From the Editor

CASE: McRobert’s maneuver fails
You are attempting an early term vaginal delivery of a 31-year-old G2P1 woman with type 2 diabetes mellitus and an estimated fetal weight of 4,100 g. The fetal head has delivered but retracted against the perineum, producing the “turtle sign.”

You call a shoulder dystocia emergency and request help. In sequence, you tell the mother to stop pushing, check for a nuchal cord, and cut a mediolateral episiotomy. Working seamlessly with your nurse, you place the patient at the edge of the bed, perform the McRobert’s maneuver, provide suprapubic pressure and apply gentle downward guidance to the fetal head. Unfortunately, with these maneuvers the baby does not deliver.

What is your next obstetric maneuver?

With alacrity, move on to an advanced maneuver. In this article, I outline your options for this advanced maneuver and describe the technique for execution. First, however, I discuss the amount of time you have to work with.

How long do you have to perform advanced maneuvers?
In managing a difficult shoulder dystocia, critical goals are to avoid permanent injury to the newborn, including brachial plexus injury, fetal asphyxia, central nervous system injury, and death. Many experts believe that the accoucheur has approximately 4 or 5 minutes to deliver the impacted fetus before the risk of these adverse outcomes rises substantially.^1-3 In one study, a head-to-body delivery interval of less than 5 minutes and 5 minutes or longer were associated with rates of hypoxic ischemic encephalopathy of 0.5% and 24%, respectively.²

Stay calm, move on. Given the time pressure for management, it is important to initiate an advanced maneuver, such as rotation of the fetal body or delivery of the posterior arm, when the initial sequence of McRobert’s maneuver, suprapubic pressure, and gentle downward guidance on the fetal head do not result in delivery. Repetitively repeating these initial maneuvers will increase the risk of an adverse fetal outcome. Stay calm and quickly move on to an advanced maneuver.

Advanced maneuvers
The two advanced shoulder dystocia maneuvers that often result in a successful birth are:

• rotation of the fetal shoulders
• delivery of the posterior arm.^4,5

In a prior editorial, I described in detail the Woods and Rubin rotational maneuvers.⁶ In this editorial, I focus on the technique for delivery of the posterior arm.

Delivery of the posterior arm
This maneuver to resolve difficult shoulder dystocia deliveries has been in the armamentarium of obstetricians since at least the mid-18th Century.⁷ The delivery of the posterior arm reduces the presenting fetal diameter from the larger bisacromial diameter to the smaller axilloacromial diameter. Experts estimate that this change results in a 2-cm decrease in the presenting fetal diameter, thereby facilitating delivery.^8,9

In describing posterior arm delivery, it is important to clearly define the anatomy of the upper extremity. The arm is the portion of the upper extremity from the shoulder to the elbow joint.  The long bone of the arm is the humerus. The forearm is the portion of the upper extremity from the elbow to the wrist. The long bones of the forearm are the radius and ulna.

Descriptions of how to deliver the posterior arm range from concise to detailed. A concise description recommends “inserting a hand in the vagina, grasping the fetal arm, and sweeping it across the chest.”⁹

These detailed instructions are provided by Dr. John Rodis, Chief of Obstetrics and Gynecology at St. Francis Hospital in Hartford Connecticut, in UpToDate:

Additional technical guidance. After grasping the fetal wrist and hand, pull the upper extremity against the fetal chest. Approaching the vaginal introitus, pull the wrist and hand toward the fetal ear nearest the maternal symphysis pubis.¹¹ These maneuvers may result in a fracture to the humerus, but this complication is acceptable given the risk of fetal asphyxia and death.

Approaches to grasping the posterior arm
The posterior arm may be in one of three positions, and your approach to each position will be different.

Fetal hand near the chin. Delivery of the posterior arm is relatively easy when the fetal hand is in this position. Grasp the wrist gently and guide it out of the vagina. The fetal wrist should be pulled toward the fetal ear closest to the maternal symphysis.

Fetal hand on the abdomen. In this position, the operator can exert pressure on the antecubital fossa with the index and middle fingers, resulting in flexion of the forearm at the elbow. This will bring the fetal hand and wrist to the upper chest. The wrist then can be grasped and pronated over the fetal chest. The wrist and forearm are then pulled upward along the chest toward the fetal ear closest to the maternal symphysis. 

Fetal upper extremity is extended with the hand next to the thigh. The most challenging situation is when the upper extremity of the fetus is extended along the trunk or behind the buttocks. In this situation the hand and wrist may be near the fetal thigh and very difficult to reach. In addition, the upper extremity may be tightly pinned between fetal trunk and maternal tissues, making it impossible to flex the forearm by gentle pressure on the antecubital fossa.

In this situation the operator’s hand must reach the fetal wrist and distal forearm, grasp these structures, and pull hard across the trunk to free the pinned upper extremity. The fetal wrist and distal forearm can be securely grasped using techniques pictured in the Figure. It can take 30 to 90 seconds for the operator to place a hand in the vagina, identify the posterior shoulder, follow the extended arm to the hand, and secure the wrist. Given the amount of time that it may take to accomplish the first steps of the maneuver, the nurse in the room should call out the time elapsed since the birth of the head at regular intervals to assist the obstetrician in pacing the speed of the intervention.

___________________________________________________________________________________________________

		Figure. When the fetal upper extremity is extended and the hand is near the fetal thigh the fetal upper extremity may be tightly pinned between maternal and fetal tissues. Gentle pressure in the antecubital fossa may not cause the forearm to flex toward the vaginal introitus. In this situation it may be very difficult to grasp the fetal wrist or forearm. The operator should be prepared to place their entire hand and forearm into the vagina to reach the fetal wrist (Top left). Two options for grasping the fetal wrist are with the index finger and middle finger (Top right), or by encircling the wrist with the thumb and index finger (Bottom left). For many obstetricians, the index and middle fingers extend much further from their wrist than the thumb. Consequently, when the fetal wrist and hand are against the fetal thigh it may be easier to reach the fetal wrist with the operator’s index and middle finger. However, many obstetricians find that the thumb and index finger provide a more secure grip of the fetal wrist.

______________________________________________________________________________________________________

When the posterior arm is fully extended and pinned between fetal trunk and maternal tissues it can be very difficult to reach the fetal wrist. To help successfully complete the maneuver, the obstetrician should visualize placing his or her hand and entire forearm up to the elbow in the vagina to reach the fetal wrist. It may not be necessary to insert the entire forearm in the vagina, but the operator should visualize this step so he or she is prepared for the possibility.Surprisingly, the hollow of the sacrum often provides sufficient space for inserting the hand and entire forearm of the operator. In this process the operator’s hand and forearm may be strongly compressed by maternal and fetal tissues, cutting off circulation to the upper extremity. The operator’s upper extremity may quickly become numb, resulting in a reduction in tactile sensation and strength.

If the posterior arm is positioned behind the back of the fetus, maneuvers similar to those described above can be used to grasp the wrist and pull the arm to the anterior side of the fetal trunk, followed by delivery of the posterior arm.

Practice, practice, and practice some more
Obstetric emergencies create a rush of adrenaline and great stress for the obstetrician. This may adversely impact motor performance, decision-making, and communication skills.¹² Low- and high-fidelity simulation exercises permit the obstetrics team to practice the sequence of maneuvers necessary to successfully resolve a shoulder dystocia, thereby reducing stress and improving performance when the emergency actually occurs.¹³ Simulating obstetric emergencies and visualizing the steps necessary to resolve an emergency are good approaches to prepare obstetricians for the most challenging emergencies. For the difficult to resolve shoulder dystocia, my recommendation is: “Deliver the posterior arm.”

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

CASE: McRobert’s maneuver fails
You are attempting an early term vaginal delivery of a 31-year-old G2P1 woman with type 2 diabetes mellitus and an estimated fetal weight of 4,100 g. The fetal head has delivered but retracted against the perineum, producing the “turtle sign.”

You call a shoulder dystocia emergency and request help. In sequence, you tell the mother to stop pushing, check for a nuchal cord, and cut a mediolateral episiotomy. Working seamlessly with your nurse, you place the patient at the edge of the bed, perform the McRobert’s maneuver, provide suprapubic pressure and apply gentle downward guidance to the fetal head. Unfortunately, with these maneuvers the baby does not deliver.

What is your next obstetric maneuver?

With alacrity, move on to an advanced maneuver. In this article, I outline your options for this advanced maneuver and describe the technique for execution. First, however, I discuss the amount of time you have to work with.

