Doug Brunk

SAN DIEGO – An early and accurate diagnosis of placenta accreta is crucial because maternal mortality can be as high as 7% and perinatal mortality can be as high as 10%.

"Historically, the clinical presentation of placenta accreta was a prolonged third-stage or retained placenta after delivery of the baby and subsequent onset of hemorrhage or the onset of hemorrhage at the time of the termination of pregnancy," Dr. Gladys Ramos said at the University of California, San Diego, Critical Care Summer Session. "Now, with predelivery diagnosis, we have changed the management and the clinical presentation."

Placenta accreta is defined as the abnormal presence of villi attached to the myometrium due to a defect in the decidua basalis. In the 1980s, placenta accreta was believed to be rare. However, a study from 2005 showed an increase in the rate of placenta accreta (Am. J. Obstet. Gynecol. 2005;192:1458-61). The condition now occurs in 1 in every 533 pregnancies.

"Mirroring this rise is a rise in cesarean deliveries," said Dr. Ramos, a perinatologist at the UCSD Medical Center. "We think these two conditions are related. At UCSD, we take care of about 3,200 deliveries per year, and from 1990 to 2008 we have seen a linear increase in the rate of placenta accreta. We take care of about two patients per month with this condition."

Risk factors for the placenta accreta are prior uterine surgery, placenta previa, advanced maternal age, parity, and smoking. The published rate of detection by ultrasound ranges from 80% to 100%, "with a low false-positive rate," Dr. Ramos said. Telltale signs on ultrasound include loss of myometrial interface, a heterogeneous "Swiss cheese–looking" appearance to the placenta, an increase in the vascularity of the placenta, and evidence of bladder invasion.

MRI can be used as an adjunct to ultrasound diagnosis. The published detection rate with MRI ranges from 80% to 88%, "with a very low false-positive rate, which is why we use it as an adjunct to an ultrasound," she said. "We see similar findings on MRI that we do on ultrasound: thickened, dark nodular contour to the placenta; extension of the dark bands within the placenta; and mass effect causing a bulge on T1."

Nurses and sonographers at UCSD have been trained to ask patients upon presentation about risk factors for the condition." Then we look for signs of placenta accreta on ultrasound, including endovaginal ultrasound," Dr. Ramos said. "If we are concerned, we plan ahead with a multidisciplinary approach. If we’re still not sure, we proceed with MRI for diagnosis."

In 1995, clinicians at UCSD developed a multidisciplinary approach to treating patients with placenta accreta, mindful that "it took a cast of thousands to be able to make sure our outcomes were optimal for both mom and baby," said Pat Inzano, R.N., an administrative nurse in labor and delivery at UCSD. "Over the years, we’ve recognized the risk factors and the importance of early and accurate diagnosis."

The approach includes detailed maternal counseling and meticulous planning with colleagues at every conceivable step along the way in the care of the mom and baby, from neonatology and gynecologic surgery to surgical ICU staff and social workers. "When a mother gets the news [of placenta accreta], not only does she probably not understand the pathophysiology of what’s going on, but it takes a long time for her to digest this information," Ms. Inzano explained. "One of the things that’s so important at every level is getting her and her family to understand the diagnosis and reminding her that she’s [receiving] the best possible care."

The multidisciplinary team stages a conference to discuss the patient’s hospital delivery and care; availability of blood products; the need for anesthesia, surgical, and radiological expertise in house; and intensive care capability. Proper consents are also required "because the surgery will involve removing the patient’s uterus and rendering her sterile," she said. "We want to get the patient and the family as comfortable as possible with what’s going to happen. We found that providing tours of every single area that she will be ‘parking in’ is stress-relieving for her and her family, including labor and delivery and the neonatal ICU. We also provide consultations with all of the specialties involved in the case. All of this is education and counseling on a lot of different levels."

The team develops a time-line and schedules a planned delivery, including admission to the hospital, cesarean section/hysterectomy in the main operating room (OR), and unit transfers for epidural, central lines, and femoral balloons. In addition, the team coordinates a hospital tour for the patient and family. Most recommended deliveries are at week 34 because "we don’t want her to get near term and go into labor, which would aggravate a bleed of the placenta accreta," Ms. Inzano said.

The team also crafts a "plan B" for emergent delivery, including a detailed list of whom to contact and their pager numbers. "If we need to emergency deliver this patient in the main OR at 3 in the morning, we have our attending physician call the attending trauma physician to put us on trauma bypass in case we need the blood products," she said. "If we don’t have the type and cross-matched blood available, we activate an [obstetric] hemorrhage protocol in order to obtain O-negative blood in massive quantities until she’s cross-matched."

Ms. Inzano said that the multidisciplinary approach to placenta accreta "has become a smooth operation at our institution, but we never drop our awareness of the severity of what can happen. With the multidisciplinary effort, it brings everyone together; everyone’s on the same page, and everyone knows what to anticipate."

Neither Dr. Ramos nor Ms. Inzano had relevant financial conflicts.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

SAN DIEGO – An early and accurate diagnosis of placenta accreta is crucial because maternal mortality can be as high as 7% and perinatal mortality can be as high as 10%.

"Historically, the clinical presentation of placenta accreta was a prolonged third-stage or retained placenta after delivery of the baby and subsequent onset of hemorrhage or the onset of hemorrhage at the time of the termination of pregnancy," Dr. Gladys Ramos said at the University of California, San Diego, Critical Care Summer Session. "Now, with predelivery diagnosis, we have changed the management and the clinical presentation."

Placenta accreta is defined as the abnormal presence of villi attached to the myometrium due to a defect in the decidua basalis. In the 1980s, placenta accreta was believed to be rare. However, a study from 2005 showed an increase in the rate of placenta accreta (Am. J. Obstet. Gynecol. 2005;192:1458-61). The condition now occurs in 1 in every 533 pregnancies.

"Mirroring this rise is a rise in cesarean deliveries," said Dr. Ramos, a perinatologist at the UCSD Medical Center. "We think these two conditions are related. At UCSD, we take care of about 3,200 deliveries per year, and from 1990 to 2008 we have seen a linear increase in the rate of placenta accreta. We take care of about two patients per month with this condition."

Risk factors for the placenta accreta are prior uterine surgery, placenta previa, advanced maternal age, parity, and smoking. The published rate of detection by ultrasound ranges from 80% to 100%, "with a low false-positive rate," Dr. Ramos said. Telltale signs on ultrasound include loss of myometrial interface, a heterogeneous "Swiss cheese–looking" appearance to the placenta, an increase in the vascularity of the placenta, and evidence of bladder invasion.

MRI can be used as an adjunct to ultrasound diagnosis. The published detection rate with MRI ranges from 80% to 88%, "with a very low false-positive rate, which is why we use it as an adjunct to an ultrasound," she said. "We see similar findings on MRI that we do on ultrasound: thickened, dark nodular contour to the placenta; extension of the dark bands within the placenta; and mass effect causing a bulge on T1."

Nurses and sonographers at UCSD have been trained to ask patients upon presentation about risk factors for the condition." Then we look for signs of placenta accreta on ultrasound, including endovaginal ultrasound," Dr. Ramos said. "If we are concerned, we plan ahead with a multidisciplinary approach. If we’re still not sure, we proceed with MRI for diagnosis."

In 1995, clinicians at UCSD developed a multidisciplinary approach to treating patients with placenta accreta, mindful that "it took a cast of thousands to be able to make sure our outcomes were optimal for both mom and baby," said Pat Inzano, R.N., an administrative nurse in labor and delivery at UCSD. "Over the years, we’ve recognized the risk factors and the importance of early and accurate diagnosis."

The approach includes detailed maternal counseling and meticulous planning with colleagues at every conceivable step along the way in the care of the mom and baby, from neonatology and gynecologic surgery to surgical ICU staff and social workers. "When a mother gets the news [of placenta accreta], not only does she probably not understand the pathophysiology of what’s going on, but it takes a long time for her to digest this information," Ms. Inzano explained. "One of the things that’s so important at every level is getting her and her family to understand the diagnosis and reminding her that she’s [receiving] the best possible care."

The multidisciplinary team stages a conference to discuss the patient’s hospital delivery and care; availability of blood products; the need for anesthesia, surgical, and radiological expertise in house; and intensive care capability. Proper consents are also required "because the surgery will involve removing the patient’s uterus and rendering her sterile," she said. "We want to get the patient and the family as comfortable as possible with what’s going to happen. We found that providing tours of every single area that she will be ‘parking in’ is stress-relieving for her and her family, including labor and delivery and the neonatal ICU. We also provide consultations with all of the specialties involved in the case. All of this is education and counseling on a lot of different levels."

The team develops a time-line and schedules a planned delivery, including admission to the hospital, cesarean section/hysterectomy in the main operating room (OR), and unit transfers for epidural, central lines, and femoral balloons. In addition, the team coordinates a hospital tour for the patient and family. Most recommended deliveries are at week 34 because "we don’t want her to get near term and go into labor, which would aggravate a bleed of the placenta accreta," Ms. Inzano said.

The team also crafts a "plan B" for emergent delivery, including a detailed list of whom to contact and their pager numbers. "If we need to emergency deliver this patient in the main OR at 3 in the morning, we have our attending physician call the attending trauma physician to put us on trauma bypass in case we need the blood products," she said. "If we don’t have the type and cross-matched blood available, we activate an [obstetric] hemorrhage protocol in order to obtain O-negative blood in massive quantities until she’s cross-matched."

Ms. Inzano said that the multidisciplinary approach to placenta accreta "has become a smooth operation at our institution, but we never drop our awareness of the severity of what can happen. With the multidisciplinary effort, it brings everyone together; everyone’s on the same page, and everyone knows what to anticipate."

Neither Dr. Ramos nor Ms. Inzano had relevant financial conflicts.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

SAN DIEGO – An early and accurate diagnosis of placenta accreta is crucial because maternal mortality can be as high as 7% and perinatal mortality can be as high as 10%.

"Historically, the clinical presentation of placenta accreta was a prolonged third-stage or retained placenta after delivery of the baby and subsequent onset of hemorrhage or the onset of hemorrhage at the time of the termination of pregnancy," Dr. Gladys Ramos said at the University of California, San Diego, Critical Care Summer Session. "Now, with predelivery diagnosis, we have changed the management and the clinical presentation."

Placenta accreta is defined as the abnormal presence of villi attached to the myometrium due to a defect in the decidua basalis. In the 1980s, placenta accreta was believed to be rare. However, a study from 2005 showed an increase in the rate of placenta accreta (Am. J. Obstet. Gynecol. 2005;192:1458-61). The condition now occurs in 1 in every 533 pregnancies.

"Mirroring this rise is a rise in cesarean deliveries," said Dr. Ramos, a perinatologist at the UCSD Medical Center. "We think these two conditions are related. At UCSD, we take care of about 3,200 deliveries per year, and from 1990 to 2008 we have seen a linear increase in the rate of placenta accreta. We take care of about two patients per month with this condition."

Risk factors for the placenta accreta are prior uterine surgery, placenta previa, advanced maternal age, parity, and smoking. The published rate of detection by ultrasound ranges from 80% to 100%, "with a low false-positive rate," Dr. Ramos said. Telltale signs on ultrasound include loss of myometrial interface, a heterogeneous "Swiss cheese–looking" appearance to the placenta, an increase in the vascularity of the placenta, and evidence of bladder invasion.

MRI can be used as an adjunct to ultrasound diagnosis. The published detection rate with MRI ranges from 80% to 88%, "with a very low false-positive rate, which is why we use it as an adjunct to an ultrasound," she said. "We see similar findings on MRI that we do on ultrasound: thickened, dark nodular contour to the placenta; extension of the dark bands within the placenta; and mass effect causing a bulge on T1."

Nurses and sonographers at UCSD have been trained to ask patients upon presentation about risk factors for the condition." Then we look for signs of placenta accreta on ultrasound, including endovaginal ultrasound," Dr. Ramos said. "If we are concerned, we plan ahead with a multidisciplinary approach. If we’re still not sure, we proceed with MRI for diagnosis."

In 1995, clinicians at UCSD developed a multidisciplinary approach to treating patients with placenta accreta, mindful that "it took a cast of thousands to be able to make sure our outcomes were optimal for both mom and baby," said Pat Inzano, R.N., an administrative nurse in labor and delivery at UCSD. "Over the years, we’ve recognized the risk factors and the importance of early and accurate diagnosis."

