at Montefiore Medical Center, New York, and his coinvestigators.

The risk was highest in women with cardiovascular disease, hypertension, and stage III and IV disease, they said.

“Although this is a retrospective study, it generates the hypothesis that venous thromboembolism prophylaxis may be beneficial in women with active uterine serous carcinoma, at least while receiving treatment such as neoadjuvant or adjuvant chemotherapy,” Dr. Gressel and his coauthors noted.

Historically, clinical practice guidelines have focused on risk stratification in the perioperative period due to the strong association between cancer-related VTE and surgery, the authors wrote.

To better assess the timing and risk factors associated with clot development, Dr. Gressel and his colleagues abstracted clinical data from the medical records of 413 patients with uterine serous carcinoma between 1999 and 2016 at one center in New York, about half of whom identified as black and one-quarter as Hispanic.

Eighty-four percent of the patients were diagnosed with VTE before or after the 6-week postoperative window when thromboprophylaxis typically is recommended, and 31% developed clots during chemotherapy, the investigators reported. The median time to clot development was 7.2 months after diagnosis, and, after excluding patients who developed clots preoperatively or during chemotherapy, the investigators found the median time from surgery to VTE was 13.2 months.

Patients with stage III and IV disease were, respectively, 2.6 and 4 times more likely to develop thrombosis, compared with patients with stage I disease. Conversely, age, body mass index, and race were not associated with VTE diagnosis.

Patients who developed VTE on chemotherapy had a median Khorana score of 1, which corresponds to an intermediate risk of VTE, the investigators said, adding that pharmacologic prophylaxis is recommended only in patients with scores of 3 or higher.

“Ours is not the first report to posit that currently available venous thromboembolism risk stratification tools are of limited utility in gynecologic oncology patients,” said Dr. Gressel and his coauthors.

However, larger prospective studies are needed, not only to look at the utility of Khorana scoring in this high-risk histologic subtype, they said, but also to test their hypothesis that VTE prophylaxis may be beneficial during chemotherapy or other active treatment.

Dr. Gressel and his colleagues reported no conflicts of interest. The study was supported by the National Institutes of Health and a grant from the National Center for Advancing Translational Science.

SOURCE: Gressel GM et al. Obstet Gynecol. 2018 Oct 5;132:1130-6.

Uterine serous carcinoma patients may have a high risk of venous thromboembolism (VTE), not just in the postoperative period, but throughout the natural history of the disease, results of a retrospective analysis suggest.

Most patients developed VTE either before staging surgery or more than 6 months postoperatively, according to results of the analysis reported in Obstetrics & Gynecology.

Nearly one-third (31%) of the women developed VTE while receiving chemotherapy, reported Gregory M. Gressel, MD, a gynecologic oncology fellow at Montefiore Medical Center, New York, and his coinvestigators.

The risk was highest in women with cardiovascular disease, hypertension, and stage III and IV disease, they said.

“Although this is a retrospective study, it generates the hypothesis that venous thromboembolism prophylaxis may be beneficial in women with active uterine serous carcinoma, at least while receiving treatment such as neoadjuvant or adjuvant chemotherapy,” Dr. Gressel and his coauthors noted.

Historically, clinical practice guidelines have focused on risk stratification in the perioperative period due to the strong association between cancer-related VTE and surgery, the authors wrote.

To better assess the timing and risk factors associated with clot development, Dr. Gressel and his colleagues abstracted clinical data from the medical records of 413 patients with uterine serous carcinoma between 1999 and 2016 at one center in New York, about half of whom identified as black and one-quarter as Hispanic.

Eighty-four percent of the patients were diagnosed with VTE before or after the 6-week postoperative window when thromboprophylaxis typically is recommended, and 31% developed clots during chemotherapy, the investigators reported. The median time to clot development was 7.2 months after diagnosis, and, after excluding patients who developed clots preoperatively or during chemotherapy, the investigators found the median time from surgery to VTE was 13.2 months.

Patients with stage III and IV disease were, respectively, 2.6 and 4 times more likely to develop thrombosis, compared with patients with stage I disease. Conversely, age, body mass index, and race were not associated with VTE diagnosis.

Patients who developed VTE on chemotherapy had a median Khorana score of 1, which corresponds to an intermediate risk of VTE, the investigators said, adding that pharmacologic prophylaxis is recommended only in patients with scores of 3 or higher.

“Ours is not the first report to posit that currently available venous thromboembolism risk stratification tools are of limited utility in gynecologic oncology patients,” said Dr. Gressel and his coauthors.

However, larger prospective studies are needed, not only to look at the utility of Khorana scoring in this high-risk histologic subtype, they said, but also to test their hypothesis that VTE prophylaxis may be beneficial during chemotherapy or other active treatment.

Dr. Gressel and his colleagues reported no conflicts of interest. The study was supported by the National Institutes of Health and a grant from the National Center for Advancing Translational Science.

SOURCE: Gressel GM et al. Obstet Gynecol. 2018 Oct 5;132:1130-6.

Single-nucleotide polymorphisms linked to increased bleeding risk have been identified in patients of African descent taking warfarin, investigators have reported.

Four single-nucleotide polymorphisms (SNPs) were associated with increased major bleeding risk in African Americans at an international normalized ratio (INR) of less than 4, according to results of their preliminary, retrospective study.

The preliminary findings could have implications for patients of African descent, but independent validation of the study results are needed, according to Minoli A. Perera, PharmD, PhD, of Northwestern University, Chicago, and her coauthors.

“Identifying these variants may help physicians make safer choices in anticoagulation therapy for this understudied patient population,” Dr. Perera and her colleagues wrote in JAMA.

Most prior studies looking at warfarin-related bleeding risk have included predominantly white patients and don’t account for differences in warfarin responsiveness between ethnic groups, they wrote.

Moreover, bleeding-associated SNPs have been identified, but in populations of European ancestry, they added.

The report covered results of a discovery cohort based on African American patients from a genome-wide study conducted at the University of Chicago, and a replication cohort based on patients who self-identified as African American and had routinely received care at University of Chicago hospitals.

The discovery cohort included 31 patients with major bleeding that occurred at an INR less than 4 and 184 controls with no documented history of bleeding related to warfarin.

In that cohort, Dr. Perera and her coinvestigators found four SNPs in linkage disequilibrium on chromosome 6 associated with warfarin-related bleeding, including rs115112393, rs16871327, rs78132896, and rs114504854. In particular, the rs78132896 SNP was found in 35.5% of cases (n = 11) and just 4.9% of controls (n = 9), with an odds ratio of 8.31 (95% confidence interval, 3.2-21.5).

The replication cohort, including 40 cases and 148 warfarin-treated controls, was genotyped specifically for rs78132896. That SNP was similarly found in 35.0% of cases (n = 14) and 4.8% of controls (n = 7), with an odds ratio of 8.24 (95% CI, 3.1-25.3).

“Genome-wide significance of this cohort was achieved when the cohorts were combined via meta-analysis,” said the investigators, who reported an odds ratio of 8.27 for that analysis (95% CI, 4.18-16.38).

Compared with wild-type alleles, the rs16871327 and rs78132896 risk alleles increased EPHA7 gene transcription, results of gene assay analyses further showed.

Expression of the EPHA7 gene on vascular endothelial cells and peripheral lymphocytes is increased during inflammation, according to Dr. Perera and her coauthors. Increased EPHA7 expression might lead to bleeding in patients who are taking warfarin.

