Introduction

Since the election, many of the psychiatrists and psychologists in our office have reported a wave of anxiety among our patients. These fears have sometimes come from watching television commercials that highlight the faults of the other party or from watching the debates themselves. Children have reported fears of a nuclear war, of being taken away from family, or of being harmed or killed because of racial, religious, immigration, disability, gender, or sexual orientation status. In addition, some children are reporting remarks by peers.

Case summary

Discussion

How can we support our patients and their parents in responding to this surge in anxiety? First, we can reiterate the central importance of family. What the family models in values, behavior, and coping is central to how children respond to stress and winning and losing. Parents who manage their own emotions model how to cope with both victory and defeat, demonstrating appropriate celebration as well as grief and anger. Coping strategies for parents can include reaching out to supports from family and friends, using relaxation strategies, and then planning practical next steps to take.

Parents should reassure their children that they are there to keep their children safe. Modeling self-care and keeping the family routine as stable as possible is a powerful source of this sense of safety. As always, parents should think about what their children are consuming in the way of electronics.

In talking to children, listening is a first step. Help children find the words for what they are feeling. Consider your own words and the rhetoric of the election. Withering scorn of the other side has become increasingly common and not only damages our ability to understand other points of view and resolve conflicts but is also leading to intense anxiety in our children. The extreme nature of some of these words has led some children to believe that complete disaster is imminent should the other side win. Try to avoid using words that intensify fear. Acknowledge the feelings that children have, but provide reassurance of safety and hope.

Using the principles of cognitive-behavioral therapy, a therapist or parent can help a child think through how their thoughts are connected with feelings and behavior. When we are fearful, we often think that the absolute worst is going to happen, or we imagine that we definitely know the future. Sometimes an extreme thought can magnify feelings to the point that constructive behavior is blocked. A therapist might acknowledge feelings, but also help enlarge the child’s perspective. There are many reasons why people voted for or against candidates, and we don’t know everything about them just because of how they chose to vote. Discussing the three branches of government and the system of checks and balances that bring many people together to think over a problem can help a child see that the government is more than just one person. Parents or therapists can talk about protections in the Constitution such as freedom of the press, which allows us to be informed of what is going on. Parents might want to talk about the reality that we are one country, and that the vast majority of people on both sides share many, if not all, values.

Helping a child consider other perspectives isn’t saying that there are no reasons at all for anxiety, but that there are many possibilities for the future, and that a family can think together about what behaviors they want to engage in. There may be specific actions a child or family might want to take to have a voice in how the country moves forward.

Treatment plan for Jane

• Psychotherapy. Continue cognitive-behavioral therapy with a focus on identifying thoughts tied to anxiety that are overgeneralizations or exaggerations. Discuss alternative thoughts with greater perspective.

• Parents. Discuss supporting the child through listening, reassurance of safety, reestablishment of family routine, and family discussion about what actions to take to promote values.

• Health promotion. Discuss using exercise, pleasant activities, mindfulness, and minimizing of screen time as ways to cope with stress.

• Medications. There is no need to use medications for the child’s acute stress response.

Resources

1. Psychological First Aid: Field Operations Manual , 2nd ed. (National Child Traumatic Stress Network, National Center for PTSD, 2006).

2. Cognitive Behavioral Therapy for Anxious Children: Therapist Manual, 3rd edition. (Ardmore, Pa.: Workbook Publishing, 2006).

Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. She said she had no relevant financial disclosures.

Introduction

Since the election, many of the psychiatrists and psychologists in our office have reported a wave of anxiety among our patients. These fears have sometimes come from watching television commercials that highlight the faults of the other party or from watching the debates themselves. Children have reported fears of a nuclear war, of being taken away from family, or of being harmed or killed because of racial, religious, immigration, disability, gender, or sexual orientation status. In addition, some children are reporting remarks by peers.

Case summary

Discussion

How can we support our patients and their parents in responding to this surge in anxiety? First, we can reiterate the central importance of family. What the family models in values, behavior, and coping is central to how children respond to stress and winning and losing. Parents who manage their own emotions model how to cope with both victory and defeat, demonstrating appropriate celebration as well as grief and anger. Coping strategies for parents can include reaching out to supports from family and friends, using relaxation strategies, and then planning practical next steps to take.

Parents should reassure their children that they are there to keep their children safe. Modeling self-care and keeping the family routine as stable as possible is a powerful source of this sense of safety. As always, parents should think about what their children are consuming in the way of electronics.

In talking to children, listening is a first step. Help children find the words for what they are feeling. Consider your own words and the rhetoric of the election. Withering scorn of the other side has become increasingly common and not only damages our ability to understand other points of view and resolve conflicts but is also leading to intense anxiety in our children. The extreme nature of some of these words has led some children to believe that complete disaster is imminent should the other side win. Try to avoid using words that intensify fear. Acknowledge the feelings that children have, but provide reassurance of safety and hope.

Using the principles of cognitive-behavioral therapy, a therapist or parent can help a child think through how their thoughts are connected with feelings and behavior. When we are fearful, we often think that the absolute worst is going to happen, or we imagine that we definitely know the future. Sometimes an extreme thought can magnify feelings to the point that constructive behavior is blocked. A therapist might acknowledge feelings, but also help enlarge the child’s perspective. There are many reasons why people voted for or against candidates, and we don’t know everything about them just because of how they chose to vote. Discussing the three branches of government and the system of checks and balances that bring many people together to think over a problem can help a child see that the government is more than just one person. Parents or therapists can talk about protections in the Constitution such as freedom of the press, which allows us to be informed of what is going on. Parents might want to talk about the reality that we are one country, and that the vast majority of people on both sides share many, if not all, values.

Helping a child consider other perspectives isn’t saying that there are no reasons at all for anxiety, but that there are many possibilities for the future, and that a family can think together about what behaviors they want to engage in. There may be specific actions a child or family might want to take to have a voice in how the country moves forward.

Treatment plan for Jane

• Psychotherapy. Continue cognitive-behavioral therapy with a focus on identifying thoughts tied to anxiety that are overgeneralizations or exaggerations. Discuss alternative thoughts with greater perspective.

• Parents. Discuss supporting the child through listening, reassurance of safety, reestablishment of family routine, and family discussion about what actions to take to promote values.

• Health promotion. Discuss using exercise, pleasant activities, mindfulness, and minimizing of screen time as ways to cope with stress.

• Medications. There is no need to use medications for the child’s acute stress response.

Resources

1. Psychological First Aid: Field Operations Manual , 2nd ed. (National Child Traumatic Stress Network, National Center for PTSD, 2006).

2. Cognitive Behavioral Therapy for Anxious Children: Therapist Manual, 3rd edition. (Ardmore, Pa.: Workbook Publishing, 2006).

Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. She said she had no relevant financial disclosures.

Introduction

Since the election, many of the psychiatrists and psychologists in our office have reported a wave of anxiety among our patients. These fears have sometimes come from watching television commercials that highlight the faults of the other party or from watching the debates themselves. Children have reported fears of a nuclear war, of being taken away from family, or of being harmed or killed because of racial, religious, immigration, disability, gender, or sexual orientation status. In addition, some children are reporting remarks by peers.

Case summary

Discussion

How can we support our patients and their parents in responding to this surge in anxiety? First, we can reiterate the central importance of family. What the family models in values, behavior, and coping is central to how children respond to stress and winning and losing. Parents who manage their own emotions model how to cope with both victory and defeat, demonstrating appropriate celebration as well as grief and anger. Coping strategies for parents can include reaching out to supports from family and friends, using relaxation strategies, and then planning practical next steps to take.

Parents should reassure their children that they are there to keep their children safe. Modeling self-care and keeping the family routine as stable as possible is a powerful source of this sense of safety. As always, parents should think about what their children are consuming in the way of electronics.

In talking to children, listening is a first step. Help children find the words for what they are feeling. Consider your own words and the rhetoric of the election. Withering scorn of the other side has become increasingly common and not only damages our ability to understand other points of view and resolve conflicts but is also leading to intense anxiety in our children. The extreme nature of some of these words has led some children to believe that complete disaster is imminent should the other side win. Try to avoid using words that intensify fear. Acknowledge the feelings that children have, but provide reassurance of safety and hope.

Using the principles of cognitive-behavioral therapy, a therapist or parent can help a child think through how their thoughts are connected with feelings and behavior. When we are fearful, we often think that the absolute worst is going to happen, or we imagine that we definitely know the future. Sometimes an extreme thought can magnify feelings to the point that constructive behavior is blocked. A therapist might acknowledge feelings, but also help enlarge the child’s perspective. There are many reasons why people voted for or against candidates, and we don’t know everything about them just because of how they chose to vote. Discussing the three branches of government and the system of checks and balances that bring many people together to think over a problem can help a child see that the government is more than just one person. Parents or therapists can talk about protections in the Constitution such as freedom of the press, which allows us to be informed of what is going on. Parents might want to talk about the reality that we are one country, and that the vast majority of people on both sides share many, if not all, values.

Helping a child consider other perspectives isn’t saying that there are no reasons at all for anxiety, but that there are many possibilities for the future, and that a family can think together about what behaviors they want to engage in. There may be specific actions a child or family might want to take to have a voice in how the country moves forward.

Treatment plan for Jane

• Psychotherapy. Continue cognitive-behavioral therapy with a focus on identifying thoughts tied to anxiety that are overgeneralizations or exaggerations. Discuss alternative thoughts with greater perspective.

• Parents. Discuss supporting the child through listening, reassurance of safety, reestablishment of family routine, and family discussion about what actions to take to promote values.

• Health promotion. Discuss using exercise, pleasant activities, mindfulness, and minimizing of screen time as ways to cope with stress.

• Medications. There is no need to use medications for the child’s acute stress response.

Resources

1. Psychological First Aid: Field Operations Manual , 2nd ed. (National Child Traumatic Stress Network, National Center for PTSD, 2006).

2. Cognitive Behavioral Therapy for Anxious Children: Therapist Manual, 3rd edition. (Ardmore, Pa.: Workbook Publishing, 2006).

Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. She said she had no relevant financial disclosures.

The modern term orthopedics stems from the older word orthopedia, which was the title of a book published in 1741 by Nicholas Andry, a professor of medicine at the University of Paris.¹ The term orthopedia is a composite of 2 Greek words: orthos, meaning “straight and free from deformity,” and paidios, meaning “child.” Together, orthopedics literally means straight child, suggesting the importance of pediatric injuries and deformities in the development of this field. Interestingly, Andry’s book also depicted a crooked young tree attached to a straight and strong staff, which has become the universal symbol of orthopedic surgery and underscores the focus on correcting deformities in the young (Figure).¹

Orthopedic surgery is a rapidly advancing medical field with several recent advances noted within orthopedic subspecialties,^2-4 basic science,⁵ and clinical research.⁶ It is important to recognize the role of history with regards to innovation and research, especially for young trainees and medical students interested in a particular medical specialty. More specifically, it is important to understand the successes and failures of the past in order to advance research and practice, and ultimately improve patient care and outcomes.

In the recent literature, there is no concise yet comprehensive article focusing on the history of orthopedic surgery. The goal of this review is to provide an overview of the history and development of orthopedic surgery from ancient practices to the modern era.

Ancient Orthopedics

While the evidence is limited, the practice of orthopedics dates back to the primitive man.⁷ Fossil evidence suggests that the orthopedic pathology of today, such as fractures and traumatic amputations, existed in primitive times.⁸ The union of fractures in fair alignment has also been observed, which emphasizes the efficacy of nonoperative orthopedics and suggests the early use of splints and rehabilitation practices.^8,9 Since procedures such as trepanation and crude amputations occurred during the New Stone Age, it is feasible that sophisticated techniques had also been developed for the treatment of injuries.^7-9 However, evidence continues to remain limited.⁷

Later civilizations also developed creative ways to manage orthopedic injuries. For example, the Shoshone Indians, who were known to exist around 700-2000 BCE, made a splint of fresh rawhide that had been soaked in water.^9,10 Similarly, some South Australian tribes made splints of clay, which when dried were as good as plaster of Paris.⁹ Furthermore, bone-setting or reductions was practiced as a profession in many tribes, underscoring the importance of orthopedic injuries in early civilizations.^8,9

Ancient Egypt

The ancient Egyptians seemed to have carried on the practices of splinting. For example, 2 splinted specimens were discovered during the Hearst Egyptian Expedition in 1903.⁷ More specifically, these specimens included a femur and forearm and dated to approximately 300 BCE.⁷ Other examples of splints made of bamboo and reed padded with linen have been found on mummies as well.⁸ Similarly, crutches were also used by this civilization, as depicted on a carving made on an Egyptian tomb in 2830 BCE.⁸

One of the earliest and most significant documents on medicine was discovered in 1862, known as the Edwin Smith papyrus. This document is thought to have been composed by Imhotep, a prominent Egyptian physician, astrologer, architect, and politician, and it specifically categorizes diseases and treatments. Many scholars recognize this medical document as the oldest surgical textbook.^11,12 With regards to orthopedic conditions, this document describes the reduction of a dislocated mandible, signs of spinal or vertebral injuries, description of torticollis, and the treatment of fractures such as clavicle fractures.⁸ This document also discusses ryt, which refers to the purulent discharge from osteomyelitis.⁸ The following is an excerpt from this ancient document:⁹

“Instructions on erring a break in his upper arm…Thou shouldst spread out with his two shoulders in order to stretch apart his upper arm until that break falls into its place. Thou shouldst make for him two splints of linen, and thou shouldst apply for him one of them both on the inside of his arm, and the other of them both on the underside of his arm.”

This account illustrates the methodical and meticulous nature of this textbook, and it highlights some of the essentials of medical practice from diagnosis to medical decision-making to treatment.

There are various other contributions to the field of medicine from the Far East; however, many of these pertain to the fields of plastic surgery and general surgery.⁹

Greeks and Romans

The Greeks are considered to be the first to systematically employ the scientific approach to medicine.⁸ In the period between 430 BCE to 330 BCE, the Corpus Hippocrates was compiled, which is a Greek text on medicine. It is named for Hippocrates (460 BCE-370 BCE), the father of medicine, and it contains text that applies specifically to the field of orthopedic surgery. For example, this text discuses shoulder dislocations and describes various reduction maneuvers. Hippocrates had a keen understanding of the principles of traction and countertraction, especially as it pertains to the musculoskeletal system.⁸ In fact, the Hippocratic method is still used for reducing anterior shoulder dislocations, and its description can be found in several modern orthopedic texts, including recent articles.¹³ The Corpus Hippocrates also describes the correction of clubfoot deformity, and the treatment of infected open fractures with pitch cerate and wine compresses.⁸

Hippocrates also described the treatment of fractures, the principles of traction, and the implications of malunions. For example, Hippocrates wrote, “For the arm, when shortened, might be concealed and the mistake will not be great, but a shortened thigh bone will leave a man maimed.”¹ In addition, spinal deformities were recognized by the Greeks, and Hippocrates devised an extension bench for the correction of such deformities.¹ From their contributions to anatomy and surgical practice, the Greeks have made significant contributions to the field of surgery.⁹

During the Roman period, another Greek surgeon by the name of Galen described the musculoskeletal and nervous systems. He served as a gladiatorial surgeon in Rome, and today, he is considered to be the father of sports medicine.⁸ He is also credited with coining the terms scoliosis, kyphosis, and lordosis to denote the spinal deformities that were first described by Hippocrates.¹ In the Roman period, amputations were also performed, and primitive prostheses were developed.⁹

The Middle Ages

There was relatively little progress in the study of medicine for a thousand years after the fall of the Roman Empire.⁹ This stagnation was predominantly due to the early Christian Church inhibiting freedom of thought and observation, as well as prohibiting human dissection and the study of anatomy. The first medical school in Europe was established in Salerno, Italy, during the ninth century. This school provided primarily pedantic teaching to its students and perpetuated the theories of the elements and humors. Later on, the University of Bologna became one of the first academic institutions to offer hands-on surgical training.⁹ One of the most famous surgeons of the Middle Ages was Guy de Chuauliac, who studied at Montpellier and Bologna. He was a leader in the ethical principles of surgery as well as the practice of surgery, and wrote the following with regards to femur fractures:⁹

“After the application of splints, I attach to the foot a mass of lead as a weight, taking care to pass the cord which supports the weight over a small pulley in such a manner that it shall pull on the leg in a horizontal direction.”

