News

In the Navajo area, 1 in 5 Native Americans has diabetes, and about 75,000 have prediabetes. That is the impetus for IHS’s new campaign, launched at the Northern Navajo Medical Center, to raise awareness and knowledge of prediabetes—and to let people know it can be reversed.

The “Do I Have Prediabetes?” campaign by the Shiprock Health Promotion Program is intended to help people assess their risk and reverse prediabetes before their blood sugar level is high enough to be type 2 diabetes. The program builds on the groundwork of a 2016 CDC national prediabetes awareness campaign. Materials include posters, an infographic that depicts the risk factors, roadside billboards, and a video for waiting rooms.

The IHS has already made progress against at least 1 diabetes-related issue: kidney failure. Through the Special Diabetes Program for Indians, innovative evidence-based interventions helped reduce kidney failure from diabetes among Native American adults by 54% between 1996 and 2013. Kidney failure from diabetes in Native Americans was the highest of any ethnic group but now has dropped the fastest.  The Shiprock program will continue through early 2018.

In the Navajo area, 1 in 5 Native Americans has diabetes, and about 75,000 have prediabetes. That is the impetus for IHS’s new campaign, launched at the Northern Navajo Medical Center, to raise awareness and knowledge of prediabetes—and to let people know it can be reversed.

The “Do I Have Prediabetes?” campaign by the Shiprock Health Promotion Program is intended to help people assess their risk and reverse prediabetes before their blood sugar level is high enough to be type 2 diabetes. The program builds on the groundwork of a 2016 CDC national prediabetes awareness campaign. Materials include posters, an infographic that depicts the risk factors, roadside billboards, and a video for waiting rooms.

The IHS has already made progress against at least 1 diabetes-related issue: kidney failure. Through the Special Diabetes Program for Indians, innovative evidence-based interventions helped reduce kidney failure from diabetes among Native American adults by 54% between 1996 and 2013. Kidney failure from diabetes in Native Americans was the highest of any ethnic group but now has dropped the fastest.  The Shiprock program will continue through early 2018.

In the Navajo area, 1 in 5 Native Americans has diabetes, and about 75,000 have prediabetes. That is the impetus for IHS’s new campaign, launched at the Northern Navajo Medical Center, to raise awareness and knowledge of prediabetes—and to let people know it can be reversed.

The “Do I Have Prediabetes?” campaign by the Shiprock Health Promotion Program is intended to help people assess their risk and reverse prediabetes before their blood sugar level is high enough to be type 2 diabetes. The program builds on the groundwork of a 2016 CDC national prediabetes awareness campaign. Materials include posters, an infographic that depicts the risk factors, roadside billboards, and a video for waiting rooms.

The IHS has already made progress against at least 1 diabetes-related issue: kidney failure. Through the Special Diabetes Program for Indians, innovative evidence-based interventions helped reduce kidney failure from diabetes among Native American adults by 54% between 1996 and 2013. Kidney failure from diabetes in Native Americans was the highest of any ethnic group but now has dropped the fastest.  The Shiprock program will continue through early 2018.

LUGANO, SWITZERLAND – Copanlisib, an investigational intravenous inhibitor of phosphatidylinositol 3-kinase (PI3K), was associated with “promising” efficacy and a better safety profile than has been seen with oral PI3K inhibitors in patients with relapsed or refractory indolent lymphomas.

In a phase 2 trial of the drug as monotherapy in patients with indolent lymphomas, copanlisib was associated with an overall response rate of 58.6% among 104 patients with follicular lymphoma (FL), including 14.4% complete responses (CR) and 44.2% partial responses (PR), reported Martin Dreyling, MD, of the Universität München-Grosshadern in Munich, Germany.

“The favorable risk-benefit profile of this compound suggests further [need for] testing in follicular lymphoma. My personal interpretation is that the different safety profile is due to the intermittent dosing and the IV application, avoiding adverse cause-effect both in the gut and the liver,” he said at the 14th International Conference on Malignant Lymphoma.

Dr. Dreyling noted that the oral PI3K inhibitor idelalisib (Zydelig) is approved for the treatment of patients with relapsed chronic lymphocytic leukemia in combination with rituximab and in patients with relapsed FL or small lymphocytic lymphomas (SLL) who have received at least two prior lines of systemic therapy. This agent, however, carries a black box warning about fatal and serious toxicities, including hepatic events, severe diarrhea, colitis, pneumonitis, infections, and intestinal perforation.

Copanlisib inhibits all isoforms of P13K but is predominantly active against the alpha and delta isoforms of the kinase. The alpha form, expressed in many cell types, is involved in insulin signaling and angiogenesis and in resistance mechanisms to lymphoma. The delta form, expressed in leukocytes, is involved in B-cell signaling, development, and survival, making PIK3 an attractive target, Dr. Dreyling explained.

The study included patients with indolent B-cell lymphomas, including FL grades 1-3a, marginal zone lymphoma, SLL, or lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM) for whom at least two prior lines of therapy had failed.

The patients received copanlisib 60 mg IV on days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.

Of 142 assigned to and started on treatment, 46 patients (32.3%) remained on treatment at the time of data cutoff. Of the 96 patients (67.7%) who discontinued, 35 did so because of adverse events, 36 discontinued for radiologic or clinical evidence of progression, 16 withdrew, 5 were discontinued on the treating physician’s decision, and 4 stopped for other, unspecified reasons.

Among all 142 patients, the median duration of therapy was 22 weeks and the median number of cycles was 5.5. In all, 26.1% of patients required a dosage reduction to 45 mg, and 5.6% required reduction to 30 mg.

As noted, the objective tumor response rate (ORR) among patients was 58.6% for 104 patients with FL. For the 23 patients with marginal zone lymphoma, the ORR was 69.6%, consisting of two complete and 14 partial responses. Among eight patients with SLL, there were six partial responses and no complete responses. For the six patients with LPL/WM, there was one partial response.

The overall median duration of response was 22.6 months. Among patients with refractory disease and in all patients with FL the median duration of response was 12.2 months.

The median progression-free survival after 24 months of follow-up was 11.2 months for all patients. The median overall survival has not been reached.

The most frequent adverse events of grade 3 or 4 were hyperglycemia in 40.1% (33.1% grade 3 and 7.0% grade 4) and hypertension in 22.5% (all grade 3).

Grade 3 diarrhea, a significant problem with idelalisib, occurred in 4.2% of patients, and there were no grade 4 events.

Grade 3 pneumonitis was seen in two patients, and one had grade 4 colitis. There were three drug related deaths, including one patient each from lung infection, respiratory failure, or thromboembolic event..

The study was supported by Bayer. Dr. Dreyling disclosed receiving honoraria from the company and serving on a scientific/advisory board for the company.

LUGANO, SWITZERLAND – Copanlisib, an investigational intravenous inhibitor of phosphatidylinositol 3-kinase (PI3K), was associated with “promising” efficacy and a better safety profile than has been seen with oral PI3K inhibitors in patients with relapsed or refractory indolent lymphomas.

In a phase 2 trial of the drug as monotherapy in patients with indolent lymphomas, copanlisib was associated with an overall response rate of 58.6% among 104 patients with follicular lymphoma (FL), including 14.4% complete responses (CR) and 44.2% partial responses (PR), reported Martin Dreyling, MD, of the Universität München-Grosshadern in Munich, Germany.

“The favorable risk-benefit profile of this compound suggests further [need for] testing in follicular lymphoma. My personal interpretation is that the different safety profile is due to the intermittent dosing and the IV application, avoiding adverse cause-effect both in the gut and the liver,” he said at the 14th International Conference on Malignant Lymphoma.

