More than 102,000 people in Colombia have been infected with Zika virus since October 2015—when their epidemic began—and more than 18,000 of those are pregnant women. In the U.S., 731 women have been diagnosed with laboratory evidence of possible Zika infection, as have 1,156 in U.S. territories.

To help keep those numbers from rising, the CDC and Colombia’s Instituto Nacional de Salud have signed a memorandum of understanding to collaborate on Zika virus response in Colombia. The collaboration—including surveillance and epidemiology—will provide “critical scientific information to help the United States, Colombia, and other countries prepare for the unprecedented challenges posed by Zika,” says CDC Director Thomas R. Frieden, MD.

Colombia has been a “superb partner” in efforts thus far, Frieden says: Since 2016, the CDC and the Instituto Nacional de Salud  have worked together on Proyecto VEZ (Vigilancia de Embarazadas con Zika) to enhance surveillance of women infected with Zika during pregnancy in 3 sites in Colombia. To date, the project has enrolled more than 900 women.

The 2 agencies are also beginning a prospective study, ZEN Colombia (Zika en Embarazadas y Niños en Colombia) to investigate the long-term effects of the virus infection in pregnant women, their male partners, and their children.

More than 102,000 people in Colombia have been infected with Zika virus since October 2015—when their epidemic began—and more than 18,000 of those are pregnant women. In the U.S., 731 women have been diagnosed with laboratory evidence of possible Zika infection, as have 1,156 in U.S. territories.

To help keep those numbers from rising, the CDC and Colombia’s Instituto Nacional de Salud have signed a memorandum of understanding to collaborate on Zika virus response in Colombia. The collaboration—including surveillance and epidemiology—will provide “critical scientific information to help the United States, Colombia, and other countries prepare for the unprecedented challenges posed by Zika,” says CDC Director Thomas R. Frieden, MD.

Colombia has been a “superb partner” in efforts thus far, Frieden says: Since 2016, the CDC and the Instituto Nacional de Salud  have worked together on Proyecto VEZ (Vigilancia de Embarazadas con Zika) to enhance surveillance of women infected with Zika during pregnancy in 3 sites in Colombia. To date, the project has enrolled more than 900 women.

The 2 agencies are also beginning a prospective study, ZEN Colombia (Zika en Embarazadas y Niños en Colombia) to investigate the long-term effects of the virus infection in pregnant women, their male partners, and their children.

More than 102,000 people in Colombia have been infected with Zika virus since October 2015—when their epidemic began—and more than 18,000 of those are pregnant women. In the U.S., 731 women have been diagnosed with laboratory evidence of possible Zika infection, as have 1,156 in U.S. territories.

To help keep those numbers from rising, the CDC and Colombia’s Instituto Nacional de Salud have signed a memorandum of understanding to collaborate on Zika virus response in Colombia. The collaboration—including surveillance and epidemiology—will provide “critical scientific information to help the United States, Colombia, and other countries prepare for the unprecedented challenges posed by Zika,” says CDC Director Thomas R. Frieden, MD.

Colombia has been a “superb partner” in efforts thus far, Frieden says: Since 2016, the CDC and the Instituto Nacional de Salud  have worked together on Proyecto VEZ (Vigilancia de Embarazadas con Zika) to enhance surveillance of women infected with Zika during pregnancy in 3 sites in Colombia. To date, the project has enrolled more than 900 women.

The 2 agencies are also beginning a prospective study, ZEN Colombia (Zika en Embarazadas y Niños en Colombia) to investigate the long-term effects of the virus infection in pregnant women, their male partners, and their children.

Many years ago during medical school, I took time out to pursue graduate studies in philosophy. At that time, I took a number of courses that explored various approaches to the philosophical questions of morality and ethics. My ultimate goal, even back then, was to focus on ethical issues in the practice of medicine.

I often found the philosophical discussions from the “giants” in philosophy were not always easy to apply to everyday problems. After completing my graduate studies in philosophy and nearing the end of medical school, I found that I was drawn to surgery. Not surprisingly, many surgical faculty that I interviewed with for my residency saw little application of my philosophy studies to the practice of surgery. Although I felt confident that ethics was central to the practice of surgery, I let pass the general suggestions from many senior surgeons that surgery and philosophical analysis have little in common.

In recent years, however, I have increasingly seen an area of overlap that I believe will be central to the future of surgery. The options for the treatment of critically ill surgical patients across all areas of surgery have increased dramatically. Just in the area of cardiovascular disease, patients with failing hearts have the option of mechanical assist devices. Patients with multiple comorbidities and vascular problems can have numerous endovascular procedures done that years ago would have been unthinkable. Consider a patient with a ventricular assist device on a ventilator who is being dialyzed. Such a patient may be supported for weeks or months beyond what was possible just a few decades ago.

Whereas our surgical forefathers were constantly asking the question, “What can be done for this patient?” those caring for critically ill patients today must repeatedly ask, “What should we do for this patient?” Years ago, the statement, “there is nothing more that we can offer” was much more commonly heard than it is today. The critical question for today – “What should be done?” – is often more challenging and nuanced than “what can be done?” Whenever we ask “what should be done?” we must take into account the values of the patient and weigh the possible outcomes and the inherent risks of the possible interventions with the patient’s goals.

The current necessity to answer “what should be done?” has several striking parallels with the classical philosophical problem of “is” and “ought.” Over the centuries, many philosophers have considered whether we can derive an “ought” from an “is.” In other words, just because one can show that something is the case in the world, it does not automatically follow that it ought to be that way. David Hume, the Scottish philosopher (1711-1776), famously argued that there is a tremendous difference between statements about what is and statements about what ought to be. In particular, Hume argued that we cannot logically derive an “ought” from an “is.”

Despite the centuries that have passed since Hume’s days, I believe that his analysis has much to teach modern surgery. Just because we can undertake many interventions for our patients, it does not follow that we should undertake all of those interventions. A central aspect of what many of us refer to commonly as “surgical judgment” is deciding among the many possible interventions for a patient, what specific ones ought we offer. Although this entire discussion may seem theoretical (and possibly even arcane) to some surgeons, I firmly believe that one of the greatest challenges to the future of surgery is whether surgeons are willing to address the question of what should be done for every patient.

Excellent surgeons have traditionally been seen as having both technical mastery and sound judgment. In the current era in which surgeons are increasingly pushed to do more cases and maximize RVUs, multiple forces are encouraging surgeons to increasingly become pure technicians. Technicians can answer the question “what can be done?” However, “what should be done for this specific patient?” is a question that only a physician can answer. In the decades to come, we must ensure that surgeons continue to engage in the harder questions of “what should be done?” so that we do not forget that “is” and “ought” are different. The mastery of surgery involves not only the technical expertise that can be applied on behalf of a patient, but also the appreciation and understanding of the patient’s values so that surgeons can make recommendations about what should be done for their patients.

Dr. Angelos is the Linda Kohler Anderson Professor of Surgery and Surgical Ethics; chief, endocrine surgery; and associate director of the MacLean Center for Clinical Medical Ethics at the University of Chicago.

Many years ago during medical school, I took time out to pursue graduate studies in philosophy. At that time, I took a number of courses that explored various approaches to the philosophical questions of morality and ethics. My ultimate goal, even back then, was to focus on ethical issues in the practice of medicine.

I often found the philosophical discussions from the “giants” in philosophy were not always easy to apply to everyday problems. After completing my graduate studies in philosophy and nearing the end of medical school, I found that I was drawn to surgery. Not surprisingly, many surgical faculty that I interviewed with for my residency saw little application of my philosophy studies to the practice of surgery. Although I felt confident that ethics was central to the practice of surgery, I let pass the general suggestions from many senior surgeons that surgery and philosophical analysis have little in common.

In recent years, however, I have increasingly seen an area of overlap that I believe will be central to the future of surgery. The options for the treatment of critically ill surgical patients across all areas of surgery have increased dramatically. Just in the area of cardiovascular disease, patients with failing hearts have the option of mechanical assist devices. Patients with multiple comorbidities and vascular problems can have numerous endovascular procedures done that years ago would have been unthinkable. Consider a patient with a ventricular assist device on a ventilator who is being dialyzed. Such a patient may be supported for weeks or months beyond what was possible just a few decades ago.

Whereas our surgical forefathers were constantly asking the question, “What can be done for this patient?” those caring for critically ill patients today must repeatedly ask, “What should we do for this patient?” Years ago, the statement, “there is nothing more that we can offer” was much more commonly heard than it is today. The critical question for today – “What should be done?” – is often more challenging and nuanced than “what can be done?” Whenever we ask “what should be done?” we must take into account the values of the patient and weigh the possible outcomes and the inherent risks of the possible interventions with the patient’s goals.

The current necessity to answer “what should be done?” has several striking parallels with the classical philosophical problem of “is” and “ought.” Over the centuries, many philosophers have considered whether we can derive an “ought” from an “is.” In other words, just because one can show that something is the case in the world, it does not automatically follow that it ought to be that way. David Hume, the Scottish philosopher (1711-1776), famously argued that there is a tremendous difference between statements about what is and statements about what ought to be. In particular, Hume argued that we cannot logically derive an “ought” from an “is.”

Despite the centuries that have passed since Hume’s days, I believe that his analysis has much to teach modern surgery. Just because we can undertake many interventions for our patients, it does not follow that we should undertake all of those interventions. A central aspect of what many of us refer to commonly as “surgical judgment” is deciding among the many possible interventions for a patient, what specific ones ought we offer. Although this entire discussion may seem theoretical (and possibly even arcane) to some surgeons, I firmly believe that one of the greatest challenges to the future of surgery is whether surgeons are willing to address the question of what should be done for every patient.

Excellent surgeons have traditionally been seen as having both technical mastery and sound judgment. In the current era in which surgeons are increasingly pushed to do more cases and maximize RVUs, multiple forces are encouraging surgeons to increasingly become pure technicians. Technicians can answer the question “what can be done?” However, “what should be done for this specific patient?” is a question that only a physician can answer. In the decades to come, we must ensure that surgeons continue to engage in the harder questions of “what should be done?” so that we do not forget that “is” and “ought” are different. The mastery of surgery involves not only the technical expertise that can be applied on behalf of a patient, but also the appreciation and understanding of the patient’s values so that surgeons can make recommendations about what should be done for their patients.

Dr. Angelos is the Linda Kohler Anderson Professor of Surgery and Surgical Ethics; chief, endocrine surgery; and associate director of the MacLean Center for Clinical Medical Ethics at the University of Chicago.