How long do you have to perform advanced maneuvers?
In managing a difficult shoulder dystocia, critical goals are to avoid permanent injury to the newborn, including brachial plexus injury, fetal asphyxia, central nervous system injury, and death. Many experts believe that the accoucheur has approximately 4 or 5 minutes to deliver the impacted fetus before the risk of these adverse outcomes rises substantially.^1-3 In one study, a head-to-body delivery interval of less than 5 minutes and 5 minutes or longer were associated with rates of hypoxic ischemic encephalopathy of 0.5% and 24%, respectively.²

Stay calm, move on. Given the time pressure for management, it is important to initiate an advanced maneuver, such as rotation of the fetal body or delivery of the posterior arm, when the initial sequence of McRobert’s maneuver, suprapubic pressure, and gentle downward guidance on the fetal head do not result in delivery. Repetitively repeating these initial maneuvers will increase the risk of an adverse fetal outcome. Stay calm and quickly move on to an advanced maneuver.

Advanced maneuvers
The two advanced shoulder dystocia maneuvers that often result in a successful birth are:

• rotation of the fetal shoulders
• delivery of the posterior arm.^4,5

In a prior editorial, I described in detail the Woods and Rubin rotational maneuvers.⁶ In this editorial, I focus on the technique for delivery of the posterior arm.

Delivery of the posterior arm
This maneuver to resolve difficult shoulder dystocia deliveries has been in the armamentarium of obstetricians since at least the mid-18th Century.⁷ The delivery of the posterior arm reduces the presenting fetal diameter from the larger bisacromial diameter to the smaller axilloacromial diameter. Experts estimate that this change results in a 2-cm decrease in the presenting fetal diameter, thereby facilitating delivery.^8,9

In describing posterior arm delivery, it is important to clearly define the anatomy of the upper extremity. The arm is the portion of the upper extremity from the shoulder to the elbow joint.  The long bone of the arm is the humerus. The forearm is the portion of the upper extremity from the elbow to the wrist. The long bones of the forearm are the radius and ulna.

Descriptions of how to deliver the posterior arm range from concise to detailed. A concise description recommends “inserting a hand in the vagina, grasping the fetal arm, and sweeping it across the chest.”⁹

These detailed instructions are provided by Dr. John Rodis, Chief of Obstetrics and Gynecology at St. Francis Hospital in Hartford Connecticut, in UpToDate:

Additional technical guidance. After grasping the fetal wrist and hand, pull the upper extremity against the fetal chest. Approaching the vaginal introitus, pull the wrist and hand toward the fetal ear nearest the maternal symphysis pubis.¹¹ These maneuvers may result in a fracture to the humerus, but this complication is acceptable given the risk of fetal asphyxia and death.

Approaches to grasping the posterior arm
The posterior arm may be in one of three positions, and your approach to each position will be different.

Fetal hand near the chin. Delivery of the posterior arm is relatively easy when the fetal hand is in this position. Grasp the wrist gently and guide it out of the vagina. The fetal wrist should be pulled toward the fetal ear closest to the maternal symphysis.

Fetal hand on the abdomen. In this position, the operator can exert pressure on the antecubital fossa with the index and middle fingers, resulting in flexion of the forearm at the elbow. This will bring the fetal hand and wrist to the upper chest. The wrist then can be grasped and pronated over the fetal chest. The wrist and forearm are then pulled upward along the chest toward the fetal ear closest to the maternal symphysis. 

Fetal upper extremity is extended with the hand next to the thigh. The most challenging situation is when the upper extremity of the fetus is extended along the trunk or behind the buttocks. In this situation the hand and wrist may be near the fetal thigh and very difficult to reach. In addition, the upper extremity may be tightly pinned between fetal trunk and maternal tissues, making it impossible to flex the forearm by gentle pressure on the antecubital fossa.

In this situation the operator’s hand must reach the fetal wrist and distal forearm, grasp these structures, and pull hard across the trunk to free the pinned upper extremity. The fetal wrist and distal forearm can be securely grasped using techniques pictured in the Figure. It can take 30 to 90 seconds for the operator to place a hand in the vagina, identify the posterior shoulder, follow the extended arm to the hand, and secure the wrist. Given the amount of time that it may take to accomplish the first steps of the maneuver, the nurse in the room should call out the time elapsed since the birth of the head at regular intervals to assist the obstetrician in pacing the speed of the intervention.

___________________________________________________________________________________________________

		Figure. When the fetal upper extremity is extended and the hand is near the fetal thigh the fetal upper extremity may be tightly pinned between maternal and fetal tissues. Gentle pressure in the antecubital fossa may not cause the forearm to flex toward the vaginal introitus. In this situation it may be very difficult to grasp the fetal wrist or forearm. The operator should be prepared to place their entire hand and forearm into the vagina to reach the fetal wrist (Top left). Two options for grasping the fetal wrist are with the index finger and middle finger (Top right), or by encircling the wrist with the thumb and index finger (Bottom left). For many obstetricians, the index and middle fingers extend much further from their wrist than the thumb. Consequently, when the fetal wrist and hand are against the fetal thigh it may be easier to reach the fetal wrist with the operator’s index and middle finger. However, many obstetricians find that the thumb and index finger provide a more secure grip of the fetal wrist.

______________________________________________________________________________________________________

When the posterior arm is fully extended and pinned between fetal trunk and maternal tissues it can be very difficult to reach the fetal wrist. To help successfully complete the maneuver, the obstetrician should visualize placing his or her hand and entire forearm up to the elbow in the vagina to reach the fetal wrist. It may not be necessary to insert the entire forearm in the vagina, but the operator should visualize this step so he or she is prepared for the possibility.Surprisingly, the hollow of the sacrum often provides sufficient space for inserting the hand and entire forearm of the operator. In this process the operator’s hand and forearm may be strongly compressed by maternal and fetal tissues, cutting off circulation to the upper extremity. The operator’s upper extremity may quickly become numb, resulting in a reduction in tactile sensation and strength.

If the posterior arm is positioned behind the back of the fetus, maneuvers similar to those described above can be used to grasp the wrist and pull the arm to the anterior side of the fetal trunk, followed by delivery of the posterior arm.

Practice, practice, and practice some more
Obstetric emergencies create a rush of adrenaline and great stress for the obstetrician. This may adversely impact motor performance, decision-making, and communication skills.¹² Low- and high-fidelity simulation exercises permit the obstetrics team to practice the sequence of maneuvers necessary to successfully resolve a shoulder dystocia, thereby reducing stress and improving performance when the emergency actually occurs.¹³ Simulating obstetric emergencies and visualizing the steps necessary to resolve an emergency are good approaches to prepare obstetricians for the most challenging emergencies. For the difficult to resolve shoulder dystocia, my recommendation is: “Deliver the posterior arm.”

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

CASE: McRobert’s maneuver fails
You are attempting an early term vaginal delivery of a 31-year-old G2P1 woman with type 2 diabetes mellitus and an estimated fetal weight of 4,100 g. The fetal head has delivered but retracted against the perineum, producing the “turtle sign.”

You call a shoulder dystocia emergency and request help. In sequence, you tell the mother to stop pushing, check for a nuchal cord, and cut a mediolateral episiotomy. Working seamlessly with your nurse, you place the patient at the edge of the bed, perform the McRobert’s maneuver, provide suprapubic pressure and apply gentle downward guidance to the fetal head. Unfortunately, with these maneuvers the baby does not deliver.

What is your next obstetric maneuver?

With alacrity, move on to an advanced maneuver. In this article, I outline your options for this advanced maneuver and describe the technique for execution. First, however, I discuss the amount of time you have to work with.

How long do you have to perform advanced maneuvers?
In managing a difficult shoulder dystocia, critical goals are to avoid permanent injury to the newborn, including brachial plexus injury, fetal asphyxia, central nervous system injury, and death. Many experts believe that the accoucheur has approximately 4 or 5 minutes to deliver the impacted fetus before the risk of these adverse outcomes rises substantially.^1-3 In one study, a head-to-body delivery interval of less than 5 minutes and 5 minutes or longer were associated with rates of hypoxic ischemic encephalopathy of 0.5% and 24%, respectively.²

Stay calm, move on. Given the time pressure for management, it is important to initiate an advanced maneuver, such as rotation of the fetal body or delivery of the posterior arm, when the initial sequence of McRobert’s maneuver, suprapubic pressure, and gentle downward guidance on the fetal head do not result in delivery. Repetitively repeating these initial maneuvers will increase the risk of an adverse fetal outcome. Stay calm and quickly move on to an advanced maneuver.

Advanced maneuvers
The two advanced shoulder dystocia maneuvers that often result in a successful birth are:

• rotation of the fetal shoulders
• delivery of the posterior arm.^4,5

In a prior editorial, I described in detail the Woods and Rubin rotational maneuvers.⁶ In this editorial, I focus on the technique for delivery of the posterior arm.