“This haplotype might also have potential implications for bleeding risk with direct oral anticoagulants,” they said.

Dr. Perera and her coauthors reported no conflicts of interest related to their work on this study, which was funded by grants from the National Heart, Lung, and Blood Institute; the National Institute of General Medicine; the National Institutes of Health; and the American Heart Association Midwest Affiliate; as well as a research award from the University of Illinois at Chicago College of Pharmacy.

SOURCE: Perera MA et al. JAMA. 2018 Oct 23. doi: 10.1001/jama.2018.14955.

Single-nucleotide polymorphisms linked to increased bleeding risk have been identified in patients of African descent taking warfarin, investigators have reported.

Four single-nucleotide polymorphisms (SNPs) were associated with increased major bleeding risk in African Americans at an international normalized ratio (INR) of less than 4, according to results of their preliminary, retrospective study.

The preliminary findings could have implications for patients of African descent, but independent validation of the study results are needed, according to Minoli A. Perera, PharmD, PhD, of Northwestern University, Chicago, and her coauthors.

“Identifying these variants may help physicians make safer choices in anticoagulation therapy for this understudied patient population,” Dr. Perera and her colleagues wrote in JAMA.

Most prior studies looking at warfarin-related bleeding risk have included predominantly white patients and don’t account for differences in warfarin responsiveness between ethnic groups, they wrote.

Moreover, bleeding-associated SNPs have been identified, but in populations of European ancestry, they added.

The report covered results of a discovery cohort based on African American patients from a genome-wide study conducted at the University of Chicago, and a replication cohort based on patients who self-identified as African American and had routinely received care at University of Chicago hospitals.

The discovery cohort included 31 patients with major bleeding that occurred at an INR less than 4 and 184 controls with no documented history of bleeding related to warfarin.

In that cohort, Dr. Perera and her coinvestigators found four SNPs in linkage disequilibrium on chromosome 6 associated with warfarin-related bleeding, including rs115112393, rs16871327, rs78132896, and rs114504854. In particular, the rs78132896 SNP was found in 35.5% of cases (n = 11) and just 4.9% of controls (n = 9), with an odds ratio of 8.31 (95% confidence interval, 3.2-21.5).

The replication cohort, including 40 cases and 148 warfarin-treated controls, was genotyped specifically for rs78132896. That SNP was similarly found in 35.0% of cases (n = 14) and 4.8% of controls (n = 7), with an odds ratio of 8.24 (95% CI, 3.1-25.3).

“Genome-wide significance of this cohort was achieved when the cohorts were combined via meta-analysis,” said the investigators, who reported an odds ratio of 8.27 for that analysis (95% CI, 4.18-16.38).

Compared with wild-type alleles, the rs16871327 and rs78132896 risk alleles increased EPHA7 gene transcription, results of gene assay analyses further showed.

Expression of the EPHA7 gene on vascular endothelial cells and peripheral lymphocytes is increased during inflammation, according to Dr. Perera and her coauthors. Increased EPHA7 expression might lead to bleeding in patients who are taking warfarin.

“This haplotype might also have potential implications for bleeding risk with direct oral anticoagulants,” they said.

Dr. Perera and her coauthors reported no conflicts of interest related to their work on this study, which was funded by grants from the National Heart, Lung, and Blood Institute; the National Institute of General Medicine; the National Institutes of Health; and the American Heart Association Midwest Affiliate; as well as a research award from the University of Illinois at Chicago College of Pharmacy.

SOURCE: Perera MA et al. JAMA. 2018 Oct 23. doi: 10.1001/jama.2018.14955.

Single-nucleotide polymorphisms linked to increased bleeding risk have been identified in patients of African descent taking warfarin, investigators have reported.

Four single-nucleotide polymorphisms (SNPs) were associated with increased major bleeding risk in African Americans at an international normalized ratio (INR) of less than 4, according to results of their preliminary, retrospective study.

The preliminary findings could have implications for patients of African descent, but independent validation of the study results are needed, according to Minoli A. Perera, PharmD, PhD, of Northwestern University, Chicago, and her coauthors.

“Identifying these variants may help physicians make safer choices in anticoagulation therapy for this understudied patient population,” Dr. Perera and her colleagues wrote in JAMA.

Most prior studies looking at warfarin-related bleeding risk have included predominantly white patients and don’t account for differences in warfarin responsiveness between ethnic groups, they wrote.

Moreover, bleeding-associated SNPs have been identified, but in populations of European ancestry, they added.

The report covered results of a discovery cohort based on African American patients from a genome-wide study conducted at the University of Chicago, and a replication cohort based on patients who self-identified as African American and had routinely received care at University of Chicago hospitals.

The discovery cohort included 31 patients with major bleeding that occurred at an INR less than 4 and 184 controls with no documented history of bleeding related to warfarin.

In that cohort, Dr. Perera and her coinvestigators found four SNPs in linkage disequilibrium on chromosome 6 associated with warfarin-related bleeding, including rs115112393, rs16871327, rs78132896, and rs114504854. In particular, the rs78132896 SNP was found in 35.5% of cases (n = 11) and just 4.9% of controls (n = 9), with an odds ratio of 8.31 (95% confidence interval, 3.2-21.5).

The replication cohort, including 40 cases and 148 warfarin-treated controls, was genotyped specifically for rs78132896. That SNP was similarly found in 35.0% of cases (n = 14) and 4.8% of controls (n = 7), with an odds ratio of 8.24 (95% CI, 3.1-25.3).

“Genome-wide significance of this cohort was achieved when the cohorts were combined via meta-analysis,” said the investigators, who reported an odds ratio of 8.27 for that analysis (95% CI, 4.18-16.38).

Compared with wild-type alleles, the rs16871327 and rs78132896 risk alleles increased EPHA7 gene transcription, results of gene assay analyses further showed.

Expression of the EPHA7 gene on vascular endothelial cells and peripheral lymphocytes is increased during inflammation, according to Dr. Perera and her coauthors. Increased EPHA7 expression might lead to bleeding in patients who are taking warfarin.

“This haplotype might also have potential implications for bleeding risk with direct oral anticoagulants,” they said.

Dr. Perera and her coauthors reported no conflicts of interest related to their work on this study, which was funded by grants from the National Heart, Lung, and Blood Institute; the National Institute of General Medicine; the National Institutes of Health; and the American Heart Association Midwest Affiliate; as well as a research award from the University of Illinois at Chicago College of Pharmacy.

SOURCE: Perera MA et al. JAMA. 2018 Oct 23. doi: 10.1001/jama.2018.14955.

Palindromic rheumatism, while often challenging to distinguish from persistent arthritis, has a distinct imaging pattern characterized by extracapsular inflammation, often with no synovitis, results of a recent prospective study show.

Finding the phenotype on ultrasound evaluation may help to separate cases of inflammatory arthritis, which may need early disease-modifying treatment, from palindromic rheumatism, which can be managed conservatively, the study authors reported in Annals of the Rheumatic Diseases.

“These findings may refine diagnosis and improve management of this important condition,” wrote Kulveer Mankia, MD, of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine, and his coauthors.

High-resolution imaging studies in palindromic rheumatism have been sparse, in part because of the sporadic nature of flares in these patients, according to Dr. Mankia and his colleagues.

Their report included 79 patients with palindromic rheumatism recruited from two U.K. rheumatology clinics and a national primary care program and compared them with other populations.

