User login
VIDEO: When to consider systemic exposure in patients with contact dermatitis
SAN FRANCISCO – When patients with contact dermatitis who have had a patch test positive to an allergen and are not improving despite avoiding cutaneous exposure, it’s important to consider the possibility of systemic exposure, according to Nina Botto, MD, of the department of dermatology, at the University of California, San Francisco.
“Theoretically, any allergen can cause a systemic contact dermatitis. The ones that we think about and encounter more frequently are earth metals like nickel and balsam of Peru, which is a component of many fragrances and flavorings,” she said in a video interview at the annual meeting of the Pacific Dermatologic Association.
In the interview, Dr. Botto, who is codirector of the Occupational and Contact Dermatitis Clinic at UCSF, provides recommendations on how to approach patients with systemic contact dermatitis, including dietary avoidance. But following these diets can be challenging. She recommends starting with avoiding cutaneous exposure to the suspected allergen. For patients not improving after two months of avoidance, “it may be reasonable to consider a diet,”she advised.
Dr. Botto cited the following two publications with tables and guidelines for diets as helpful resources for patients: Dermatitis. 2013 Jul-Aug;24(4):153-60 (for a diet low in balsam of Peru); and Dermatitis. 2013 Jul-Aug; 24(4):190-5 (for a diet low in nickel).
Another useful resource is the American Contact Dermatitis Society website, which produces a customized list of safe products for patients after they enter the allergen into the system.
Dr. Botto had no disclosures.
SAN FRANCISCO – When patients with contact dermatitis who have had a patch test positive to an allergen and are not improving despite avoiding cutaneous exposure, it’s important to consider the possibility of systemic exposure, according to Nina Botto, MD, of the department of dermatology, at the University of California, San Francisco.
“Theoretically, any allergen can cause a systemic contact dermatitis. The ones that we think about and encounter more frequently are earth metals like nickel and balsam of Peru, which is a component of many fragrances and flavorings,” she said in a video interview at the annual meeting of the Pacific Dermatologic Association.
In the interview, Dr. Botto, who is codirector of the Occupational and Contact Dermatitis Clinic at UCSF, provides recommendations on how to approach patients with systemic contact dermatitis, including dietary avoidance. But following these diets can be challenging. She recommends starting with avoiding cutaneous exposure to the suspected allergen. For patients not improving after two months of avoidance, “it may be reasonable to consider a diet,”she advised.
Dr. Botto cited the following two publications with tables and guidelines for diets as helpful resources for patients: Dermatitis. 2013 Jul-Aug;24(4):153-60 (for a diet low in balsam of Peru); and Dermatitis. 2013 Jul-Aug; 24(4):190-5 (for a diet low in nickel).
Another useful resource is the American Contact Dermatitis Society website, which produces a customized list of safe products for patients after they enter the allergen into the system.
Dr. Botto had no disclosures.
SAN FRANCISCO – When patients with contact dermatitis who have had a patch test positive to an allergen and are not improving despite avoiding cutaneous exposure, it’s important to consider the possibility of systemic exposure, according to Nina Botto, MD, of the department of dermatology, at the University of California, San Francisco.
“Theoretically, any allergen can cause a systemic contact dermatitis. The ones that we think about and encounter more frequently are earth metals like nickel and balsam of Peru, which is a component of many fragrances and flavorings,” she said in a video interview at the annual meeting of the Pacific Dermatologic Association.
In the interview, Dr. Botto, who is codirector of the Occupational and Contact Dermatitis Clinic at UCSF, provides recommendations on how to approach patients with systemic contact dermatitis, including dietary avoidance. But following these diets can be challenging. She recommends starting with avoiding cutaneous exposure to the suspected allergen. For patients not improving after two months of avoidance, “it may be reasonable to consider a diet,”she advised.
Dr. Botto cited the following two publications with tables and guidelines for diets as helpful resources for patients: Dermatitis. 2013 Jul-Aug;24(4):153-60 (for a diet low in balsam of Peru); and Dermatitis. 2013 Jul-Aug; 24(4):190-5 (for a diet low in nickel).
Another useful resource is the American Contact Dermatitis Society website, which produces a customized list of safe products for patients after they enter the allergen into the system.
Dr. Botto had no disclosures.
AT THE ANNUAL MEETING OF THE PACIFIC DERMATOLOGIC ASSOCIATION
Personal models of illness
Cognitive reappraisal is a top-down emotional regulation skill associated with resilience – the capacity to adaptively overcome adversity.
A person with this ability, also known as cognitive flexibility or reframing, monitors negative thoughts or situations and intentionally changes the way he or she views them. This reframing can involve retaining a positive outlook, trying to create meaning from a difficult situation, or finding ways to exert control over specific circumstances (Front Behav Neurosci. 2013 Feb 15;7:10). Some individuals cope with their mental illness by creating their own models of their illness (Achieving Cultural Competency: A Case-Based Approach to Training Health Professionals, Hoboken, N.J.: Wiley-Blackwell Publishing, 2009).
Creating a model of illness is a type of reframing to help explain what’s happening to an individual by placing the locus of control either inside our ourselves, adjacent, or far away and uncontrollable. Depending on the model, there might be choice that results in action taken to face the mental illness. Sometimes, there is surrender, either to the illness or the treatment.
In one of my weekly phone conversations with my mother in Texas, she told me that Ricardo, the husband of close family friend, had sunk into a deep depression to the point where he could no longer leave the house for work. Ricardo is an unauthorized immigrant, having crossed the border from Mexico into Texas 17 years ago with his wife and 2-year-old son. He lives a story common to many families in Texas: two undocumented parents working in local businesses, one child with a DACA (Deferred Action for Childhood Arrivals) permit and their second child born in the United States, all assimilated into American culture. With Ricardo’s descent into personal darkness, their American dream was fraying. Family and neighbors were gossiping about what could have happened – had Ricardo gotten into trouble with drugs and alcohol? Perhaps his wife had bewitched him; perhaps this was a godly test that only prayer could overcome.
I called his wife to see if I could offer her help navigating the local mental health system. She recounted a story of severe depression, and, most worryingly, a recent self-aborted hanging. Because of cultural beliefs, stigma of mental illness, and his immigration status, Ricardo would not call the local mental health authority for assessment and treatment.
So I made a trip to Texas to see Ricardo as a friend and psychiatrist, despite not quite knowing how to navigate the moral and legal ambiguity of this situation. I could at least offer a comprehensive psychiatric assessment and provide him with some understanding of his illness to help guide his decisions. My conversation with Ricardo found a man helpless and confused as to how and why he lost all drive, energy, and desire to live. We spoke about his and my understanding of depression. I tried to help Ricardo by shifting his perception of his illness from fear of an unknown specter to the idea that his current state of mind could be attributed to a treatable brain disease.
The trip to Texas was also an opportunity to see my older brother’s newly purchased home. This was a serious achievement, following 2 years where he had lived with our parents to save money for a down payment. He had initially been forced to live at home because of legal consequences related to his struggles with addiction and depression, both backdrops to his life as a devoted math teacher. In the car ride to his new house, he told me about his twice weekly, state-mandated addiction counseling group sessions. He has benefited from the instruction to fill his sober time with positive forces, telling me that he could not have bought his house and started working a second, part-time job without his sobriety.
Yet, he disagrees when the counselor tells his class that addiction is a disease that compromises his free will, and compared to his peers, he has less control over his mind when exposed to alcohol. He says it’s a mixed message – be proactive and take control over a new sober life, but be careful, your brain is too weak and diseased to ever have a healthy relationship with alcohol.
I was affected when he told me that he was afraid to ever drink again; that he cannot trust himself. He is afraid to fail and lose the life he is building for himself. Now he lives in conflict between two models of his illness: the determinism of addiction versus free will to overcome his abusive relationship with alcohol. To overcome this conflict, he has surrendered himself to a self-designed treatment program, working two jobs to fill his days and nights, and guarantee fatigue and sleep by the end of the day. No time to think or drink; just time to work and sleep.
The night before I flew to Texas, I had an overnight call in the emergency department. I encountered a young woman whom I’ll call Laura. She was in her mid 30s with HIV/AIDS with a CD4 count of less than 30, and had not taken medication for her HIV in years. Mostly, she lived in and out of hospitals, both psychiatric and medical wards. I was called to assess her suicidal ideation with a stated plan to slip and fall in her shower in order to hit her head and die. She was cachectic, tired, withdrawn, disheveled, buried under a heap of blankets.
Our interview was an awkward dance around why she could not and would not take medications for either her HIV/AIDS or posttraumatic stress disorder and depression. No money, no transport, intermittently homeless, no desire to live nor a future to live for.
In our conversation, I searched for reasons for Laura to live, and she countered with reasons why it was easier to die. It was a level of apathy I have encountered with other severely ill AIDS patients – the brain is so immunocompromised and muddled, the body so tired, the spirit so damaged. Her three children living with a sister had lost their potency as motivation to desire recovery of her physical and mental health. I doubted the active nature of her suicidality, and her apathy and physical deterioration made me question her ability to act on a plan. Nonetheless, I admitted Laura to the psychiatric unit for safety. Two weeks later, I learned she had died in hospital of AIDS-related sepsis. She had 10 days of treatment on the psychiatric unit with no movement in her depressive symptoms and apathy. Eventually, she physically crashed and was sent to the ICU, where she died.
As psychiatrists, we create our own models of what mental illness and treatments are, and we apply some version of the model to each patient. With the concepts of cultural psychiatry and therapeutic alliance, we learn to work within our patients’ models of disease to enhance their response to treatment. My initial reaction to Laura’s death was surprise, fear, and guilt that maybe I had missed a pressing medical issue that contributed to her death. Then I just felt resigned to her death, probably as she did. She told me in the emergency department she was set on dying, and her actions, well before this last admission, had indirectly ensured an early death. We psychiatrists feel failure when we are unable to prevent a suicide. What was Laura’s death: Was it a suicide by apathy that a psychiatrist could have prevented? Or just an expected complication of an untreated chronic illness? Many residents had done their job by admitting her again and again for either psychiatric or medical illness. Yet none of us could understand why she refused to treat her HIV/AIDS, and none of us was able to address the model she had created of her illness. Her model, that her HIV was a death sentence, was anathema to our training.
Because of that dissonance, it was difficult to understand her narrative, let alone find a way to help her reframe it. Her model of illness was misunderstood by a wide swathe of medical professionals, and together we were unable to tailor a treatment to her needs. Since, I’ve worked to reframe her death in my own mind as a way to better understand models of illness, learning from her as well as from my brother and my friend Ricardo. Both the patient’s and physician’s conceptualization of illness affects prognosis of whether to surrender to a treatment or the illness. As psychiatrists, we must strive to understand all models of illness, so we can plan and implement our treatment intervention accordingly.
I asked my friend from home and my brother for their permission and sent them this piece to make sure they approved. I changed certain details about Ricardo’s story to protect his identity. With my brother, there was no way to change his identity, but he was touched and happy to be included. I also changed key facts about the patient I called Laura.
Dr. Posada is a third-year resident in the psychiatry and behavioral sciences department at George Washington University, Washington. She completed a bachelor’s degree at George Washington University. For 2 years after her undergraduate education, she worked at the National Institutes of Allergy and Infectious Diseases studying HIV pathogenesis. Dr. Posada completed her medical degree at the University of Texas Medical Branch in Galveston. Her interests include public psychiatry, health care policy, and health disparities, and she plans to pursue a fellowship in consult liaison psychiatry.
Cognitive reappraisal is a top-down emotional regulation skill associated with resilience – the capacity to adaptively overcome adversity.
A person with this ability, also known as cognitive flexibility or reframing, monitors negative thoughts or situations and intentionally changes the way he or she views them. This reframing can involve retaining a positive outlook, trying to create meaning from a difficult situation, or finding ways to exert control over specific circumstances (Front Behav Neurosci. 2013 Feb 15;7:10). Some individuals cope with their mental illness by creating their own models of their illness (Achieving Cultural Competency: A Case-Based Approach to Training Health Professionals, Hoboken, N.J.: Wiley-Blackwell Publishing, 2009).
Creating a model of illness is a type of reframing to help explain what’s happening to an individual by placing the locus of control either inside our ourselves, adjacent, or far away and uncontrollable. Depending on the model, there might be choice that results in action taken to face the mental illness. Sometimes, there is surrender, either to the illness or the treatment.
In one of my weekly phone conversations with my mother in Texas, she told me that Ricardo, the husband of close family friend, had sunk into a deep depression to the point where he could no longer leave the house for work. Ricardo is an unauthorized immigrant, having crossed the border from Mexico into Texas 17 years ago with his wife and 2-year-old son. He lives a story common to many families in Texas: two undocumented parents working in local businesses, one child with a DACA (Deferred Action for Childhood Arrivals) permit and their second child born in the United States, all assimilated into American culture. With Ricardo’s descent into personal darkness, their American dream was fraying. Family and neighbors were gossiping about what could have happened – had Ricardo gotten into trouble with drugs and alcohol? Perhaps his wife had bewitched him; perhaps this was a godly test that only prayer could overcome.
I called his wife to see if I could offer her help navigating the local mental health system. She recounted a story of severe depression, and, most worryingly, a recent self-aborted hanging. Because of cultural beliefs, stigma of mental illness, and his immigration status, Ricardo would not call the local mental health authority for assessment and treatment.
So I made a trip to Texas to see Ricardo as a friend and psychiatrist, despite not quite knowing how to navigate the moral and legal ambiguity of this situation. I could at least offer a comprehensive psychiatric assessment and provide him with some understanding of his illness to help guide his decisions. My conversation with Ricardo found a man helpless and confused as to how and why he lost all drive, energy, and desire to live. We spoke about his and my understanding of depression. I tried to help Ricardo by shifting his perception of his illness from fear of an unknown specter to the idea that his current state of mind could be attributed to a treatable brain disease.
The trip to Texas was also an opportunity to see my older brother’s newly purchased home. This was a serious achievement, following 2 years where he had lived with our parents to save money for a down payment. He had initially been forced to live at home because of legal consequences related to his struggles with addiction and depression, both backdrops to his life as a devoted math teacher. In the car ride to his new house, he told me about his twice weekly, state-mandated addiction counseling group sessions. He has benefited from the instruction to fill his sober time with positive forces, telling me that he could not have bought his house and started working a second, part-time job without his sobriety.