Dr. Dreyling noted that the oral PI3K inhibitor idelalisib (Zydelig) is approved for the treatment of patients with relapsed chronic lymphocytic leukemia in combination with rituximab and in patients with relapsed FL or small lymphocytic lymphomas (SLL) who have received at least two prior lines of systemic therapy. This agent, however, carries a black box warning about fatal and serious toxicities, including hepatic events, severe diarrhea, colitis, pneumonitis, infections, and intestinal perforation.

Copanlisib inhibits all isoforms of P13K but is predominantly active against the alpha and delta isoforms of the kinase. The alpha form, expressed in many cell types, is involved in insulin signaling and angiogenesis and in resistance mechanisms to lymphoma. The delta form, expressed in leukocytes, is involved in B-cell signaling, development, and survival, making PIK3 an attractive target, Dr. Dreyling explained.

The study included patients with indolent B-cell lymphomas, including FL grades 1-3a, marginal zone lymphoma, SLL, or lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM) for whom at least two prior lines of therapy had failed.

The patients received copanlisib 60 mg IV on days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.

Of 142 assigned to and started on treatment, 46 patients (32.3%) remained on treatment at the time of data cutoff. Of the 96 patients (67.7%) who discontinued, 35 did so because of adverse events, 36 discontinued for radiologic or clinical evidence of progression, 16 withdrew, 5 were discontinued on the treating physician’s decision, and 4 stopped for other, unspecified reasons.

Among all 142 patients, the median duration of therapy was 22 weeks and the median number of cycles was 5.5. In all, 26.1% of patients required a dosage reduction to 45 mg, and 5.6% required reduction to 30 mg.

As noted, the objective tumor response rate (ORR) among patients was 58.6% for 104 patients with FL. For the 23 patients with marginal zone lymphoma, the ORR was 69.6%, consisting of two complete and 14 partial responses. Among eight patients with SLL, there were six partial responses and no complete responses. For the six patients with LPL/WM, there was one partial response.

The overall median duration of response was 22.6 months. Among patients with refractory disease and in all patients with FL the median duration of response was 12.2 months.

The median progression-free survival after 24 months of follow-up was 11.2 months for all patients. The median overall survival has not been reached.

The most frequent adverse events of grade 3 or 4 were hyperglycemia in 40.1% (33.1% grade 3 and 7.0% grade 4) and hypertension in 22.5% (all grade 3).

Grade 3 diarrhea, a significant problem with idelalisib, occurred in 4.2% of patients, and there were no grade 4 events.

Grade 3 pneumonitis was seen in two patients, and one had grade 4 colitis. There were three drug related deaths, including one patient each from lung infection, respiratory failure, or thromboembolic event..

The study was supported by Bayer. Dr. Dreyling disclosed receiving honoraria from the company and serving on a scientific/advisory board for the company.

LUGANO, SWITZERLAND – Copanlisib, an investigational intravenous inhibitor of phosphatidylinositol 3-kinase (PI3K), was associated with “promising” efficacy and a better safety profile than has been seen with oral PI3K inhibitors in patients with relapsed or refractory indolent lymphomas.

In a phase 2 trial of the drug as monotherapy in patients with indolent lymphomas, copanlisib was associated with an overall response rate of 58.6% among 104 patients with follicular lymphoma (FL), including 14.4% complete responses (CR) and 44.2% partial responses (PR), reported Martin Dreyling, MD, of the Universität München-Grosshadern in Munich, Germany.

“The favorable risk-benefit profile of this compound suggests further [need for] testing in follicular lymphoma. My personal interpretation is that the different safety profile is due to the intermittent dosing and the IV application, avoiding adverse cause-effect both in the gut and the liver,” he said at the 14th International Conference on Malignant Lymphoma.

Dr. Dreyling noted that the oral PI3K inhibitor idelalisib (Zydelig) is approved for the treatment of patients with relapsed chronic lymphocytic leukemia in combination with rituximab and in patients with relapsed FL or small lymphocytic lymphomas (SLL) who have received at least two prior lines of systemic therapy. This agent, however, carries a black box warning about fatal and serious toxicities, including hepatic events, severe diarrhea, colitis, pneumonitis, infections, and intestinal perforation.

Copanlisib inhibits all isoforms of P13K but is predominantly active against the alpha and delta isoforms of the kinase. The alpha form, expressed in many cell types, is involved in insulin signaling and angiogenesis and in resistance mechanisms to lymphoma. The delta form, expressed in leukocytes, is involved in B-cell signaling, development, and survival, making PIK3 an attractive target, Dr. Dreyling explained.

The study included patients with indolent B-cell lymphomas, including FL grades 1-3a, marginal zone lymphoma, SLL, or lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM) for whom at least two prior lines of therapy had failed.

The patients received copanlisib 60 mg IV on days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.

Of 142 assigned to and started on treatment, 46 patients (32.3%) remained on treatment at the time of data cutoff. Of the 96 patients (67.7%) who discontinued, 35 did so because of adverse events, 36 discontinued for radiologic or clinical evidence of progression, 16 withdrew, 5 were discontinued on the treating physician’s decision, and 4 stopped for other, unspecified reasons.

Among all 142 patients, the median duration of therapy was 22 weeks and the median number of cycles was 5.5. In all, 26.1% of patients required a dosage reduction to 45 mg, and 5.6% required reduction to 30 mg.

As noted, the objective tumor response rate (ORR) among patients was 58.6% for 104 patients with FL. For the 23 patients with marginal zone lymphoma, the ORR was 69.6%, consisting of two complete and 14 partial responses. Among eight patients with SLL, there were six partial responses and no complete responses. For the six patients with LPL/WM, there was one partial response.

The overall median duration of response was 22.6 months. Among patients with refractory disease and in all patients with FL the median duration of response was 12.2 months.

The median progression-free survival after 24 months of follow-up was 11.2 months for all patients. The median overall survival has not been reached.

The most frequent adverse events of grade 3 or 4 were hyperglycemia in 40.1% (33.1% grade 3 and 7.0% grade 4) and hypertension in 22.5% (all grade 3).

Grade 3 diarrhea, a significant problem with idelalisib, occurred in 4.2% of patients, and there were no grade 4 events.

Grade 3 pneumonitis was seen in two patients, and one had grade 4 colitis. There were three drug related deaths, including one patient each from lung infection, respiratory failure, or thromboembolic event..

The study was supported by Bayer. Dr. Dreyling disclosed receiving honoraria from the company and serving on a scientific/advisory board for the company.

Metabolic syndrome (MetS) is common among patients with coronary artery disease (CAD) and highly prevalent in those with acute ST-elevation myocardial infarction (STEMI). But are all elements of MetS equally good predictors of clinical severity and prognosis?

To find out, researchers from Sestre Milosrdnice University Hospital Center in Zagreb, Croatia, prospectively analyzed data of 250 patients with acute STEMI who were treated with primary percutaneous coronary intervention. Metabolic syndrome was defined according to the revised National Cholesterol Education Program-Adult Treatment Panel III and the International Diabetes Federation.

Patients with and without MetS were analyzed according to obesity indexes: body mass index (BMI); central-body adiposity index (BAI); conicity index (Cindex); visceral adiposity index (VAI); waist circumference (WC); waist-to-hip ratio (WHR); and waist-to-height ratio (WHtR).

During hospitalization, 19 patients died; 231 were included in the 12-month follow-up.