The approach includes detailed maternal counseling and meticulous planning with colleagues at every conceivable step along the way in the care of the mom and baby, from neonatology and gynecologic surgery to surgical ICU staff and social workers. "When a mother gets the news [of placenta accreta], not only does she probably not understand the pathophysiology of what’s going on, but it takes a long time for her to digest this information," Ms. Inzano explained. "One of the things that’s so important at every level is getting her and her family to understand the diagnosis and reminding her that she’s [receiving] the best possible care."

The multidisciplinary team stages a conference to discuss the patient’s hospital delivery and care; availability of blood products; the need for anesthesia, surgical, and radiological expertise in house; and intensive care capability. Proper consents are also required "because the surgery will involve removing the patient’s uterus and rendering her sterile," she said. "We want to get the patient and the family as comfortable as possible with what’s going to happen. We found that providing tours of every single area that she will be ‘parking in’ is stress-relieving for her and her family, including labor and delivery and the neonatal ICU. We also provide consultations with all of the specialties involved in the case. All of this is education and counseling on a lot of different levels."

The team develops a time-line and schedules a planned delivery, including admission to the hospital, cesarean section/hysterectomy in the main operating room (OR), and unit transfers for epidural, central lines, and femoral balloons. In addition, the team coordinates a hospital tour for the patient and family. Most recommended deliveries are at week 34 because "we don’t want her to get near term and go into labor, which would aggravate a bleed of the placenta accreta," Ms. Inzano said.

The team also crafts a "plan B" for emergent delivery, including a detailed list of whom to contact and their pager numbers. "If we need to emergency deliver this patient in the main OR at 3 in the morning, we have our attending physician call the attending trauma physician to put us on trauma bypass in case we need the blood products," she said. "If we don’t have the type and cross-matched blood available, we activate an [obstetric] hemorrhage protocol in order to obtain O-negative blood in massive quantities until she’s cross-matched."

Ms. Inzano said that the multidisciplinary approach to placenta accreta "has become a smooth operation at our institution, but we never drop our awareness of the severity of what can happen. With the multidisciplinary effort, it brings everyone together; everyone’s on the same page, and everyone knows what to anticipate."

Neither Dr. Ramos nor Ms. Inzano had relevant financial conflicts.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

SAN FRANCISCO – People who live in "walkable" neighborhoods have a 15% lower rate of diabetes, compared with those who live in areas that require reliance on automobile transportation, a large Canadian study found.

"It’s become clear that the way we build and design our cities has an important impact on our health," Dr. Gillian L. Booth said at the annual scientific sessions of the American Diabetes Association. "Neighborhoods that were designed for pedestrian use are more conducive for walking. They tend to be older areas that are more densely populated, have more street connections, and are zoned in a way that retail and other services are embedded within residential areas. That means that there are more walkable destinations."

Sprawling suburban communities, on the other hand, tend to be more sparsely populated, and have fewer connections between streets, "and the zoning is such that retail and other services are separated and far away from where people live, thus increasing one’s reliance on automobiles for transportation," continued Dr. Booth, an endocrinologist and research scientist at St. Michael’s Hospital and the University of Toronto "There’s mounting literature that these types of neighborhood features are associated with lower rates of walking and physical activity and higher levels of obesity. They also lead to more time spent in cars, which in itself has been linked to a higher risk of becoming obese."

Until recently, there have been few prospective studies looking at neighborhood design and the development of diabetes. Limitations to previous studies include the fact that those who prefer to live in one neighborhood over another may differ systematically from those who choose to live in other neighborhoods. To account for this, Dr. Booth and her associates used Inverse Probability of Treatment Weighting to create balanced groups of adults aged 30-64 years living in high- and low-walkability areas.

"We asked the question, are individuals living in more walkable areas at a lower risk of developing diabetes? If this is true, does that still hold after we account for other confounders?" These confounders included age, sex, presence of comorbidities, previous hypertension, stroke, health care use, socioeconomic status, and ethnicity.

The study area consisted of 15 Canadian municipalities, including Toronto, which have a combined population of more than 7 million people. The researchers used anonymous health data from provincial databases of people who were free of diabetes and living in high- or low-walkability neighborhoods in April 2002, and followed them through March 2012 for the development of diabetes. The investigators excluded people with a prior diagnosis of diabetes.

Dr. Booth and her associates identified new cases of diabetes via the Ontario Diabetes Database, an electronic registry based on hospital and physician service claims. The walkability index was based on four features: population density (number of residents per square kilometer); residential density (number of dwellings per square kilometer); street connectivity (number of intersections per square kilometer), and walkable destinations (the number of stores and services within a 10-minute walk).

The study population consisted of 958,567 Canadian residents; their mean age was 49 years and 49% were male. Over the 10-year follow-up period, 90,922 new cases of diabetes were observed, for an incidence rate of 1.03/100 person-years. The researchers observed a 15% lower diabetes incidence among those living in the highest-walkability areas, compared with the lowest-walkability areas, in all study regions (hazard ratio of 0.85). They observed similar findings when they stratified people by income (HR of 0.86 and 0.82 for lower- and higher-income areas, respectively) and immigration status (HR of 0.85 among long-term residents and 0.87 among those who had been Canadian citizens for fewer than 10 years).

She concluded that high neighborhood walkability appears to be protective against the development of diabetes in young and middle-aged urban populations. "This suggests that changes in zoning, urban planning, and design that promote walking and other forms of active transportation may help to curb the ongoing rise in obesity and diabetes," she said. "Further research is needed to understand the full impact that such interventions will have."

The study was funded by the Canadian Institutes of Health Research. Dr. Booth said that she had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN FRANCISCO – People who live in "walkable" neighborhoods have a 15% lower rate of diabetes, compared with those who live in areas that require reliance on automobile transportation, a large Canadian study found.

"It’s become clear that the way we build and design our cities has an important impact on our health," Dr. Gillian L. Booth said at the annual scientific sessions of the American Diabetes Association. "Neighborhoods that were designed for pedestrian use are more conducive for walking. They tend to be older areas that are more densely populated, have more street connections, and are zoned in a way that retail and other services are embedded within residential areas. That means that there are more walkable destinations."

Sprawling suburban communities, on the other hand, tend to be more sparsely populated, and have fewer connections between streets, "and the zoning is such that retail and other services are separated and far away from where people live, thus increasing one’s reliance on automobiles for transportation," continued Dr. Booth, an endocrinologist and research scientist at St. Michael’s Hospital and the University of Toronto "There’s mounting literature that these types of neighborhood features are associated with lower rates of walking and physical activity and higher levels of obesity. They also lead to more time spent in cars, which in itself has been linked to a higher risk of becoming obese."

Until recently, there have been few prospective studies looking at neighborhood design and the development of diabetes. Limitations to previous studies include the fact that those who prefer to live in one neighborhood over another may differ systematically from those who choose to live in other neighborhoods. To account for this, Dr. Booth and her associates used Inverse Probability of Treatment Weighting to create balanced groups of adults aged 30-64 years living in high- and low-walkability areas.

"We asked the question, are individuals living in more walkable areas at a lower risk of developing diabetes? If this is true, does that still hold after we account for other confounders?" These confounders included age, sex, presence of comorbidities, previous hypertension, stroke, health care use, socioeconomic status, and ethnicity.

The study area consisted of 15 Canadian municipalities, including Toronto, which have a combined population of more than 7 million people. The researchers used anonymous health data from provincial databases of people who were free of diabetes and living in high- or low-walkability neighborhoods in April 2002, and followed them through March 2012 for the development of diabetes. The investigators excluded people with a prior diagnosis of diabetes.

Dr. Booth and her associates identified new cases of diabetes via the Ontario Diabetes Database, an electronic registry based on hospital and physician service claims. The walkability index was based on four features: population density (number of residents per square kilometer); residential density (number of dwellings per square kilometer); street connectivity (number of intersections per square kilometer), and walkable destinations (the number of stores and services within a 10-minute walk).

The study population consisted of 958,567 Canadian residents; their mean age was 49 years and 49% were male. Over the 10-year follow-up period, 90,922 new cases of diabetes were observed, for an incidence rate of 1.03/100 person-years. The researchers observed a 15% lower diabetes incidence among those living in the highest-walkability areas, compared with the lowest-walkability areas, in all study regions (hazard ratio of 0.85). They observed similar findings when they stratified people by income (HR of 0.86 and 0.82 for lower- and higher-income areas, respectively) and immigration status (HR of 0.85 among long-term residents and 0.87 among those who had been Canadian citizens for fewer than 10 years).

She concluded that high neighborhood walkability appears to be protective against the development of diabetes in young and middle-aged urban populations. "This suggests that changes in zoning, urban planning, and design that promote walking and other forms of active transportation may help to curb the ongoing rise in obesity and diabetes," she said. "Further research is needed to understand the full impact that such interventions will have."

The study was funded by the Canadian Institutes of Health Research. Dr. Booth said that she had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN FRANCISCO – People who live in "walkable" neighborhoods have a 15% lower rate of diabetes, compared with those who live in areas that require reliance on automobile transportation, a large Canadian study found.

"It’s become clear that the way we build and design our cities has an important impact on our health," Dr. Gillian L. Booth said at the annual scientific sessions of the American Diabetes Association. "Neighborhoods that were designed for pedestrian use are more conducive for walking. They tend to be older areas that are more densely populated, have more street connections, and are zoned in a way that retail and other services are embedded within residential areas. That means that there are more walkable destinations."

Sprawling suburban communities, on the other hand, tend to be more sparsely populated, and have fewer connections between streets, "and the zoning is such that retail and other services are separated and far away from where people live, thus increasing one’s reliance on automobiles for transportation," continued Dr. Booth, an endocrinologist and research scientist at St. Michael’s Hospital and the University of Toronto "There’s mounting literature that these types of neighborhood features are associated with lower rates of walking and physical activity and higher levels of obesity. They also lead to more time spent in cars, which in itself has been linked to a higher risk of becoming obese."

Until recently, there have been few prospective studies looking at neighborhood design and the development of diabetes. Limitations to previous studies include the fact that those who prefer to live in one neighborhood over another may differ systematically from those who choose to live in other neighborhoods. To account for this, Dr. Booth and her associates used Inverse Probability of Treatment Weighting to create balanced groups of adults aged 30-64 years living in high- and low-walkability areas.

"We asked the question, are individuals living in more walkable areas at a lower risk of developing diabetes? If this is true, does that still hold after we account for other confounders?" These confounders included age, sex, presence of comorbidities, previous hypertension, stroke, health care use, socioeconomic status, and ethnicity.

The study area consisted of 15 Canadian municipalities, including Toronto, which have a combined population of more than 7 million people. The researchers used anonymous health data from provincial databases of people who were free of diabetes and living in high- or low-walkability neighborhoods in April 2002, and followed them through March 2012 for the development of diabetes. The investigators excluded people with a prior diagnosis of diabetes.

Dr. Booth and her associates identified new cases of diabetes via the Ontario Diabetes Database, an electronic registry based on hospital and physician service claims. The walkability index was based on four features: population density (number of residents per square kilometer); residential density (number of dwellings per square kilometer); street connectivity (number of intersections per square kilometer), and walkable destinations (the number of stores and services within a 10-minute walk).

The study population consisted of 958,567 Canadian residents; their mean age was 49 years and 49% were male. Over the 10-year follow-up period, 90,922 new cases of diabetes were observed, for an incidence rate of 1.03/100 person-years. The researchers observed a 15% lower diabetes incidence among those living in the highest-walkability areas, compared with the lowest-walkability areas, in all study regions (hazard ratio of 0.85). They observed similar findings when they stratified people by income (HR of 0.86 and 0.82 for lower- and higher-income areas, respectively) and immigration status (HR of 0.85 among long-term residents and 0.87 among those who had been Canadian citizens for fewer than 10 years).

She concluded that high neighborhood walkability appears to be protective against the development of diabetes in young and middle-aged urban populations. "This suggests that changes in zoning, urban planning, and design that promote walking and other forms of active transportation may help to curb the ongoing rise in obesity and diabetes," she said. "Further research is needed to understand the full impact that such interventions will have."

The study was funded by the Canadian Institutes of Health Research. Dr. Booth said that she had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN FRANCISCO – Among patients with implantable cardiac defibrillators and cardiac resynchronization therapy defibrillators, mortality was lower in patients who received only antitachycardia pacing, compared with those who were treated with at least one ICD shock, results from a large database analysis showed.

"Over the past 5 or 10 years, there’s been an association of increasing mortality in people who get ICD shocks," lead author Dr. Adam Strickberger said in an interview at the annual scientific sessions of the Heart Rhythm Society, where the study was presented. "Trying to tease that apart has been hard to do. This study does not give us the mechanism of action for the association, but the message is that avoiding ICD shocks when you can is probably a good thing."