Yet, he disagrees when the counselor tells his class that addiction is a disease that compromises his free will, and compared to his peers, he has less control over his mind when exposed to alcohol. He says it’s a mixed message – be proactive and take control over a new sober life, but be careful, your brain is too weak and diseased to ever have a healthy relationship with alcohol.
I was affected when he told me that he was afraid to ever drink again; that he cannot trust himself. He is afraid to fail and lose the life he is building for himself. Now he lives in conflict between two models of his illness: the determinism of addiction versus free will to overcome his abusive relationship with alcohol. To overcome this conflict, he has surrendered himself to a self-designed treatment program, working two jobs to fill his days and nights, and guarantee fatigue and sleep by the end of the day. No time to think or drink; just time to work and sleep.
The night before I flew to Texas, I had an overnight call in the emergency department. I encountered a young woman whom I’ll call Laura. She was in her mid 30s with HIV/AIDS with a CD4 count of less than 30, and had not taken medication for her HIV in years. Mostly, she lived in and out of hospitals, both psychiatric and medical wards. I was called to assess her suicidal ideation with a stated plan to slip and fall in her shower in order to hit her head and die. She was cachectic, tired, withdrawn, disheveled, buried under a heap of blankets.
Our interview was an awkward dance around why she could not and would not take medications for either her HIV/AIDS or posttraumatic stress disorder and depression. No money, no transport, intermittently homeless, no desire to live nor a future to live for.
In our conversation, I searched for reasons for Laura to live, and she countered with reasons why it was easier to die. It was a level of apathy I have encountered with other severely ill AIDS patients – the brain is so immunocompromised and muddled, the body so tired, the spirit so damaged. Her three children living with a sister had lost their potency as motivation to desire recovery of her physical and mental health. I doubted the active nature of her suicidality, and her apathy and physical deterioration made me question her ability to act on a plan. Nonetheless, I admitted Laura to the psychiatric unit for safety. Two weeks later, I learned she had died in hospital of AIDS-related sepsis. She had 10 days of treatment on the psychiatric unit with no movement in her depressive symptoms and apathy. Eventually, she physically crashed and was sent to the ICU, where she died.
As psychiatrists, we create our own models of what mental illness and treatments are, and we apply some version of the model to each patient. With the concepts of cultural psychiatry and therapeutic alliance, we learn to work within our patients’ models of disease to enhance their response to treatment. My initial reaction to Laura’s death was surprise, fear, and guilt that maybe I had missed a pressing medical issue that contributed to her death. Then I just felt resigned to her death, probably as she did. She told me in the emergency department she was set on dying, and her actions, well before this last admission, had indirectly ensured an early death. We psychiatrists feel failure when we are unable to prevent a suicide. What was Laura’s death: Was it a suicide by apathy that a psychiatrist could have prevented? Or just an expected complication of an untreated chronic illness? Many residents had done their job by admitting her again and again for either psychiatric or medical illness. Yet none of us could understand why she refused to treat her HIV/AIDS, and none of us was able to address the model she had created of her illness. Her model, that her HIV was a death sentence, was anathema to our training.
Because of that dissonance, it was difficult to understand her narrative, let alone find a way to help her reframe it. Her model of illness was misunderstood by a wide swathe of medical professionals, and together we were unable to tailor a treatment to her needs. Since, I’ve worked to reframe her death in my own mind as a way to better understand models of illness, learning from her as well as from my brother and my friend Ricardo. Both the patient’s and physician’s conceptualization of illness affects prognosis of whether to surrender to a treatment or the illness. As psychiatrists, we must strive to understand all models of illness, so we can plan and implement our treatment intervention accordingly.
I asked my friend from home and my brother for their permission and sent them this piece to make sure they approved. I changed certain details about Ricardo’s story to protect his identity. With my brother, there was no way to change his identity, but he was touched and happy to be included. I also changed key facts about the patient I called Laura.
Dr. Posada is a third-year resident in the psychiatry and behavioral sciences department at George Washington University, Washington. She completed a bachelor’s degree at George Washington University. For 2 years after her undergraduate education, she worked at the National Institutes of Allergy and Infectious Diseases studying HIV pathogenesis. Dr. Posada completed her medical degree at the University of Texas Medical Branch in Galveston. Her interests include public psychiatry, health care policy, and health disparities, and she plans to pursue a fellowship in consult liaison psychiatry.
Cognitive reappraisal is a top-down emotional regulation skill associated with resilience – the capacity to adaptively overcome adversity.
A person with this ability, also known as cognitive flexibility or reframing, monitors negative thoughts or situations and intentionally changes the way he or she views them. This reframing can involve retaining a positive outlook, trying to create meaning from a difficult situation, or finding ways to exert control over specific circumstances (Front Behav Neurosci. 2013 Feb 15;7:10). Some individuals cope with their mental illness by creating their own models of their illness (Achieving Cultural Competency: A Case-Based Approach to Training Health Professionals, Hoboken, N.J.: Wiley-Blackwell Publishing, 2009).
Creating a model of illness is a type of reframing to help explain what’s happening to an individual by placing the locus of control either inside our ourselves, adjacent, or far away and uncontrollable. Depending on the model, there might be choice that results in action taken to face the mental illness. Sometimes, there is surrender, either to the illness or the treatment.
In one of my weekly phone conversations with my mother in Texas, she told me that Ricardo, the husband of close family friend, had sunk into a deep depression to the point where he could no longer leave the house for work. Ricardo is an unauthorized immigrant, having crossed the border from Mexico into Texas 17 years ago with his wife and 2-year-old son. He lives a story common to many families in Texas: two undocumented parents working in local businesses, one child with a DACA (Deferred Action for Childhood Arrivals) permit and their second child born in the United States, all assimilated into American culture. With Ricardo’s descent into personal darkness, their American dream was fraying. Family and neighbors were gossiping about what could have happened – had Ricardo gotten into trouble with drugs and alcohol? Perhaps his wife had bewitched him; perhaps this was a godly test that only prayer could overcome.
I called his wife to see if I could offer her help navigating the local mental health system. She recounted a story of severe depression, and, most worryingly, a recent self-aborted hanging. Because of cultural beliefs, stigma of mental illness, and his immigration status, Ricardo would not call the local mental health authority for assessment and treatment.
So I made a trip to Texas to see Ricardo as a friend and psychiatrist, despite not quite knowing how to navigate the moral and legal ambiguity of this situation. I could at least offer a comprehensive psychiatric assessment and provide him with some understanding of his illness to help guide his decisions. My conversation with Ricardo found a man helpless and confused as to how and why he lost all drive, energy, and desire to live. We spoke about his and my understanding of depression. I tried to help Ricardo by shifting his perception of his illness from fear of an unknown specter to the idea that his current state of mind could be attributed to a treatable brain disease.
The trip to Texas was also an opportunity to see my older brother’s newly purchased home. This was a serious achievement, following 2 years where he had lived with our parents to save money for a down payment. He had initially been forced to live at home because of legal consequences related to his struggles with addiction and depression, both backdrops to his life as a devoted math teacher. In the car ride to his new house, he told me about his twice weekly, state-mandated addiction counseling group sessions. He has benefited from the instruction to fill his sober time with positive forces, telling me that he could not have bought his house and started working a second, part-time job without his sobriety.
Yet, he disagrees when the counselor tells his class that addiction is a disease that compromises his free will, and compared to his peers, he has less control over his mind when exposed to alcohol. He says it’s a mixed message – be proactive and take control over a new sober life, but be careful, your brain is too weak and diseased to ever have a healthy relationship with alcohol.
I was affected when he told me that he was afraid to ever drink again; that he cannot trust himself. He is afraid to fail and lose the life he is building for himself. Now he lives in conflict between two models of his illness: the determinism of addiction versus free will to overcome his abusive relationship with alcohol. To overcome this conflict, he has surrendered himself to a self-designed treatment program, working two jobs to fill his days and nights, and guarantee fatigue and sleep by the end of the day. No time to think or drink; just time to work and sleep.
The night before I flew to Texas, I had an overnight call in the emergency department. I encountered a young woman whom I’ll call Laura. She was in her mid 30s with HIV/AIDS with a CD4 count of less than 30, and had not taken medication for her HIV in years. Mostly, she lived in and out of hospitals, both psychiatric and medical wards. I was called to assess her suicidal ideation with a stated plan to slip and fall in her shower in order to hit her head and die. She was cachectic, tired, withdrawn, disheveled, buried under a heap of blankets.
Our interview was an awkward dance around why she could not and would not take medications for either her HIV/AIDS or posttraumatic stress disorder and depression. No money, no transport, intermittently homeless, no desire to live nor a future to live for.
In our conversation, I searched for reasons for Laura to live, and she countered with reasons why it was easier to die. It was a level of apathy I have encountered with other severely ill AIDS patients – the brain is so immunocompromised and muddled, the body so tired, the spirit so damaged. Her three children living with a sister had lost their potency as motivation to desire recovery of her physical and mental health. I doubted the active nature of her suicidality, and her apathy and physical deterioration made me question her ability to act on a plan. Nonetheless, I admitted Laura to the psychiatric unit for safety. Two weeks later, I learned she had died in hospital of AIDS-related sepsis. She had 10 days of treatment on the psychiatric unit with no movement in her depressive symptoms and apathy. Eventually, she physically crashed and was sent to the ICU, where she died.
As psychiatrists, we create our own models of what mental illness and treatments are, and we apply some version of the model to each patient. With the concepts of cultural psychiatry and therapeutic alliance, we learn to work within our patients’ models of disease to enhance their response to treatment. My initial reaction to Laura’s death was surprise, fear, and guilt that maybe I had missed a pressing medical issue that contributed to her death. Then I just felt resigned to her death, probably as she did. She told me in the emergency department she was set on dying, and her actions, well before this last admission, had indirectly ensured an early death. We psychiatrists feel failure when we are unable to prevent a suicide. What was Laura’s death: Was it a suicide by apathy that a psychiatrist could have prevented? Or just an expected complication of an untreated chronic illness? Many residents had done their job by admitting her again and again for either psychiatric or medical illness. Yet none of us could understand why she refused to treat her HIV/AIDS, and none of us was able to address the model she had created of her illness. Her model, that her HIV was a death sentence, was anathema to our training.
Because of that dissonance, it was difficult to understand her narrative, let alone find a way to help her reframe it. Her model of illness was misunderstood by a wide swathe of medical professionals, and together we were unable to tailor a treatment to her needs. Since, I’ve worked to reframe her death in my own mind as a way to better understand models of illness, learning from her as well as from my brother and my friend Ricardo. Both the patient’s and physician’s conceptualization of illness affects prognosis of whether to surrender to a treatment or the illness. As psychiatrists, we must strive to understand all models of illness, so we can plan and implement our treatment intervention accordingly.
I asked my friend from home and my brother for their permission and sent them this piece to make sure they approved. I changed certain details about Ricardo’s story to protect his identity. With my brother, there was no way to change his identity, but he was touched and happy to be included. I also changed key facts about the patient I called Laura.
Dr. Posada is a third-year resident in the psychiatry and behavioral sciences department at George Washington University, Washington. She completed a bachelor’s degree at George Washington University. For 2 years after her undergraduate education, she worked at the National Institutes of Allergy and Infectious Diseases studying HIV pathogenesis. Dr. Posada completed her medical degree at the University of Texas Medical Branch in Galveston. Her interests include public psychiatry, health care policy, and health disparities, and she plans to pursue a fellowship in consult liaison psychiatry.
A Howling Cause of Pancytopenia
A 15-year-old African American girl presented to the emergency department with 3 days of fever, sore throat, nausea, vomiting, and poor appetite. She reported a 4-week history of fatigue, right hand pain and swelling, and a 6-kilogram weight loss for which she had seen her primary care provider several times. She reported no recent travel, sick contacts, or new medications.
It appears that there are potentially at least 2 separate problems: an acute one (past 3 days) and a more chronic one (past 4 weeks). These 2 problems may be directly related (ie, acute worsening of the more chronic problem), indirectly related (ie, the more chronic problem is leading to increased susceptibility to the acute problem, for instance, an evolving immunodeficiency predisposing to an opportunistic infection), or “true, true, but unrelated.” The clinical challenge is to keep one’s mind open to each of these potential scenarios and to avoid the tendency to focus on one of the problems and not pay enough attention to the other. Occam’s razor likely does not apply here.
Numerous common and typically transient diseases could cause the symptoms of the past 3 days, particularly infectious etiologies such as streptococcal pharyngitis or a viral infection. One cannot forget about these possibilities while contemplating the more worrisome symptoms of the past 4 weeks, especially weight loss in a growing adolescent. Patients may unintentionally lose weight for a variety of reasons, which can be broadly categorized by decreased caloric supply, gastrointestinal losses or malabsorption, and increased caloric demand; these categories are not mutually exclusive.
Lastly, 1 symptom may provide a more specific direction: the right hand pain and swelling of the past 4 weeks. More specifics, including the extent of the hand swelling, other areas of involvement, and the nature of her pain, will be helpful.
Her temperature was 99.5°F, heart rate 100 beats per minute, respiratory rate 18 breaths per minute, oxygen saturation 95% while breathing ambient air, blood pressure 99/56 mmHg, weight 44 kilograms, height 161 centimeters, and body mass index 17. She appeared generally ill and underweight. She had edematous and violaceous eyelids, dry cracked lips, and pharyngeal erythema with ulcerations of the hard palate. She had nontender cervical and inguinal lymphadenopathy. Her abdomen was tender to palpation in the lower quadrants without guarding or rebound; there was no organomegaly. A right knee effusion with overlying warmth was present without redness or decreased range of motion. She also had an enlarged third proximal interphalangeal joint and loss of palpable metacarpal phalangeal joint landmarks on her right hand. She was noted to be using her arms to move her legs when repositioning in bed.
These exam findings clearly point toward a systemic process but not 1 specific diagnosis. The presence of at least 2 inflamed joints points toward rheumatologic/inflammatory or infectious diseases. Localized edema (eyelids and right metacarpal phalangeal joints), oral ulcers, possible myositis, and arthritis point toward a systemic vasculitis (eg, granulomatosis with polyangiitis, Behçet disease). While Kawasaki disease is also a systemic vasculitis, the presence of oral ulcers and generalized lymphadenopathy argues against it. Inflammatory myopathies like polymyositis, and especially juvenile dermatomyositis, fit many aspects of this presentation with the violaceous eyelids and possible myositis, though no other cutaneous stigmata of this disease are evident (eg, no Gottron’s papules). Polyarthritis, violaceous eyelids, and possible myositis could be consistent with systemic lupus erythematosus (SLE).