Delivery of the posterior arm
This maneuver to resolve difficult shoulder dystocia deliveries has been in the armamentarium of obstetricians since at least the mid-18th Century.⁷ The delivery of the posterior arm reduces the presenting fetal diameter from the larger bisacromial diameter to the smaller axilloacromial diameter. Experts estimate that this change results in a 2-cm decrease in the presenting fetal diameter, thereby facilitating delivery.^8,9

In describing posterior arm delivery, it is important to clearly define the anatomy of the upper extremity. The arm is the portion of the upper extremity from the shoulder to the elbow joint.  The long bone of the arm is the humerus. The forearm is the portion of the upper extremity from the elbow to the wrist. The long bones of the forearm are the radius and ulna.

Descriptions of how to deliver the posterior arm range from concise to detailed. A concise description recommends “inserting a hand in the vagina, grasping the fetal arm, and sweeping it across the chest.”⁹

These detailed instructions are provided by Dr. John Rodis, Chief of Obstetrics and Gynecology at St. Francis Hospital in Hartford Connecticut, in UpToDate:

Additional technical guidance. After grasping the fetal wrist and hand, pull the upper extremity against the fetal chest. Approaching the vaginal introitus, pull the wrist and hand toward the fetal ear nearest the maternal symphysis pubis.¹¹ These maneuvers may result in a fracture to the humerus, but this complication is acceptable given the risk of fetal asphyxia and death.

Approaches to grasping the posterior arm
The posterior arm may be in one of three positions, and your approach to each position will be different.

Fetal hand near the chin. Delivery of the posterior arm is relatively easy when the fetal hand is in this position. Grasp the wrist gently and guide it out of the vagina. The fetal wrist should be pulled toward the fetal ear closest to the maternal symphysis.

Fetal hand on the abdomen. In this position, the operator can exert pressure on the antecubital fossa with the index and middle fingers, resulting in flexion of the forearm at the elbow. This will bring the fetal hand and wrist to the upper chest. The wrist then can be grasped and pronated over the fetal chest. The wrist and forearm are then pulled upward along the chest toward the fetal ear closest to the maternal symphysis. 

Fetal upper extremity is extended with the hand next to the thigh. The most challenging situation is when the upper extremity of the fetus is extended along the trunk or behind the buttocks. In this situation the hand and wrist may be near the fetal thigh and very difficult to reach. In addition, the upper extremity may be tightly pinned between fetal trunk and maternal tissues, making it impossible to flex the forearm by gentle pressure on the antecubital fossa.

In this situation the operator’s hand must reach the fetal wrist and distal forearm, grasp these structures, and pull hard across the trunk to free the pinned upper extremity. The fetal wrist and distal forearm can be securely grasped using techniques pictured in the Figure. It can take 30 to 90 seconds for the operator to place a hand in the vagina, identify the posterior shoulder, follow the extended arm to the hand, and secure the wrist. Given the amount of time that it may take to accomplish the first steps of the maneuver, the nurse in the room should call out the time elapsed since the birth of the head at regular intervals to assist the obstetrician in pacing the speed of the intervention.

___________________________________________________________________________________________________

		Figure. When the fetal upper extremity is extended and the hand is near the fetal thigh the fetal upper extremity may be tightly pinned between maternal and fetal tissues. Gentle pressure in the antecubital fossa may not cause the forearm to flex toward the vaginal introitus. In this situation it may be very difficult to grasp the fetal wrist or forearm. The operator should be prepared to place their entire hand and forearm into the vagina to reach the fetal wrist (Top left). Two options for grasping the fetal wrist are with the index finger and middle finger (Top right), or by encircling the wrist with the thumb and index finger (Bottom left). For many obstetricians, the index and middle fingers extend much further from their wrist than the thumb. Consequently, when the fetal wrist and hand are against the fetal thigh it may be easier to reach the fetal wrist with the operator’s index and middle finger. However, many obstetricians find that the thumb and index finger provide a more secure grip of the fetal wrist.

______________________________________________________________________________________________________

When the posterior arm is fully extended and pinned between fetal trunk and maternal tissues it can be very difficult to reach the fetal wrist. To help successfully complete the maneuver, the obstetrician should visualize placing his or her hand and entire forearm up to the elbow in the vagina to reach the fetal wrist. It may not be necessary to insert the entire forearm in the vagina, but the operator should visualize this step so he or she is prepared for the possibility.Surprisingly, the hollow of the sacrum often provides sufficient space for inserting the hand and entire forearm of the operator. In this process the operator’s hand and forearm may be strongly compressed by maternal and fetal tissues, cutting off circulation to the upper extremity. The operator’s upper extremity may quickly become numb, resulting in a reduction in tactile sensation and strength.

If the posterior arm is positioned behind the back of the fetus, maneuvers similar to those described above can be used to grasp the wrist and pull the arm to the anterior side of the fetal trunk, followed by delivery of the posterior arm.

Practice, practice, and practice some more
Obstetric emergencies create a rush of adrenaline and great stress for the obstetrician. This may adversely impact motor performance, decision-making, and communication skills.¹² Low- and high-fidelity simulation exercises permit the obstetrics team to practice the sequence of maneuvers necessary to successfully resolve a shoulder dystocia, thereby reducing stress and improving performance when the emergency actually occurs.¹³ Simulating obstetric emergencies and visualizing the steps necessary to resolve an emergency are good approaches to prepare obstetricians for the most challenging emergencies. For the difficult to resolve shoulder dystocia, my recommendation is: “Deliver the posterior arm.”

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Summer is winding down as we go to press with this month’s issue, and while we might well reflect a little sadly on its departure, we can also look forward to the fall season with its promise of renewal and adventure. As I settled back in to my familiar work routine after the Labor Day weekend, I was reminded of how, despite the remarkable clinical advances in oncology, we are still caregivers, involved in our patients’ everyday lives and that we can never forget our humanity. The advent of high-tech personalized medicine or precision oncology, as I prefer to call it, has given oncologists a remarkable cache of treatment options for their patients and the hope that more – and better – therapies are to come. Next-generation diagnostics are helping us identify the cellular targets we need to take aim at to kill the tumor and globally, research is yielding more and more therapeutics to subdue those targets and hence the tumor.

Click on the PDF icon at the top of this introduction to read the full article.

Summer is winding down as we go to press with this month’s issue, and while we might well reflect a little sadly on its departure, we can also look forward to the fall season with its promise of renewal and adventure. As I settled back in to my familiar work routine after the Labor Day weekend, I was reminded of how, despite the remarkable clinical advances in oncology, we are still caregivers, involved in our patients’ everyday lives and that we can never forget our humanity. The advent of high-tech personalized medicine or precision oncology, as I prefer to call it, has given oncologists a remarkable cache of treatment options for their patients and the hope that more – and better – therapies are to come. Next-generation diagnostics are helping us identify the cellular targets we need to take aim at to kill the tumor and globally, research is yielding more and more therapeutics to subdue those targets and hence the tumor.

Click on the PDF icon at the top of this introduction to read the full article.

Summer is winding down as we go to press with this month’s issue, and while we might well reflect a little sadly on its departure, we can also look forward to the fall season with its promise of renewal and adventure. As I settled back in to my familiar work routine after the Labor Day weekend, I was reminded of how, despite the remarkable clinical advances in oncology, we are still caregivers, involved in our patients’ everyday lives and that we can never forget our humanity. The advent of high-tech personalized medicine or precision oncology, as I prefer to call it, has given oncologists a remarkable cache of treatment options for their patients and the hope that more – and better – therapies are to come. Next-generation diagnostics are helping us identify the cellular targets we need to take aim at to kill the tumor and globally, research is yielding more and more therapeutics to subdue those targets and hence the tumor.

Click on the PDF icon at the top of this introduction to read the full article.

Since clozapine was launched in 1989, miraculous improvements and “awak­enings” have been reported in many patients afflicted with severe schizo­phrenia and considered hopelessly refractory to antipsychotic pharmaco­therapy. Not only do severely disabled patients regain their sanity and return to normal functioning, but the joy that their family and treating psychiatrist experi­ence is priceless.

That’s why I am perplexed by how infrequently clozapine is used in the United States (in about 5% of patients)—even though approximately 25% of patients who have schizophrenia are either treatment-resistant or have refrac­tory hallucinations or delusions.

Consider Bethany’s case. She was one of my young patients, who, after taking clozapine, recovered fully and resumed a productive life, after years of homeless­ness during which she was controlled by auditory hallucinations.