The patients underwent ultrasound evaluation by experienced rheumatologists and sonographers, as well as MRI on the most symptomatic region during flares. Those results were compared with clinical and ultrasound assessments in a cohort of patients with new-onset RA, and a second cohort of anticyclic citrullinated peptide (CCP)–positive at-risk individuals.

The investigators were able to assess 31 of the palindromic rheumatism patients during a flare episode. Extracapsular inflammation was frequently found during these episodes, with one or more instances of periarticular inflammation, peritendinous edema, or subcutaneous edema occurring in 19 (61%) of 31 patients.


However, tenosynovitis was detected in just seven of those patients (23%), while peritendinous edema was seen in three (10%).

By contrast, ultrasound abnormalities were infrequent in 27 nonflare evaluations taken in those 31 patients. For example, just four scans (15%) showed extracapsular inflammation.

Overall, extracapsular inflammation was found in 65% of palindromic rheumatism patients, compared with just 29% of new-onset RA cases (P less than .023).

Of particular note, extracapsular inflammation without synovitis was specific for palindromic rheumatism, occurring in 42%, compared with only 4% of RA cases (P = .003) and 6% of anti–CCP-positive at-risk patients (P = .0012).

A total of 13 of the 79 palindromic rheumatism patients (16%) went on to develop persistent inflammatory arthritis over a median follow-up of 42-49 days. Of the 31 patients evaluated during flare, 7 (23%) developed persistent inflammatory arthritis over the follow-up period. Those seven patients all met American College of Rheumatology/European League Against Rheumatism (EULAR) 2010 classification criteria for RA.

The MRI studies concurred with the ultrasound findings and identified some additional abnormalities, the investigators reported.

Altogether, these imaging findings are important to note because of the “variable” progression seen in palindromic rheumatism, Dr. Mankia and his colleagues wrote.

While anti-CCP antibody positivity confers high risk of progression in palindromic rheumatism, presence of this marker does not always mean the patient will develop persistent arthritis on follow-up, they added. In fact, this study showed that, among 47 anti–CCP-positive palindromic rheumatism patients, 35 (74%) did not develop persistent inflammatory arthritis in follow-up.

“In clinical practice, these patients may be inappropriately treated [e.g., with methotrexate] as they often meet ACR/EULAR criteria for rheumatoid arthritis,” the investigators wrote in their report.

Funding for the study came from the National Institute for Health Research Leeds Clinical Research Facility with additional support from an Arthritis Research U.K. grant. The authors reported no competing interests related to their study.

SOURCE: Mankia K et al. Ann Rheum Dis. 2018 Oct 8. doi: 10.1136/annrheumdis-2018-214175.

Palindromic rheumatism, while often challenging to distinguish from persistent arthritis, has a distinct imaging pattern characterized by extracapsular inflammation, often with no synovitis, results of a recent prospective study show.

Finding the phenotype on ultrasound evaluation may help to separate cases of inflammatory arthritis, which may need early disease-modifying treatment, from palindromic rheumatism, which can be managed conservatively, the study authors reported in Annals of the Rheumatic Diseases.

“These findings may refine diagnosis and improve management of this important condition,” wrote Kulveer Mankia, MD, of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine, and his coauthors.

High-resolution imaging studies in palindromic rheumatism have been sparse, in part because of the sporadic nature of flares in these patients, according to Dr. Mankia and his colleagues.

Their report included 79 patients with palindromic rheumatism recruited from two U.K. rheumatology clinics and a national primary care program and compared them with other populations.

The patients underwent ultrasound evaluation by experienced rheumatologists and sonographers, as well as MRI on the most symptomatic region during flares. Those results were compared with clinical and ultrasound assessments in a cohort of patients with new-onset RA, and a second cohort of anticyclic citrullinated peptide (CCP)–positive at-risk individuals.

The investigators were able to assess 31 of the palindromic rheumatism patients during a flare episode. Extracapsular inflammation was frequently found during these episodes, with one or more instances of periarticular inflammation, peritendinous edema, or subcutaneous edema occurring in 19 (61%) of 31 patients.


However, tenosynovitis was detected in just seven of those patients (23%), while peritendinous edema was seen in three (10%).

By contrast, ultrasound abnormalities were infrequent in 27 nonflare evaluations taken in those 31 patients. For example, just four scans (15%) showed extracapsular inflammation.

Overall, extracapsular inflammation was found in 65% of palindromic rheumatism patients, compared with just 29% of new-onset RA cases (P less than .023).

Of particular note, extracapsular inflammation without synovitis was specific for palindromic rheumatism, occurring in 42%, compared with only 4% of RA cases (P = .003) and 6% of anti–CCP-positive at-risk patients (P = .0012).

A total of 13 of the 79 palindromic rheumatism patients (16%) went on to develop persistent inflammatory arthritis over a median follow-up of 42-49 days. Of the 31 patients evaluated during flare, 7 (23%) developed persistent inflammatory arthritis over the follow-up period. Those seven patients all met American College of Rheumatology/European League Against Rheumatism (EULAR) 2010 classification criteria for RA.

The MRI studies concurred with the ultrasound findings and identified some additional abnormalities, the investigators reported.

Altogether, these imaging findings are important to note because of the “variable” progression seen in palindromic rheumatism, Dr. Mankia and his colleagues wrote.

While anti-CCP antibody positivity confers high risk of progression in palindromic rheumatism, presence of this marker does not always mean the patient will develop persistent arthritis on follow-up, they added. In fact, this study showed that, among 47 anti–CCP-positive palindromic rheumatism patients, 35 (74%) did not develop persistent inflammatory arthritis in follow-up.

“In clinical practice, these patients may be inappropriately treated [e.g., with methotrexate] as they often meet ACR/EULAR criteria for rheumatoid arthritis,” the investigators wrote in their report.

Funding for the study came from the National Institute for Health Research Leeds Clinical Research Facility with additional support from an Arthritis Research U.K. grant. The authors reported no competing interests related to their study.

SOURCE: Mankia K et al. Ann Rheum Dis. 2018 Oct 8. doi: 10.1136/annrheumdis-2018-214175.

Palindromic rheumatism, while often challenging to distinguish from persistent arthritis, has a distinct imaging pattern characterized by extracapsular inflammation, often with no synovitis, results of a recent prospective study show.

Finding the phenotype on ultrasound evaluation may help to separate cases of inflammatory arthritis, which may need early disease-modifying treatment, from palindromic rheumatism, which can be managed conservatively, the study authors reported in Annals of the Rheumatic Diseases.

“These findings may refine diagnosis and improve management of this important condition,” wrote Kulveer Mankia, MD, of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine, and his coauthors.

High-resolution imaging studies in palindromic rheumatism have been sparse, in part because of the sporadic nature of flares in these patients, according to Dr. Mankia and his colleagues.

Their report included 79 patients with palindromic rheumatism recruited from two U.K. rheumatology clinics and a national primary care program and compared them with other populations.

The patients underwent ultrasound evaluation by experienced rheumatologists and sonographers, as well as MRI on the most symptomatic region during flares. Those results were compared with clinical and ultrasound assessments in a cohort of patients with new-onset RA, and a second cohort of anticyclic citrullinated peptide (CCP)–positive at-risk individuals.

The investigators were able to assess 31 of the palindromic rheumatism patients during a flare episode. Extracapsular inflammation was frequently found during these episodes, with one or more instances of periarticular inflammation, peritendinous edema, or subcutaneous edema occurring in 19 (61%) of 31 patients.