For the study, Dr. Strickberger and his associates evaluated the records of 71,691 patients who were implanted with a St. Jude Medical ICD and CRT-D device during January 2007–May 2012 and monitored on Merlin.net. They used Merlin.net to assess the remote transmission of tachycardia therapy records from January 2007 to November 2012, St. Jude’s device tracking registry to determine patient demographics at time of implant, and Social Security Death Index information to determine survival status as of 2012. Outcomes of interest were effectiveness of antitachycardia pacing (ATP) and mortality. ATP was considered effective if it was not followed by a shock and the patient survived the episode.

The mean age of the patients was 68 years and 73% were male. During a mean follow-up time of 2.5 years, ATP was effective in 89% of the 218,561 episodes delivered in 18,670 patients. In 77% of all ventricular tachycardia/ventricular fibrillation episodes, ATP was the only ICD therapy required.

The researchers also found that patients who received at least one ICD shock had higher mortality, compared with those who received ATP only (hazard ratio, 1.33 vs. 1.20, respectively; P value less than 0.001).

Dr. Strickberger, who is in a group arrhythmia physician practice in Fairfax, Va., acknowledged certain limitations of the study, including the fact that "it was not known what the underlying heart disease was, we don’t know ejection fraction, heart failure status, and we don’t know if the shocks delivered were appropriate or inappropriate."

Dr. Strickberger receives consulting fees from St. Jude Medical. Five of the study’s coauthors are employees of the company.

dbrunk@frontlinemedcom.com

SAN FRANCISCO – Among patients with implantable cardiac defibrillators and cardiac resynchronization therapy defibrillators, mortality was lower in patients who received only antitachycardia pacing, compared with those who were treated with at least one ICD shock, results from a large database analysis showed.

"Over the past 5 or 10 years, there’s been an association of increasing mortality in people who get ICD shocks," lead author Dr. Adam Strickberger said in an interview at the annual scientific sessions of the Heart Rhythm Society, where the study was presented. "Trying to tease that apart has been hard to do. This study does not give us the mechanism of action for the association, but the message is that avoiding ICD shocks when you can is probably a good thing."

For the study, Dr. Strickberger and his associates evaluated the records of 71,691 patients who were implanted with a St. Jude Medical ICD and CRT-D device during January 2007–May 2012 and monitored on Merlin.net. They used Merlin.net to assess the remote transmission of tachycardia therapy records from January 2007 to November 2012, St. Jude’s device tracking registry to determine patient demographics at time of implant, and Social Security Death Index information to determine survival status as of 2012. Outcomes of interest were effectiveness of antitachycardia pacing (ATP) and mortality. ATP was considered effective if it was not followed by a shock and the patient survived the episode.

The mean age of the patients was 68 years and 73% were male. During a mean follow-up time of 2.5 years, ATP was effective in 89% of the 218,561 episodes delivered in 18,670 patients. In 77% of all ventricular tachycardia/ventricular fibrillation episodes, ATP was the only ICD therapy required.

The researchers also found that patients who received at least one ICD shock had higher mortality, compared with those who received ATP only (hazard ratio, 1.33 vs. 1.20, respectively; P value less than 0.001).

Dr. Strickberger, who is in a group arrhythmia physician practice in Fairfax, Va., acknowledged certain limitations of the study, including the fact that "it was not known what the underlying heart disease was, we don’t know ejection fraction, heart failure status, and we don’t know if the shocks delivered were appropriate or inappropriate."

Dr. Strickberger receives consulting fees from St. Jude Medical. Five of the study’s coauthors are employees of the company.

dbrunk@frontlinemedcom.com

SAN FRANCISCO – Among patients with implantable cardiac defibrillators and cardiac resynchronization therapy defibrillators, mortality was lower in patients who received only antitachycardia pacing, compared with those who were treated with at least one ICD shock, results from a large database analysis showed.

"Over the past 5 or 10 years, there’s been an association of increasing mortality in people who get ICD shocks," lead author Dr. Adam Strickberger said in an interview at the annual scientific sessions of the Heart Rhythm Society, where the study was presented. "Trying to tease that apart has been hard to do. This study does not give us the mechanism of action for the association, but the message is that avoiding ICD shocks when you can is probably a good thing."

For the study, Dr. Strickberger and his associates evaluated the records of 71,691 patients who were implanted with a St. Jude Medical ICD and CRT-D device during January 2007–May 2012 and monitored on Merlin.net. They used Merlin.net to assess the remote transmission of tachycardia therapy records from January 2007 to November 2012, St. Jude’s device tracking registry to determine patient demographics at time of implant, and Social Security Death Index information to determine survival status as of 2012. Outcomes of interest were effectiveness of antitachycardia pacing (ATP) and mortality. ATP was considered effective if it was not followed by a shock and the patient survived the episode.

The mean age of the patients was 68 years and 73% were male. During a mean follow-up time of 2.5 years, ATP was effective in 89% of the 218,561 episodes delivered in 18,670 patients. In 77% of all ventricular tachycardia/ventricular fibrillation episodes, ATP was the only ICD therapy required.

The researchers also found that patients who received at least one ICD shock had higher mortality, compared with those who received ATP only (hazard ratio, 1.33 vs. 1.20, respectively; P value less than 0.001).

Dr. Strickberger, who is in a group arrhythmia physician practice in Fairfax, Va., acknowledged certain limitations of the study, including the fact that "it was not known what the underlying heart disease was, we don’t know ejection fraction, heart failure status, and we don’t know if the shocks delivered were appropriate or inappropriate."

Dr. Strickberger receives consulting fees from St. Jude Medical. Five of the study’s coauthors are employees of the company.

dbrunk@frontlinemedcom.com

SAN FRANCISCO – Wireless endocardial left ventricular pacing provides an alternative approach to cardiac resynchronization pacing in heart failure patients, according to preliminary results from an ongoing multicenter trial.

At the annual scientific sessions of the Heart Rhythm Society, Dr. Vivek Y. Reddy presented preliminary results from 19 patients enrolled in the SELECT-LV (Safety and Performance of Electrodes Implanted in the Left Ventricle) study. The purpose of the open-label trial is to evaluate the safety and feasibility of leadless, ultrasound-based pacing using a wireless cardiac stimulation system (WiCS-LV) developed by EBR Systems.

"The idea is to use an existing standard ICD [implantable cardioverter defibrillator] or pacemaker and place this device, which has a transmitter as well as a battery, in a subcutaneous location, and then place a receiver-electrode ‘pellet’ on the left ventricle endocardial wall," explained Dr. Reddy, professor of medicine at Mount Sinai Hospital, New York. "The idea is that the transmitter emits ultrasound impulses detected by the pellet. In turn, the pellet transduces the ultrasound impulse into an electrical pacing pulse to stimulate the heart."

The battery, which is 42 cc in size, is placed subcutaneously in the subaxillary region. The transmitter, which is 13 cc in size, is placed between the ribs "in an optimal position so that there is an echo window which allows you to see the left ventricle," Dr. Reddy said. "Then, on the same day or the next day, the pellet (which is 0.05 cc in size) is placed on the left ventricle via a transfemoral catheter approach."

The SELECT-LV investigators intend to enroll 40 patients at seven centers to evaluate the performance and efficacy of the approach. The primary endpoints are device- and procedure-related complications perioperatively and at 1 month, and biventricular pacing capture on 12-lead ECG at 1 month. Secondary endpoints are device-related or major complications up to 6 months and LV pacing capture at 1, 2, and 6 months, as well as biventricular capture at 6 months on 12-lead ECG. Preliminary efficacy is measured by a composite score of all-cause mortality, heart failure hospitalization, New York Heart Association (NYHA) class, and patient global assessment at 6 months, as well as LV end systolic/diastolic volumes and LV ejection fraction at 6 months.

Patients are eligible for the trial if they have a failed implant of a coronary sinus lead or a chronic issue with their CS lead; if they have no clinical status improvement in 6 months of cardiac resynchronization pacing (CRT); or if they have a previously implanted pacemaker or ICD with a new indication for biventricular pacing but are at risk for a CRT upgrade due to venous occlusion or other factors.

Of the 19 patients who have been implanted to date, 16 (84%) were male, their mean age was 68 years, and they were relatively evenly split between ischemic and nonischemic substrates. Nearly half (47%) had a failed CS lead implant and their mean LV ejection fraction at baseline was 26%.

Primary and secondary endpoint data were available for 15 of the 19 patients, and 6-month data were available for 8 patients. At 1 month, all 15 patients demonstrated Bi-V pacing on 12-lead ECG. The QRS narrowed by 46 ms at 1 month and by 23 ms at 6 months. NYHA class also significantly improved between baseline and 6 months (from II to I; decline of 0.63 points). All patients experienced improvements on their clinical composite score.

No periprocedural adverse events and no device-related serious adverse events occurred within the first month of implant, but 10 serious adverse events occurred in six patients within the first 6 months, including one patient with a hematoma at the transmitter pocket and one patient who had a stroke 3 days after the procedure. "This is a patient who had atrial fibrillation," Dr. Reddy noted. "At the time of the procedure the [warfarin] was stopped. The patient was implanted, did well, but the [warfarin] hadn’t been restarted at the 3-day time point and the patient suffered a stroke. After this experience, we altered the protocol so that patients on anticoagulation for any indication need to continue active coagulation [with no interruption]. We’ll see how that fares."

The study was funded by EBR Systems. Dr. Reddy is a consultant to the company.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

SAN FRANCISCO – Wireless endocardial left ventricular pacing provides an alternative approach to cardiac resynchronization pacing in heart failure patients, according to preliminary results from an ongoing multicenter trial.

At the annual scientific sessions of the Heart Rhythm Society, Dr. Vivek Y. Reddy presented preliminary results from 19 patients enrolled in the SELECT-LV (Safety and Performance of Electrodes Implanted in the Left Ventricle) study. The purpose of the open-label trial is to evaluate the safety and feasibility of leadless, ultrasound-based pacing using a wireless cardiac stimulation system (WiCS-LV) developed by EBR Systems.

"The idea is to use an existing standard ICD [implantable cardioverter defibrillator] or pacemaker and place this device, which has a transmitter as well as a battery, in a subcutaneous location, and then place a receiver-electrode ‘pellet’ on the left ventricle endocardial wall," explained Dr. Reddy, professor of medicine at Mount Sinai Hospital, New York. "The idea is that the transmitter emits ultrasound impulses detected by the pellet. In turn, the pellet transduces the ultrasound impulse into an electrical pacing pulse to stimulate the heart."

The battery, which is 42 cc in size, is placed subcutaneously in the subaxillary region. The transmitter, which is 13 cc in size, is placed between the ribs "in an optimal position so that there is an echo window which allows you to see the left ventricle," Dr. Reddy said. "Then, on the same day or the next day, the pellet (which is 0.05 cc in size) is placed on the left ventricle via a transfemoral catheter approach."

The SELECT-LV investigators intend to enroll 40 patients at seven centers to evaluate the performance and efficacy of the approach. The primary endpoints are device- and procedure-related complications perioperatively and at 1 month, and biventricular pacing capture on 12-lead ECG at 1 month. Secondary endpoints are device-related or major complications up to 6 months and LV pacing capture at 1, 2, and 6 months, as well as biventricular capture at 6 months on 12-lead ECG. Preliminary efficacy is measured by a composite score of all-cause mortality, heart failure hospitalization, New York Heart Association (NYHA) class, and patient global assessment at 6 months, as well as LV end systolic/diastolic volumes and LV ejection fraction at 6 months.

Patients are eligible for the trial if they have a failed implant of a coronary sinus lead or a chronic issue with their CS lead; if they have no clinical status improvement in 6 months of cardiac resynchronization pacing (CRT); or if they have a previously implanted pacemaker or ICD with a new indication for biventricular pacing but are at risk for a CRT upgrade due to venous occlusion or other factors.

Of the 19 patients who have been implanted to date, 16 (84%) were male, their mean age was 68 years, and they were relatively evenly split between ischemic and nonischemic substrates. Nearly half (47%) had a failed CS lead implant and their mean LV ejection fraction at baseline was 26%.

Primary and secondary endpoint data were available for 15 of the 19 patients, and 6-month data were available for 8 patients. At 1 month, all 15 patients demonstrated Bi-V pacing on 12-lead ECG. The QRS narrowed by 46 ms at 1 month and by 23 ms at 6 months. NYHA class also significantly improved between baseline and 6 months (from II to I; decline of 0.63 points). All patients experienced improvements on their clinical composite score.