Bethany’s story began well…
Bethany grew up in a loving home, smart and talented, an “A” student in high school and talented violin­ist. She received a scholarship to a prestigious private university at 16 and left her parent’s home in Ohio to major in molecular biol­ogy. Her goal was to attend medical school. She excelled during her first 3 years of college, and even published 2 papers in top-tier science journals.

In her senior year, after returning from a trip to Africa, Bethany began to change. She neglected her studies and focused on raising money for HIV clinics in Africa. She began getting F’s instead of A’s, lost her scholarship and her residence hall room, and had to drop out of college. Soon, she began hearing voices commanding her every action.

..but took a really bad turn
Bethany became homeless for the next 4.5 years. She ate discarded food from garbage cans, had no change of clothes, and slept on a concrete slab behind a downtown church in a major city in California. Her parents lost track of her, although her mother, a retired nurse, frantically and relentlessly tried to find out what happened to her only daughter during that time.

Eventually, Bethany was arrested when she was found screaming back at the voices, at midnight in a residential area of the city. She was hospitalized on a psychiatric ward and given antipsychot­ics, but with only modest improvement.

Her parents were contacted; immedi­ately, they flew to California to see her. The treating psychiatrist told them that their daughter had schizophrenia, and that they should lower their expectations because she would be totally disabled for the rest of her life. They brought Bethany back to Ohio where, after a tumultuous year of failed trials of several antipsy­chotics to suppress the auditory halluci­nations, we gave her clozapine.

Gradually, Bethany improved, but she still could not read a book or maga­zine (which I urged her to do) without the voices intensifying and preventing her from reading.


Bethany recovers
After 6 to 8 months on clozapine, however, Bethany’s auditory hal­lucinations faded away. With my encouragement, she enrolled at the University of Cincinnati and took 1 course at a time. She began to get A’s again—in advanced courses, such as genetics, physics, and molecular biol­ogy. She completed her degree require­ments and graduated with honors, with a Bachelor of Science degree in molecular biology. She also served as a marshal in the commencement ceremony procession.

Over the next year, with strong encouragement, Bethany wrote a book about her remark­able recovery from refractory psychosis.¹ In addition, her mother wrote a deeply emo­tional book that described the gut-wrenching ordeal that she and her husband went through during the years that Bethany disappeared.² I urge you to read these inspiring books (Figure) about the remarkable recovery from refractory psychosis and the heavy family burden of schizophrenia.

No doubt, clozapine is associated with serious side effects¹⁵—but so is chemotherapy for cancer, and oncolo­gists do not hesitate to use it to save their patients from physical death. Severe schizophrenia is like a can­cer of the mind, and clozapine is its chemotherapy.

Fortunately for Bethany, she had almost no physical adverse effects from clozapine except for intense sedation, which was mitigated with modafinil.

We should use clozapine more than we do
Clozapine has the potential to have a healing effect for many patients whose schizophrenia is resistant to treatment. Most such patients, however, never receive a trial of the drug. Furthermore, few practitioners use clozapine for schizophrenia patients with suicidal ten­dencies, despite the high rate of suicide completion in schizophrenia.¹⁶

Clozapine remains, regrettably, an underutilized agent in psychiatry. Until other breakthrough drugs are discovered, its use ought to be double or triple what it is now because there are many people like Bethany who are not being given a chance to recover from their illness.

Since clozapine was launched in 1989, miraculous improvements and “awak­enings” have been reported in many patients afflicted with severe schizo­phrenia and considered hopelessly refractory to antipsychotic pharmaco­therapy. Not only do severely disabled patients regain their sanity and return to normal functioning, but the joy that their family and treating psychiatrist experi­ence is priceless.

That’s why I am perplexed by how infrequently clozapine is used in the United States (in about 5% of patients)—even though approximately 25% of patients who have schizophrenia are either treatment-resistant or have refrac­tory hallucinations or delusions.

Consider Bethany’s case. She was one of my young patients, who, after taking clozapine, recovered fully and resumed a productive life, after years of homeless­ness during which she was controlled by auditory hallucinations.

Bethany’s story began well…
Bethany grew up in a loving home, smart and talented, an “A” student in high school and talented violin­ist. She received a scholarship to a prestigious private university at 16 and left her parent’s home in Ohio to major in molecular biol­ogy. Her goal was to attend medical school. She excelled during her first 3 years of college, and even published 2 papers in top-tier science journals.

In her senior year, after returning from a trip to Africa, Bethany began to change. She neglected her studies and focused on raising money for HIV clinics in Africa. She began getting F’s instead of A’s, lost her scholarship and her residence hall room, and had to drop out of college. Soon, she began hearing voices commanding her every action.

..but took a really bad turn
Bethany became homeless for the next 4.5 years. She ate discarded food from garbage cans, had no change of clothes, and slept on a concrete slab behind a downtown church in a major city in California. Her parents lost track of her, although her mother, a retired nurse, frantically and relentlessly tried to find out what happened to her only daughter during that time.

Eventually, Bethany was arrested when she was found screaming back at the voices, at midnight in a residential area of the city. She was hospitalized on a psychiatric ward and given antipsychot­ics, but with only modest improvement.

Her parents were contacted; immedi­ately, they flew to California to see her. The treating psychiatrist told them that their daughter had schizophrenia, and that they should lower their expectations because she would be totally disabled for the rest of her life. They brought Bethany back to Ohio where, after a tumultuous year of failed trials of several antipsy­chotics to suppress the auditory halluci­nations, we gave her clozapine.

Gradually, Bethany improved, but she still could not read a book or maga­zine (which I urged her to do) without the voices intensifying and preventing her from reading.


Bethany recovers
After 6 to 8 months on clozapine, however, Bethany’s auditory hal­lucinations faded away. With my encouragement, she enrolled at the University of Cincinnati and took 1 course at a time. She began to get A’s again—in advanced courses, such as genetics, physics, and molecular biol­ogy. She completed her degree require­ments and graduated with honors, with a Bachelor of Science degree in molecular biology. She also served as a marshal in the commencement ceremony procession.

Over the next year, with strong encouragement, Bethany wrote a book about her remark­able recovery from refractory psychosis.¹ In addition, her mother wrote a deeply emo­tional book that described the gut-wrenching ordeal that she and her husband went through during the years that Bethany disappeared.² I urge you to read these inspiring books (Figure) about the remarkable recovery from refractory psychosis and the heavy family burden of schizophrenia.

No doubt, clozapine is associated with serious side effects¹⁵—but so is chemotherapy for cancer, and oncolo­gists do not hesitate to use it to save their patients from physical death. Severe schizophrenia is like a can­cer of the mind, and clozapine is its chemotherapy.

Fortunately for Bethany, she had almost no physical adverse effects from clozapine except for intense sedation, which was mitigated with modafinil.

We should use clozapine more than we do
Clozapine has the potential to have a healing effect for many patients whose schizophrenia is resistant to treatment. Most such patients, however, never receive a trial of the drug. Furthermore, few practitioners use clozapine for schizophrenia patients with suicidal ten­dencies, despite the high rate of suicide completion in schizophrenia.¹⁶

Clozapine remains, regrettably, an underutilized agent in psychiatry. Until other breakthrough drugs are discovered, its use ought to be double or triple what it is now because there are many people like Bethany who are not being given a chance to recover from their illness.

Since clozapine was launched in 1989, miraculous improvements and “awak­enings” have been reported in many patients afflicted with severe schizo­phrenia and considered hopelessly refractory to antipsychotic pharmaco­therapy. Not only do severely disabled patients regain their sanity and return to normal functioning, but the joy that their family and treating psychiatrist experi­ence is priceless.

That’s why I am perplexed by how infrequently clozapine is used in the United States (in about 5% of patients)—even though approximately 25% of patients who have schizophrenia are either treatment-resistant or have refrac­tory hallucinations or delusions.

Consider Bethany’s case. She was one of my young patients, who, after taking clozapine, recovered fully and resumed a productive life, after years of homeless­ness during which she was controlled by auditory hallucinations.

Bethany’s story began well…
Bethany grew up in a loving home, smart and talented, an “A” student in high school and talented violin­ist. She received a scholarship to a prestigious private university at 16 and left her parent’s home in Ohio to major in molecular biol­ogy. Her goal was to attend medical school. She excelled during her first 3 years of college, and even published 2 papers in top-tier science journals.

In her senior year, after returning from a trip to Africa, Bethany began to change. She neglected her studies and focused on raising money for HIV clinics in Africa. She began getting F’s instead of A’s, lost her scholarship and her residence hall room, and had to drop out of college. Soon, she began hearing voices commanding her every action.

..but took a really bad turn
Bethany became homeless for the next 4.5 years. She ate discarded food from garbage cans, had no change of clothes, and slept on a concrete slab behind a downtown church in a major city in California. Her parents lost track of her, although her mother, a retired nurse, frantically and relentlessly tried to find out what happened to her only daughter during that time.

