I drive a 10-year-old pickup truck. The air conditioner no longer works – not a real problem here in Maine. It has hand-operated roll down windows ... a real plus should I back too far down the boat ramp and find myself in the cold waters of the Atlantic. If I ever decide to lock it, I will need to use a real key. But the pile of mismatched work gloves and rusty garden tools stashed behind the front seat hasn’t seemed to attract any burglars. Its dented body sits on a new frame, thanks to a generous recall from the manufacturer.

It’s a four-wheel drive, handy in the winter. But what I really like about it is that my old truck has a standard manual transmission. I still have that boyish enthusiasm for shifting gears. I can imagine myself driving a low-slung sports car or operating some gargantuan piece of heavy machinery.

Driving a stick shift vehicle demands a level of engagement and concentration several levels above that of simply aiming a car equipped with an automatic transmission. While I am sure some have tried, shifting gears is a serious deterrent to texting at the wheel.

The fact that our three children learned to drive on a standard shift station wagon is a tribute to their parents’ ability to tolerate repeated whiplash injuries. But it also may be one of the reasons that they survived those deadly middle teenage years. Nichole Morris, a researcher at the Human FIRST Laboratory of the University of Minnesota has said, “If you are going to have an early, untimely death, the most dangerous 2 years of your life are between 16 and 17, and the reason for that is driving” (“Teenage Drivers? Be Very Afraid,” by Bruce Feiler, New York Times, March 19, 2016). Six teenagers a day die from motor vehicle accident–related injuries, according to the Centers for Disease Control and Prevention. There are more deaths from motor vehicle accidents in this age group than from suicides, cancer, and other accidents.

©Thinkstock.com

An unfortunate combination of perceived invincibility and inexperience in an environment richly decorated with distractions makes those first years behind the wheel so dangerous. Charlie Klauer, a researcher at Virginia Tech’s Transportation Institute, believes that one in four teenagers will be involved in a motor vehicle crash in his or her first 6 months of driving. My personal experience supports her observation. Luckily, my daughter’s first accident was a low speed rear-ender into a giant pickup truck that sustained no obvious damage.

Given these frightening statistics, it is surprising that any parents would ever allow their teenage children to start on the path toward a driver’s license. As physicians committed to the health and safety of children, why haven’t pediatricians done more to prevent this tragic loss of life? The honest answer is simply that the motor vehicle is too tightly woven into our culture. We have tried, but we could probably do more.

Technological advances such as self-braking cars that are spinning off from the development of autonomous vehicles may save a few teenage drivers. But, watching your 17-year-old child take the wheel for the first time will continue to be an anxiety-provoking experience for the foreseeable future. We can help by reminding parents that the driving is a privilege that can easily be revoked. We must continue to urge parents to create and enforce rules about the use of cell phones behind the wheel. Many states have enacted laws that restrict teenage drivers from driving with other teens in the car, a well-known and often fatal distraction. But parents must be reminded that they are the first line of enforcement.

Enduring those neck-snapping sessions that are unavoidable when your child is learning to drive a standard shift vehicle was a sacrifice my wife and I made gladly. Manual transmissions aren’t coming back. But there are still plenty of sacrifices for today’s parents to make if they want their children to survive those deadly midteen years.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.”

I drive a 10-year-old pickup truck. The air conditioner no longer works – not a real problem here in Maine. It has hand-operated roll down windows ... a real plus should I back too far down the boat ramp and find myself in the cold waters of the Atlantic. If I ever decide to lock it, I will need to use a real key. But the pile of mismatched work gloves and rusty garden tools stashed behind the front seat hasn’t seemed to attract any burglars. Its dented body sits on a new frame, thanks to a generous recall from the manufacturer.

It’s a four-wheel drive, handy in the winter. But what I really like about it is that my old truck has a standard manual transmission. I still have that boyish enthusiasm for shifting gears. I can imagine myself driving a low-slung sports car or operating some gargantuan piece of heavy machinery.

Driving a stick shift vehicle demands a level of engagement and concentration several levels above that of simply aiming a car equipped with an automatic transmission. While I am sure some have tried, shifting gears is a serious deterrent to texting at the wheel.

The fact that our three children learned to drive on a standard shift station wagon is a tribute to their parents’ ability to tolerate repeated whiplash injuries. But it also may be one of the reasons that they survived those deadly middle teenage years. Nichole Morris, a researcher at the Human FIRST Laboratory of the University of Minnesota has said, “If you are going to have an early, untimely death, the most dangerous 2 years of your life are between 16 and 17, and the reason for that is driving” (“Teenage Drivers? Be Very Afraid,” by Bruce Feiler, New York Times, March 19, 2016). Six teenagers a day die from motor vehicle accident–related injuries, according to the Centers for Disease Control and Prevention. There are more deaths from motor vehicle accidents in this age group than from suicides, cancer, and other accidents.

©Thinkstock.com

An unfortunate combination of perceived invincibility and inexperience in an environment richly decorated with distractions makes those first years behind the wheel so dangerous. Charlie Klauer, a researcher at Virginia Tech’s Transportation Institute, believes that one in four teenagers will be involved in a motor vehicle crash in his or her first 6 months of driving. My personal experience supports her observation. Luckily, my daughter’s first accident was a low speed rear-ender into a giant pickup truck that sustained no obvious damage.

Given these frightening statistics, it is surprising that any parents would ever allow their teenage children to start on the path toward a driver’s license. As physicians committed to the health and safety of children, why haven’t pediatricians done more to prevent this tragic loss of life? The honest answer is simply that the motor vehicle is too tightly woven into our culture. We have tried, but we could probably do more.

Technological advances such as self-braking cars that are spinning off from the development of autonomous vehicles may save a few teenage drivers. But, watching your 17-year-old child take the wheel for the first time will continue to be an anxiety-provoking experience for the foreseeable future. We can help by reminding parents that the driving is a privilege that can easily be revoked. We must continue to urge parents to create and enforce rules about the use of cell phones behind the wheel. Many states have enacted laws that restrict teenage drivers from driving with other teens in the car, a well-known and often fatal distraction. But parents must be reminded that they are the first line of enforcement.

Enduring those neck-snapping sessions that are unavoidable when your child is learning to drive a standard shift vehicle was a sacrifice my wife and I made gladly. Manual transmissions aren’t coming back. But there are still plenty of sacrifices for today’s parents to make if they want their children to survive those deadly midteen years.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.”

I drive a 10-year-old pickup truck. The air conditioner no longer works – not a real problem here in Maine. It has hand-operated roll down windows ... a real plus should I back too far down the boat ramp and find myself in the cold waters of the Atlantic. If I ever decide to lock it, I will need to use a real key. But the pile of mismatched work gloves and rusty garden tools stashed behind the front seat hasn’t seemed to attract any burglars. Its dented body sits on a new frame, thanks to a generous recall from the manufacturer.

It’s a four-wheel drive, handy in the winter. But what I really like about it is that my old truck has a standard manual transmission. I still have that boyish enthusiasm for shifting gears. I can imagine myself driving a low-slung sports car or operating some gargantuan piece of heavy machinery.

Driving a stick shift vehicle demands a level of engagement and concentration several levels above that of simply aiming a car equipped with an automatic transmission. While I am sure some have tried, shifting gears is a serious deterrent to texting at the wheel.

The fact that our three children learned to drive on a standard shift station wagon is a tribute to their parents’ ability to tolerate repeated whiplash injuries. But it also may be one of the reasons that they survived those deadly middle teenage years. Nichole Morris, a researcher at the Human FIRST Laboratory of the University of Minnesota has said, “If you are going to have an early, untimely death, the most dangerous 2 years of your life are between 16 and 17, and the reason for that is driving” (“Teenage Drivers? Be Very Afraid,” by Bruce Feiler, New York Times, March 19, 2016). Six teenagers a day die from motor vehicle accident–related injuries, according to the Centers for Disease Control and Prevention. There are more deaths from motor vehicle accidents in this age group than from suicides, cancer, and other accidents.

©Thinkstock.com

An unfortunate combination of perceived invincibility and inexperience in an environment richly decorated with distractions makes those first years behind the wheel so dangerous. Charlie Klauer, a researcher at Virginia Tech’s Transportation Institute, believes that one in four teenagers will be involved in a motor vehicle crash in his or her first 6 months of driving. My personal experience supports her observation. Luckily, my daughter’s first accident was a low speed rear-ender into a giant pickup truck that sustained no obvious damage.

Given these frightening statistics, it is surprising that any parents would ever allow their teenage children to start on the path toward a driver’s license. As physicians committed to the health and safety of children, why haven’t pediatricians done more to prevent this tragic loss of life? The honest answer is simply that the motor vehicle is too tightly woven into our culture. We have tried, but we could probably do more.

Technological advances such as self-braking cars that are spinning off from the development of autonomous vehicles may save a few teenage drivers. But, watching your 17-year-old child take the wheel for the first time will continue to be an anxiety-provoking experience for the foreseeable future. We can help by reminding parents that the driving is a privilege that can easily be revoked. We must continue to urge parents to create and enforce rules about the use of cell phones behind the wheel. Many states have enacted laws that restrict teenage drivers from driving with other teens in the car, a well-known and often fatal distraction. But parents must be reminded that they are the first line of enforcement.

Enduring those neck-snapping sessions that are unavoidable when your child is learning to drive a standard shift vehicle was a sacrifice my wife and I made gladly. Manual transmissions aren’t coming back. But there are still plenty of sacrifices for today’s parents to make if they want their children to survive those deadly midteen years.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.”

Hollywood, FLA. – Although patients and physicians should always be partners in medical decision making, guiding patients into making medically sound choices may involve a lot of listening and empathy, often followed by a little friendly persuasion, suggests an expert in health care decision making,

“Even when you get to a situation where the clinical practice guideline would point toward shared decision making, we’ve got to do shared decision making right or the guideline just doesn’t do the work for us. We clinicians have to know how to partner with our patients to make decisions when their values matter,” said Dr. Peter A Ubel, professor of business, public policy, and medicine at Duke University, Durham, N.H.

Dr. Ubel discussed how to understand and use patient preferences in cancer treatment decisions at the annual conference of the National Comprehensive Cancer Network.

In the case of early-stage prostate cancer, for example, treatment options include surveillance or active treatment with surgery or radiation, but the risk/benefit trade-offs require careful discussion.

“The different approaches have different pros and cons: If you get active treatment, there’s a pretty good chance you’ll experience incontinence or erectile dysfunction, whereas if you undergo surveillance you won’t experience those as side effects of the surveillance strategy, but you will live with a cancer inside your body, the accompanying anxiety, and wondering every 6 months whether it has advanced,” Dr. Ubel said.

“The question is how do we go figure out which treatment is best for which patient?” he added.

What doctors say not always what patients hear

To examine how decisions are made, Dr. Ubel and his colleagues conducted a study in which patients scheduled for biopsy for suspicion of prostate cancer were approached at the time of their clinic visits and asked to participate in a study about prostate cancer decision making. Patients were given a booklet aimed at the seventh-grade reading level describing prostate cancer and its treatment, and were asked, once they had finished, what course of therapy they might pursue if the diagnosis turned out to be positive, and why. They also were asked if it was important to them to maintain natural sexual function.

The encounter between the patients and their urologists at the time of diagnosis were audio recorded, so that investigators could see whether physicians recommend specific treatments and why.