However, tenosynovitis was detected in just seven of those patients (23%), while peritendinous edema was seen in three (10%).

By contrast, ultrasound abnormalities were infrequent in 27 nonflare evaluations taken in those 31 patients. For example, just four scans (15%) showed extracapsular inflammation.

Overall, extracapsular inflammation was found in 65% of palindromic rheumatism patients, compared with just 29% of new-onset RA cases (P less than .023).

Of particular note, extracapsular inflammation without synovitis was specific for palindromic rheumatism, occurring in 42%, compared with only 4% of RA cases (P = .003) and 6% of anti–CCP-positive at-risk patients (P = .0012).

A total of 13 of the 79 palindromic rheumatism patients (16%) went on to develop persistent inflammatory arthritis over a median follow-up of 42-49 days. Of the 31 patients evaluated during flare, 7 (23%) developed persistent inflammatory arthritis over the follow-up period. Those seven patients all met American College of Rheumatology/European League Against Rheumatism (EULAR) 2010 classification criteria for RA.

The MRI studies concurred with the ultrasound findings and identified some additional abnormalities, the investigators reported.

Altogether, these imaging findings are important to note because of the “variable” progression seen in palindromic rheumatism, Dr. Mankia and his colleagues wrote.

While anti-CCP antibody positivity confers high risk of progression in palindromic rheumatism, presence of this marker does not always mean the patient will develop persistent arthritis on follow-up, they added. In fact, this study showed that, among 47 anti–CCP-positive palindromic rheumatism patients, 35 (74%) did not develop persistent inflammatory arthritis in follow-up.

“In clinical practice, these patients may be inappropriately treated [e.g., with methotrexate] as they often meet ACR/EULAR criteria for rheumatoid arthritis,” the investigators wrote in their report.

Funding for the study came from the National Institute for Health Research Leeds Clinical Research Facility with additional support from an Arthritis Research U.K. grant. The authors reported no competing interests related to their study.

SOURCE: Mankia K et al. Ann Rheum Dis. 2018 Oct 8. doi: 10.1136/annrheumdis-2018-214175.

An improvement of nearly 4 points on a 30-point, patient-scored disease severity index appears to be clinically meaningful for adults with active RA, according to a recent clinical trial analysis.

Richard Clark, NIAMS

A 3.8-point decrease represented the minimal clinically important improvement in the Routine Assessment of Patient Index Data 3 (RAPID-3) index, investigators reported in The Journal of Rheumatology.

“Clinicians may feel comfortable documenting and monitoring patient status, recognizing an improvement of 3.8 units in patients with active RA to be meaningful in routine patient care,” Michael M. Ward, MD, PhD, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and his coinvestigators wrote.

The RAPID-3 index consists of three patient self-report measures out of the seven-item RA Core Data Set: physical function, pain, and patient’s global assessment. The index was initially designed to be feasible in routine care, such that a patient could fill it out in the waiting area, Dr. Ward and his colleagues noted in their report.

Previous investigations have shown that RAPID-3 is highly correlated with the 28-joint count Disease Activity Score (DAS28) and the Clinical Disease Activity Index, and in one study, it was more likely than erythrocyte sedimentation rate (ESR) to identify incomplete responses to methotrexate.

However, prior to the present study, there were no reported estimates of the minimal clinically important improvement for the RAPID-3 index.

Knowing whether or not a decrease in RAPID-3 is clinically meaningful to patients would help clinicians interpret those changes in response to treatment, Dr. Ward and his coauthors wrote.

In the current study, RAPID-3 was calculated before and after escalation of treatment in a prospective study involving 250 adults with active RA, including 195 women (78%). The mean age of the patients was 51 years, and the median duration of RA was more than 6 years.

At the patients’ baseline visit and evaluation, rheumatologists prescribed prednisone, a new disease-modifying treatment, a new biologic, or increased the dose of a current treatment. The follow-up visit occurred at 4 months for most patients, though follow-up was at 1 month for prednisone-treated patients because of an expected rapid response.

At baseline, the mean RAPID-3 score was 16.3, which improved to 11.1 at the follow-up visit, for a mean change of –5.2 points, according to the investigators. The standardized response mean was –0.79 (95% confidence interval, –0.71 to –0.88), which investigators said demonstrated good sensitivity to change.

They found that the minimal clinically important improvement was –3.8 in a statistical analysis that optimized sensitivity and specificity, and –3.5 and –4.1 by alternate statistical criteria.

However, Dr. Ward and his coauthors cautioned that these estimates should be applied only to patient groups that have high levels of RA activity, similar to this study, in which patients had a baseline mean DAS28-ESR of 6.16 and a mean Simplified Disease Activity Index of 38.6.

Patients with low RA activity are closer to an acceptable symptom state, making the minimal clinically important improvement less relevant. “The margin for symptom improvement becomes smaller and ultimately indiscernible as the level of activity decreases,” they explained in their report.

The study was supported in part through the NIAMS Intramural Research Program and a grant from the U.S. Public Health Service. No conflicts of interest were reported.

SOURCE: Ward MM et al. J Rheumatol. 2018 Oct 15. doi: 10.3899/jrheum.180153.

An improvement of nearly 4 points on a 30-point, patient-scored disease severity index appears to be clinically meaningful for adults with active RA, according to a recent clinical trial analysis.

Richard Clark, NIAMS

A 3.8-point decrease represented the minimal clinically important improvement in the Routine Assessment of Patient Index Data 3 (RAPID-3) index, investigators reported in The Journal of Rheumatology.

“Clinicians may feel comfortable documenting and monitoring patient status, recognizing an improvement of 3.8 units in patients with active RA to be meaningful in routine patient care,” Michael M. Ward, MD, PhD, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and his coinvestigators wrote.

The RAPID-3 index consists of three patient self-report measures out of the seven-item RA Core Data Set: physical function, pain, and patient’s global assessment. The index was initially designed to be feasible in routine care, such that a patient could fill it out in the waiting area, Dr. Ward and his colleagues noted in their report.

Previous investigations have shown that RAPID-3 is highly correlated with the 28-joint count Disease Activity Score (DAS28) and the Clinical Disease Activity Index, and in one study, it was more likely than erythrocyte sedimentation rate (ESR) to identify incomplete responses to methotrexate.

However, prior to the present study, there were no reported estimates of the minimal clinically important improvement for the RAPID-3 index.

Knowing whether or not a decrease in RAPID-3 is clinically meaningful to patients would help clinicians interpret those changes in response to treatment, Dr. Ward and his coauthors wrote.

In the current study, RAPID-3 was calculated before and after escalation of treatment in a prospective study involving 250 adults with active RA, including 195 women (78%). The mean age of the patients was 51 years, and the median duration of RA was more than 6 years.

At the patients’ baseline visit and evaluation, rheumatologists prescribed prednisone, a new disease-modifying treatment, a new biologic, or increased the dose of a current treatment. The follow-up visit occurred at 4 months for most patients, though follow-up was at 1 month for prednisone-treated patients because of an expected rapid response.

At baseline, the mean RAPID-3 score was 16.3, which improved to 11.1 at the follow-up visit, for a mean change of –5.2 points, according to the investigators. The standardized response mean was –0.79 (95% confidence interval, –0.71 to –0.88), which investigators said demonstrated good sensitivity to change.