This description is strikingly similar to the modern-day nonoperative management of femur fractures, and underscores the importance of traction, which as mentioned above, was first described by Hippocrates.

Eventually, medicine began to separate from the Church, most likely due to an increase in the complexity of medical theories, the rise of secular universities, and an increase in medical knowledge from Eastern and Middle-Eastern groups.⁹

The Renaissance and the Foundations of Modern Orthopedics

Until the 16^th century, the majority of medical theories were heavily influenced by the work of Hippocrates.⁸ The scientific study of anatomy gained prominence during this time, especially due to the work done by great artists, such as Leonardo Di Vinci.⁹ The Table

After a period of rapid expansion of the field of orthopedics, and following the Renaissance, many hospitals were built focusing on the sick and disabled, which solidified orthopedics’ position as a major medical specialty.¹ For example, in 1863, James Knight founded the Hospital for the Ruptured and Crippled in New York City. This hospital became the oldest orthopedic hospital in the United States, and it later became known as the Hospital for Special Surgery.^14,15 Several additional orthopedic institutions were formed, including the New York Orthopedic Dispensary in 1886 and Hospital for Deformities and Joint Diseases in 1917. Orthopedic surgery residency programs also began to be developed in the late 1800s.¹⁴ More specifically, Virgil Gibney at Hospital for the Ruptured and Crippled began the first orthopedic training program in the United States in 1888. Young doctors in this program trained for 1 year as junior assistant, senior assistant, and house surgeon, and began to be known as resident doctors.¹⁴

The Modern Era

In the 20th century, rapid development continued to better control infections as well as develop and introduce novel technology. For example, the invention of x-ray in 1895 by Wilhelm Conrad Röntgen improved our ability to diagnose and manage orthopedic conditions ranging from fractures to avascular necrosis of the femoral head to osteoarthritis.^8,14 Spinal surgery also developed rapidly with Russell Hibbs describing a technique for spinal fusion at the New York Orthopedic Hospital.⁸ Similarly, the World Wars served as a catalyst in the development of the subspecialty of orthopedic trauma, with increasing attention placed on open wounds and proficiency with amputations, internal fixation, and wound care. In 1942, Austin Moore performed the first metal hip arthroplasty, and the field of joint replacement was subsequently advanced by the work of Sir John Charnley in the 1960s.⁸

Conclusion

Despite its relatively recent specialization, orthopedic surgery has a rich history rooted in ancient practices dating back to the primitive man. Over time, there has been significant development in the field in terms of surgical and nonsurgical treatment of orthopedic pathology and disease. Various cultures have played an instrumental role in developing this field, and it is remarkable to see that several practices have persisted since the time of these ancient civilizations. During the Renaissance, there was a considerable emphasis placed on pediatric deformity, but orthopedic surgeons have now branched out to subspecialty practice ranging from orthopedic trauma to joint replacement to oncology.¹ For students of medicine and orthopedics, it is important to learn about the origins of this field and to appreciate its gradual development. Orthopedic surgery is a diverse and fascinating field that will most likely continue to develop with increased subspecialization and improved research at the molecular and population level. With a growing emphasis placed on outcomes and healthcare cost by today’s society, it will be fascinating to see how this field continues to evolve in the future.

Am J Orthop. 2016;45(7):E434-E438. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

The modern term orthopedics stems from the older word orthopedia, which was the title of a book published in 1741 by Nicholas Andry, a professor of medicine at the University of Paris.¹ The term orthopedia is a composite of 2 Greek words: orthos, meaning “straight and free from deformity,” and paidios, meaning “child.” Together, orthopedics literally means straight child, suggesting the importance of pediatric injuries and deformities in the development of this field. Interestingly, Andry’s book also depicted a crooked young tree attached to a straight and strong staff, which has become the universal symbol of orthopedic surgery and underscores the focus on correcting deformities in the young (Figure).¹

Orthopedic surgery is a rapidly advancing medical field with several recent advances noted within orthopedic subspecialties,^2-4 basic science,⁵ and clinical research.⁶ It is important to recognize the role of history with regards to innovation and research, especially for young trainees and medical students interested in a particular medical specialty. More specifically, it is important to understand the successes and failures of the past in order to advance research and practice, and ultimately improve patient care and outcomes.

In the recent literature, there is no concise yet comprehensive article focusing on the history of orthopedic surgery. The goal of this review is to provide an overview of the history and development of orthopedic surgery from ancient practices to the modern era.

Ancient Orthopedics

While the evidence is limited, the practice of orthopedics dates back to the primitive man.⁷ Fossil evidence suggests that the orthopedic pathology of today, such as fractures and traumatic amputations, existed in primitive times.⁸ The union of fractures in fair alignment has also been observed, which emphasizes the efficacy of nonoperative orthopedics and suggests the early use of splints and rehabilitation practices.^8,9 Since procedures such as trepanation and crude amputations occurred during the New Stone Age, it is feasible that sophisticated techniques had also been developed for the treatment of injuries.^7-9 However, evidence continues to remain limited.⁷

Later civilizations also developed creative ways to manage orthopedic injuries. For example, the Shoshone Indians, who were known to exist around 700-2000 BCE, made a splint of fresh rawhide that had been soaked in water.^9,10 Similarly, some South Australian tribes made splints of clay, which when dried were as good as plaster of Paris.⁹ Furthermore, bone-setting or reductions was practiced as a profession in many tribes, underscoring the importance of orthopedic injuries in early civilizations.^8,9

Ancient Egypt

The ancient Egyptians seemed to have carried on the practices of splinting. For example, 2 splinted specimens were discovered during the Hearst Egyptian Expedition in 1903.⁷ More specifically, these specimens included a femur and forearm and dated to approximately 300 BCE.⁷ Other examples of splints made of bamboo and reed padded with linen have been found on mummies as well.⁸ Similarly, crutches were also used by this civilization, as depicted on a carving made on an Egyptian tomb in 2830 BCE.⁸

One of the earliest and most significant documents on medicine was discovered in 1862, known as the Edwin Smith papyrus. This document is thought to have been composed by Imhotep, a prominent Egyptian physician, astrologer, architect, and politician, and it specifically categorizes diseases and treatments. Many scholars recognize this medical document as the oldest surgical textbook.^11,12 With regards to orthopedic conditions, this document describes the reduction of a dislocated mandible, signs of spinal or vertebral injuries, description of torticollis, and the treatment of fractures such as clavicle fractures.⁸ This document also discusses ryt, which refers to the purulent discharge from osteomyelitis.⁸ The following is an excerpt from this ancient document:⁹

“Instructions on erring a break in his upper arm…Thou shouldst spread out with his two shoulders in order to stretch apart his upper arm until that break falls into its place. Thou shouldst make for him two splints of linen, and thou shouldst apply for him one of them both on the inside of his arm, and the other of them both on the underside of his arm.”

This account illustrates the methodical and meticulous nature of this textbook, and it highlights some of the essentials of medical practice from diagnosis to medical decision-making to treatment.

There are various other contributions to the field of medicine from the Far East; however, many of these pertain to the fields of plastic surgery and general surgery.⁹

Greeks and Romans

The Greeks are considered to be the first to systematically employ the scientific approach to medicine.⁸ In the period between 430 BCE to 330 BCE, the Corpus Hippocrates was compiled, which is a Greek text on medicine. It is named for Hippocrates (460 BCE-370 BCE), the father of medicine, and it contains text that applies specifically to the field of orthopedic surgery. For example, this text discuses shoulder dislocations and describes various reduction maneuvers. Hippocrates had a keen understanding of the principles of traction and countertraction, especially as it pertains to the musculoskeletal system.⁸ In fact, the Hippocratic method is still used for reducing anterior shoulder dislocations, and its description can be found in several modern orthopedic texts, including recent articles.¹³ The Corpus Hippocrates also describes the correction of clubfoot deformity, and the treatment of infected open fractures with pitch cerate and wine compresses.⁸

Hippocrates also described the treatment of fractures, the principles of traction, and the implications of malunions. For example, Hippocrates wrote, “For the arm, when shortened, might be concealed and the mistake will not be great, but a shortened thigh bone will leave a man maimed.”¹ In addition, spinal deformities were recognized by the Greeks, and Hippocrates devised an extension bench for the correction of such deformities.¹ From their contributions to anatomy and surgical practice, the Greeks have made significant contributions to the field of surgery.⁹

During the Roman period, another Greek surgeon by the name of Galen described the musculoskeletal and nervous systems. He served as a gladiatorial surgeon in Rome, and today, he is considered to be the father of sports medicine.⁸ He is also credited with coining the terms scoliosis, kyphosis, and lordosis to denote the spinal deformities that were first described by Hippocrates.¹ In the Roman period, amputations were also performed, and primitive prostheses were developed.⁹

The Middle Ages

There was relatively little progress in the study of medicine for a thousand years after the fall of the Roman Empire.⁹ This stagnation was predominantly due to the early Christian Church inhibiting freedom of thought and observation, as well as prohibiting human dissection and the study of anatomy. The first medical school in Europe was established in Salerno, Italy, during the ninth century. This school provided primarily pedantic teaching to its students and perpetuated the theories of the elements and humors. Later on, the University of Bologna became one of the first academic institutions to offer hands-on surgical training.⁹ One of the most famous surgeons of the Middle Ages was Guy de Chuauliac, who studied at Montpellier and Bologna. He was a leader in the ethical principles of surgery as well as the practice of surgery, and wrote the following with regards to femur fractures:⁹

“After the application of splints, I attach to the foot a mass of lead as a weight, taking care to pass the cord which supports the weight over a small pulley in such a manner that it shall pull on the leg in a horizontal direction.”

This description is strikingly similar to the modern-day nonoperative management of femur fractures, and underscores the importance of traction, which as mentioned above, was first described by Hippocrates.

Eventually, medicine began to separate from the Church, most likely due to an increase in the complexity of medical theories, the rise of secular universities, and an increase in medical knowledge from Eastern and Middle-Eastern groups.⁹

The Renaissance and the Foundations of Modern Orthopedics

Until the 16^th century, the majority of medical theories were heavily influenced by the work of Hippocrates.⁸ The scientific study of anatomy gained prominence during this time, especially due to the work done by great artists, such as Leonardo Di Vinci.⁹ The Table

After a period of rapid expansion of the field of orthopedics, and following the Renaissance, many hospitals were built focusing on the sick and disabled, which solidified orthopedics’ position as a major medical specialty.¹ For example, in 1863, James Knight founded the Hospital for the Ruptured and Crippled in New York City. This hospital became the oldest orthopedic hospital in the United States, and it later became known as the Hospital for Special Surgery.^14,15 Several additional orthopedic institutions were formed, including the New York Orthopedic Dispensary in 1886 and Hospital for Deformities and Joint Diseases in 1917. Orthopedic surgery residency programs also began to be developed in the late 1800s.¹⁴ More specifically, Virgil Gibney at Hospital for the Ruptured and Crippled began the first orthopedic training program in the United States in 1888. Young doctors in this program trained for 1 year as junior assistant, senior assistant, and house surgeon, and began to be known as resident doctors.¹⁴

The Modern Era

In the 20th century, rapid development continued to better control infections as well as develop and introduce novel technology. For example, the invention of x-ray in 1895 by Wilhelm Conrad Röntgen improved our ability to diagnose and manage orthopedic conditions ranging from fractures to avascular necrosis of the femoral head to osteoarthritis.^8,14 Spinal surgery also developed rapidly with Russell Hibbs describing a technique for spinal fusion at the New York Orthopedic Hospital.⁸ Similarly, the World Wars served as a catalyst in the development of the subspecialty of orthopedic trauma, with increasing attention placed on open wounds and proficiency with amputations, internal fixation, and wound care. In 1942, Austin Moore performed the first metal hip arthroplasty, and the field of joint replacement was subsequently advanced by the work of Sir John Charnley in the 1960s.⁸

Conclusion

Despite its relatively recent specialization, orthopedic surgery has a rich history rooted in ancient practices dating back to the primitive man. Over time, there has been significant development in the field in terms of surgical and nonsurgical treatment of orthopedic pathology and disease. Various cultures have played an instrumental role in developing this field, and it is remarkable to see that several practices have persisted since the time of these ancient civilizations. During the Renaissance, there was a considerable emphasis placed on pediatric deformity, but orthopedic surgeons have now branched out to subspecialty practice ranging from orthopedic trauma to joint replacement to oncology.¹ For students of medicine and orthopedics, it is important to learn about the origins of this field and to appreciate its gradual development. Orthopedic surgery is a diverse and fascinating field that will most likely continue to develop with increased subspecialization and improved research at the molecular and population level. With a growing emphasis placed on outcomes and healthcare cost by today’s society, it will be fascinating to see how this field continues to evolve in the future.

Am J Orthop. 2016;45(7):E434-E438. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

The modern term orthopedics stems from the older word orthopedia, which was the title of a book published in 1741 by Nicholas Andry, a professor of medicine at the University of Paris.¹ The term orthopedia is a composite of 2 Greek words: orthos, meaning “straight and free from deformity,” and paidios, meaning “child.” Together, orthopedics literally means straight child, suggesting the importance of pediatric injuries and deformities in the development of this field. Interestingly, Andry’s book also depicted a crooked young tree attached to a straight and strong staff, which has become the universal symbol of orthopedic surgery and underscores the focus on correcting deformities in the young (Figure).¹

Orthopedic surgery is a rapidly advancing medical field with several recent advances noted within orthopedic subspecialties,^2-4 basic science,⁵ and clinical research.⁶ It is important to recognize the role of history with regards to innovation and research, especially for young trainees and medical students interested in a particular medical specialty. More specifically, it is important to understand the successes and failures of the past in order to advance research and practice, and ultimately improve patient care and outcomes.

In the recent literature, there is no concise yet comprehensive article focusing on the history of orthopedic surgery. The goal of this review is to provide an overview of the history and development of orthopedic surgery from ancient practices to the modern era.

Ancient Orthopedics

While the evidence is limited, the practice of orthopedics dates back to the primitive man.⁷ Fossil evidence suggests that the orthopedic pathology of today, such as fractures and traumatic amputations, existed in primitive times.⁸ The union of fractures in fair alignment has also been observed, which emphasizes the efficacy of nonoperative orthopedics and suggests the early use of splints and rehabilitation practices.^8,9 Since procedures such as trepanation and crude amputations occurred during the New Stone Age, it is feasible that sophisticated techniques had also been developed for the treatment of injuries.^7-9 However, evidence continues to remain limited.⁷

Later civilizations also developed creative ways to manage orthopedic injuries. For example, the Shoshone Indians, who were known to exist around 700-2000 BCE, made a splint of fresh rawhide that had been soaked in water.^9,10 Similarly, some South Australian tribes made splints of clay, which when dried were as good as plaster of Paris.⁹ Furthermore, bone-setting or reductions was practiced as a profession in many tribes, underscoring the importance of orthopedic injuries in early civilizations.^8,9

Ancient Egypt

The ancient Egyptians seemed to have carried on the practices of splinting. For example, 2 splinted specimens were discovered during the Hearst Egyptian Expedition in 1903.⁷ More specifically, these specimens included a femur and forearm and dated to approximately 300 BCE.⁷ Other examples of splints made of bamboo and reed padded with linen have been found on mummies as well.⁸ Similarly, crutches were also used by this civilization, as depicted on a carving made on an Egyptian tomb in 2830 BCE.⁸

One of the earliest and most significant documents on medicine was discovered in 1862, known as the Edwin Smith papyrus. This document is thought to have been composed by Imhotep, a prominent Egyptian physician, astrologer, architect, and politician, and it specifically categorizes diseases and treatments. Many scholars recognize this medical document as the oldest surgical textbook.^11,12 With regards to orthopedic conditions, this document describes the reduction of a dislocated mandible, signs of spinal or vertebral injuries, description of torticollis, and the treatment of fractures such as clavicle fractures.⁸ This document also discusses ryt, which refers to the purulent discharge from osteomyelitis.⁸ The following is an excerpt from this ancient document:⁹

“Instructions on erring a break in his upper arm…Thou shouldst spread out with his two shoulders in order to stretch apart his upper arm until that break falls into its place. Thou shouldst make for him two splints of linen, and thou shouldst apply for him one of them both on the inside of his arm, and the other of them both on the underside of his arm.”