Many years ago during medical school, I took time out to pursue graduate studies in philosophy. At that time, I took a number of courses that explored various approaches to the philosophical questions of morality and ethics. My ultimate goal, even back then, was to focus on ethical issues in the practice of medicine.

I often found the philosophical discussions from the “giants” in philosophy were not always easy to apply to everyday problems. After completing my graduate studies in philosophy and nearing the end of medical school, I found that I was drawn to surgery. Not surprisingly, many surgical faculty that I interviewed with for my residency saw little application of my philosophy studies to the practice of surgery. Although I felt confident that ethics was central to the practice of surgery, I let pass the general suggestions from many senior surgeons that surgery and philosophical analysis have little in common.

In recent years, however, I have increasingly seen an area of overlap that I believe will be central to the future of surgery. The options for the treatment of critically ill surgical patients across all areas of surgery have increased dramatically. Just in the area of cardiovascular disease, patients with failing hearts have the option of mechanical assist devices. Patients with multiple comorbidities and vascular problems can have numerous endovascular procedures done that years ago would have been unthinkable. Consider a patient with a ventricular assist device on a ventilator who is being dialyzed. Such a patient may be supported for weeks or months beyond what was possible just a few decades ago.

Whereas our surgical forefathers were constantly asking the question, “What can be done for this patient?” those caring for critically ill patients today must repeatedly ask, “What should we do for this patient?” Years ago, the statement, “there is nothing more that we can offer” was much more commonly heard than it is today. The critical question for today – “What should be done?” – is often more challenging and nuanced than “what can be done?” Whenever we ask “what should be done?” we must take into account the values of the patient and weigh the possible outcomes and the inherent risks of the possible interventions with the patient’s goals.

The current necessity to answer “what should be done?” has several striking parallels with the classical philosophical problem of “is” and “ought.” Over the centuries, many philosophers have considered whether we can derive an “ought” from an “is.” In other words, just because one can show that something is the case in the world, it does not automatically follow that it ought to be that way. David Hume, the Scottish philosopher (1711-1776), famously argued that there is a tremendous difference between statements about what is and statements about what ought to be. In particular, Hume argued that we cannot logically derive an “ought” from an “is.”

Despite the centuries that have passed since Hume’s days, I believe that his analysis has much to teach modern surgery. Just because we can undertake many interventions for our patients, it does not follow that we should undertake all of those interventions. A central aspect of what many of us refer to commonly as “surgical judgment” is deciding among the many possible interventions for a patient, what specific ones ought we offer. Although this entire discussion may seem theoretical (and possibly even arcane) to some surgeons, I firmly believe that one of the greatest challenges to the future of surgery is whether surgeons are willing to address the question of what should be done for every patient.

Excellent surgeons have traditionally been seen as having both technical mastery and sound judgment. In the current era in which surgeons are increasingly pushed to do more cases and maximize RVUs, multiple forces are encouraging surgeons to increasingly become pure technicians. Technicians can answer the question “what can be done?” However, “what should be done for this specific patient?” is a question that only a physician can answer. In the decades to come, we must ensure that surgeons continue to engage in the harder questions of “what should be done?” so that we do not forget that “is” and “ought” are different. The mastery of surgery involves not only the technical expertise that can be applied on behalf of a patient, but also the appreciation and understanding of the patient’s values so that surgeons can make recommendations about what should be done for their patients.

Dr. Angelos is the Linda Kohler Anderson Professor of Surgery and Surgical Ethics; chief, endocrine surgery; and associate director of the MacLean Center for Clinical Medical Ethics at the University of Chicago.

Detection of thyroid cancer is widespread, increasing by about 4.5% annually. In the past year, approximately 64,300 new cases were identified. An estimated one in 100 people will be diagnosed with thyroid cancer during their lifetime, making it the eighth most common cancer in the United States.¹

Incidental thyroid nodules found on carotid ultrasounds and other neck imaging may account for much of the increase; evaluation of these “incidentalomas” may account for the doubling incidence of thyroid cancer cases. (For more on thyroid nodules, see “To Cut or Not to Cut?” Clinician Reviews. 2016;26[8]:34-36.) If this pace continues, thyroid cancer may become the third most common cancer among women in the US by 2019.²

RISK FACTORS

Generally, women are diagnosed with thyroid cancer more frequently than men.³ Other risk factors include

• Age (40 to 60 in women; 60 to 80 in men; median age at diagnosis, 51)
• Inherited conditions, such as multiple endocrine neoplasia (MEN) or familial medullary and nonmedullary thyroid carcinoma
• Other cancers, including breast cancer and familial adenomatous polyposis
• Iodine deficiency
• Radiation exposure, particularly head and neck radiation in childhood. This can be through treatment of acne, tinea capitis, enlarged tonsils, or adenoids (usually prior to 1960); treatment of lymphoma, Wilms tumor, or neuroblastoma; or proximity to Chernobyl in 1986.^1,2

BIOPSY RECOMMENDATIONS

While thyroid nodules are fairly common, only 7% to 15% of nodules are found to be malignant.² However, all patients presenting with a palpable thyroid nodule should undergo thyroid ultrasound for further evaluation.

According to American Thyroid Association guidelines, all nodules 2 cm or larger should be evaluated with fine needle aspiration (FNA) due to a concern for metastatic thyroid cancer in larger nodules.² Some clinicians prefer to aspirate nodules 1 cm or larger. Nodules that are smaller than 2 cm with sonographic features suspicious for thyroid cancer (see Table 1) should be biopsied.

Nodules that are spongiform in appearance or are completely cystic with no solid components may be monitored without FNA.²

The FNA is typically performed by an endocrinologist under ultrasound guidance. No anesthetic is required, but a topical ethyl chloride spray can assist with patient comfort. Three to four passes are made into the nodule with a 27-gauge needle; most patients describe pressure or a pinching sensation, rather than pain, during the procedure. After the procedure, ice applied to the FNA area may help with patient comfort.

 

 

TYPES OF THYROID CANCER

Four possible types of thyroid cancer are identified on pathology after FNA: papillary, follicular, medullary, and anaplastic. Differentiated thyroid cancers, which encompass papillary and follicular cancers, are the most commonly diagnosed. Approximately 90% of thyroid cancers fall into this category.²

In most cases of differentiated thyroid cancer, patients can be treated with thyroidectomy alone if the cancer remains confined to the thyroid.² Just over two-thirds of differentiated thyroid cancer cases are localized in the thyroid. The five-year survival rate for these patients is nearly 100%.¹

About 27% of differentiated thyroid cancer is also found in neck lymph nodes; these patients may be treated with thyroidectomy and radioactive iodine.² The five-year survival rate in these cases is nearly 98%.¹ Chemotherapy is generally not needed for differentiated thyroid cancers.

Medullary thyroid cancer (MTC) is diagnosed in up to 4% of thyroid cancer patients. Characterized by high levels of calcitonin, MTC can be genetically mediated or sporadic. MTC is associated with a variety of RET oncogene mutations; genetic testing of family members is recommended, as well as prophylactic thyroidectomy when high-risk RET oncogenes are detected.³

The 10-year survival prognosis for MTC patients varies according to stage at diagnosis (see Table 2). Up to 70% of patients with a palpable MTC nodule present with metastasis consistent with stage III or IV disease.³

Medullary thyroid cancer is treated with total thyroidectomy and cervical lymph node dissection. Radioactive iodine has not been proven effective for MTC patients, unless there is also papillary or follicular thyroid cancer present.³

Anaplastic thyroid cancer has the highest mortality rate of all types of thyroid cancer. Fortunately, it is relatively rare, occurring in only 1.7% of thyroid cancer patients. The one-year survival rate is 20%, with a median postdiagnosis survival prognosis of approximately five months. Anaplastic thyroid cancer is treated with total thyroidectomy and radical neck dissection when it is considered resectable. Metastatic lesions in the brain or spine are often indicators of unresectable disease. In some cases, external beam radiation therapy is used as palliative treatment.⁴

 

 

PEDIATRIC INCIDENCE

Thyroid cancer in children is rare, making up only 1.8% of all pediatric cancers diagnosed in the US annually. Patients are most often between ages 15 and 19, but it is possible for thyroid cancer to manifest in younger patients. Thyroid nodules are more likely to be malignant in children, with a greater incidence of metastatic disease at diagnosis. Prognosis is generally better in children than in adults, however, even with extensive disease.⁵

Children with prior history of other types of cancer treated with radiation, such as Hodgkin lymphoma or leukemia, are at increased risk for thyroid cancer and should be monitored.⁵ Children with a family history of MEN or MTC and evidence of RET oncogenes should be monitored starting as early as age 3 with thyroid exam, ultrasound, and measurement of calcitonin levels.³ Prophylactic thyroidectomy is an option in the first few months of life, depending on the presence of specific RET oncogenes.³

CHEMOTHERAPY

Chemotherapy may be helpful for metastatic medullary or anaplastic thyroid cancer, particularly in patients with unresectable disease. Though not usually curative, it may increase progression-free survival time. New chemotherapy agents approved for use in metastatic MTC include cabozantinib and vandetanib.³ Carboplatin, docetaxel, doxorubicin, and pac­litaxel are used in treatment of anaplastic thyroid cancer.⁴

 

 

LONG-TERM PATIENT MANAGEMENT

After thyroidectomy and radioactive iodine treatment, follicular cell cancers (eg, papillary, follicular, anaplastic) are managed by following patients’ thyroid-stimulating hormone (TSH), thyroglobulin, and antithyroglobulin antibody levels. A cervical ultrasound is performed to detect possible disease in lymph nodes.²

Levothyroxine is dosed to suppress TSH below the recommended levels for hypothyroid patients in order to prevent disease recurrence. Low-risk patients may have TSH suppression below 1 to 2 mU/L, while high-risk patients may be managed with TSH levels below 0.1 mU/L.²

Lab levels should be checked annually and a cervical ultrasound performed at six to 12 months, then periodically thereafter depending on patient risk status.² Patients with long-term TSH suppression must be monitored for atrial fibrillation and osteoporosis.

Patients who have been treated for medullary thyroid cancer require a different long-term management strategy. Patients should have ultrasound and measurement of TSH as well as calcitonin and carcinoembryonic antigen levels every six to 12 months.³ TSH suppression is not required; TSH may be maintained at typical euthyroid levels.