No periprocedural adverse events and no device-related serious adverse events occurred within the first month of implant, but 10 serious adverse events occurred in six patients within the first 6 months, including one patient with a hematoma at the transmitter pocket and one patient who had a stroke 3 days after the procedure. "This is a patient who had atrial fibrillation," Dr. Reddy noted. "At the time of the procedure the [warfarin] was stopped. The patient was implanted, did well, but the [warfarin] hadn’t been restarted at the 3-day time point and the patient suffered a stroke. After this experience, we altered the protocol so that patients on anticoagulation for any indication need to continue active coagulation [with no interruption]. We’ll see how that fares."

The study was funded by EBR Systems. Dr. Reddy is a consultant to the company.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

SAN FRANCISCO – Wireless endocardial left ventricular pacing provides an alternative approach to cardiac resynchronization pacing in heart failure patients, according to preliminary results from an ongoing multicenter trial.

At the annual scientific sessions of the Heart Rhythm Society, Dr. Vivek Y. Reddy presented preliminary results from 19 patients enrolled in the SELECT-LV (Safety and Performance of Electrodes Implanted in the Left Ventricle) study. The purpose of the open-label trial is to evaluate the safety and feasibility of leadless, ultrasound-based pacing using a wireless cardiac stimulation system (WiCS-LV) developed by EBR Systems.

"The idea is to use an existing standard ICD [implantable cardioverter defibrillator] or pacemaker and place this device, which has a transmitter as well as a battery, in a subcutaneous location, and then place a receiver-electrode ‘pellet’ on the left ventricle endocardial wall," explained Dr. Reddy, professor of medicine at Mount Sinai Hospital, New York. "The idea is that the transmitter emits ultrasound impulses detected by the pellet. In turn, the pellet transduces the ultrasound impulse into an electrical pacing pulse to stimulate the heart."

The battery, which is 42 cc in size, is placed subcutaneously in the subaxillary region. The transmitter, which is 13 cc in size, is placed between the ribs "in an optimal position so that there is an echo window which allows you to see the left ventricle," Dr. Reddy said. "Then, on the same day or the next day, the pellet (which is 0.05 cc in size) is placed on the left ventricle via a transfemoral catheter approach."

The SELECT-LV investigators intend to enroll 40 patients at seven centers to evaluate the performance and efficacy of the approach. The primary endpoints are device- and procedure-related complications perioperatively and at 1 month, and biventricular pacing capture on 12-lead ECG at 1 month. Secondary endpoints are device-related or major complications up to 6 months and LV pacing capture at 1, 2, and 6 months, as well as biventricular capture at 6 months on 12-lead ECG. Preliminary efficacy is measured by a composite score of all-cause mortality, heart failure hospitalization, New York Heart Association (NYHA) class, and patient global assessment at 6 months, as well as LV end systolic/diastolic volumes and LV ejection fraction at 6 months.

Patients are eligible for the trial if they have a failed implant of a coronary sinus lead or a chronic issue with their CS lead; if they have no clinical status improvement in 6 months of cardiac resynchronization pacing (CRT); or if they have a previously implanted pacemaker or ICD with a new indication for biventricular pacing but are at risk for a CRT upgrade due to venous occlusion or other factors.

Of the 19 patients who have been implanted to date, 16 (84%) were male, their mean age was 68 years, and they were relatively evenly split between ischemic and nonischemic substrates. Nearly half (47%) had a failed CS lead implant and their mean LV ejection fraction at baseline was 26%.

Primary and secondary endpoint data were available for 15 of the 19 patients, and 6-month data were available for 8 patients. At 1 month, all 15 patients demonstrated Bi-V pacing on 12-lead ECG. The QRS narrowed by 46 ms at 1 month and by 23 ms at 6 months. NYHA class also significantly improved between baseline and 6 months (from II to I; decline of 0.63 points). All patients experienced improvements on their clinical composite score.

No periprocedural adverse events and no device-related serious adverse events occurred within the first month of implant, but 10 serious adverse events occurred in six patients within the first 6 months, including one patient with a hematoma at the transmitter pocket and one patient who had a stroke 3 days after the procedure. "This is a patient who had atrial fibrillation," Dr. Reddy noted. "At the time of the procedure the [warfarin] was stopped. The patient was implanted, did well, but the [warfarin] hadn’t been restarted at the 3-day time point and the patient suffered a stroke. After this experience, we altered the protocol so that patients on anticoagulation for any indication need to continue active coagulation [with no interruption]. We’ll see how that fares."

The study was funded by EBR Systems. Dr. Reddy is a consultant to the company.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

SAN FRANCISCO – The investigative liver-selective glucokinase activator TTP399 lowered glucose and did not increase lipids in subjects with type 2 diabetes, results from a randomized study demonstrated.

"The compound was extremely well tolerated," Carmen Valcarce, Ph.D., said at the annual scientific sessions of the American Diabetes Association.

Results were presented from a phase Ib/IIa double-blind, 6-week, multiple-dose trial studying TTP399 in 120 type 2 diabetes patients on stable doses of metformin. Three doses were tested: 400 mg twice daily, 800 mg once daily, and 800 mg twice daily, plus a placebo group. The major objective was to assess the safety and tolerability of TTP399 and to evaluate its pharmacodynamics and pharmacokinetics.

The mean age of study participants was 57 years, their mean body mass index was 31.4 kg/m², their mean HbA_1c was 8.2%, and their mean duration of diabetes was about 7 years.

Dr. Valcarce, TransTech Pharma’s senior vice president and scientific liaison, reported that the most frequent adverse event was headache, followed by dizziness and diarrhea. There was only one case of symptomatic hypoglycemia, which occurred in the placebo group. There were no increases in fasting triglycerides, cholesterol, lactate, insulin, or C-peptide.

The researchers observed decreases in the mean daily glucose profile in all treatment groups. In well-controlled subjects (defined as those with a baseline hemoglobin A_1c of 7.5% or lower), 85% of those in the 800-mg twice-daily arm and 40% of those receiving any dose of TTP399 achieved normalization. None of the placebo-treated subjects reached an HbA_1c of 6.5% or less.

"The clinical results to date are completely consistent with preclinical data and with the mechanism of action of liver-selective glucokinase activators," Dr. Valcarce said.

The study was funded and conducted by Forest Laboratories under a license agreement with TransTech Pharma, which is now continuing the development of TTP399 and will soon begin a 6-month phase IIb study. Dr. Valcarce is an employee of TransTech.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

SAN FRANCISCO – The investigative liver-selective glucokinase activator TTP399 lowered glucose and did not increase lipids in subjects with type 2 diabetes, results from a randomized study demonstrated.

"The compound was extremely well tolerated," Carmen Valcarce, Ph.D., said at the annual scientific sessions of the American Diabetes Association.

Results were presented from a phase Ib/IIa double-blind, 6-week, multiple-dose trial studying TTP399 in 120 type 2 diabetes patients on stable doses of metformin. Three doses were tested: 400 mg twice daily, 800 mg once daily, and 800 mg twice daily, plus a placebo group. The major objective was to assess the safety and tolerability of TTP399 and to evaluate its pharmacodynamics and pharmacokinetics.

The mean age of study participants was 57 years, their mean body mass index was 31.4 kg/m², their mean HbA_1c was 8.2%, and their mean duration of diabetes was about 7 years.

Dr. Valcarce, TransTech Pharma’s senior vice president and scientific liaison, reported that the most frequent adverse event was headache, followed by dizziness and diarrhea. There was only one case of symptomatic hypoglycemia, which occurred in the placebo group. There were no increases in fasting triglycerides, cholesterol, lactate, insulin, or C-peptide.

The researchers observed decreases in the mean daily glucose profile in all treatment groups. In well-controlled subjects (defined as those with a baseline hemoglobin A_1c of 7.5% or lower), 85% of those in the 800-mg twice-daily arm and 40% of those receiving any dose of TTP399 achieved normalization. None of the placebo-treated subjects reached an HbA_1c of 6.5% or less.

"The clinical results to date are completely consistent with preclinical data and with the mechanism of action of liver-selective glucokinase activators," Dr. Valcarce said.

The study was funded and conducted by Forest Laboratories under a license agreement with TransTech Pharma, which is now continuing the development of TTP399 and will soon begin a 6-month phase IIb study. Dr. Valcarce is an employee of TransTech.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

SAN FRANCISCO – The investigative liver-selective glucokinase activator TTP399 lowered glucose and did not increase lipids in subjects with type 2 diabetes, results from a randomized study demonstrated.

"The compound was extremely well tolerated," Carmen Valcarce, Ph.D., said at the annual scientific sessions of the American Diabetes Association.

Results were presented from a phase Ib/IIa double-blind, 6-week, multiple-dose trial studying TTP399 in 120 type 2 diabetes patients on stable doses of metformin. Three doses were tested: 400 mg twice daily, 800 mg once daily, and 800 mg twice daily, plus a placebo group. The major objective was to assess the safety and tolerability of TTP399 and to evaluate its pharmacodynamics and pharmacokinetics.

The mean age of study participants was 57 years, their mean body mass index was 31.4 kg/m², their mean HbA_1c was 8.2%, and their mean duration of diabetes was about 7 years.

Dr. Valcarce, TransTech Pharma’s senior vice president and scientific liaison, reported that the most frequent adverse event was headache, followed by dizziness and diarrhea. There was only one case of symptomatic hypoglycemia, which occurred in the placebo group. There were no increases in fasting triglycerides, cholesterol, lactate, insulin, or C-peptide.

The researchers observed decreases in the mean daily glucose profile in all treatment groups. In well-controlled subjects (defined as those with a baseline hemoglobin A_1c of 7.5% or lower), 85% of those in the 800-mg twice-daily arm and 40% of those receiving any dose of TTP399 achieved normalization. None of the placebo-treated subjects reached an HbA_1c of 6.5% or less.

"The clinical results to date are completely consistent with preclinical data and with the mechanism of action of liver-selective glucokinase activators," Dr. Valcarce said.

The study was funded and conducted by Forest Laboratories under a license agreement with TransTech Pharma, which is now continuing the development of TTP399 and will soon begin a 6-month phase IIb study. Dr. Valcarce is an employee of TransTech.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

SAN FRANCISCO – Among diabetes patients, the risk of cancer was significantly increased before diagnosis and 3 months after diabetes diagnosis, but not beyond that time point, results from a population-based study showed.

"Previous studies have focused on the risk of cancer following diabetes diagnosis or else compared risk of cancer between the pre- and postdiabetes period without taking into account the time period immediately following the diagnosis of diabetes," lead investigator Dr. Iliana C. Lega said in an interview prior to the annual scientific sessions of the American Diabetes Association, where the research was presented.

"We found that risk of cancer was highest in the prediabetes period and in the first 3 months following diabetes diagnosis, suggesting a role for hyperinsulinemia in the pathogenesis of cancer in the diabetes population. Furthermore, increased detection of preexisting cancers in the period following diabetes diagnosis may also contribute to the observed elevated risk of cancer," she said.

Dr. Lega, a clinician scientist with the division of endocrinology and metabolism at the University of Toronto, and her associates used population-based data from Ontario during 1997-2009 to identify incident diabetic cohorts that were matched 1:1 by age and gender to patients without diabetes. The researchers used time-varying Cox regression models to compare the relative risk of any invasive cancer between patients with and without diabetes in three separate time frames: 10 years prior to diagnosis, 3 months after diagnosis, and more than 3 months after diabetes diagnosis.

Dr. Lega and her associates evaluated cancer risk before diabetes diagnosis in 186,441 diabetes patients and matched controls and after diabetes in 51,463 diabetes patients and matched controls. Among diabetes patients, the risk of cancer was significantly increased before diabetes diagnosis (hazard ratio, 1.23) and 3 months after diabetes diagnosis (HR, 1.69), but the association abated beyond 3 months after diabetes diagnosis.

The findings "support a role for hyperinsulinemia in the relationship between diabetes and cancer, over surveillance bias," the researchers concluded in their abstract. "While further research is needed, these results support enhanced cancer screening in patients with diagnoses of prediabetes or diabetes."

Dr. Lega acknowledged certain limitations of the study, including the fact that other risk factors for cancer such as clinical features, smoking history, chronic alcoholism, and family history could not be taken into account.

Dr. Lega said that she had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk 

SAN FRANCISCO – Among diabetes patients, the risk of cancer was significantly increased before diagnosis and 3 months after diabetes diagnosis, but not beyond that time point, results from a population-based study showed.

"Previous studies have focused on the risk of cancer following diabetes diagnosis or else compared risk of cancer between the pre- and postdiabetes period without taking into account the time period immediately following the diagnosis of diabetes," lead investigator Dr. Iliana C. Lega said in an interview prior to the annual scientific sessions of the American Diabetes Association, where the research was presented.