Patients with acute STEMI had high rates of central obesity, increased VAI, WHtR, and very high BAI, dyslipidemia, and hypertension. However, they had lower rates of overall obesity and hyperglycemia.

The researchers found MetS and several obesity indexes were superior to overall obesity BMI in predicting acute STEMI severity: clinical presentation, in-hospital complications, and severity of CAD. Waist circumference and MetS had no influence on prognosis. Moreover, MetS and obesity indexes had no influence on prognosis of major adverse cardiovascular events (MACE).

The researchers also found Cindex > 1.25/1.18, very high BAI, and WHtR ≥ 63/58 increased the risk of total in-hospital complications, dyspnea, and heart failure, respectively. The number of significantly stenosed coronary arteries increased the risk of total MACE. Waist-to-hip ratio independently increased the risk of significant stenosis of the coronary segment 1 and proximal/middle coronary artery (CA) segments.

In a previous study, the researchers had found that MetS patients had longer hospitalization and severe CAD. However, although MetS increased the risk of > 1 significantly stenosed CAs and total in-hospital complications, none of the MetS components per se significantly influenced clinical severity or prognosis; except hyperglycemia, which increased the risk of heart failure. The researchers found that was still true in this study, but Cindex was a stronger predictor of total in-hospital complications. The researchers concluded that VAI is more reliable than WC for predicting clinical severity of acute STEMI.

Source:

Jelavic MM, Barbic Z, Pintaric H. Arch Med Sci. 2017;13(4):795-806.

doi: https://doi.org/10.5114/aoms.2016.59703.

Metabolic syndrome (MetS) is common among patients with coronary artery disease (CAD) and highly prevalent in those with acute ST-elevation myocardial infarction (STEMI). But are all elements of MetS equally good predictors of clinical severity and prognosis?

To find out, researchers from Sestre Milosrdnice University Hospital Center in Zagreb, Croatia, prospectively analyzed data of 250 patients with acute STEMI who were treated with primary percutaneous coronary intervention. Metabolic syndrome was defined according to the revised National Cholesterol Education Program-Adult Treatment Panel III and the International Diabetes Federation.

Patients with and without MetS were analyzed according to obesity indexes: body mass index (BMI); central-body adiposity index (BAI); conicity index (Cindex); visceral adiposity index (VAI); waist circumference (WC); waist-to-hip ratio (WHR); and waist-to-height ratio (WHtR).

During hospitalization, 19 patients died; 231 were included in the 12-month follow-up.

Patients with acute STEMI had high rates of central obesity, increased VAI, WHtR, and very high BAI, dyslipidemia, and hypertension. However, they had lower rates of overall obesity and hyperglycemia.

The researchers found MetS and several obesity indexes were superior to overall obesity BMI in predicting acute STEMI severity: clinical presentation, in-hospital complications, and severity of CAD. Waist circumference and MetS had no influence on prognosis. Moreover, MetS and obesity indexes had no influence on prognosis of major adverse cardiovascular events (MACE).

The researchers also found Cindex > 1.25/1.18, very high BAI, and WHtR ≥ 63/58 increased the risk of total in-hospital complications, dyspnea, and heart failure, respectively. The number of significantly stenosed coronary arteries increased the risk of total MACE. Waist-to-hip ratio independently increased the risk of significant stenosis of the coronary segment 1 and proximal/middle coronary artery (CA) segments.

In a previous study, the researchers had found that MetS patients had longer hospitalization and severe CAD. However, although MetS increased the risk of > 1 significantly stenosed CAs and total in-hospital complications, none of the MetS components per se significantly influenced clinical severity or prognosis; except hyperglycemia, which increased the risk of heart failure. The researchers found that was still true in this study, but Cindex was a stronger predictor of total in-hospital complications. The researchers concluded that VAI is more reliable than WC for predicting clinical severity of acute STEMI.

Source:

Jelavic MM, Barbic Z, Pintaric H. Arch Med Sci. 2017;13(4):795-806.

doi: https://doi.org/10.5114/aoms.2016.59703.

Metabolic syndrome (MetS) is common among patients with coronary artery disease (CAD) and highly prevalent in those with acute ST-elevation myocardial infarction (STEMI). But are all elements of MetS equally good predictors of clinical severity and prognosis?

To find out, researchers from Sestre Milosrdnice University Hospital Center in Zagreb, Croatia, prospectively analyzed data of 250 patients with acute STEMI who were treated with primary percutaneous coronary intervention. Metabolic syndrome was defined according to the revised National Cholesterol Education Program-Adult Treatment Panel III and the International Diabetes Federation.

Patients with and without MetS were analyzed according to obesity indexes: body mass index (BMI); central-body adiposity index (BAI); conicity index (Cindex); visceral adiposity index (VAI); waist circumference (WC); waist-to-hip ratio (WHR); and waist-to-height ratio (WHtR).

During hospitalization, 19 patients died; 231 were included in the 12-month follow-up.

Patients with acute STEMI had high rates of central obesity, increased VAI, WHtR, and very high BAI, dyslipidemia, and hypertension. However, they had lower rates of overall obesity and hyperglycemia.

The researchers found MetS and several obesity indexes were superior to overall obesity BMI in predicting acute STEMI severity: clinical presentation, in-hospital complications, and severity of CAD. Waist circumference and MetS had no influence on prognosis. Moreover, MetS and obesity indexes had no influence on prognosis of major adverse cardiovascular events (MACE).

The researchers also found Cindex > 1.25/1.18, very high BAI, and WHtR ≥ 63/58 increased the risk of total in-hospital complications, dyspnea, and heart failure, respectively. The number of significantly stenosed coronary arteries increased the risk of total MACE. Waist-to-hip ratio independently increased the risk of significant stenosis of the coronary segment 1 and proximal/middle coronary artery (CA) segments.

In a previous study, the researchers had found that MetS patients had longer hospitalization and severe CAD. However, although MetS increased the risk of > 1 significantly stenosed CAs and total in-hospital complications, none of the MetS components per se significantly influenced clinical severity or prognosis; except hyperglycemia, which increased the risk of heart failure. The researchers found that was still true in this study, but Cindex was a stronger predictor of total in-hospital complications. The researchers concluded that VAI is more reliable than WC for predicting clinical severity of acute STEMI.

Source:

Jelavic MM, Barbic Z, Pintaric H. Arch Med Sci. 2017;13(4):795-806.

doi: https://doi.org/10.5114/aoms.2016.59703.

ICD-9 codes were poor at picking out idiopathic pulmonary fibrosis patients from administrative databases for epidemiologic studies, but a new tool could improve diagnostic accuracy, according to Kaiser Permanente and University of California, San Francisco (UCSF), investigators.

“In the age of large administrative databases and electronic medical records, there is rich opportunity to conduct population-based studies” of disease behavior, outcomes, health care use, and other matters, but researchers first need to be able to accurately identify patients with idiopathic pulmonary fibrosis (IPF) in large data sets, said investigators led by Brett Ley, MD, an assistant professor of medicine at UCSF.

The research community has traditionally relied on claims for specific IPF diagnostic codes – ICD-9 code 516.3 or ICD-9-CM code 516.31 – to identify patients, but the approach had never been validated. To see how well it works, the investigators applied it to the nearly 5.4 million adults in the Kaiser Permanente Northern California system during 2000-2014. After patients with interstitial lung disease-associated codes entered on or after the day of the last IPF code were excluded, the algorithm identified 2,608 patients as having IPF (Ann Am Thorac Soc. 2017 Jun;14[6]:880-7).