They found that the minimal clinically important improvement was –3.8 in a statistical analysis that optimized sensitivity and specificity, and –3.5 and –4.1 by alternate statistical criteria.

However, Dr. Ward and his coauthors cautioned that these estimates should be applied only to patient groups that have high levels of RA activity, similar to this study, in which patients had a baseline mean DAS28-ESR of 6.16 and a mean Simplified Disease Activity Index of 38.6.

Patients with low RA activity are closer to an acceptable symptom state, making the minimal clinically important improvement less relevant. “The margin for symptom improvement becomes smaller and ultimately indiscernible as the level of activity decreases,” they explained in their report.

The study was supported in part through the NIAMS Intramural Research Program and a grant from the U.S. Public Health Service. No conflicts of interest were reported.

SOURCE: Ward MM et al. J Rheumatol. 2018 Oct 15. doi: 10.3899/jrheum.180153.

An improvement of nearly 4 points on a 30-point, patient-scored disease severity index appears to be clinically meaningful for adults with active RA, according to a recent clinical trial analysis.

Richard Clark, NIAMS

A 3.8-point decrease represented the minimal clinically important improvement in the Routine Assessment of Patient Index Data 3 (RAPID-3) index, investigators reported in The Journal of Rheumatology.

“Clinicians may feel comfortable documenting and monitoring patient status, recognizing an improvement of 3.8 units in patients with active RA to be meaningful in routine patient care,” Michael M. Ward, MD, PhD, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and his coinvestigators wrote.

The RAPID-3 index consists of three patient self-report measures out of the seven-item RA Core Data Set: physical function, pain, and patient’s global assessment. The index was initially designed to be feasible in routine care, such that a patient could fill it out in the waiting area, Dr. Ward and his colleagues noted in their report.

Previous investigations have shown that RAPID-3 is highly correlated with the 28-joint count Disease Activity Score (DAS28) and the Clinical Disease Activity Index, and in one study, it was more likely than erythrocyte sedimentation rate (ESR) to identify incomplete responses to methotrexate.

However, prior to the present study, there were no reported estimates of the minimal clinically important improvement for the RAPID-3 index.

Knowing whether or not a decrease in RAPID-3 is clinically meaningful to patients would help clinicians interpret those changes in response to treatment, Dr. Ward and his coauthors wrote.

In the current study, RAPID-3 was calculated before and after escalation of treatment in a prospective study involving 250 adults with active RA, including 195 women (78%). The mean age of the patients was 51 years, and the median duration of RA was more than 6 years.

At the patients’ baseline visit and evaluation, rheumatologists prescribed prednisone, a new disease-modifying treatment, a new biologic, or increased the dose of a current treatment. The follow-up visit occurred at 4 months for most patients, though follow-up was at 1 month for prednisone-treated patients because of an expected rapid response.

At baseline, the mean RAPID-3 score was 16.3, which improved to 11.1 at the follow-up visit, for a mean change of –5.2 points, according to the investigators. The standardized response mean was –0.79 (95% confidence interval, –0.71 to –0.88), which investigators said demonstrated good sensitivity to change.

They found that the minimal clinically important improvement was –3.8 in a statistical analysis that optimized sensitivity and specificity, and –3.5 and –4.1 by alternate statistical criteria.

However, Dr. Ward and his coauthors cautioned that these estimates should be applied only to patient groups that have high levels of RA activity, similar to this study, in which patients had a baseline mean DAS28-ESR of 6.16 and a mean Simplified Disease Activity Index of 38.6.

Patients with low RA activity are closer to an acceptable symptom state, making the minimal clinically important improvement less relevant. “The margin for symptom improvement becomes smaller and ultimately indiscernible as the level of activity decreases,” they explained in their report.

The study was supported in part through the NIAMS Intramural Research Program and a grant from the U.S. Public Health Service. No conflicts of interest were reported.

SOURCE: Ward MM et al. J Rheumatol. 2018 Oct 15. doi: 10.3899/jrheum.180153.

Adding a next-generation corrector to dual corrector-potentiator therapy is safe and effective in cystic fibrosis patients with one or two Phe508del alleles, results of two randomized phase 2, proof-of-concept clinical trials suggest.

CTRPhotos /thinkstock

The two trials, which evaluated the use of VX-445 or VX-659, respectively, in combination with tezacaftor-ivacaftor (Symdeko), were reported in the New England Journal of Medicine.

Both triple combinations improved lung function for patients heterozygous for the Phe508del cystic fibrosis transmembrane conductance regulator (CFTR) mutation and a minimal function mutation (Phe508del-MF) who had not previously received CFTR modulators, according to the investigators, who reported results simultaneously at the North American Cystic Fibrosis Conference in Denver.

These therapies also were effective in patients homozygous for Phe508del CFTR mutation (Phe508del-Phe508del) who had previously been treated with tezacaftor-ivacaftor, the results show.

No dose-limiting side effects or toxic effects were observed in the phase 2 studies, which included 4-week treatment periods.

“These trials provide proof of the concept that targeting the Phe508del CFTR protein with a triple-combination corrector–potentiator regimen can restore CFTR function and has the potential to represent a clinical advance for patients with cystic fibrosis who harbor either one or two Phe508del alleles, approximately 9 of every 10 patients with the disease,” Steven M. Rowe, MD, of the University of Alabama at Birmingham and his coauthors said in the report on VX-659 phase 2 study.

In that report, 63 patients with the Phe508del-MF genotype were randomized to one of three VX-659 doses in combination with tezacaftor and ivacaftor versus triple placebo for 4 weeks, while 29 Phe508del-Phe508del patients underwent a 4-week tezacaftor-ivacaftor run-in phase before starting 4 weeks of the triple combination.

The primary efficacy endpoint of the study was the absolute increase in percentage of predicted forced expiratory volume in 1 second (FEV₁).

In the Phe508del-MF patients, adding VX-659 improved that endpoint by up to 13.3 points versus baseline (P less than .001), whereas the absolute change was just 0.4 in the placebo group, the report shows. In the Phe508del-phe508del group, there was a 9.7-point increase over baseline.

Similarly, the companion study on VX-445, reported by Jennifer L. Taylor‑Cousar, MD, of National Jewish Health, Denver, and her colleagues, showed an increase in percentage of predicted FEV₁ of up to 13.8 points for Phe508del-MF patients (P less than .001), and an increase of 11.0 points in the Phe508del-Phe508del group (P less than .001).

Those results suggest that targeting the Phe508del CFTR mutation with a combination of two correctors and a potentiator can produce effective CFTR function in patients who have these forms of cystic fibrosis, according to Dr. Taylor-Cousar and her colleagues.

“Lung function was improved by a magnitude similar to that achieved with the CFTR modulator ivacaftor in patients with gating mutations, in whom treatment has been disease modifying,” the researchers wrote in their report.

Sweat chloride concentrations were reduced and respiratory domain scores were improved in patients receiving triple therapy, investigators reported.

Triple therapy improved Phe508del CFTR protein processing and trafficking, and chloride transport more so than any two agents in combination, according in vitro results, also described in the studies.

Phase 3 trials of these compounds are now underway, they said.

Both studies were supported by Vertex Pharmaceuticals, which received funding from the Cystic Fibrosis Foundation for the development of both VX-445 and VX-659. Dr. Rowe and Dr. Taylor-Cousar reported grants, personal fees, and nonfinancial support from Vertex while conducting the study. Study authors also reported disclosures related to AstraZeneca, Novartis, Bayer, Proteostasis, Gilead, Galapagos/AbbVie, and Celtaxsys, among other entities. Full disclosures for all authors were provided in the journal.