This account illustrates the methodical and meticulous nature of this textbook, and it highlights some of the essentials of medical practice from diagnosis to medical decision-making to treatment.

There are various other contributions to the field of medicine from the Far East; however, many of these pertain to the fields of plastic surgery and general surgery.⁹

Greeks and Romans

The Greeks are considered to be the first to systematically employ the scientific approach to medicine.⁸ In the period between 430 BCE to 330 BCE, the Corpus Hippocrates was compiled, which is a Greek text on medicine. It is named for Hippocrates (460 BCE-370 BCE), the father of medicine, and it contains text that applies specifically to the field of orthopedic surgery. For example, this text discuses shoulder dislocations and describes various reduction maneuvers. Hippocrates had a keen understanding of the principles of traction and countertraction, especially as it pertains to the musculoskeletal system.⁸ In fact, the Hippocratic method is still used for reducing anterior shoulder dislocations, and its description can be found in several modern orthopedic texts, including recent articles.¹³ The Corpus Hippocrates also describes the correction of clubfoot deformity, and the treatment of infected open fractures with pitch cerate and wine compresses.⁸

Hippocrates also described the treatment of fractures, the principles of traction, and the implications of malunions. For example, Hippocrates wrote, “For the arm, when shortened, might be concealed and the mistake will not be great, but a shortened thigh bone will leave a man maimed.”¹ In addition, spinal deformities were recognized by the Greeks, and Hippocrates devised an extension bench for the correction of such deformities.¹ From their contributions to anatomy and surgical practice, the Greeks have made significant contributions to the field of surgery.⁹

During the Roman period, another Greek surgeon by the name of Galen described the musculoskeletal and nervous systems. He served as a gladiatorial surgeon in Rome, and today, he is considered to be the father of sports medicine.⁸ He is also credited with coining the terms scoliosis, kyphosis, and lordosis to denote the spinal deformities that were first described by Hippocrates.¹ In the Roman period, amputations were also performed, and primitive prostheses were developed.⁹

The Middle Ages

There was relatively little progress in the study of medicine for a thousand years after the fall of the Roman Empire.⁹ This stagnation was predominantly due to the early Christian Church inhibiting freedom of thought and observation, as well as prohibiting human dissection and the study of anatomy. The first medical school in Europe was established in Salerno, Italy, during the ninth century. This school provided primarily pedantic teaching to its students and perpetuated the theories of the elements and humors. Later on, the University of Bologna became one of the first academic institutions to offer hands-on surgical training.⁹ One of the most famous surgeons of the Middle Ages was Guy de Chuauliac, who studied at Montpellier and Bologna. He was a leader in the ethical principles of surgery as well as the practice of surgery, and wrote the following with regards to femur fractures:⁹

“After the application of splints, I attach to the foot a mass of lead as a weight, taking care to pass the cord which supports the weight over a small pulley in such a manner that it shall pull on the leg in a horizontal direction.”

This description is strikingly similar to the modern-day nonoperative management of femur fractures, and underscores the importance of traction, which as mentioned above, was first described by Hippocrates.

Eventually, medicine began to separate from the Church, most likely due to an increase in the complexity of medical theories, the rise of secular universities, and an increase in medical knowledge from Eastern and Middle-Eastern groups.⁹

The Renaissance and the Foundations of Modern Orthopedics

Until the 16^th century, the majority of medical theories were heavily influenced by the work of Hippocrates.⁸ The scientific study of anatomy gained prominence during this time, especially due to the work done by great artists, such as Leonardo Di Vinci.⁹ The Table

After a period of rapid expansion of the field of orthopedics, and following the Renaissance, many hospitals were built focusing on the sick and disabled, which solidified orthopedics’ position as a major medical specialty.¹ For example, in 1863, James Knight founded the Hospital for the Ruptured and Crippled in New York City. This hospital became the oldest orthopedic hospital in the United States, and it later became known as the Hospital for Special Surgery.^14,15 Several additional orthopedic institutions were formed, including the New York Orthopedic Dispensary in 1886 and Hospital for Deformities and Joint Diseases in 1917. Orthopedic surgery residency programs also began to be developed in the late 1800s.¹⁴ More specifically, Virgil Gibney at Hospital for the Ruptured and Crippled began the first orthopedic training program in the United States in 1888. Young doctors in this program trained for 1 year as junior assistant, senior assistant, and house surgeon, and began to be known as resident doctors.¹⁴

The Modern Era

In the 20th century, rapid development continued to better control infections as well as develop and introduce novel technology. For example, the invention of x-ray in 1895 by Wilhelm Conrad Röntgen improved our ability to diagnose and manage orthopedic conditions ranging from fractures to avascular necrosis of the femoral head to osteoarthritis.^8,14 Spinal surgery also developed rapidly with Russell Hibbs describing a technique for spinal fusion at the New York Orthopedic Hospital.⁸ Similarly, the World Wars served as a catalyst in the development of the subspecialty of orthopedic trauma, with increasing attention placed on open wounds and proficiency with amputations, internal fixation, and wound care. In 1942, Austin Moore performed the first metal hip arthroplasty, and the field of joint replacement was subsequently advanced by the work of Sir John Charnley in the 1960s.⁸

Conclusion

Despite its relatively recent specialization, orthopedic surgery has a rich history rooted in ancient practices dating back to the primitive man. Over time, there has been significant development in the field in terms of surgical and nonsurgical treatment of orthopedic pathology and disease. Various cultures have played an instrumental role in developing this field, and it is remarkable to see that several practices have persisted since the time of these ancient civilizations. During the Renaissance, there was a considerable emphasis placed on pediatric deformity, but orthopedic surgeons have now branched out to subspecialty practice ranging from orthopedic trauma to joint replacement to oncology.¹ For students of medicine and orthopedics, it is important to learn about the origins of this field and to appreciate its gradual development. Orthopedic surgery is a diverse and fascinating field that will most likely continue to develop with increased subspecialization and improved research at the molecular and population level. With a growing emphasis placed on outcomes and healthcare cost by today’s society, it will be fascinating to see how this field continues to evolve in the future.

Am J Orthop. 2016;45(7):E434-E438. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Oren is 11. I often see him around the neighborhood.

The other day I gave his father a lift. “Oren had a rash on his face,” said Ben, slipping into the passenger seat. “The pediatrician said she thought it was eczema, but she gave him an acne medicine.”

I raised my eyebrows, but said nothing.

Dr. Rockoff practices dermatology in Brookline, Mass, and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His new book “Act Like a Doctor, Think Like a Patient” is now available at amazon.com and barnesandnoble.com. This is his second book. Write to him at [email protected].

Oren is 11. I often see him around the neighborhood.

The other day I gave his father a lift. “Oren had a rash on his face,” said Ben, slipping into the passenger seat. “The pediatrician said she thought it was eczema, but she gave him an acne medicine.”

I raised my eyebrows, but said nothing.

Dr. Rockoff practices dermatology in Brookline, Mass, and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His new book “Act Like a Doctor, Think Like a Patient” is now available at amazon.com and barnesandnoble.com. This is his second book. Write to him at [email protected].

Oren is 11. I often see him around the neighborhood.

The other day I gave his father a lift. “Oren had a rash on his face,” said Ben, slipping into the passenger seat. “The pediatrician said she thought it was eczema, but she gave him an acne medicine.”

I raised my eyebrows, but said nothing.

Dr. Rockoff practices dermatology in Brookline, Mass, and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His new book “Act Like a Doctor, Think Like a Patient” is now available at amazon.com and barnesandnoble.com. This is his second book. Write to him at [email protected].

Preparing for HSCT

Photo by Chad McNeeley

Palliative care can be beneficial for patients undergoing hematopoietic stem cell transplant (HSCT) to treat hematologic malignancies, according to research published in JAMA.

The single-center study suggested that palliative care can improve HSCT recipients’ quality of life, relieve symptoms associated with the procedure, and reduce depression and anxiety.

Researchers observed such benefits during hospitalization for HSCT and a few months later.

In addition, caregivers of patients receiving palliative care experienced less depression and were better at coping with the stress associated with the illness of their loved one.

“Palliative care clinicians are increasingly asked to help care for patients with solid tumors but are rarely consulted for patients with hematologic malignancies, especially those receiving therapy designed to cure their disease,” said study author Areej El-Jawahri, MD, of Massachusette General Hospital in Boston.

“The physical and psychological symptoms associated with HSCT are sometimes regarded as expected and unavoidable, which, combined with the persistent misperception that equates palliative care with end-of-life care, has contributed to a lack of involvement of palliative care clinicians in the care of these patients.”

Intervention

Dr El-Jawahri and her colleagues studied 160 patients who underwent autologous or allogeneic HSCT to treat a variety of hematologic malignancies from August 2014 into January 2016.

Participants were randomized to receive either standard care (n=79) or the palliative care intervention (n=81).

Within 3 days of their admission to the hospital, patients in the intervention group had an initial meeting with a palliative care clinician—a physician or advance practice nurse—who continued to meet with them at least twice a week during their hospitalization.

At the meetings, which could be attended by a family member or friend of the patient, clinicians first focused on establishing a rapport with patients and their caregivers.

Clinicians addressed ways of managing the physical and psychological symptoms patients were experiencing and provided support and strategies for coping with distress. Patients received an average of 8 palliative care visits during their hospitalizations, which lasted on average 20 days.

At the outset of the study and 2 weeks into the process, a time when symptoms tend to be at their worst, patients in both groups and participating caregivers completed questionnaires assessing their mood and quality of life.

Patients also completed questionnaires asking about symptoms of their illness and those associated with the procedure. Patients completed additional assessments 3 months after HSCT as well.

Results

The study’s primary endpoint was change in quality of life from baseline to week 2. Patients receiving the palliative care intervention had significantly better quality of life scores at week 2 than patients in the control group.

Also at the 2-week mark, patients receiving the palliative care intervention reported lower levels of depression, anxiety, and symptoms than the control group, but there was no significant difference between the groups with regard to fatigue.

At 3 months, patients receiving the palliative care intervention still had higher quality of life scores and less depression than controls, but there were no significant between-group differences in anxiety, fatigue, or symptom burden.

Caregivers attended 42% of the palliative care sessions. At the 2-week assessment, caregivers in the intervention group were found to have fewer depressive symptoms and improved coping skills, compared with caregivers in the control group.

“Caregivers play a crucial role in supporting patients during the transplant process, and they are substantially impacted as they watch their loved ones struggle with side effects that can be emotionally challenging,” Dr El-Jawahri said.

She and her colleagues noted that additional, larger studies are needed to assess caregiver impacts more completely, to replicate patient results at centers with more diverse patient populations, to assess the inclusion of more complete palliative care teams, to collect cost data, and to adapt the palliative care intervention to assist patients receiving other potentially curative treatment for hematologic or other cancers.

Preparing for HSCT

Photo by Chad McNeeley

Palliative care can be beneficial for patients undergoing hematopoietic stem cell transplant (HSCT) to treat hematologic malignancies, according to research published in JAMA.

The single-center study suggested that palliative care can improve HSCT recipients’ quality of life, relieve symptoms associated with the procedure, and reduce depression and anxiety.

Researchers observed such benefits during hospitalization for HSCT and a few months later.

In addition, caregivers of patients receiving palliative care experienced less depression and were better at coping with the stress associated with the illness of their loved one.

“Palliative care clinicians are increasingly asked to help care for patients with solid tumors but are rarely consulted for patients with hematologic malignancies, especially those receiving therapy designed to cure their disease,” said study author Areej El-Jawahri, MD, of Massachusette General Hospital in Boston.

“The physical and psychological symptoms associated with HSCT are sometimes regarded as expected and unavoidable, which, combined with the persistent misperception that equates palliative care with end-of-life care, has contributed to a lack of involvement of palliative care clinicians in the care of these patients.”

Intervention

Dr El-Jawahri and her colleagues studied 160 patients who underwent autologous or allogeneic HSCT to treat a variety of hematologic malignancies from August 2014 into January 2016.

Participants were randomized to receive either standard care (n=79) or the palliative care intervention (n=81).

Within 3 days of their admission to the hospital, patients in the intervention group had an initial meeting with a palliative care clinician—a physician or advance practice nurse—who continued to meet with them at least twice a week during their hospitalization.

At the meetings, which could be attended by a family member or friend of the patient, clinicians first focused on establishing a rapport with patients and their caregivers.

Clinicians addressed ways of managing the physical and psychological symptoms patients were experiencing and provided support and strategies for coping with distress. Patients received an average of 8 palliative care visits during their hospitalizations, which lasted on average 20 days.

At the outset of the study and 2 weeks into the process, a time when symptoms tend to be at their worst, patients in both groups and participating caregivers completed questionnaires assessing their mood and quality of life.

Patients also completed questionnaires asking about symptoms of their illness and those associated with the procedure. Patients completed additional assessments 3 months after HSCT as well.

Results

The study’s primary endpoint was change in quality of life from baseline to week 2. Patients receiving the palliative care intervention had significantly better quality of life scores at week 2 than patients in the control group.

Also at the 2-week mark, patients receiving the palliative care intervention reported lower levels of depression, anxiety, and symptoms than the control group, but there was no significant difference between the groups with regard to fatigue.

At 3 months, patients receiving the palliative care intervention still had higher quality of life scores and less depression than controls, but there were no significant between-group differences in anxiety, fatigue, or symptom burden.

Caregivers attended 42% of the palliative care sessions. At the 2-week assessment, caregivers in the intervention group were found to have fewer depressive symptoms and improved coping skills, compared with caregivers in the control group.

“Caregivers play a crucial role in supporting patients during the transplant process, and they are substantially impacted as they watch their loved ones struggle with side effects that can be emotionally challenging,” Dr El-Jawahri said.

She and her colleagues noted that additional, larger studies are needed to assess caregiver impacts more completely, to replicate patient results at centers with more diverse patient populations, to assess the inclusion of more complete palliative care teams, to collect cost data, and to adapt the palliative care intervention to assist patients receiving other potentially curative treatment for hematologic or other cancers.

Preparing for HSCT

Photo by Chad McNeeley

Palliative care can be beneficial for patients undergoing hematopoietic stem cell transplant (HSCT) to treat hematologic malignancies, according to research published in JAMA.

The single-center study suggested that palliative care can improve HSCT recipients’ quality of life, relieve symptoms associated with the procedure, and reduce depression and anxiety.

Researchers observed such benefits during hospitalization for HSCT and a few months later.

In addition, caregivers of patients receiving palliative care experienced less depression and were better at coping with the stress associated with the illness of their loved one.

“Palliative care clinicians are increasingly asked to help care for patients with solid tumors but are rarely consulted for patients with hematologic malignancies, especially those receiving therapy designed to cure their disease,” said study author Areej El-Jawahri, MD, of Massachusette General Hospital in Boston.

“The physical and psychological symptoms associated with HSCT are sometimes regarded as expected and unavoidable, which, combined with the persistent misperception that equates palliative care with end-of-life care, has contributed to a lack of involvement of palliative care clinicians in the care of these patients.”

Intervention

Dr El-Jawahri and her colleagues studied 160 patients who underwent autologous or allogeneic HSCT to treat a variety of hematologic malignancies from August 2014 into January 2016.

Participants were randomized to receive either standard care (n=79) or the palliative care intervention (n=81).

Within 3 days of their admission to the hospital, patients in the intervention group had an initial meeting with a palliative care clinician—a physician or advance practice nurse—who continued to meet with them at least twice a week during their hospitalization.