Next, the investigators randomly selected 150 of those patients and examined their medical records, procedure codes, CTs, and other patient-level data to see how many of them really had IPF. The results weren’t good. The positive predictive value of the IPF code-based algorithm was only 42.2%, with a sensitivity 55.6%.

The widely used code-based IPF algorithm does “not generate accurate estimates of IPF incidence and prevalence. ... Over half of the patients identified as having IPF ... did not have IPF on case review. Alarmingly, whereas half of the misclassified cases had an alternative [interstitial lung disease] diagnosis, the other half had no clinical or radiologic evidence of ILD [interstitial lung disease] at all.” The algorithm also “likely misses a substantial proportion of patients who do have IPF,” Dr. Ley and his colleagues said.

“We can only speculate about the reasons. ... It seems likely to be due to a combination of misdiagnosis at the clinical level and miscoding at the administrative level,” they said.

To try to improve the situation, the team tweaked the algorithm to include only patients 50 years or older who had at least two 516.3 or 516.31 claims 1 month or more apart and a chest CT procedure code beforehand. They again excluded ILD-associated claims on or after the day of the last IPF code.

Although the sensitivity of the modified algorithm was lower than the original, it had a more robust positive predictive value of 70.4% in the derivation cohort and 61.8% in the validation cohort, both derived from the 150 patients used to validate the original algorithm.

“By making a few simple, empirically derived changes to the IPF algorithm,” it’s possible to “more reliably identif[y] patients” with IPF. “We believe the modified IPF algorithm will be useful for population-based studies of IPF ... that require high diagnostic certainty,” the investigators concluded.

The traditional algorithm found an incidence of 6.8 cases per 100,000 person-years, which was on the low end of previous reports, perhaps because of the relative health and youth of the 5.4 million patient pool. As in past studies, IPF incidence increased with older age and was highest in white patients and men.

“Whether the more specific codes provided by the ICD-10 system will allow for improved case classification of IPF requires further study,” the investigators noted.

The work was funded by the National Institutes of Health. Dr. Ley reported speaker’s fees from Genentech, and one of the authors was an employee of the company. The senior author Harold Collard, MD, an associate professor in UCSF’s Division of Pulmonary and Critical Care Medicine, reported personal fees from Takeda, ImmuneWorks, Parexel, Pharma Capital Partners, and others.
 

aotto@frontlinemedcom.com

ICD-9 codes were poor at picking out idiopathic pulmonary fibrosis patients from administrative databases for epidemiologic studies, but a new tool could improve diagnostic accuracy, according to Kaiser Permanente and University of California, San Francisco (UCSF), investigators.

“In the age of large administrative databases and electronic medical records, there is rich opportunity to conduct population-based studies” of disease behavior, outcomes, health care use, and other matters, but researchers first need to be able to accurately identify patients with idiopathic pulmonary fibrosis (IPF) in large data sets, said investigators led by Brett Ley, MD, an assistant professor of medicine at UCSF.

The research community has traditionally relied on claims for specific IPF diagnostic codes – ICD-9 code 516.3 or ICD-9-CM code 516.31 – to identify patients, but the approach had never been validated. To see how well it works, the investigators applied it to the nearly 5.4 million adults in the Kaiser Permanente Northern California system during 2000-2014. After patients with interstitial lung disease-associated codes entered on or after the day of the last IPF code were excluded, the algorithm identified 2,608 patients as having IPF (Ann Am Thorac Soc. 2017 Jun;14[6]:880-7).

Next, the investigators randomly selected 150 of those patients and examined their medical records, procedure codes, CTs, and other patient-level data to see how many of them really had IPF. The results weren’t good. The positive predictive value of the IPF code-based algorithm was only 42.2%, with a sensitivity 55.6%.

The widely used code-based IPF algorithm does “not generate accurate estimates of IPF incidence and prevalence. ... Over half of the patients identified as having IPF ... did not have IPF on case review. Alarmingly, whereas half of the misclassified cases had an alternative [interstitial lung disease] diagnosis, the other half had no clinical or radiologic evidence of ILD [interstitial lung disease] at all.” The algorithm also “likely misses a substantial proportion of patients who do have IPF,” Dr. Ley and his colleagues said.

“We can only speculate about the reasons. ... It seems likely to be due to a combination of misdiagnosis at the clinical level and miscoding at the administrative level,” they said.

To try to improve the situation, the team tweaked the algorithm to include only patients 50 years or older who had at least two 516.3 or 516.31 claims 1 month or more apart and a chest CT procedure code beforehand. They again excluded ILD-associated claims on or after the day of the last IPF code.

Although the sensitivity of the modified algorithm was lower than the original, it had a more robust positive predictive value of 70.4% in the derivation cohort and 61.8% in the validation cohort, both derived from the 150 patients used to validate the original algorithm.

“By making a few simple, empirically derived changes to the IPF algorithm,” it’s possible to “more reliably identif[y] patients” with IPF. “We believe the modified IPF algorithm will be useful for population-based studies of IPF ... that require high diagnostic certainty,” the investigators concluded.

The traditional algorithm found an incidence of 6.8 cases per 100,000 person-years, which was on the low end of previous reports, perhaps because of the relative health and youth of the 5.4 million patient pool. As in past studies, IPF incidence increased with older age and was highest in white patients and men.

“Whether the more specific codes provided by the ICD-10 system will allow for improved case classification of IPF requires further study,” the investigators noted.

The work was funded by the National Institutes of Health. Dr. Ley reported speaker’s fees from Genentech, and one of the authors was an employee of the company. The senior author Harold Collard, MD, an associate professor in UCSF’s Division of Pulmonary and Critical Care Medicine, reported personal fees from Takeda, ImmuneWorks, Parexel, Pharma Capital Partners, and others.
 

aotto@frontlinemedcom.com

ICD-9 codes were poor at picking out idiopathic pulmonary fibrosis patients from administrative databases for epidemiologic studies, but a new tool could improve diagnostic accuracy, according to Kaiser Permanente and University of California, San Francisco (UCSF), investigators.

“In the age of large administrative databases and electronic medical records, there is rich opportunity to conduct population-based studies” of disease behavior, outcomes, health care use, and other matters, but researchers first need to be able to accurately identify patients with idiopathic pulmonary fibrosis (IPF) in large data sets, said investigators led by Brett Ley, MD, an assistant professor of medicine at UCSF.

The research community has traditionally relied on claims for specific IPF diagnostic codes – ICD-9 code 516.3 or ICD-9-CM code 516.31 – to identify patients, but the approach had never been validated. To see how well it works, the investigators applied it to the nearly 5.4 million adults in the Kaiser Permanente Northern California system during 2000-2014. After patients with interstitial lung disease-associated codes entered on or after the day of the last IPF code were excluded, the algorithm identified 2,608 patients as having IPF (Ann Am Thorac Soc. 2017 Jun;14[6]:880-7).

Next, the investigators randomly selected 150 of those patients and examined their medical records, procedure codes, CTs, and other patient-level data to see how many of them really had IPF. The results weren’t good. The positive predictive value of the IPF code-based algorithm was only 42.2%, with a sensitivity 55.6%.

The widely used code-based IPF algorithm does “not generate accurate estimates of IPF incidence and prevalence. ... Over half of the patients identified as having IPF ... did not have IPF on case review. Alarmingly, whereas half of the misclassified cases had an alternative [interstitial lung disease] diagnosis, the other half had no clinical or radiologic evidence of ILD [interstitial lung disease] at all.” The algorithm also “likely misses a substantial proportion of patients who do have IPF,” Dr. Ley and his colleagues said.