A FINAL THOUGHT

For clinicians, it’s easy to attempt to minimize thyroid cancer, since the disease is curable for most patients without the burden of chemotherapy and external radiation. However, for a patient, this is still a cancer diagnosis, with the accompanying surgery and required lifelong monitoring. It can be very disruptive to the lives of both patients and their families.

Support groups are available to help patients navigate their new reality. The Thyroid Cancer Survivors’ Association (www.thyca.org) has resources that may be beneficial to patients (and caregivers) as they learn how to live as a thyroid cancer survivor.

Detection of thyroid cancer is widespread, increasing by about 4.5% annually. In the past year, approximately 64,300 new cases were identified. An estimated one in 100 people will be diagnosed with thyroid cancer during their lifetime, making it the eighth most common cancer in the United States.¹

Incidental thyroid nodules found on carotid ultrasounds and other neck imaging may account for much of the increase; evaluation of these “incidentalomas” may account for the doubling incidence of thyroid cancer cases. (For more on thyroid nodules, see “To Cut or Not to Cut?” Clinician Reviews. 2016;26[8]:34-36.) If this pace continues, thyroid cancer may become the third most common cancer among women in the US by 2019.²

RISK FACTORS

Generally, women are diagnosed with thyroid cancer more frequently than men.³ Other risk factors include

• Age (40 to 60 in women; 60 to 80 in men; median age at diagnosis, 51)
• Inherited conditions, such as multiple endocrine neoplasia (MEN) or familial medullary and nonmedullary thyroid carcinoma
• Other cancers, including breast cancer and familial adenomatous polyposis
• Iodine deficiency
• Radiation exposure, particularly head and neck radiation in childhood. This can be through treatment of acne, tinea capitis, enlarged tonsils, or adenoids (usually prior to 1960); treatment of lymphoma, Wilms tumor, or neuroblastoma; or proximity to Chernobyl in 1986.^1,2

BIOPSY RECOMMENDATIONS

While thyroid nodules are fairly common, only 7% to 15% of nodules are found to be malignant.² However, all patients presenting with a palpable thyroid nodule should undergo thyroid ultrasound for further evaluation.

According to American Thyroid Association guidelines, all nodules 2 cm or larger should be evaluated with fine needle aspiration (FNA) due to a concern for metastatic thyroid cancer in larger nodules.² Some clinicians prefer to aspirate nodules 1 cm or larger. Nodules that are smaller than 2 cm with sonographic features suspicious for thyroid cancer (see Table 1) should be biopsied.

Nodules that are spongiform in appearance or are completely cystic with no solid components may be monitored without FNA.²

The FNA is typically performed by an endocrinologist under ultrasound guidance. No anesthetic is required, but a topical ethyl chloride spray can assist with patient comfort. Three to four passes are made into the nodule with a 27-gauge needle; most patients describe pressure or a pinching sensation, rather than pain, during the procedure. After the procedure, ice applied to the FNA area may help with patient comfort.

 

 

TYPES OF THYROID CANCER

Four possible types of thyroid cancer are identified on pathology after FNA: papillary, follicular, medullary, and anaplastic. Differentiated thyroid cancers, which encompass papillary and follicular cancers, are the most commonly diagnosed. Approximately 90% of thyroid cancers fall into this category.²

In most cases of differentiated thyroid cancer, patients can be treated with thyroidectomy alone if the cancer remains confined to the thyroid.² Just over two-thirds of differentiated thyroid cancer cases are localized in the thyroid. The five-year survival rate for these patients is nearly 100%.¹

About 27% of differentiated thyroid cancer is also found in neck lymph nodes; these patients may be treated with thyroidectomy and radioactive iodine.² The five-year survival rate in these cases is nearly 98%.¹ Chemotherapy is generally not needed for differentiated thyroid cancers.

Medullary thyroid cancer (MTC) is diagnosed in up to 4% of thyroid cancer patients. Characterized by high levels of calcitonin, MTC can be genetically mediated or sporadic. MTC is associated with a variety of RET oncogene mutations; genetic testing of family members is recommended, as well as prophylactic thyroidectomy when high-risk RET oncogenes are detected.³

The 10-year survival prognosis for MTC patients varies according to stage at diagnosis (see Table 2). Up to 70% of patients with a palpable MTC nodule present with metastasis consistent with stage III or IV disease.³

Medullary thyroid cancer is treated with total thyroidectomy and cervical lymph node dissection. Radioactive iodine has not been proven effective for MTC patients, unless there is also papillary or follicular thyroid cancer present.³

Anaplastic thyroid cancer has the highest mortality rate of all types of thyroid cancer. Fortunately, it is relatively rare, occurring in only 1.7% of thyroid cancer patients. The one-year survival rate is 20%, with a median postdiagnosis survival prognosis of approximately five months. Anaplastic thyroid cancer is treated with total thyroidectomy and radical neck dissection when it is considered resectable. Metastatic lesions in the brain or spine are often indicators of unresectable disease. In some cases, external beam radiation therapy is used as palliative treatment.⁴

 

 

PEDIATRIC INCIDENCE

Thyroid cancer in children is rare, making up only 1.8% of all pediatric cancers diagnosed in the US annually. Patients are most often between ages 15 and 19, but it is possible for thyroid cancer to manifest in younger patients. Thyroid nodules are more likely to be malignant in children, with a greater incidence of metastatic disease at diagnosis. Prognosis is generally better in children than in adults, however, even with extensive disease.⁵

Children with prior history of other types of cancer treated with radiation, such as Hodgkin lymphoma or leukemia, are at increased risk for thyroid cancer and should be monitored.⁵ Children with a family history of MEN or MTC and evidence of RET oncogenes should be monitored starting as early as age 3 with thyroid exam, ultrasound, and measurement of calcitonin levels.³ Prophylactic thyroidectomy is an option in the first few months of life, depending on the presence of specific RET oncogenes.³

CHEMOTHERAPY

Chemotherapy may be helpful for metastatic medullary or anaplastic thyroid cancer, particularly in patients with unresectable disease. Though not usually curative, it may increase progression-free survival time. New chemotherapy agents approved for use in metastatic MTC include cabozantinib and vandetanib.³ Carboplatin, docetaxel, doxorubicin, and pac­litaxel are used in treatment of anaplastic thyroid cancer.⁴

 

 

LONG-TERM PATIENT MANAGEMENT

After thyroidectomy and radioactive iodine treatment, follicular cell cancers (eg, papillary, follicular, anaplastic) are managed by following patients’ thyroid-stimulating hormone (TSH), thyroglobulin, and antithyroglobulin antibody levels. A cervical ultrasound is performed to detect possible disease in lymph nodes.²

Levothyroxine is dosed to suppress TSH below the recommended levels for hypothyroid patients in order to prevent disease recurrence. Low-risk patients may have TSH suppression below 1 to 2 mU/L, while high-risk patients may be managed with TSH levels below 0.1 mU/L.²

Lab levels should be checked annually and a cervical ultrasound performed at six to 12 months, then periodically thereafter depending on patient risk status.² Patients with long-term TSH suppression must be monitored for atrial fibrillation and osteoporosis.

Patients who have been treated for medullary thyroid cancer require a different long-term management strategy. Patients should have ultrasound and measurement of TSH as well as calcitonin and carcinoembryonic antigen levels every six to 12 months.³ TSH suppression is not required; TSH may be maintained at typical euthyroid levels.

A FINAL THOUGHT

For clinicians, it’s easy to attempt to minimize thyroid cancer, since the disease is curable for most patients without the burden of chemotherapy and external radiation. However, for a patient, this is still a cancer diagnosis, with the accompanying surgery and required lifelong monitoring. It can be very disruptive to the lives of both patients and their families.

Support groups are available to help patients navigate their new reality. The Thyroid Cancer Survivors’ Association (www.thyca.org) has resources that may be beneficial to patients (and caregivers) as they learn how to live as a thyroid cancer survivor.

Detection of thyroid cancer is widespread, increasing by about 4.5% annually. In the past year, approximately 64,300 new cases were identified. An estimated one in 100 people will be diagnosed with thyroid cancer during their lifetime, making it the eighth most common cancer in the United States.¹

Incidental thyroid nodules found on carotid ultrasounds and other neck imaging may account for much of the increase; evaluation of these “incidentalomas” may account for the doubling incidence of thyroid cancer cases. (For more on thyroid nodules, see “To Cut or Not to Cut?” Clinician Reviews. 2016;26[8]:34-36.) If this pace continues, thyroid cancer may become the third most common cancer among women in the US by 2019.²

RISK FACTORS

Generally, women are diagnosed with thyroid cancer more frequently than men.³ Other risk factors include

• Age (40 to 60 in women; 60 to 80 in men; median age at diagnosis, 51)
• Inherited conditions, such as multiple endocrine neoplasia (MEN) or familial medullary and nonmedullary thyroid carcinoma
• Other cancers, including breast cancer and familial adenomatous polyposis
• Iodine deficiency
• Radiation exposure, particularly head and neck radiation in childhood. This can be through treatment of acne, tinea capitis, enlarged tonsils, or adenoids (usually prior to 1960); treatment of lymphoma, Wilms tumor, or neuroblastoma; or proximity to Chernobyl in 1986.^1,2

BIOPSY RECOMMENDATIONS

While thyroid nodules are fairly common, only 7% to 15% of nodules are found to be malignant.² However, all patients presenting with a palpable thyroid nodule should undergo thyroid ultrasound for further evaluation.

According to American Thyroid Association guidelines, all nodules 2 cm or larger should be evaluated with fine needle aspiration (FNA) due to a concern for metastatic thyroid cancer in larger nodules.² Some clinicians prefer to aspirate nodules 1 cm or larger. Nodules that are smaller than 2 cm with sonographic features suspicious for thyroid cancer (see Table 1) should be biopsied.

Nodules that are spongiform in appearance or are completely cystic with no solid components may be monitored without FNA.²

The FNA is typically performed by an endocrinologist under ultrasound guidance. No anesthetic is required, but a topical ethyl chloride spray can assist with patient comfort. Three to four passes are made into the nodule with a 27-gauge needle; most patients describe pressure or a pinching sensation, rather than pain, during the procedure. After the procedure, ice applied to the FNA area may help with patient comfort.