At the meetings, which could be attended by a family member or friend of the patient, clinicians first focused on establishing a rapport with patients and their caregivers.

Clinicians addressed ways of managing the physical and psychological symptoms patients were experiencing and provided support and strategies for coping with distress. Patients received an average of 8 palliative care visits during their hospitalizations, which lasted on average 20 days.

At the outset of the study and 2 weeks into the process, a time when symptoms tend to be at their worst, patients in both groups and participating caregivers completed questionnaires assessing their mood and quality of life.

Patients also completed questionnaires asking about symptoms of their illness and those associated with the procedure. Patients completed additional assessments 3 months after HSCT as well.

Results

The study’s primary endpoint was change in quality of life from baseline to week 2. Patients receiving the palliative care intervention had significantly better quality of life scores at week 2 than patients in the control group.

Also at the 2-week mark, patients receiving the palliative care intervention reported lower levels of depression, anxiety, and symptoms than the control group, but there was no significant difference between the groups with regard to fatigue.

At 3 months, patients receiving the palliative care intervention still had higher quality of life scores and less depression than controls, but there were no significant between-group differences in anxiety, fatigue, or symptom burden.

Caregivers attended 42% of the palliative care sessions. At the 2-week assessment, caregivers in the intervention group were found to have fewer depressive symptoms and improved coping skills, compared with caregivers in the control group.

“Caregivers play a crucial role in supporting patients during the transplant process, and they are substantially impacted as they watch their loved ones struggle with side effects that can be emotionally challenging,” Dr El-Jawahri said.

She and her colleagues noted that additional, larger studies are needed to assess caregiver impacts more completely, to replicate patient results at centers with more diverse patient populations, to assess the inclusion of more complete palliative care teams, to collect cost data, and to adapt the palliative care intervention to assist patients receiving other potentially curative treatment for hematologic or other cancers.

Nivolumab (Opdivo)

Photo from Business Wire

The European Commission (EC) has approved nivolumab (Opdivo) for the treatment of adults with relapsed or refractory classical Hodgkin lymphoma (cHL) who have already received an autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV).

Nivolumab is the first PD-1 inhibitor approved in the European Economic Area as a treatment for a hematologic malignancy.

The EC previously approved nivolumab to treat advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. In Europe, nivolumab is marketed by Bristol-Myers Squibb.

Trials in cHL

The EC’s approval of nivolumab in cHL is based on an integrated analysis of data from 2 trials—the phase 1 CheckMate -039 trial and the phase 2 CheckMate -205 trial.

In CheckMate -039, researchers evaluated nivolumab in patients with cHL, non-Hodgkin lymphoma, and multiple myeloma. Results from this trial were presented at the 13th International Congress on Malignant Lymphoma in June 2015.

In CheckMate -205, researchers are evaluating nivolumab in 4 cohorts of cHL patients. Cohort A includes patients who previously received auto-HSCT and were BV-naïve at enrollment (n=63). Cohort B includes patients who previously received auto-HSCT followed by BV (n=80).

Cohort C includes patients who previously received BV before and/or after auto-HSCT (n=100). And cohort D, which is currently enrolling, is an evaluation of nivolumab in combination with chemotherapy in newly diagnosed, advanced-stage cHL patients who are treatment-naïve (n=50).

Results from cohort B were presented at the 21st Congress of the European Hematology Association in June 2016. Results from cohort C were presented at the 10th International Symposium on Hodgkin Lymphoma last month.

Integrated analysis

The analysis included cHL patients from CheckMate -205 and -039 who had received auto-HSCT and BV.

In the efficacy population (n=95), the objective response rate was 66%. The percentage of patients with a complete response was 6%. Twenty-three percent of patients had stable disease.

The median time to response was 2.0 months (range, 0.7-11.1), and the median duration of response was 13.1 months (range, 0.0+, 23.1+). At 12 months, the progression-free survival rate was 57%.

The safety of nivolumab in cHL was evaluated in 263 patients from CheckMate -205 (n=240) and CheckMate -039 (n=23). Serious adverse events (AEs) occurred in 21% of these patients.

The most common serious AEs (reported in at least 1% of patients) were infusion-related reactions, pneumonia, pleural effusion, pyrexia, rash, and pneumonitis.

The most common AEs (reported in at least 20% of patients) were fatigue (32%), upper respiratory tract infection (28%), pyrexia (24%), diarrhea (23%), and cough (22%).

Twenty-three percent of patients had a dose delay resulting from an AE, and 4.2% of patients discontinued treatment due to AEs.

Forty patients went on to allogeneic HSCT after nivolumab, and 6 of these patients died from complications of the transplant. The 40 patients had a median follow-up from allogeneic HSCT of 2.9 months (range, 0-22).

Because of these deaths, the US Food and Drug Administration asked Bristol-Myers Squibb to study the safety of allogeneic HSCT after nivolumab.

Nivolumab (Opdivo)

Photo from Business Wire

The European Commission (EC) has approved nivolumab (Opdivo) for the treatment of adults with relapsed or refractory classical Hodgkin lymphoma (cHL) who have already received an autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV).

Nivolumab is the first PD-1 inhibitor approved in the European Economic Area as a treatment for a hematologic malignancy.

The EC previously approved nivolumab to treat advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. In Europe, nivolumab is marketed by Bristol-Myers Squibb.

Trials in cHL

The EC’s approval of nivolumab in cHL is based on an integrated analysis of data from 2 trials—the phase 1 CheckMate -039 trial and the phase 2 CheckMate -205 trial.

In CheckMate -039, researchers evaluated nivolumab in patients with cHL, non-Hodgkin lymphoma, and multiple myeloma. Results from this trial were presented at the 13th International Congress on Malignant Lymphoma in June 2015.

In CheckMate -205, researchers are evaluating nivolumab in 4 cohorts of cHL patients. Cohort A includes patients who previously received auto-HSCT and were BV-naïve at enrollment (n=63). Cohort B includes patients who previously received auto-HSCT followed by BV (n=80).

Cohort C includes patients who previously received BV before and/or after auto-HSCT (n=100). And cohort D, which is currently enrolling, is an evaluation of nivolumab in combination with chemotherapy in newly diagnosed, advanced-stage cHL patients who are treatment-naïve (n=50).

Results from cohort B were presented at the 21st Congress of the European Hematology Association in June 2016. Results from cohort C were presented at the 10th International Symposium on Hodgkin Lymphoma last month.

Integrated analysis

The analysis included cHL patients from CheckMate -205 and -039 who had received auto-HSCT and BV.

In the efficacy population (n=95), the objective response rate was 66%. The percentage of patients with a complete response was 6%. Twenty-three percent of patients had stable disease.

The median time to response was 2.0 months (range, 0.7-11.1), and the median duration of response was 13.1 months (range, 0.0+, 23.1+). At 12 months, the progression-free survival rate was 57%.

The safety of nivolumab in cHL was evaluated in 263 patients from CheckMate -205 (n=240) and CheckMate -039 (n=23). Serious adverse events (AEs) occurred in 21% of these patients.

The most common serious AEs (reported in at least 1% of patients) were infusion-related reactions, pneumonia, pleural effusion, pyrexia, rash, and pneumonitis.

The most common AEs (reported in at least 20% of patients) were fatigue (32%), upper respiratory tract infection (28%), pyrexia (24%), diarrhea (23%), and cough (22%).

Twenty-three percent of patients had a dose delay resulting from an AE, and 4.2% of patients discontinued treatment due to AEs.

Forty patients went on to allogeneic HSCT after nivolumab, and 6 of these patients died from complications of the transplant. The 40 patients had a median follow-up from allogeneic HSCT of 2.9 months (range, 0-22).

Because of these deaths, the US Food and Drug Administration asked Bristol-Myers Squibb to study the safety of allogeneic HSCT after nivolumab.

Nivolumab (Opdivo)

Photo from Business Wire

The European Commission (EC) has approved nivolumab (Opdivo) for the treatment of adults with relapsed or refractory classical Hodgkin lymphoma (cHL) who have already received an autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV).

Nivolumab is the first PD-1 inhibitor approved in the European Economic Area as a treatment for a hematologic malignancy.

The EC previously approved nivolumab to treat advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. In Europe, nivolumab is marketed by Bristol-Myers Squibb.

Trials in cHL

The EC’s approval of nivolumab in cHL is based on an integrated analysis of data from 2 trials—the phase 1 CheckMate -039 trial and the phase 2 CheckMate -205 trial.

In CheckMate -039, researchers evaluated nivolumab in patients with cHL, non-Hodgkin lymphoma, and multiple myeloma. Results from this trial were presented at the 13th International Congress on Malignant Lymphoma in June 2015.

In CheckMate -205, researchers are evaluating nivolumab in 4 cohorts of cHL patients. Cohort A includes patients who previously received auto-HSCT and were BV-naïve at enrollment (n=63). Cohort B includes patients who previously received auto-HSCT followed by BV (n=80).

Cohort C includes patients who previously received BV before and/or after auto-HSCT (n=100). And cohort D, which is currently enrolling, is an evaluation of nivolumab in combination with chemotherapy in newly diagnosed, advanced-stage cHL patients who are treatment-naïve (n=50).

Results from cohort B were presented at the 21st Congress of the European Hematology Association in June 2016. Results from cohort C were presented at the 10th International Symposium on Hodgkin Lymphoma last month.

Integrated analysis

The analysis included cHL patients from CheckMate -205 and -039 who had received auto-HSCT and BV.

In the efficacy population (n=95), the objective response rate was 66%. The percentage of patients with a complete response was 6%. Twenty-three percent of patients had stable disease.

The median time to response was 2.0 months (range, 0.7-11.1), and the median duration of response was 13.1 months (range, 0.0+, 23.1+). At 12 months, the progression-free survival rate was 57%.

The safety of nivolumab in cHL was evaluated in 263 patients from CheckMate -205 (n=240) and CheckMate -039 (n=23). Serious adverse events (AEs) occurred in 21% of these patients.

The most common serious AEs (reported in at least 1% of patients) were infusion-related reactions, pneumonia, pleural effusion, pyrexia, rash, and pneumonitis.

The most common AEs (reported in at least 20% of patients) were fatigue (32%), upper respiratory tract infection (28%), pyrexia (24%), diarrhea (23%), and cough (22%).

Twenty-three percent of patients had a dose delay resulting from an AE, and 4.2% of patients discontinued treatment due to AEs.

Forty patients went on to allogeneic HSCT after nivolumab, and 6 of these patients died from complications of the transplant. The 40 patients had a median follow-up from allogeneic HSCT of 2.9 months (range, 0-22).

Because of these deaths, the US Food and Drug Administration asked Bristol-Myers Squibb to study the safety of allogeneic HSCT after nivolumab.

The very nature of America’s hospitals is changing. At one time in the not too distant past, hospitals could charge “cost-plus,” tacking on a profit above their actual expenses. Hospitals generated most of their revenue from procedures on horizontal patients with long stays in house. Physicians viewed the hospital as a swap meet, with each physician having an autonomous booth and not caring much what went on elsewhere in the facility.

Today, hospitals are under tough cost pressures, with changes in payments from Medicare, Medicaid, and private insurers. Many hospitals now get more than 50% of their revenue from vertical patients from what was previously considered the outpatient segment of healthcare. Physicians have moved from being revenue providers to being potential competitors or, in the best-case scenario, active partners and teammates with their hospital.

And hospitalists are right in the middle of this changing dynamic.

Because the hospital and the healthcare system are rapidly evolving, it should not surprise anyone that the very nature of hospital medicine is changing rapidly. Some would say too rapidly.

At a strategic planning session I led almost 20 years when the National Association of Inpatient Physicians (NAIP), the precursor to SHM, was just starting out, the prevailing consensus was that hospitalists might take over inpatient services for 50% of family physicians and 25% of internists. Obviously, the penetrance of hospital medicine into almost every hospital in the U.S. and the transfer of the acute-care management of most of the inpatients previously handled by family physicians and internists are just part of the growth in hospital medicine.

Even more innovative and disruptive has been the almost relentless scope creep as hospitalists now actively comanage many surgical and subspecialty patients. As the neurologists have given up most of their acute-care duties, hospitalists are now the de facto inpatient neurologists. Hospitalists also now manage the majority of inpatient senior citizens and have become the inpatient geriatricians without the formal training. In-hospital procedures (e.g., central line, ultrasound, intubation, etc.) previously done by surgeons or critical-care or primary-care physicians now are done by default by hospitalists.

But these expansions of hospitalist scope pale in comparison with the continued broadening of responsibilities that continues to stretch even the most well-trained hospitalists beyond their training or capacity.

Palliative Care

There are not enough trained and certified palliative-care physicians to allocate one of them to each hospital. Yet treatment and survival of cancer and other serious diseases as well as the aging of the population demand that hospitals be prepared to provide the most compassionate and up-to-date palliative approach possible. Palliative care is more than just end-of-life care. It involves hospice as well as pain and symptom management. It is aimed at improvement in quality of life and is used in the presence or absence of curative strategies.

Hospitalists have been thrust into the breach and are being asked more and more to provide palliative-care services. SHM has recognized the gap between the increasing demand on hospitalists and the inadequate training we all receive in residency. That’s why we’re working with palliative-care societies and experts to develop educational and training initiatives to close these gaps.

Critical Care

Our hospitals are becoming increasingly critical care intensive as simpler cases are treated as outpatients and only the very ill come to be admitted to hospital. This has created an increasing demand for more physicians trained in critical care at a time when older intensivists are retiring or going into sleep medicine and younger physicians, who might have chosen a career in critical care, are becoming hospitalists. The shortage of trained critical-care providers is reaching a crisis point in many American hospitals, with hospitalists being asked to be the critical-care extender.

Over the years, SHM has partnered with the Society of Critical Care Medicine (SCCM) to propose innovative training options (e.g., one-year critical-care fellowship obtained midcareer), but the boards and others in the critical-care establishment have not been supportive. SHM plans to continue to work with open-minded critical-care thought leaders to develop and promote additional training in critical-care skills for hospitalists, who continue to be thrust into this role at their local hospitals.

Post-Acute Care

For many of hospital medicine’s larger national and regional companies, the management of the care in the post-acute-care space of skilled nursing facilities, long-term acute-care facilities, and the like has been the fastest-growing part of their business in the last few years. Skills and process improvement that have helped improve effectiveness and efficiency in our nation’s hospitals are being applied to post-acute-care facilities. Once again, hospitalists are finding themselves being asked to perform at a high level in environments that are new to them.

In this arena, the hospitalist’s ability to impact care is evident in managing transfers and information as well as providing leadership in patient safety. Determining the correct postdischarge disposition is the largest driver of costs in the acute-care and post-acute-care setting. Hospitalists and the hospital medicine organizations are providing key direction.

Preoperative Care

Many may not know that bundled into the anesthesia fee is the funding to cover pre-op assessment and post-op management as well as the intraoperative oversight of anesthesia and vital signs for the surgical patient. In reality, the role of perioperative management has fallen for many years initially to internists and more recently to hospitalists.

Hospitalists have been active in optimizing the patient for surgery and medically clearing the patient. Hospitalists work with surgeons to manage comorbidities; prevent complications, such as infections, DVTs, and pulmonary emboli; and help with pain management and transitions to discharge from the hospital. Hospitalists have worked with surgeons to create efficiencies like reduced length of stay and prevention of readmission as well as to help the patient return to function postoperatively.

SHM’s Perioperative Care Work Group is publishing a set of Perioperative Care Guidelines in the Journal of Hospital Medicine. SHM is actively working with the American College of Surgeons on a teamwork approach to the surgical patient as well as innovative alternative payment models with bundling at the level of the individual surgical patients, which the Centers for Medicare & Medicaid Services is currently evaluating.

Working through a Dilemma

The one thing all these expansions of scope have in common is that there is an unfilled need and hospitalists are being thrust onto the front lines, thrown into the deep water without the benefit of thorough training that should be requisite with the responsibilities. This is not a turf battle where we have stolen someone’s cheese. This is pure and simple where need is trumping training, and if not done properly, the patient may suffer, and hospitalists will bear the uncomfortable feeling of being asked to do more than we should.