“One of the things that really jumped out in this study was just how much language, how much explanation urologists use to help patients understand their diagnosis,” Dr. Ubel said.

In one encounter, the urologist explained to the patient that 3 out of 12 biopsy cores had less than 30% cancer involvement, suggesting moderately low-risk disease, but then went on to talk about Gleason scores, tumor grades and patterns, and risk categories.

“When a patient just finds out he has prostate cancer, it’s a tough time to put a whole bunch of information in front of him for him to absorb and make a decision,” Dr. Ubel said. Patients need time to absorb the shock of a cancer diagnosis first – even a diagnosis of an early, easily treated cancer – and information overload may actually reduce their ability to comprehend their choices or retain the information, he added. The urologist in this scenario is making a very earnest effort to tell the patient that he doesn’t have the kind of cancer that’s ever going to kill him, or that it is highly unlikely to cause any problems for the next 10-15 years, and there is ample time to decide how to treat it.

“But the doctor kind of forgets that the patient doesn’t speak medicalese, and the doctor feels like you really have to give them thorough informed consent, after all. So you need to inform the heck out of patients with all of the medical detail you believe is necessary to understand the decision, instead of the translation of the medical detail into terms the patient can understand,” he said.

An important part of shared decision making, therefore, is to make sure that patients can understand their alternatives, but not to overwhelm them with detail, because they may give up and ask the physician, “What do you think I should do?” which can introduce physician bias that may not always lead to the right choice for that patient.

“I actually morally don’t recommend that. I think instead we should give the right amount of information at the right time so they can actually get engaged in the choice,” Dr. Ubel said.

Discussion informs choices

The investigators looked at how prediagnosis education materials and discussions with urologists shaped patient decisions about treatment choice. Patients were called before their appointments to ensure that they had read the booklet, and then just before the appointment were asked which way they were leaning if the diagnosis turned out to be positive.

The investigators found that of 44 patients who expressed a preference for active surveillance before the appointment, 55% actually went on to receive active treatment. Among 119 patients with no expressed preference for surveillance or active therapy, 46% went on to treatment, and of 118 expressing previsit preference only for active surveillance, 54% went on to receive it.

“The leaning that they had before seeing the doctor had no influence on what treatment they got,” Dr. Ubel said. Instead, physicians’ recommendations had a strong influence on treatment choice. Recommendations are an essential part of the discussion, “but I don’t think we often do them well,” he said.

Ask patients to think out loud about what they have read or have been told, and ask them to repeat in their own words what they heard the doctor say, Dr. Ubel suggested. It’s incumbent on the physician to try to understand the patient’s preferences, and say something like, “I’m the expert on medical facts, but you’re the expert on you,” or “What sounds good and bad to you about that treatment alternative?”

Finally, physicians need to make recommendations based on patient preferences, he said.

For example, in one recorded encounter, the physician asked the patient, “Are you the kind of person where the idea of just watching your PSA is that unsettling to you?” When the patient replied “Yeah, I think I would be,” the physician was able to make an informed recommendation, saying “then I don’t think you’d be a good candidate for surveillance.”

“This doctor did not just make a recommendation; he tried to find out something about the patient first, and that’s critical to giving good advice,” Dr. Ubel said.

Hollywood, FLA. – Although patients and physicians should always be partners in medical decision making, guiding patients into making medically sound choices may involve a lot of listening and empathy, often followed by a little friendly persuasion, suggests an expert in health care decision making,

“Even when you get to a situation where the clinical practice guideline would point toward shared decision making, we’ve got to do shared decision making right or the guideline just doesn’t do the work for us. We clinicians have to know how to partner with our patients to make decisions when their values matter,” said Dr. Peter A Ubel, professor of business, public policy, and medicine at Duke University, Durham, N.H.

Dr. Ubel discussed how to understand and use patient preferences in cancer treatment decisions at the annual conference of the National Comprehensive Cancer Network.

In the case of early-stage prostate cancer, for example, treatment options include surveillance or active treatment with surgery or radiation, but the risk/benefit trade-offs require careful discussion.

“The different approaches have different pros and cons: If you get active treatment, there’s a pretty good chance you’ll experience incontinence or erectile dysfunction, whereas if you undergo surveillance you won’t experience those as side effects of the surveillance strategy, but you will live with a cancer inside your body, the accompanying anxiety, and wondering every 6 months whether it has advanced,” Dr. Ubel said.

“The question is how do we go figure out which treatment is best for which patient?” he added.

What doctors say not always what patients hear

To examine how decisions are made, Dr. Ubel and his colleagues conducted a study in which patients scheduled for biopsy for suspicion of prostate cancer were approached at the time of their clinic visits and asked to participate in a study about prostate cancer decision making. Patients were given a booklet aimed at the seventh-grade reading level describing prostate cancer and its treatment, and were asked, once they had finished, what course of therapy they might pursue if the diagnosis turned out to be positive, and why. They also were asked if it was important to them to maintain natural sexual function.

The encounter between the patients and their urologists at the time of diagnosis were audio recorded, so that investigators could see whether physicians recommend specific treatments and why.

“One of the things that really jumped out in this study was just how much language, how much explanation urologists use to help patients understand their diagnosis,” Dr. Ubel said.

In one encounter, the urologist explained to the patient that 3 out of 12 biopsy cores had less than 30% cancer involvement, suggesting moderately low-risk disease, but then went on to talk about Gleason scores, tumor grades and patterns, and risk categories.

“When a patient just finds out he has prostate cancer, it’s a tough time to put a whole bunch of information in front of him for him to absorb and make a decision,” Dr. Ubel said. Patients need time to absorb the shock of a cancer diagnosis first – even a diagnosis of an early, easily treated cancer – and information overload may actually reduce their ability to comprehend their choices or retain the information, he added. The urologist in this scenario is making a very earnest effort to tell the patient that he doesn’t have the kind of cancer that’s ever going to kill him, or that it is highly unlikely to cause any problems for the next 10-15 years, and there is ample time to decide how to treat it.

“But the doctor kind of forgets that the patient doesn’t speak medicalese, and the doctor feels like you really have to give them thorough informed consent, after all. So you need to inform the heck out of patients with all of the medical detail you believe is necessary to understand the decision, instead of the translation of the medical detail into terms the patient can understand,” he said.

An important part of shared decision making, therefore, is to make sure that patients can understand their alternatives, but not to overwhelm them with detail, because they may give up and ask the physician, “What do you think I should do?” which can introduce physician bias that may not always lead to the right choice for that patient.

“I actually morally don’t recommend that. I think instead we should give the right amount of information at the right time so they can actually get engaged in the choice,” Dr. Ubel said.

Discussion informs choices

The investigators looked at how prediagnosis education materials and discussions with urologists shaped patient decisions about treatment choice. Patients were called before their appointments to ensure that they had read the booklet, and then just before the appointment were asked which way they were leaning if the diagnosis turned out to be positive.

The investigators found that of 44 patients who expressed a preference for active surveillance before the appointment, 55% actually went on to receive active treatment. Among 119 patients with no expressed preference for surveillance or active therapy, 46% went on to treatment, and of 118 expressing previsit preference only for active surveillance, 54% went on to receive it.

“The leaning that they had before seeing the doctor had no influence on what treatment they got,” Dr. Ubel said. Instead, physicians’ recommendations had a strong influence on treatment choice. Recommendations are an essential part of the discussion, “but I don’t think we often do them well,” he said.

Ask patients to think out loud about what they have read or have been told, and ask them to repeat in their own words what they heard the doctor say, Dr. Ubel suggested. It’s incumbent on the physician to try to understand the patient’s preferences, and say something like, “I’m the expert on medical facts, but you’re the expert on you,” or “What sounds good and bad to you about that treatment alternative?”

Finally, physicians need to make recommendations based on patient preferences, he said.

For example, in one recorded encounter, the physician asked the patient, “Are you the kind of person where the idea of just watching your PSA is that unsettling to you?” When the patient replied “Yeah, I think I would be,” the physician was able to make an informed recommendation, saying “then I don’t think you’d be a good candidate for surveillance.”

“This doctor did not just make a recommendation; he tried to find out something about the patient first, and that’s critical to giving good advice,” Dr. Ubel said.

Hollywood, FLA. – Although patients and physicians should always be partners in medical decision making, guiding patients into making medically sound choices may involve a lot of listening and empathy, often followed by a little friendly persuasion, suggests an expert in health care decision making,

“Even when you get to a situation where the clinical practice guideline would point toward shared decision making, we’ve got to do shared decision making right or the guideline just doesn’t do the work for us. We clinicians have to know how to partner with our patients to make decisions when their values matter,” said Dr. Peter A Ubel, professor of business, public policy, and medicine at Duke University, Durham, N.H.

Dr. Ubel discussed how to understand and use patient preferences in cancer treatment decisions at the annual conference of the National Comprehensive Cancer Network.

In the case of early-stage prostate cancer, for example, treatment options include surveillance or active treatment with surgery or radiation, but the risk/benefit trade-offs require careful discussion.

“The different approaches have different pros and cons: If you get active treatment, there’s a pretty good chance you’ll experience incontinence or erectile dysfunction, whereas if you undergo surveillance you won’t experience those as side effects of the surveillance strategy, but you will live with a cancer inside your body, the accompanying anxiety, and wondering every 6 months whether it has advanced,” Dr. Ubel said.

“The question is how do we go figure out which treatment is best for which patient?” he added.

What doctors say not always what patients hear

To examine how decisions are made, Dr. Ubel and his colleagues conducted a study in which patients scheduled for biopsy for suspicion of prostate cancer were approached at the time of their clinic visits and asked to participate in a study about prostate cancer decision making. Patients were given a booklet aimed at the seventh-grade reading level describing prostate cancer and its treatment, and were asked, once they had finished, what course of therapy they might pursue if the diagnosis turned out to be positive, and why. They also were asked if it was important to them to maintain natural sexual function.

The encounter between the patients and their urologists at the time of diagnosis were audio recorded, so that investigators could see whether physicians recommend specific treatments and why.

“One of the things that really jumped out in this study was just how much language, how much explanation urologists use to help patients understand their diagnosis,” Dr. Ubel said.

In one encounter, the urologist explained to the patient that 3 out of 12 biopsy cores had less than 30% cancer involvement, suggesting moderately low-risk disease, but then went on to talk about Gleason scores, tumor grades and patterns, and risk categories.

“When a patient just finds out he has prostate cancer, it’s a tough time to put a whole bunch of information in front of him for him to absorb and make a decision,” Dr. Ubel said. Patients need time to absorb the shock of a cancer diagnosis first – even a diagnosis of an early, easily treated cancer – and information overload may actually reduce their ability to comprehend their choices or retain the information, he added. The urologist in this scenario is making a very earnest effort to tell the patient that he doesn’t have the kind of cancer that’s ever going to kill him, or that it is highly unlikely to cause any problems for the next 10-15 years, and there is ample time to decide how to treat it.

“But the doctor kind of forgets that the patient doesn’t speak medicalese, and the doctor feels like you really have to give them thorough informed consent, after all. So you need to inform the heck out of patients with all of the medical detail you believe is necessary to understand the decision, instead of the translation of the medical detail into terms the patient can understand,” he said.

An important part of shared decision making, therefore, is to make sure that patients can understand their alternatives, but not to overwhelm them with detail, because they may give up and ask the physician, “What do you think I should do?” which can introduce physician bias that may not always lead to the right choice for that patient.