Eventually, Bethany was arrested when she was found screaming back at the voices, at midnight in a residential area of the city. She was hospitalized on a psychiatric ward and given antipsychot­ics, but with only modest improvement.

Her parents were contacted; immedi­ately, they flew to California to see her. The treating psychiatrist told them that their daughter had schizophrenia, and that they should lower their expectations because she would be totally disabled for the rest of her life. They brought Bethany back to Ohio where, after a tumultuous year of failed trials of several antipsy­chotics to suppress the auditory halluci­nations, we gave her clozapine.

Gradually, Bethany improved, but she still could not read a book or maga­zine (which I urged her to do) without the voices intensifying and preventing her from reading.


Bethany recovers
After 6 to 8 months on clozapine, however, Bethany’s auditory hal­lucinations faded away. With my encouragement, she enrolled at the University of Cincinnati and took 1 course at a time. She began to get A’s again—in advanced courses, such as genetics, physics, and molecular biol­ogy. She completed her degree require­ments and graduated with honors, with a Bachelor of Science degree in molecular biology. She also served as a marshal in the commencement ceremony procession.

Over the next year, with strong encouragement, Bethany wrote a book about her remark­able recovery from refractory psychosis.¹ In addition, her mother wrote a deeply emo­tional book that described the gut-wrenching ordeal that she and her husband went through during the years that Bethany disappeared.² I urge you to read these inspiring books (Figure) about the remarkable recovery from refractory psychosis and the heavy family burden of schizophrenia.

No doubt, clozapine is associated with serious side effects¹⁵—but so is chemotherapy for cancer, and oncolo­gists do not hesitate to use it to save their patients from physical death. Severe schizophrenia is like a can­cer of the mind, and clozapine is its chemotherapy.

Fortunately for Bethany, she had almost no physical adverse effects from clozapine except for intense sedation, which was mitigated with modafinil.

We should use clozapine more than we do
Clozapine has the potential to have a healing effect for many patients whose schizophrenia is resistant to treatment. Most such patients, however, never receive a trial of the drug. Furthermore, few practitioners use clozapine for schizophrenia patients with suicidal ten­dencies, despite the high rate of suicide completion in schizophrenia.¹⁶

Clozapine remains, regrettably, an underutilized agent in psychiatry. Until other breakthrough drugs are discovered, its use ought to be double or triple what it is now because there are many people like Bethany who are not being given a chance to recover from their illness.

In oncology clinical trials, overall survival (OS) remains the gold standard for clinical benefit. However, because there are so many available treatment options for most types of cancer, survival analysis in clinical trials is often confounded by subsequent therapies. Progression-free survival (PFS) is an endpoint not so confounded, and one that requires fewer patients and less time to arrive at a conclusion about a new therapy. As a result, an ever-increasing number of oncology clinical trials are launched in which PFS is used as the primary endpoint. Several years ago, Pazdur¹ emphasized that the time-to-progression endpoint must use the same evaluation techniques and schedules for all treatment arms and he recommended blinding of trials or at minimum, the use of an external blinded radiographic review committee. He also noted that improvement in disease-related symptoms qualifies as clinical benefit and may therefore be an appropriate endpoint for drug approval.

Click on the PDF icon at the top of this introduction to read the full article.

In oncology clinical trials, overall survival (OS) remains the gold standard for clinical benefit. However, because there are so many available treatment options for most types of cancer, survival analysis in clinical trials is often confounded by subsequent therapies. Progression-free survival (PFS) is an endpoint not so confounded, and one that requires fewer patients and less time to arrive at a conclusion about a new therapy. As a result, an ever-increasing number of oncology clinical trials are launched in which PFS is used as the primary endpoint. Several years ago, Pazdur¹ emphasized that the time-to-progression endpoint must use the same evaluation techniques and schedules for all treatment arms and he recommended blinding of trials or at minimum, the use of an external blinded radiographic review committee. He also noted that improvement in disease-related symptoms qualifies as clinical benefit and may therefore be an appropriate endpoint for drug approval.

Click on the PDF icon at the top of this introduction to read the full article.

In oncology clinical trials, overall survival (OS) remains the gold standard for clinical benefit. However, because there are so many available treatment options for most types of cancer, survival analysis in clinical trials is often confounded by subsequent therapies. Progression-free survival (PFS) is an endpoint not so confounded, and one that requires fewer patients and less time to arrive at a conclusion about a new therapy. As a result, an ever-increasing number of oncology clinical trials are launched in which PFS is used as the primary endpoint. Several years ago, Pazdur¹ emphasized that the time-to-progression endpoint must use the same evaluation techniques and schedules for all treatment arms and he recommended blinding of trials or at minimum, the use of an external blinded radiographic review committee. He also noted that improvement in disease-related symptoms qualifies as clinical benefit and may therefore be an appropriate endpoint for drug approval.

Click on the PDF icon at the top of this introduction to read the full article.

 Recent examples come quickly to mind:
   • $100 million from the Lieber family to fund the Lieber Institute for Brain Development at Johns Hopkins University
   • $300 million from Microsoft co-founder Paul G. Allen to create the Allen Institute for Brain Science
   • $650 million from Ted Stanley for the Stanley Center at the Broad Institute.
Such generosity is cause for celebra­tion by psychiatrists and their long-suffering patients who are disabled by a brain disorder. Private money supple­ments research funding by the National Institutes of Health and will bolster the war against mental illness,¹ which costs >$300 billion annually (Box,²page 12).

Although philanthropy will help, many needs in psychiatry are unmet, and not all can be addressed with money. Consider a number of areas of need.

Unmet clinical needs
Models of disease. Psychiatry is in desperate need of an objective, valid diagnostic system that transcends the DSM model of symptom clusters. The Research Domain Criteria³ repre­sents the effort to find an alternative. To achieve that goal, it’s necessary to identify biomarkers and establish their utility—a task that requires a huge amount of funding.

Therapeutics. Clinicians are hungry for innovative, safe pharmaceuticals and non-drug treatments that modify disease, not just alleviate symptoms. Obsessive-compulsive disorder always has lacked such therapies; so have dementia, schizophrenia, personality disorders, dissociative disorders, and sexual pathologies. In fact, >80% of DSM disorders do not have an FDA-approved, evidence-based treatment,⁴ and many available medications are only partially efficacious, poorly toler­ated, or unsafe.

There are more unmet needs in therapeutics:
   • Development of promising non-drug therapies, such as neuromodula­tion, proceeds slowly.
   • Research into neurobiological mechanisms of psychotherapy is in its infancy.
   • A foolproof method to monitor adherence does not exist, and countless patients relapse needlessly and deterio­rate functionally.
   • Effective, evidence-based rehabili­tation for serious psychiatric disorders is used narrowly and vastly underfunded.
   • Insurers continue to thumb their nose at laws that require parity for treating mental illness—thus impeding access to, delaying, or truncating psy­chiatric care.
 

Unmet scientific needs
Translational investigators. Despite increased funding for basic neuroscien­tific study and breathtaking discover­ies in animal molecular neurobiology, a trickle of findings has been applied to clinical medicine. This translational gap has many causes, including a short­age of translational neuroscientists (MD-PhD psychiatrists and neurolo­gists), insufficient long-term funding to develop such clinician-researchers, and complex regulatory oversight of human research.

Stalled progress in drug devel­opment. Development of novel-mechanism therapeutics for brain disorders is languishing. Some phar­maceutical manufacturers have aban­doned the development of drugs that act on the CNS in favor of less complex, more lucrative areas such as oncology and cardiology; others have reduced their investment in CNS products. Developing treatments for knotty disorders of the most com­plex structure in the known universe requires mammoth investment. Why are stakeholders bailing out on the greatest challenge for science and medicine for easier endeavors?

Discovering new genes for every dev­astating neuropsychiatric syndrome, such as schizophrenia, is cause for cel­ebration, but the champagne won’t flow until the coding of every gene is unscrambled so that specific biological interventions can be developed. The cost of the chase might be orders of mag­nitude greater than what is invested in research today. Conceptualizing new models of brain disorders is a critical part of scientific progress and an antidote to the inertia of perpetual group-think. Depression, for example, is being reconceptualized as a disorder of impaired neuroplasticity and neurotropic deficiency, rather than a shortage of serotonin and norepineph­rine. Rapid reversal of severe depres­sion to euthymia—in 1 or 2 hours—with IV ketamine shattered the dogma that depression takes weeks to lift, and is ushering in unprecedented new think­ing and models likely to revolutionize treatment of severe depression. We need such breakthroughs for other psychiat­ric brain disorders.  