"We found that risk of cancer was highest in the prediabetes period and in the first 3 months following diabetes diagnosis, suggesting a role for hyperinsulinemia in the pathogenesis of cancer in the diabetes population. Furthermore, increased detection of preexisting cancers in the period following diabetes diagnosis may also contribute to the observed elevated risk of cancer," she said.

Dr. Lega, a clinician scientist with the division of endocrinology and metabolism at the University of Toronto, and her associates used population-based data from Ontario during 1997-2009 to identify incident diabetic cohorts that were matched 1:1 by age and gender to patients without diabetes. The researchers used time-varying Cox regression models to compare the relative risk of any invasive cancer between patients with and without diabetes in three separate time frames: 10 years prior to diagnosis, 3 months after diagnosis, and more than 3 months after diabetes diagnosis.

Dr. Lega and her associates evaluated cancer risk before diabetes diagnosis in 186,441 diabetes patients and matched controls and after diabetes in 51,463 diabetes patients and matched controls. Among diabetes patients, the risk of cancer was significantly increased before diabetes diagnosis (hazard ratio, 1.23) and 3 months after diabetes diagnosis (HR, 1.69), but the association abated beyond 3 months after diabetes diagnosis.

The findings "support a role for hyperinsulinemia in the relationship between diabetes and cancer, over surveillance bias," the researchers concluded in their abstract. "While further research is needed, these results support enhanced cancer screening in patients with diagnoses of prediabetes or diabetes."

Dr. Lega acknowledged certain limitations of the study, including the fact that other risk factors for cancer such as clinical features, smoking history, chronic alcoholism, and family history could not be taken into account.

Dr. Lega said that she had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk 

SAN FRANCISCO – Among diabetes patients, the risk of cancer was significantly increased before diagnosis and 3 months after diabetes diagnosis, but not beyond that time point, results from a population-based study showed.

"Previous studies have focused on the risk of cancer following diabetes diagnosis or else compared risk of cancer between the pre- and postdiabetes period without taking into account the time period immediately following the diagnosis of diabetes," lead investigator Dr. Iliana C. Lega said in an interview prior to the annual scientific sessions of the American Diabetes Association, where the research was presented.

"We found that risk of cancer was highest in the prediabetes period and in the first 3 months following diabetes diagnosis, suggesting a role for hyperinsulinemia in the pathogenesis of cancer in the diabetes population. Furthermore, increased detection of preexisting cancers in the period following diabetes diagnosis may also contribute to the observed elevated risk of cancer," she said.

Dr. Lega, a clinician scientist with the division of endocrinology and metabolism at the University of Toronto, and her associates used population-based data from Ontario during 1997-2009 to identify incident diabetic cohorts that were matched 1:1 by age and gender to patients without diabetes. The researchers used time-varying Cox regression models to compare the relative risk of any invasive cancer between patients with and without diabetes in three separate time frames: 10 years prior to diagnosis, 3 months after diagnosis, and more than 3 months after diabetes diagnosis.

Dr. Lega and her associates evaluated cancer risk before diabetes diagnosis in 186,441 diabetes patients and matched controls and after diabetes in 51,463 diabetes patients and matched controls. Among diabetes patients, the risk of cancer was significantly increased before diabetes diagnosis (hazard ratio, 1.23) and 3 months after diabetes diagnosis (HR, 1.69), but the association abated beyond 3 months after diabetes diagnosis.

The findings "support a role for hyperinsulinemia in the relationship between diabetes and cancer, over surveillance bias," the researchers concluded in their abstract. "While further research is needed, these results support enhanced cancer screening in patients with diagnoses of prediabetes or diabetes."

Dr. Lega acknowledged certain limitations of the study, including the fact that other risk factors for cancer such as clinical features, smoking history, chronic alcoholism, and family history could not be taken into account.

Dr. Lega said that she had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk 

SAN FRANCISCO – Imeglimin, the first in a new tetrahydrotriazine-containing class of oral glucose–lowering agents, markedly increased glucose-dependent insulin sensitivity and improved beta-cell function, a small randomized trial showed.

The agent, developed by Lyon, France–based Poxel, is currently in phase IIb development in the United States and Europe, regulates mitochondrial bioenergetics, and targets the liver, muscle, and pancreas, Dr. Michael Roden said at the annual scientific sessions of the American Diabetes Association. Imeglimin "has been shown to improve liver and muscle insulin sensitivity, and it is also efficient in untreated, metformin- or sitagliptin-treated type 2 diabetes without safety concerns," said Dr. Roden, director of the German Diabetes Center, Düsseldorf.

The aim of the current study was to examine the subacute effect of imeglimin on glucose-stimulated insulin secretion (GSIS) in vivo during hyperglycemic glucose clamp tests. The researchers enrolled 30 patients with type 2 diabetes who were either drug naive or on previous metformin monotherapy for at least 12 weeks. Their mean age was 61 years, their mean body mass index was 29.7 kg/m², and "they were reasonably well controlled at baseline, with a hemoglobin A_1c of 6.5%-7.5% at the first screening visit," Dr. Roden said.

After a 2-week metformin wash-out period, he and his associates compared imeglimin 1,500 mg twice daily for 1 week with placebo. A 90-minute hyperglycemic clamp was performed with administration of arginine at 45 minutes to assess the maximal response. The primary endpoint of the study was insulin secretion assessed by total insulin response given as the incremental area under the curve from 0 to 45 minutes as well as insulin secretion rate (ISR) calculated from C-peptide deconvolution. First-phase insulin sensitivity was defined as that which occurred in the first 8 minutes of administration while second-phase insulin sensitivity was defined as that which occurred after 25-45 minutes of administration.

Beta-cell glucose sensitivity was measured as the ratio of incremental ISR at steady state to mean incremental glucose levels during the same period, hepatic insulin extraction was measured by mathematical modeling from insulin and C-peptide concentrations, and insulin clearance was measured as a ratio of second-phase ISR and the corresponding area under the curve of insulin concentrations.

Dr. Roden reported that in drug-naive or metformin-treated patients with type 2 diabetes, imeglimin treatment for 7 days raised insulin response to glucose by 112% (P = .03), increased first-phase ISR by 110% (P = .034), increased second-phase ISR by 30% (P = .031), and improved beta-cell glucose sensitivity by 36% (P = .034). It also tended to decrease hepatic insulin extraction. "Imeglimin improves beta-cell function in humans, which may explain its glucose-lowering effect in longer-lasting trials," he said.

Poxel supported the study. Two of the study authors are employed by the company. Dr. Roden disclosed that he serves on advisory boards for Poxel.

dbrunk@frontlinemedcom.com

SAN FRANCISCO – Imeglimin, the first in a new tetrahydrotriazine-containing class of oral glucose–lowering agents, markedly increased glucose-dependent insulin sensitivity and improved beta-cell function, a small randomized trial showed.

The agent, developed by Lyon, France–based Poxel, is currently in phase IIb development in the United States and Europe, regulates mitochondrial bioenergetics, and targets the liver, muscle, and pancreas, Dr. Michael Roden said at the annual scientific sessions of the American Diabetes Association. Imeglimin "has been shown to improve liver and muscle insulin sensitivity, and it is also efficient in untreated, metformin- or sitagliptin-treated type 2 diabetes without safety concerns," said Dr. Roden, director of the German Diabetes Center, Düsseldorf.

The aim of the current study was to examine the subacute effect of imeglimin on glucose-stimulated insulin secretion (GSIS) in vivo during hyperglycemic glucose clamp tests. The researchers enrolled 30 patients with type 2 diabetes who were either drug naive or on previous metformin monotherapy for at least 12 weeks. Their mean age was 61 years, their mean body mass index was 29.7 kg/m², and "they were reasonably well controlled at baseline, with a hemoglobin A_1c of 6.5%-7.5% at the first screening visit," Dr. Roden said.

After a 2-week metformin wash-out period, he and his associates compared imeglimin 1,500 mg twice daily for 1 week with placebo. A 90-minute hyperglycemic clamp was performed with administration of arginine at 45 minutes to assess the maximal response. The primary endpoint of the study was insulin secretion assessed by total insulin response given as the incremental area under the curve from 0 to 45 minutes as well as insulin secretion rate (ISR) calculated from C-peptide deconvolution. First-phase insulin sensitivity was defined as that which occurred in the first 8 minutes of administration while second-phase insulin sensitivity was defined as that which occurred after 25-45 minutes of administration.

Beta-cell glucose sensitivity was measured as the ratio of incremental ISR at steady state to mean incremental glucose levels during the same period, hepatic insulin extraction was measured by mathematical modeling from insulin and C-peptide concentrations, and insulin clearance was measured as a ratio of second-phase ISR and the corresponding area under the curve of insulin concentrations.

Dr. Roden reported that in drug-naive or metformin-treated patients with type 2 diabetes, imeglimin treatment for 7 days raised insulin response to glucose by 112% (P = .03), increased first-phase ISR by 110% (P = .034), increased second-phase ISR by 30% (P = .031), and improved beta-cell glucose sensitivity by 36% (P = .034). It also tended to decrease hepatic insulin extraction. "Imeglimin improves beta-cell function in humans, which may explain its glucose-lowering effect in longer-lasting trials," he said.

Poxel supported the study. Two of the study authors are employed by the company. Dr. Roden disclosed that he serves on advisory boards for Poxel.

dbrunk@frontlinemedcom.com

SAN FRANCISCO – Imeglimin, the first in a new tetrahydrotriazine-containing class of oral glucose–lowering agents, markedly increased glucose-dependent insulin sensitivity and improved beta-cell function, a small randomized trial showed.

The agent, developed by Lyon, France–based Poxel, is currently in phase IIb development in the United States and Europe, regulates mitochondrial bioenergetics, and targets the liver, muscle, and pancreas, Dr. Michael Roden said at the annual scientific sessions of the American Diabetes Association. Imeglimin "has been shown to improve liver and muscle insulin sensitivity, and it is also efficient in untreated, metformin- or sitagliptin-treated type 2 diabetes without safety concerns," said Dr. Roden, director of the German Diabetes Center, Düsseldorf.

The aim of the current study was to examine the subacute effect of imeglimin on glucose-stimulated insulin secretion (GSIS) in vivo during hyperglycemic glucose clamp tests. The researchers enrolled 30 patients with type 2 diabetes who were either drug naive or on previous metformin monotherapy for at least 12 weeks. Their mean age was 61 years, their mean body mass index was 29.7 kg/m², and "they were reasonably well controlled at baseline, with a hemoglobin A_1c of 6.5%-7.5% at the first screening visit," Dr. Roden said.

After a 2-week metformin wash-out period, he and his associates compared imeglimin 1,500 mg twice daily for 1 week with placebo. A 90-minute hyperglycemic clamp was performed with administration of arginine at 45 minutes to assess the maximal response. The primary endpoint of the study was insulin secretion assessed by total insulin response given as the incremental area under the curve from 0 to 45 minutes as well as insulin secretion rate (ISR) calculated from C-peptide deconvolution. First-phase insulin sensitivity was defined as that which occurred in the first 8 minutes of administration while second-phase insulin sensitivity was defined as that which occurred after 25-45 minutes of administration.

Beta-cell glucose sensitivity was measured as the ratio of incremental ISR at steady state to mean incremental glucose levels during the same period, hepatic insulin extraction was measured by mathematical modeling from insulin and C-peptide concentrations, and insulin clearance was measured as a ratio of second-phase ISR and the corresponding area under the curve of insulin concentrations.

Dr. Roden reported that in drug-naive or metformin-treated patients with type 2 diabetes, imeglimin treatment for 7 days raised insulin response to glucose by 112% (P = .03), increased first-phase ISR by 110% (P = .034), increased second-phase ISR by 30% (P = .031), and improved beta-cell glucose sensitivity by 36% (P = .034). It also tended to decrease hepatic insulin extraction. "Imeglimin improves beta-cell function in humans, which may explain its glucose-lowering effect in longer-lasting trials," he said.

Poxel supported the study. Two of the study authors are employed by the company. Dr. Roden disclosed that he serves on advisory boards for Poxel.

dbrunk@frontlinemedcom.com

The absolute 20-year survival benefit from contralateral prophylactic mastectomy stands at less than 1%, regardless of age, estrogen receptor status, and cancer stage, a decision analysis demonstrated.

"Long-term survival in women with unilateral breast cancer treated with or without CPM depends upon several factors, including mortality of the primary breast cancer, risk of CBC [contralateral breast cancer], stage and mortality of the CBC, and the individual patient’s overall life expectancy," wrote Dr. Pamela R. Portschy of the University of Minnesota, Minneapolis.