“I actually morally don’t recommend that. I think instead we should give the right amount of information at the right time so they can actually get engaged in the choice,” Dr. Ubel said.

Discussion informs choices

The investigators looked at how prediagnosis education materials and discussions with urologists shaped patient decisions about treatment choice. Patients were called before their appointments to ensure that they had read the booklet, and then just before the appointment were asked which way they were leaning if the diagnosis turned out to be positive.

The investigators found that of 44 patients who expressed a preference for active surveillance before the appointment, 55% actually went on to receive active treatment. Among 119 patients with no expressed preference for surveillance or active therapy, 46% went on to treatment, and of 118 expressing previsit preference only for active surveillance, 54% went on to receive it.

“The leaning that they had before seeing the doctor had no influence on what treatment they got,” Dr. Ubel said. Instead, physicians’ recommendations had a strong influence on treatment choice. Recommendations are an essential part of the discussion, “but I don’t think we often do them well,” he said.

Ask patients to think out loud about what they have read or have been told, and ask them to repeat in their own words what they heard the doctor say, Dr. Ubel suggested. It’s incumbent on the physician to try to understand the patient’s preferences, and say something like, “I’m the expert on medical facts, but you’re the expert on you,” or “What sounds good and bad to you about that treatment alternative?”

Finally, physicians need to make recommendations based on patient preferences, he said.

For example, in one recorded encounter, the physician asked the patient, “Are you the kind of person where the idea of just watching your PSA is that unsettling to you?” When the patient replied “Yeah, I think I would be,” the physician was able to make an informed recommendation, saying “then I don’t think you’d be a good candidate for surveillance.”

“This doctor did not just make a recommendation; he tried to find out something about the patient first, and that’s critical to giving good advice,” Dr. Ubel said.

The Diagnosis: Superficial Acral Fibromyxoma

Superficial acral fibromyxoma (SAF) was first described in 2001 by Fetsch et al.¹ Subsequently, the term digital fibromyxoma was proposed in 2012 by Hollmann et al² to describe a distinctive, slow-growing, soft-tissue tumor with a predilection for the periungual or subungual regions of the fingers and toes. The benign growth typically presents as a painless or tender nodule in middle-aged adults with a slight male predominance (1.3:1 ratio).^1,2 In a case series (N=124) described by Hollmann et al,² 9 of 25 patients (36%) who had imaging studies showed bone involvement by an erosive or lytic lesion. Reports of SAF with bone involvement also have been described in the radiologic and orthopedic surgery literature.^3,4 Radiographically, the soft-tissue invasion of the bone is demonstrated by scalloping on plain radiographs (Figure 1).³

Histologically, SAFs are moderately cellular with spindled or stellate fibroblastlike cells within a myxoid or collagenous matrix (Figure 2).¹ The vasculature is mildly accentuated and an increase in mast cells usually is observed. The nuclei have a low degree of atypia with few mitotic figures, and the stellate cells exhibit positive immunohistochemical staining for CD34 (Figure 3), epithelial membrane antigen, and CD99.¹ Hollmann et al² found that 66 of 95 tumors (69.5%) infiltrated the dermal collagen, 26 (27.4%) infiltrated fat, and 3 (3.2%) invaded bone. Of the 47 cases that were evaluated on follow-up, 10 tumors (21.3%) recurred locally (all near the nail unit of the fingers or toes) after a mean interval of 27 months. Although invasion of underlying tissues and recurrence of the tumor has been demonstrated, this growth is considered benign. The histologic differential diagnosis includes neurofibroma, myxoma, fibroma, low-grade fibromyxoid sarcoma, dermatofibroma, superficial angiomyxoma, and dermatofibrosarcoma protuberans.²

The primary treatment of SAF is local excision. The incidence of local recurrence found in the case series by Hollmann et al² was directly linked to positive margins after the first excision (10/47 [21.3%] recurrent lesions had positive margins). To date, there are no known reports of metastatic disease in SAF.² Our case manifested with a late recurrence of the tumor and bone involvement requiring surgical excision, which illustrates the role of adjuvant imaging and close follow-up following excision of any soft-tissue tumors of the fingers and toes that have been histologically confirmed as SAF, particularly those of the periungual region.

The Diagnosis: Superficial Acral Fibromyxoma

Superficial acral fibromyxoma (SAF) was first described in 2001 by Fetsch et al.¹ Subsequently, the term digital fibromyxoma was proposed in 2012 by Hollmann et al² to describe a distinctive, slow-growing, soft-tissue tumor with a predilection for the periungual or subungual regions of the fingers and toes. The benign growth typically presents as a painless or tender nodule in middle-aged adults with a slight male predominance (1.3:1 ratio).^1,2 In a case series (N=124) described by Hollmann et al,² 9 of 25 patients (36%) who had imaging studies showed bone involvement by an erosive or lytic lesion. Reports of SAF with bone involvement also have been described in the radiologic and orthopedic surgery literature.^3,4 Radiographically, the soft-tissue invasion of the bone is demonstrated by scalloping on plain radiographs (Figure 1).³

Histologically, SAFs are moderately cellular with spindled or stellate fibroblastlike cells within a myxoid or collagenous matrix (Figure 2).¹ The vasculature is mildly accentuated and an increase in mast cells usually is observed. The nuclei have a low degree of atypia with few mitotic figures, and the stellate cells exhibit positive immunohistochemical staining for CD34 (Figure 3), epithelial membrane antigen, and CD99.¹ Hollmann et al² found that 66 of 95 tumors (69.5%) infiltrated the dermal collagen, 26 (27.4%) infiltrated fat, and 3 (3.2%) invaded bone. Of the 47 cases that were evaluated on follow-up, 10 tumors (21.3%) recurred locally (all near the nail unit of the fingers or toes) after a mean interval of 27 months. Although invasion of underlying tissues and recurrence of the tumor has been demonstrated, this growth is considered benign. The histologic differential diagnosis includes neurofibroma, myxoma, fibroma, low-grade fibromyxoid sarcoma, dermatofibroma, superficial angiomyxoma, and dermatofibrosarcoma protuberans.²

The primary treatment of SAF is local excision. The incidence of local recurrence found in the case series by Hollmann et al² was directly linked to positive margins after the first excision (10/47 [21.3%] recurrent lesions had positive margins). To date, there are no known reports of metastatic disease in SAF.² Our case manifested with a late recurrence of the tumor and bone involvement requiring surgical excision, which illustrates the role of adjuvant imaging and close follow-up following excision of any soft-tissue tumors of the fingers and toes that have been histologically confirmed as SAF, particularly those of the periungual region.

The Diagnosis: Superficial Acral Fibromyxoma

Superficial acral fibromyxoma (SAF) was first described in 2001 by Fetsch et al.¹ Subsequently, the term digital fibromyxoma was proposed in 2012 by Hollmann et al² to describe a distinctive, slow-growing, soft-tissue tumor with a predilection for the periungual or subungual regions of the fingers and toes. The benign growth typically presents as a painless or tender nodule in middle-aged adults with a slight male predominance (1.3:1 ratio).^1,2 In a case series (N=124) described by Hollmann et al,² 9 of 25 patients (36%) who had imaging studies showed bone involvement by an erosive or lytic lesion. Reports of SAF with bone involvement also have been described in the radiologic and orthopedic surgery literature.^3,4 Radiographically, the soft-tissue invasion of the bone is demonstrated by scalloping on plain radiographs (Figure 1).³

Histologically, SAFs are moderately cellular with spindled or stellate fibroblastlike cells within a myxoid or collagenous matrix (Figure 2).¹ The vasculature is mildly accentuated and an increase in mast cells usually is observed. The nuclei have a low degree of atypia with few mitotic figures, and the stellate cells exhibit positive immunohistochemical staining for CD34 (Figure 3), epithelial membrane antigen, and CD99.¹ Hollmann et al² found that 66 of 95 tumors (69.5%) infiltrated the dermal collagen, 26 (27.4%) infiltrated fat, and 3 (3.2%) invaded bone. Of the 47 cases that were evaluated on follow-up, 10 tumors (21.3%) recurred locally (all near the nail unit of the fingers or toes) after a mean interval of 27 months. Although invasion of underlying tissues and recurrence of the tumor has been demonstrated, this growth is considered benign. The histologic differential diagnosis includes neurofibroma, myxoma, fibroma, low-grade fibromyxoid sarcoma, dermatofibroma, superficial angiomyxoma, and dermatofibrosarcoma protuberans.²

The primary treatment of SAF is local excision. The incidence of local recurrence found in the case series by Hollmann et al² was directly linked to positive margins after the first excision (10/47 [21.3%] recurrent lesions had positive margins). To date, there are no known reports of metastatic disease in SAF.² Our case manifested with a late recurrence of the tumor and bone involvement requiring surgical excision, which illustrates the role of adjuvant imaging and close follow-up following excision of any soft-tissue tumors of the fingers and toes that have been histologically confirmed as SAF, particularly those of the periungual region.

What do your patients need to know at the first visit?

Patients with chronic dermatitis are frequently referred for patch testing. An in-depth conversation reviewing the patch test procedure and the many potential causes of dermatitis (eg, endogenous, allergic, irritant, seborrheic) is needed. Patients should understand the patch test process. The testing extends over a week, requiring 3 days of visits. The patches are applied at day 1 and must be kept dry and in place for 48 hours, then they are removed and evaluated. A second follow-up visit at 96 hours to 1 week after the patches are applied is done to perform a final read, interpret, and explain the final results. The patient needs to know that we are looking for an allergen that might be causing the eruption through contact exposure with the skin. The difference between patch testing and prick testing often needs to be discussed, as patients are not always aware of the difference. Explaining the need to avoid topical steroids at the patch test site, sunburn, or systemic steroids during the patch test period is also important to obtain optimal testing conditions.

Querying all exposures including work, home, personal care products, and hobbies is important to help determine which allergen series should be tested to obtain the best results. Patients need to understand that even small intermittent exposures can cause an ongoing dermatitis. If a causative allergen(s) is identified, strict avoidance can lead to clearance and resolution.

Setting expectations is important, and therefore you should discuss the possibility that no allergen will be identified while letting the patient know that this information is also useful. Also, let patients know there are other things that can be done if patch testing is negative to try and gain control of the dermatitis including laboratory tests and biopsies, which may be needed to help direct future management.

What are your go-to treatments? What are the side effects?

The beauty of patch testing is that finding a relevant allergen and subsequent avoidance of that allergen often is sufficient to improve or clear the dermatitis. Detailed education regarding the allergen, where it is found, and how to avoid it are imperative in patient management. I provide the patient with information sheets or narratives found on the American Contact Dermatitis Society website (http://www.contactderm.org) as well as a list of safe products found on the Contact Allergen Management Program (CAMP) area of the site. These tools help in patient compliance.

Go-to treatments for relevant patch test dermatitis involve topical steroids to calm the acute dermatitis while educating and instituting a personal environment free of the identified allergens. Occasionally, systemic steroids are used to provide relief and calm down an extensive dermatitis while educating, identifying, and eliminating known allergens from the patient’s environment. Identifying and eliminating an allergen can mitigate the need for chronic steroids, and the resultant side effects of hypertension, osteoporosis, avascular necrosis, hyperglycemia, and gastrointestinal tract problems can be avoided. Likewise, avoidance of allergens can lead to the elimination of the need for chronic topical steroids and the resultant atrophy and striae.