 

 

TYPES OF THYROID CANCER

Four possible types of thyroid cancer are identified on pathology after FNA: papillary, follicular, medullary, and anaplastic. Differentiated thyroid cancers, which encompass papillary and follicular cancers, are the most commonly diagnosed. Approximately 90% of thyroid cancers fall into this category.²

In most cases of differentiated thyroid cancer, patients can be treated with thyroidectomy alone if the cancer remains confined to the thyroid.² Just over two-thirds of differentiated thyroid cancer cases are localized in the thyroid. The five-year survival rate for these patients is nearly 100%.¹

About 27% of differentiated thyroid cancer is also found in neck lymph nodes; these patients may be treated with thyroidectomy and radioactive iodine.² The five-year survival rate in these cases is nearly 98%.¹ Chemotherapy is generally not needed for differentiated thyroid cancers.

Medullary thyroid cancer (MTC) is diagnosed in up to 4% of thyroid cancer patients. Characterized by high levels of calcitonin, MTC can be genetically mediated or sporadic. MTC is associated with a variety of RET oncogene mutations; genetic testing of family members is recommended, as well as prophylactic thyroidectomy when high-risk RET oncogenes are detected.³

The 10-year survival prognosis for MTC patients varies according to stage at diagnosis (see Table 2). Up to 70% of patients with a palpable MTC nodule present with metastasis consistent with stage III or IV disease.³

Medullary thyroid cancer is treated with total thyroidectomy and cervical lymph node dissection. Radioactive iodine has not been proven effective for MTC patients, unless there is also papillary or follicular thyroid cancer present.³

Anaplastic thyroid cancer has the highest mortality rate of all types of thyroid cancer. Fortunately, it is relatively rare, occurring in only 1.7% of thyroid cancer patients. The one-year survival rate is 20%, with a median postdiagnosis survival prognosis of approximately five months. Anaplastic thyroid cancer is treated with total thyroidectomy and radical neck dissection when it is considered resectable. Metastatic lesions in the brain or spine are often indicators of unresectable disease. In some cases, external beam radiation therapy is used as palliative treatment.⁴

 

 

PEDIATRIC INCIDENCE

Thyroid cancer in children is rare, making up only 1.8% of all pediatric cancers diagnosed in the US annually. Patients are most often between ages 15 and 19, but it is possible for thyroid cancer to manifest in younger patients. Thyroid nodules are more likely to be malignant in children, with a greater incidence of metastatic disease at diagnosis. Prognosis is generally better in children than in adults, however, even with extensive disease.⁵

Children with prior history of other types of cancer treated with radiation, such as Hodgkin lymphoma or leukemia, are at increased risk for thyroid cancer and should be monitored.⁵ Children with a family history of MEN or MTC and evidence of RET oncogenes should be monitored starting as early as age 3 with thyroid exam, ultrasound, and measurement of calcitonin levels.³ Prophylactic thyroidectomy is an option in the first few months of life, depending on the presence of specific RET oncogenes.³

CHEMOTHERAPY

Chemotherapy may be helpful for metastatic medullary or anaplastic thyroid cancer, particularly in patients with unresectable disease. Though not usually curative, it may increase progression-free survival time. New chemotherapy agents approved for use in metastatic MTC include cabozantinib and vandetanib.³ Carboplatin, docetaxel, doxorubicin, and pac­litaxel are used in treatment of anaplastic thyroid cancer.⁴

 

 

LONG-TERM PATIENT MANAGEMENT

After thyroidectomy and radioactive iodine treatment, follicular cell cancers (eg, papillary, follicular, anaplastic) are managed by following patients’ thyroid-stimulating hormone (TSH), thyroglobulin, and antithyroglobulin antibody levels. A cervical ultrasound is performed to detect possible disease in lymph nodes.²

Levothyroxine is dosed to suppress TSH below the recommended levels for hypothyroid patients in order to prevent disease recurrence. Low-risk patients may have TSH suppression below 1 to 2 mU/L, while high-risk patients may be managed with TSH levels below 0.1 mU/L.²

Lab levels should be checked annually and a cervical ultrasound performed at six to 12 months, then periodically thereafter depending on patient risk status.² Patients with long-term TSH suppression must be monitored for atrial fibrillation and osteoporosis.

Patients who have been treated for medullary thyroid cancer require a different long-term management strategy. Patients should have ultrasound and measurement of TSH as well as calcitonin and carcinoembryonic antigen levels every six to 12 months.³ TSH suppression is not required; TSH may be maintained at typical euthyroid levels.

A FINAL THOUGHT

For clinicians, it’s easy to attempt to minimize thyroid cancer, since the disease is curable for most patients without the burden of chemotherapy and external radiation. However, for a patient, this is still a cancer diagnosis, with the accompanying surgery and required lifelong monitoring. It can be very disruptive to the lives of both patients and their families.

Support groups are available to help patients navigate their new reality. The Thyroid Cancer Survivors’ Association (www.thyca.org) has resources that may be beneficial to patients (and caregivers) as they learn how to live as a thyroid cancer survivor.

The email came with the words, “It is with sadness we report that Frank Moody died. …” I was instantly transported to the last time I saw the man and a flood of emotions swept over me. The name Frank Moody will ring a distant bell or none at all to some in our profession. Like many of the greats of surgery, he belongs to the ages.

I remember the first time I asked a student, “Who is Michael DeBakey?” I was dumbfounded to be greeted with a blank stare. How could a student of medicine not know of Dr. DeBakey? A few years later, the same question prompted a smart aleck reply that he was the man who invented DeBakey forceps. Well, of course he did invent the forceps, but to know nothing further of the man who was the world’s expert on ulcer disease in the 1940s, the progenitor of the National Medical Library, and among the foremost pioneers of heart surgery seemed beyond belief.

Photo credit: Dwight Andrews/UTHealth

My mentor, Ernest Poulos, has long since left the active surgical scene. At times he would note the passing of one of his heroes like Carl Moyer (look it up!) and say, “Sic transit gloria mundi.” At 27 and anxious to get the right to cut into my fellow human beings, I would cock my head like a confounded puppy and wonder what that meant. I looked up the translation and meaning long ago, but now with age I understand the phrase in my bones.

I have long been a hanger-on at surgical meetings, hoping to meet those mighty figures that shaped surgical history. I saw W. Dean Warren once and had a very long hour with the great Mark Ravitch. Oliver Beahrs once performed magic tricks at a dinner I attended. At every surgical meeting there is an old guy (and now occasionally with the change in our profession, an elderly lady) getting on the bus to go to the reception or dinner dance. Often they are alone, their spouses having departed before them. As a young man, I wondered why the heck they came to the meetings. Just like every generation before, ours was eager to grab the reins, and in our ardor for future glory, we were polite but also restless for them to move aside. I hadn’t yet learned the importance of history and of listening.

What I missed while carousing with my young colleagues was an opportunity to hear history first hand and to learn that, what we thought was so cutting edge, these men and women had long ago considered. Many of our living legends imagined some of today’s innovations but they lacked the technology to bring their dreams to fruition, or time and age defeated them before they reached the final chapter of their research. It was when I was about 50 that I wised up and began seeking out living legends like Frank Moody and Frank Spencer.

In the case of Frank Moody, he was quite elderly when I first met him. For some reason, he knew who I was and shook my hand softly. I didn’t recognize him initially, but at the sound of his name, I knew I was in the presence of a major figure in 20th century gastrointestinal surgery. He had been at the University of California, San Francisco, during an historic time when George Sheldon, Donald Trunkey and other great surgeons trained there with J. Englebert Dunphy as their chief. Dr. Moody’s CV lists 141 articles in basic and clinical science that have had a profound impact on how we view the gastrointestinal tract. He was Chief at the University of Utah and the University of Alabama and finished his career as professor at the University of Texas-Houston. His awards and achievements were legion.

Parkinson’s had only recently really begun to affect him when I met him, and as the years went by his voice became so very faint that I had to lean in to hear him. We would sit together at the back of the dinner dance room so that we could hear each other. And while the other guests entertained themselves, Dr. Moody and I would discuss his life, scientific method and philosophy as well as his insights into his own case of Parkinsonism. I would see him at meetings, making his way slowly but steadily along a corridor while others briskly walked by, unaware that the man they just passed was among the most important surgical pioneers of our time. It was not sad that Dr. Moody was elderly and unrecognized, but that we younger surgeons missed knowing a great man in our tendency to rush past history.

History is not facts and dates, but rather, it is people and their lives. Yes, the history of our profession is embodied by pioneers like Frank Moody and the others I’ve mentioned.

We have many Fellows among us who are living history, still contributing – maybe not at the dais but at the dinner table, speaking softly and walking a bit slower than their juniors. Thanks to LaMar McGinnis who started it and Don Nakayama who continues it, the College has a History Community on the ACS Communities, an active Surgical History Group, and a will to acknowledge the history that lives and breathes among us. The Surgical History Group has organized a full program of events at the Clinical Congress and I hope many attendees take the opportunity to attend.

Take a moment at your next meeting or at the Clinical Congress and look for those historic surgeons still with us. Be smarter than I was at a young age and get to know them. You may learn something from them you can’t learn anyplace else.

Dr. Hughes is clinical professor in the department of surgery and director of medical education at the Kansas University School of Medicine, Salina Campus, and Co-Editor of ACS Surgery News.

The email came with the words, “It is with sadness we report that Frank Moody died. …” I was instantly transported to the last time I saw the man and a flood of emotions swept over me. The name Frank Moody will ring a distant bell or none at all to some in our profession. Like many of the greats of surgery, he belongs to the ages.

I remember the first time I asked a student, “Who is Michael DeBakey?” I was dumbfounded to be greeted with a blank stare. How could a student of medicine not know of Dr. DeBakey? A few years later, the same question prompted a smart aleck reply that he was the man who invented DeBakey forceps. Well, of course he did invent the forceps, but to know nothing further of the man who was the world’s expert on ulcer disease in the 1940s, the progenitor of the National Medical Library, and among the foremost pioneers of heart surgery seemed beyond belief.

Photo credit: Dwight Andrews/UTHealth

My mentor, Ernest Poulos, has long since left the active surgical scene. At times he would note the passing of one of his heroes like Carl Moyer (look it up!) and say, “Sic transit gloria mundi.” At 27 and anxious to get the right to cut into my fellow human beings, I would cock my head like a confounded puppy and wonder what that meant. I looked up the translation and meaning long ago, but now with age I understand the phrase in my bones.