The presence of oral ulcers and arthritis make other systemic inflammatory conditions, such as inflammatory bowel disease with arthritis and autoimmune- or infection-related hepatitis, possible. Infectious etiologies alone or in combination with a rheumatologic process are also possible given fevers and lymphadenopathy. In particular, herpesvirus infections (Epstein-Barr virus [EBV], cytomegalovirus [CMV], herpes simplex virus, or human herpes virus 6), human immunodeficiency virus (HIV), hepatitis C virus (HCV), and syphilis can cause oral ulcers and lymphadenopathy. Other potential infectious etiologies include subacute bacterial endocarditis and disseminated gonococcal infection given the presence of polyarthritis, but these infections are less likely as they do not explain all of the symptoms.
In summary, the differential diagnosis is broad and should be prioritized to consider systemic inflammatory conditions, including autoimmune and infectious (especially viral) syndromes, and initial work-up should focus on these etiologies.
The pancytopenia is obviously notable. It raises the possibility that the oral ulcerations are due to the neutropenia rather than a primary disease manifestation. Other possible causes of pancytopenia include SLE, antiphospholipid antibody syndrome, and related rheumatologic diagnoses, including hemophagocytic lymphohistiocytosis (HLH). Given her age and subacute presentation, secondary forms of HLH seem more likely than primary (genetic) forms, which typically present within the first few years of life. Secondary forms of HLH can occur in association with rheumatic diseases and are then referred to as Macrophage Activation Syndrome (MAS). The most common rheumatologic diseases associated with MAS are systemic juvenile idiopathic arthritis, SLE, and Kawasaki disease. Secondary HLH can also occur with infectious diseases, particularly viral infections such as EBV. It is also important to consider thrombotic thrombocytopenic purpura and other forms of thrombotic microangiopathy, especially if her violaceous eyelids actually represent purpura. The presence of pancytopenia also expands the differential diagnosis to include leukemia, lymphoma, and other oncologic diseases. After obtaining results from pending infectious disease studies, additional diagnostic work-up should include examination of the bone marrow and a peripheral blood smear to evaluate for hemophagocytosis and/or malignancy. Testing for double-stranded DNA antibodies and antinuclear antibodies (ANA) should be sent to evaluate for SLE, and antiphospholipid antibodies should also be checked. Renal function must also be evaluated.
Additional laboratory work-up revealed a reticulocyte count of 0.2%, a positive Coombs immunoglobulin G (IgG) test, haptoglobin less than 80 mg/L, and lactate dehydrogenase (LDH) 25.2 µkat/L (1509 units/L); coagulation studies were normal. Her chemistries showed electrolytes, blood urea nitrogen, and creatinine were within normal limits; her aspartate aminotransferase was 216 units/L, and alanine aminotransferase was 56 units/L. Her spot urine protein-to-creatinine ratio was 1.28. Complement and inflammatory studies showed C3 0.14 g/L (14 mg/dL, normal 83-151 mg/dL), C4 0.05 g/L (5 mg/dL, normal 13-37 mg/dL), erythrocyte sedimentation rate (ESR) 103 mm/hr (normal 0-20 mm/hr), and C-reactive protein (CRP) 3.2 mg/L (normal 0.7-1.7 mg/L). Additional studies showed elevated triglycerides (376 mg/dL), elevated creatine kinase (2437 units/L), and elevated ferritin (22,295.5 ng/mL). An ANA screen and specific autoantibody studies were sent, including antidouble stranded DNA antibody, antiribonucleoprotein antibody, anti-Smith antibody, anti-Ro antibody, and anti-La antibody. A bone marrow biopsy was performed.
The hematologic studies provide a mixed picture. There is evidence of an autoimmune hemolytic anemia (AIHA). Typically, AIHA is associated with reticulocytosis rather than reticulocytopenia. Reticulocytopenia can occur in AIHA, however, because of antibodies directed against erythroid precursors or if 2 processes are occurring simultaneously—ie, AIHA plus bone marrow destructive/failure process. The latter scenario is more likely here. Specifically, the pancytopenia, elevated triglycerides, and extreme hyperferritinemia strongly support the diagnosis of HLH. The very low C3 and C4 suggest a complement-consumptive process, and SLE is the most likely etiology. Proteinuria and Coombs-positive anemia are also features of SLE. The discordance between the ESR (markedly elevated) and CRP (mild elevation) is surprising in the setting of systemic inflammation. However, her other clinical features are consistent with marked systemic inflammation, and it is important not to dismiss a likely diagnosis simply on the basis of a few incongruous features. At this point, the diagnosis of SLE complicated by secondary HLH is favored, remembering that both these entities can be triggered by a viral infection. Therefore, diligent follow-up of the aforementioned specific autoantibody studies and the bone marrow biopsy is the next logical step, along with the still-pending infectious disease studies.
These findings are consistent with the diagnosis of SLE complicated by secondary HLH (ie, MAS). It remains possible, but unlikely, that the patient has genetic or familial HLH (fHLH), as this entity is exceedingly rare with distinct underlying genetic aberrations separate from SLE. Ideally, the NK cell function studies would be repeated after the current episode of HLH is controlled and the patient is off of immunosuppressive therapies, but this will likely not be possible given the underlying SLE. Patients with fHLH have reduced or absent NK cell function at baseline (ie, not only during an acute episode of HLH and not because of immunosuppressive medications). Alternatively, one could consider genetic testing for fHLH. The clinical importance of doing this is that patients with fHLH are candidates for bone marrow or stem cell transplantation. There currently is not a published standard of care for the work-up and management of MAS in children with rheumatic disease, so the decision to repeat NK cell function testing and/or genetic testing would be left to the discretion of the treating physician and would depend on the patient’s ongoing clinical course.
The patient required red blood cell and platelet transfusions. She received pulse dose intravenous methylprednisolone for treatment of SLE and MAS; she clinically improved within 48 hours of starting steroids. Cyclosporine was added for management of MAS. The patient was transitioned to oral corticosteroids and discharged home. All cell counts normalized within 1 month of discharge. She was weaned off corticosteroids and cyclosporine was discontinued. Her maintenance SLE therapy includes hydroxychloroquine and mycophenolate mofetil.
COMMENTARY
Because the differential diagnosis for new-onset pancytopenia encompasses many diseases across several medical subspecialties, a thorough history and physical exam are necessary to form a tailored clinical approach.1 The primary causes of pediatric pancytopenia vary depending on geographic location because of the local prevalence of infectious agents and nutritional deficiency patterns. A retrospective study investigating the primary cause of pancytopenia in children without existing malignancy presenting to a US tertiary care hospital found that 64% of cases were due to infection, 28% were due to hematologic disease (most frequently aplastic anemia), and 8% were due to miscellaneous etiologies, including adverse drug reactions and autoimmune diseases.2 In contrast, the most common cause of pancytopenia in pediatric patients presenting to a tertiary care hospital in India was megaloblastic anemia (28%), followed by infections (21%), acute leukemia (21%), and aplastic anemia (20%).3 While clinicians do (and should) consider malignancy as a cause of pancytopenia, there is sparse literature regarding the frequency of pancytopenia associated with the presentations of childhood malignancies.4 A study of pediatric patients with acute lymphoblastic anemia found that only 11% of newly diagnosed patients had pancytopenia at initial presentation.4
There are no official guidelines for the work-up of pediatric pancytopenia from any of the academic societies. Depending on the clinical history, initial laboratory investigation for pediatric pancytopenia may include complete blood cell count with differential, reticulocyte count, peripheral blood smear, complete metabolic panel, hemolysis labs (haptoglobin, LDH, Coombs test) and inflammatory markers (ESR, CRP, fibrinogen). Further investigation to clarify the specific etiology of pancytopenia can be guided by the results of these initial tests.
Hematologic abnormalities are present in greater than 70% of pediatric SLE cases.10,11 The pathogenesis of hematologic abnormalities in SLE is heterogeneous, involving actions of autoreactive lymphocytes, autoantibodies, and proinflammatory cytokines that can disrupt bone marrow production and cause peripheral blood cell destruction.12,13 While pancytopenia is common in children with SLE, other coexisting diagnoses should be considered in patients with SLE and pancytopenia. Concurrent diagnoses that can lead to pancytopenia in patients with SLE include infection, pharmacologic side effects, and secondary HLH,14,15 each of which has differing implications for prognosis and treatment.
Secondary HLH is a severe and often acute complication of systemic inflammatory disorders caused by the proliferation and activation of T cells and macrophages, leading to an enhanced inflammatory state. When HLH occurs in the setting of an underlying autoimmune or autoinflammatory process, it is typically termed MAS. MAS affects an estimated 0.9% to 4.6% of patients with SLE.16 Early diagnosis and treatment of MAS is important because MAS can be rapidly fatal, with a mortality rate of 8% to 20% in pediatric patients.17,18 Clinical features of MAS include physical exam findings of fever and splenomegaly as well as laboratory abnormalities, including pancytopenia, elevated ferritin, elevated triglycerides, and low fibrinogen.18 A bone marrow biopsy showing hemophagocytosis in the absence of malignancy is diagnostic of MAS. Although a bone marrow biopsy is not required to diagnose MAS, it is often obtained to exclude other etiologies of pancytopenia such as malignancy.19 Specialized diagnostic testing for MAS includes NK cell counts and functional studies, including expression of perforin and granzyme B (NK cell proteins triggering apoptosis in target cells), soluble IL-2R (marker of activated lymphocytes), and CD163 (transmembrane protein of hemophagocytic macrophages). There is no standardized protocol for treating MAS.20 It is most commonly treated with highdose corticosteroids; additional agents, including cyclosporine and biologic therapies, are also utilized.16,20
KEY POINTS
- Children with SLE tend to have greater involvement of major organ systems and more rapid accrual of organ damage than adults with SLE. Therefore, it is sometimes necessary to initiate immunosuppressive therapies before full diagnostic criteria are met, provided that malignancy and infection have been ruled out.
- While pancytopenia is common in pediatric patients with SLE, providers should make sure to consider coexisting diagnoses such as infection and MAS, both of which require different treatment strategies.
- It is important to consider HLH/MAS early in the work-up of pancytopenia, because early diagnosis and treatment improves clinical outcomes. Obtaining a ferritin level can aid in the work-up of pancytopenia because it is both a sensitive and specific marker of HLH/MAS when dramatically elevated.
Disclosure
The authors report no conflicts of interest.
1. Weinzierl EP, Arber DA. The Differential Diagnosis and Bone Marrow Evaluation of New-Onset Pancytopenia. Am J Clin Pathol. 2012;139(1):9-29. doi:10.1309/AJCP50AEEYGREWUZ. PubMed
2. Pine M, Walter AW. Pancytopenia in hospitalized children: a five-year review. J Pediatr Hematol Oncol. 2010;32(5):e192-e194. doi:10.1097/MPH.0b013e3181e03082. PubMed
3. Bhatnagar SK. Pancytopenia in Children: Etiological Profile. J Trop Pediatr. 2005;51(4):236-239. doi:10.1093/tropej/fmi010. PubMed
4. Kulkarni KP, Marwaha RK. Acute lymphoblastic leukemia with pancytopenia at presentation: clinical correlates, prognostic impact, and association with survival. J Pediatr Hematol Oncol. 2013;35(7):573-576. doi:10.1097/MPH.0b013e31829d46f3. PubMed
5. Holubar, K. Terminology and iconography of lupus erythematosus: A historical vignette. Am J Dermatopathol. 1980;2(3):239-242. PubMed
6. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725. doi: 10.1002/art.1780400928. PubMed
7. Petri M, Orbai, A, Alarcon GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677-2686. doi:10.1002/art.34473. PubMed
8. Tucker L. Review: Making the diagnosis of systemic lupus erythematosus in children and adolescents. Lupus. 2007;16(8):546-549. doi:10.1177/0961203307078068. PubMed
9. Brunner HI, Gladman DD, Ibañez D, Urowitz MD, Silverman ED. Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus. Arthritis Rheum. 2008;58(2):556-562. doi:10.1002/art.23204. PubMed
10. Benseler SM, Silverman ED. Systemic Lupus Erythematosus. Rheum Dis Clin North Am. 2007;33(3):471-498. doi:10.1016/j.rdc.2007.07.008. PubMed
11. Gokce M, Bilginer Y, Besbas N, et al. Hematological features of pediatric systemic lupus erythematosus: suggesting management strategies in children. Lupus. 2012;21(8):878-884. doi:10.1177/0961203312443721. PubMed
12. Voulgarelis M, Giannouli S, Tasidou A, Anagnostou D, Ziakas PD, Tzioufas AG. Bone marrow histological findings in systemic lupus erythematosus with hematologic abnormalities: A clinicopathological study. Am J Hematol. 2006;81(8):590-597. doi:10.1002/ajh.20593. PubMed
13. Pereira RM, Velloso ER, Menezes Y, Gualandro S, Vassalo J, Yoshinari NH. Bone marrow findings in systemic lupus erythematosus patients with peripheral cytopenias. Clin Rheumatol. 1998;17(3):219-222. PubMed
14. Avčin T, Tse SML, Schneider R, Ngan B, Silverman ED. Macrophage activation syndrome as the presenting manifestation of rheumatic diseases in childhood. J Pediatr. 2006;148(5):683-686. doi:10.1016/j.jpeds.2005.12.070. PubMed
15. Lambotte O, Khellaf M, Harmouche H, et al. Characteristics and Long-Term Outcome of 15 Episodes of Systemic Lupus Erythematosus-Associated Hemophagocytic Syndrome. Medicine. 2006;85(3):169-182. doi:10.1097/01.md.0000224708.62510.d1. PubMed
16. Fukaya S, Yasuda S, Hashimoto T, et al. Clinical features of haemophagocytic syndrome in patients with systemic autoimmune diseases: analysis of 30 cases. Rheumatology. 2008;47(11):1686-1691. doi:10.1093/rheumatology/ken342. PubMed
17. Stephan JL. Reactive haemophagocytic syndrome in children with inflammatory disorders. A retrospective study of 24 patients. Rheumatology. 2001;40(11):1285-1292. doi:10.1093/rheumatology/40.11.1285. PubMed
18. Sawhney S, Woo P, Murray KJ. Macrophage activation syndrome: a potentially fatal complication of rheumatic disorders. Arch Dis Child. 2001;85(5):421-426. PubMed
19. Henter JI, Horne A, Aricó M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124-131. doi:10.1002/pbc.21039. PubMed
20. Lin CI, Yu HH, Lee JH, et al. Clinical analysis of macrophage activation syndrome in pediatric patients with autoimmune diseases. Clin Rheumatol. 2012;31(8):1223-1230. doi:10.1007/s10067-012-1998-0. PubMed
A 15-year-old African American girl presented to the emergency department with 3 days of fever, sore throat, nausea, vomiting, and poor appetite. She reported a 4-week history of fatigue, right hand pain and swelling, and a 6-kilogram weight loss for which she had seen her primary care provider several times. She reported no recent travel, sick contacts, or new medications.