The report was published July 16 in the Journal of the National Cancer Institute.

"Prospective randomized trials comparing CPM with no CPM are not feasible. Retrospective studies evaluating a potential survival benefit with CPM are limited by short follow-up, potential selection bias, and lack of important clinical information," noted Dr. Portschy and her associates.

They limited their analysis to women with stage I and II breast cancer without BRCA mutations. They developed a Markov model to simulate survival outcomes among those who did and did not have contralateral prophylactic mastectomy (CPM), and they used published studies to estimate probabilities for developing CBC, dying from CBC, dying from primary breast cancer, and age-specific mortality rates. Data were extracted from numerous sources including Surveillance, Epidemiology, and End Results (SEER), the Early Breast Cancer Trialists’ Collaborative Group, and the Oregon State Cancer Registry.

The researchers estimated the 20-year overall survival and life expectancy, but not quality of life or cost, and their analysis considered variation in age, estrogen receptor status, and cancer stage (J. Natl. Cancer Inst. 2014 July 16 [doi:10.1093/jnci/dju160]).

The predicted life expectancy gain from CPM ranged from .13 to .59 years for women with stage I breast cancer, and .08 to .29 years for those with stage II breast cancer. CPM conferred a life expectancy benefit among younger women and among those who had stage I and estrogen receptor–positive disease. "The potential benefit of CPM was consistently lower for patients with stage II breast cancer because of the worse prognosis associated with the primary breast cancer," the researchers wrote. "Similarly, the potential benefits of CPM are more modest for older women because they have relatively fewer years remaining of [life expectancy]."

Dr. Portschy and her associates could not identify any cohort of women that had a greater than 1% absolute survival difference at 20 years. In fact, the predicted 20-year survival differences ranged from .56 to .94% for women with stage I breast cancer and .36 to .61% for those with stage II breast cancer.

The researchers acknowledged limitations of the study, including the fact that the results "do not apply to BRCA gene mutation carriers with unilateral breast cancer who have a cumulative 10-year risk of CBC of approximately 30% to 40%," they wrote. "The outcomes of this analysis were limited to overall and disease-specific survival; we did not evaluate other important outcomes such as surgical complications and quality of life. Also, we assumed the mortality of CBC was the same as the mortality of the index cancer reported by SEER."

They also noted that survival is not the only potential benefit of a cancer risk reduction strategy. "Effects on cancer-related anxiety, cosmesis, and self-image are also important in the decision-making process," they wrote. "For some women, the negative impact of CPM on quality of life may outweigh a potential survival benefit. For others who are very anxious about CBC, CPM may result in a psychological benefit even if survival benefits are minimal."

They concluded that the survival estimates from their Markov model "may be useful for physicians and breast cancer patients to arrive at evidence-based informed decisions regarding CPM. Moreover, the use of accurate and easily understood decision aids may reverse some of the mastectomy trends recently observed in the United States."

The researchers stated that they had no relevant financial conflicts to disclose.

View on the news: Some patients may still benefit from the procedure >>

View on the news: Some patients may still benefit from the procedure

The decision of whether or not to undergo a contralateral prophylactic mastectomy after being treated for breast cancer is a difficult one for many women. The goal of such aggressive therapy is to lower the likelihood of a second primary carcinoma. The downsides are operative risk, impairment of the woman’s self-image, and short-term and long-term morbidities.

This is a well done analysis from an experienced group of investigators and is based on the currently available data. Given the JNCI audience, we shall refrain from niggling points about modeling. Rather, we will stick to the big picture and clinical implications. Although the survival benefit from CPM is small as demonstrated in this model, it is greater than zero, which suggests that for some patients even that small gain may be enough to make it a not unreasonable choice.

From a societal perspective, which was not addressed by Portschy et al., the associated costs of CPM, including the procedure, its complications, reconstruction, and perhaps psychotherapy, may outweigh the modest benefit CPM provides. The small denominator of the cost-effectiveness ratio, were one to be calculated, would imply that the ratio would be very high, making CPM a suboptimal use of health care dollars. Further, we suspect that adding quality of life to the analysis would diminish the benefit and well might turn it into a net harm, in particular for patients with high concern for negative impact of CPM on cosmesis, self image, and morbidity. However, in a fraction of patients who are very troubled by a 0.7% risk of a second, contralateral cancer, CPM might provide an acceptable benefit. The balance between harm and benefit depends on the patient’s preferences and highlights the importance of capturing the patient’s values and expectations before considering CPM.

Of course, these conclusions are based on analysis of women who are at average risk for a contralateral second primary. In women at substantially higher risk (based either on family history or genetics), the benefit of CPM might be far greater, and CPM might be a good choice for the patient or for society.

Dr. Stephen G. Pauker and Dr. Mohamed Alseiari are with the division of clinical decision making in the department of medicine at Tufts Medical Center, Boston. They reported no relevant financial conflicts. This was excerpted from an editorial (J. Natl. Cancer Inst. 2014 July 16 [doi:10.1093/jnci/dju175]).

The absolute 20-year survival benefit from contralateral prophylactic mastectomy stands at less than 1%, regardless of age, estrogen receptor status, and cancer stage, a decision analysis demonstrated.

"Long-term survival in women with unilateral breast cancer treated with or without CPM depends upon several factors, including mortality of the primary breast cancer, risk of CBC [contralateral breast cancer], stage and mortality of the CBC, and the individual patient’s overall life expectancy," wrote Dr. Pamela R. Portschy of the University of Minnesota, Minneapolis.

The report was published July 16 in the Journal of the National Cancer Institute.

"Prospective randomized trials comparing CPM with no CPM are not feasible. Retrospective studies evaluating a potential survival benefit with CPM are limited by short follow-up, potential selection bias, and lack of important clinical information," noted Dr. Portschy and her associates.

They limited their analysis to women with stage I and II breast cancer without BRCA mutations. They developed a Markov model to simulate survival outcomes among those who did and did not have contralateral prophylactic mastectomy (CPM), and they used published studies to estimate probabilities for developing CBC, dying from CBC, dying from primary breast cancer, and age-specific mortality rates. Data were extracted from numerous sources including Surveillance, Epidemiology, and End Results (SEER), the Early Breast Cancer Trialists’ Collaborative Group, and the Oregon State Cancer Registry.

The researchers estimated the 20-year overall survival and life expectancy, but not quality of life or cost, and their analysis considered variation in age, estrogen receptor status, and cancer stage (J. Natl. Cancer Inst. 2014 July 16 [doi:10.1093/jnci/dju160]).

The predicted life expectancy gain from CPM ranged from .13 to .59 years for women with stage I breast cancer, and .08 to .29 years for those with stage II breast cancer. CPM conferred a life expectancy benefit among younger women and among those who had stage I and estrogen receptor–positive disease. "The potential benefit of CPM was consistently lower for patients with stage II breast cancer because of the worse prognosis associated with the primary breast cancer," the researchers wrote. "Similarly, the potential benefits of CPM are more modest for older women because they have relatively fewer years remaining of [life expectancy]."

Dr. Portschy and her associates could not identify any cohort of women that had a greater than 1% absolute survival difference at 20 years. In fact, the predicted 20-year survival differences ranged from .56 to .94% for women with stage I breast cancer and .36 to .61% for those with stage II breast cancer.

The researchers acknowledged limitations of the study, including the fact that the results "do not apply to BRCA gene mutation carriers with unilateral breast cancer who have a cumulative 10-year risk of CBC of approximately 30% to 40%," they wrote. "The outcomes of this analysis were limited to overall and disease-specific survival; we did not evaluate other important outcomes such as surgical complications and quality of life. Also, we assumed the mortality of CBC was the same as the mortality of the index cancer reported by SEER."

They also noted that survival is not the only potential benefit of a cancer risk reduction strategy. "Effects on cancer-related anxiety, cosmesis, and self-image are also important in the decision-making process," they wrote. "For some women, the negative impact of CPM on quality of life may outweigh a potential survival benefit. For others who are very anxious about CBC, CPM may result in a psychological benefit even if survival benefits are minimal."

They concluded that the survival estimates from their Markov model "may be useful for physicians and breast cancer patients to arrive at evidence-based informed decisions regarding CPM. Moreover, the use of accurate and easily understood decision aids may reverse some of the mastectomy trends recently observed in the United States."

The researchers stated that they had no relevant financial conflicts to disclose.

View on the news: Some patients may still benefit from the procedure >>

View on the news: Some patients may still benefit from the procedure

The decision of whether or not to undergo a contralateral prophylactic mastectomy after being treated for breast cancer is a difficult one for many women. The goal of such aggressive therapy is to lower the likelihood of a second primary carcinoma. The downsides are operative risk, impairment of the woman’s self-image, and short-term and long-term morbidities.

This is a well done analysis from an experienced group of investigators and is based on the currently available data. Given the JNCI audience, we shall refrain from niggling points about modeling. Rather, we will stick to the big picture and clinical implications. Although the survival benefit from CPM is small as demonstrated in this model, it is greater than zero, which suggests that for some patients even that small gain may be enough to make it a not unreasonable choice.

From a societal perspective, which was not addressed by Portschy et al., the associated costs of CPM, including the procedure, its complications, reconstruction, and perhaps psychotherapy, may outweigh the modest benefit CPM provides. The small denominator of the cost-effectiveness ratio, were one to be calculated, would imply that the ratio would be very high, making CPM a suboptimal use of health care dollars. Further, we suspect that adding quality of life to the analysis would diminish the benefit and well might turn it into a net harm, in particular for patients with high concern for negative impact of CPM on cosmesis, self image, and morbidity. However, in a fraction of patients who are very troubled by a 0.7% risk of a second, contralateral cancer, CPM might provide an acceptable benefit. The balance between harm and benefit depends on the patient’s preferences and highlights the importance of capturing the patient’s values and expectations before considering CPM.

Of course, these conclusions are based on analysis of women who are at average risk for a contralateral second primary. In women at substantially higher risk (based either on family history or genetics), the benefit of CPM might be far greater, and CPM might be a good choice for the patient or for society.

Dr. Stephen G. Pauker and Dr. Mohamed Alseiari are with the division of clinical decision making in the department of medicine at Tufts Medical Center, Boston. They reported no relevant financial conflicts. This was excerpted from an editorial (J. Natl. Cancer Inst. 2014 July 16 [doi:10.1093/jnci/dju175]).

The absolute 20-year survival benefit from contralateral prophylactic mastectomy stands at less than 1%, regardless of age, estrogen receptor status, and cancer stage, a decision analysis demonstrated.

"Long-term survival in women with unilateral breast cancer treated with or without CPM depends upon several factors, including mortality of the primary breast cancer, risk of CBC [contralateral breast cancer], stage and mortality of the CBC, and the individual patient’s overall life expectancy," wrote Dr. Pamela R. Portschy of the University of Minnesota, Minneapolis.

The report was published July 16 in the Journal of the National Cancer Institute.

"Prospective randomized trials comparing CPM with no CPM are not feasible. Retrospective studies evaluating a potential survival benefit with CPM are limited by short follow-up, potential selection bias, and lack of important clinical information," noted Dr. Portschy and her associates.

They limited their analysis to women with stage I and II breast cancer without BRCA mutations. They developed a Markov model to simulate survival outcomes among those who did and did not have contralateral prophylactic mastectomy (CPM), and they used published studies to estimate probabilities for developing CBC, dying from CBC, dying from primary breast cancer, and age-specific mortality rates. Data were extracted from numerous sources including Surveillance, Epidemiology, and End Results (SEER), the Early Breast Cancer Trialists’ Collaborative Group, and the Oregon State Cancer Registry.

The researchers estimated the 20-year overall survival and life expectancy, but not quality of life or cost, and their analysis considered variation in age, estrogen receptor status, and cancer stage (J. Natl. Cancer Inst. 2014 July 16 [doi:10.1093/jnci/dju160]).

The predicted life expectancy gain from CPM ranged from .13 to .59 years for women with stage I breast cancer, and .08 to .29 years for those with stage II breast cancer. CPM conferred a life expectancy benefit among younger women and among those who had stage I and estrogen receptor–positive disease. "The potential benefit of CPM was consistently lower for patients with stage II breast cancer because of the worse prognosis associated with the primary breast cancer," the researchers wrote. "Similarly, the potential benefits of CPM are more modest for older women because they have relatively fewer years remaining of [life expectancy]."

Dr. Portschy and her associates could not identify any cohort of women that had a greater than 1% absolute survival difference at 20 years. In fact, the predicted 20-year survival differences ranged from .56 to .94% for women with stage I breast cancer and .36 to .61% for those with stage II breast cancer.