I have long been a hanger-on at surgical meetings, hoping to meet those mighty figures that shaped surgical history. I saw W. Dean Warren once and had a very long hour with the great Mark Ravitch. Oliver Beahrs once performed magic tricks at a dinner I attended. At every surgical meeting there is an old guy (and now occasionally with the change in our profession, an elderly lady) getting on the bus to go to the reception or dinner dance. Often they are alone, their spouses having departed before them. As a young man, I wondered why the heck they came to the meetings. Just like every generation before, ours was eager to grab the reins, and in our ardor for future glory, we were polite but also restless for them to move aside. I hadn’t yet learned the importance of history and of listening.

What I missed while carousing with my young colleagues was an opportunity to hear history first hand and to learn that, what we thought was so cutting edge, these men and women had long ago considered. Many of our living legends imagined some of today’s innovations but they lacked the technology to bring their dreams to fruition, or time and age defeated them before they reached the final chapter of their research. It was when I was about 50 that I wised up and began seeking out living legends like Frank Moody and Frank Spencer.

In the case of Frank Moody, he was quite elderly when I first met him. For some reason, he knew who I was and shook my hand softly. I didn’t recognize him initially, but at the sound of his name, I knew I was in the presence of a major figure in 20th century gastrointestinal surgery. He had been at the University of California, San Francisco, during an historic time when George Sheldon, Donald Trunkey and other great surgeons trained there with J. Englebert Dunphy as their chief. Dr. Moody’s CV lists 141 articles in basic and clinical science that have had a profound impact on how we view the gastrointestinal tract. He was Chief at the University of Utah and the University of Alabama and finished his career as professor at the University of Texas-Houston. His awards and achievements were legion.

Parkinson’s had only recently really begun to affect him when I met him, and as the years went by his voice became so very faint that I had to lean in to hear him. We would sit together at the back of the dinner dance room so that we could hear each other. And while the other guests entertained themselves, Dr. Moody and I would discuss his life, scientific method and philosophy as well as his insights into his own case of Parkinsonism. I would see him at meetings, making his way slowly but steadily along a corridor while others briskly walked by, unaware that the man they just passed was among the most important surgical pioneers of our time. It was not sad that Dr. Moody was elderly and unrecognized, but that we younger surgeons missed knowing a great man in our tendency to rush past history.

History is not facts and dates, but rather, it is people and their lives. Yes, the history of our profession is embodied by pioneers like Frank Moody and the others I’ve mentioned.

We have many Fellows among us who are living history, still contributing – maybe not at the dais but at the dinner table, speaking softly and walking a bit slower than their juniors. Thanks to LaMar McGinnis who started it and Don Nakayama who continues it, the College has a History Community on the ACS Communities, an active Surgical History Group, and a will to acknowledge the history that lives and breathes among us. The Surgical History Group has organized a full program of events at the Clinical Congress and I hope many attendees take the opportunity to attend.

Take a moment at your next meeting or at the Clinical Congress and look for those historic surgeons still with us. Be smarter than I was at a young age and get to know them. You may learn something from them you can’t learn anyplace else.

Dr. Hughes is clinical professor in the department of surgery and director of medical education at the Kansas University School of Medicine, Salina Campus, and Co-Editor of ACS Surgery News.

The email came with the words, “It is with sadness we report that Frank Moody died. …” I was instantly transported to the last time I saw the man and a flood of emotions swept over me. The name Frank Moody will ring a distant bell or none at all to some in our profession. Like many of the greats of surgery, he belongs to the ages.

I remember the first time I asked a student, “Who is Michael DeBakey?” I was dumbfounded to be greeted with a blank stare. How could a student of medicine not know of Dr. DeBakey? A few years later, the same question prompted a smart aleck reply that he was the man who invented DeBakey forceps. Well, of course he did invent the forceps, but to know nothing further of the man who was the world’s expert on ulcer disease in the 1940s, the progenitor of the National Medical Library, and among the foremost pioneers of heart surgery seemed beyond belief.

Photo credit: Dwight Andrews/UTHealth

My mentor, Ernest Poulos, has long since left the active surgical scene. At times he would note the passing of one of his heroes like Carl Moyer (look it up!) and say, “Sic transit gloria mundi.” At 27 and anxious to get the right to cut into my fellow human beings, I would cock my head like a confounded puppy and wonder what that meant. I looked up the translation and meaning long ago, but now with age I understand the phrase in my bones.

I have long been a hanger-on at surgical meetings, hoping to meet those mighty figures that shaped surgical history. I saw W. Dean Warren once and had a very long hour with the great Mark Ravitch. Oliver Beahrs once performed magic tricks at a dinner I attended. At every surgical meeting there is an old guy (and now occasionally with the change in our profession, an elderly lady) getting on the bus to go to the reception or dinner dance. Often they are alone, their spouses having departed before them. As a young man, I wondered why the heck they came to the meetings. Just like every generation before, ours was eager to grab the reins, and in our ardor for future glory, we were polite but also restless for them to move aside. I hadn’t yet learned the importance of history and of listening.

What I missed while carousing with my young colleagues was an opportunity to hear history first hand and to learn that, what we thought was so cutting edge, these men and women had long ago considered. Many of our living legends imagined some of today’s innovations but they lacked the technology to bring their dreams to fruition, or time and age defeated them before they reached the final chapter of their research. It was when I was about 50 that I wised up and began seeking out living legends like Frank Moody and Frank Spencer.

In the case of Frank Moody, he was quite elderly when I first met him. For some reason, he knew who I was and shook my hand softly. I didn’t recognize him initially, but at the sound of his name, I knew I was in the presence of a major figure in 20th century gastrointestinal surgery. He had been at the University of California, San Francisco, during an historic time when George Sheldon, Donald Trunkey and other great surgeons trained there with J. Englebert Dunphy as their chief. Dr. Moody’s CV lists 141 articles in basic and clinical science that have had a profound impact on how we view the gastrointestinal tract. He was Chief at the University of Utah and the University of Alabama and finished his career as professor at the University of Texas-Houston. His awards and achievements were legion.

Parkinson’s had only recently really begun to affect him when I met him, and as the years went by his voice became so very faint that I had to lean in to hear him. We would sit together at the back of the dinner dance room so that we could hear each other. And while the other guests entertained themselves, Dr. Moody and I would discuss his life, scientific method and philosophy as well as his insights into his own case of Parkinsonism. I would see him at meetings, making his way slowly but steadily along a corridor while others briskly walked by, unaware that the man they just passed was among the most important surgical pioneers of our time. It was not sad that Dr. Moody was elderly and unrecognized, but that we younger surgeons missed knowing a great man in our tendency to rush past history.

History is not facts and dates, but rather, it is people and their lives. Yes, the history of our profession is embodied by pioneers like Frank Moody and the others I’ve mentioned.

We have many Fellows among us who are living history, still contributing – maybe not at the dais but at the dinner table, speaking softly and walking a bit slower than their juniors. Thanks to LaMar McGinnis who started it and Don Nakayama who continues it, the College has a History Community on the ACS Communities, an active Surgical History Group, and a will to acknowledge the history that lives and breathes among us. The Surgical History Group has organized a full program of events at the Clinical Congress and I hope many attendees take the opportunity to attend.

Take a moment at your next meeting or at the Clinical Congress and look for those historic surgeons still with us. Be smarter than I was at a young age and get to know them. You may learn something from them you can’t learn anyplace else.

Dr. Hughes is clinical professor in the department of surgery and director of medical education at the Kansas University School of Medicine, Salina Campus, and Co-Editor of ACS Surgery News.

LONDON—Significant treatment effect versus placebo of cladribine tablets given to patients with clinically isolated syndrome during the initial treatment period continues to be observed in patients who convert to clinically definite multiple sclerosis (MS) and switch to treatment with a different disease-modifying drug (ie, subcutaneous interferon beta-1a), according to data presented at the 32nd Congress of the European Committee for Treatment and Research in MS (ECTRIMS).

Giancarlo Comi, MD, Professor of Neurology and Chairman of the Department of Neurology at Vita-Salute San Raffaele University in Milan, and colleagues reported that patients with clinically isolated syndrome who had been treated with cladribine tablets and who had converted to MS during the Oral Cladribine in Early MS (ORACLE-MS) initial treatment period had lower annualized relapse rates during the open-label maintenance period, relative to those patients who had received placebo during the ORACLE-MS initial treatment period.

The CLARITY (CLAdRIbine Tablets treating MS orallY) study in patients with active MS showed that annualized relapse rates and sustained disability worsening were reduced in patients treated with cladribine tablets annually for two years in short-duration courses, compared with placebo. The efficacy observed in the CLARITY study was maintained without further active treatment during the CLARITY extension study. In the ORACLE-MS study in patients with a first demyelinating event, cladribine tablets (3.5 mg/kg and 5.25 mg/kg) significantly reduced the risk of conversion to clinically definite MS, compared with placebo. If clinically definite MS occurred in the double-blinded, initial treatment period, patients were treated with subcutaneous interferon beta-1a in an open-label maintenance period.

The present study was designed to assess the annualized relapse rate during the ORACLE-MS open-label maintenance period in patients randomized to cladribine (3.5 mg/kg and 5.25 mg/kg) or placebo in the initial treatment period.

Similar to previous trials, participation in the ORACLE-MS open-label maintenance period was dependent upon the clinical course of the patient’s disease in the initial treatment period. Patients in ORACLE-MS who converted to clinically definite MS (according to Poser criteria) during the initial treatment period entered the open-label maintenance period and were treated with subcutaneous interferon beta-1a (titrated over four weeks up to the dose of 44 μg) administered three times per week.

A total of 109 patients in ORACLE-MS converted to clinically definite MS in the initial treatment period and received at least one dose of interferon beta-1a. The median time on interferon beta-1a was 56.0 weeks. Estimated annualized relapse rates in the open-label maintenance period were 0.14 for patients originally treated with cladribine 3.5 mg/kg (n = 25), 0.24 for patients originally treated with cladribine 5.25 mg/kg (n = 24), and 0.42 for patients who originally received placebo in the initial treatment period (n = 60).

According to the researchers, durable efficacy of cladribine tablets in ORACLE-MS into the open-label maintenance period is consistent with results of the CLARITY and CLARITY extension studies.

This study was sponsored by EMD Serono.

—Glenn S. Williams

Suggested Reading

Cook S, Vermersch P, Comi G, et al. Safety and tolerability of cladribine tablets in multiple sclerosis: the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study. Mult Scler. 2011;17(5):578-593.

Leist TP, Comi G, Cree BA, et al. Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial. Lancet Neurol. 2014;13(3):257-267.