Unmet professional and sociopolitical needs
Broadening of training. Psychiatrists have focused on the mind but insuf­ficiently attended to the biology of the brain. For psychiatry to rise to the next level as a medical specialty and brain discipline, training must incorporate more neurology than it does now. The converse is true in neurology.

Hospitalization not incarceration. It is unconscionable that people suffer­ing from a medical illness that impairs their judgment and behavior are locked up as criminals. Psychiatry must forcefully lobby so that the seriously mentally ill are treated in secure hospitals staffed by physi­cians, nurses, and mental health professionals.

That’s right: Bring back the asylum to address this unmet medical, political, and ethical need for psychiatric patients.^a A serious mental disorder must be accepted as a fault-free illness.

^aTo read more about this, I recommend my March 2008 editorial, “Bring back the asylums?,” at CurrentPsychiatry.com, and Dr. George Paulson’s excellent book, Closing the asylums: Causes and consequences of the deinstitutionalization movement (Jefferson, NC: McFarland & Co. Inc; 2012).

Full integration of psychiatry into the rest of medicine remains an unmet need, despite good progress. Because almost every medical illness can cause psychiatric symp­toms, DSM-5 mandates that general medical conditions be ruled out before a primary psychiatric diagnosis is made.

Along the same lines, most severely mentally ill persons suffer from medical and neurologic ailments before their first episode,⁵ and many die prematurely from cardiovas­cular causes that often are the result of unhealthy lifestyle; iatrogenic complications; and lack of primary care inter­ventions.⁶ Psychiatric patients must always receive stan­dard general medical evaluation and management, side by side with their psychiatric care.

Philanthropy for psychiatry
Philanthropic support of psychiatry is a salutary trend. Some unmet needs in psychiatry, however, require not only money but a change in attitude (such as eliminating the absurd and discriminatory stigma of mental illness), better training, and forceful political activism by all of us.

 Recent examples come quickly to mind:
   • $100 million from the Lieber family to fund the Lieber Institute for Brain Development at Johns Hopkins University
   • $300 million from Microsoft co-founder Paul G. Allen to create the Allen Institute for Brain Science
   • $650 million from Ted Stanley for the Stanley Center at the Broad Institute.
Such generosity is cause for celebra­tion by psychiatrists and their long-suffering patients who are disabled by a brain disorder. Private money supple­ments research funding by the National Institutes of Health and will bolster the war against mental illness,¹ which costs >$300 billion annually (Box,²page 12).

Although philanthropy will help, many needs in psychiatry are unmet, and not all can be addressed with money. Consider a number of areas of need.

Unmet clinical needs
Models of disease. Psychiatry is in desperate need of an objective, valid diagnostic system that transcends the DSM model of symptom clusters. The Research Domain Criteria³ repre­sents the effort to find an alternative. To achieve that goal, it’s necessary to identify biomarkers and establish their utility—a task that requires a huge amount of funding.

Therapeutics. Clinicians are hungry for innovative, safe pharmaceuticals and non-drug treatments that modify disease, not just alleviate symptoms. Obsessive-compulsive disorder always has lacked such therapies; so have dementia, schizophrenia, personality disorders, dissociative disorders, and sexual pathologies. In fact, >80% of DSM disorders do not have an FDA-approved, evidence-based treatment,⁴ and many available medications are only partially efficacious, poorly toler­ated, or unsafe.

There are more unmet needs in therapeutics:
   • Development of promising non-drug therapies, such as neuromodula­tion, proceeds slowly.
   • Research into neurobiological mechanisms of psychotherapy is in its infancy.
   • A foolproof method to monitor adherence does not exist, and countless patients relapse needlessly and deterio­rate functionally.
   • Effective, evidence-based rehabili­tation for serious psychiatric disorders is used narrowly and vastly underfunded.
   • Insurers continue to thumb their nose at laws that require parity for treating mental illness—thus impeding access to, delaying, or truncating psy­chiatric care.
 

Unmet scientific needs
Translational investigators. Despite increased funding for basic neuroscien­tific study and breathtaking discover­ies in animal molecular neurobiology, a trickle of findings has been applied to clinical medicine. This translational gap has many causes, including a short­age of translational neuroscientists (MD-PhD psychiatrists and neurolo­gists), insufficient long-term funding to develop such clinician-researchers, and complex regulatory oversight of human research.

Stalled progress in drug devel­opment. Development of novel-mechanism therapeutics for brain disorders is languishing. Some phar­maceutical manufacturers have aban­doned the development of drugs that act on the CNS in favor of less complex, more lucrative areas such as oncology and cardiology; others have reduced their investment in CNS products. Developing treatments for knotty disorders of the most com­plex structure in the known universe requires mammoth investment. Why are stakeholders bailing out on the greatest challenge for science and medicine for easier endeavors?

Discovering new genes for every dev­astating neuropsychiatric syndrome, such as schizophrenia, is cause for cel­ebration, but the champagne won’t flow until the coding of every gene is unscrambled so that specific biological interventions can be developed. The cost of the chase might be orders of mag­nitude greater than what is invested in research today. Conceptualizing new models of brain disorders is a critical part of scientific progress and an antidote to the inertia of perpetual group-think. Depression, for example, is being reconceptualized as a disorder of impaired neuroplasticity and neurotropic deficiency, rather than a shortage of serotonin and norepineph­rine. Rapid reversal of severe depres­sion to euthymia—in 1 or 2 hours—with IV ketamine shattered the dogma that depression takes weeks to lift, and is ushering in unprecedented new think­ing and models likely to revolutionize treatment of severe depression. We need such breakthroughs for other psychiat­ric brain disorders.  

Unmet professional and sociopolitical needs
Broadening of training. Psychiatrists have focused on the mind but insuf­ficiently attended to the biology of the brain. For psychiatry to rise to the next level as a medical specialty and brain discipline, training must incorporate more neurology than it does now. The converse is true in neurology.

Hospitalization not incarceration. It is unconscionable that people suffer­ing from a medical illness that impairs their judgment and behavior are locked up as criminals. Psychiatry must forcefully lobby so that the seriously mentally ill are treated in secure hospitals staffed by physi­cians, nurses, and mental health professionals.

That’s right: Bring back the asylum to address this unmet medical, political, and ethical need for psychiatric patients.^a A serious mental disorder must be accepted as a fault-free illness.

^aTo read more about this, I recommend my March 2008 editorial, “Bring back the asylums?,” at CurrentPsychiatry.com, and Dr. George Paulson’s excellent book, Closing the asylums: Causes and consequences of the deinstitutionalization movement (Jefferson, NC: McFarland & Co. Inc; 2012).

Full integration of psychiatry into the rest of medicine remains an unmet need, despite good progress. Because almost every medical illness can cause psychiatric symp­toms, DSM-5 mandates that general medical conditions be ruled out before a primary psychiatric diagnosis is made.

Along the same lines, most severely mentally ill persons suffer from medical and neurologic ailments before their first episode,⁵ and many die prematurely from cardiovas­cular causes that often are the result of unhealthy lifestyle; iatrogenic complications; and lack of primary care inter­ventions.⁶ Psychiatric patients must always receive stan­dard general medical evaluation and management, side by side with their psychiatric care.

Philanthropy for psychiatry
Philanthropic support of psychiatry is a salutary trend. Some unmet needs in psychiatry, however, require not only money but a change in attitude (such as eliminating the absurd and discriminatory stigma of mental illness), better training, and forceful political activism by all of us.

 Recent examples come quickly to mind:
   • $100 million from the Lieber family to fund the Lieber Institute for Brain Development at Johns Hopkins University
   • $300 million from Microsoft co-founder Paul G. Allen to create the Allen Institute for Brain Science
   • $650 million from Ted Stanley for the Stanley Center at the Broad Institute.
Such generosity is cause for celebra­tion by psychiatrists and their long-suffering patients who are disabled by a brain disorder. Private money supple­ments research funding by the National Institutes of Health and will bolster the war against mental illness,¹ which costs >$300 billion annually (Box,²page 12).

Although philanthropy will help, many needs in psychiatry are unmet, and not all can be addressed with money. Consider a number of areas of need.

Unmet clinical needs
Models of disease. Psychiatry is in desperate need of an objective, valid diagnostic system that transcends the DSM model of symptom clusters. The Research Domain Criteria³ repre­sents the effort to find an alternative. To achieve that goal, it’s necessary to identify biomarkers and establish their utility—a task that requires a huge amount of funding.