“We can only speculate about the reasons. ... It seems likely to be due to a combination of misdiagnosis at the clinical level and miscoding at the administrative level,” they said.

To try to improve the situation, the team tweaked the algorithm to include only patients 50 years or older who had at least two 516.3 or 516.31 claims 1 month or more apart and a chest CT procedure code beforehand. They again excluded ILD-associated claims on or after the day of the last IPF code.

Although the sensitivity of the modified algorithm was lower than the original, it had a more robust positive predictive value of 70.4% in the derivation cohort and 61.8% in the validation cohort, both derived from the 150 patients used to validate the original algorithm.

“By making a few simple, empirically derived changes to the IPF algorithm,” it’s possible to “more reliably identif[y] patients” with IPF. “We believe the modified IPF algorithm will be useful for population-based studies of IPF ... that require high diagnostic certainty,” the investigators concluded.

The traditional algorithm found an incidence of 6.8 cases per 100,000 person-years, which was on the low end of previous reports, perhaps because of the relative health and youth of the 5.4 million patient pool. As in past studies, IPF incidence increased with older age and was highest in white patients and men.

“Whether the more specific codes provided by the ICD-10 system will allow for improved case classification of IPF requires further study,” the investigators noted.

The work was funded by the National Institutes of Health. Dr. Ley reported speaker’s fees from Genentech, and one of the authors was an employee of the company. The senior author Harold Collard, MD, an associate professor in UCSF’s Division of Pulmonary and Critical Care Medicine, reported personal fees from Takeda, ImmuneWorks, Parexel, Pharma Capital Partners, and others.
 

aotto@frontlinemedcom.com

High-dose chemotherapy with upfront autologous stem cell transplantation did not meaningfully improve survival at 5 years in a phase 3 trial of 399 patients under age 66 years with intermediate to high– or high-risk untreated diffuse large B-cell lymphoma.

Rates of treatment failure-free survival at 2 years were 71% for patients who received rituximab dose–dense chemotherapy followed by autologous stem cell transplantation (ASCT) and 62% for patients who received only the rituximab regimen (hazard ratio, 0.65; 95% confidence interval, 0.47-0.91; P = .01), Annalisa Chiappella, MD, of Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino (Italy) reported with her associates in Lancet Oncology.

hematologynews@frontlinemedcom.com

High-dose chemotherapy with upfront autologous stem cell transplantation did not meaningfully improve survival at 5 years in a phase 3 trial of 399 patients under age 66 years with intermediate to high– or high-risk untreated diffuse large B-cell lymphoma.

Rates of treatment failure-free survival at 2 years were 71% for patients who received rituximab dose–dense chemotherapy followed by autologous stem cell transplantation (ASCT) and 62% for patients who received only the rituximab regimen (hazard ratio, 0.65; 95% confidence interval, 0.47-0.91; P = .01), Annalisa Chiappella, MD, of Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino (Italy) reported with her associates in Lancet Oncology.

hematologynews@frontlinemedcom.com

High-dose chemotherapy with upfront autologous stem cell transplantation did not meaningfully improve survival at 5 years in a phase 3 trial of 399 patients under age 66 years with intermediate to high– or high-risk untreated diffuse large B-cell lymphoma.

Rates of treatment failure-free survival at 2 years were 71% for patients who received rituximab dose–dense chemotherapy followed by autologous stem cell transplantation (ASCT) and 62% for patients who received only the rituximab regimen (hazard ratio, 0.65; 95% confidence interval, 0.47-0.91; P = .01), Annalisa Chiappella, MD, of Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino (Italy) reported with her associates in Lancet Oncology.

hematologynews@frontlinemedcom.com

LUGANO, SWITZERLAND – Tazemetostat, a first-in-class experimental agent that inhibits an oncogenic protein, shows efficacy in patients with heavily pretreated, relapsed/refractory follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL), interim results from a phase II study suggest.

Among patients with relapsed/refractory FL who had mutations in EZH2 (enhancer of zeste homolog 2), a member of a family of proteins that are involved in epigenetic gene silencing, the overall response rate (ORR) was 92%, reported Franck Morschhauser, MD, PhD, of the University of Lille, France.

Neil Osterweil/Frontline Medical News

Large multicenter study

Dr. Morschhauser reported interim results from a global, multi-center open-label study of tazemetostat in six cohorts of patients with relapsed/refractory FL (two monotherapy cohorts of 45 patients each) or DLBCL (three monotherapy cohorts of 60 patients each). A sixth cohort consisting of 70 patients with DLBCL treated with tazemetostat and prednisolone was added in 2017.

In the ongoing trial, patients receive oral tazemetostat 800 mg twice daily until disease progression or withdrawal from study, and are being followed for ORR, progression-free survival, overall survival, duration-of response, safety, and pharmacokinetics.

The longest follow-up at the time of data cutoff was approximately 18 months. Among 13 evaluable patients with FL with EZH2 mutations, the ORR was 92%, including one complete response (CR) and 11 partial responses (PR). In contrast, the ORR for 54 patients with FL and wild-type EZH2 was 28%, consisting of three CRs and 11 PRs. One patient with mutated EZH2 and 23 with wild-type EZH2 had stable disease.

Among 17 patients with DLBCL and EZH2 mutations, the ORR was 29%, consisting of 5 PR. For 119 patients with wild-type EZH2, the ORR was 15%, consisting of 10 CR and 8 PR. Six patients with mutations and 22 with wild-type EZH2 had stable disease.

Among the patients with FL, 75% had significant reduction in tumor burden.

The time to response ranged from 2 months to 1 year, with a median of approximately 4 months.

The variability in time to response “makes it a little bit tricky to calculate response duration,” Dr. Morschhauser said.

The drug had a “favorable” safety profile, with treatment-related adverse events of grade 3 or greater in more than 5% of patients including thrombocytopenias in 6% of patients, anemias in 4%, and neutropenias in 6%. Treatment-emergent adverse events leading to dose reductions occurred in 4% of patients, and those leading to drug discontinuation or study withdrawal occurred in 12% of patients.

In a retrospective analysis, the investigators performed molecular profiling studies using next-generation sequencing to look for predictors of response to tazemetostat. They found that patients most likely to respond to tazemetostat were those with activating mutations in EZH2 and MYD88. In contrast, patients with mutations HIST1H1E or MYC were not likely to respond.

Thomas E. Witzig, MD, of the Mayo Clinic in Rochester, Minn., the invited discussant, said that the study is important because “it provides proof of principle that attacking the methylation issue, attacking one of these enzymes, is very important and can produce single-agent responses.

“It also demonstrates the value of mutation status, and this trial knowledge of that mutation status has actually changed the trial design, so that now they are only putting patients on with mutations,” he said.

The trial also raises the possibility of targeting other parts of the methylation pathway to treat cancer, he added.

The study was sponsored by Epizyme, the maker of tazemetostat. Dr. Morschhauser disclosed receiving honoraria from and serving on advisory boards for both companies. Dr. Witzig has disclosed grants for clinical trials from Novartis and Wyeth, and he has served on advisory boards for Cephalon, Novartis, and Wyeth.

LUGANO, SWITZERLAND – Tazemetostat, a first-in-class experimental agent that inhibits an oncogenic protein, shows efficacy in patients with heavily pretreated, relapsed/refractory follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL), interim results from a phase II study suggest.