It appears that there are potentially at least 2 separate problems: an acute one (past 3 days) and a more chronic one (past 4 weeks). These 2 problems may be directly related (ie, acute worsening of the more chronic problem), indirectly related (ie, the more chronic problem is leading to increased susceptibility to the acute problem, for instance, an evolving immunodeficiency predisposing to an opportunistic infection), or “true, true, but unrelated.” The clinical challenge is to keep one’s mind open to each of these potential scenarios and to avoid the tendency to focus on one of the problems and not pay enough attention to the other. Occam’s razor likely does not apply here.
Numerous common and typically transient diseases could cause the symptoms of the past 3 days, particularly infectious etiologies such as streptococcal pharyngitis or a viral infection. One cannot forget about these possibilities while contemplating the more worrisome symptoms of the past 4 weeks, especially weight loss in a growing adolescent. Patients may unintentionally lose weight for a variety of reasons, which can be broadly categorized by decreased caloric supply, gastrointestinal losses or malabsorption, and increased caloric demand; these categories are not mutually exclusive.
Lastly, 1 symptom may provide a more specific direction: the right hand pain and swelling of the past 4 weeks. More specifics, including the extent of the hand swelling, other areas of involvement, and the nature of her pain, will be helpful.
Her temperature was 99.5°F, heart rate 100 beats per minute, respiratory rate 18 breaths per minute, oxygen saturation 95% while breathing ambient air, blood pressure 99/56 mmHg, weight 44 kilograms, height 161 centimeters, and body mass index 17. She appeared generally ill and underweight. She had edematous and violaceous eyelids, dry cracked lips, and pharyngeal erythema with ulcerations of the hard palate. She had nontender cervical and inguinal lymphadenopathy. Her abdomen was tender to palpation in the lower quadrants without guarding or rebound; there was no organomegaly. A right knee effusion with overlying warmth was present without redness or decreased range of motion. She also had an enlarged third proximal interphalangeal joint and loss of palpable metacarpal phalangeal joint landmarks on her right hand. She was noted to be using her arms to move her legs when repositioning in bed.
These exam findings clearly point toward a systemic process but not 1 specific diagnosis. The presence of at least 2 inflamed joints points toward rheumatologic/inflammatory or infectious diseases. Localized edema (eyelids and right metacarpal phalangeal joints), oral ulcers, possible myositis, and arthritis point toward a systemic vasculitis (eg, granulomatosis with polyangiitis, Behçet disease). While Kawasaki disease is also a systemic vasculitis, the presence of oral ulcers and generalized lymphadenopathy argues against it. Inflammatory myopathies like polymyositis, and especially juvenile dermatomyositis, fit many aspects of this presentation with the violaceous eyelids and possible myositis, though no other cutaneous stigmata of this disease are evident (eg, no Gottron’s papules). Polyarthritis, violaceous eyelids, and possible myositis could be consistent with systemic lupus erythematosus (SLE).
The presence of oral ulcers and arthritis make other systemic inflammatory conditions, such as inflammatory bowel disease with arthritis and autoimmune- or infection-related hepatitis, possible. Infectious etiologies alone or in combination with a rheumatologic process are also possible given fevers and lymphadenopathy. In particular, herpesvirus infections (Epstein-Barr virus [EBV], cytomegalovirus [CMV], herpes simplex virus, or human herpes virus 6), human immunodeficiency virus (HIV), hepatitis C virus (HCV), and syphilis can cause oral ulcers and lymphadenopathy. Other potential infectious etiologies include subacute bacterial endocarditis and disseminated gonococcal infection given the presence of polyarthritis, but these infections are less likely as they do not explain all of the symptoms.
In summary, the differential diagnosis is broad and should be prioritized to consider systemic inflammatory conditions, including autoimmune and infectious (especially viral) syndromes, and initial work-up should focus on these etiologies.
The pancytopenia is obviously notable. It raises the possibility that the oral ulcerations are due to the neutropenia rather than a primary disease manifestation. Other possible causes of pancytopenia include SLE, antiphospholipid antibody syndrome, and related rheumatologic diagnoses, including hemophagocytic lymphohistiocytosis (HLH). Given her age and subacute presentation, secondary forms of HLH seem more likely than primary (genetic) forms, which typically present within the first few years of life. Secondary forms of HLH can occur in association with rheumatic diseases and are then referred to as Macrophage Activation Syndrome (MAS). The most common rheumatologic diseases associated with MAS are systemic juvenile idiopathic arthritis, SLE, and Kawasaki disease. Secondary HLH can also occur with infectious diseases, particularly viral infections such as EBV. It is also important to consider thrombotic thrombocytopenic purpura and other forms of thrombotic microangiopathy, especially if her violaceous eyelids actually represent purpura. The presence of pancytopenia also expands the differential diagnosis to include leukemia, lymphoma, and other oncologic diseases. After obtaining results from pending infectious disease studies, additional diagnostic work-up should include examination of the bone marrow and a peripheral blood smear to evaluate for hemophagocytosis and/or malignancy. Testing for double-stranded DNA antibodies and antinuclear antibodies (ANA) should be sent to evaluate for SLE, and antiphospholipid antibodies should also be checked. Renal function must also be evaluated.
Additional laboratory work-up revealed a reticulocyte count of 0.2%, a positive Coombs immunoglobulin G (IgG) test, haptoglobin less than 80 mg/L, and lactate dehydrogenase (LDH) 25.2 µkat/L (1509 units/L); coagulation studies were normal. Her chemistries showed electrolytes, blood urea nitrogen, and creatinine were within normal limits; her aspartate aminotransferase was 216 units/L, and alanine aminotransferase was 56 units/L. Her spot urine protein-to-creatinine ratio was 1.28. Complement and inflammatory studies showed C3 0.14 g/L (14 mg/dL, normal 83-151 mg/dL), C4 0.05 g/L (5 mg/dL, normal 13-37 mg/dL), erythrocyte sedimentation rate (ESR) 103 mm/hr (normal 0-20 mm/hr), and C-reactive protein (CRP) 3.2 mg/L (normal 0.7-1.7 mg/L). Additional studies showed elevated triglycerides (376 mg/dL), elevated creatine kinase (2437 units/L), and elevated ferritin (22,295.5 ng/mL). An ANA screen and specific autoantibody studies were sent, including antidouble stranded DNA antibody, antiribonucleoprotein antibody, anti-Smith antibody, anti-Ro antibody, and anti-La antibody. A bone marrow biopsy was performed.
The hematologic studies provide a mixed picture. There is evidence of an autoimmune hemolytic anemia (AIHA). Typically, AIHA is associated with reticulocytosis rather than reticulocytopenia. Reticulocytopenia can occur in AIHA, however, because of antibodies directed against erythroid precursors or if 2 processes are occurring simultaneously—ie, AIHA plus bone marrow destructive/failure process. The latter scenario is more likely here. Specifically, the pancytopenia, elevated triglycerides, and extreme hyperferritinemia strongly support the diagnosis of HLH. The very low C3 and C4 suggest a complement-consumptive process, and SLE is the most likely etiology. Proteinuria and Coombs-positive anemia are also features of SLE. The discordance between the ESR (markedly elevated) and CRP (mild elevation) is surprising in the setting of systemic inflammation. However, her other clinical features are consistent with marked systemic inflammation, and it is important not to dismiss a likely diagnosis simply on the basis of a few incongruous features. At this point, the diagnosis of SLE complicated by secondary HLH is favored, remembering that both these entities can be triggered by a viral infection. Therefore, diligent follow-up of the aforementioned specific autoantibody studies and the bone marrow biopsy is the next logical step, along with the still-pending infectious disease studies.
These findings are consistent with the diagnosis of SLE complicated by secondary HLH (ie, MAS). It remains possible, but unlikely, that the patient has genetic or familial HLH (fHLH), as this entity is exceedingly rare with distinct underlying genetic aberrations separate from SLE. Ideally, the NK cell function studies would be repeated after the current episode of HLH is controlled and the patient is off of immunosuppressive therapies, but this will likely not be possible given the underlying SLE. Patients with fHLH have reduced or absent NK cell function at baseline (ie, not only during an acute episode of HLH and not because of immunosuppressive medications). Alternatively, one could consider genetic testing for fHLH. The clinical importance of doing this is that patients with fHLH are candidates for bone marrow or stem cell transplantation. There currently is not a published standard of care for the work-up and management of MAS in children with rheumatic disease, so the decision to repeat NK cell function testing and/or genetic testing would be left to the discretion of the treating physician and would depend on the patient’s ongoing clinical course.
The patient required red blood cell and platelet transfusions. She received pulse dose intravenous methylprednisolone for treatment of SLE and MAS; she clinically improved within 48 hours of starting steroids. Cyclosporine was added for management of MAS. The patient was transitioned to oral corticosteroids and discharged home. All cell counts normalized within 1 month of discharge. She was weaned off corticosteroids and cyclosporine was discontinued. Her maintenance SLE therapy includes hydroxychloroquine and mycophenolate mofetil.
COMMENTARY
Because the differential diagnosis for new-onset pancytopenia encompasses many diseases across several medical subspecialties, a thorough history and physical exam are necessary to form a tailored clinical approach.1 The primary causes of pediatric pancytopenia vary depending on geographic location because of the local prevalence of infectious agents and nutritional deficiency patterns. A retrospective study investigating the primary cause of pancytopenia in children without existing malignancy presenting to a US tertiary care hospital found that 64% of cases were due to infection, 28% were due to hematologic disease (most frequently aplastic anemia), and 8% were due to miscellaneous etiologies, including adverse drug reactions and autoimmune diseases.2 In contrast, the most common cause of pancytopenia in pediatric patients presenting to a tertiary care hospital in India was megaloblastic anemia (28%), followed by infections (21%), acute leukemia (21%), and aplastic anemia (20%).3 While clinicians do (and should) consider malignancy as a cause of pancytopenia, there is sparse literature regarding the frequency of pancytopenia associated with the presentations of childhood malignancies.4 A study of pediatric patients with acute lymphoblastic anemia found that only 11% of newly diagnosed patients had pancytopenia at initial presentation.4
There are no official guidelines for the work-up of pediatric pancytopenia from any of the academic societies. Depending on the clinical history, initial laboratory investigation for pediatric pancytopenia may include complete blood cell count with differential, reticulocyte count, peripheral blood smear, complete metabolic panel, hemolysis labs (haptoglobin, LDH, Coombs test) and inflammatory markers (ESR, CRP, fibrinogen). Further investigation to clarify the specific etiology of pancytopenia can be guided by the results of these initial tests.
Hematologic abnormalities are present in greater than 70% of pediatric SLE cases.10,11 The pathogenesis of hematologic abnormalities in SLE is heterogeneous, involving actions of autoreactive lymphocytes, autoantibodies, and proinflammatory cytokines that can disrupt bone marrow production and cause peripheral blood cell destruction.12,13 While pancytopenia is common in children with SLE, other coexisting diagnoses should be considered in patients with SLE and pancytopenia. Concurrent diagnoses that can lead to pancytopenia in patients with SLE include infection, pharmacologic side effects, and secondary HLH,14,15 each of which has differing implications for prognosis and treatment.
Secondary HLH is a severe and often acute complication of systemic inflammatory disorders caused by the proliferation and activation of T cells and macrophages, leading to an enhanced inflammatory state. When HLH occurs in the setting of an underlying autoimmune or autoinflammatory process, it is typically termed MAS. MAS affects an estimated 0.9% to 4.6% of patients with SLE.16 Early diagnosis and treatment of MAS is important because MAS can be rapidly fatal, with a mortality rate of 8% to 20% in pediatric patients.17,18 Clinical features of MAS include physical exam findings of fever and splenomegaly as well as laboratory abnormalities, including pancytopenia, elevated ferritin, elevated triglycerides, and low fibrinogen.18 A bone marrow biopsy showing hemophagocytosis in the absence of malignancy is diagnostic of MAS. Although a bone marrow biopsy is not required to diagnose MAS, it is often obtained to exclude other etiologies of pancytopenia such as malignancy.19 Specialized diagnostic testing for MAS includes NK cell counts and functional studies, including expression of perforin and granzyme B (NK cell proteins triggering apoptosis in target cells), soluble IL-2R (marker of activated lymphocytes), and CD163 (transmembrane protein of hemophagocytic macrophages). There is no standardized protocol for treating MAS.20 It is most commonly treated with highdose corticosteroids; additional agents, including cyclosporine and biologic therapies, are also utilized.16,20
KEY POINTS
- Children with SLE tend to have greater involvement of major organ systems and more rapid accrual of organ damage than adults with SLE. Therefore, it is sometimes necessary to initiate immunosuppressive therapies before full diagnostic criteria are met, provided that malignancy and infection have been ruled out.
- While pancytopenia is common in pediatric patients with SLE, providers should make sure to consider coexisting diagnoses such as infection and MAS, both of which require different treatment strategies.
- It is important to consider HLH/MAS early in the work-up of pancytopenia, because early diagnosis and treatment improves clinical outcomes. Obtaining a ferritin level can aid in the work-up of pancytopenia because it is both a sensitive and specific marker of HLH/MAS when dramatically elevated.
Disclosure
The authors report no conflicts of interest.
A 15-year-old African American girl presented to the emergency department with 3 days of fever, sore throat, nausea, vomiting, and poor appetite. She reported a 4-week history of fatigue, right hand pain and swelling, and a 6-kilogram weight loss for which she had seen her primary care provider several times. She reported no recent travel, sick contacts, or new medications.