Therapeutics. Clinicians are hungry for innovative, safe pharmaceuticals and non-drug treatments that modify disease, not just alleviate symptoms. Obsessive-compulsive disorder always has lacked such therapies; so have dementia, schizophrenia, personality disorders, dissociative disorders, and sexual pathologies. In fact, >80% of DSM disorders do not have an FDA-approved, evidence-based treatment,⁴ and many available medications are only partially efficacious, poorly toler­ated, or unsafe.

There are more unmet needs in therapeutics:
   • Development of promising non-drug therapies, such as neuromodula­tion, proceeds slowly.
   • Research into neurobiological mechanisms of psychotherapy is in its infancy.
   • A foolproof method to monitor adherence does not exist, and countless patients relapse needlessly and deterio­rate functionally.
   • Effective, evidence-based rehabili­tation for serious psychiatric disorders is used narrowly and vastly underfunded.
   • Insurers continue to thumb their nose at laws that require parity for treating mental illness—thus impeding access to, delaying, or truncating psy­chiatric care.
 

Unmet scientific needs
Translational investigators. Despite increased funding for basic neuroscien­tific study and breathtaking discover­ies in animal molecular neurobiology, a trickle of findings has been applied to clinical medicine. This translational gap has many causes, including a short­age of translational neuroscientists (MD-PhD psychiatrists and neurolo­gists), insufficient long-term funding to develop such clinician-researchers, and complex regulatory oversight of human research.

Stalled progress in drug devel­opment. Development of novel-mechanism therapeutics for brain disorders is languishing. Some phar­maceutical manufacturers have aban­doned the development of drugs that act on the CNS in favor of less complex, more lucrative areas such as oncology and cardiology; others have reduced their investment in CNS products. Developing treatments for knotty disorders of the most com­plex structure in the known universe requires mammoth investment. Why are stakeholders bailing out on the greatest challenge for science and medicine for easier endeavors?

Discovering new genes for every dev­astating neuropsychiatric syndrome, such as schizophrenia, is cause for cel­ebration, but the champagne won’t flow until the coding of every gene is unscrambled so that specific biological interventions can be developed. The cost of the chase might be orders of mag­nitude greater than what is invested in research today. Conceptualizing new models of brain disorders is a critical part of scientific progress and an antidote to the inertia of perpetual group-think. Depression, for example, is being reconceptualized as a disorder of impaired neuroplasticity and neurotropic deficiency, rather than a shortage of serotonin and norepineph­rine. Rapid reversal of severe depres­sion to euthymia—in 1 or 2 hours—with IV ketamine shattered the dogma that depression takes weeks to lift, and is ushering in unprecedented new think­ing and models likely to revolutionize treatment of severe depression. We need such breakthroughs for other psychiat­ric brain disorders.  

Unmet professional and sociopolitical needs
Broadening of training. Psychiatrists have focused on the mind but insuf­ficiently attended to the biology of the brain. For psychiatry to rise to the next level as a medical specialty and brain discipline, training must incorporate more neurology than it does now. The converse is true in neurology.

Hospitalization not incarceration. It is unconscionable that people suffer­ing from a medical illness that impairs their judgment and behavior are locked up as criminals. Psychiatry must forcefully lobby so that the seriously mentally ill are treated in secure hospitals staffed by physi­cians, nurses, and mental health professionals.

That’s right: Bring back the asylum to address this unmet medical, political, and ethical need for psychiatric patients.^a A serious mental disorder must be accepted as a fault-free illness.

^aTo read more about this, I recommend my March 2008 editorial, “Bring back the asylums?,” at CurrentPsychiatry.com, and Dr. George Paulson’s excellent book, Closing the asylums: Causes and consequences of the deinstitutionalization movement (Jefferson, NC: McFarland & Co. Inc; 2012).

Full integration of psychiatry into the rest of medicine remains an unmet need, despite good progress. Because almost every medical illness can cause psychiatric symp­toms, DSM-5 mandates that general medical conditions be ruled out before a primary psychiatric diagnosis is made.

Along the same lines, most severely mentally ill persons suffer from medical and neurologic ailments before their first episode,⁵ and many die prematurely from cardiovas­cular causes that often are the result of unhealthy lifestyle; iatrogenic complications; and lack of primary care inter­ventions.⁶ Psychiatric patients must always receive stan­dard general medical evaluation and management, side by side with their psychiatric care.

Philanthropy for psychiatry
Philanthropic support of psychiatry is a salutary trend. Some unmet needs in psychiatry, however, require not only money but a change in attitude (such as eliminating the absurd and discriminatory stigma of mental illness), better training, and forceful political activism by all of us.

Peer review is the filter that determines what is published in the scientific literature and what is not allowed to see the light of day. It has been considered "the gatekeeper of science." In modern times, peer review has consisted of a journal editor sending a submitted article to a limited number of experts in the field who then judge its worth for publication. Many specialists see reviewing manuscripts as a service to their profession, put considerable effort into their analysis, and provide extensive comments on revisions needed to strengthen papers.

However, the value of this venerable process as it is presently constituted has been questioned by numerous critics. Because manuscripts are reviewed by a limited number of often rival scientists in a highly specialized field, the practice is prone to bias. Innovation may be stifled when reviewers reject outlier concepts that may be correct but that do not fit into the mainstream of thought. Critiques are often superficial as they are performed by otherwise busy individuals who receive no compensation for their efforts. Finally, journal editors are given undue power in the process. Not only do they make the final decision to publish or reject a manuscript, they are also responsible for selecting reviewers and are then free to ignore or accept their recommendations.

These criticisms of this time-honored system have led to a strong impetus for change. Coincident with the motivation for modifying this essential component of the publication process have been technological advancements that are facilitating new approaches. The Internet has provided a mechanism for making peer review a more open, inclusive process with any member of the scientific community who so desires having the opportunity to contribute to the evaluation of published work. A recent incident highlights how uninvited, but valuable, input from the wider scientific community can rapidly and effectively improve the accuracy of the literature.

On July 2, 2014, National Public Radio’s Morning Edition broadcast "Easy method for making stem cells was too good to be true" and a New York Times headline proclaimed "Stem cell research papers are retracted." In January 2014, Haruko Obokata of the RIKEN Centre for Developmental Biology in Japan published an innovative and considerably simpler method of producing stem cells than extracting them from embryos or making them from skin cells in a complicated and prolonged process (Nature 2014;505: 641-7). At the time of publication, the work was viewed by many to be potentially Nobel Prize-worthy research—that is, until the stem cell research community chimed in with its extensive and detailed post-publication peer review.

A number of research groups questioned Obokata’s conclusions. Some even attempted to replicate the experiments, but with no success. Soon the critics’ findings and opinions appeared on a variety of websites and blogs, including the Nature website. The RIKEN Centre took notice and appointed a committee to investigate the research. The committee found that Obokata had manipulated her data on at least two occasions and concluded that she had participated in research misconduct. Pressure mounted, which led to the recent voluntary retraction of the article by its authors.

This case represents an extreme outcome resulting from a failure of pre-publication vetting followed by a successful post-hoc peer review. But it demonstrates how the emerging and more comprehensive means of evaluating published research is rapidly working its way into the fabric of how science and the reporting of it operate. It would be ideal if this extensive vetting of potentially important research could be done prior to rather than after its release to the general public. Physics academicians have accomplished this by posting their research papers as pre-prints on-line for their colleagues to evaluate. Only after a successful conclusion of this process is a work deemed acceptable for entry into the physics literature. Submission of biomedical research to a similar process has a significant downside in that new, possibly harmful therapies, not yet peer-reviewed, could be adopted by practitioners and/or patients before their time. However, some modification of it will likely evolve and lead to a more accurate assessment of submitted work than the present process allows.

How publications are valued is also being modified thanks to the omnibus means of rapid communication allowed by an ever-expanding Internet. Bibliometrics, most notably the number of times an article is subsequently cited in print, has been the mainstay in determining the value of individual articles. The journal impact factor, which has historically been the main measure of a journal\'s standing compared to that of others in its field, is derived from the aggregate of citations for all articles over a period of time. With the advent of the Internet, a new set of alternative metrics (altmetrics) is now contributing to the evaluation of published work. While print citations take years to accumulate, article downloads, mentions on Facebook, number of tweets on Twitter, and numerous other altmetrics have the considerable advantage of immediacy and can be logged by any reader, not only those authors who decide to subsequently cite certain publications. Although these new metrics are unlikely to replace traditional citations in assigning value to individual articles, along with them, they will be helpful in determining what must be read to maintain currency in one’s specialty.

So, readers of the surgical literature feel your newly found power and exert it. You along with your colleagues around the globe can, and in fact have an obligation to, play a role in determining what is worth reading from an ever-expanding volume of new information. Many eyes will almost certainly be better than relying solely on the opinions of a chosen few.

Dr. Rikkers is Editor in Chief of ACS Surgery News.