Side effects of the patch test procedure itself include an allergic reaction to one of the chemicals tested (eg, gold), which is what you are looking for; persistent reactions; flaring of existing dermatitis; irritation; hyperpigmentation; and rarely anaphylaxis or infection at a patch test site. If no allergy is found, treatment of generalized dermatitis can include topical steroids. Topical calcineurin inhibitors can be useful as well as narrowband UV light. Several oral medications can be used for recalcitrant patch test–negative dermatitis and the selection of the right medication is based on the patient’s comorbidities and extent of dermatitis, including systemic steroids, though long-term use is not recommended. Mycophenolate mofetil, methotrexate, cyclosporine, and azathioprine all have side effects including liver and renal toxicity, immunosuppression, and risk for malignancy and therefore need to be considered on a case-by-case basis.

How do you keep the patient compliant with treatment?

Treating allergic contact dermatitis once an allergen(s) has been identified can be challenging. Education is key so that the patient understands where the allergen is found in his/her environment and how to avoid it. Teaching the patient to read labels also is important. Providing a list of safe products simplifies compliance. Reinforcing the need for ongoing vigilance in allergen avoidance is critical to resolution of the dermatitis. Reinforcing the need for continuous avoidance is imperative, as patients sometimes become less vigilant once the dermatitis resolves and the allergen can sneak back into their environment.

What do I do if a patient refuses treatment?

Sometimes patients are so attached to a product that they do not want to stop using it even though they know it is the cause of their dermatitis. If I can help them identify a comparable product, I introduce them to it, but ultimately they get to decide if they prefer to use a product that they know is the cause of their rash or if they want to avoid it and be clear of the dermatitis. For those who do not have an allergen identified through patch testing, alternative treatments can be used. If they do not want systemic medication, I try and optimize their skin care regimen with mild soaps, bland moisturizing creams, and short lukewarm showers, which often is not enough and eventually due to ongoing itch patients decide to discuss and pursue treatment options.

What do your patients need to know at the first visit?

Patients with chronic dermatitis are frequently referred for patch testing. An in-depth conversation reviewing the patch test procedure and the many potential causes of dermatitis (eg, endogenous, allergic, irritant, seborrheic) is needed. Patients should understand the patch test process. The testing extends over a week, requiring 3 days of visits. The patches are applied at day 1 and must be kept dry and in place for 48 hours, then they are removed and evaluated. A second follow-up visit at 96 hours to 1 week after the patches are applied is done to perform a final read, interpret, and explain the final results. The patient needs to know that we are looking for an allergen that might be causing the eruption through contact exposure with the skin. The difference between patch testing and prick testing often needs to be discussed, as patients are not always aware of the difference. Explaining the need to avoid topical steroids at the patch test site, sunburn, or systemic steroids during the patch test period is also important to obtain optimal testing conditions.

Querying all exposures including work, home, personal care products, and hobbies is important to help determine which allergen series should be tested to obtain the best results. Patients need to understand that even small intermittent exposures can cause an ongoing dermatitis. If a causative allergen(s) is identified, strict avoidance can lead to clearance and resolution.

Setting expectations is important, and therefore you should discuss the possibility that no allergen will be identified while letting the patient know that this information is also useful. Also, let patients know there are other things that can be done if patch testing is negative to try and gain control of the dermatitis including laboratory tests and biopsies, which may be needed to help direct future management.

What are your go-to treatments? What are the side effects?

The beauty of patch testing is that finding a relevant allergen and subsequent avoidance of that allergen often is sufficient to improve or clear the dermatitis. Detailed education regarding the allergen, where it is found, and how to avoid it are imperative in patient management. I provide the patient with information sheets or narratives found on the American Contact Dermatitis Society website (http://www.contactderm.org) as well as a list of safe products found on the Contact Allergen Management Program (CAMP) area of the site. These tools help in patient compliance.

Go-to treatments for relevant patch test dermatitis involve topical steroids to calm the acute dermatitis while educating and instituting a personal environment free of the identified allergens. Occasionally, systemic steroids are used to provide relief and calm down an extensive dermatitis while educating, identifying, and eliminating known allergens from the patient’s environment. Identifying and eliminating an allergen can mitigate the need for chronic steroids, and the resultant side effects of hypertension, osteoporosis, avascular necrosis, hyperglycemia, and gastrointestinal tract problems can be avoided. Likewise, avoidance of allergens can lead to the elimination of the need for chronic topical steroids and the resultant atrophy and striae.

Side effects of the patch test procedure itself include an allergic reaction to one of the chemicals tested (eg, gold), which is what you are looking for; persistent reactions; flaring of existing dermatitis; irritation; hyperpigmentation; and rarely anaphylaxis or infection at a patch test site. If no allergy is found, treatment of generalized dermatitis can include topical steroids. Topical calcineurin inhibitors can be useful as well as narrowband UV light. Several oral medications can be used for recalcitrant patch test–negative dermatitis and the selection of the right medication is based on the patient’s comorbidities and extent of dermatitis, including systemic steroids, though long-term use is not recommended. Mycophenolate mofetil, methotrexate, cyclosporine, and azathioprine all have side effects including liver and renal toxicity, immunosuppression, and risk for malignancy and therefore need to be considered on a case-by-case basis.

How do you keep the patient compliant with treatment?

Treating allergic contact dermatitis once an allergen(s) has been identified can be challenging. Education is key so that the patient understands where the allergen is found in his/her environment and how to avoid it. Teaching the patient to read labels also is important. Providing a list of safe products simplifies compliance. Reinforcing the need for ongoing vigilance in allergen avoidance is critical to resolution of the dermatitis. Reinforcing the need for continuous avoidance is imperative, as patients sometimes become less vigilant once the dermatitis resolves and the allergen can sneak back into their environment.

What do I do if a patient refuses treatment?

Sometimes patients are so attached to a product that they do not want to stop using it even though they know it is the cause of their dermatitis. If I can help them identify a comparable product, I introduce them to it, but ultimately they get to decide if they prefer to use a product that they know is the cause of their rash or if they want to avoid it and be clear of the dermatitis. For those who do not have an allergen identified through patch testing, alternative treatments can be used. If they do not want systemic medication, I try and optimize their skin care regimen with mild soaps, bland moisturizing creams, and short lukewarm showers, which often is not enough and eventually due to ongoing itch patients decide to discuss and pursue treatment options.

What do your patients need to know at the first visit?

Patients with chronic dermatitis are frequently referred for patch testing. An in-depth conversation reviewing the patch test procedure and the many potential causes of dermatitis (eg, endogenous, allergic, irritant, seborrheic) is needed. Patients should understand the patch test process. The testing extends over a week, requiring 3 days of visits. The patches are applied at day 1 and must be kept dry and in place for 48 hours, then they are removed and evaluated. A second follow-up visit at 96 hours to 1 week after the patches are applied is done to perform a final read, interpret, and explain the final results. The patient needs to know that we are looking for an allergen that might be causing the eruption through contact exposure with the skin. The difference between patch testing and prick testing often needs to be discussed, as patients are not always aware of the difference. Explaining the need to avoid topical steroids at the patch test site, sunburn, or systemic steroids during the patch test period is also important to obtain optimal testing conditions.

Querying all exposures including work, home, personal care products, and hobbies is important to help determine which allergen series should be tested to obtain the best results. Patients need to understand that even small intermittent exposures can cause an ongoing dermatitis. If a causative allergen(s) is identified, strict avoidance can lead to clearance and resolution.

Setting expectations is important, and therefore you should discuss the possibility that no allergen will be identified while letting the patient know that this information is also useful. Also, let patients know there are other things that can be done if patch testing is negative to try and gain control of the dermatitis including laboratory tests and biopsies, which may be needed to help direct future management.

What are your go-to treatments? What are the side effects?

The beauty of patch testing is that finding a relevant allergen and subsequent avoidance of that allergen often is sufficient to improve or clear the dermatitis. Detailed education regarding the allergen, where it is found, and how to avoid it are imperative in patient management. I provide the patient with information sheets or narratives found on the American Contact Dermatitis Society website (http://www.contactderm.org) as well as a list of safe products found on the Contact Allergen Management Program (CAMP) area of the site. These tools help in patient compliance.

Go-to treatments for relevant patch test dermatitis involve topical steroids to calm the acute dermatitis while educating and instituting a personal environment free of the identified allergens. Occasionally, systemic steroids are used to provide relief and calm down an extensive dermatitis while educating, identifying, and eliminating known allergens from the patient’s environment. Identifying and eliminating an allergen can mitigate the need for chronic steroids, and the resultant side effects of hypertension, osteoporosis, avascular necrosis, hyperglycemia, and gastrointestinal tract problems can be avoided. Likewise, avoidance of allergens can lead to the elimination of the need for chronic topical steroids and the resultant atrophy and striae.

Side effects of the patch test procedure itself include an allergic reaction to one of the chemicals tested (eg, gold), which is what you are looking for; persistent reactions; flaring of existing dermatitis; irritation; hyperpigmentation; and rarely anaphylaxis or infection at a patch test site. If no allergy is found, treatment of generalized dermatitis can include topical steroids. Topical calcineurin inhibitors can be useful as well as narrowband UV light. Several oral medications can be used for recalcitrant patch test–negative dermatitis and the selection of the right medication is based on the patient’s comorbidities and extent of dermatitis, including systemic steroids, though long-term use is not recommended. Mycophenolate mofetil, methotrexate, cyclosporine, and azathioprine all have side effects including liver and renal toxicity, immunosuppression, and risk for malignancy and therefore need to be considered on a case-by-case basis.

How do you keep the patient compliant with treatment?

Treating allergic contact dermatitis once an allergen(s) has been identified can be challenging. Education is key so that the patient understands where the allergen is found in his/her environment and how to avoid it. Teaching the patient to read labels also is important. Providing a list of safe products simplifies compliance. Reinforcing the need for ongoing vigilance in allergen avoidance is critical to resolution of the dermatitis. Reinforcing the need for continuous avoidance is imperative, as patients sometimes become less vigilant once the dermatitis resolves and the allergen can sneak back into their environment.

What do I do if a patient refuses treatment?

Sometimes patients are so attached to a product that they do not want to stop using it even though they know it is the cause of their dermatitis. If I can help them identify a comparable product, I introduce them to it, but ultimately they get to decide if they prefer to use a product that they know is the cause of their rash or if they want to avoid it and be clear of the dermatitis. For those who do not have an allergen identified through patch testing, alternative treatments can be used. If they do not want systemic medication, I try and optimize their skin care regimen with mild soaps, bland moisturizing creams, and short lukewarm showers, which often is not enough and eventually due to ongoing itch patients decide to discuss and pursue treatment options.

Patients with inflammatory bowel disease (IBD) may have a higher risk of oral cancer, according to a study at Mount Sinai Medical Center. Researchers collected data on 7,294 patients from 2000 through 2011. The results were published in the March issue of Clinical Gastroenterology and Hepatology.

Related: Exercise and Inflammatory Bowel Disease

In the study, the expected incidence of oral cancer was calculated for the patients who were stratified by gender and age using the Surveillance, Epidemiology and End Results (SEER) 18 registry data. Seven men and 4 women had biopsy-proven oral cancer. Six had cancer of the tongue, 2 had cancer of the hard palate, and 3 had tonsillar, buccal, or mandibular sarcoma. Seven patients had been treated for IBD before the cancer diagnosis.