LONDON—Significant treatment effect versus placebo of cladribine tablets given to patients with clinically isolated syndrome during the initial treatment period continues to be observed in patients who convert to clinically definite multiple sclerosis (MS) and switch to treatment with a different disease-modifying drug (ie, subcutaneous interferon beta-1a), according to data presented at the 32nd Congress of the European Committee for Treatment and Research in MS (ECTRIMS).

Giancarlo Comi, MD, Professor of Neurology and Chairman of the Department of Neurology at Vita-Salute San Raffaele University in Milan, and colleagues reported that patients with clinically isolated syndrome who had been treated with cladribine tablets and who had converted to MS during the Oral Cladribine in Early MS (ORACLE-MS) initial treatment period had lower annualized relapse rates during the open-label maintenance period, relative to those patients who had received placebo during the ORACLE-MS initial treatment period.

The CLARITY (CLAdRIbine Tablets treating MS orallY) study in patients with active MS showed that annualized relapse rates and sustained disability worsening were reduced in patients treated with cladribine tablets annually for two years in short-duration courses, compared with placebo. The efficacy observed in the CLARITY study was maintained without further active treatment during the CLARITY extension study. In the ORACLE-MS study in patients with a first demyelinating event, cladribine tablets (3.5 mg/kg and 5.25 mg/kg) significantly reduced the risk of conversion to clinically definite MS, compared with placebo. If clinically definite MS occurred in the double-blinded, initial treatment period, patients were treated with subcutaneous interferon beta-1a in an open-label maintenance period.

The present study was designed to assess the annualized relapse rate during the ORACLE-MS open-label maintenance period in patients randomized to cladribine (3.5 mg/kg and 5.25 mg/kg) or placebo in the initial treatment period.

Similar to previous trials, participation in the ORACLE-MS open-label maintenance period was dependent upon the clinical course of the patient’s disease in the initial treatment period. Patients in ORACLE-MS who converted to clinically definite MS (according to Poser criteria) during the initial treatment period entered the open-label maintenance period and were treated with subcutaneous interferon beta-1a (titrated over four weeks up to the dose of 44 μg) administered three times per week.

A total of 109 patients in ORACLE-MS converted to clinically definite MS in the initial treatment period and received at least one dose of interferon beta-1a. The median time on interferon beta-1a was 56.0 weeks. Estimated annualized relapse rates in the open-label maintenance period were 0.14 for patients originally treated with cladribine 3.5 mg/kg (n = 25), 0.24 for patients originally treated with cladribine 5.25 mg/kg (n = 24), and 0.42 for patients who originally received placebo in the initial treatment period (n = 60).

According to the researchers, durable efficacy of cladribine tablets in ORACLE-MS into the open-label maintenance period is consistent with results of the CLARITY and CLARITY extension studies.

This study was sponsored by EMD Serono.

—Glenn S. Williams

Suggested Reading

Cook S, Vermersch P, Comi G, et al. Safety and tolerability of cladribine tablets in multiple sclerosis: the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study. Mult Scler. 2011;17(5):578-593.

Leist TP, Comi G, Cree BA, et al. Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial. Lancet Neurol. 2014;13(3):257-267.

LONDON—Significant treatment effect versus placebo of cladribine tablets given to patients with clinically isolated syndrome during the initial treatment period continues to be observed in patients who convert to clinically definite multiple sclerosis (MS) and switch to treatment with a different disease-modifying drug (ie, subcutaneous interferon beta-1a), according to data presented at the 32nd Congress of the European Committee for Treatment and Research in MS (ECTRIMS).

Giancarlo Comi, MD, Professor of Neurology and Chairman of the Department of Neurology at Vita-Salute San Raffaele University in Milan, and colleagues reported that patients with clinically isolated syndrome who had been treated with cladribine tablets and who had converted to MS during the Oral Cladribine in Early MS (ORACLE-MS) initial treatment period had lower annualized relapse rates during the open-label maintenance period, relative to those patients who had received placebo during the ORACLE-MS initial treatment period.

The CLARITY (CLAdRIbine Tablets treating MS orallY) study in patients with active MS showed that annualized relapse rates and sustained disability worsening were reduced in patients treated with cladribine tablets annually for two years in short-duration courses, compared with placebo. The efficacy observed in the CLARITY study was maintained without further active treatment during the CLARITY extension study. In the ORACLE-MS study in patients with a first demyelinating event, cladribine tablets (3.5 mg/kg and 5.25 mg/kg) significantly reduced the risk of conversion to clinically definite MS, compared with placebo. If clinically definite MS occurred in the double-blinded, initial treatment period, patients were treated with subcutaneous interferon beta-1a in an open-label maintenance period.

The present study was designed to assess the annualized relapse rate during the ORACLE-MS open-label maintenance period in patients randomized to cladribine (3.5 mg/kg and 5.25 mg/kg) or placebo in the initial treatment period.

Similar to previous trials, participation in the ORACLE-MS open-label maintenance period was dependent upon the clinical course of the patient’s disease in the initial treatment period. Patients in ORACLE-MS who converted to clinically definite MS (according to Poser criteria) during the initial treatment period entered the open-label maintenance period and were treated with subcutaneous interferon beta-1a (titrated over four weeks up to the dose of 44 μg) administered three times per week.

A total of 109 patients in ORACLE-MS converted to clinically definite MS in the initial treatment period and received at least one dose of interferon beta-1a. The median time on interferon beta-1a was 56.0 weeks. Estimated annualized relapse rates in the open-label maintenance period were 0.14 for patients originally treated with cladribine 3.5 mg/kg (n = 25), 0.24 for patients originally treated with cladribine 5.25 mg/kg (n = 24), and 0.42 for patients who originally received placebo in the initial treatment period (n = 60).

According to the researchers, durable efficacy of cladribine tablets in ORACLE-MS into the open-label maintenance period is consistent with results of the CLARITY and CLARITY extension studies.

This study was sponsored by EMD Serono.

—Glenn S. Williams

Suggested Reading

Cook S, Vermersch P, Comi G, et al. Safety and tolerability of cladribine tablets in multiple sclerosis: the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study. Mult Scler. 2011;17(5):578-593.

Leist TP, Comi G, Cree BA, et al. Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial. Lancet Neurol. 2014;13(3):257-267.

Reports in Brazil of Zika transmitted via blood transfusion call attention to the need for better ways to protect the blood supply. To that end, a blood screening test is getting a boost from the Office of the Assistant Secretary for Preparedness and Response (ASPR), with a $4.1 million agreement with Hologic, Inc., of Marlborough, Mass. This is the second screening test ASPR’s Biomedical Advanced Research and Development Authority (BARDA) is helping advance that may be used to test donated blood for Zika. Last April, ASPR announced support of a clinical study of a test developed by Roche Molecular Systems, Inc., of Branchburg, New Jersey.

Under the 1-year agreement, Hologic will advance development of its Procleix Zika Virus Assay, which is designed to detect Zika virus RNA in donated blood plasma up to 7 days post-infection. It runs on Hologic’s Panther automated system, which is already FDA cleared for some infectious disease in vitro diagnostic testing.

The contract could be extended to 18 months with an additional $6.2 million to support the clinical study to evaluate the sensitivity and specificity of the blood donation screening test in actual use, a necessary step before FDA approval.

The money is part of the $374 million HHS has repurposed for domestic Zika response and preparedness activities. BARDA has obligated $41.4 million of these “reprogrammed” funds to develop Zika vaccines, diagnostics, blood screening tests, and pathogen reduction technologies through private sector partners.

Reports in Brazil of Zika transmitted via blood transfusion call attention to the need for better ways to protect the blood supply. To that end, a blood screening test is getting a boost from the Office of the Assistant Secretary for Preparedness and Response (ASPR), with a $4.1 million agreement with Hologic, Inc., of Marlborough, Mass. This is the second screening test ASPR’s Biomedical Advanced Research and Development Authority (BARDA) is helping advance that may be used to test donated blood for Zika. Last April, ASPR announced support of a clinical study of a test developed by Roche Molecular Systems, Inc., of Branchburg, New Jersey.

Under the 1-year agreement, Hologic will advance development of its Procleix Zika Virus Assay, which is designed to detect Zika virus RNA in donated blood plasma up to 7 days post-infection. It runs on Hologic’s Panther automated system, which is already FDA cleared for some infectious disease in vitro diagnostic testing.

The contract could be extended to 18 months with an additional $6.2 million to support the clinical study to evaluate the sensitivity and specificity of the blood donation screening test in actual use, a necessary step before FDA approval.

The money is part of the $374 million HHS has repurposed for domestic Zika response and preparedness activities. BARDA has obligated $41.4 million of these “reprogrammed” funds to develop Zika vaccines, diagnostics, blood screening tests, and pathogen reduction technologies through private sector partners.

Reports in Brazil of Zika transmitted via blood transfusion call attention to the need for better ways to protect the blood supply. To that end, a blood screening test is getting a boost from the Office of the Assistant Secretary for Preparedness and Response (ASPR), with a $4.1 million agreement with Hologic, Inc., of Marlborough, Mass. This is the second screening test ASPR’s Biomedical Advanced Research and Development Authority (BARDA) is helping advance that may be used to test donated blood for Zika. Last April, ASPR announced support of a clinical study of a test developed by Roche Molecular Systems, Inc., of Branchburg, New Jersey.

Under the 1-year agreement, Hologic will advance development of its Procleix Zika Virus Assay, which is designed to detect Zika virus RNA in donated blood plasma up to 7 days post-infection. It runs on Hologic’s Panther automated system, which is already FDA cleared for some infectious disease in vitro diagnostic testing.

The contract could be extended to 18 months with an additional $6.2 million to support the clinical study to evaluate the sensitivity and specificity of the blood donation screening test in actual use, a necessary step before FDA approval.

The money is part of the $374 million HHS has repurposed for domestic Zika response and preparedness activities. BARDA has obligated $41.4 million of these “reprogrammed” funds to develop Zika vaccines, diagnostics, blood screening tests, and pathogen reduction technologies through private sector partners.

Clinical Question: Which oral anticoagulants are safest and most effective in nonvalvular atrial fibrillation?

Background: Use of direct oral anticoagulants (DOACs) has been increasing since their introduction and widespread marketing. While dosing is a challenge for warfarin, certain medical conditions limit the use of DOACs. Choosing the optimal oral anticoagulant is challenging with the increasing complexity of patients.

Study Design: Nationwide observational cohort study.

Setting: Three national Danish databases, from August 2011 to October 2015.