Peer review is the filter that determines what is published in the scientific literature and what is not allowed to see the light of day. It has been considered "the gatekeeper of science." In modern times, peer review has consisted of a journal editor sending a submitted article to a limited number of experts in the field who then judge its worth for publication. Many specialists see reviewing manuscripts as a service to their profession, put considerable effort into their analysis, and provide extensive comments on revisions needed to strengthen papers.

However, the value of this venerable process as it is presently constituted has been questioned by numerous critics. Because manuscripts are reviewed by a limited number of often rival scientists in a highly specialized field, the practice is prone to bias. Innovation may be stifled when reviewers reject outlier concepts that may be correct but that do not fit into the mainstream of thought. Critiques are often superficial as they are performed by otherwise busy individuals who receive no compensation for their efforts. Finally, journal editors are given undue power in the process. Not only do they make the final decision to publish or reject a manuscript, they are also responsible for selecting reviewers and are then free to ignore or accept their recommendations.

These criticisms of this time-honored system have led to a strong impetus for change. Coincident with the motivation for modifying this essential component of the publication process have been technological advancements that are facilitating new approaches. The Internet has provided a mechanism for making peer review a more open, inclusive process with any member of the scientific community who so desires having the opportunity to contribute to the evaluation of published work. A recent incident highlights how uninvited, but valuable, input from the wider scientific community can rapidly and effectively improve the accuracy of the literature.

On July 2, 2014, National Public Radio’s Morning Edition broadcast "Easy method for making stem cells was too good to be true" and a New York Times headline proclaimed "Stem cell research papers are retracted." In January 2014, Haruko Obokata of the RIKEN Centre for Developmental Biology in Japan published an innovative and considerably simpler method of producing stem cells than extracting them from embryos or making them from skin cells in a complicated and prolonged process (Nature 2014;505: 641-7). At the time of publication, the work was viewed by many to be potentially Nobel Prize-worthy research—that is, until the stem cell research community chimed in with its extensive and detailed post-publication peer review.

A number of research groups questioned Obokata’s conclusions. Some even attempted to replicate the experiments, but with no success. Soon the critics’ findings and opinions appeared on a variety of websites and blogs, including the Nature website. The RIKEN Centre took notice and appointed a committee to investigate the research. The committee found that Obokata had manipulated her data on at least two occasions and concluded that she had participated in research misconduct. Pressure mounted, which led to the recent voluntary retraction of the article by its authors.

This case represents an extreme outcome resulting from a failure of pre-publication vetting followed by a successful post-hoc peer review. But it demonstrates how the emerging and more comprehensive means of evaluating published research is rapidly working its way into the fabric of how science and the reporting of it operate. It would be ideal if this extensive vetting of potentially important research could be done prior to rather than after its release to the general public. Physics academicians have accomplished this by posting their research papers as pre-prints on-line for their colleagues to evaluate. Only after a successful conclusion of this process is a work deemed acceptable for entry into the physics literature. Submission of biomedical research to a similar process has a significant downside in that new, possibly harmful therapies, not yet peer-reviewed, could be adopted by practitioners and/or patients before their time. However, some modification of it will likely evolve and lead to a more accurate assessment of submitted work than the present process allows.

How publications are valued is also being modified thanks to the omnibus means of rapid communication allowed by an ever-expanding Internet. Bibliometrics, most notably the number of times an article is subsequently cited in print, has been the mainstay in determining the value of individual articles. The journal impact factor, which has historically been the main measure of a journal\'s standing compared to that of others in its field, is derived from the aggregate of citations for all articles over a period of time. With the advent of the Internet, a new set of alternative metrics (altmetrics) is now contributing to the evaluation of published work. While print citations take years to accumulate, article downloads, mentions on Facebook, number of tweets on Twitter, and numerous other altmetrics have the considerable advantage of immediacy and can be logged by any reader, not only those authors who decide to subsequently cite certain publications. Although these new metrics are unlikely to replace traditional citations in assigning value to individual articles, along with them, they will be helpful in determining what must be read to maintain currency in one’s specialty.

So, readers of the surgical literature feel your newly found power and exert it. You along with your colleagues around the globe can, and in fact have an obligation to, play a role in determining what is worth reading from an ever-expanding volume of new information. Many eyes will almost certainly be better than relying solely on the opinions of a chosen few.

Dr. Rikkers is Editor in Chief of ACS Surgery News.

Peer review is the filter that determines what is published in the scientific literature and what is not allowed to see the light of day. It has been considered "the gatekeeper of science." In modern times, peer review has consisted of a journal editor sending a submitted article to a limited number of experts in the field who then judge its worth for publication. Many specialists see reviewing manuscripts as a service to their profession, put considerable effort into their analysis, and provide extensive comments on revisions needed to strengthen papers.

However, the value of this venerable process as it is presently constituted has been questioned by numerous critics. Because manuscripts are reviewed by a limited number of often rival scientists in a highly specialized field, the practice is prone to bias. Innovation may be stifled when reviewers reject outlier concepts that may be correct but that do not fit into the mainstream of thought. Critiques are often superficial as they are performed by otherwise busy individuals who receive no compensation for their efforts. Finally, journal editors are given undue power in the process. Not only do they make the final decision to publish or reject a manuscript, they are also responsible for selecting reviewers and are then free to ignore or accept their recommendations.

These criticisms of this time-honored system have led to a strong impetus for change. Coincident with the motivation for modifying this essential component of the publication process have been technological advancements that are facilitating new approaches. The Internet has provided a mechanism for making peer review a more open, inclusive process with any member of the scientific community who so desires having the opportunity to contribute to the evaluation of published work. A recent incident highlights how uninvited, but valuable, input from the wider scientific community can rapidly and effectively improve the accuracy of the literature.

On July 2, 2014, National Public Radio’s Morning Edition broadcast "Easy method for making stem cells was too good to be true" and a New York Times headline proclaimed "Stem cell research papers are retracted." In January 2014, Haruko Obokata of the RIKEN Centre for Developmental Biology in Japan published an innovative and considerably simpler method of producing stem cells than extracting them from embryos or making them from skin cells in a complicated and prolonged process (Nature 2014;505: 641-7). At the time of publication, the work was viewed by many to be potentially Nobel Prize-worthy research—that is, until the stem cell research community chimed in with its extensive and detailed post-publication peer review.

A number of research groups questioned Obokata’s conclusions. Some even attempted to replicate the experiments, but with no success. Soon the critics’ findings and opinions appeared on a variety of websites and blogs, including the Nature website. The RIKEN Centre took notice and appointed a committee to investigate the research. The committee found that Obokata had manipulated her data on at least two occasions and concluded that she had participated in research misconduct. Pressure mounted, which led to the recent voluntary retraction of the article by its authors.

This case represents an extreme outcome resulting from a failure of pre-publication vetting followed by a successful post-hoc peer review. But it demonstrates how the emerging and more comprehensive means of evaluating published research is rapidly working its way into the fabric of how science and the reporting of it operate. It would be ideal if this extensive vetting of potentially important research could be done prior to rather than after its release to the general public. Physics academicians have accomplished this by posting their research papers as pre-prints on-line for their colleagues to evaluate. Only after a successful conclusion of this process is a work deemed acceptable for entry into the physics literature. Submission of biomedical research to a similar process has a significant downside in that new, possibly harmful therapies, not yet peer-reviewed, could be adopted by practitioners and/or patients before their time. However, some modification of it will likely evolve and lead to a more accurate assessment of submitted work than the present process allows.

How publications are valued is also being modified thanks to the omnibus means of rapid communication allowed by an ever-expanding Internet. Bibliometrics, most notably the number of times an article is subsequently cited in print, has been the mainstay in determining the value of individual articles. The journal impact factor, which has historically been the main measure of a journal\'s standing compared to that of others in its field, is derived from the aggregate of citations for all articles over a period of time. With the advent of the Internet, a new set of alternative metrics (altmetrics) is now contributing to the evaluation of published work. While print citations take years to accumulate, article downloads, mentions on Facebook, number of tweets on Twitter, and numerous other altmetrics have the considerable advantage of immediacy and can be logged by any reader, not only those authors who decide to subsequently cite certain publications. Although these new metrics are unlikely to replace traditional citations in assigning value to individual articles, along with them, they will be helpful in determining what must be read to maintain currency in one’s specialty.

So, readers of the surgical literature feel your newly found power and exert it. You along with your colleagues around the globe can, and in fact have an obligation to, play a role in determining what is worth reading from an ever-expanding volume of new information. Many eyes will almost certainly be better than relying solely on the opinions of a chosen few.

Dr. Rikkers is Editor in Chief of ACS Surgery News.