The researchers acknowledged limitations of the study, including the fact that the results "do not apply to BRCA gene mutation carriers with unilateral breast cancer who have a cumulative 10-year risk of CBC of approximately 30% to 40%," they wrote. "The outcomes of this analysis were limited to overall and disease-specific survival; we did not evaluate other important outcomes such as surgical complications and quality of life. Also, we assumed the mortality of CBC was the same as the mortality of the index cancer reported by SEER."

They also noted that survival is not the only potential benefit of a cancer risk reduction strategy. "Effects on cancer-related anxiety, cosmesis, and self-image are also important in the decision-making process," they wrote. "For some women, the negative impact of CPM on quality of life may outweigh a potential survival benefit. For others who are very anxious about CBC, CPM may result in a psychological benefit even if survival benefits are minimal."

They concluded that the survival estimates from their Markov model "may be useful for physicians and breast cancer patients to arrive at evidence-based informed decisions regarding CPM. Moreover, the use of accurate and easily understood decision aids may reverse some of the mastectomy trends recently observed in the United States."

The researchers stated that they had no relevant financial conflicts to disclose.

View on the news: Some patients may still benefit from the procedure >>

View on the news: Some patients may still benefit from the procedure

The decision of whether or not to undergo a contralateral prophylactic mastectomy after being treated for breast cancer is a difficult one for many women. The goal of such aggressive therapy is to lower the likelihood of a second primary carcinoma. The downsides are operative risk, impairment of the woman’s self-image, and short-term and long-term morbidities.

This is a well done analysis from an experienced group of investigators and is based on the currently available data. Given the JNCI audience, we shall refrain from niggling points about modeling. Rather, we will stick to the big picture and clinical implications. Although the survival benefit from CPM is small as demonstrated in this model, it is greater than zero, which suggests that for some patients even that small gain may be enough to make it a not unreasonable choice.

From a societal perspective, which was not addressed by Portschy et al., the associated costs of CPM, including the procedure, its complications, reconstruction, and perhaps psychotherapy, may outweigh the modest benefit CPM provides. The small denominator of the cost-effectiveness ratio, were one to be calculated, would imply that the ratio would be very high, making CPM a suboptimal use of health care dollars. Further, we suspect that adding quality of life to the analysis would diminish the benefit and well might turn it into a net harm, in particular for patients with high concern for negative impact of CPM on cosmesis, self image, and morbidity. However, in a fraction of patients who are very troubled by a 0.7% risk of a second, contralateral cancer, CPM might provide an acceptable benefit. The balance between harm and benefit depends on the patient’s preferences and highlights the importance of capturing the patient’s values and expectations before considering CPM.

Of course, these conclusions are based on analysis of women who are at average risk for a contralateral second primary. In women at substantially higher risk (based either on family history or genetics), the benefit of CPM might be far greater, and CPM might be a good choice for the patient or for society.

Dr. Stephen G. Pauker and Dr. Mohamed Alseiari are with the division of clinical decision making in the department of medicine at Tufts Medical Center, Boston. They reported no relevant financial conflicts. This was excerpted from an editorial (J. Natl. Cancer Inst. 2014 July 16 [doi:10.1093/jnci/dju175]).

The use of nonsteroidal anti-inflammatory drugs before hospital admission for severe blunt injury is associated with a reduced incidence of trauma-induced coagulopathy, results from a secondary analysis of a prospective cohort study demonstrated.

"Although trauma-induced coagulopathy [TIC] has been increasingly recognized as a critical component of the pathophysiology of trauma and hemorrhagic shock, factors that predict the development of TIC remain largely unexplored," researchers led by Dr. Matthew D. Neal wrote in a study published in Annals of Surgery.

Copyright thinkstockphotos.com

"The lack of ability to predict TIC makes the design of therapeutic interventions challenging, especially considering that TIC seems to develop rapidly and early after injury."

They noted that previous studies from the trauma literature "have linked the development of TIC to alterations in the thrombomodulin protein C pathway and excessive activated protein C activation, resulting in impaired coagulation. These data present a potential link between TIC and inflammation, which is a common finding in other conditions where both sterile (such as myocardial infarction) and pathogen-mediated (sepsis) diseases present with coagulopathy."

In an effort to investigate whether the use of prehospital NSAIDs may lead to a reduced incidence of TIC, the researchers performed a secondary analysis of 1,897 subjects in the Inflammation and the Host Response to Injury program, which is a large-scale, multicenter study of adults who present with hemorrhagic shock after blunt injury and is designed to characterize the genomic and proteomic response after injury. The key outcome of interest was TIC, which was defined as an admission international normalized ratio (INR) of more than 1.5, or clinically significant coagulopathy, which was defined as that which required transfusion of more than 2 units of fresh frozen plasma or more than 1 pack of platelets in the first 6 hours after admission to the trauma center.

Dr. Neal, of the division of general surgery in the department of surgery at the University of Pittsburgh Medical Center, and his associates used logistic regression to evaluate the association between TIC and prehospital medications and comorbidities (Ann. Surg. 2014;260:378-82). A total of 15 medications or medication classes were assessed, including NSAIDs, aspirin, beta-blockers, antihypertensive medications, oral contraceptives, and corticosteroids.

The mean age of the study population was 40 years, 66% were male, and the mean time from injury to admission was 78 minutes. Nearly one-quarter of the subjects (22%) presented with an INR of more than 1.5, 46% received more than 2 units of fresh frozen plasma or more than 1 pack of platelets in the first 6 hours after admission, and 15% met criteria for both TIC and significant coagulopathy. The most common prehospital medications were antihypertensive medications (12%) and statins (6%).

After performing stepwise logistic regression of the data, the researchers found that prehospital use of NSAIDs was associated with a 72% reduced risk of TIC and was the only medication to retain significance in the model. Stepwise logistic regression also demonstrated that the prehospital use of NSAIDs was associated with a 66% lower risk of clinical significant coagulopathy. The findings were independent of comorbid conditions linked to NSAID use. "None of the interaction terms for NSAID use and associated comorbidities reached significance, and, in fact, two of these, myocardial infarction and hyperlipidemia, were actually associated with an increased risk of clinically significant coagulopathy," the researchers wrote.

Reasons that other anti-inflammatory agents did not have the same association with reduced incidence of TIC "could be explained by a potential off-target effect of NSAIDs or may be due to the complexity of the link between the inflammatory cascade and the induction of coagulopathy."

Dr. Neal and his associates acknowledged certain limitations of the study, including the fact that it was a secondary analysis of a prospective cohort study; that variables regarding medication use, dose, and compliance were not recorded; and that all patients in the cohort were injured by blunt means and presented in hemorrhagic shock. "This may limit the applicability of the results and conclusions to other cohorts," they wrote. "Potential unknown or unmeasured confounding variables may be responsible for the associations described and the conclusions formulated."

The study was supported by a grant from the National Institutes of Health. The researchers had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

The use of nonsteroidal anti-inflammatory drugs before hospital admission for severe blunt injury is associated with a reduced incidence of trauma-induced coagulopathy, results from a secondary analysis of a prospective cohort study demonstrated.

"Although trauma-induced coagulopathy [TIC] has been increasingly recognized as a critical component of the pathophysiology of trauma and hemorrhagic shock, factors that predict the development of TIC remain largely unexplored," researchers led by Dr. Matthew D. Neal wrote in a study published in Annals of Surgery.

Copyright thinkstockphotos.com

"The lack of ability to predict TIC makes the design of therapeutic interventions challenging, especially considering that TIC seems to develop rapidly and early after injury."

They noted that previous studies from the trauma literature "have linked the development of TIC to alterations in the thrombomodulin protein C pathway and excessive activated protein C activation, resulting in impaired coagulation. These data present a potential link between TIC and inflammation, which is a common finding in other conditions where both sterile (such as myocardial infarction) and pathogen-mediated (sepsis) diseases present with coagulopathy."

In an effort to investigate whether the use of prehospital NSAIDs may lead to a reduced incidence of TIC, the researchers performed a secondary analysis of 1,897 subjects in the Inflammation and the Host Response to Injury program, which is a large-scale, multicenter study of adults who present with hemorrhagic shock after blunt injury and is designed to characterize the genomic and proteomic response after injury. The key outcome of interest was TIC, which was defined as an admission international normalized ratio (INR) of more than 1.5, or clinically significant coagulopathy, which was defined as that which required transfusion of more than 2 units of fresh frozen plasma or more than 1 pack of platelets in the first 6 hours after admission to the trauma center.

Dr. Neal, of the division of general surgery in the department of surgery at the University of Pittsburgh Medical Center, and his associates used logistic regression to evaluate the association between TIC and prehospital medications and comorbidities (Ann. Surg. 2014;260:378-82). A total of 15 medications or medication classes were assessed, including NSAIDs, aspirin, beta-blockers, antihypertensive medications, oral contraceptives, and corticosteroids.

The mean age of the study population was 40 years, 66% were male, and the mean time from injury to admission was 78 minutes. Nearly one-quarter of the subjects (22%) presented with an INR of more than 1.5, 46% received more than 2 units of fresh frozen plasma or more than 1 pack of platelets in the first 6 hours after admission, and 15% met criteria for both TIC and significant coagulopathy. The most common prehospital medications were antihypertensive medications (12%) and statins (6%).

After performing stepwise logistic regression of the data, the researchers found that prehospital use of NSAIDs was associated with a 72% reduced risk of TIC and was the only medication to retain significance in the model. Stepwise logistic regression also demonstrated that the prehospital use of NSAIDs was associated with a 66% lower risk of clinical significant coagulopathy. The findings were independent of comorbid conditions linked to NSAID use. "None of the interaction terms for NSAID use and associated comorbidities reached significance, and, in fact, two of these, myocardial infarction and hyperlipidemia, were actually associated with an increased risk of clinically significant coagulopathy," the researchers wrote.

Reasons that other anti-inflammatory agents did not have the same association with reduced incidence of TIC "could be explained by a potential off-target effect of NSAIDs or may be due to the complexity of the link between the inflammatory cascade and the induction of coagulopathy."

Dr. Neal and his associates acknowledged certain limitations of the study, including the fact that it was a secondary analysis of a prospective cohort study; that variables regarding medication use, dose, and compliance were not recorded; and that all patients in the cohort were injured by blunt means and presented in hemorrhagic shock. "This may limit the applicability of the results and conclusions to other cohorts," they wrote. "Potential unknown or unmeasured confounding variables may be responsible for the associations described and the conclusions formulated."

The study was supported by a grant from the National Institutes of Health. The researchers had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

The use of nonsteroidal anti-inflammatory drugs before hospital admission for severe blunt injury is associated with a reduced incidence of trauma-induced coagulopathy, results from a secondary analysis of a prospective cohort study demonstrated.

"Although trauma-induced coagulopathy [TIC] has been increasingly recognized as a critical component of the pathophysiology of trauma and hemorrhagic shock, factors that predict the development of TIC remain largely unexplored," researchers led by Dr. Matthew D. Neal wrote in a study published in Annals of Surgery.

Copyright thinkstockphotos.com

"The lack of ability to predict TIC makes the design of therapeutic interventions challenging, especially considering that TIC seems to develop rapidly and early after injury."

They noted that previous studies from the trauma literature "have linked the development of TIC to alterations in the thrombomodulin protein C pathway and excessive activated protein C activation, resulting in impaired coagulation. These data present a potential link between TIC and inflammation, which is a common finding in other conditions where both sterile (such as myocardial infarction) and pathogen-mediated (sepsis) diseases present with coagulopathy."

In an effort to investigate whether the use of prehospital NSAIDs may lead to a reduced incidence of TIC, the researchers performed a secondary analysis of 1,897 subjects in the Inflammation and the Host Response to Injury program, which is a large-scale, multicenter study of adults who present with hemorrhagic shock after blunt injury and is designed to characterize the genomic and proteomic response after injury. The key outcome of interest was TIC, which was defined as an admission international normalized ratio (INR) of more than 1.5, or clinically significant coagulopathy, which was defined as that which required transfusion of more than 2 units of fresh frozen plasma or more than 1 pack of platelets in the first 6 hours after admission to the trauma center.

Dr. Neal, of the division of general surgery in the department of surgery at the University of Pittsburgh Medical Center, and his associates used logistic regression to evaluate the association between TIC and prehospital medications and comorbidities (Ann. Surg. 2014;260:378-82). A total of 15 medications or medication classes were assessed, including NSAIDs, aspirin, beta-blockers, antihypertensive medications, oral contraceptives, and corticosteroids.