SHM and our national hospitalist thought leaders see this dilemma. We are working diligently with other professional medical societies and key specialty educators and thought leaders to create training pathways to support the expansion of the hospitalist’s scope. This is building the boat while you are going down a rapidly moving river. It is not easy stuff. But our patients and our hospitalists demand this, and SHM will step up. Help is on the way.

Larry Wellikson, MD, MHM, is CEO of the Society of Hospital Medicine.

The very nature of America’s hospitals is changing. At one time in the not too distant past, hospitals could charge “cost-plus,” tacking on a profit above their actual expenses. Hospitals generated most of their revenue from procedures on horizontal patients with long stays in house. Physicians viewed the hospital as a swap meet, with each physician having an autonomous booth and not caring much what went on elsewhere in the facility.

Today, hospitals are under tough cost pressures, with changes in payments from Medicare, Medicaid, and private insurers. Many hospitals now get more than 50% of their revenue from vertical patients from what was previously considered the outpatient segment of healthcare. Physicians have moved from being revenue providers to being potential competitors or, in the best-case scenario, active partners and teammates with their hospital.

And hospitalists are right in the middle of this changing dynamic.

Because the hospital and the healthcare system are rapidly evolving, it should not surprise anyone that the very nature of hospital medicine is changing rapidly. Some would say too rapidly.

At a strategic planning session I led almost 20 years when the National Association of Inpatient Physicians (NAIP), the precursor to SHM, was just starting out, the prevailing consensus was that hospitalists might take over inpatient services for 50% of family physicians and 25% of internists. Obviously, the penetrance of hospital medicine into almost every hospital in the U.S. and the transfer of the acute-care management of most of the inpatients previously handled by family physicians and internists are just part of the growth in hospital medicine.

Even more innovative and disruptive has been the almost relentless scope creep as hospitalists now actively comanage many surgical and subspecialty patients. As the neurologists have given up most of their acute-care duties, hospitalists are now the de facto inpatient neurologists. Hospitalists also now manage the majority of inpatient senior citizens and have become the inpatient geriatricians without the formal training. In-hospital procedures (e.g., central line, ultrasound, intubation, etc.) previously done by surgeons or critical-care or primary-care physicians now are done by default by hospitalists.

But these expansions of hospitalist scope pale in comparison with the continued broadening of responsibilities that continues to stretch even the most well-trained hospitalists beyond their training or capacity.

Palliative Care

There are not enough trained and certified palliative-care physicians to allocate one of them to each hospital. Yet treatment and survival of cancer and other serious diseases as well as the aging of the population demand that hospitals be prepared to provide the most compassionate and up-to-date palliative approach possible. Palliative care is more than just end-of-life care. It involves hospice as well as pain and symptom management. It is aimed at improvement in quality of life and is used in the presence or absence of curative strategies.

Hospitalists have been thrust into the breach and are being asked more and more to provide palliative-care services. SHM has recognized the gap between the increasing demand on hospitalists and the inadequate training we all receive in residency. That’s why we’re working with palliative-care societies and experts to develop educational and training initiatives to close these gaps.

Critical Care

Our hospitals are becoming increasingly critical care intensive as simpler cases are treated as outpatients and only the very ill come to be admitted to hospital. This has created an increasing demand for more physicians trained in critical care at a time when older intensivists are retiring or going into sleep medicine and younger physicians, who might have chosen a career in critical care, are becoming hospitalists. The shortage of trained critical-care providers is reaching a crisis point in many American hospitals, with hospitalists being asked to be the critical-care extender.

Over the years, SHM has partnered with the Society of Critical Care Medicine (SCCM) to propose innovative training options (e.g., one-year critical-care fellowship obtained midcareer), but the boards and others in the critical-care establishment have not been supportive. SHM plans to continue to work with open-minded critical-care thought leaders to develop and promote additional training in critical-care skills for hospitalists, who continue to be thrust into this role at their local hospitals.

Post-Acute Care

For many of hospital medicine’s larger national and regional companies, the management of the care in the post-acute-care space of skilled nursing facilities, long-term acute-care facilities, and the like has been the fastest-growing part of their business in the last few years. Skills and process improvement that have helped improve effectiveness and efficiency in our nation’s hospitals are being applied to post-acute-care facilities. Once again, hospitalists are finding themselves being asked to perform at a high level in environments that are new to them.

In this arena, the hospitalist’s ability to impact care is evident in managing transfers and information as well as providing leadership in patient safety. Determining the correct postdischarge disposition is the largest driver of costs in the acute-care and post-acute-care setting. Hospitalists and the hospital medicine organizations are providing key direction.

Preoperative Care

Many may not know that bundled into the anesthesia fee is the funding to cover pre-op assessment and post-op management as well as the intraoperative oversight of anesthesia and vital signs for the surgical patient. In reality, the role of perioperative management has fallen for many years initially to internists and more recently to hospitalists.

Hospitalists have been active in optimizing the patient for surgery and medically clearing the patient. Hospitalists work with surgeons to manage comorbidities; prevent complications, such as infections, DVTs, and pulmonary emboli; and help with pain management and transitions to discharge from the hospital. Hospitalists have worked with surgeons to create efficiencies like reduced length of stay and prevention of readmission as well as to help the patient return to function postoperatively.

SHM’s Perioperative Care Work Group is publishing a set of Perioperative Care Guidelines in the Journal of Hospital Medicine. SHM is actively working with the American College of Surgeons on a teamwork approach to the surgical patient as well as innovative alternative payment models with bundling at the level of the individual surgical patients, which the Centers for Medicare & Medicaid Services is currently evaluating.

Working through a Dilemma

The one thing all these expansions of scope have in common is that there is an unfilled need and hospitalists are being thrust onto the front lines, thrown into the deep water without the benefit of thorough training that should be requisite with the responsibilities. This is not a turf battle where we have stolen someone’s cheese. This is pure and simple where need is trumping training, and if not done properly, the patient may suffer, and hospitalists will bear the uncomfortable feeling of being asked to do more than we should.

SHM and our national hospitalist thought leaders see this dilemma. We are working diligently with other professional medical societies and key specialty educators and thought leaders to create training pathways to support the expansion of the hospitalist’s scope. This is building the boat while you are going down a rapidly moving river. It is not easy stuff. But our patients and our hospitalists demand this, and SHM will step up. Help is on the way.

Larry Wellikson, MD, MHM, is CEO of the Society of Hospital Medicine.

The very nature of America’s hospitals is changing. At one time in the not too distant past, hospitals could charge “cost-plus,” tacking on a profit above their actual expenses. Hospitals generated most of their revenue from procedures on horizontal patients with long stays in house. Physicians viewed the hospital as a swap meet, with each physician having an autonomous booth and not caring much what went on elsewhere in the facility.

Today, hospitals are under tough cost pressures, with changes in payments from Medicare, Medicaid, and private insurers. Many hospitals now get more than 50% of their revenue from vertical patients from what was previously considered the outpatient segment of healthcare. Physicians have moved from being revenue providers to being potential competitors or, in the best-case scenario, active partners and teammates with their hospital.

And hospitalists are right in the middle of this changing dynamic.

Because the hospital and the healthcare system are rapidly evolving, it should not surprise anyone that the very nature of hospital medicine is changing rapidly. Some would say too rapidly.

At a strategic planning session I led almost 20 years when the National Association of Inpatient Physicians (NAIP), the precursor to SHM, was just starting out, the prevailing consensus was that hospitalists might take over inpatient services for 50% of family physicians and 25% of internists. Obviously, the penetrance of hospital medicine into almost every hospital in the U.S. and the transfer of the acute-care management of most of the inpatients previously handled by family physicians and internists are just part of the growth in hospital medicine.

Even more innovative and disruptive has been the almost relentless scope creep as hospitalists now actively comanage many surgical and subspecialty patients. As the neurologists have given up most of their acute-care duties, hospitalists are now the de facto inpatient neurologists. Hospitalists also now manage the majority of inpatient senior citizens and have become the inpatient geriatricians without the formal training. In-hospital procedures (e.g., central line, ultrasound, intubation, etc.) previously done by surgeons or critical-care or primary-care physicians now are done by default by hospitalists.

But these expansions of hospitalist scope pale in comparison with the continued broadening of responsibilities that continues to stretch even the most well-trained hospitalists beyond their training or capacity.

Palliative Care

There are not enough trained and certified palliative-care physicians to allocate one of them to each hospital. Yet treatment and survival of cancer and other serious diseases as well as the aging of the population demand that hospitals be prepared to provide the most compassionate and up-to-date palliative approach possible. Palliative care is more than just end-of-life care. It involves hospice as well as pain and symptom management. It is aimed at improvement in quality of life and is used in the presence or absence of curative strategies.

Hospitalists have been thrust into the breach and are being asked more and more to provide palliative-care services. SHM has recognized the gap between the increasing demand on hospitalists and the inadequate training we all receive in residency. That’s why we’re working with palliative-care societies and experts to develop educational and training initiatives to close these gaps.

Critical Care

Our hospitals are becoming increasingly critical care intensive as simpler cases are treated as outpatients and only the very ill come to be admitted to hospital. This has created an increasing demand for more physicians trained in critical care at a time when older intensivists are retiring or going into sleep medicine and younger physicians, who might have chosen a career in critical care, are becoming hospitalists. The shortage of trained critical-care providers is reaching a crisis point in many American hospitals, with hospitalists being asked to be the critical-care extender.

Over the years, SHM has partnered with the Society of Critical Care Medicine (SCCM) to propose innovative training options (e.g., one-year critical-care fellowship obtained midcareer), but the boards and others in the critical-care establishment have not been supportive. SHM plans to continue to work with open-minded critical-care thought leaders to develop and promote additional training in critical-care skills for hospitalists, who continue to be thrust into this role at their local hospitals.

Post-Acute Care

For many of hospital medicine’s larger national and regional companies, the management of the care in the post-acute-care space of skilled nursing facilities, long-term acute-care facilities, and the like has been the fastest-growing part of their business in the last few years. Skills and process improvement that have helped improve effectiveness and efficiency in our nation’s hospitals are being applied to post-acute-care facilities. Once again, hospitalists are finding themselves being asked to perform at a high level in environments that are new to them.

In this arena, the hospitalist’s ability to impact care is evident in managing transfers and information as well as providing leadership in patient safety. Determining the correct postdischarge disposition is the largest driver of costs in the acute-care and post-acute-care setting. Hospitalists and the hospital medicine organizations are providing key direction.

Preoperative Care

Many may not know that bundled into the anesthesia fee is the funding to cover pre-op assessment and post-op management as well as the intraoperative oversight of anesthesia and vital signs for the surgical patient. In reality, the role of perioperative management has fallen for many years initially to internists and more recently to hospitalists.

Hospitalists have been active in optimizing the patient for surgery and medically clearing the patient. Hospitalists work with surgeons to manage comorbidities; prevent complications, such as infections, DVTs, and pulmonary emboli; and help with pain management and transitions to discharge from the hospital. Hospitalists have worked with surgeons to create efficiencies like reduced length of stay and prevention of readmission as well as to help the patient return to function postoperatively.

SHM’s Perioperative Care Work Group is publishing a set of Perioperative Care Guidelines in the Journal of Hospital Medicine. SHM is actively working with the American College of Surgeons on a teamwork approach to the surgical patient as well as innovative alternative payment models with bundling at the level of the individual surgical patients, which the Centers for Medicare & Medicaid Services is currently evaluating.

Working through a Dilemma

The one thing all these expansions of scope have in common is that there is an unfilled need and hospitalists are being thrust onto the front lines, thrown into the deep water without the benefit of thorough training that should be requisite with the responsibilities. This is not a turf battle where we have stolen someone’s cheese. This is pure and simple where need is trumping training, and if not done properly, the patient may suffer, and hospitalists will bear the uncomfortable feeling of being asked to do more than we should.

SHM and our national hospitalist thought leaders see this dilemma. We are working diligently with other professional medical societies and key specialty educators and thought leaders to create training pathways to support the expansion of the hospitalist’s scope. This is building the boat while you are going down a rapidly moving river. It is not easy stuff. But our patients and our hospitalists demand this, and SHM will step up. Help is on the way.

Larry Wellikson, MD, MHM, is CEO of the Society of Hospital Medicine.

When tobacco and cancer are mentioned, many people automatically assume lung cancer. But the 70-plus carcinogens identified in tobacco smoke cause at least 12 types of cancer, according to a Vital Signs report, including cancers of the stomach, kidney and renal pelvis, urinary bladder, and cervix. “Smokeless” products such as chewing tobacco carry 28 identified carcinogens.

Related: Quitting Smoking During Substance Abuse Treatment

Researchers from the CDC and National Cancer Institute analyzed data from the U.S. Cancer Statistics 2004-2013 to assess incidence and death rates for cancers caused by tobacco use. During that time, the incidence of tobacco-related cancer went down 1.3% per year, and mortality dropped 1.6% each year. Tobacco-related cancer incidence declined significantly in 44 states. Rates were lowest in the West and dropped the slowest in the Midwest.

However, the burden remains high, the researchers note, and  disparities persist among certain groups. For instance, the incidence of tobacco-related cancer rose with age: Two-fifths of deaths were among people aged ≥ 75 years. And the incidence of cancer and death rates were highest but decreased fastest among blacks.

Related: Impact of a Drop-in Group Medical Appointment on Tobacco Quit Rates

There’s no question that lung cancer remains the cancer most linked to smoking. Lung cancer accounted for about one-third of tobacco-related cancer cases and almost one-half of tobacco-related cancer deaths. Between 2009 and 2013, about 101,300 men and 65,700 women died each year of cancers attributable to cigarette smoking—most died of lung cancer. Exposure to secondhand smoke accounted for another 7,300 deaths by lung cancer among nonsmokers.

Roughly 6 million people may die prematurely of a tobacco-related cancer unless they can take advantage of more sustained, comprehensive, and evidence-based interventions, the researchers say. States that have invested in smoking prevention and control programs, they point out, have seen larger declines in youth and adult smoking, decreases in lung cancer, and reduced tobacco-related health care costs.

Related: CDC Media Campaign Helps Americans Quit Smoking

The researchers also emphasize the benefits of smoking-cessation counseling and treatment as well as screening for cervical, colorectal, and lung cancers, to help detect them at earlier more easily treatable stages. Vaccination against hepatitis B virus and human papillomavirus can prevent liver and cervix cancer,  to which tobacco can contribute.

According to Vital Signs, the CDC funds 65 comprehensive cancer control programs to prevent cancer, increase access to early detection and care for tobacco-related cancers, help cancer survivors quit using tobacco, and improve cancer outcomes, especially in communities with higher tobacco-related rates of cancer and deaths. The CDC also urges health care providers to encourage patients to quit—or not start—smoking, to be aware of screenings, and to remember that there’s no “risk-free” level of secondhand smoke.

Source:
Henley SJ, Thomas CC, Sharapova SR, et al. MMWR. 2016;65(44):1212-1218.

When tobacco and cancer are mentioned, many people automatically assume lung cancer. But the 70-plus carcinogens identified in tobacco smoke cause at least 12 types of cancer, according to a Vital Signs report, including cancers of the stomach, kidney and renal pelvis, urinary bladder, and cervix. “Smokeless” products such as chewing tobacco carry 28 identified carcinogens.

Related: Quitting Smoking During Substance Abuse Treatment

Researchers from the CDC and National Cancer Institute analyzed data from the U.S. Cancer Statistics 2004-2013 to assess incidence and death rates for cancers caused by tobacco use. During that time, the incidence of tobacco-related cancer went down 1.3% per year, and mortality dropped 1.6% each year. Tobacco-related cancer incidence declined significantly in 44 states. Rates were lowest in the West and dropped the slowest in the Midwest.

However, the burden remains high, the researchers note, and  disparities persist among certain groups. For instance, the incidence of tobacco-related cancer rose with age: Two-fifths of deaths were among people aged ≥ 75 years. And the incidence of cancer and death rates were highest but decreased fastest among blacks.