It appears that there are potentially at least 2 separate problems: an acute one (past 3 days) and a more chronic one (past 4 weeks). These 2 problems may be directly related (ie, acute worsening of the more chronic problem), indirectly related (ie, the more chronic problem is leading to increased susceptibility to the acute problem, for instance, an evolving immunodeficiency predisposing to an opportunistic infection), or “true, true, but unrelated.” The clinical challenge is to keep one’s mind open to each of these potential scenarios and to avoid the tendency to focus on one of the problems and not pay enough attention to the other. Occam’s razor likely does not apply here.
Numerous common and typically transient diseases could cause the symptoms of the past 3 days, particularly infectious etiologies such as streptococcal pharyngitis or a viral infection. One cannot forget about these possibilities while contemplating the more worrisome symptoms of the past 4 weeks, especially weight loss in a growing adolescent. Patients may unintentionally lose weight for a variety of reasons, which can be broadly categorized by decreased caloric supply, gastrointestinal losses or malabsorption, and increased caloric demand; these categories are not mutually exclusive.
Lastly, 1 symptom may provide a more specific direction: the right hand pain and swelling of the past 4 weeks. More specifics, including the extent of the hand swelling, other areas of involvement, and the nature of her pain, will be helpful.
Her temperature was 99.5°F, heart rate 100 beats per minute, respiratory rate 18 breaths per minute, oxygen saturation 95% while breathing ambient air, blood pressure 99/56 mmHg, weight 44 kilograms, height 161 centimeters, and body mass index 17. She appeared generally ill and underweight. She had edematous and violaceous eyelids, dry cracked lips, and pharyngeal erythema with ulcerations of the hard palate. She had nontender cervical and inguinal lymphadenopathy. Her abdomen was tender to palpation in the lower quadrants without guarding or rebound; there was no organomegaly. A right knee effusion with overlying warmth was present without redness or decreased range of motion. She also had an enlarged third proximal interphalangeal joint and loss of palpable metacarpal phalangeal joint landmarks on her right hand. She was noted to be using her arms to move her legs when repositioning in bed.
These exam findings clearly point toward a systemic process but not 1 specific diagnosis. The presence of at least 2 inflamed joints points toward rheumatologic/inflammatory or infectious diseases. Localized edema (eyelids and right metacarpal phalangeal joints), oral ulcers, possible myositis, and arthritis point toward a systemic vasculitis (eg, granulomatosis with polyangiitis, Behçet disease). While Kawasaki disease is also a systemic vasculitis, the presence of oral ulcers and generalized lymphadenopathy argues against it. Inflammatory myopathies like polymyositis, and especially juvenile dermatomyositis, fit many aspects of this presentation with the violaceous eyelids and possible myositis, though no other cutaneous stigmata of this disease are evident (eg, no Gottron’s papules). Polyarthritis, violaceous eyelids, and possible myositis could be consistent with systemic lupus erythematosus (SLE).
The presence of oral ulcers and arthritis make other systemic inflammatory conditions, such as inflammatory bowel disease with arthritis and autoimmune- or infection-related hepatitis, possible. Infectious etiologies alone or in combination with a rheumatologic process are also possible given fevers and lymphadenopathy. In particular, herpesvirus infections (Epstein-Barr virus [EBV], cytomegalovirus [CMV], herpes simplex virus, or human herpes virus 6), human immunodeficiency virus (HIV), hepatitis C virus (HCV), and syphilis can cause oral ulcers and lymphadenopathy. Other potential infectious etiologies include subacute bacterial endocarditis and disseminated gonococcal infection given the presence of polyarthritis, but these infections are less likely as they do not explain all of the symptoms.
In summary, the differential diagnosis is broad and should be prioritized to consider systemic inflammatory conditions, including autoimmune and infectious (especially viral) syndromes, and initial work-up should focus on these etiologies.
The pancytopenia is obviously notable. It raises the possibility that the oral ulcerations are due to the neutropenia rather than a primary disease manifestation. Other possible causes of pancytopenia include SLE, antiphospholipid antibody syndrome, and related rheumatologic diagnoses, including hemophagocytic lymphohistiocytosis (HLH). Given her age and subacute presentation, secondary forms of HLH seem more likely than primary (genetic) forms, which typically present within the first few years of life. Secondary forms of HLH can occur in association with rheumatic diseases and are then referred to as Macrophage Activation Syndrome (MAS). The most common rheumatologic diseases associated with MAS are systemic juvenile idiopathic arthritis, SLE, and Kawasaki disease. Secondary HLH can also occur with infectious diseases, particularly viral infections such as EBV. It is also important to consider thrombotic thrombocytopenic purpura and other forms of thrombotic microangiopathy, especially if her violaceous eyelids actually represent purpura. The presence of pancytopenia also expands the differential diagnosis to include leukemia, lymphoma, and other oncologic diseases. After obtaining results from pending infectious disease studies, additional diagnostic work-up should include examination of the bone marrow and a peripheral blood smear to evaluate for hemophagocytosis and/or malignancy. Testing for double-stranded DNA antibodies and antinuclear antibodies (ANA) should be sent to evaluate for SLE, and antiphospholipid antibodies should also be checked. Renal function must also be evaluated.
Additional laboratory work-up revealed a reticulocyte count of 0.2%, a positive Coombs immunoglobulin G (IgG) test, haptoglobin less than 80 mg/L, and lactate dehydrogenase (LDH) 25.2 µkat/L (1509 units/L); coagulation studies were normal. Her chemistries showed electrolytes, blood urea nitrogen, and creatinine were within normal limits; her aspartate aminotransferase was 216 units/L, and alanine aminotransferase was 56 units/L. Her spot urine protein-to-creatinine ratio was 1.28. Complement and inflammatory studies showed C3 0.14 g/L (14 mg/dL, normal 83-151 mg/dL), C4 0.05 g/L (5 mg/dL, normal 13-37 mg/dL), erythrocyte sedimentation rate (ESR) 103 mm/hr (normal 0-20 mm/hr), and C-reactive protein (CRP) 3.2 mg/L (normal 0.7-1.7 mg/L). Additional studies showed elevated triglycerides (376 mg/dL), elevated creatine kinase (2437 units/L), and elevated ferritin (22,295.5 ng/mL). An ANA screen and specific autoantibody studies were sent, including antidouble stranded DNA antibody, antiribonucleoprotein antibody, anti-Smith antibody, anti-Ro antibody, and anti-La antibody. A bone marrow biopsy was performed.
The hematologic studies provide a mixed picture. There is evidence of an autoimmune hemolytic anemia (AIHA). Typically, AIHA is associated with reticulocytosis rather than reticulocytopenia. Reticulocytopenia can occur in AIHA, however, because of antibodies directed against erythroid precursors or if 2 processes are occurring simultaneously—ie, AIHA plus bone marrow destructive/failure process. The latter scenario is more likely here. Specifically, the pancytopenia, elevated triglycerides, and extreme hyperferritinemia strongly support the diagnosis of HLH. The very low C3 and C4 suggest a complement-consumptive process, and SLE is the most likely etiology. Proteinuria and Coombs-positive anemia are also features of SLE. The discordance between the ESR (markedly elevated) and CRP (mild elevation) is surprising in the setting of systemic inflammation. However, her other clinical features are consistent with marked systemic inflammation, and it is important not to dismiss a likely diagnosis simply on the basis of a few incongruous features. At this point, the diagnosis of SLE complicated by secondary HLH is favored, remembering that both these entities can be triggered by a viral infection. Therefore, diligent follow-up of the aforementioned specific autoantibody studies and the bone marrow biopsy is the next logical step, along with the still-pending infectious disease studies.
These findings are consistent with the diagnosis of SLE complicated by secondary HLH (ie, MAS). It remains possible, but unlikely, that the patient has genetic or familial HLH (fHLH), as this entity is exceedingly rare with distinct underlying genetic aberrations separate from SLE. Ideally, the NK cell function studies would be repeated after the current episode of HLH is controlled and the patient is off of immunosuppressive therapies, but this will likely not be possible given the underlying SLE. Patients with fHLH have reduced or absent NK cell function at baseline (ie, not only during an acute episode of HLH and not because of immunosuppressive medications). Alternatively, one could consider genetic testing for fHLH. The clinical importance of doing this is that patients with fHLH are candidates for bone marrow or stem cell transplantation. There currently is not a published standard of care for the work-up and management of MAS in children with rheumatic disease, so the decision to repeat NK cell function testing and/or genetic testing would be left to the discretion of the treating physician and would depend on the patient’s ongoing clinical course.
The patient required red blood cell and platelet transfusions. She received pulse dose intravenous methylprednisolone for treatment of SLE and MAS; she clinically improved within 48 hours of starting steroids. Cyclosporine was added for management of MAS. The patient was transitioned to oral corticosteroids and discharged home. All cell counts normalized within 1 month of discharge. She was weaned off corticosteroids and cyclosporine was discontinued. Her maintenance SLE therapy includes hydroxychloroquine and mycophenolate mofetil.
COMMENTARY
Because the differential diagnosis for new-onset pancytopenia encompasses many diseases across several medical subspecialties, a thorough history and physical exam are necessary to form a tailored clinical approach.1 The primary causes of pediatric pancytopenia vary depending on geographic location because of the local prevalence of infectious agents and nutritional deficiency patterns. A retrospective study investigating the primary cause of pancytopenia in children without existing malignancy presenting to a US tertiary care hospital found that 64% of cases were due to infection, 28% were due to hematologic disease (most frequently aplastic anemia), and 8% were due to miscellaneous etiologies, including adverse drug reactions and autoimmune diseases.2 In contrast, the most common cause of pancytopenia in pediatric patients presenting to a tertiary care hospital in India was megaloblastic anemia (28%), followed by infections (21%), acute leukemia (21%), and aplastic anemia (20%).3 While clinicians do (and should) consider malignancy as a cause of pancytopenia, there is sparse literature regarding the frequency of pancytopenia associated with the presentations of childhood malignancies.4 A study of pediatric patients with acute lymphoblastic anemia found that only 11% of newly diagnosed patients had pancytopenia at initial presentation.4
There are no official guidelines for the work-up of pediatric pancytopenia from any of the academic societies. Depending on the clinical history, initial laboratory investigation for pediatric pancytopenia may include complete blood cell count with differential, reticulocyte count, peripheral blood smear, complete metabolic panel, hemolysis labs (haptoglobin, LDH, Coombs test) and inflammatory markers (ESR, CRP, fibrinogen). Further investigation to clarify the specific etiology of pancytopenia can be guided by the results of these initial tests.
Hematologic abnormalities are present in greater than 70% of pediatric SLE cases.10,11 The pathogenesis of hematologic abnormalities in SLE is heterogeneous, involving actions of autoreactive lymphocytes, autoantibodies, and proinflammatory cytokines that can disrupt bone marrow production and cause peripheral blood cell destruction.12,13 While pancytopenia is common in children with SLE, other coexisting diagnoses should be considered in patients with SLE and pancytopenia. Concurrent diagnoses that can lead to pancytopenia in patients with SLE include infection, pharmacologic side effects, and secondary HLH,14,15 each of which has differing implications for prognosis and treatment.
Secondary HLH is a severe and often acute complication of systemic inflammatory disorders caused by the proliferation and activation of T cells and macrophages, leading to an enhanced inflammatory state. When HLH occurs in the setting of an underlying autoimmune or autoinflammatory process, it is typically termed MAS. MAS affects an estimated 0.9% to 4.6% of patients with SLE.16 Early diagnosis and treatment of MAS is important because MAS can be rapidly fatal, with a mortality rate of 8% to 20% in pediatric patients.17,18 Clinical features of MAS include physical exam findings of fever and splenomegaly as well as laboratory abnormalities, including pancytopenia, elevated ferritin, elevated triglycerides, and low fibrinogen.18 A bone marrow biopsy showing hemophagocytosis in the absence of malignancy is diagnostic of MAS. Although a bone marrow biopsy is not required to diagnose MAS, it is often obtained to exclude other etiologies of pancytopenia such as malignancy.19 Specialized diagnostic testing for MAS includes NK cell counts and functional studies, including expression of perforin and granzyme B (NK cell proteins triggering apoptosis in target cells), soluble IL-2R (marker of activated lymphocytes), and CD163 (transmembrane protein of hemophagocytic macrophages). There is no standardized protocol for treating MAS.20 It is most commonly treated with highdose corticosteroids; additional agents, including cyclosporine and biologic therapies, are also utilized.16,20
KEY POINTS
- Children with SLE tend to have greater involvement of major organ systems and more rapid accrual of organ damage than adults with SLE. Therefore, it is sometimes necessary to initiate immunosuppressive therapies before full diagnostic criteria are met, provided that malignancy and infection have been ruled out.
- While pancytopenia is common in pediatric patients with SLE, providers should make sure to consider coexisting diagnoses such as infection and MAS, both of which require different treatment strategies.
- It is important to consider HLH/MAS early in the work-up of pancytopenia, because early diagnosis and treatment improves clinical outcomes. Obtaining a ferritin level can aid in the work-up of pancytopenia because it is both a sensitive and specific marker of HLH/MAS when dramatically elevated.
Disclosure
The authors report no conflicts of interest.