Synopsis: Authors reviewed data from 61,678 patients with nonvalvular atrial fibrillation who were new to oral anticoagulants. The study compared the efficacy, safety, and patient characteristics of DOACs and warfarin. Ischemic stroke, systemic embolism, and death were evaluated separately and as a composite measure of efficacy. Any bleeding, intracranial bleeding, and major bleeding were measured as safety outcomes. DOACs patients were younger and had lower CHA2DS2-VASc and HAS-BLED scores. No significant difference in risk of ischemic stroke was identified between DOACs and warfarin. Rivaroxaban was associated with lower rates of ischemic stroke and systemic embolism but had bleeding rates that were similar to warfarin. Any bleeding and major bleeding rates were lowest for dabigatran and apixaban. All-cause mortality was lowest in the dabigatran group and highest in the warfarin group.

Limitations were the retrospective, observational study design, with an average follow-up of only 1.9 years.

Bottom Line: All DOACs appear to be safer and more effective alternatives to warfarin. Oral anticoagulant selection needs to be based on individual patient clinical profile.

Citation: Larsen TB, Skjoth F, Nielsen PB, Kjaeldgaard JN, Lip GY. Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ. 2016;353:i3189.

Short Take

Mortality and Long-Acting Opiates

This retrospective cohort study raises questions about the safety of long-acting opioids for chronic noncancer pain. When compared with anticonvulsants or antidepressants, the adjusted hazard ratio was 1.64 for total mortality.

Citation: Ray W, Chung CP, Murray KT, Hall K, Stein CM. Prescription of long-acting opioids and mortality in patients with chronic noncancer pain. JAMA. 2016;315(22):2415-2423.

Clinical Question: Which oral anticoagulants are safest and most effective in nonvalvular atrial fibrillation?

Background: Use of direct oral anticoagulants (DOACs) has been increasing since their introduction and widespread marketing. While dosing is a challenge for warfarin, certain medical conditions limit the use of DOACs. Choosing the optimal oral anticoagulant is challenging with the increasing complexity of patients.

Study Design: Nationwide observational cohort study.

Setting: Three national Danish databases, from August 2011 to October 2015.

Synopsis: Authors reviewed data from 61,678 patients with nonvalvular atrial fibrillation who were new to oral anticoagulants. The study compared the efficacy, safety, and patient characteristics of DOACs and warfarin. Ischemic stroke, systemic embolism, and death were evaluated separately and as a composite measure of efficacy. Any bleeding, intracranial bleeding, and major bleeding were measured as safety outcomes. DOACs patients were younger and had lower CHA2DS2-VASc and HAS-BLED scores. No significant difference in risk of ischemic stroke was identified between DOACs and warfarin. Rivaroxaban was associated with lower rates of ischemic stroke and systemic embolism but had bleeding rates that were similar to warfarin. Any bleeding and major bleeding rates were lowest for dabigatran and apixaban. All-cause mortality was lowest in the dabigatran group and highest in the warfarin group.

Limitations were the retrospective, observational study design, with an average follow-up of only 1.9 years.

Bottom Line: All DOACs appear to be safer and more effective alternatives to warfarin. Oral anticoagulant selection needs to be based on individual patient clinical profile.

Citation: Larsen TB, Skjoth F, Nielsen PB, Kjaeldgaard JN, Lip GY. Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ. 2016;353:i3189.

Short Take

Mortality and Long-Acting Opiates

This retrospective cohort study raises questions about the safety of long-acting opioids for chronic noncancer pain. When compared with anticonvulsants or antidepressants, the adjusted hazard ratio was 1.64 for total mortality.

Citation: Ray W, Chung CP, Murray KT, Hall K, Stein CM. Prescription of long-acting opioids and mortality in patients with chronic noncancer pain. JAMA. 2016;315(22):2415-2423.

Clinical Question: Which oral anticoagulants are safest and most effective in nonvalvular atrial fibrillation?

Background: Use of direct oral anticoagulants (DOACs) has been increasing since their introduction and widespread marketing. While dosing is a challenge for warfarin, certain medical conditions limit the use of DOACs. Choosing the optimal oral anticoagulant is challenging with the increasing complexity of patients.

Study Design: Nationwide observational cohort study.

Setting: Three national Danish databases, from August 2011 to October 2015.

Synopsis: Authors reviewed data from 61,678 patients with nonvalvular atrial fibrillation who were new to oral anticoagulants. The study compared the efficacy, safety, and patient characteristics of DOACs and warfarin. Ischemic stroke, systemic embolism, and death were evaluated separately and as a composite measure of efficacy. Any bleeding, intracranial bleeding, and major bleeding were measured as safety outcomes. DOACs patients were younger and had lower CHA2DS2-VASc and HAS-BLED scores. No significant difference in risk of ischemic stroke was identified between DOACs and warfarin. Rivaroxaban was associated with lower rates of ischemic stroke and systemic embolism but had bleeding rates that were similar to warfarin. Any bleeding and major bleeding rates were lowest for dabigatran and apixaban. All-cause mortality was lowest in the dabigatran group and highest in the warfarin group.

Limitations were the retrospective, observational study design, with an average follow-up of only 1.9 years.

Bottom Line: All DOACs appear to be safer and more effective alternatives to warfarin. Oral anticoagulant selection needs to be based on individual patient clinical profile.

Citation: Larsen TB, Skjoth F, Nielsen PB, Kjaeldgaard JN, Lip GY. Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ. 2016;353:i3189.

Short Take

Mortality and Long-Acting Opiates

This retrospective cohort study raises questions about the safety of long-acting opioids for chronic noncancer pain. When compared with anticonvulsants or antidepressants, the adjusted hazard ratio was 1.64 for total mortality.

Citation: Ray W, Chung CP, Murray KT, Hall K, Stein CM. Prescription of long-acting opioids and mortality in patients with chronic noncancer pain. JAMA. 2016;315(22):2415-2423.

Background: Unintentional opioid overdose is a major public health issue. Studies have shown that provision of naloxone to at-risk patients reduces mortality and improves survival. The CDC recommends considering naloxone prescription in high-risk patients. This study focused on patient education and prescription habits of providers rather than just making naloxone available.

Study Design: Non-randomized interventional study.

Setting: Six safety-net primary-care clinics in San Francisco.

Synopsis: The authors identified 1,985 adults on long-term opioid treatment, of which 759 were prescribed naloxone. Providers were encouraged to prescribe naloxone along with opioids. Patients were educated about use of the intranasal naloxone device. Outcomes included opioid-related emergency department visits and prescribed dosage. They noted that patients on a higher dose of opioids and with opioid-related ED visits in the prior 12 months were more likely to be prescribed naloxone. When compared to patients who were not prescribed naloxone, patients who received naloxone had 47% fewer ED visits per month in the first six months and 63% fewer ED visits over 12 months. Limitations include lack of randomization and being a single-center study.

Hospitalists can prioritize patients and consider providing naloxone prescription to reduce ED visits and perhaps readmissions. Further studies are needed focusing on patients who get discharged from the hospital.

Bottom Line: Naloxone prescription in patients on long-term opioid treatment may prevent opioid-related ED visits.

Citation: Coffin PO, Behar E, Rowe C, et al. Nonrandomized intervention study of naloxone coprescription for primary care patients receiving long-term opioid therapy for pain. Ann Intern Med. 2016;165(4):245-252.

Short Take

Mortality and Long-Acting Opiates

This retrospective cohort study raises questions about the safety of long-acting opioids for chronic noncancer pain. When compared with anticonvulsants or antidepressants, the adjusted hazard ratio was 1.64 for total mortality.

Citation: Ray W, Chung CP, Murray KT, Hall K, Stein CM. Prescription of long-acting opioids and mortality in patients with chronic noncancer pain. JAMA. 2016;315(22):2415-2423.

Background: Unintentional opioid overdose is a major public health issue. Studies have shown that provision of naloxone to at-risk patients reduces mortality and improves survival. The CDC recommends considering naloxone prescription in high-risk patients. This study focused on patient education and prescription habits of providers rather than just making naloxone available.

Study Design: Non-randomized interventional study.

Setting: Six safety-net primary-care clinics in San Francisco.

Synopsis: The authors identified 1,985 adults on long-term opioid treatment, of which 759 were prescribed naloxone. Providers were encouraged to prescribe naloxone along with opioids. Patients were educated about use of the intranasal naloxone device. Outcomes included opioid-related emergency department visits and prescribed dosage. They noted that patients on a higher dose of opioids and with opioid-related ED visits in the prior 12 months were more likely to be prescribed naloxone. When compared to patients who were not prescribed naloxone, patients who received naloxone had 47% fewer ED visits per month in the first six months and 63% fewer ED visits over 12 months. Limitations include lack of randomization and being a single-center study.

Hospitalists can prioritize patients and consider providing naloxone prescription to reduce ED visits and perhaps readmissions. Further studies are needed focusing on patients who get discharged from the hospital.

Bottom Line: Naloxone prescription in patients on long-term opioid treatment may prevent opioid-related ED visits.

Citation: Coffin PO, Behar E, Rowe C, et al. Nonrandomized intervention study of naloxone coprescription for primary care patients receiving long-term opioid therapy for pain. Ann Intern Med. 2016;165(4):245-252.

Short Take

Mortality and Long-Acting Opiates

This retrospective cohort study raises questions about the safety of long-acting opioids for chronic noncancer pain. When compared with anticonvulsants or antidepressants, the adjusted hazard ratio was 1.64 for total mortality.

Citation: Ray W, Chung CP, Murray KT, Hall K, Stein CM. Prescription of long-acting opioids and mortality in patients with chronic noncancer pain. JAMA. 2016;315(22):2415-2423.

Background: Unintentional opioid overdose is a major public health issue. Studies have shown that provision of naloxone to at-risk patients reduces mortality and improves survival. The CDC recommends considering naloxone prescription in high-risk patients. This study focused on patient education and prescription habits of providers rather than just making naloxone available.

Study Design: Non-randomized interventional study.

Setting: Six safety-net primary-care clinics in San Francisco.

Synopsis: The authors identified 1,985 adults on long-term opioid treatment, of which 759 were prescribed naloxone. Providers were encouraged to prescribe naloxone along with opioids. Patients were educated about use of the intranasal naloxone device. Outcomes included opioid-related emergency department visits and prescribed dosage. They noted that patients on a higher dose of opioids and with opioid-related ED visits in the prior 12 months were more likely to be prescribed naloxone. When compared to patients who were not prescribed naloxone, patients who received naloxone had 47% fewer ED visits per month in the first six months and 63% fewer ED visits over 12 months. Limitations include lack of randomization and being a single-center study.