SOURCES: Keating D et al. N Engl J Med. 2018 Oct 18. doi: 10.1056/NEJMoa1807120; Davies JC et al. N Engl J Med. 2018 Oct 18. doi: 10.1056/NEJMoa1807119.

Adding a next-generation corrector to dual corrector-potentiator therapy is safe and effective in cystic fibrosis patients with one or two Phe508del alleles, results of two randomized phase 2, proof-of-concept clinical trials suggest.

CTRPhotos /thinkstock

The two trials, which evaluated the use of VX-445 or VX-659, respectively, in combination with tezacaftor-ivacaftor (Symdeko), were reported in the New England Journal of Medicine.

Both triple combinations improved lung function for patients heterozygous for the Phe508del cystic fibrosis transmembrane conductance regulator (CFTR) mutation and a minimal function mutation (Phe508del-MF) who had not previously received CFTR modulators, according to the investigators, who reported results simultaneously at the North American Cystic Fibrosis Conference in Denver.

These therapies also were effective in patients homozygous for Phe508del CFTR mutation (Phe508del-Phe508del) who had previously been treated with tezacaftor-ivacaftor, the results show.

No dose-limiting side effects or toxic effects were observed in the phase 2 studies, which included 4-week treatment periods.

“These trials provide proof of the concept that targeting the Phe508del CFTR protein with a triple-combination corrector–potentiator regimen can restore CFTR function and has the potential to represent a clinical advance for patients with cystic fibrosis who harbor either one or two Phe508del alleles, approximately 9 of every 10 patients with the disease,” Steven M. Rowe, MD, of the University of Alabama at Birmingham and his coauthors said in the report on VX-659 phase 2 study.

In that report, 63 patients with the Phe508del-MF genotype were randomized to one of three VX-659 doses in combination with tezacaftor and ivacaftor versus triple placebo for 4 weeks, while 29 Phe508del-Phe508del patients underwent a 4-week tezacaftor-ivacaftor run-in phase before starting 4 weeks of the triple combination.

The primary efficacy endpoint of the study was the absolute increase in percentage of predicted forced expiratory volume in 1 second (FEV₁).

In the Phe508del-MF patients, adding VX-659 improved that endpoint by up to 13.3 points versus baseline (P less than .001), whereas the absolute change was just 0.4 in the placebo group, the report shows. In the Phe508del-phe508del group, there was a 9.7-point increase over baseline.

Similarly, the companion study on VX-445, reported by Jennifer L. Taylor‑Cousar, MD, of National Jewish Health, Denver, and her colleagues, showed an increase in percentage of predicted FEV₁ of up to 13.8 points for Phe508del-MF patients (P less than .001), and an increase of 11.0 points in the Phe508del-Phe508del group (P less than .001).

Those results suggest that targeting the Phe508del CFTR mutation with a combination of two correctors and a potentiator can produce effective CFTR function in patients who have these forms of cystic fibrosis, according to Dr. Taylor-Cousar and her colleagues.

“Lung function was improved by a magnitude similar to that achieved with the CFTR modulator ivacaftor in patients with gating mutations, in whom treatment has been disease modifying,” the researchers wrote in their report.

Sweat chloride concentrations were reduced and respiratory domain scores were improved in patients receiving triple therapy, investigators reported.

Triple therapy improved Phe508del CFTR protein processing and trafficking, and chloride transport more so than any two agents in combination, according in vitro results, also described in the studies.

Phase 3 trials of these compounds are now underway, they said.

Both studies were supported by Vertex Pharmaceuticals, which received funding from the Cystic Fibrosis Foundation for the development of both VX-445 and VX-659. Dr. Rowe and Dr. Taylor-Cousar reported grants, personal fees, and nonfinancial support from Vertex while conducting the study. Study authors also reported disclosures related to AstraZeneca, Novartis, Bayer, Proteostasis, Gilead, Galapagos/AbbVie, and Celtaxsys, among other entities. Full disclosures for all authors were provided in the journal.

SOURCES: Keating D et al. N Engl J Med. 2018 Oct 18. doi: 10.1056/NEJMoa1807120; Davies JC et al. N Engl J Med. 2018 Oct 18. doi: 10.1056/NEJMoa1807119.

Adding a next-generation corrector to dual corrector-potentiator therapy is safe and effective in cystic fibrosis patients with one or two Phe508del alleles, results of two randomized phase 2, proof-of-concept clinical trials suggest.

CTRPhotos /thinkstock

The two trials, which evaluated the use of VX-445 or VX-659, respectively, in combination with tezacaftor-ivacaftor (Symdeko), were reported in the New England Journal of Medicine.

Both triple combinations improved lung function for patients heterozygous for the Phe508del cystic fibrosis transmembrane conductance regulator (CFTR) mutation and a minimal function mutation (Phe508del-MF) who had not previously received CFTR modulators, according to the investigators, who reported results simultaneously at the North American Cystic Fibrosis Conference in Denver.

These therapies also were effective in patients homozygous for Phe508del CFTR mutation (Phe508del-Phe508del) who had previously been treated with tezacaftor-ivacaftor, the results show.

No dose-limiting side effects or toxic effects were observed in the phase 2 studies, which included 4-week treatment periods.

“These trials provide proof of the concept that targeting the Phe508del CFTR protein with a triple-combination corrector–potentiator regimen can restore CFTR function and has the potential to represent a clinical advance for patients with cystic fibrosis who harbor either one or two Phe508del alleles, approximately 9 of every 10 patients with the disease,” Steven M. Rowe, MD, of the University of Alabama at Birmingham and his coauthors said in the report on VX-659 phase 2 study.

In that report, 63 patients with the Phe508del-MF genotype were randomized to one of three VX-659 doses in combination with tezacaftor and ivacaftor versus triple placebo for 4 weeks, while 29 Phe508del-Phe508del patients underwent a 4-week tezacaftor-ivacaftor run-in phase before starting 4 weeks of the triple combination.

The primary efficacy endpoint of the study was the absolute increase in percentage of predicted forced expiratory volume in 1 second (FEV₁).

In the Phe508del-MF patients, adding VX-659 improved that endpoint by up to 13.3 points versus baseline (P less than .001), whereas the absolute change was just 0.4 in the placebo group, the report shows. In the Phe508del-phe508del group, there was a 9.7-point increase over baseline.

Similarly, the companion study on VX-445, reported by Jennifer L. Taylor‑Cousar, MD, of National Jewish Health, Denver, and her colleagues, showed an increase in percentage of predicted FEV₁ of up to 13.8 points for Phe508del-MF patients (P less than .001), and an increase of 11.0 points in the Phe508del-Phe508del group (P less than .001).

Those results suggest that targeting the Phe508del CFTR mutation with a combination of two correctors and a potentiator can produce effective CFTR function in patients who have these forms of cystic fibrosis, according to Dr. Taylor-Cousar and her colleagues.

“Lung function was improved by a magnitude similar to that achieved with the CFTR modulator ivacaftor in patients with gating mutations, in whom treatment has been disease modifying,” the researchers wrote in their report.

Sweat chloride concentrations were reduced and respiratory domain scores were improved in patients receiving triple therapy, investigators reported.

Triple therapy improved Phe508del CFTR protein processing and trafficking, and chloride transport more so than any two agents in combination, according in vitro results, also described in the studies.