1. Weinzierl EP, Arber DA. The Differential Diagnosis and Bone Marrow Evaluation of New-Onset Pancytopenia. Am J Clin Pathol. 2012;139(1):9-29. doi:10.1309/AJCP50AEEYGREWUZ. PubMed
2. Pine M, Walter AW. Pancytopenia in hospitalized children: a five-year review. J Pediatr Hematol Oncol. 2010;32(5):e192-e194. doi:10.1097/MPH.0b013e3181e03082. PubMed
3. Bhatnagar SK. Pancytopenia in Children: Etiological Profile. J Trop Pediatr. 2005;51(4):236-239. doi:10.1093/tropej/fmi010. PubMed
4. Kulkarni KP, Marwaha RK. Acute lymphoblastic leukemia with pancytopenia at presentation: clinical correlates, prognostic impact, and association with survival. J Pediatr Hematol Oncol. 2013;35(7):573-576. doi:10.1097/MPH.0b013e31829d46f3. PubMed
5. Holubar, K. Terminology and iconography of lupus erythematosus: A historical vignette. Am J Dermatopathol. 1980;2(3):239-242. PubMed
6. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725. doi: 10.1002/art.1780400928. PubMed
7. Petri M, Orbai, A, Alarcon GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677-2686. doi:10.1002/art.34473. PubMed
8. Tucker L. Review: Making the diagnosis of systemic lupus erythematosus in children and adolescents. Lupus. 2007;16(8):546-549. doi:10.1177/0961203307078068. PubMed
9. Brunner HI, Gladman DD, Ibañez D, Urowitz MD, Silverman ED. Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus. Arthritis Rheum. 2008;58(2):556-562. doi:10.1002/art.23204. PubMed
10. Benseler SM, Silverman ED. Systemic Lupus Erythematosus. Rheum Dis Clin North Am. 2007;33(3):471-498. doi:10.1016/j.rdc.2007.07.008. PubMed
11. Gokce M, Bilginer Y, Besbas N, et al. Hematological features of pediatric systemic lupus erythematosus: suggesting management strategies in children. Lupus. 2012;21(8):878-884. doi:10.1177/0961203312443721. PubMed
12. Voulgarelis M, Giannouli S, Tasidou A, Anagnostou D, Ziakas PD, Tzioufas AG. Bone marrow histological findings in systemic lupus erythematosus with hematologic abnormalities: A clinicopathological study. Am J Hematol. 2006;81(8):590-597. doi:10.1002/ajh.20593. PubMed
13. Pereira RM, Velloso ER, Menezes Y, Gualandro S, Vassalo J, Yoshinari NH. Bone marrow findings in systemic lupus erythematosus patients with peripheral cytopenias. Clin Rheumatol. 1998;17(3):219-222. PubMed
14. Avčin T, Tse SML, Schneider R, Ngan B, Silverman ED. Macrophage activation syndrome as the presenting manifestation of rheumatic diseases in childhood. J Pediatr. 2006;148(5):683-686. doi:10.1016/j.jpeds.2005.12.070. PubMed
15. Lambotte O, Khellaf M, Harmouche H, et al. Characteristics and Long-Term Outcome of 15 Episodes of Systemic Lupus Erythematosus-Associated Hemophagocytic Syndrome. Medicine. 2006;85(3):169-182. doi:10.1097/01.md.0000224708.62510.d1. PubMed
16. Fukaya S, Yasuda S, Hashimoto T, et al. Clinical features of haemophagocytic syndrome in patients with systemic autoimmune diseases: analysis of 30 cases. Rheumatology. 2008;47(11):1686-1691. doi:10.1093/rheumatology/ken342. PubMed
17. Stephan JL. Reactive haemophagocytic syndrome in children with inflammatory disorders. A retrospective study of 24 patients. Rheumatology. 2001;40(11):1285-1292. doi:10.1093/rheumatology/40.11.1285. PubMed
18. Sawhney S, Woo P, Murray KJ. Macrophage activation syndrome: a potentially fatal complication of rheumatic disorders. Arch Dis Child. 2001;85(5):421-426. PubMed
19. Henter JI, Horne A, Aricó M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124-131. doi:10.1002/pbc.21039. PubMed
20. Lin CI, Yu HH, Lee JH, et al. Clinical analysis of macrophage activation syndrome in pediatric patients with autoimmune diseases. Clin Rheumatol. 2012;31(8):1223-1230. doi:10.1007/s10067-012-1998-0. PubMed
1. Weinzierl EP, Arber DA. The Differential Diagnosis and Bone Marrow Evaluation of New-Onset Pancytopenia. Am J Clin Pathol. 2012;139(1):9-29. doi:10.1309/AJCP50AEEYGREWUZ. PubMed
2. Pine M, Walter AW. Pancytopenia in hospitalized children: a five-year review. J Pediatr Hematol Oncol. 2010;32(5):e192-e194. doi:10.1097/MPH.0b013e3181e03082. PubMed
3. Bhatnagar SK. Pancytopenia in Children: Etiological Profile. J Trop Pediatr. 2005;51(4):236-239. doi:10.1093/tropej/fmi010. PubMed
4. Kulkarni KP, Marwaha RK. Acute lymphoblastic leukemia with pancytopenia at presentation: clinical correlates, prognostic impact, and association with survival. J Pediatr Hematol Oncol. 2013;35(7):573-576. doi:10.1097/MPH.0b013e31829d46f3. PubMed
5. Holubar, K. Terminology and iconography of lupus erythematosus: A historical vignette. Am J Dermatopathol. 1980;2(3):239-242. PubMed
6. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725. doi: 10.1002/art.1780400928. PubMed
7. Petri M, Orbai, A, Alarcon GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677-2686. doi:10.1002/art.34473. PubMed
8. Tucker L. Review: Making the diagnosis of systemic lupus erythematosus in children and adolescents. Lupus. 2007;16(8):546-549. doi:10.1177/0961203307078068. PubMed
9. Brunner HI, Gladman DD, Ibañez D, Urowitz MD, Silverman ED. Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus. Arthritis Rheum. 2008;58(2):556-562. doi:10.1002/art.23204. PubMed
10. Benseler SM, Silverman ED. Systemic Lupus Erythematosus. Rheum Dis Clin North Am. 2007;33(3):471-498. doi:10.1016/j.rdc.2007.07.008. PubMed
11. Gokce M, Bilginer Y, Besbas N, et al. Hematological features of pediatric systemic lupus erythematosus: suggesting management strategies in children. Lupus. 2012;21(8):878-884. doi:10.1177/0961203312443721. PubMed
12. Voulgarelis M, Giannouli S, Tasidou A, Anagnostou D, Ziakas PD, Tzioufas AG. Bone marrow histological findings in systemic lupus erythematosus with hematologic abnormalities: A clinicopathological study. Am J Hematol. 2006;81(8):590-597. doi:10.1002/ajh.20593. PubMed
13. Pereira RM, Velloso ER, Menezes Y, Gualandro S, Vassalo J, Yoshinari NH. Bone marrow findings in systemic lupus erythematosus patients with peripheral cytopenias. Clin Rheumatol. 1998;17(3):219-222. PubMed
14. Avčin T, Tse SML, Schneider R, Ngan B, Silverman ED. Macrophage activation syndrome as the presenting manifestation of rheumatic diseases in childhood. J Pediatr. 2006;148(5):683-686. doi:10.1016/j.jpeds.2005.12.070. PubMed
15. Lambotte O, Khellaf M, Harmouche H, et al. Characteristics and Long-Term Outcome of 15 Episodes of Systemic Lupus Erythematosus-Associated Hemophagocytic Syndrome. Medicine. 2006;85(3):169-182. doi:10.1097/01.md.0000224708.62510.d1. PubMed
16. Fukaya S, Yasuda S, Hashimoto T, et al. Clinical features of haemophagocytic syndrome in patients with systemic autoimmune diseases: analysis of 30 cases. Rheumatology. 2008;47(11):1686-1691. doi:10.1093/rheumatology/ken342. PubMed
17. Stephan JL. Reactive haemophagocytic syndrome in children with inflammatory disorders. A retrospective study of 24 patients. Rheumatology. 2001;40(11):1285-1292. doi:10.1093/rheumatology/40.11.1285. PubMed
18. Sawhney S, Woo P, Murray KJ. Macrophage activation syndrome: a potentially fatal complication of rheumatic disorders. Arch Dis Child. 2001;85(5):421-426. PubMed
19. Henter JI, Horne A, Aricó M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124-131. doi:10.1002/pbc.21039. PubMed
20. Lin CI, Yu HH, Lee JH, et al. Clinical analysis of macrophage activation syndrome in pediatric patients with autoimmune diseases. Clin Rheumatol. 2012;31(8):1223-1230. doi:10.1007/s10067-012-1998-0. PubMed
© 2018 Society of Hospital Medicine
The Pipeline From Abstract Presentation to Publication in Pediatric Hospital Medicine
Pediatric hospital medicine (PHM) is one of the most rapidly growing disciplines in pediatrics,1 with 8% of pediatric residency graduates each year entering the field.2 Research plays an important role in advancing care in the field and is a critical component for board certification and fellowship accreditation.3-6 The annual PHM conference, which has been jointly sponsored by the Academic Pediatric Association, the American Academy of Pediatrics, and the Society of Hospital Medicine, is an important venue for the dissemination of research findings. Abstract selection is determined by peer review; however, reviewers are provided with only a brief snapshot of the research, which may not contain sufficient information to fully evaluate the methodological quality of the work.7-10 Additionally, while instructions are provided, reviewers often lack formal training in abstract review. Consequently, scores may vary.9
Publication in a peer-reviewed journal is considered a measure of research success because it requires more rigorous peer review than the abstract selection process at scientific meetings.11-16 Rates of subsequent journal publication differ based on specialty and meeting, and they have been reported at 23% to 78%.10,12,14-18 In pediatrics, publication rates after presentation at scientific meetings range from 36% to 63%, with mean time to publication ranging from 20 to 26 months following the meeting.11,19,20 No studies have reviewed abstract submissions to the annual PHM meeting to determine if selection or presentation format is associated with subsequent publication in a peer-reviewed journal.
We sought to identify the publication rate of abstracts submitted to the 2014 PHM conference and determine whether presentation format was associated with the likelihood of subsequent journal publication or time to publication.
METHODS
Study Design
Data for this retrospective cohort study were obtained from a database of all abstracts submitted for presentation at the 2014 PHM conference in Lake Buena Vista, Florida.
Main Exposures
The main exposure was presentation format, which was categorized as not presented (ie, rejected), poster presentation, or oral presentation. PHM has a blinded abstract peer-review process; in 2014, an average of 10 reviewers scored each abstract. Reviewers graded abstracts on a scale of 1 (best in category) to 7 (unacceptable for presentation) according to the following criteria: originality, scientific importance, methodological rigor, and quality of presentation. Abstracts with the lowest average scores in each content area, usually less than or equal to 3, were accepted as oral presentations while most abstracts with scores greater than 5 were rejected. For this study, information collected from each abstract included authors, if the primary author was a trainee, title, content area, and presentation format. Content areas included clinical research, educational research, health services research (HSR) and/or epidemiology, practice management research, and quality improvement. Abstracts were then grouped by presentation format and content area for analysis. The Pediatric Academic Societies (PAS) annual meeting, another common venue for the presentation of pediatric research, precedes the PHM conference. Because acceptance for PAS presentation may represent more strongly developed abstract submissions for PHM, we identified which abstracts had also been presented at the PAS conference that same year by cross-referencing authors and abstract titles with the PAS 2014 program.
Main Outcome Measures
All submissions were assessed for subsequent publication in peer-reviewed journals through January 2017 (30 months following the July 2014 PHM conference). To identify abstracts that went on to full publication, 2 authors (JC and LEH) independently searched for the lead author’s name and the presentation title in PubMed, Google Scholar, and MedEdPORTAL in January 2017. PubMed was searched using both the general search box and an advanced search for author and title. Google Scholar was added to capture manuscripts that may not have been indexed in PubMed at the time of our search. MedEdPORTAL, a common venue for the publication of educational initiatives that are not currently indexed in PubMed, was searched by lead author name via the general search box. If a full manuscript was published discussing similar outcomes or results and was written by the same authors who had submitted a PHM conference abstract, it was considered to have been published. The journal, month, and year of publication were recorded. For journals published every 2 months, the date of publication was recorded as falling between the 2 months. For those journals with biannual publication in the spring and fall, the months of March and October were used, respectively. The impact factor of the publication journal was also recorded for the year preceding publication. A journal’s impact factor is frequently used as a quantitative measure of journal quality and reflects the frequency with which a journal’s articles are cited in the scientific literature.21 Journals without an impact factor (eg, newer journals) were assigned a 0.
Data Analysis
All abstracts submitted to the PHM conference were analyzed based on content area and presentation format. The proportion of all abstracts subsequently published was determined for each format type and content area, and the odds ratio (OR) for publication after abstract submission was calculated using logistic regression. We calculated an adjusted OR for subsequent publication controlling for PAS presentation and the trainee status of the primary author. The journals most frequently publishing abstracts submitted to the PHM conference were identified. Median time to publication was calculated using the number of months elapsed between the PHM conference and publication date and compared across all abstract formats using Cox proportional hazards models adjusted for PAS presentation and trainee status. Kaplan-Meier survival curves were also generated for each of the 3 formats and compared using log-rank tests. The median impact factor was determined for each abstract format and compared using Wilcoxon rank-sum tests. Median impact factor by content area was compared using a Kruskal-Wallis test. All statistical analyses were performed using SAS version 9.2 (SAS Institute, Cary, NC). P values < 0.05 were considered statistically significant. In accordance with the Common Rule22 and the policies of the Cincinnati Children’s Hospital Medical Center Institutional Review Board, this research was not considered human subjects research.
RESULTS
For the 2014 PHM meeting, 226 abstracts were submitted, of which 183 (81.0%) were selected for presentation, including 154 (68.0%) as poster presentations and 29 (12.8%) as oral presentations. Of all submitted abstracts, 82 (36.3%) were published within 30 months following the meeting. Eighty-one of these (98.8%) were identified via PubMed, and 1 was found only in MedEdPORTAL. No additional publications were found via Google Scholar. The presenting author for the PHM abstract was the first author for 87.8% (n = 72) of the publications. A trainee was the presenting author for only 2 of these abstracts. For the publications in which the first author was not the presenting author, the presenting author was the senior author in 2 of the publications and the second or third author on the remaining 8. Of the abstracts accepted for presentation, 70 (38.3%) were subsequently published. Abstracts accepted for oral presentation had almost 7-fold greater odds of subsequent publication than those that were rejected (Table 1; OR 6.8; 95% confidence interval [CI], 2.4-19.4). Differences in the odds of publication for rejected abstracts compared with those accepted for poster presentation were not statistically significant (OR 1.2; 95% CI, 0.5-2.5).
DISCUSSION
About one-third of abstracts submitted to the 2014 PHM conference were subsequently published in peer-reviewed journals within 30 months of the conference. Compared with rejected abstracts, the rate of publication was significantly higher for abstracts selected for oral presentation but not for those selected for poster presentation. For abstracts ultimately published in journals, selection for oral presentation was significantly associated with both a shorter time to publication and a higher median journal impact factor compared with rejected abstracts. Time to publication and median journal impact factor were similar between rejected abstracts and those accepted for poster presentation. Our findings suggest that abstract reviewers may be able to identify which abstracts will ultimately withstand more stringent peer review in the publication process when accepting abstracts for oral presentation. However, the selection for poster presentation versus rejection may not be indicative of future publication or the impact factor of the subsequent publication journal.