Among patients with relapsed/refractory FL who had mutations in EZH2 (enhancer of zeste homolog 2), a member of a family of proteins that are involved in epigenetic gene silencing, the overall response rate (ORR) was 92%, reported Franck Morschhauser, MD, PhD, of the University of Lille, France.

Neil Osterweil/Frontline Medical News

Large multicenter study

Dr. Morschhauser reported interim results from a global, multi-center open-label study of tazemetostat in six cohorts of patients with relapsed/refractory FL (two monotherapy cohorts of 45 patients each) or DLBCL (three monotherapy cohorts of 60 patients each). A sixth cohort consisting of 70 patients with DLBCL treated with tazemetostat and prednisolone was added in 2017.

In the ongoing trial, patients receive oral tazemetostat 800 mg twice daily until disease progression or withdrawal from study, and are being followed for ORR, progression-free survival, overall survival, duration-of response, safety, and pharmacokinetics.

The longest follow-up at the time of data cutoff was approximately 18 months. Among 13 evaluable patients with FL with EZH2 mutations, the ORR was 92%, including one complete response (CR) and 11 partial responses (PR). In contrast, the ORR for 54 patients with FL and wild-type EZH2 was 28%, consisting of three CRs and 11 PRs. One patient with mutated EZH2 and 23 with wild-type EZH2 had stable disease.

Among 17 patients with DLBCL and EZH2 mutations, the ORR was 29%, consisting of 5 PR. For 119 patients with wild-type EZH2, the ORR was 15%, consisting of 10 CR and 8 PR. Six patients with mutations and 22 with wild-type EZH2 had stable disease.

Among the patients with FL, 75% had significant reduction in tumor burden.

The time to response ranged from 2 months to 1 year, with a median of approximately 4 months.

The variability in time to response “makes it a little bit tricky to calculate response duration,” Dr. Morschhauser said.

The drug had a “favorable” safety profile, with treatment-related adverse events of grade 3 or greater in more than 5% of patients including thrombocytopenias in 6% of patients, anemias in 4%, and neutropenias in 6%. Treatment-emergent adverse events leading to dose reductions occurred in 4% of patients, and those leading to drug discontinuation or study withdrawal occurred in 12% of patients.

In a retrospective analysis, the investigators performed molecular profiling studies using next-generation sequencing to look for predictors of response to tazemetostat. They found that patients most likely to respond to tazemetostat were those with activating mutations in EZH2 and MYD88. In contrast, patients with mutations HIST1H1E or MYC were not likely to respond.

Thomas E. Witzig, MD, of the Mayo Clinic in Rochester, Minn., the invited discussant, said that the study is important because “it provides proof of principle that attacking the methylation issue, attacking one of these enzymes, is very important and can produce single-agent responses.

“It also demonstrates the value of mutation status, and this trial knowledge of that mutation status has actually changed the trial design, so that now they are only putting patients on with mutations,” he said.

The trial also raises the possibility of targeting other parts of the methylation pathway to treat cancer, he added.

The study was sponsored by Epizyme, the maker of tazemetostat. Dr. Morschhauser disclosed receiving honoraria from and serving on advisory boards for both companies. Dr. Witzig has disclosed grants for clinical trials from Novartis and Wyeth, and he has served on advisory boards for Cephalon, Novartis, and Wyeth.

LUGANO, SWITZERLAND – Tazemetostat, a first-in-class experimental agent that inhibits an oncogenic protein, shows efficacy in patients with heavily pretreated, relapsed/refractory follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL), interim results from a phase II study suggest.

Among patients with relapsed/refractory FL who had mutations in EZH2 (enhancer of zeste homolog 2), a member of a family of proteins that are involved in epigenetic gene silencing, the overall response rate (ORR) was 92%, reported Franck Morschhauser, MD, PhD, of the University of Lille, France.

Neil Osterweil/Frontline Medical News

Large multicenter study

Dr. Morschhauser reported interim results from a global, multi-center open-label study of tazemetostat in six cohorts of patients with relapsed/refractory FL (two monotherapy cohorts of 45 patients each) or DLBCL (three monotherapy cohorts of 60 patients each). A sixth cohort consisting of 70 patients with DLBCL treated with tazemetostat and prednisolone was added in 2017.

In the ongoing trial, patients receive oral tazemetostat 800 mg twice daily until disease progression or withdrawal from study, and are being followed for ORR, progression-free survival, overall survival, duration-of response, safety, and pharmacokinetics.

The longest follow-up at the time of data cutoff was approximately 18 months. Among 13 evaluable patients with FL with EZH2 mutations, the ORR was 92%, including one complete response (CR) and 11 partial responses (PR). In contrast, the ORR for 54 patients with FL and wild-type EZH2 was 28%, consisting of three CRs and 11 PRs. One patient with mutated EZH2 and 23 with wild-type EZH2 had stable disease.

Among 17 patients with DLBCL and EZH2 mutations, the ORR was 29%, consisting of 5 PR. For 119 patients with wild-type EZH2, the ORR was 15%, consisting of 10 CR and 8 PR. Six patients with mutations and 22 with wild-type EZH2 had stable disease.

Among the patients with FL, 75% had significant reduction in tumor burden.

The time to response ranged from 2 months to 1 year, with a median of approximately 4 months.

The variability in time to response “makes it a little bit tricky to calculate response duration,” Dr. Morschhauser said.

The drug had a “favorable” safety profile, with treatment-related adverse events of grade 3 or greater in more than 5% of patients including thrombocytopenias in 6% of patients, anemias in 4%, and neutropenias in 6%. Treatment-emergent adverse events leading to dose reductions occurred in 4% of patients, and those leading to drug discontinuation or study withdrawal occurred in 12% of patients.

In a retrospective analysis, the investigators performed molecular profiling studies using next-generation sequencing to look for predictors of response to tazemetostat. They found that patients most likely to respond to tazemetostat were those with activating mutations in EZH2 and MYD88. In contrast, patients with mutations HIST1H1E or MYC were not likely to respond.

Thomas E. Witzig, MD, of the Mayo Clinic in Rochester, Minn., the invited discussant, said that the study is important because “it provides proof of principle that attacking the methylation issue, attacking one of these enzymes, is very important and can produce single-agent responses.

“It also demonstrates the value of mutation status, and this trial knowledge of that mutation status has actually changed the trial design, so that now they are only putting patients on with mutations,” he said.

The trial also raises the possibility of targeting other parts of the methylation pathway to treat cancer, he added.

The study was sponsored by Epizyme, the maker of tazemetostat. Dr. Morschhauser disclosed receiving honoraria from and serving on advisory boards for both companies. Dr. Witzig has disclosed grants for clinical trials from Novartis and Wyeth, and he has served on advisory boards for Cephalon, Novartis, and Wyeth.

As more people are surviving breast cancer, more will be given bisphosphonate (BP) for bone metastases—and may be at risk for treatment adverse effects, such as atypical femoral fracture (AFF). Clinicians from Royal Victoria Hospital, Belfast, United Kingdom, describe what they learned in the first reported case of AFF caused by daily ibandronate.

The patient, a 55-year-old woman, had been diagnosed and treated for breast cancer. Twelve years later, she began having hip and lower back pain and was diagnosed with bony metastatic spread. She was started on hormone-suppressing therapy as well as daily ibandronic acid. Four years later, she began having new lower limb and groin pain. Radiography, bone scans and other tests indicated further metastatic spread to her left femur.