Related: Impact of a Drop-in Group Medical Appointment on Tobacco Quit Rates

There’s no question that lung cancer remains the cancer most linked to smoking. Lung cancer accounted for about one-third of tobacco-related cancer cases and almost one-half of tobacco-related cancer deaths. Between 2009 and 2013, about 101,300 men and 65,700 women died each year of cancers attributable to cigarette smoking—most died of lung cancer. Exposure to secondhand smoke accounted for another 7,300 deaths by lung cancer among nonsmokers.

Roughly 6 million people may die prematurely of a tobacco-related cancer unless they can take advantage of more sustained, comprehensive, and evidence-based interventions, the researchers say. States that have invested in smoking prevention and control programs, they point out, have seen larger declines in youth and adult smoking, decreases in lung cancer, and reduced tobacco-related health care costs.

Related: CDC Media Campaign Helps Americans Quit Smoking

The researchers also emphasize the benefits of smoking-cessation counseling and treatment as well as screening for cervical, colorectal, and lung cancers, to help detect them at earlier more easily treatable stages. Vaccination against hepatitis B virus and human papillomavirus can prevent liver and cervix cancer,  to which tobacco can contribute.

According to Vital Signs, the CDC funds 65 comprehensive cancer control programs to prevent cancer, increase access to early detection and care for tobacco-related cancers, help cancer survivors quit using tobacco, and improve cancer outcomes, especially in communities with higher tobacco-related rates of cancer and deaths. The CDC also urges health care providers to encourage patients to quit—or not start—smoking, to be aware of screenings, and to remember that there’s no “risk-free” level of secondhand smoke.

Source:
Henley SJ, Thomas CC, Sharapova SR, et al. MMWR. 2016;65(44):1212-1218.

When tobacco and cancer are mentioned, many people automatically assume lung cancer. But the 70-plus carcinogens identified in tobacco smoke cause at least 12 types of cancer, according to a Vital Signs report, including cancers of the stomach, kidney and renal pelvis, urinary bladder, and cervix. “Smokeless” products such as chewing tobacco carry 28 identified carcinogens.

Related: Quitting Smoking During Substance Abuse Treatment

Researchers from the CDC and National Cancer Institute analyzed data from the U.S. Cancer Statistics 2004-2013 to assess incidence and death rates for cancers caused by tobacco use. During that time, the incidence of tobacco-related cancer went down 1.3% per year, and mortality dropped 1.6% each year. Tobacco-related cancer incidence declined significantly in 44 states. Rates were lowest in the West and dropped the slowest in the Midwest.

However, the burden remains high, the researchers note, and  disparities persist among certain groups. For instance, the incidence of tobacco-related cancer rose with age: Two-fifths of deaths were among people aged ≥ 75 years. And the incidence of cancer and death rates were highest but decreased fastest among blacks.

Related: Impact of a Drop-in Group Medical Appointment on Tobacco Quit Rates

There’s no question that lung cancer remains the cancer most linked to smoking. Lung cancer accounted for about one-third of tobacco-related cancer cases and almost one-half of tobacco-related cancer deaths. Between 2009 and 2013, about 101,300 men and 65,700 women died each year of cancers attributable to cigarette smoking—most died of lung cancer. Exposure to secondhand smoke accounted for another 7,300 deaths by lung cancer among nonsmokers.

Roughly 6 million people may die prematurely of a tobacco-related cancer unless they can take advantage of more sustained, comprehensive, and evidence-based interventions, the researchers say. States that have invested in smoking prevention and control programs, they point out, have seen larger declines in youth and adult smoking, decreases in lung cancer, and reduced tobacco-related health care costs.

Related: CDC Media Campaign Helps Americans Quit Smoking

The researchers also emphasize the benefits of smoking-cessation counseling and treatment as well as screening for cervical, colorectal, and lung cancers, to help detect them at earlier more easily treatable stages. Vaccination against hepatitis B virus and human papillomavirus can prevent liver and cervix cancer,  to which tobacco can contribute.

According to Vital Signs, the CDC funds 65 comprehensive cancer control programs to prevent cancer, increase access to early detection and care for tobacco-related cancers, help cancer survivors quit using tobacco, and improve cancer outcomes, especially in communities with higher tobacco-related rates of cancer and deaths. The CDC also urges health care providers to encourage patients to quit—or not start—smoking, to be aware of screenings, and to remember that there’s no “risk-free” level of secondhand smoke.

Source:
Henley SJ, Thomas CC, Sharapova SR, et al. MMWR. 2016;65(44):1212-1218.

Fatal opioid overdoses have quadrupled in the U.S. from 1999 to 2013.¹ In 2013, 43,982 deaths in the U.S. were attributable to drug overdoses, and 37% of them involved opioids.¹ Data from 2005 suggested that veterans are at an increased risk with a 2-fold rise in overdose observed.² In 2013, there were 17,124 encounters at VA facilities for the treatment of opioid overdose.³ In response to this opioid epidemic, individual VA facilities began implementing Overdose Education and Naloxone Distribution (OEND) programs in 2013.⁴ In May 2014, the Under Secretary for Health mandated the implementation of OEND programs across all VA facilities, and the VA became the only health care system in the U.S. with a national OEND program.⁴

Naloxone

Naloxone is a pure opioid antagonist that competes with and displaces opioids at opioid receptors. In an overdose, opioids occupying opioid receptor sites can lead to respiratory depression, which can lead to death. Patients can experience rapid reversal of respiratory depression and opioid overdose with the first dose of naloxone 0.4 mg. Naloxone has a short half-life relative to opioids, whereas opioids can bind to opioid receptors once again after naloxone is eliminated, risking the reemergence of overdose symptoms. For this reason, a second dose of naloxone is often given. When administered appropriately with close monitoring, naloxone can provide a safe and effective way to reverse a potentially life-threatening opioid overdose.

Availability

In April 2014, Evzio, an intramuscular/subcutaneous formulation of naloxone, was FDA approved as an emergency treatment for known or suspected opioid overdose. Shortly after, in November 2015, Narcan, a nasal spray formulation of naloxone, also was approved. Each formulation has been instrumental in fulfilling an unmet medical need in the U.S. Both Evzio and Narcan have been used in opioid-overdose prevention programs to train health care professionals and lay persons to respond in the event of suspected overdose and administer naloxone.

Maxwell and colleagues implemented a naloxone distribution program in Chicago, Illinois, in January 2001 after a 4-fold increase in heroin-related overdose deaths was observed.⁵ Within a year, Chicago experienced a 20% decrease in heroin-related overdose deaths, and this trend continued with additional 10% reductions in heroin-related overdoses in 2002 and 2003. Similarly, Piper and colleagues implemented a naloxone distribution program and found that 82% of injection drug users felt “comfortable” to “very comfortable” administering naloxone in the event of an overdose, and 86% of subjects reported they would want naloxone in the event of an overdose.⁶

Naloxone is available for over-the-counter purchase in Rhode Island, which is a bordering state to VA Connecticut Healthcare System (VACT). In 2015 new legislation permitted the training and certification of Connecticut community pharmacists to prescribe naloxone. Furthermore, in May 2016, Connecticut passed legislation to permit qualified individuals to carry naloxone and administer it to another person that he or she, believes is experiencing an opioid-related drug overdose. Given the increase in naloxone availability both nationally and locally, VACT sought to implement a naloxone distribution program to offer the same access to veterans. The primary objective of this article is to describe the development, implementation, and preliminary results of this OEND program.

Development

In accordance with VA guidance, the VACT OEND program development and implementation process included 4 steps that required program coordinators to identify target populations, garner support, train staff members, and implement the OEND program.

A multidisciplinary team of representatives from pharmacy, mental health (MH), and substance abuse (SA) departments was established to draft hospital policy. The hospital policy detailed job functions related to the OEND program for prescribing, educating, verifying, and dispensing naloxone. This policy also served as a document to identify the target population.

With resources from the National VA Pharmacy Benefits Manager, the target population for VACT listed veterans with an opioid use disorder, prescription opioid use disorder, and injection opioid use disorder. Also listed were veterans at risk of an opioid overdose, such as those encountered in medication-assisted treatment programs for opioid use disorder, recent inpatient withdrawal management for opioid use disorder, HIV education/prevention programs, syringe access programs, outpatient and residential opioid use disorder treatment programs, community meetings/support group programs for opioid use disorder, emergency departments for opioid overdose or intoxication, domiciliary care or community-based treatment for homeless veterans, and primary health care for follow-up of recent opioid overdose or intoxication. The aim of the broad description of veterans was to ensure that naloxone access remained inclusive.

The program overview and hospital policy were presented to the VACT medication management committee (MMC), which approved a small pilot project for veterans engaged in SA treatment from January 2015 to April 2015. Barriers to implementation were encountered at this time, which included a belief that only MH or SA providers should prescribe naloxone rescue kits. Reasons for this were largely related to the belief that MH and SA providers are more familiar with substance use disorders. These barriers were addressed by increasing education to providers by detailing previous success stories regarding naloxone programs to highlight that the benefits outweighed any associated risks.

Implementation

Naloxone kits were assembled in preparation for program implementation. Each kit contained 2 vials of naloxone (each vial contains 1 dose), 2 needleless luer-lock syringes, and 1 atomizer with visual instructions for product assembly. Next, a template was created for entry into the veteran’s electronic health record (EHR) each time a naloxone kit was dispensed. The template tracked diagnosis, history of naloxone kit use, and aspects of the OEND program that were discussed with the veteran. Embedded within the template is a hyperlink to the Substance Abuse and Mental Health Services Administration Opioid Overdose Prevention Toolkit booklet, which serves as an education guide and take-home material for the veteran.

Once the naloxone kits were assembled and the template created, SA providers were able to engage in OEND program training. Training required providers to attend a 60-minute, 75-slide PowerPoint seminar, highlighting risk factors and prevention strategies for opioid overdose, proper identification and management of an opioid overdose, appropriate administration of naloxone, and monitoring parameters after administration. Providers were not screened for baseline knowledge, nor was a posttraining proficiency evaluation performed. However, providers were allowed to ask questions and request further clarification about any unclear aspects of training.

Each month, data were collected on the number of providers trained and naloxone kits dispensed. Implementation began in January 2015, and veterans were either educated during individual or group sessions led by a trained OEND provider. An institutional review board-approved quality improvement (QI) process ran concurrently that sought to improve the OEND program. Phase 1 of this QI project anonymously surveyed OEND providers to evaluate knowledge, comfort, attitude, and fear of consequences regarding naloxone distribution in an attempt to understand barriers to program implementation or success.⁷ In phase 2, veterans who received a naloxone kit will be interviewed regarding knowledge retention of OEND program education and subsequent opioid abuse and naloxone use after receiving a naloxone kit.

Results

From January 2015 through preliminary data analysis in April 2015, the facility trained 19 providers and dispensed naloxone kits to 49 veterans. In the first 4 months of program implementation, there were no reports of attempted opioid overdose reversals with naloxone in the 49 veterans who had received a naloxone kit. Of note, past studies have demonstrated that 1 death is prevented for every 227 naloxone kits distributed.⁸ Therefore, it is possible that the analysis was too early to detect an impact.

As of October 2016, VACT has dispensed 538 naloxone kits to 441 veterans, as some patients have received naloxone kit refills for various reasons (ie, lost, used, confiscated, stolen, etc). The OEND program implementation team has been made aware that at least 5 of the 441 veterans have used naloxone kits, though it is unclear whether naloxone kits were used on the veteran themselves or someone else. This is likely an underestimate of naloxone kit use, as veterans could be sent to alternative hospitals in the event of an opioid overdose, or veterans may not disclose actual use of naloxone kit to VACT providers. Phase 2 of the QI project is designed to extract an estimation of actual naloxone kit use in the VACT veteran population.

Discussion

Naloxone, a pure opioid antagonist, is readily available in many communities. In order to extend the same continuity of care to veterans, VACT implemented the OEND program to increase access to naloxone kits. This program serves as an opportunity to educate veterans regarding safe practices with opioids and provides a life-saving measure in the event of an overdose.

The 4-step approach to implementation was a feasible method of quickly implementing an OEND program. Despite ongoing prescriber interest in participating in the OEND program, barriers to implementation were encountered. The largest barrier was provider concerns related to an increase in opioid use given the availability of a reversal agent. However, the medical literature suggests that opioid use tends to decrease when naloxone programs are implemented. Additionally, OEND implementation barriers were internally analyzed in an effort to foster a successful OEND program with continuous evaluation and improvement.⁷

Clark and colleagues examined 19 published studies regarding community-based naloxone programs in order to assess whether naloxone distribution reduced fatal and nonfatal overdose rates.⁹ Naloxone was used successfully across 1,949 patients, and 8 studies reported survival rates of 83% to 96% after naloxone, while 11 studies reported 100% survival rate. The authors of a study of the Chicago Recovery Alliance program found an overall decrease in heroin overdose, and the initial downward trend was seen during the year of naloxone implementation.⁹

In addition, the cost of program implementation was minimal at the local level. Given that implementation of OENDs is a national VA mandate, all naloxone kits are provided to individual VA facilities at no cost from the Consolidated Mail Outpatient Pharmacy, which is the only foreseeable tangible cost. Therefore, intangible costs may include time spent implementing the OEND program, time spent maintaining naloxone inventory, time spent discussing and educating patients on naloxone, and time spent dispensing naloxone kits to patients. However, the intangible costs of the program are predicted to be reduced or offset by the cost-savings measure of reduced emergency department visits and hospitalizations for opioid overdose.

By implementing the OEND program at VACT, veterans are able to engage in primary prophylaxis via education regarding safe practices of opioids. These veterans are also able to obtain tertiary prophylaxis by receiving a naloxone kit and associated training. It is predicted that deaths due to opioid overdose will decrease in this veteran population with the expansion of the OEND program.

Scientific Significance

The OEND programs increase naloxone access and can potentially decrease the incidence of opioid misuse and fatal opioid overdose.

Conclusion

An OEND program can be easily implemented to dispense naloxone kits and deliver education regarding safe opioid use.

Fatal opioid overdoses have quadrupled in the U.S. from 1999 to 2013.¹ In 2013, 43,982 deaths in the U.S. were attributable to drug overdoses, and 37% of them involved opioids.¹ Data from 2005 suggested that veterans are at an increased risk with a 2-fold rise in overdose observed.² In 2013, there were 17,124 encounters at VA facilities for the treatment of opioid overdose.³ In response to this opioid epidemic, individual VA facilities began implementing Overdose Education and Naloxone Distribution (OEND) programs in 2013.⁴ In May 2014, the Under Secretary for Health mandated the implementation of OEND programs across all VA facilities, and the VA became the only health care system in the U.S. with a national OEND program.⁴

Naloxone

Naloxone is a pure opioid antagonist that competes with and displaces opioids at opioid receptors. In an overdose, opioids occupying opioid receptor sites can lead to respiratory depression, which can lead to death. Patients can experience rapid reversal of respiratory depression and opioid overdose with the first dose of naloxone 0.4 mg. Naloxone has a short half-life relative to opioids, whereas opioids can bind to opioid receptors once again after naloxone is eliminated, risking the reemergence of overdose symptoms. For this reason, a second dose of naloxone is often given. When administered appropriately with close monitoring, naloxone can provide a safe and effective way to reverse a potentially life-threatening opioid overdose.

Availability

In April 2014, Evzio, an intramuscular/subcutaneous formulation of naloxone, was FDA approved as an emergency treatment for known or suspected opioid overdose. Shortly after, in November 2015, Narcan, a nasal spray formulation of naloxone, also was approved. Each formulation has been instrumental in fulfilling an unmet medical need in the U.S. Both Evzio and Narcan have been used in opioid-overdose prevention programs to train health care professionals and lay persons to respond in the event of suspected overdose and administer naloxone.