Women had a higher risk of oral cancer. Adjusted for age and sex, the incidence ratio for oral cancer in patients with IBD was 9.77:12.07 for women12.07 and 9.77:8.49 for men. The age-adjusted incidence ratio for tongue cancer was 18.91: 17.06 for men, 22.10 for women.

Related: More Illnesses Linked to Camp Lejeune Water

The authors concluded that, “we found patients with IBD to be at increased risk for oral cancers, especially tongue cancer. Women are at higher risk than men.”

Source:
Katsanos KH, Roda G, McBride RB, Cohen B, Colombel JF. Clin Gastroenterol Hepatol. 2016;14(3):413-420
doi: 10.1016/j.cgh.2015.09.041. 

Patients with inflammatory bowel disease (IBD) may have a higher risk of oral cancer, according to a study at Mount Sinai Medical Center. Researchers collected data on 7,294 patients from 2000 through 2011. The results were published in the March issue of Clinical Gastroenterology and Hepatology.

Related: Exercise and Inflammatory Bowel Disease

In the study, the expected incidence of oral cancer was calculated for the patients who were stratified by gender and age using the Surveillance, Epidemiology and End Results (SEER) 18 registry data. Seven men and 4 women had biopsy-proven oral cancer. Six had cancer of the tongue, 2 had cancer of the hard palate, and 3 had tonsillar, buccal, or mandibular sarcoma. Seven patients had been treated for IBD before the cancer diagnosis.

Women had a higher risk of oral cancer. Adjusted for age and sex, the incidence ratio for oral cancer in patients with IBD was 9.77:12.07 for women12.07 and 9.77:8.49 for men. The age-adjusted incidence ratio for tongue cancer was 18.91: 17.06 for men, 22.10 for women.

Related: More Illnesses Linked to Camp Lejeune Water

The authors concluded that, “we found patients with IBD to be at increased risk for oral cancers, especially tongue cancer. Women are at higher risk than men.”

Source:
Katsanos KH, Roda G, McBride RB, Cohen B, Colombel JF. Clin Gastroenterol Hepatol. 2016;14(3):413-420
doi: 10.1016/j.cgh.2015.09.041. 

Patients with inflammatory bowel disease (IBD) may have a higher risk of oral cancer, according to a study at Mount Sinai Medical Center. Researchers collected data on 7,294 patients from 2000 through 2011. The results were published in the March issue of Clinical Gastroenterology and Hepatology.

Related: Exercise and Inflammatory Bowel Disease

In the study, the expected incidence of oral cancer was calculated for the patients who were stratified by gender and age using the Surveillance, Epidemiology and End Results (SEER) 18 registry data. Seven men and 4 women had biopsy-proven oral cancer. Six had cancer of the tongue, 2 had cancer of the hard palate, and 3 had tonsillar, buccal, or mandibular sarcoma. Seven patients had been treated for IBD before the cancer diagnosis.

Women had a higher risk of oral cancer. Adjusted for age and sex, the incidence ratio for oral cancer in patients with IBD was 9.77:12.07 for women12.07 and 9.77:8.49 for men. The age-adjusted incidence ratio for tongue cancer was 18.91: 17.06 for men, 22.10 for women.

Related: More Illnesses Linked to Camp Lejeune Water

The authors concluded that, “we found patients with IBD to be at increased risk for oral cancers, especially tongue cancer. Women are at higher risk than men.”

Source:
Katsanos KH, Roda G, McBride RB, Cohen B, Colombel JF. Clin Gastroenterol Hepatol. 2016;14(3):413-420
doi: 10.1016/j.cgh.2015.09.041. 

An increased risk of acute lymphoblastic leukemia (ALL) was seen in young children born by prelabor cesarean delivery, in a pooled analysis of 13 case-control studies from nine countries.

The odds ratio was significant at 1.23 for an association between prelabor cesarean delivery and ALL (P = .018); there was not a significant association between ALL and all indications of cesarean delivery nor was there an association with emergency cesarean delivery. Further, the risk for childhood AML was not associated with cesarean delivery, prelabor cesarean delivery, or emergency cesarean delivery, reported Erin L. Marcotte, Ph.D., of the University of Minnesota, Minneapolis, and her associates.

VashiDonsk/Creative Commons/CC ASA 3.0

The association between ALL and prelabor cesarean delivery is based on 13 case-control studies from the Childhood Leukemia International Consortium. Birth delivery method was known for 97%-99% of 8,780 ALL cases, 1,332 AML cases, and 23,459 controls in those studies. In four of the studies, the indications for cesarean delivery were known for 1,061 of 4,313 ALL cases, 138 of 664 AML cases, and 1,401 of 5,884 controls. The multivariable logistic regression models used for the analysis were adjusted for birth weight, sex, age, ethnic origin, parental education, maternal age, and study.

If the association proves to be causal, “maladaptive immune activation due to an absence of stress response before birth in children born by prelabor caesarean delivery could be considered as a potential mechanism,” the researchers wrote (Lancet Haematol. 2016;3[4]:e176–e185).

ALL involves genetic and developmental aberrations that are probably modified by exposure and response to infectious agents. Early exposure to a variety of infections seems to decrease risk, and a vigorous response to infections (quantified by physician visits for infections) increases risk. During vaginal birth, the newborn is exposed to commensal bacteria that modulate immune development, Joseph Weimels, Ph.D., of the University of California at San Francisco, and Xiaomei Ma, Ph.D., of the Yale School of Public Health, New Haven, Conn., wrote in an editorial published in the same issue of The Lancet Haematology. Children delivered vaginally have different gut microbiomes and T-cell reactivity persisting up to age 2 years compared with children born by cesarean, they wrote.

The National Cancer Institute funded the study. The researchers had no relevant disclosures.

[email protected]

On Twitter @maryjodales

An increased risk of acute lymphoblastic leukemia (ALL) was seen in young children born by prelabor cesarean delivery, in a pooled analysis of 13 case-control studies from nine countries.

The odds ratio was significant at 1.23 for an association between prelabor cesarean delivery and ALL (P = .018); there was not a significant association between ALL and all indications of cesarean delivery nor was there an association with emergency cesarean delivery. Further, the risk for childhood AML was not associated with cesarean delivery, prelabor cesarean delivery, or emergency cesarean delivery, reported Erin L. Marcotte, Ph.D., of the University of Minnesota, Minneapolis, and her associates.

VashiDonsk/Creative Commons/CC ASA 3.0

The association between ALL and prelabor cesarean delivery is based on 13 case-control studies from the Childhood Leukemia International Consortium. Birth delivery method was known for 97%-99% of 8,780 ALL cases, 1,332 AML cases, and 23,459 controls in those studies. In four of the studies, the indications for cesarean delivery were known for 1,061 of 4,313 ALL cases, 138 of 664 AML cases, and 1,401 of 5,884 controls. The multivariable logistic regression models used for the analysis were adjusted for birth weight, sex, age, ethnic origin, parental education, maternal age, and study.

If the association proves to be causal, “maladaptive immune activation due to an absence of stress response before birth in children born by prelabor caesarean delivery could be considered as a potential mechanism,” the researchers wrote (Lancet Haematol. 2016;3[4]:e176–e185).

ALL involves genetic and developmental aberrations that are probably modified by exposure and response to infectious agents. Early exposure to a variety of infections seems to decrease risk, and a vigorous response to infections (quantified by physician visits for infections) increases risk. During vaginal birth, the newborn is exposed to commensal bacteria that modulate immune development, Joseph Weimels, Ph.D., of the University of California at San Francisco, and Xiaomei Ma, Ph.D., of the Yale School of Public Health, New Haven, Conn., wrote in an editorial published in the same issue of The Lancet Haematology. Children delivered vaginally have different gut microbiomes and T-cell reactivity persisting up to age 2 years compared with children born by cesarean, they wrote.

The National Cancer Institute funded the study. The researchers had no relevant disclosures.

[email protected]

On Twitter @maryjodales

An increased risk of acute lymphoblastic leukemia (ALL) was seen in young children born by prelabor cesarean delivery, in a pooled analysis of 13 case-control studies from nine countries.

The odds ratio was significant at 1.23 for an association between prelabor cesarean delivery and ALL (P = .018); there was not a significant association between ALL and all indications of cesarean delivery nor was there an association with emergency cesarean delivery. Further, the risk for childhood AML was not associated with cesarean delivery, prelabor cesarean delivery, or emergency cesarean delivery, reported Erin L. Marcotte, Ph.D., of the University of Minnesota, Minneapolis, and her associates.

VashiDonsk/Creative Commons/CC ASA 3.0

The association between ALL and prelabor cesarean delivery is based on 13 case-control studies from the Childhood Leukemia International Consortium. Birth delivery method was known for 97%-99% of 8,780 ALL cases, 1,332 AML cases, and 23,459 controls in those studies. In four of the studies, the indications for cesarean delivery were known for 1,061 of 4,313 ALL cases, 138 of 664 AML cases, and 1,401 of 5,884 controls. The multivariable logistic regression models used for the analysis were adjusted for birth weight, sex, age, ethnic origin, parental education, maternal age, and study.

If the association proves to be causal, “maladaptive immune activation due to an absence of stress response before birth in children born by prelabor caesarean delivery could be considered as a potential mechanism,” the researchers wrote (Lancet Haematol. 2016;3[4]:e176–e185).

ALL involves genetic and developmental aberrations that are probably modified by exposure and response to infectious agents. Early exposure to a variety of infections seems to decrease risk, and a vigorous response to infections (quantified by physician visits for infections) increases risk. During vaginal birth, the newborn is exposed to commensal bacteria that modulate immune development, Joseph Weimels, Ph.D., of the University of California at San Francisco, and Xiaomei Ma, Ph.D., of the Yale School of Public Health, New Haven, Conn., wrote in an editorial published in the same issue of The Lancet Haematology. Children delivered vaginally have different gut microbiomes and T-cell reactivity persisting up to age 2 years compared with children born by cesarean, they wrote.

The National Cancer Institute funded the study. The researchers had no relevant disclosures.

[email protected]

On Twitter @maryjodales

AMSTERDAM – Physical therapy is underused as a first conservative treatment option for knee osteoarthritis, according to a review of data of more than 130,000 men and women serving in the U.S. military.

Data from the Military Health System Data Repository (MDR) show that clinical practice is often out of step with guidelines, as many patients are treated with intra-articular corticosteroid injections rather than physical therapy.

©Nandyphotos/Thinkstock.com

Within a week of an initial episode of knee OA, patients were four times more likely to be given steroid injections than receive physical therapy (14,290 vs. 3,177 patients), although a similar number of patients received injections or physical therapy within 30 days (8,228 vs. 8,407) and 90 days (9,125 vs. 10,059). Of the patients given injections early, 12,311 received them on the day of the index episode.

“What was interesting, anecdotally, was how few patients had been to physical therapy prior to surgery and how many of them had had injections before physical therapy,” Dr. Dan Rhon, director of physical therapy at Brooke Army Medical Center, Houston, said in an interview at the World Congress on Osteoarthritis.

“We wanted to look at the practice patterns because guidelines generally say that you should try physical therapy before surgery and that invasive procedures such as injections should be utilized further down the road,” he said at the meeting, which was sponsored by Osteoarthritis Research Society International.