While she was waiting for scheduled radiotherapy, she fell, fracturing her left femur. Radiographs revealed AFF, presumed secondary to her BP therapy rather than metastasis. She underwent intramedullary nail fixation.

Evidence suggests that AFFs are stress fractures, the clinicians say. Repetitive loading on bone can lead to micro cracks, which are even more vulnerable to stress when BPs suppress the normal bone repair process.

Atypical femoral fracture is rare. Most cases have been patients receiving intravenous BP; to the clinicians’ knowledge this is the first report of AFF with an oral BP prescribed for bone metastatic breast cancer. But incidence of AFF grows with prolonged treatment, and the risk is raised with oral dosing, which is much higher in cancer cases, the clinicians note, compared with osteoporosis.

Because patients often have prodromal pain before an overt break, the clinicians suggest asking all oncology patients on BP about pain in thigh, hip, or groin. Bone scans and magnetic resonance imaging may reveal an imminent fracture. The clinicians caution that AFFs can be bilateral, so the opposite side also should be imaged.

Source:

Espey R, Grimes S, Heyburn G, Kealey WD. BMJ Case Rep. 2017;2017. pii: bcr-2016-217489.
doi: 10.1136/bcr-2016-217489.

As more people are surviving breast cancer, more will be given bisphosphonate (BP) for bone metastases—and may be at risk for treatment adverse effects, such as atypical femoral fracture (AFF). Clinicians from Royal Victoria Hospital, Belfast, United Kingdom, describe what they learned in the first reported case of AFF caused by daily ibandronate.

The patient, a 55-year-old woman, had been diagnosed and treated for breast cancer. Twelve years later, she began having hip and lower back pain and was diagnosed with bony metastatic spread. She was started on hormone-suppressing therapy as well as daily ibandronic acid. Four years later, she began having new lower limb and groin pain. Radiography, bone scans and other tests indicated further metastatic spread to her left femur.

While she was waiting for scheduled radiotherapy, she fell, fracturing her left femur. Radiographs revealed AFF, presumed secondary to her BP therapy rather than metastasis. She underwent intramedullary nail fixation.

Evidence suggests that AFFs are stress fractures, the clinicians say. Repetitive loading on bone can lead to micro cracks, which are even more vulnerable to stress when BPs suppress the normal bone repair process.

Atypical femoral fracture is rare. Most cases have been patients receiving intravenous BP; to the clinicians’ knowledge this is the first report of AFF with an oral BP prescribed for bone metastatic breast cancer. But incidence of AFF grows with prolonged treatment, and the risk is raised with oral dosing, which is much higher in cancer cases, the clinicians note, compared with osteoporosis.

Because patients often have prodromal pain before an overt break, the clinicians suggest asking all oncology patients on BP about pain in thigh, hip, or groin. Bone scans and magnetic resonance imaging may reveal an imminent fracture. The clinicians caution that AFFs can be bilateral, so the opposite side also should be imaged.

Source:

Espey R, Grimes S, Heyburn G, Kealey WD. BMJ Case Rep. 2017;2017. pii: bcr-2016-217489.
doi: 10.1136/bcr-2016-217489.

As more people are surviving breast cancer, more will be given bisphosphonate (BP) for bone metastases—and may be at risk for treatment adverse effects, such as atypical femoral fracture (AFF). Clinicians from Royal Victoria Hospital, Belfast, United Kingdom, describe what they learned in the first reported case of AFF caused by daily ibandronate.

The patient, a 55-year-old woman, had been diagnosed and treated for breast cancer. Twelve years later, she began having hip and lower back pain and was diagnosed with bony metastatic spread. She was started on hormone-suppressing therapy as well as daily ibandronic acid. Four years later, she began having new lower limb and groin pain. Radiography, bone scans and other tests indicated further metastatic spread to her left femur.

While she was waiting for scheduled radiotherapy, she fell, fracturing her left femur. Radiographs revealed AFF, presumed secondary to her BP therapy rather than metastasis. She underwent intramedullary nail fixation.

Evidence suggests that AFFs are stress fractures, the clinicians say. Repetitive loading on bone can lead to micro cracks, which are even more vulnerable to stress when BPs suppress the normal bone repair process.

Atypical femoral fracture is rare. Most cases have been patients receiving intravenous BP; to the clinicians’ knowledge this is the first report of AFF with an oral BP prescribed for bone metastatic breast cancer. But incidence of AFF grows with prolonged treatment, and the risk is raised with oral dosing, which is much higher in cancer cases, the clinicians note, compared with osteoporosis.

Because patients often have prodromal pain before an overt break, the clinicians suggest asking all oncology patients on BP about pain in thigh, hip, or groin. Bone scans and magnetic resonance imaging may reveal an imminent fracture. The clinicians caution that AFFs can be bilateral, so the opposite side also should be imaged.

Source:

Espey R, Grimes S, Heyburn G, Kealey WD. BMJ Case Rep. 2017;2017. pii: bcr-2016-217489.
doi: 10.1136/bcr-2016-217489.

In an “important first,” the FDA has fast-tracked a cancer treatment based on a biomarker rather than on the location of the tumor.

Pembrolizumab (Keytruda) has already been approved for certain patients with metastatic melanoma, metastatic non-small cell lung cancer, and other cancers. With the new approval, pembrolizumab is now indicated for adult and pediatric patients with unresectable or metastatic solid tumors that have a biomarker known as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). Microsatellite instability-high and dMMR tumors have abnormalities that affect the proper repair of DNA inside the cell. Pembrolizumab blocks a cellular pathway (PD-1/PD-L1—proteins found in immune cells and some cancer cells), which may help the immune system fight the cancer cells.

Tumors with the biomarkers are most commonly found in colorectal, endometrial, and gastrointestinal cancers. About 5% of patients with metastatic colorectal cancer have MSI-H or dMMR tumors. Less commonly, they are found in cancers in the breast, prostate, bladder, thyroid gland, and other locations.

In 5 clinical trials, of 149 patients treated with pembrolizumab for 15 cancer types, 40% had a complete or partial response. For most of those patients, the response lasted ≥ 6 months.

In an “important first,” the FDA has fast-tracked a cancer treatment based on a biomarker rather than on the location of the tumor.

Pembrolizumab (Keytruda) has already been approved for certain patients with metastatic melanoma, metastatic non-small cell lung cancer, and other cancers. With the new approval, pembrolizumab is now indicated for adult and pediatric patients with unresectable or metastatic solid tumors that have a biomarker known as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). Microsatellite instability-high and dMMR tumors have abnormalities that affect the proper repair of DNA inside the cell. Pembrolizumab blocks a cellular pathway (PD-1/PD-L1—proteins found in immune cells and some cancer cells), which may help the immune system fight the cancer cells.

Tumors with the biomarkers are most commonly found in colorectal, endometrial, and gastrointestinal cancers. About 5% of patients with metastatic colorectal cancer have MSI-H or dMMR tumors. Less commonly, they are found in cancers in the breast, prostate, bladder, thyroid gland, and other locations.

In 5 clinical trials, of 149 patients treated with pembrolizumab for 15 cancer types, 40% had a complete or partial response. For most of those patients, the response lasted ≥ 6 months.

In an “important first,” the FDA has fast-tracked a cancer treatment based on a biomarker rather than on the location of the tumor.

Pembrolizumab (Keytruda) has already been approved for certain patients with metastatic melanoma, metastatic non-small cell lung cancer, and other cancers. With the new approval, pembrolizumab is now indicated for adult and pediatric patients with unresectable or metastatic solid tumors that have a biomarker known as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). Microsatellite instability-high and dMMR tumors have abnormalities that affect the proper repair of DNA inside the cell. Pembrolizumab blocks a cellular pathway (PD-1/PD-L1—proteins found in immune cells and some cancer cells), which may help the immune system fight the cancer cells.