Previous studies have reviewed publication rates after meetings of the European Society for Pediatric Urology (publication rate of 47%),11 the Ambulatory Pediatric Association (now the Academic Pediatric Association; publication rate of 47%), the American Pediatric Society/Society for Pediatric Research (publication rate of 54%), and the PAS (publication rate of 45%).19,20 Our lower publication rate of 36.3% may be attributed to the shorter follow-up time in our study (30 months from the PHM conference), whereas prior studies monitored for publication up to 60 months after the PAS conference.20 Factors associated with subsequent publication include statistically significant results, a large sample size, and a randomized controlled trial study design.15,16 The primary reason for nonpublication for up to 80% of abstracts is failure to submit a manuscript for publication.23 A lack of time and fear of rejection after peer review are commonly cited explanations.18,23,24 Individuals may view acceptance for an oral presentation as positive reinforcement and be more motivated to pursue subsequent manuscript publication than individuals whose abstracts are offered poster presentations or are rejected. Trainees frequently present abstracts at scientific meetings, representing 40.3% of primary authors submitting abstracts to PHM in 2014, but may not have sufficient time or mentorship to develop a complete manuscript.18 To our knowledge, there have been no publications that assess the impact of trainee status on subsequent publication after conference submission.
Our study demonstrated that selection for oral presentation was associated with subsequent publication, shorter time to publication, and publication in journals with higher impact factors. A 2005 Cochrane review also demonstrated that selection for oral presentation was associated with subsequent journal publication.16 Abstracts accepted for oral publication may represent work further along in the research process, with more developed methodology and results. The shorter time to publication for abstracts accepted for oral presentation could also reflect feedback provided by conference attendees after the presentation, whereas poster sessions frequently lack a formalized process for critique.
Carroll et al. found no difference in time to publication between abstracts accepted for presentation at the PAS and rejected abstracts.20 Previous studies demonstrate that most abstracts presented at scientific meetings that are subsequently accepted for publication are published within 2 to 3 years of the meeting,12 with publication rates as high as 98% within 3 years of presentation.17 In contrast to Carroll et al., we found that abstracts accepted for oral presentation had a 4-fold greater likelihood of publication at each month than rejected abstracts. However, abstracts accepted for poster presentation did not have a significant difference in the proportional hazard ratio models for publication compared with rejected abstracts. Because space considerations limit the number of abstracts that can be accepted for presentation at a conference, some abstracts that are suitable for future publication may have been rejected due to a lack of space. Because researchers often use scientific meetings as a forum to receive peer feedback,12 authors who present at conferences may take more time to write a manuscript in order to incorporate this feedback.
The most common journal in which submitted abstracts were subsequently published was Hospital Pediatrics, representing twice as many published manuscripts as the second most frequent journal, Pediatrics. Hospital Pediatrics, which was first published in 2011, did not have an impact factor assigned during the study period. Yet, as a peer-reviewed journal dedicated to the field of PHM, it is well aligned with the research presented at the PHM meeting. It is unclear if Hospital Pediatrics is a journal to which pediatric hospitalists tend to submit manuscripts initially or if manuscripts are frequently submitted elsewhere prior to their publication in Hospital Pediatrics. Submission to other journals first likely extends the time to publication, especially for abstracts accepted for poster presentation, which may describe studies with less developed methods or results.
This study has several limitations. Previous studies have demonstrated mean time to publication of 12 to 32 months following abstract presentation with a median time of 19.6 months.16 Because we only have a 30-month follow-up, there may be abstracts still in the review process that are yet to be published, especially because the length of the review process varies by journal. We based our literature search on the first author of each PHM conference abstract submission, assuming that this presenting author would be one of the publishing authors even if not remaining first author; if this was not the case, we may have missed some abstracts that were subsequently published in full. Likewise, if a presenting author’s last name changed prior to the publication of a manuscript, a publication may have been missed. This limitation would cause us to underestimate the overall publication rate. It is not clear whether this would differentially affect the method of presentation. However, in this study, there was concordance between the presenting author and the publication’s first author in 87.8% of the abstracts subsequently published in full. Presenting authors who did not remain the first author on the published manuscript maintained authorship as either the senior author or second or third author, which may represent changes in the degree of involvement or a division of responsibilities for individuals working on a project together. While our search methods were comprehensive, there is a possibility that abstracts may have been published in a venue that was not searched. Additionally, we only reviewed abstracts submitted to PHM for 1 year. As the field matures and the number of fellowship programs increases, the quality of submitted abstracts may increase, leading to higher publication rates or shorter times to publication. It is also possible that the publication rate may not be reflective of PHM as a field because hospitalists may submit their work to conferences other than the PHM. Lastly, it may be more challenging to interpret any differences in impact factor because some journals, including Hospital Pediatrics (which represented a plurality of poster presentation abstracts that were subsequently published and is a relatively new journal), did not have an impact factor assigned during the study period. Assigning a 0 to journals without an impact factor may artificially lower the average impact factor reported. Furthermore, an impact factor, which is based on the frequency with which an individual journal’s articles are cited in scientific or medical publications, may not necessarily reflect a journal’s quality.
CONCLUSIONS
Of the 226 abstracts submitted to the 2014 PHM conference, approximately one-third were published in peer-reviewed journals within 30 months of the conference. Selection for oral presentation was found to be associated with subsequent publication as well as publication in journals with higher impact factors. The overall low publication rate may indicate a need for increased mentorship and resources for research development in this growing specialty. Improved mechanisms for author feedback at poster sessions may provide constructive suggestions for further development of these projects into full manuscripts or opportunities for trainees and early-career hospitalists to network with more experienced researchers in the field.
Disclosure
Drs. Herrmann, Hall, Kyler, Andrews, Williams, and Shah and Mr. Cochran have nothing to disclose. Dr. Wilson reports personal fees from the American Academy of Pediatrics during the conduct of the study. The authors have no financial relationships relevant to this article to disclose.
1. Stucky ER, Ottolini MC, Maniscalco J. Pediatric hospital medicine core competencies: development and methodology. J Hosp Med. 2010;5(6):339-343. PubMed
2. Freed GL, McGuinness GA, Althouse LA, Moran LM, Spera L. Long-term plans for those selecting hospital medicine as an initial career choice. Hosp Pediatr. 2015;5(4):169-174. PubMed
3. Rauch D. Pediatric Hospital Medicine Subspecialty. 2016; https://www.aap.org/en-us/about-the-aap/Committees-Councils-Sections/Section-on-Hospital-Medicine/Pages/Pediatric-Hospital-Medicine-Subspecialty.aspx. Accessed November 28, 2016.
4. Bekmezian A, Teufel RJ, Wilson KM. Research needs of pediatric hospitalists. Hosp Pediatr. 2011;1(1):38-44. PubMed
5. Teufel RJ, Bekmezian A, Wilson K. Pediatric hospitalist research productivity: predictors of success at presenting abstracts and publishing peer-reviewed manuscripts among pediatric hospitalists. Hosp Pediatr. 2012;2(3):149-160. PubMed
6. Wilson KM, Shah SS, Simon TD, Srivastava R, Tieder JS. The challenge of pediatric hospital medicine research. Hosp Pediatr. 2012;2(1):8-9. PubMed
7. Froom P, Froom J. Presentation Deficiencies in structured medical abstracts. J Clin Epidemiol. 1993;46(7):591-594. PubMed
8. Relman AS. News reports of medical meetings: how reliable are abstracts? N Engl J Med. 1980;303(5):277-278. PubMed
9. Soffer A. Beware the 200-word abstract! Arch Intern Med. 1976;136(11):1232-1233. PubMed
10. Bhandari M, Devereaux P, Guyatt GH, et al. An observational study of orthopaedic abstracts and subsequent full-text publications. J Bone Joint Surg Am. 2002;84(4):615-621. PubMed
11. Castagnetti M, Subramaniam R, El-Ghoneimi A. Abstracts presented at the European Society for Pediatric Urology (ESPU) meetings (2003–2010): Characteristics and outcome. J Pediatr Urol. 2014;10(2):355-360. PubMed
12. Halikman R, Scolnik D, Rimon A, Glatstein MM. Peer-Reviewed Journal Publication of Abstracts Presented at an International Emergency Medicine Scientific Meeting: Outcomes and Comparison With the Previous Meeting. Pediatr Emerg Care. 2016. PubMed
13. Relman AS. Peer review in scientific journals--what good is it? West J Med. 1990;153(5):520. PubMed
14. Riordan F. Do presenters to paediatric meetings get their work published? Arch Dis Child. 2000;83(6):524-526. PubMed
15. Scherer RW, Dickersin K, Langenberg P. Full publication of results initially presented in abstracts: a meta-analysis. JAMA. 1994;272(2):158-162. PubMed
16. Scherer RW, Langenberg P, Elm E. Full publication of results initially presented in abstracts. Cochrane Database Syst Rev. 2005. PubMed
17. Marx WF, Cloft HJ, Do HM, Kallmes DF. The fate of neuroradiologic abstracts presented at national meetings in 1993: rate of subsequent publication in peer-reviewed, indexed journals. Am J Neuroradiol. 1999;20(6):1173-1177. PubMed
18. Roy D, Sankar V, Hughes J, Jones A, Fenton J. Publication rates of scientific papers presented at the Otorhinolarygological Research Society meetings. Clin Otolaryngol Allied Sci. 2001;26(3):253-256. PubMed
19. McCormick MC, Holmes JH. Publication of research presented at the pediatric meetings: change in selection. Am J Dis Child. 1985;139(2):122-126. PubMed
20. Carroll AE, Sox CM, Tarini BA, Ringold S, Christakis DA. Does presentation format at the Pediatric Academic Societies’ annual meeting predict subsequent publication? Pediatrics. 2003;112(6):1238-1241. PubMed
21. Saha S, Saint S, Christakis DA. Impact factor: a valid measure of journal quality? J Med Libr Assoc. 2003;91(1):42. PubMed
22. Office for Human Research Protections. Code of Federal Regulations, Title 45 Public Welfare: Part 46, Protection of Human Subjects, §46.102(f ). http://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr-46/index.html#46.102. Accessed October 21, 2016.
23. Weber EJ, Callaham ML, Wears RL, Barton C, Young G. Unpublished research from a medical specialty meeting: why investigators fail to publish. JAMA. 1998;280(3):257-259. PubMed
24. Timmer A, Hilsden RJ, Cole J, Hailey D, Sutherland LR. Publication bias in gastroenterological research–a retrospective cohort study based on abstracts submitted to a scientific meeting. BMC Med Res Methodol. 2002;2(1):1. PubMed
Pediatric hospital medicine (PHM) is one of the most rapidly growing disciplines in pediatrics,1 with 8% of pediatric residency graduates each year entering the field.2 Research plays an important role in advancing care in the field and is a critical component for board certification and fellowship accreditation.3-6 The annual PHM conference, which has been jointly sponsored by the Academic Pediatric Association, the American Academy of Pediatrics, and the Society of Hospital Medicine, is an important venue for the dissemination of research findings. Abstract selection is determined by peer review; however, reviewers are provided with only a brief snapshot of the research, which may not contain sufficient information to fully evaluate the methodological quality of the work.7-10 Additionally, while instructions are provided, reviewers often lack formal training in abstract review. Consequently, scores may vary.9
Publication in a peer-reviewed journal is considered a measure of research success because it requires more rigorous peer review than the abstract selection process at scientific meetings.11-16 Rates of subsequent journal publication differ based on specialty and meeting, and they have been reported at 23% to 78%.10,12,14-18 In pediatrics, publication rates after presentation at scientific meetings range from 36% to 63%, with mean time to publication ranging from 20 to 26 months following the meeting.11,19,20 No studies have reviewed abstract submissions to the annual PHM meeting to determine if selection or presentation format is associated with subsequent publication in a peer-reviewed journal.
We sought to identify the publication rate of abstracts submitted to the 2014 PHM conference and determine whether presentation format was associated with the likelihood of subsequent journal publication or time to publication.
METHODS
Study Design
Data for this retrospective cohort study were obtained from a database of all abstracts submitted for presentation at the 2014 PHM conference in Lake Buena Vista, Florida.
Main Exposures
The main exposure was presentation format, which was categorized as not presented (ie, rejected), poster presentation, or oral presentation. PHM has a blinded abstract peer-review process; in 2014, an average of 10 reviewers scored each abstract. Reviewers graded abstracts on a scale of 1 (best in category) to 7 (unacceptable for presentation) according to the following criteria: originality, scientific importance, methodological rigor, and quality of presentation. Abstracts with the lowest average scores in each content area, usually less than or equal to 3, were accepted as oral presentations while most abstracts with scores greater than 5 were rejected. For this study, information collected from each abstract included authors, if the primary author was a trainee, title, content area, and presentation format. Content areas included clinical research, educational research, health services research (HSR) and/or epidemiology, practice management research, and quality improvement. Abstracts were then grouped by presentation format and content area for analysis. The Pediatric Academic Societies (PAS) annual meeting, another common venue for the presentation of pediatric research, precedes the PHM conference. Because acceptance for PAS presentation may represent more strongly developed abstract submissions for PHM, we identified which abstracts had also been presented at the PAS conference that same year by cross-referencing authors and abstract titles with the PAS 2014 program.
Main Outcome Measures
All submissions were assessed for subsequent publication in peer-reviewed journals through January 2017 (30 months following the July 2014 PHM conference). To identify abstracts that went on to full publication, 2 authors (JC and LEH) independently searched for the lead author’s name and the presentation title in PubMed, Google Scholar, and MedEdPORTAL in January 2017. PubMed was searched using both the general search box and an advanced search for author and title. Google Scholar was added to capture manuscripts that may not have been indexed in PubMed at the time of our search. MedEdPORTAL, a common venue for the publication of educational initiatives that are not currently indexed in PubMed, was searched by lead author name via the general search box. If a full manuscript was published discussing similar outcomes or results and was written by the same authors who had submitted a PHM conference abstract, it was considered to have been published. The journal, month, and year of publication were recorded. For journals published every 2 months, the date of publication was recorded as falling between the 2 months. For those journals with biannual publication in the spring and fall, the months of March and October were used, respectively. The impact factor of the publication journal was also recorded for the year preceding publication. A journal’s impact factor is frequently used as a quantitative measure of journal quality and reflects the frequency with which a journal’s articles are cited in the scientific literature.21 Journals without an impact factor (eg, newer journals) were assigned a 0.