Phase 3 trials of these compounds are now underway, they said.

Both studies were supported by Vertex Pharmaceuticals, which received funding from the Cystic Fibrosis Foundation for the development of both VX-445 and VX-659. Dr. Rowe and Dr. Taylor-Cousar reported grants, personal fees, and nonfinancial support from Vertex while conducting the study. Study authors also reported disclosures related to AstraZeneca, Novartis, Bayer, Proteostasis, Gilead, Galapagos/AbbVie, and Celtaxsys, among other entities. Full disclosures for all authors were provided in the journal.

SOURCES: Keating D et al. N Engl J Med. 2018 Oct 18. doi: 10.1056/NEJMoa1807120; Davies JC et al. N Engl J Med. 2018 Oct 18. doi: 10.1056/NEJMoa1807119.

College of Georgia

SAN ANTONIO—The recommended approach to evaluating suspected pulmonary embolism (PE) is “greatly underutilized” in the Veterans Health Administration system, according to a speaker at CHEST 2018.

A survey showed that, contrary to guideline recommendations, most Veterans Affairs sites did not require incorporation of a clinical decision rule (CDR) and D-dimer prior to the ordering of computed tomographic pulmonary angiography (CTPA) for suspected PE.

Therefore, CTPA was overused.

Nancy Hsu, MD, a pulmonologist in Los Angeles, California, discussed this finding at the meeting.

She noted that CTPA has become the imaging modality of choice for evaluating suspected PE, but it is overused and potentially avoidable in one-third of cases.

“In the 10 years following the advent of CTPA use, there was a 14-fold increase in usage, but there was no change in mortality,” Dr. Hsu said. “This is consistent with overdiagnosis.”

Indiscriminate use of CTPA results in unnecessary and avoidable radiation exposure, contrast-related reactions, and treatment-related bleeding, Dr. Hsu noted.

She and a colleague discovered CTPA overuse in the Veterans Health Administration system by conducting a survey of stakeholders at 18 Veterans Integrated Service Networks and 143 medical centers.

A total of 120 fully completed questionnaires were analyzed. Most respondents (63%) were chief physicians, and 80% had 11 or more years of experience.

Most respondents (85%) said CDR with or without D-dimer was not required before ordering CTPA. Less than 7% of respondents said they required both CDR and D-dimer before CTPA.

The biggest barrier to optimal practice may be the fear of having a patient who “falls through the cracks” based on false-negative CDR and D-dimer data, according to Dr. Hsu.

On the other hand, judicious use of CTPA likely avoids negative sequelae related to radiation, contrast exposure, and treatment-related bleeding, she said.

Dr. Hsu and her colleague, Guy Soo Hoo, MD, said they had no relationships relevant to this research.

College of Georgia

SAN ANTONIO—The recommended approach to evaluating suspected pulmonary embolism (PE) is “greatly underutilized” in the Veterans Health Administration system, according to a speaker at CHEST 2018.

A survey showed that, contrary to guideline recommendations, most Veterans Affairs sites did not require incorporation of a clinical decision rule (CDR) and D-dimer prior to the ordering of computed tomographic pulmonary angiography (CTPA) for suspected PE.

Therefore, CTPA was overused.

Nancy Hsu, MD, a pulmonologist in Los Angeles, California, discussed this finding at the meeting.

She noted that CTPA has become the imaging modality of choice for evaluating suspected PE, but it is overused and potentially avoidable in one-third of cases.

“In the 10 years following the advent of CTPA use, there was a 14-fold increase in usage, but there was no change in mortality,” Dr. Hsu said. “This is consistent with overdiagnosis.”

Indiscriminate use of CTPA results in unnecessary and avoidable radiation exposure, contrast-related reactions, and treatment-related bleeding, Dr. Hsu noted.

She and a colleague discovered CTPA overuse in the Veterans Health Administration system by conducting a survey of stakeholders at 18 Veterans Integrated Service Networks and 143 medical centers.

A total of 120 fully completed questionnaires were analyzed. Most respondents (63%) were chief physicians, and 80% had 11 or more years of experience.

Most respondents (85%) said CDR with or without D-dimer was not required before ordering CTPA. Less than 7% of respondents said they required both CDR and D-dimer before CTPA.

The biggest barrier to optimal practice may be the fear of having a patient who “falls through the cracks” based on false-negative CDR and D-dimer data, according to Dr. Hsu.

On the other hand, judicious use of CTPA likely avoids negative sequelae related to radiation, contrast exposure, and treatment-related bleeding, she said.

Dr. Hsu and her colleague, Guy Soo Hoo, MD, said they had no relationships relevant to this research.

College of Georgia

SAN ANTONIO—The recommended approach to evaluating suspected pulmonary embolism (PE) is “greatly underutilized” in the Veterans Health Administration system, according to a speaker at CHEST 2018.

A survey showed that, contrary to guideline recommendations, most Veterans Affairs sites did not require incorporation of a clinical decision rule (CDR) and D-dimer prior to the ordering of computed tomographic pulmonary angiography (CTPA) for suspected PE.

Therefore, CTPA was overused.

Nancy Hsu, MD, a pulmonologist in Los Angeles, California, discussed this finding at the meeting.

She noted that CTPA has become the imaging modality of choice for evaluating suspected PE, but it is overused and potentially avoidable in one-third of cases.

“In the 10 years following the advent of CTPA use, there was a 14-fold increase in usage, but there was no change in mortality,” Dr. Hsu said. “This is consistent with overdiagnosis.”

Indiscriminate use of CTPA results in unnecessary and avoidable radiation exposure, contrast-related reactions, and treatment-related bleeding, Dr. Hsu noted.

She and a colleague discovered CTPA overuse in the Veterans Health Administration system by conducting a survey of stakeholders at 18 Veterans Integrated Service Networks and 143 medical centers.

A total of 120 fully completed questionnaires were analyzed. Most respondents (63%) were chief physicians, and 80% had 11 or more years of experience.

Most respondents (85%) said CDR with or without D-dimer was not required before ordering CTPA. Less than 7% of respondents said they required both CDR and D-dimer before CTPA.

The biggest barrier to optimal practice may be the fear of having a patient who “falls through the cracks” based on false-negative CDR and D-dimer data, according to Dr. Hsu.

On the other hand, judicious use of CTPA likely avoids negative sequelae related to radiation, contrast exposure, and treatment-related bleeding, she said.

Dr. Hsu and her colleague, Guy Soo Hoo, MD, said they had no relationships relevant to this research.

In contrast to other recent studies, androgen deprivation therapy (ADT) had no link to dementia in a observational cohort study of more than 45,000 men with prostate cancer who received definitive radiotherapy, investigators have reported.

No significant associations were found between ADT and Alzheimer’s disease or vascular dementia, or between shorter or longer courses of ADT and any dementia studied, according to Rishi Deka, PhD, of Veterans Affairs San Diego Health Care System, La Jolla, Calif., and coinvestigators.

“These results may mitigate concerns regarding the long-term risks of ADT on cognitive health in the treatment of prostate cancer,” Dr. Deka and colleagues wrote in JAMA Oncology.

Two other recent studies showed strong, statistically significant associations between ADT and dementia in prostate cancer. However, those studies combined patients with local and metastatic disease, receiving ADT in the upfront or recurrent settings, while the present study looked specifically at men with nonmetastatic prostate cancer who received radiotherapy.