Maxwell and colleagues implemented a naloxone distribution program in Chicago, Illinois, in January 2001 after a 4-fold increase in heroin-related overdose deaths was observed.⁵ Within a year, Chicago experienced a 20% decrease in heroin-related overdose deaths, and this trend continued with additional 10% reductions in heroin-related overdoses in 2002 and 2003. Similarly, Piper and colleagues implemented a naloxone distribution program and found that 82% of injection drug users felt “comfortable” to “very comfortable” administering naloxone in the event of an overdose, and 86% of subjects reported they would want naloxone in the event of an overdose.⁶

Naloxone is available for over-the-counter purchase in Rhode Island, which is a bordering state to VA Connecticut Healthcare System (VACT). In 2015 new legislation permitted the training and certification of Connecticut community pharmacists to prescribe naloxone. Furthermore, in May 2016, Connecticut passed legislation to permit qualified individuals to carry naloxone and administer it to another person that he or she, believes is experiencing an opioid-related drug overdose. Given the increase in naloxone availability both nationally and locally, VACT sought to implement a naloxone distribution program to offer the same access to veterans. The primary objective of this article is to describe the development, implementation, and preliminary results of this OEND program.

Development

In accordance with VA guidance, the VACT OEND program development and implementation process included 4 steps that required program coordinators to identify target populations, garner support, train staff members, and implement the OEND program.

A multidisciplinary team of representatives from pharmacy, mental health (MH), and substance abuse (SA) departments was established to draft hospital policy. The hospital policy detailed job functions related to the OEND program for prescribing, educating, verifying, and dispensing naloxone. This policy also served as a document to identify the target population.

With resources from the National VA Pharmacy Benefits Manager, the target population for VACT listed veterans with an opioid use disorder, prescription opioid use disorder, and injection opioid use disorder. Also listed were veterans at risk of an opioid overdose, such as those encountered in medication-assisted treatment programs for opioid use disorder, recent inpatient withdrawal management for opioid use disorder, HIV education/prevention programs, syringe access programs, outpatient and residential opioid use disorder treatment programs, community meetings/support group programs for opioid use disorder, emergency departments for opioid overdose or intoxication, domiciliary care or community-based treatment for homeless veterans, and primary health care for follow-up of recent opioid overdose or intoxication. The aim of the broad description of veterans was to ensure that naloxone access remained inclusive.

The program overview and hospital policy were presented to the VACT medication management committee (MMC), which approved a small pilot project for veterans engaged in SA treatment from January 2015 to April 2015. Barriers to implementation were encountered at this time, which included a belief that only MH or SA providers should prescribe naloxone rescue kits. Reasons for this were largely related to the belief that MH and SA providers are more familiar with substance use disorders. These barriers were addressed by increasing education to providers by detailing previous success stories regarding naloxone programs to highlight that the benefits outweighed any associated risks.

Implementation

Naloxone kits were assembled in preparation for program implementation. Each kit contained 2 vials of naloxone (each vial contains 1 dose), 2 needleless luer-lock syringes, and 1 atomizer with visual instructions for product assembly. Next, a template was created for entry into the veteran’s electronic health record (EHR) each time a naloxone kit was dispensed. The template tracked diagnosis, history of naloxone kit use, and aspects of the OEND program that were discussed with the veteran. Embedded within the template is a hyperlink to the Substance Abuse and Mental Health Services Administration Opioid Overdose Prevention Toolkit booklet, which serves as an education guide and take-home material for the veteran.

Once the naloxone kits were assembled and the template created, SA providers were able to engage in OEND program training. Training required providers to attend a 60-minute, 75-slide PowerPoint seminar, highlighting risk factors and prevention strategies for opioid overdose, proper identification and management of an opioid overdose, appropriate administration of naloxone, and monitoring parameters after administration. Providers were not screened for baseline knowledge, nor was a posttraining proficiency evaluation performed. However, providers were allowed to ask questions and request further clarification about any unclear aspects of training.

Each month, data were collected on the number of providers trained and naloxone kits dispensed. Implementation began in January 2015, and veterans were either educated during individual or group sessions led by a trained OEND provider. An institutional review board-approved quality improvement (QI) process ran concurrently that sought to improve the OEND program. Phase 1 of this QI project anonymously surveyed OEND providers to evaluate knowledge, comfort, attitude, and fear of consequences regarding naloxone distribution in an attempt to understand barriers to program implementation or success.⁷ In phase 2, veterans who received a naloxone kit will be interviewed regarding knowledge retention of OEND program education and subsequent opioid abuse and naloxone use after receiving a naloxone kit.

Results

From January 2015 through preliminary data analysis in April 2015, the facility trained 19 providers and dispensed naloxone kits to 49 veterans. In the first 4 months of program implementation, there were no reports of attempted opioid overdose reversals with naloxone in the 49 veterans who had received a naloxone kit. Of note, past studies have demonstrated that 1 death is prevented for every 227 naloxone kits distributed.⁸ Therefore, it is possible that the analysis was too early to detect an impact.

As of October 2016, VACT has dispensed 538 naloxone kits to 441 veterans, as some patients have received naloxone kit refills for various reasons (ie, lost, used, confiscated, stolen, etc). The OEND program implementation team has been made aware that at least 5 of the 441 veterans have used naloxone kits, though it is unclear whether naloxone kits were used on the veteran themselves or someone else. This is likely an underestimate of naloxone kit use, as veterans could be sent to alternative hospitals in the event of an opioid overdose, or veterans may not disclose actual use of naloxone kit to VACT providers. Phase 2 of the QI project is designed to extract an estimation of actual naloxone kit use in the VACT veteran population.

Discussion

Naloxone, a pure opioid antagonist, is readily available in many communities. In order to extend the same continuity of care to veterans, VACT implemented the OEND program to increase access to naloxone kits. This program serves as an opportunity to educate veterans regarding safe practices with opioids and provides a life-saving measure in the event of an overdose.

The 4-step approach to implementation was a feasible method of quickly implementing an OEND program. Despite ongoing prescriber interest in participating in the OEND program, barriers to implementation were encountered. The largest barrier was provider concerns related to an increase in opioid use given the availability of a reversal agent. However, the medical literature suggests that opioid use tends to decrease when naloxone programs are implemented. Additionally, OEND implementation barriers were internally analyzed in an effort to foster a successful OEND program with continuous evaluation and improvement.⁷

Clark and colleagues examined 19 published studies regarding community-based naloxone programs in order to assess whether naloxone distribution reduced fatal and nonfatal overdose rates.⁹ Naloxone was used successfully across 1,949 patients, and 8 studies reported survival rates of 83% to 96% after naloxone, while 11 studies reported 100% survival rate. The authors of a study of the Chicago Recovery Alliance program found an overall decrease in heroin overdose, and the initial downward trend was seen during the year of naloxone implementation.⁹

In addition, the cost of program implementation was minimal at the local level. Given that implementation of OENDs is a national VA mandate, all naloxone kits are provided to individual VA facilities at no cost from the Consolidated Mail Outpatient Pharmacy, which is the only foreseeable tangible cost. Therefore, intangible costs may include time spent implementing the OEND program, time spent maintaining naloxone inventory, time spent discussing and educating patients on naloxone, and time spent dispensing naloxone kits to patients. However, the intangible costs of the program are predicted to be reduced or offset by the cost-savings measure of reduced emergency department visits and hospitalizations for opioid overdose.

By implementing the OEND program at VACT, veterans are able to engage in primary prophylaxis via education regarding safe practices of opioids. These veterans are also able to obtain tertiary prophylaxis by receiving a naloxone kit and associated training. It is predicted that deaths due to opioid overdose will decrease in this veteran population with the expansion of the OEND program.

Scientific Significance

The OEND programs increase naloxone access and can potentially decrease the incidence of opioid misuse and fatal opioid overdose.

Conclusion

An OEND program can be easily implemented to dispense naloxone kits and deliver education regarding safe opioid use.

Fatal opioid overdoses have quadrupled in the U.S. from 1999 to 2013.¹ In 2013, 43,982 deaths in the U.S. were attributable to drug overdoses, and 37% of them involved opioids.¹ Data from 2005 suggested that veterans are at an increased risk with a 2-fold rise in overdose observed.² In 2013, there were 17,124 encounters at VA facilities for the treatment of opioid overdose.³ In response to this opioid epidemic, individual VA facilities began implementing Overdose Education and Naloxone Distribution (OEND) programs in 2013.⁴ In May 2014, the Under Secretary for Health mandated the implementation of OEND programs across all VA facilities, and the VA became the only health care system in the U.S. with a national OEND program.⁴

Naloxone

Naloxone is a pure opioid antagonist that competes with and displaces opioids at opioid receptors. In an overdose, opioids occupying opioid receptor sites can lead to respiratory depression, which can lead to death. Patients can experience rapid reversal of respiratory depression and opioid overdose with the first dose of naloxone 0.4 mg. Naloxone has a short half-life relative to opioids, whereas opioids can bind to opioid receptors once again after naloxone is eliminated, risking the reemergence of overdose symptoms. For this reason, a second dose of naloxone is often given. When administered appropriately with close monitoring, naloxone can provide a safe and effective way to reverse a potentially life-threatening opioid overdose.

Availability

In April 2014, Evzio, an intramuscular/subcutaneous formulation of naloxone, was FDA approved as an emergency treatment for known or suspected opioid overdose. Shortly after, in November 2015, Narcan, a nasal spray formulation of naloxone, also was approved. Each formulation has been instrumental in fulfilling an unmet medical need in the U.S. Both Evzio and Narcan have been used in opioid-overdose prevention programs to train health care professionals and lay persons to respond in the event of suspected overdose and administer naloxone.

Maxwell and colleagues implemented a naloxone distribution program in Chicago, Illinois, in January 2001 after a 4-fold increase in heroin-related overdose deaths was observed.⁵ Within a year, Chicago experienced a 20% decrease in heroin-related overdose deaths, and this trend continued with additional 10% reductions in heroin-related overdoses in 2002 and 2003. Similarly, Piper and colleagues implemented a naloxone distribution program and found that 82% of injection drug users felt “comfortable” to “very comfortable” administering naloxone in the event of an overdose, and 86% of subjects reported they would want naloxone in the event of an overdose.⁶

Naloxone is available for over-the-counter purchase in Rhode Island, which is a bordering state to VA Connecticut Healthcare System (VACT). In 2015 new legislation permitted the training and certification of Connecticut community pharmacists to prescribe naloxone. Furthermore, in May 2016, Connecticut passed legislation to permit qualified individuals to carry naloxone and administer it to another person that he or she, believes is experiencing an opioid-related drug overdose. Given the increase in naloxone availability both nationally and locally, VACT sought to implement a naloxone distribution program to offer the same access to veterans. The primary objective of this article is to describe the development, implementation, and preliminary results of this OEND program.

Development

In accordance with VA guidance, the VACT OEND program development and implementation process included 4 steps that required program coordinators to identify target populations, garner support, train staff members, and implement the OEND program.

A multidisciplinary team of representatives from pharmacy, mental health (MH), and substance abuse (SA) departments was established to draft hospital policy. The hospital policy detailed job functions related to the OEND program for prescribing, educating, verifying, and dispensing naloxone. This policy also served as a document to identify the target population.

With resources from the National VA Pharmacy Benefits Manager, the target population for VACT listed veterans with an opioid use disorder, prescription opioid use disorder, and injection opioid use disorder. Also listed were veterans at risk of an opioid overdose, such as those encountered in medication-assisted treatment programs for opioid use disorder, recent inpatient withdrawal management for opioid use disorder, HIV education/prevention programs, syringe access programs, outpatient and residential opioid use disorder treatment programs, community meetings/support group programs for opioid use disorder, emergency departments for opioid overdose or intoxication, domiciliary care or community-based treatment for homeless veterans, and primary health care for follow-up of recent opioid overdose or intoxication. The aim of the broad description of veterans was to ensure that naloxone access remained inclusive.

The program overview and hospital policy were presented to the VACT medication management committee (MMC), which approved a small pilot project for veterans engaged in SA treatment from January 2015 to April 2015. Barriers to implementation were encountered at this time, which included a belief that only MH or SA providers should prescribe naloxone rescue kits. Reasons for this were largely related to the belief that MH and SA providers are more familiar with substance use disorders. These barriers were addressed by increasing education to providers by detailing previous success stories regarding naloxone programs to highlight that the benefits outweighed any associated risks.

Implementation

Naloxone kits were assembled in preparation for program implementation. Each kit contained 2 vials of naloxone (each vial contains 1 dose), 2 needleless luer-lock syringes, and 1 atomizer with visual instructions for product assembly. Next, a template was created for entry into the veteran’s electronic health record (EHR) each time a naloxone kit was dispensed. The template tracked diagnosis, history of naloxone kit use, and aspects of the OEND program that were discussed with the veteran. Embedded within the template is a hyperlink to the Substance Abuse and Mental Health Services Administration Opioid Overdose Prevention Toolkit booklet, which serves as an education guide and take-home material for the veteran.

Once the naloxone kits were assembled and the template created, SA providers were able to engage in OEND program training. Training required providers to attend a 60-minute, 75-slide PowerPoint seminar, highlighting risk factors and prevention strategies for opioid overdose, proper identification and management of an opioid overdose, appropriate administration of naloxone, and monitoring parameters after administration. Providers were not screened for baseline knowledge, nor was a posttraining proficiency evaluation performed. However, providers were allowed to ask questions and request further clarification about any unclear aspects of training.

Each month, data were collected on the number of providers trained and naloxone kits dispensed. Implementation began in January 2015, and veterans were either educated during individual or group sessions led by a trained OEND provider. An institutional review board-approved quality improvement (QI) process ran concurrently that sought to improve the OEND program. Phase 1 of this QI project anonymously surveyed OEND providers to evaluate knowledge, comfort, attitude, and fear of consequences regarding naloxone distribution in an attempt to understand barriers to program implementation or success.⁷ In phase 2, veterans who received a naloxone kit will be interviewed regarding knowledge retention of OEND program education and subsequent opioid abuse and naloxone use after receiving a naloxone kit.

Results

From January 2015 through preliminary data analysis in April 2015, the facility trained 19 providers and dispensed naloxone kits to 49 veterans. In the first 4 months of program implementation, there were no reports of attempted opioid overdose reversals with naloxone in the 49 veterans who had received a naloxone kit. Of note, past studies have demonstrated that 1 death is prevented for every 227 naloxone kits distributed.⁸ Therefore, it is possible that the analysis was too early to detect an impact.

As of October 2016, VACT has dispensed 538 naloxone kits to 441 veterans, as some patients have received naloxone kit refills for various reasons (ie, lost, used, confiscated, stolen, etc). The OEND program implementation team has been made aware that at least 5 of the 441 veterans have used naloxone kits, though it is unclear whether naloxone kits were used on the veteran themselves or someone else. This is likely an underestimate of naloxone kit use, as veterans could be sent to alternative hospitals in the event of an opioid overdose, or veterans may not disclose actual use of naloxone kit to VACT providers. Phase 2 of the QI project is designed to extract an estimation of actual naloxone kit use in the VACT veteran population.

Discussion

Naloxone, a pure opioid antagonist, is readily available in many communities. In order to extend the same continuity of care to veterans, VACT implemented the OEND program to increase access to naloxone kits. This program serves as an opportunity to educate veterans regarding safe practices with opioids and provides a life-saving measure in the event of an overdose.

The 4-step approach to implementation was a feasible method of quickly implementing an OEND program. Despite ongoing prescriber interest in participating in the OEND program, barriers to implementation were encountered. The largest barrier was provider concerns related to an increase in opioid use given the availability of a reversal agent. However, the medical literature suggests that opioid use tends to decrease when naloxone programs are implemented. Additionally, OEND implementation barriers were internally analyzed in an effort to foster a successful OEND program with continuous evaluation and improvement.⁷

Clark and colleagues examined 19 published studies regarding community-based naloxone programs in order to assess whether naloxone distribution reduced fatal and nonfatal overdose rates.⁹ Naloxone was used successfully across 1,949 patients, and 8 studies reported survival rates of 83% to 96% after naloxone, while 11 studies reported 100% survival rate. The authors of a study of the Chicago Recovery Alliance program found an overall decrease in heroin overdose, and the initial downward trend was seen during the year of naloxone implementation.⁹

In addition, the cost of program implementation was minimal at the local level. Given that implementation of OENDs is a national VA mandate, all naloxone kits are provided to individual VA facilities at no cost from the Consolidated Mail Outpatient Pharmacy, which is the only foreseeable tangible cost. Therefore, intangible costs may include time spent implementing the OEND program, time spent maintaining naloxone inventory, time spent discussing and educating patients on naloxone, and time spent dispensing naloxone kits to patients. However, the intangible costs of the program are predicted to be reduced or offset by the cost-savings measure of reduced emergency department visits and hospitalizations for opioid overdose.