Tumors with the biomarkers are most commonly found in colorectal, endometrial, and gastrointestinal cancers. About 5% of patients with metastatic colorectal cancer have MSI-H or dMMR tumors. Less commonly, they are found in cancers in the breast, prostate, bladder, thyroid gland, and other locations.

In 5 clinical trials, of 149 patients treated with pembrolizumab for 15 cancer types, 40% had a complete or partial response. For most of those patients, the response lasted ≥ 6 months.

WASHINGTON – If patients have sleep disordered breathing with obstructive sleep apnea, will its treatment have cardiovascular disease benefits, especially in terms of the incidence or severity of atrial fibrillation?

Observational evidence suggests that apnea interventions may help these patients, but no clear case yet exists to prove that a breathing intervention works, experts say, and, as a result, U.S. practice is mixed when it comes to using treatment for obstructive sleep apnea (OSA), specifically continuous positive airway pressure (CPAP), to prevent or treat atrial fibrillation.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

This article was updated on 7/10/17.

WASHINGTON – If patients have sleep disordered breathing with obstructive sleep apnea, will its treatment have cardiovascular disease benefits, especially in terms of the incidence or severity of atrial fibrillation?

Observational evidence suggests that apnea interventions may help these patients, but no clear case yet exists to prove that a breathing intervention works, experts say, and, as a result, U.S. practice is mixed when it comes to using treatment for obstructive sleep apnea (OSA), specifically continuous positive airway pressure (CPAP), to prevent or treat atrial fibrillation.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

This article was updated on 7/10/17.

WASHINGTON – If patients have sleep disordered breathing with obstructive sleep apnea, will its treatment have cardiovascular disease benefits, especially in terms of the incidence or severity of atrial fibrillation?

Observational evidence suggests that apnea interventions may help these patients, but no clear case yet exists to prove that a breathing intervention works, experts say, and, as a result, U.S. practice is mixed when it comes to using treatment for obstructive sleep apnea (OSA), specifically continuous positive airway pressure (CPAP), to prevent or treat atrial fibrillation.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

This article was updated on 7/10/17.

Living in a racially segregated neighborhood can be bad for the blood pressure (BP) if you are a black adult, according to Northwestern University researchers. They found that simply moving away from that neighborhood is enough to reduce systolic blood pressure 1 to 5 points.

In the study, which was partly funded by the NIH, the researchers examined BP readings for 2,280 black adults who participated in the Coronary Artery Risk Development in Young Adults (CARDIA) study. The participants were initially screened in 1985 and 1986 then reexamined several times over the next 25 years. The Northwestern study is the first to look at the longitudinal effects of segregation on BP compare the effect within the same individuals. Previous research had looked at single points in time.

The researchers categorized neighborhood segregation as high, medium, or low, using a scale that compareed the percentage of black residents in a neighborhood to the surrounding area. When neighborhoods were more segregated, the participants had small but statistically significant increases in systolic BP. Less segregation equaled a “notable” drop in BP.

Participants who lived in a highly segregated neighborhood and moved to a less segregated one saw the most significant improvements. Those who moved temporarily saw a 1 mm Hg drop. A permanent move equaled 3 to 5 mm Hg. That’s a “powerful effect,” said lead author Kiarri Kershaw, assistant professor of preventive medicine at Northwestern. Just 1 mm Hg lower at the population level, she notes, could mean “meaningful” reductions in heart attacks, strokes, and heart failure. The associations persisted even after the researchers accounted for marital status, body mass index, smoking history, physical activity, and socioeconomic status of the community.

The changes in blood pressure were not related to poverty or household income. Kershaw says less stress, achieved by reducing exposure to violence and improving opportunities for socioeconomic mobility, is “likely a key factor.” Other factors that could help include improving access to health-promoting resources, such as full-service grocery stores, recreation centers, and health care clinics.

Living in a racially segregated neighborhood can be bad for the blood pressure (BP) if you are a black adult, according to Northwestern University researchers. They found that simply moving away from that neighborhood is enough to reduce systolic blood pressure 1 to 5 points.

In the study, which was partly funded by the NIH, the researchers examined BP readings for 2,280 black adults who participated in the Coronary Artery Risk Development in Young Adults (CARDIA) study. The participants were initially screened in 1985 and 1986 then reexamined several times over the next 25 years. The Northwestern study is the first to look at the longitudinal effects of segregation on BP compare the effect within the same individuals. Previous research had looked at single points in time.

The researchers categorized neighborhood segregation as high, medium, or low, using a scale that compareed the percentage of black residents in a neighborhood to the surrounding area. When neighborhoods were more segregated, the participants had small but statistically significant increases in systolic BP. Less segregation equaled a “notable” drop in BP.

Participants who lived in a highly segregated neighborhood and moved to a less segregated one saw the most significant improvements. Those who moved temporarily saw a 1 mm Hg drop. A permanent move equaled 3 to 5 mm Hg. That’s a “powerful effect,” said lead author Kiarri Kershaw, assistant professor of preventive medicine at Northwestern. Just 1 mm Hg lower at the population level, she notes, could mean “meaningful” reductions in heart attacks, strokes, and heart failure. The associations persisted even after the researchers accounted for marital status, body mass index, smoking history, physical activity, and socioeconomic status of the community.

The changes in blood pressure were not related to poverty or household income. Kershaw says less stress, achieved by reducing exposure to violence and improving opportunities for socioeconomic mobility, is “likely a key factor.” Other factors that could help include improving access to health-promoting resources, such as full-service grocery stores, recreation centers, and health care clinics.

Living in a racially segregated neighborhood can be bad for the blood pressure (BP) if you are a black adult, according to Northwestern University researchers. They found that simply moving away from that neighborhood is enough to reduce systolic blood pressure 1 to 5 points.

In the study, which was partly funded by the NIH, the researchers examined BP readings for 2,280 black adults who participated in the Coronary Artery Risk Development in Young Adults (CARDIA) study. The participants were initially screened in 1985 and 1986 then reexamined several times over the next 25 years. The Northwestern study is the first to look at the longitudinal effects of segregation on BP compare the effect within the same individuals. Previous research had looked at single points in time.

The researchers categorized neighborhood segregation as high, medium, or low, using a scale that compareed the percentage of black residents in a neighborhood to the surrounding area. When neighborhoods were more segregated, the participants had small but statistically significant increases in systolic BP. Less segregation equaled a “notable” drop in BP.

Participants who lived in a highly segregated neighborhood and moved to a less segregated one saw the most significant improvements. Those who moved temporarily saw a 1 mm Hg drop. A permanent move equaled 3 to 5 mm Hg. That’s a “powerful effect,” said lead author Kiarri Kershaw, assistant professor of preventive medicine at Northwestern. Just 1 mm Hg lower at the population level, she notes, could mean “meaningful” reductions in heart attacks, strokes, and heart failure. The associations persisted even after the researchers accounted for marital status, body mass index, smoking history, physical activity, and socioeconomic status of the community.

The changes in blood pressure were not related to poverty or household income. Kershaw says less stress, achieved by reducing exposure to violence and improving opportunities for socioeconomic mobility, is “likely a key factor.” Other factors that could help include improving access to health-promoting resources, such as full-service grocery stores, recreation centers, and health care clinics.