“Different treatment modalities and disease stages are associated with substantial selection bias that may predispose results to false associations,” noted Dr. Deka and coauthors.

Their observational cohort study comprised 45,218 men diagnosed with nonmetastatic prostate cancer at the U.S. Department of Veterans Affairs who underwent radiotherapy with or without ADT. The investigators excluded men who had a diagnosis of dementia within 1 year of the prostate cancer diagnosis or who had prior diagnoses of dementia, stroke, or cognitive impairment.

A total of 1,497 patients were diagnosed with dementia over a median of 6.8 years of follow-up: 404 with Alzheimer disease, 335 with vascular dementia, and 758 with other types or unclassified dementias.

The investigators found no significant association between use of ADT and development of any dementia, the primary outcome of the analysis (subdistribution hazard ratio [SHR], 1.04; 95% confidence interval, 0.94-1.16; P = .43).

Likewise, there was no association between ADT and vascular dementia, specifically, with an SHR of 1.20 (95% CI, 0.97-1.50; P = .10) or Alzheimer’s disease, with an SHR of 1.11 (95% CI, 0.91-1.36; P = .29).

Duration of ADT longer than 1 year was not significantly associated with dementia, nor was duration shorter than 1 year, with SHRs, of 1.08 and 1.01 respectively, the analysis shows.

The SHRs in these and other analysis reported ranged from 1.00 to 1.21. That is substantially lower than hazard ratios of 1.66 to 2.32 in one previous study linking ADT to dementia, according to the investigators, suggesting that the results of the current analysis were not due to inadequate power to detect differences.

Nevertheless, the findings may not be generalizable to some other populations, they cautioned, since it was focused demographically on veterans, and was limited to radiotherapy-treated patients.

Dr. Deka and coauthors reported no conflict of interest. Their study was funded by grants from the University of California San Diego Center for Precision Radiation Medicine.

SOURCE: Deka R et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4423.

In contrast to other recent studies, androgen deprivation therapy (ADT) had no link to dementia in a observational cohort study of more than 45,000 men with prostate cancer who received definitive radiotherapy, investigators have reported.

No significant associations were found between ADT and Alzheimer’s disease or vascular dementia, or between shorter or longer courses of ADT and any dementia studied, according to Rishi Deka, PhD, of Veterans Affairs San Diego Health Care System, La Jolla, Calif., and coinvestigators.

“These results may mitigate concerns regarding the long-term risks of ADT on cognitive health in the treatment of prostate cancer,” Dr. Deka and colleagues wrote in JAMA Oncology.

Two other recent studies showed strong, statistically significant associations between ADT and dementia in prostate cancer. However, those studies combined patients with local and metastatic disease, receiving ADT in the upfront or recurrent settings, while the present study looked specifically at men with nonmetastatic prostate cancer who received radiotherapy.

“Different treatment modalities and disease stages are associated with substantial selection bias that may predispose results to false associations,” noted Dr. Deka and coauthors.

Their observational cohort study comprised 45,218 men diagnosed with nonmetastatic prostate cancer at the U.S. Department of Veterans Affairs who underwent radiotherapy with or without ADT. The investigators excluded men who had a diagnosis of dementia within 1 year of the prostate cancer diagnosis or who had prior diagnoses of dementia, stroke, or cognitive impairment.

A total of 1,497 patients were diagnosed with dementia over a median of 6.8 years of follow-up: 404 with Alzheimer disease, 335 with vascular dementia, and 758 with other types or unclassified dementias.

The investigators found no significant association between use of ADT and development of any dementia, the primary outcome of the analysis (subdistribution hazard ratio [SHR], 1.04; 95% confidence interval, 0.94-1.16; P = .43).

Likewise, there was no association between ADT and vascular dementia, specifically, with an SHR of 1.20 (95% CI, 0.97-1.50; P = .10) or Alzheimer’s disease, with an SHR of 1.11 (95% CI, 0.91-1.36; P = .29).

Duration of ADT longer than 1 year was not significantly associated with dementia, nor was duration shorter than 1 year, with SHRs, of 1.08 and 1.01 respectively, the analysis shows.

The SHRs in these and other analysis reported ranged from 1.00 to 1.21. That is substantially lower than hazard ratios of 1.66 to 2.32 in one previous study linking ADT to dementia, according to the investigators, suggesting that the results of the current analysis were not due to inadequate power to detect differences.

Nevertheless, the findings may not be generalizable to some other populations, they cautioned, since it was focused demographically on veterans, and was limited to radiotherapy-treated patients.

Dr. Deka and coauthors reported no conflict of interest. Their study was funded by grants from the University of California San Diego Center for Precision Radiation Medicine.

SOURCE: Deka R et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4423.

In contrast to other recent studies, androgen deprivation therapy (ADT) had no link to dementia in a observational cohort study of more than 45,000 men with prostate cancer who received definitive radiotherapy, investigators have reported.

No significant associations were found between ADT and Alzheimer’s disease or vascular dementia, or between shorter or longer courses of ADT and any dementia studied, according to Rishi Deka, PhD, of Veterans Affairs San Diego Health Care System, La Jolla, Calif., and coinvestigators.

“These results may mitigate concerns regarding the long-term risks of ADT on cognitive health in the treatment of prostate cancer,” Dr. Deka and colleagues wrote in JAMA Oncology.

Two other recent studies showed strong, statistically significant associations between ADT and dementia in prostate cancer. However, those studies combined patients with local and metastatic disease, receiving ADT in the upfront or recurrent settings, while the present study looked specifically at men with nonmetastatic prostate cancer who received radiotherapy.

“Different treatment modalities and disease stages are associated with substantial selection bias that may predispose results to false associations,” noted Dr. Deka and coauthors.

Their observational cohort study comprised 45,218 men diagnosed with nonmetastatic prostate cancer at the U.S. Department of Veterans Affairs who underwent radiotherapy with or without ADT. The investigators excluded men who had a diagnosis of dementia within 1 year of the prostate cancer diagnosis or who had prior diagnoses of dementia, stroke, or cognitive impairment.

A total of 1,497 patients were diagnosed with dementia over a median of 6.8 years of follow-up: 404 with Alzheimer disease, 335 with vascular dementia, and 758 with other types or unclassified dementias.

The investigators found no significant association between use of ADT and development of any dementia, the primary outcome of the analysis (subdistribution hazard ratio [SHR], 1.04; 95% confidence interval, 0.94-1.16; P = .43).

Likewise, there was no association between ADT and vascular dementia, specifically, with an SHR of 1.20 (95% CI, 0.97-1.50; P = .10) or Alzheimer’s disease, with an SHR of 1.11 (95% CI, 0.91-1.36; P = .29).

Duration of ADT longer than 1 year was not significantly associated with dementia, nor was duration shorter than 1 year, with SHRs, of 1.08 and 1.01 respectively, the analysis shows.

The SHRs in these and other analysis reported ranged from 1.00 to 1.21. That is substantially lower than hazard ratios of 1.66 to 2.32 in one previous study linking ADT to dementia, according to the investigators, suggesting that the results of the current analysis were not due to inadequate power to detect differences.

Nevertheless, the findings may not be generalizable to some other populations, they cautioned, since it was focused demographically on veterans, and was limited to radiotherapy-treated patients.

Dr. Deka and coauthors reported no conflict of interest. Their study was funded by grants from the University of California San Diego Center for Precision Radiation Medicine.

SOURCE: Deka R et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4423.