The mean age of the study population was 40 years, 66% were male, and the mean time from injury to admission was 78 minutes. Nearly one-quarter of the subjects (22%) presented with an INR of more than 1.5, 46% received more than 2 units of fresh frozen plasma or more than 1 pack of platelets in the first 6 hours after admission, and 15% met criteria for both TIC and significant coagulopathy. The most common prehospital medications were antihypertensive medications (12%) and statins (6%).

After performing stepwise logistic regression of the data, the researchers found that prehospital use of NSAIDs was associated with a 72% reduced risk of TIC and was the only medication to retain significance in the model. Stepwise logistic regression also demonstrated that the prehospital use of NSAIDs was associated with a 66% lower risk of clinical significant coagulopathy. The findings were independent of comorbid conditions linked to NSAID use. "None of the interaction terms for NSAID use and associated comorbidities reached significance, and, in fact, two of these, myocardial infarction and hyperlipidemia, were actually associated with an increased risk of clinically significant coagulopathy," the researchers wrote.

Reasons that other anti-inflammatory agents did not have the same association with reduced incidence of TIC "could be explained by a potential off-target effect of NSAIDs or may be due to the complexity of the link between the inflammatory cascade and the induction of coagulopathy."

Dr. Neal and his associates acknowledged certain limitations of the study, including the fact that it was a secondary analysis of a prospective cohort study; that variables regarding medication use, dose, and compliance were not recorded; and that all patients in the cohort were injured by blunt means and presented in hemorrhagic shock. "This may limit the applicability of the results and conclusions to other cohorts," they wrote. "Potential unknown or unmeasured confounding variables may be responsible for the associations described and the conclusions formulated."

The study was supported by a grant from the National Institutes of Health. The researchers had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

The use of nonsteroidal anti-inflammatory drugs before hospital admission for severe blunt injury is associated with a reduced incidence of trauma-induced coagulopathy, results from a secondary analysis of a prospective cohort study demonstrated.

"Although trauma-induced coagulopathy [TIC] has been increasingly recognized as a critical component of the pathophysiology of trauma and hemorrhagic shock, factors that predict the development of TIC remain largely unexplored," researchers led by Dr. Matthew D. Neal wrote in a study published in Annals of Surgery.

Copyright thinkstockphotos.com

"The lack of ability to predict TIC makes the design of therapeutic interventions challenging, especially considering that TIC seems to develop rapidly and early after injury."

They noted that previous studies from the trauma literature "have linked the development of TIC to alterations in the thrombomodulin protein C pathway and excessive activated protein C activation, resulting in impaired coagulation. These data present a potential link between TIC and inflammation, which is a common finding in other conditions where both sterile (such as myocardial infarction) and pathogen-mediated (sepsis) diseases present with coagulopathy."

In an effort to investigate whether the use of prehospital NSAIDs may lead to a reduced incidence of TIC, the researchers performed a secondary analysis of 1,897 subjects in the Inflammation and the Host Response to Injury program, which is a large-scale, multicenter study of adults who present with hemorrhagic shock after blunt injury and is designed to characterize the genomic and proteomic response after injury. The key outcome of interest was TIC, which was defined as an admission international normalized ratio (INR) of more than 1.5, or clinically significant coagulopathy, which was defined as that which required transfusion of more than 2 units of fresh frozen plasma or more than 1 pack of platelets in the first 6 hours after admission to the trauma center.

Dr. Neal, of the division of general surgery in the department of surgery at the University of Pittsburgh Medical Center, and his associates used logistic regression to evaluate the association between TIC and prehospital medications and comorbidities (Ann. Surg. 2014;260:378-82). A total of 15 medications or medication classes were assessed, including NSAIDs, aspirin, beta-blockers, antihypertensive medications, oral contraceptives, and corticosteroids.

The mean age of the study population was 40 years, 66% were male, and the mean time from injury to admission was 78 minutes. Nearly one-quarter of the subjects (22%) presented with an INR of more than 1.5, 46% received more than 2 units of fresh frozen plasma or more than 1 pack of platelets in the first 6 hours after admission, and 15% met criteria for both TIC and significant coagulopathy. The most common prehospital medications were antihypertensive medications (12%) and statins (6%).

After performing stepwise logistic regression of the data, the researchers found that prehospital use of NSAIDs was associated with a 72% reduced risk of TIC and was the only medication to retain significance in the model. Stepwise logistic regression also demonstrated that the prehospital use of NSAIDs was associated with a 66% lower risk of clinical significant coagulopathy. The findings were independent of comorbid conditions linked to NSAID use. "None of the interaction terms for NSAID use and associated comorbidities reached significance, and, in fact, two of these, myocardial infarction and hyperlipidemia, were actually associated with an increased risk of clinically significant coagulopathy," the researchers wrote.

Reasons that other anti-inflammatory agents did not have the same association with reduced incidence of TIC "could be explained by a potential off-target effect of NSAIDs or may be due to the complexity of the link between the inflammatory cascade and the induction of coagulopathy."

Dr. Neal and his associates acknowledged certain limitations of the study, including the fact that it was a secondary analysis of a prospective cohort study; that variables regarding medication use, dose, and compliance were not recorded; and that all patients in the cohort were injured by blunt means and presented in hemorrhagic shock. "This may limit the applicability of the results and conclusions to other cohorts," they wrote. "Potential unknown or unmeasured confounding variables may be responsible for the associations described and the conclusions formulated."

The study was supported by a grant from the National Institutes of Health. The researchers had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

The use of nonsteroidal anti-inflammatory drugs before hospital admission for severe blunt injury is associated with a reduced incidence of trauma-induced coagulopathy, results from a secondary analysis of a prospective cohort study demonstrated.

"Although trauma-induced coagulopathy [TIC] has been increasingly recognized as a critical component of the pathophysiology of trauma and hemorrhagic shock, factors that predict the development of TIC remain largely unexplored," researchers led by Dr. Matthew D. Neal wrote in a study published in Annals of Surgery.

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"The lack of ability to predict TIC makes the design of therapeutic interventions challenging, especially considering that TIC seems to develop rapidly and early after injury."

They noted that previous studies from the trauma literature "have linked the development of TIC to alterations in the thrombomodulin protein C pathway and excessive activated protein C activation, resulting in impaired coagulation. These data present a potential link between TIC and inflammation, which is a common finding in other conditions where both sterile (such as myocardial infarction) and pathogen-mediated (sepsis) diseases present with coagulopathy."

In an effort to investigate whether the use of prehospital NSAIDs may lead to a reduced incidence of TIC, the researchers performed a secondary analysis of 1,897 subjects in the Inflammation and the Host Response to Injury program, which is a large-scale, multicenter study of adults who present with hemorrhagic shock after blunt injury and is designed to characterize the genomic and proteomic response after injury. The key outcome of interest was TIC, which was defined as an admission international normalized ratio (INR) of more than 1.5, or clinically significant coagulopathy, which was defined as that which required transfusion of more than 2 units of fresh frozen plasma or more than 1 pack of platelets in the first 6 hours after admission to the trauma center.

Dr. Neal, of the division of general surgery in the department of surgery at the University of Pittsburgh Medical Center, and his associates used logistic regression to evaluate the association between TIC and prehospital medications and comorbidities (Ann. Surg. 2014;260:378-82). A total of 15 medications or medication classes were assessed, including NSAIDs, aspirin, beta-blockers, antihypertensive medications, oral contraceptives, and corticosteroids.

The mean age of the study population was 40 years, 66% were male, and the mean time from injury to admission was 78 minutes. Nearly one-quarter of the subjects (22%) presented with an INR of more than 1.5, 46% received more than 2 units of fresh frozen plasma or more than 1 pack of platelets in the first 6 hours after admission, and 15% met criteria for both TIC and significant coagulopathy. The most common prehospital medications were antihypertensive medications (12%) and statins (6%).

After performing stepwise logistic regression of the data, the researchers found that prehospital use of NSAIDs was associated with a 72% reduced risk of TIC and was the only medication to retain significance in the model. Stepwise logistic regression also demonstrated that the prehospital use of NSAIDs was associated with a 66% lower risk of clinical significant coagulopathy. The findings were independent of comorbid conditions linked to NSAID use. "None of the interaction terms for NSAID use and associated comorbidities reached significance, and, in fact, two of these, myocardial infarction and hyperlipidemia, were actually associated with an increased risk of clinically significant coagulopathy," the researchers wrote.

Reasons that other anti-inflammatory agents did not have the same association with reduced incidence of TIC "could be explained by a potential off-target effect of NSAIDs or may be due to the complexity of the link between the inflammatory cascade and the induction of coagulopathy."

Dr. Neal and his associates acknowledged certain limitations of the study, including the fact that it was a secondary analysis of a prospective cohort study; that variables regarding medication use, dose, and compliance were not recorded; and that all patients in the cohort were injured by blunt means and presented in hemorrhagic shock. "This may limit the applicability of the results and conclusions to other cohorts," they wrote. "Potential unknown or unmeasured confounding variables may be responsible for the associations described and the conclusions formulated."

The study was supported by a grant from the National Institutes of Health. The researchers had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

The use of nonsteroidal anti-inflammatory drugs before hospital admission for severe blunt injury is associated with a reduced incidence of trauma-induced coagulopathy, results from a secondary analysis of a prospective cohort study demonstrated.

"Although trauma-induced coagulopathy [TIC] has been increasingly recognized as a critical component of the pathophysiology of trauma and hemorrhagic shock, factors that predict the development of TIC remain largely unexplored," researchers led by Dr. Matthew D. Neal wrote in a study published in Annals of Surgery.

Copyright thinkstockphotos.com

"The lack of ability to predict TIC makes the design of therapeutic interventions challenging, especially considering that TIC seems to develop rapidly and early after injury."

They noted that previous studies from the trauma literature "have linked the development of TIC to alterations in the thrombomodulin protein C pathway and excessive activated protein C activation, resulting in impaired coagulation. These data present a potential link between TIC and inflammation, which is a common finding in other conditions where both sterile (such as myocardial infarction) and pathogen-mediated (sepsis) diseases present with coagulopathy."

In an effort to investigate whether the use of prehospital NSAIDs may lead to a reduced incidence of TIC, the researchers performed a secondary analysis of 1,897 subjects in the Inflammation and the Host Response to Injury program, which is a large-scale, multicenter study of adults who present with hemorrhagic shock after blunt injury and is designed to characterize the genomic and proteomic response after injury. The key outcome of interest was TIC, which was defined as an admission international normalized ratio (INR) of more than 1.5, or clinically significant coagulopathy, which was defined as that which required transfusion of more than 2 units of fresh frozen plasma or more than 1 pack of platelets in the first 6 hours after admission to the trauma center.

Dr. Neal, of the division of general surgery in the department of surgery at the University of Pittsburgh Medical Center, and his associates used logistic regression to evaluate the association between TIC and prehospital medications and comorbidities (Ann. Surg. 2014;260:378-82). A total of 15 medications or medication classes were assessed, including NSAIDs, aspirin, beta-blockers, antihypertensive medications, oral contraceptives, and corticosteroids.

The mean age of the study population was 40 years, 66% were male, and the mean time from injury to admission was 78 minutes. Nearly one-quarter of the subjects (22%) presented with an INR of more than 1.5, 46% received more than 2 units of fresh frozen plasma or more than 1 pack of platelets in the first 6 hours after admission, and 15% met criteria for both TIC and significant coagulopathy. The most common prehospital medications were antihypertensive medications (12%) and statins (6%).

After performing stepwise logistic regression of the data, the researchers found that prehospital use of NSAIDs was associated with a 72% reduced risk of TIC and was the only medication to retain significance in the model. Stepwise logistic regression also demonstrated that the prehospital use of NSAIDs was associated with a 66% lower risk of clinical significant coagulopathy. The findings were independent of comorbid conditions linked to NSAID use. "None of the interaction terms for NSAID use and associated comorbidities reached significance, and, in fact, two of these, myocardial infarction and hyperlipidemia, were actually associated with an increased risk of clinically significant coagulopathy," the researchers wrote.

Reasons that other anti-inflammatory agents did not have the same association with reduced incidence of TIC "could be explained by a potential off-target effect of NSAIDs or may be due to the complexity of the link between the inflammatory cascade and the induction of coagulopathy."

Dr. Neal and his associates acknowledged certain limitations of the study, including the fact that it was a secondary analysis of a prospective cohort study; that variables regarding medication use, dose, and compliance were not recorded; and that all patients in the cohort were injured by blunt means and presented in hemorrhagic shock. "This may limit the applicability of the results and conclusions to other cohorts," they wrote. "Potential unknown or unmeasured confounding variables may be responsible for the associations described and the conclusions formulated."

The study was supported by a grant from the National Institutes of Health. The researchers had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com