Dr. Rhon noted that in a study of clinical practice patterns over a 5-year period from the United Healthcare Database, researchers found that physical rehabilitation was used in about one-quarter of patients, with 10% of those who went on to have surgery receiving physical therapy specific for OA, and 16% had been given intra-articular injections (Arthroscopy. 2014;30:65-71).

Results from the MDR data, which considered records from 2008 to 2013 and 1 year of follow-up, now show similar findings with 29% of patients receiving physical rehabilitation, 17.5% prior to knee arthroplasty, and 36% of patients receiving corticosteroid injections first.

What this shows, Dr. Rhon said, is that clinical practice patterns in the Military Health System do not appear to be following established guidelines. “It’s a little bit worrisome because most of these patients should at least have a trial of conservative management.” Perhaps there is some confusion over what constitutes conservative management, but when there is a choice between physical therapy and corticosteroid injections, it seems that the latter is more commonly being selected. Patients themselves could also be opting for injections over physical rehabilitation, so there may be a need for education on what options are available before surgical intervention.

Further research is needed to examine the clinical outcomes of this and perhaps look at how cost savings could be made if clinical practice more closely adhered to the OA guidelines. Looking at a longer follow-up period, say 2-5 years post diagnosis, might also give a better reflection of the use of physical therapy before surgery.

Dr. Rhon had no financial disclosures.

AMSTERDAM – Physical therapy is underused as a first conservative treatment option for knee osteoarthritis, according to a review of data of more than 130,000 men and women serving in the U.S. military.

Data from the Military Health System Data Repository (MDR) show that clinical practice is often out of step with guidelines, as many patients are treated with intra-articular corticosteroid injections rather than physical therapy.

©Nandyphotos/Thinkstock.com

Within a week of an initial episode of knee OA, patients were four times more likely to be given steroid injections than receive physical therapy (14,290 vs. 3,177 patients), although a similar number of patients received injections or physical therapy within 30 days (8,228 vs. 8,407) and 90 days (9,125 vs. 10,059). Of the patients given injections early, 12,311 received them on the day of the index episode.

“What was interesting, anecdotally, was how few patients had been to physical therapy prior to surgery and how many of them had had injections before physical therapy,” Dr. Dan Rhon, director of physical therapy at Brooke Army Medical Center, Houston, said in an interview at the World Congress on Osteoarthritis.

“We wanted to look at the practice patterns because guidelines generally say that you should try physical therapy before surgery and that invasive procedures such as injections should be utilized further down the road,” he said at the meeting, which was sponsored by Osteoarthritis Research Society International.

Dr. Rhon noted that in a study of clinical practice patterns over a 5-year period from the United Healthcare Database, researchers found that physical rehabilitation was used in about one-quarter of patients, with 10% of those who went on to have surgery receiving physical therapy specific for OA, and 16% had been given intra-articular injections (Arthroscopy. 2014;30:65-71).

Results from the MDR data, which considered records from 2008 to 2013 and 1 year of follow-up, now show similar findings with 29% of patients receiving physical rehabilitation, 17.5% prior to knee arthroplasty, and 36% of patients receiving corticosteroid injections first.

What this shows, Dr. Rhon said, is that clinical practice patterns in the Military Health System do not appear to be following established guidelines. “It’s a little bit worrisome because most of these patients should at least have a trial of conservative management.” Perhaps there is some confusion over what constitutes conservative management, but when there is a choice between physical therapy and corticosteroid injections, it seems that the latter is more commonly being selected. Patients themselves could also be opting for injections over physical rehabilitation, so there may be a need for education on what options are available before surgical intervention.

Further research is needed to examine the clinical outcomes of this and perhaps look at how cost savings could be made if clinical practice more closely adhered to the OA guidelines. Looking at a longer follow-up period, say 2-5 years post diagnosis, might also give a better reflection of the use of physical therapy before surgery.

Dr. Rhon had no financial disclosures.

AMSTERDAM – Physical therapy is underused as a first conservative treatment option for knee osteoarthritis, according to a review of data of more than 130,000 men and women serving in the U.S. military.

Data from the Military Health System Data Repository (MDR) show that clinical practice is often out of step with guidelines, as many patients are treated with intra-articular corticosteroid injections rather than physical therapy.

©Nandyphotos/Thinkstock.com

Within a week of an initial episode of knee OA, patients were four times more likely to be given steroid injections than receive physical therapy (14,290 vs. 3,177 patients), although a similar number of patients received injections or physical therapy within 30 days (8,228 vs. 8,407) and 90 days (9,125 vs. 10,059). Of the patients given injections early, 12,311 received them on the day of the index episode.

“What was interesting, anecdotally, was how few patients had been to physical therapy prior to surgery and how many of them had had injections before physical therapy,” Dr. Dan Rhon, director of physical therapy at Brooke Army Medical Center, Houston, said in an interview at the World Congress on Osteoarthritis.

“We wanted to look at the practice patterns because guidelines generally say that you should try physical therapy before surgery and that invasive procedures such as injections should be utilized further down the road,” he said at the meeting, which was sponsored by Osteoarthritis Research Society International.

Dr. Rhon noted that in a study of clinical practice patterns over a 5-year period from the United Healthcare Database, researchers found that physical rehabilitation was used in about one-quarter of patients, with 10% of those who went on to have surgery receiving physical therapy specific for OA, and 16% had been given intra-articular injections (Arthroscopy. 2014;30:65-71).

Results from the MDR data, which considered records from 2008 to 2013 and 1 year of follow-up, now show similar findings with 29% of patients receiving physical rehabilitation, 17.5% prior to knee arthroplasty, and 36% of patients receiving corticosteroid injections first.

What this shows, Dr. Rhon said, is that clinical practice patterns in the Military Health System do not appear to be following established guidelines. “It’s a little bit worrisome because most of these patients should at least have a trial of conservative management.” Perhaps there is some confusion over what constitutes conservative management, but when there is a choice between physical therapy and corticosteroid injections, it seems that the latter is more commonly being selected. Patients themselves could also be opting for injections over physical rehabilitation, so there may be a need for education on what options are available before surgical intervention.

Further research is needed to examine the clinical outcomes of this and perhaps look at how cost savings could be made if clinical practice more closely adhered to the OA guidelines. Looking at a longer follow-up period, say 2-5 years post diagnosis, might also give a better reflection of the use of physical therapy before surgery.

Dr. Rhon had no financial disclosures.

Micrograph showing CML

Image by Difu Wu

The phase 3 EPIC trial, a comparison of tyrosine kinase inhibitors (TKIs), has left some questions unanswered.

The trial did not determine whether the third-generation TKI ponatinib is more effective than the first-generation TKI imatinib for patients with previously untreated chronic myeloid leukemia (CML).

The study was terminated early due to safety concerns associated with ponatinib, so the primary endpoint could only be analyzed in a small number of patients.

Results in these patients showed no significant difference in that endpoint—major molecular response (MMR) at 12 months—between the imatinib and ponatinib arms.

Results in the entire study cohort suggested that, overall, ponatinib was more toxic than imatinib. In particular, ponatinib produced more arterial occlusive events.

However, the trial’s investigators have questioned whether reducing the dose of ponatinib might change that.

Jeffrey H. Lipton, MD, of Princess Margaret Cancer Centre in Toronto, Ontario, Canada, and his colleagues reported results from the EPIC trial in The Lancet Oncology. The trial was supported by Ariad Pharmaceuticals.

Problems with ponatinib

Ponatinib was approved by the US Food and Drug Administration (FDA) in December 2012 to treat adults with CML or Philadelphia chromosome-positive acute lymphoblastic leukemia that is resistant to or intolerant of other TKIs.

In October 2013, follow-up results from the phase 2 PACE trial suggested ponatinib can increase a patient’s risk of arterial and venous thrombotic events. So all trials of the drug were placed on partial clinical hold, with the exception of the EPIC trial, which was terminated.

That November, the FDA suspended sales and marketing of ponatinib, pending results of a safety evaluation. In December, the agency decided ponatinib could return to the market if new safety measures were implemented. In January 2014, ponatinib was put back on the market in the US.

EPIC trial

The trial enrolled 307 patients with newly diagnosed, chronic-phase CML. Patients were randomized to receive ponatinib at 45 mg (n=155) or imatinib at 400 mg (n=152) once daily until progression, unacceptable toxicity, or other criteria for withdrawal were met.

The median age was 55 (range, 18-89) in the ponatinib arm and 52 (range, 18-86) in the imatinib arm. Most patients were male—63% and 61%, respectively—and most had an ECOG performance status of 0—75% and 78%, respectively.

Patients were randomized between August 14, 2012, and October 9, 2013, and the trial was terminated on October 17, 2013.

Because of the early termination, only 10 patients in the ponatinib arm and 13 in the imatinib arm were evaluable for the primary endpoint—MMR at 12 months. Eighty percent (8/10) of the evaluable patients in the ponatinib arm and 38% (5/13) of those in the imatinib arm achieved an MMR at 12 months (P=0.074).

The investigators also evaluated the incidence of MMR at any time in patients with any post-baseline molecular response assessment. This time, the incidence of MMR was significantly higher in the ponatinib arm than the imatinib arm—41% (61/149) and 18% (25/142), respectively (P<0.0001).

All of the patients were evaluable for safety—154 in the ponatinib arm and 152 in the imatinib arm.

Arterial occlusive events occurred in 7% (n=11) of patients in the ponatinib arm and 2% (n=3) in the imatinib arm (P=0.052). These events were considered serious in 6% (n=10) and 1% (n=1), respectively (P=0.010).

Common grade 3/4 adverse events—in the ponatinib and imatinib arms, respectively—were increased lipase (14% vs 2%), thrombocytopenia (12% vs 7%), rash (6% vs 1%), and neutropenia (3% vs 8%).

Serious adverse events that occurred in 3 or more patients in the ponatinib arm were pancreatitis (n=5), atrial fibrillation (n=3), and thrombocytopenia (n=3). There were no serious adverse events that occurred in 3 or more patients in the imatinib arm.

Dr Lipton and his colleagues said the premature termination of the EPIC trial restricts the interpretation of its results, but the available data provide some insight into the activity and safety of ponatinib in previously untreated CML.

The investigators also noted that data from this trial and the clinical development program for ponatinib suggest that lowering doses of the drug could improve its vascular safety profile and, therefore, the benefit-risk balance.

Two ongoing trials (NCT02467270 and NCT02627677) may provide more insight. Both are investigating starting doses of ponatinib at 15 mg or 30 mg.

Micrograph showing CML

Image by Difu Wu

The phase 3 EPIC trial, a comparison of tyrosine kinase inhibitors (TKIs), has left some questions unanswered.

The trial did not determine whether the third-generation TKI ponatinib is more effective than the first-generation TKI imatinib for patients with previously untreated chronic myeloid leukemia (CML).

The study was terminated early due to safety concerns associated with ponatinib, so the primary endpoint could only be analyzed in a small number of patients.

Results in these patients showed no significant difference in that endpoint—major molecular response (MMR) at 12 months—between the imatinib and ponatinib arms.

Results in the entire study cohort suggested that, overall, ponatinib was more toxic than imatinib. In particular, ponatinib produced more arterial occlusive events.

However, the trial’s investigators have questioned whether reducing the dose of ponatinib might change that.