By implementing the OEND program at VACT, veterans are able to engage in primary prophylaxis via education regarding safe practices of opioids. These veterans are also able to obtain tertiary prophylaxis by receiving a naloxone kit and associated training. It is predicted that deaths due to opioid overdose will decrease in this veteran population with the expansion of the OEND program.

Scientific Significance

The OEND programs increase naloxone access and can potentially decrease the incidence of opioid misuse and fatal opioid overdose.

Conclusion

An OEND program can be easily implemented to dispense naloxone kits and deliver education regarding safe opioid use.

Tony Antoniou, PhD

Photo courtesy of

St. Michael’s Hospital

Two commonly used statins, lovastatin and simvastatin, can increase the risk of major hemorrhage in patients receiving the anticoagulant dabigatran etexilate, according to research published in the Canadian Medical Association Journal.

“We found no difference in the risk of stroke in patients receiving dabigatran who were prescribed lovastatin or simvastatin versus other statins,” said study author Tony Antoniou, PhD, of St. Michael’s Hospital in Toronto, Ontario, Canada.

“However, an increase in the risk of bleeding requiring hospital admission or emergency department visits was seen with lovastatin and simvastatin compared with the other statins.”

Dr Antoniou and his colleagues made these discoveries by conducting 2 population-based, nested case-control studies.

The studies included patients older than 65 years of age who started treatment with dabigatran etexilate between 2012 and 2014. All patients had nonvalvular atrial fibrillation and were receiving dabigatran etexilate for the prevention of stroke and systemic embolism.

In the first study, the cases were patients with ischemic stroke. In the second study, the cases were patients with major hemorrhage. Each case had up to 4 age- and sex-matched controls.

Both cases and controls received a statin. And the researchers set out to determine the association between each outcome and the use of simvastatin or lovastatin compared to other statins.

In the 45,991 patients studied, there were 397 cases of ischemic stroke and 1117 cases of major hemorrhage.

Multivariable analysis suggested that use of simvastatin or lovastatin was not associated with an increased risk of stroke or transient ischemic attack

relative to other statins. The adjusted odds ratio was 1.33.

However, the use of simvastatin and lovastatin was associated with an increased risk of major hemorrhage. The adjusted odds ratio was 1.46.

Dr Antoniou and his colleagues believe simvastatin and lovastatin increase the risk of bleeding by increasing the amount of dabigatran absorbed by the body.

The team noted that dabigatran etexilate is metabolized to dabigatran by carboxylesterase enzymes, intestinal absorption of the prodrug is opposed by P-glycoprotein, and simvastatin and lovastatin are potent inhibitors of P-glycoprotein and carboxylesterase.

The researchers said the fact that the statins inhibit P-glycoprotein appears to explain the increased risk of bleeding they observed. And the fact that simvastatin and lovastatin were not associated with an increased risk of stroke suggests carboxylesterase inhibition is of little clinical relevance in this setting.

On the other hand, the researchers also noted that the number of cases receiving lovastatin and simvastatin was small. This may have influenced the team’s power to detect an association between these drugs and stroke.

Regardless, the researchers said the results of these studies suggest there is a clinically important drug interaction between dabigatran etexilate and both simvastatin and lovastatin. Therefore, other statins should be considered in patients receiving dabigatran etexilate.

Tony Antoniou, PhD

Photo courtesy of

St. Michael’s Hospital

Two commonly used statins, lovastatin and simvastatin, can increase the risk of major hemorrhage in patients receiving the anticoagulant dabigatran etexilate, according to research published in the Canadian Medical Association Journal.

“We found no difference in the risk of stroke in patients receiving dabigatran who were prescribed lovastatin or simvastatin versus other statins,” said study author Tony Antoniou, PhD, of St. Michael’s Hospital in Toronto, Ontario, Canada.

“However, an increase in the risk of bleeding requiring hospital admission or emergency department visits was seen with lovastatin and simvastatin compared with the other statins.”

Dr Antoniou and his colleagues made these discoveries by conducting 2 population-based, nested case-control studies.

The studies included patients older than 65 years of age who started treatment with dabigatran etexilate between 2012 and 2014. All patients had nonvalvular atrial fibrillation and were receiving dabigatran etexilate for the prevention of stroke and systemic embolism.

In the first study, the cases were patients with ischemic stroke. In the second study, the cases were patients with major hemorrhage. Each case had up to 4 age- and sex-matched controls.

Both cases and controls received a statin. And the researchers set out to determine the association between each outcome and the use of simvastatin or lovastatin compared to other statins.

In the 45,991 patients studied, there were 397 cases of ischemic stroke and 1117 cases of major hemorrhage.

Multivariable analysis suggested that use of simvastatin or lovastatin was not associated with an increased risk of stroke or transient ischemic attack

relative to other statins. The adjusted odds ratio was 1.33.

However, the use of simvastatin and lovastatin was associated with an increased risk of major hemorrhage. The adjusted odds ratio was 1.46.

Dr Antoniou and his colleagues believe simvastatin and lovastatin increase the risk of bleeding by increasing the amount of dabigatran absorbed by the body.

The team noted that dabigatran etexilate is metabolized to dabigatran by carboxylesterase enzymes, intestinal absorption of the prodrug is opposed by P-glycoprotein, and simvastatin and lovastatin are potent inhibitors of P-glycoprotein and carboxylesterase.

The researchers said the fact that the statins inhibit P-glycoprotein appears to explain the increased risk of bleeding they observed. And the fact that simvastatin and lovastatin were not associated with an increased risk of stroke suggests carboxylesterase inhibition is of little clinical relevance in this setting.

On the other hand, the researchers also noted that the number of cases receiving lovastatin and simvastatin was small. This may have influenced the team’s power to detect an association between these drugs and stroke.

Regardless, the researchers said the results of these studies suggest there is a clinically important drug interaction between dabigatran etexilate and both simvastatin and lovastatin. Therefore, other statins should be considered in patients receiving dabigatran etexilate.

Tony Antoniou, PhD

Photo courtesy of

St. Michael’s Hospital

Two commonly used statins, lovastatin and simvastatin, can increase the risk of major hemorrhage in patients receiving the anticoagulant dabigatran etexilate, according to research published in the Canadian Medical Association Journal.

“We found no difference in the risk of stroke in patients receiving dabigatran who were prescribed lovastatin or simvastatin versus other statins,” said study author Tony Antoniou, PhD, of St. Michael’s Hospital in Toronto, Ontario, Canada.

“However, an increase in the risk of bleeding requiring hospital admission or emergency department visits was seen with lovastatin and simvastatin compared with the other statins.”

Dr Antoniou and his colleagues made these discoveries by conducting 2 population-based, nested case-control studies.

The studies included patients older than 65 years of age who started treatment with dabigatran etexilate between 2012 and 2014. All patients had nonvalvular atrial fibrillation and were receiving dabigatran etexilate for the prevention of stroke and systemic embolism.

In the first study, the cases were patients with ischemic stroke. In the second study, the cases were patients with major hemorrhage. Each case had up to 4 age- and sex-matched controls.

Both cases and controls received a statin. And the researchers set out to determine the association between each outcome and the use of simvastatin or lovastatin compared to other statins.

In the 45,991 patients studied, there were 397 cases of ischemic stroke and 1117 cases of major hemorrhage.

Multivariable analysis suggested that use of simvastatin or lovastatin was not associated with an increased risk of stroke or transient ischemic attack

relative to other statins. The adjusted odds ratio was 1.33.

However, the use of simvastatin and lovastatin was associated with an increased risk of major hemorrhage. The adjusted odds ratio was 1.46.

Dr Antoniou and his colleagues believe simvastatin and lovastatin increase the risk of bleeding by increasing the amount of dabigatran absorbed by the body.

The team noted that dabigatran etexilate is metabolized to dabigatran by carboxylesterase enzymes, intestinal absorption of the prodrug is opposed by P-glycoprotein, and simvastatin and lovastatin are potent inhibitors of P-glycoprotein and carboxylesterase.

The researchers said the fact that the statins inhibit P-glycoprotein appears to explain the increased risk of bleeding they observed. And the fact that simvastatin and lovastatin were not associated with an increased risk of stroke suggests carboxylesterase inhibition is of little clinical relevance in this setting.

On the other hand, the researchers also noted that the number of cases receiving lovastatin and simvastatin was small. This may have influenced the team’s power to detect an association between these drugs and stroke.

Regardless, the researchers said the results of these studies suggest there is a clinically important drug interaction between dabigatran etexilate and both simvastatin and lovastatin. Therefore, other statins should be considered in patients receiving dabigatran etexilate.

Micrograph showing APL

Image courtesy of the Armed

Forces Institute of Pathology

The European Commission (EC) has extended the approved indication for arsenic trioxide (Trisenox®) in patients with acute promyelocytic leukemia (APL).

The drug is now approved for use in combination with all-trans-retinoic acid (ATRA) to induce remission and for consolidation in adults with newly diagnosed low- to intermediate-risk APL (white blood cell count, ≤ 10 x 10³/μL) characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene.

Arsenic trioxide was previously approved by the EC to induce remission and as consolidation in adults with relapsed/refractory APL, which is characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene, whose previous treatment included a retinoid and chemotherapy.

“This [expanded] approval by the European Commission is good news for APL patients, as we now have access to a cure for an acute leukemia without using chemotherapy,” said Francesco Lo-Coco, MD, of University of Rome Tor Vergata in Italy.

“Moreover, this decision is a very positive endorsement by the European Commission, as it was made based solely on published academic research and studies.”

Arsenic trioxide is marketed by Teva Pharmaceutical Industries Ltd.

Phase 3 study results

The EC’s expanded approval of arsenic trioxide is based on results from the APL0406 Intergroup GIMEMA-AMLSG-SAL study. Previous results from this phase 3 study were published in NEJM in 2013.

Updated results include 276 adults (ages 18 to 71) with newly diagnosed, low- or intermediate-risk APL. Patients were randomized to receive ATRA plus arsenic trioxide or ATRA plus chemotherapy.

A total of 263 patients were evaluable for response to induction. One hundred percent of patients in the arsenic trioxide arm (127/127) achieved a complete response (CR), as did 97% (132/136) of patients in the chemotherapy arm (P=0.12).

After a median follow-up of 40.6 months, the event-free survival was 97.3% in the arsenic trioxide arm and 80% in the chemotherapy arm (P<0.001). The cumulative incidence of relapse was 1.9% and 13.9%, respectively (P=0.0013).

At 50 months, the overall survival was 99.2% in the arsenic trioxide arm and 92.6% in the chemotherapy arm (P=0.0073).

After induction, there were 2 relapses and 1 death in CR in the arsenic trioxide arm.

In the chemotherapy arm, there were 2 instances of molecular resistance after third consolidation, 15 relapses, 5 deaths in CR, and 2 patients who developed a therapy-related myeloid neoplasm.

Micrograph showing APL

Image courtesy of the Armed

Forces Institute of Pathology

The European Commission (EC) has extended the approved indication for arsenic trioxide (Trisenox®) in patients with acute promyelocytic leukemia (APL).

The drug is now approved for use in combination with all-trans-retinoic acid (ATRA) to induce remission and for consolidation in adults with newly diagnosed low- to intermediate-risk APL (white blood cell count, ≤ 10 x 10³/μL) characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene.

Arsenic trioxide was previously approved by the EC to induce remission and as consolidation in adults with relapsed/refractory APL, which is characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene, whose previous treatment included a retinoid and chemotherapy.

“This [expanded] approval by the European Commission is good news for APL patients, as we now have access to a cure for an acute leukemia without using chemotherapy,” said Francesco Lo-Coco, MD, of University of Rome Tor Vergata in Italy.

“Moreover, this decision is a very positive endorsement by the European Commission, as it was made based solely on published academic research and studies.”

Arsenic trioxide is marketed by Teva Pharmaceutical Industries Ltd.

Phase 3 study results

The EC’s expanded approval of arsenic trioxide is based on results from the APL0406 Intergroup GIMEMA-AMLSG-SAL study. Previous results from this phase 3 study were published in NEJM in 2013.

Updated results include 276 adults (ages 18 to 71) with newly diagnosed, low- or intermediate-risk APL. Patients were randomized to receive ATRA plus arsenic trioxide or ATRA plus chemotherapy.

A total of 263 patients were evaluable for response to induction. One hundred percent of patients in the arsenic trioxide arm (127/127) achieved a complete response (CR), as did 97% (132/136) of patients in the chemotherapy arm (P=0.12).

After a median follow-up of 40.6 months, the event-free survival was 97.3% in the arsenic trioxide arm and 80% in the chemotherapy arm (P<0.001). The cumulative incidence of relapse was 1.9% and 13.9%, respectively (P=0.0013).

At 50 months, the overall survival was 99.2% in the arsenic trioxide arm and 92.6% in the chemotherapy arm (P=0.0073).

After induction, there were 2 relapses and 1 death in CR in the arsenic trioxide arm.

In the chemotherapy arm, there were 2 instances of molecular resistance after third consolidation, 15 relapses, 5 deaths in CR, and 2 patients who developed a therapy-related myeloid neoplasm.

Micrograph showing APL

Image courtesy of the Armed

Forces Institute of Pathology

The European Commission (EC) has extended the approved indication for arsenic trioxide (Trisenox®) in patients with acute promyelocytic leukemia (APL).

The drug is now approved for use in combination with all-trans-retinoic acid (ATRA) to induce remission and for consolidation in adults with newly diagnosed low- to intermediate-risk APL (white blood cell count, ≤ 10 x 10³/μL) characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene.

Arsenic trioxide was previously approved by the EC to induce remission and as consolidation in adults with relapsed/refractory APL, which is characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene, whose previous treatment included a retinoid and chemotherapy.

“This [expanded] approval by the European Commission is good news for APL patients, as we now have access to a cure for an acute leukemia without using chemotherapy,” said Francesco Lo-Coco, MD, of University of Rome Tor Vergata in Italy.

“Moreover, this decision is a very positive endorsement by the European Commission, as it was made based solely on published academic research and studies.”

Arsenic trioxide is marketed by Teva Pharmaceutical Industries Ltd.

Phase 3 study results

The EC’s expanded approval of arsenic trioxide is based on results from the APL0406 Intergroup GIMEMA-AMLSG-SAL study. Previous results from this phase 3 study were published in NEJM in 2013.

Updated results include 276 adults (ages 18 to 71) with newly diagnosed, low- or intermediate-risk APL. Patients were randomized to receive ATRA plus arsenic trioxide or ATRA plus chemotherapy.

A total of 263 patients were evaluable for response to induction. One hundred percent of patients in the arsenic trioxide arm (127/127) achieved a complete response (CR), as did 97% (132/136) of patients in the chemotherapy arm (P=0.12).

After a median follow-up of 40.6 months, the event-free survival was 97.3% in the arsenic trioxide arm and 80% in the chemotherapy arm (P<0.001). The cumulative incidence of relapse was 1.9% and 13.9%, respectively (P=0.0013).

At 50 months, the overall survival was 99.2% in the arsenic trioxide arm and 92.6% in the chemotherapy arm (P=0.0073).

After induction, there were 2 relapses and 1 death in CR in the arsenic trioxide arm.

In the chemotherapy arm, there were 2 instances of molecular resistance after third consolidation, 15 relapses, 5 deaths in CR, and 2 patients who developed a therapy-related myeloid neoplasm.