Hospitalists can prioritize patients and consider providing naloxone prescription to reduce ED visits and perhaps readmissions. Further studies are needed focusing on patients who get discharged from the hospital.

Bottom Line: Naloxone prescription in patients on long-term opioid treatment may prevent opioid-related ED visits.

Citation: Coffin PO, Behar E, Rowe C, et al. Nonrandomized intervention study of naloxone coprescription for primary care patients receiving long-term opioid therapy for pain. Ann Intern Med. 2016;165(4):245-252.

Short Take

Mortality and Long-Acting Opiates

This retrospective cohort study raises questions about the safety of long-acting opioids for chronic noncancer pain. When compared with anticonvulsants or antidepressants, the adjusted hazard ratio was 1.64 for total mortality.

Citation: Ray W, Chung CP, Murray KT, Hall K, Stein CM. Prescription of long-acting opioids and mortality in patients with chronic noncancer pain. JAMA. 2016;315(22):2415-2423.

Daratumumab (Darzalex)

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has granted priority review for part of a supplemental biologics license application (sBLA) for daratumumab (Darzalex®).

The priority review pertains to the use of daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat patients with multiple myeloma (MM) who have received at least 1 prior therapy.

To grant an application priority review, the FDA must believe the drug would provide a significant improvement in the treatment, diagnosis, or prevention of a serious condition.

The priority review designation means the FDA’s goal is to take action on an application within 6 months, rather than the 10 months typically taken for a standard review.

The FDA has assigned a Prescription Drug User Fee Act target date of February 17, 2017, to make a decision on daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone.

Standard review

The FDA has also granted a standard review period for part of the sBLA.

The standard review pertains to the use of daratumumab in combination with pomalidomide and dexamethasone to treat patients with relapsed or refractory MM who have received at least 2 prior therapies, including a proteasome inhibitor and an immunomodulatory agent.

The Prescription Drug User Fee Act date for the combination of daratumumab with pomalidomide and dexamethasone is June 17, 2017.

Trial data

The sBLA submission included data from a pair of phase 3 studies:

• The CASTOR study, in which researchers compared the combination of daratumumab, bortezomib, and dexamethasone to bortezomib and dexamethasone in patients with relapsed or refractory MM
• The POLLUX study, in which researchers compared daratumumab in combination with lenalidomide and dexamethasone to lenalidomide and dexamethasone in patients with relapsed or refractory MM.

The sBLA submission also included data from a phase 1 study of daratumumab in combination with pomalidomide and dexamethasone in patients with relapsed or refractory MM.

About daratumumab

Daratumumab is a human IgG1k monoclonal antibody that binds to CD38, which is highly expressed on the surface of MM cells.

Daratumumab already has accelerated approval in the US as monotherapy for MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab to develop, manufacture, and commercialize daratumumab.

For more information on daratumumab, visit www.DARZALEX.com.

Daratumumab (Darzalex)

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has granted priority review for part of a supplemental biologics license application (sBLA) for daratumumab (Darzalex®).

The priority review pertains to the use of daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat patients with multiple myeloma (MM) who have received at least 1 prior therapy.

To grant an application priority review, the FDA must believe the drug would provide a significant improvement in the treatment, diagnosis, or prevention of a serious condition.

The priority review designation means the FDA’s goal is to take action on an application within 6 months, rather than the 10 months typically taken for a standard review.

The FDA has assigned a Prescription Drug User Fee Act target date of February 17, 2017, to make a decision on daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone.

Standard review

The FDA has also granted a standard review period for part of the sBLA.

The standard review pertains to the use of daratumumab in combination with pomalidomide and dexamethasone to treat patients with relapsed or refractory MM who have received at least 2 prior therapies, including a proteasome inhibitor and an immunomodulatory agent.

The Prescription Drug User Fee Act date for the combination of daratumumab with pomalidomide and dexamethasone is June 17, 2017.

Trial data

The sBLA submission included data from a pair of phase 3 studies:

• The CASTOR study, in which researchers compared the combination of daratumumab, bortezomib, and dexamethasone to bortezomib and dexamethasone in patients with relapsed or refractory MM
• The POLLUX study, in which researchers compared daratumumab in combination with lenalidomide and dexamethasone to lenalidomide and dexamethasone in patients with relapsed or refractory MM.

The sBLA submission also included data from a phase 1 study of daratumumab in combination with pomalidomide and dexamethasone in patients with relapsed or refractory MM.

About daratumumab

Daratumumab is a human IgG1k monoclonal antibody that binds to CD38, which is highly expressed on the surface of MM cells.

Daratumumab already has accelerated approval in the US as monotherapy for MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab to develop, manufacture, and commercialize daratumumab.

For more information on daratumumab, visit www.DARZALEX.com.

Daratumumab (Darzalex)

Photo courtesy of Janssen

The US Food and Drug Administration (FDA) has granted priority review for part of a supplemental biologics license application (sBLA) for daratumumab (Darzalex®).

The priority review pertains to the use of daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat patients with multiple myeloma (MM) who have received at least 1 prior therapy.

To grant an application priority review, the FDA must believe the drug would provide a significant improvement in the treatment, diagnosis, or prevention of a serious condition.

The priority review designation means the FDA’s goal is to take action on an application within 6 months, rather than the 10 months typically taken for a standard review.

The FDA has assigned a Prescription Drug User Fee Act target date of February 17, 2017, to make a decision on daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone.

Standard review

The FDA has also granted a standard review period for part of the sBLA.

The standard review pertains to the use of daratumumab in combination with pomalidomide and dexamethasone to treat patients with relapsed or refractory MM who have received at least 2 prior therapies, including a proteasome inhibitor and an immunomodulatory agent.

The Prescription Drug User Fee Act date for the combination of daratumumab with pomalidomide and dexamethasone is June 17, 2017.

Trial data

The sBLA submission included data from a pair of phase 3 studies:

• The CASTOR study, in which researchers compared the combination of daratumumab, bortezomib, and dexamethasone to bortezomib and dexamethasone in patients with relapsed or refractory MM
• The POLLUX study, in which researchers compared daratumumab in combination with lenalidomide and dexamethasone to lenalidomide and dexamethasone in patients with relapsed or refractory MM.

The sBLA submission also included data from a phase 1 study of daratumumab in combination with pomalidomide and dexamethasone in patients with relapsed or refractory MM.

About daratumumab

Daratumumab is a human IgG1k monoclonal antibody that binds to CD38, which is highly expressed on the surface of MM cells.

Daratumumab already has accelerated approval in the US as monotherapy for MM patients who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent.

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab to develop, manufacture, and commercialize daratumumab.

For more information on daratumumab, visit www.DARZALEX.com.

Very hot and very cold temperatures during pregnancy may increase the risk of preterm birth, say NIH researchers who analyzed records from 223,375 live births at 12 clinical centers.

They linked patients’ electronic records to hourly temperature records for the region surrounding each center. Because “hot” and “cold” can vary depending on the person and place, they defined cold and hot temperatures as below the 10th percentile and above the 90th percentile of average temperatures, respectively.

Related: Home-Visiting Program to Support Young Native American Families 

Women who experienced extreme cold for the first 7 weeks of their pregnancies had a 20% higher risk of delivering before 34 weeks, a 9% higher risk of delivering between 34 and 36 weeks, and 3% higher risk of delivering in weeks 37 and 38.

But the researchers found more consistent associations with early delivery after exposure to extreme heat than extreme cold. Overall, exposure to extreme heat for the duration of pregnancy was associated with increases in risk for delivery at 34 weeks and 36 to 38 weeks by 6% to 21%. The researchers suggest that during cold spells, people are more likely to seek shelter and get warm—and may be more likely to just endure hot weather.

Related: Coordinating Better Care for Opioid-Addicted Women and Their Children

The researchers theorize that the stress of temperature extremes could hinder the development of the placenta or alter blood flow to the uterus, both of which could lead to early labor.

Very hot and very cold temperatures during pregnancy may increase the risk of preterm birth, say NIH researchers who analyzed records from 223,375 live births at 12 clinical centers.

They linked patients’ electronic records to hourly temperature records for the region surrounding each center. Because “hot” and “cold” can vary depending on the person and place, they defined cold and hot temperatures as below the 10th percentile and above the 90th percentile of average temperatures, respectively.

Related: Home-Visiting Program to Support Young Native American Families 

Women who experienced extreme cold for the first 7 weeks of their pregnancies had a 20% higher risk of delivering before 34 weeks, a 9% higher risk of delivering between 34 and 36 weeks, and 3% higher risk of delivering in weeks 37 and 38.

But the researchers found more consistent associations with early delivery after exposure to extreme heat than extreme cold. Overall, exposure to extreme heat for the duration of pregnancy was associated with increases in risk for delivery at 34 weeks and 36 to 38 weeks by 6% to 21%. The researchers suggest that during cold spells, people are more likely to seek shelter and get warm—and may be more likely to just endure hot weather.

Related: Coordinating Better Care for Opioid-Addicted Women and Their Children

The researchers theorize that the stress of temperature extremes could hinder the development of the placenta or alter blood flow to the uterus, both of which could lead to early labor.

Very hot and very cold temperatures during pregnancy may increase the risk of preterm birth, say NIH researchers who analyzed records from 223,375 live births at 12 clinical centers.

They linked patients’ electronic records to hourly temperature records for the region surrounding each center. Because “hot” and “cold” can vary depending on the person and place, they defined cold and hot temperatures as below the 10th percentile and above the 90th percentile of average temperatures, respectively.

Related: Home-Visiting Program to Support Young Native American Families 

Women who experienced extreme cold for the first 7 weeks of their pregnancies had a 20% higher risk of delivering before 34 weeks, a 9% higher risk of delivering between 34 and 36 weeks, and 3% higher risk of delivering in weeks 37 and 38.

But the researchers found more consistent associations with early delivery after exposure to extreme heat than extreme cold. Overall, exposure to extreme heat for the duration of pregnancy was associated with increases in risk for delivery at 34 weeks and 36 to 38 weeks by 6% to 21%. The researchers suggest that during cold spells, people are more likely to seek shelter and get warm—and may be more likely to just endure hot weather.

Related: Coordinating Better Care for Opioid-Addicted Women and Their Children

The researchers theorize that the stress of temperature extremes could hinder the development of the placenta or alter blood flow to the uterus, both of which could lead to early labor.