Jeffrey H. Lipton, MD, of Princess Margaret Cancer Centre in Toronto, Ontario, Canada, and his colleagues reported results from the EPIC trial in The Lancet Oncology. The trial was supported by Ariad Pharmaceuticals.

Problems with ponatinib

Ponatinib was approved by the US Food and Drug Administration (FDA) in December 2012 to treat adults with CML or Philadelphia chromosome-positive acute lymphoblastic leukemia that is resistant to or intolerant of other TKIs.

In October 2013, follow-up results from the phase 2 PACE trial suggested ponatinib can increase a patient’s risk of arterial and venous thrombotic events. So all trials of the drug were placed on partial clinical hold, with the exception of the EPIC trial, which was terminated.

That November, the FDA suspended sales and marketing of ponatinib, pending results of a safety evaluation. In December, the agency decided ponatinib could return to the market if new safety measures were implemented. In January 2014, ponatinib was put back on the market in the US.

EPIC trial

The trial enrolled 307 patients with newly diagnosed, chronic-phase CML. Patients were randomized to receive ponatinib at 45 mg (n=155) or imatinib at 400 mg (n=152) once daily until progression, unacceptable toxicity, or other criteria for withdrawal were met.

The median age was 55 (range, 18-89) in the ponatinib arm and 52 (range, 18-86) in the imatinib arm. Most patients were male—63% and 61%, respectively—and most had an ECOG performance status of 0—75% and 78%, respectively.

Patients were randomized between August 14, 2012, and October 9, 2013, and the trial was terminated on October 17, 2013.

Because of the early termination, only 10 patients in the ponatinib arm and 13 in the imatinib arm were evaluable for the primary endpoint—MMR at 12 months. Eighty percent (8/10) of the evaluable patients in the ponatinib arm and 38% (5/13) of those in the imatinib arm achieved an MMR at 12 months (P=0.074).

The investigators also evaluated the incidence of MMR at any time in patients with any post-baseline molecular response assessment. This time, the incidence of MMR was significantly higher in the ponatinib arm than the imatinib arm—41% (61/149) and 18% (25/142), respectively (P<0.0001).

All of the patients were evaluable for safety—154 in the ponatinib arm and 152 in the imatinib arm.

Arterial occlusive events occurred in 7% (n=11) of patients in the ponatinib arm and 2% (n=3) in the imatinib arm (P=0.052). These events were considered serious in 6% (n=10) and 1% (n=1), respectively (P=0.010).

Common grade 3/4 adverse events—in the ponatinib and imatinib arms, respectively—were increased lipase (14% vs 2%), thrombocytopenia (12% vs 7%), rash (6% vs 1%), and neutropenia (3% vs 8%).

Serious adverse events that occurred in 3 or more patients in the ponatinib arm were pancreatitis (n=5), atrial fibrillation (n=3), and thrombocytopenia (n=3). There were no serious adverse events that occurred in 3 or more patients in the imatinib arm.

Dr Lipton and his colleagues said the premature termination of the EPIC trial restricts the interpretation of its results, but the available data provide some insight into the activity and safety of ponatinib in previously untreated CML.

The investigators also noted that data from this trial and the clinical development program for ponatinib suggest that lowering doses of the drug could improve its vascular safety profile and, therefore, the benefit-risk balance.

Two ongoing trials (NCT02467270 and NCT02627677) may provide more insight. Both are investigating starting doses of ponatinib at 15 mg or 30 mg.

Micrograph showing CML

Image by Difu Wu

The phase 3 EPIC trial, a comparison of tyrosine kinase inhibitors (TKIs), has left some questions unanswered.

The trial did not determine whether the third-generation TKI ponatinib is more effective than the first-generation TKI imatinib for patients with previously untreated chronic myeloid leukemia (CML).

The study was terminated early due to safety concerns associated with ponatinib, so the primary endpoint could only be analyzed in a small number of patients.

Results in these patients showed no significant difference in that endpoint—major molecular response (MMR) at 12 months—between the imatinib and ponatinib arms.

Results in the entire study cohort suggested that, overall, ponatinib was more toxic than imatinib. In particular, ponatinib produced more arterial occlusive events.

However, the trial’s investigators have questioned whether reducing the dose of ponatinib might change that.

Jeffrey H. Lipton, MD, of Princess Margaret Cancer Centre in Toronto, Ontario, Canada, and his colleagues reported results from the EPIC trial in The Lancet Oncology. The trial was supported by Ariad Pharmaceuticals.

Problems with ponatinib

Ponatinib was approved by the US Food and Drug Administration (FDA) in December 2012 to treat adults with CML or Philadelphia chromosome-positive acute lymphoblastic leukemia that is resistant to or intolerant of other TKIs.

In October 2013, follow-up results from the phase 2 PACE trial suggested ponatinib can increase a patient’s risk of arterial and venous thrombotic events. So all trials of the drug were placed on partial clinical hold, with the exception of the EPIC trial, which was terminated.

That November, the FDA suspended sales and marketing of ponatinib, pending results of a safety evaluation. In December, the agency decided ponatinib could return to the market if new safety measures were implemented. In January 2014, ponatinib was put back on the market in the US.

EPIC trial

The trial enrolled 307 patients with newly diagnosed, chronic-phase CML. Patients were randomized to receive ponatinib at 45 mg (n=155) or imatinib at 400 mg (n=152) once daily until progression, unacceptable toxicity, or other criteria for withdrawal were met.

The median age was 55 (range, 18-89) in the ponatinib arm and 52 (range, 18-86) in the imatinib arm. Most patients were male—63% and 61%, respectively—and most had an ECOG performance status of 0—75% and 78%, respectively.

Patients were randomized between August 14, 2012, and October 9, 2013, and the trial was terminated on October 17, 2013.

Because of the early termination, only 10 patients in the ponatinib arm and 13 in the imatinib arm were evaluable for the primary endpoint—MMR at 12 months. Eighty percent (8/10) of the evaluable patients in the ponatinib arm and 38% (5/13) of those in the imatinib arm achieved an MMR at 12 months (P=0.074).

The investigators also evaluated the incidence of MMR at any time in patients with any post-baseline molecular response assessment. This time, the incidence of MMR was significantly higher in the ponatinib arm than the imatinib arm—41% (61/149) and 18% (25/142), respectively (P<0.0001).

All of the patients were evaluable for safety—154 in the ponatinib arm and 152 in the imatinib arm.

Arterial occlusive events occurred in 7% (n=11) of patients in the ponatinib arm and 2% (n=3) in the imatinib arm (P=0.052). These events were considered serious in 6% (n=10) and 1% (n=1), respectively (P=0.010).

Common grade 3/4 adverse events—in the ponatinib and imatinib arms, respectively—were increased lipase (14% vs 2%), thrombocytopenia (12% vs 7%), rash (6% vs 1%), and neutropenia (3% vs 8%).

Serious adverse events that occurred in 3 or more patients in the ponatinib arm were pancreatitis (n=5), atrial fibrillation (n=3), and thrombocytopenia (n=3). There were no serious adverse events that occurred in 3 or more patients in the imatinib arm.

Dr Lipton and his colleagues said the premature termination of the EPIC trial restricts the interpretation of its results, but the available data provide some insight into the activity and safety of ponatinib in previously untreated CML.

The investigators also noted that data from this trial and the clinical development program for ponatinib suggest that lowering doses of the drug could improve its vascular safety profile and, therefore, the benefit-risk balance.

Two ongoing trials (NCT02467270 and NCT02627677) may provide more insight. Both are investigating starting doses of ponatinib at 15 mg or 30 mg.

NEW YORK (Reuters Health) - Ten-year results from a comparison of coronary-artery bypass grafting (CABG) with medical therapy alone has found that bypass lowers the odds of cardiovascular death by about nine percentage points in people with ischemic cardiomyopathy.

The 16% reduction in the death rate meant volunteers who received bypass grafting typically lived nearly a year and a half longer than those who received optimal nonsurgical therapy.

The findings are based on a study population of 1,212 patients with an ejection fraction of 35% or less who received bypass grafts between 2002 and 2007.

Death from any cause, the primary endpoint, occurred in 66.1% of the control patients and 58.9% of the bypass recipients (p=0.02).

When the researchers looked exclusively at cardiovascular deaths, the rates were 49.3% in the medical-therapy group and 40.5% in the group receiving bypass in addition to standard medical care (p=0.006).

The combined odds of hospitalization or death from any cause were also lower with bypass.

For death or hospitalization for cardiovascular causes, there was a 10.4 percentage point difference (p<0.001). For death or hospitalization for heart failure, the difference was 8.6 points (p<0.002). It was for 6.4 percentage points for death or hospitalization for any cause (p=0.001).

Results from the study, known as STICHES, were released April 3 at the American College of Cardiology annual scientific session in Chicago and online by the New England Journal of Medicine.

Bypass grafting "was associated with more favorable results than medical therapy alone across all clinically relevant long-term outcomes we evaluated," said the team, led by Dr. Eric Velazquez of the Duke Clinical Research Institute at Duke University, Durham, North Carolina.

The trends "resulted from a persistent and perhaps increasing effect size over time," they said. "Thus, it appears that the operative risk associated with CABG is offset by a durable effect that translates into increasing clinical benefit to at least 10 years."

Coronary artery disease kills more than 538,000 people in the United States each year. Most of the studies establishing the benefits of bypass grafting were done more than 40 years ago.

The initial version of the new study was known as STICH and it followed patients at 99 sites in 22 countries for a median of just over four and a half years. It found no significant difference between the two treatments when it came to the rate of death from any cause. However, bypass recipients were less likely to die from a cardiovascular event or to die from any cause or be hospitalized for cardiovascular causes.

STICHES extends those results to 10 years and found that any-cause death became significant.

Median survival was 7.73 years with bypass and 6.29 years without. The researchers calculated that the number needed to treat to prevent one death was 14 patients. The number needed to prevent one death from a cardiovascular cause was 11.

Other secondary measures were the rates of death combined with specific cardiovascular events. Once again, they consistently found a benefit for bypass.

There was a 15.8 percentage point difference for any cause of death or revascularization (p<0.001). For death or nonfatal myocardial infarction the difference was 6.3 points and it was for 7.2 percentage points for death or nonfatal stroke (both p=0.03).

Among the 610 people originally assigned to the bypass group, 9% did not receive a graft before the end of the trial. In the 602 assigned to medical therapy alone, 19.8% underwent bypass surgery. Eleven percent had it within the first year.

In an accompanying editorial, Drs. Robert Guyton and Andrew Smith of Emory University in Atlanta, wrote, "The STICHES 10-year results firmly extend the survival benefit of CABG in patients with advanced coronary artery disease to patients with heart failure and severe ischemic cardiomyopathy. These findings should prompt strong consideration of coronary bypass as an addition to medical therapy in shared decision making with these patients."

The National Heart Lung and Blood Institute funded this research. Two coauthors reported disclosures.

NEW YORK (Reuters Health) - Ten-year results from a comparison of coronary-artery bypass grafting (CABG) with medical therapy alone has found that bypass lowers the odds of cardiovascular death by about nine percentage points in people with ischemic cardiomyopathy.

The 16% reduction in the death rate meant volunteers who received bypass grafting typically lived nearly a year and a half longer than those who received optimal nonsurgical therapy.

The findings are based on a study population of 1,212 patients with an ejection fraction of 35% or less who received bypass grafts between 2002 and 2007.

Death from any cause, the primary endpoint, occurred in 66.1% of the control patients and 58.9% of the bypass recipients (p=0.02).

When the researchers looked exclusively at cardiovascular deaths, the rates were 49.3% in the medical-therapy group and 40.5% in the group receiving bypass in addition to standard medical care (p=0.006).

The combined odds of hospitalization or death from any cause were also lower with bypass.

For death or hospitalization for cardiovascular causes, there was a 10.4 percentage point difference (p<0.001). For death or hospitalization for heart failure, the difference was 8.6 points (p<0.002). It was for 6.4 percentage points for death or hospitalization for any cause (p=0.001).

Results from the study, known as STICHES, were released April 3 at the American College of Cardiology annual scientific session in Chicago and online by the New England Journal of Medicine.

Bypass grafting "was associated with more favorable results than medical therapy alone across all clinically relevant long-term outcomes we evaluated," said the team, led by Dr. Eric Velazquez of the Duke Clinical Research Institute at Duke University, Durham, North Carolina.

The trends "resulted from a persistent and perhaps increasing effect size over time," they said. "Thus, it appears that the operative risk associated with CABG is offset by a durable effect that translates into increasing clinical benefit to at least 10 years."

Coronary artery disease kills more than 538,000 people in the United States each year. Most of the studies establishing the benefits of bypass grafting were done more than 40 years ago.

The initial version of the new study was known as STICH and it followed patients at 99 sites in 22 countries for a median of just over four and a half years. It found no significant difference between the two treatments when it came to the rate of death from any cause. However, bypass recipients were less likely to die from a cardiovascular event or to die from any cause or be hospitalized for cardiovascular causes.

STICHES extends those results to 10 years and found that any-cause death became significant.

Median survival was 7.73 years with bypass and 6.29 years without. The researchers calculated that the number needed to treat to prevent one death was 14 patients. The number needed to prevent one death from a cardiovascular cause was 11.

Other secondary measures were the rates of death combined with specific cardiovascular events. Once again, they consistently found a benefit for bypass.

There was a 15.8 percentage point difference for any cause of death or revascularization (p<0.001). For death or nonfatal myocardial infarction the difference was 6.3 points and it was for 7.2 percentage points for death or nonfatal stroke (both p=0.03).

Among the 610 people originally assigned to the bypass group, 9% did not receive a graft before the end of the trial. In the 602 assigned to medical therapy alone, 19.8% underwent bypass surgery. Eleven percent had it within the first year.

In an accompanying editorial, Drs. Robert Guyton and Andrew Smith of Emory University in Atlanta, wrote, "The STICHES 10-year results firmly extend the survival benefit of CABG in patients with advanced coronary artery disease to patients with heart failure and severe ischemic cardiomyopathy. These findings should prompt strong consideration of coronary bypass as an addition to medical therapy in shared decision making with these patients."

The National Heart Lung and Blood Institute funded this research. Two coauthors reported disclosures.

NEW YORK (Reuters Health) - Ten-year results from a comparison of coronary-artery bypass grafting (CABG) with medical therapy alone has found that bypass lowers the odds of cardiovascular death by about nine percentage points in people with ischemic cardiomyopathy.

The 16% reduction in the death rate meant volunteers who received bypass grafting typically lived nearly a year and a half longer than those who received optimal nonsurgical therapy.

The findings are based on a study population of 1,212 patients with an ejection fraction of 35% or less who received bypass grafts between 2002 and 2007.

Death from any cause, the primary endpoint, occurred in 66.1% of the control patients and 58.9% of the bypass recipients (p=0.02).

When the researchers looked exclusively at cardiovascular deaths, the rates were 49.3% in the medical-therapy group and 40.5% in the group receiving bypass in addition to standard medical care (p=0.006).

The combined odds of hospitalization or death from any cause were also lower with bypass.

For death or hospitalization for cardiovascular causes, there was a 10.4 percentage point difference (p<0.001). For death or hospitalization for heart failure, the difference was 8.6 points (p<0.002). It was for 6.4 percentage points for death or hospitalization for any cause (p=0.001).

Results from the study, known as STICHES, were released April 3 at the American College of Cardiology annual scientific session in Chicago and online by the New England Journal of Medicine.

Bypass grafting "was associated with more favorable results than medical therapy alone across all clinically relevant long-term outcomes we evaluated," said the team, led by Dr. Eric Velazquez of the Duke Clinical Research Institute at Duke University, Durham, North Carolina.

The trends "resulted from a persistent and perhaps increasing effect size over time," they said. "Thus, it appears that the operative risk associated with CABG is offset by a durable effect that translates into increasing clinical benefit to at least 10 years."

Coronary artery disease kills more than 538,000 people in the United States each year. Most of the studies establishing the benefits of bypass grafting were done more than 40 years ago.

The initial version of the new study was known as STICH and it followed patients at 99 sites in 22 countries for a median of just over four and a half years. It found no significant difference between the two treatments when it came to the rate of death from any cause. However, bypass recipients were less likely to die from a cardiovascular event or to die from any cause or be hospitalized for cardiovascular causes.

STICHES extends those results to 10 years and found that any-cause death became significant.

Median survival was 7.73 years with bypass and 6.29 years without. The researchers calculated that the number needed to treat to prevent one death was 14 patients. The number needed to prevent one death from a cardiovascular cause was 11.

Other secondary measures were the rates of death combined with specific cardiovascular events. Once again, they consistently found a benefit for bypass.

There was a 15.8 percentage point difference for any cause of death or revascularization (p<0.001). For death or nonfatal myocardial infarction the difference was 6.3 points and it was for 7.2 percentage points for death or nonfatal stroke (both p=0.03).

Among the 610 people originally assigned to the bypass group, 9% did not receive a graft before the end of the trial. In the 602 assigned to medical therapy alone, 19.8% underwent bypass surgery. Eleven percent had it within the first year.

In an accompanying editorial, Drs. Robert Guyton and Andrew Smith of Emory University in Atlanta, wrote, "The STICHES 10-year results firmly extend the survival benefit of CABG in patients with advanced coronary artery disease to patients with heart failure and severe ischemic cardiomyopathy. These findings should prompt strong consideration of coronary bypass as an addition to medical therapy in shared decision making with these patients."

The National Heart Lung and Blood Institute funded this research. Two coauthors reported disclosures.

Pregnant woman

Photo by Nina Matthews

After reviewing existing evidence, scientists from the US Centers for Disease Control and Prevention (CDC) have concluded that Zika virus causes

microcephaly and other severe fetal brain defects.

“This study marks a turning point in the Zika outbreak,” said Tom Frieden, MD, director of the CDC.

“It is now clear that the virus causes microcephaly. We’ve now confirmed what mounting evidence has suggested.”

Details on the CDC’s review were published in NEJM.

The report notes that no single piece of evidence provides conclusive proof that Zika virus infection is a cause of microcephaly and other fetal brain defects. Rather, increasing evidence from a number of recently published studies and a careful evaluation using established scientific criteria support the authors’ conclusions.

The finding that Zika virus infection can cause microcephaly and other severe fetal brain defects means that a woman who is infected with Zika during pregnancy has an increased risk of having a baby with these health problems.

However, as we’ve seen during the current Zika outbreak, some infected women deliver babies that appear to be healthy.

The CDC said establishing the causal relationship between Zika and fetal brain defects is an important step in driving additional prevention efforts, focusing research activities, and reinforcing the need for direct communication about the risks of Zika.

However, the agency noted that many questions about the Zika virus remain. And answering these questions will be the focus of ongoing research.

The CDC also said it is not changing its current recommendations regarding the Zika virus. Pregnant women should continue to avoid travel to areas where Zika is actively spreading.

If a pregnant woman travels to or lives in an area with active Zika virus transmission, she should talk with her healthcare provider and take steps to prevent mosquito bites and sexual transmission of the virus.

The CDC also encourages women and their partners in areas with active Zika transmission to engage in pregnancy planning and counseling with their healthcare providers so they know the risks and the ways to mitigate them.

Pregnant woman

Photo by Nina Matthews

After reviewing existing evidence, scientists from the US Centers for Disease Control and Prevention (CDC) have concluded that Zika virus causes

microcephaly and other severe fetal brain defects.

“This study marks a turning point in the Zika outbreak,” said Tom Frieden, MD, director of the CDC.

“It is now clear that the virus causes microcephaly. We’ve now confirmed what mounting evidence has suggested.”

Details on the CDC’s review were published in NEJM.

The report notes that no single piece of evidence provides conclusive proof that Zika virus infection is a cause of microcephaly and other fetal brain defects. Rather, increasing evidence from a number of recently published studies and a careful evaluation using established scientific criteria support the authors’ conclusions.

The finding that Zika virus infection can cause microcephaly and other severe fetal brain defects means that a woman who is infected with Zika during pregnancy has an increased risk of having a baby with these health problems.

However, as we’ve seen during the current Zika outbreak, some infected women deliver babies that appear to be healthy.

The CDC said establishing the causal relationship between Zika and fetal brain defects is an important step in driving additional prevention efforts, focusing research activities, and reinforcing the need for direct communication about the risks of Zika.

However, the agency noted that many questions about the Zika virus remain. And answering these questions will be the focus of ongoing research.

The CDC also said it is not changing its current recommendations regarding the Zika virus. Pregnant women should continue to avoid travel to areas where Zika is actively spreading.

If a pregnant woman travels to or lives in an area with active Zika virus transmission, she should talk with her healthcare provider and take steps to prevent mosquito bites and sexual transmission of the virus.

The CDC also encourages women and their partners in areas with active Zika transmission to engage in pregnancy planning and counseling with their healthcare providers so they know the risks and the ways to mitigate them.

Pregnant woman

Photo by Nina Matthews

After reviewing existing evidence, scientists from the US Centers for Disease Control and Prevention (CDC) have concluded that Zika virus causes

microcephaly and other severe fetal brain defects.

“This study marks a turning point in the Zika outbreak,” said Tom Frieden, MD, director of the CDC.

“It is now clear that the virus causes microcephaly. We’ve now confirmed what mounting evidence has suggested.”

Details on the CDC’s review were published in NEJM.

The report notes that no single piece of evidence provides conclusive proof that Zika virus infection is a cause of microcephaly and other fetal brain defects. Rather, increasing evidence from a number of recently published studies and a careful evaluation using established scientific criteria support the authors’ conclusions.

The finding that Zika virus infection can cause microcephaly and other severe fetal brain defects means that a woman who is infected with Zika during pregnancy has an increased risk of having a baby with these health problems.

However, as we’ve seen during the current Zika outbreak, some infected women deliver babies that appear to be healthy.

The CDC said establishing the causal relationship between Zika and fetal brain defects is an important step in driving additional prevention efforts, focusing research activities, and reinforcing the need for direct communication about the risks of Zika.

However, the agency noted that many questions about the Zika virus remain. And answering these questions will be the focus of ongoing research.

The CDC also said it is not changing its current recommendations regarding the Zika virus. Pregnant women should continue to avoid travel to areas where Zika is actively spreading.

If a pregnant woman travels to or lives in an area with active Zika virus transmission, she should talk with her healthcare provider and take steps to prevent mosquito bites and sexual transmission of the virus.

The CDC also encourages women and their partners in areas with active Zika transmission to engage in pregnancy planning and counseling with their healthcare providers so they know the risks and the ways to mitigate them.