Data Analysis
All abstracts submitted to the PHM conference were analyzed based on content area and presentation format. The proportion of all abstracts subsequently published was determined for each format type and content area, and the odds ratio (OR) for publication after abstract submission was calculated using logistic regression. We calculated an adjusted OR for subsequent publication controlling for PAS presentation and the trainee status of the primary author. The journals most frequently publishing abstracts submitted to the PHM conference were identified. Median time to publication was calculated using the number of months elapsed between the PHM conference and publication date and compared across all abstract formats using Cox proportional hazards models adjusted for PAS presentation and trainee status. Kaplan-Meier survival curves were also generated for each of the 3 formats and compared using log-rank tests. The median impact factor was determined for each abstract format and compared using Wilcoxon rank-sum tests. Median impact factor by content area was compared using a Kruskal-Wallis test. All statistical analyses were performed using SAS version 9.2 (SAS Institute, Cary, NC). P values < 0.05 were considered statistically significant. In accordance with the Common Rule22 and the policies of the Cincinnati Children’s Hospital Medical Center Institutional Review Board, this research was not considered human subjects research.
RESULTS
For the 2014 PHM meeting, 226 abstracts were submitted, of which 183 (81.0%) were selected for presentation, including 154 (68.0%) as poster presentations and 29 (12.8%) as oral presentations. Of all submitted abstracts, 82 (36.3%) were published within 30 months following the meeting. Eighty-one of these (98.8%) were identified via PubMed, and 1 was found only in MedEdPORTAL. No additional publications were found via Google Scholar. The presenting author for the PHM abstract was the first author for 87.8% (n = 72) of the publications. A trainee was the presenting author for only 2 of these abstracts. For the publications in which the first author was not the presenting author, the presenting author was the senior author in 2 of the publications and the second or third author on the remaining 8. Of the abstracts accepted for presentation, 70 (38.3%) were subsequently published. Abstracts accepted for oral presentation had almost 7-fold greater odds of subsequent publication than those that were rejected (Table 1; OR 6.8; 95% confidence interval [CI], 2.4-19.4). Differences in the odds of publication for rejected abstracts compared with those accepted for poster presentation were not statistically significant (OR 1.2; 95% CI, 0.5-2.5).
DISCUSSION
About one-third of abstracts submitted to the 2014 PHM conference were subsequently published in peer-reviewed journals within 30 months of the conference. Compared with rejected abstracts, the rate of publication was significantly higher for abstracts selected for oral presentation but not for those selected for poster presentation. For abstracts ultimately published in journals, selection for oral presentation was significantly associated with both a shorter time to publication and a higher median journal impact factor compared with rejected abstracts. Time to publication and median journal impact factor were similar between rejected abstracts and those accepted for poster presentation. Our findings suggest that abstract reviewers may be able to identify which abstracts will ultimately withstand more stringent peer review in the publication process when accepting abstracts for oral presentation. However, the selection for poster presentation versus rejection may not be indicative of future publication or the impact factor of the subsequent publication journal.
Previous studies have reviewed publication rates after meetings of the European Society for Pediatric Urology (publication rate of 47%),11 the Ambulatory Pediatric Association (now the Academic Pediatric Association; publication rate of 47%), the American Pediatric Society/Society for Pediatric Research (publication rate of 54%), and the PAS (publication rate of 45%).19,20 Our lower publication rate of 36.3% may be attributed to the shorter follow-up time in our study (30 months from the PHM conference), whereas prior studies monitored for publication up to 60 months after the PAS conference.20 Factors associated with subsequent publication include statistically significant results, a large sample size, and a randomized controlled trial study design.15,16 The primary reason for nonpublication for up to 80% of abstracts is failure to submit a manuscript for publication.23 A lack of time and fear of rejection after peer review are commonly cited explanations.18,23,24 Individuals may view acceptance for an oral presentation as positive reinforcement and be more motivated to pursue subsequent manuscript publication than individuals whose abstracts are offered poster presentations or are rejected. Trainees frequently present abstracts at scientific meetings, representing 40.3% of primary authors submitting abstracts to PHM in 2014, but may not have sufficient time or mentorship to develop a complete manuscript.18 To our knowledge, there have been no publications that assess the impact of trainee status on subsequent publication after conference submission.
Our study demonstrated that selection for oral presentation was associated with subsequent publication, shorter time to publication, and publication in journals with higher impact factors. A 2005 Cochrane review also demonstrated that selection for oral presentation was associated with subsequent journal publication.16 Abstracts accepted for oral publication may represent work further along in the research process, with more developed methodology and results. The shorter time to publication for abstracts accepted for oral presentation could also reflect feedback provided by conference attendees after the presentation, whereas poster sessions frequently lack a formalized process for critique.
Carroll et al. found no difference in time to publication between abstracts accepted for presentation at the PAS and rejected abstracts.20 Previous studies demonstrate that most abstracts presented at scientific meetings that are subsequently accepted for publication are published within 2 to 3 years of the meeting,12 with publication rates as high as 98% within 3 years of presentation.17 In contrast to Carroll et al., we found that abstracts accepted for oral presentation had a 4-fold greater likelihood of publication at each month than rejected abstracts. However, abstracts accepted for poster presentation did not have a significant difference in the proportional hazard ratio models for publication compared with rejected abstracts. Because space considerations limit the number of abstracts that can be accepted for presentation at a conference, some abstracts that are suitable for future publication may have been rejected due to a lack of space. Because researchers often use scientific meetings as a forum to receive peer feedback,12 authors who present at conferences may take more time to write a manuscript in order to incorporate this feedback.
The most common journal in which submitted abstracts were subsequently published was Hospital Pediatrics, representing twice as many published manuscripts as the second most frequent journal, Pediatrics. Hospital Pediatrics, which was first published in 2011, did not have an impact factor assigned during the study period. Yet, as a peer-reviewed journal dedicated to the field of PHM, it is well aligned with the research presented at the PHM meeting. It is unclear if Hospital Pediatrics is a journal to which pediatric hospitalists tend to submit manuscripts initially or if manuscripts are frequently submitted elsewhere prior to their publication in Hospital Pediatrics. Submission to other journals first likely extends the time to publication, especially for abstracts accepted for poster presentation, which may describe studies with less developed methods or results.
This study has several limitations. Previous studies have demonstrated mean time to publication of 12 to 32 months following abstract presentation with a median time of 19.6 months.16 Because we only have a 30-month follow-up, there may be abstracts still in the review process that are yet to be published, especially because the length of the review process varies by journal. We based our literature search on the first author of each PHM conference abstract submission, assuming that this presenting author would be one of the publishing authors even if not remaining first author; if this was not the case, we may have missed some abstracts that were subsequently published in full. Likewise, if a presenting author’s last name changed prior to the publication of a manuscript, a publication may have been missed. This limitation would cause us to underestimate the overall publication rate. It is not clear whether this would differentially affect the method of presentation. However, in this study, there was concordance between the presenting author and the publication’s first author in 87.8% of the abstracts subsequently published in full. Presenting authors who did not remain the first author on the published manuscript maintained authorship as either the senior author or second or third author, which may represent changes in the degree of involvement or a division of responsibilities for individuals working on a project together. While our search methods were comprehensive, there is a possibility that abstracts may have been published in a venue that was not searched. Additionally, we only reviewed abstracts submitted to PHM for 1 year. As the field matures and the number of fellowship programs increases, the quality of submitted abstracts may increase, leading to higher publication rates or shorter times to publication. It is also possible that the publication rate may not be reflective of PHM as a field because hospitalists may submit their work to conferences other than the PHM. Lastly, it may be more challenging to interpret any differences in impact factor because some journals, including Hospital Pediatrics (which represented a plurality of poster presentation abstracts that were subsequently published and is a relatively new journal), did not have an impact factor assigned during the study period. Assigning a 0 to journals without an impact factor may artificially lower the average impact factor reported. Furthermore, an impact factor, which is based on the frequency with which an individual journal’s articles are cited in scientific or medical publications, may not necessarily reflect a journal’s quality.
CONCLUSIONS
Of the 226 abstracts submitted to the 2014 PHM conference, approximately one-third were published in peer-reviewed journals within 30 months of the conference. Selection for oral presentation was found to be associated with subsequent publication as well as publication in journals with higher impact factors. The overall low publication rate may indicate a need for increased mentorship and resources for research development in this growing specialty. Improved mechanisms for author feedback at poster sessions may provide constructive suggestions for further development of these projects into full manuscripts or opportunities for trainees and early-career hospitalists to network with more experienced researchers in the field.
Disclosure
Drs. Herrmann, Hall, Kyler, Andrews, Williams, and Shah and Mr. Cochran have nothing to disclose. Dr. Wilson reports personal fees from the American Academy of Pediatrics during the conduct of the study. The authors have no financial relationships relevant to this article to disclose.
Pediatric hospital medicine (PHM) is one of the most rapidly growing disciplines in pediatrics,1 with 8% of pediatric residency graduates each year entering the field.2 Research plays an important role in advancing care in the field and is a critical component for board certification and fellowship accreditation.3-6 The annual PHM conference, which has been jointly sponsored by the Academic Pediatric Association, the American Academy of Pediatrics, and the Society of Hospital Medicine, is an important venue for the dissemination of research findings. Abstract selection is determined by peer review; however, reviewers are provided with only a brief snapshot of the research, which may not contain sufficient information to fully evaluate the methodological quality of the work.7-10 Additionally, while instructions are provided, reviewers often lack formal training in abstract review. Consequently, scores may vary.9
Publication in a peer-reviewed journal is considered a measure of research success because it requires more rigorous peer review than the abstract selection process at scientific meetings.11-16 Rates of subsequent journal publication differ based on specialty and meeting, and they have been reported at 23% to 78%.10,12,14-18 In pediatrics, publication rates after presentation at scientific meetings range from 36% to 63%, with mean time to publication ranging from 20 to 26 months following the meeting.11,19,20 No studies have reviewed abstract submissions to the annual PHM meeting to determine if selection or presentation format is associated with subsequent publication in a peer-reviewed journal.
We sought to identify the publication rate of abstracts submitted to the 2014 PHM conference and determine whether presentation format was associated with the likelihood of subsequent journal publication or time to publication.
METHODS
Study Design
Data for this retrospective cohort study were obtained from a database of all abstracts submitted for presentation at the 2014 PHM conference in Lake Buena Vista, Florida.
Main Exposures
The main exposure was presentation format, which was categorized as not presented (ie, rejected), poster presentation, or oral presentation. PHM has a blinded abstract peer-review process; in 2014, an average of 10 reviewers scored each abstract. Reviewers graded abstracts on a scale of 1 (best in category) to 7 (unacceptable for presentation) according to the following criteria: originality, scientific importance, methodological rigor, and quality of presentation. Abstracts with the lowest average scores in each content area, usually less than or equal to 3, were accepted as oral presentations while most abstracts with scores greater than 5 were rejected. For this study, information collected from each abstract included authors, if the primary author was a trainee, title, content area, and presentation format. Content areas included clinical research, educational research, health services research (HSR) and/or epidemiology, practice management research, and quality improvement. Abstracts were then grouped by presentation format and content area for analysis. The Pediatric Academic Societies (PAS) annual meeting, another common venue for the presentation of pediatric research, precedes the PHM conference. Because acceptance for PAS presentation may represent more strongly developed abstract submissions for PHM, we identified which abstracts had also been presented at the PAS conference that same year by cross-referencing authors and abstract titles with the PAS 2014 program.
Main Outcome Measures
All submissions were assessed for subsequent publication in peer-reviewed journals through January 2017 (30 months following the July 2014 PHM conference). To identify abstracts that went on to full publication, 2 authors (JC and LEH) independently searched for the lead author’s name and the presentation title in PubMed, Google Scholar, and MedEdPORTAL in January 2017. PubMed was searched using both the general search box and an advanced search for author and title. Google Scholar was added to capture manuscripts that may not have been indexed in PubMed at the time of our search. MedEdPORTAL, a common venue for the publication of educational initiatives that are not currently indexed in PubMed, was searched by lead author name via the general search box. If a full manuscript was published discussing similar outcomes or results and was written by the same authors who had submitted a PHM conference abstract, it was considered to have been published. The journal, month, and year of publication were recorded. For journals published every 2 months, the date of publication was recorded as falling between the 2 months. For those journals with biannual publication in the spring and fall, the months of March and October were used, respectively. The impact factor of the publication journal was also recorded for the year preceding publication. A journal’s impact factor is frequently used as a quantitative measure of journal quality and reflects the frequency with which a journal’s articles are cited in the scientific literature.21 Journals without an impact factor (eg, newer journals) were assigned a 0.
Data Analysis
All abstracts submitted to the PHM conference were analyzed based on content area and presentation format. The proportion of all abstracts subsequently published was determined for each format type and content area, and the odds ratio (OR) for publication after abstract submission was calculated using logistic regression. We calculated an adjusted OR for subsequent publication controlling for PAS presentation and the trainee status of the primary author. The journals most frequently publishing abstracts submitted to the PHM conference were identified. Median time to publication was calculated using the number of months elapsed between the PHM conference and publication date and compared across all abstract formats using Cox proportional hazards models adjusted for PAS presentation and trainee status. Kaplan-Meier survival curves were also generated for each of the 3 formats and compared using log-rank tests. The median impact factor was determined for each abstract format and compared using Wilcoxon rank-sum tests. Median impact factor by content area was compared using a Kruskal-Wallis test. All statistical analyses were performed using SAS version 9.2 (SAS Institute, Cary, NC). P values < 0.05 were considered statistically significant. In accordance with the Common Rule22 and the policies of the Cincinnati Children’s Hospital Medical Center Institutional Review Board, this research was not considered human subjects research.
RESULTS
For the 2014 PHM meeting, 226 abstracts were submitted, of which 183 (81.0%) were selected for presentation, including 154 (68.0%) as poster presentations and 29 (12.8%) as oral presentations. Of all submitted abstracts, 82 (36.3%) were published within 30 months following the meeting. Eighty-one of these (98.8%) were identified via PubMed, and 1 was found only in MedEdPORTAL. No additional publications were found via Google Scholar. The presenting author for the PHM abstract was the first author for 87.8% (n = 72) of the publications. A trainee was the presenting author for only 2 of these abstracts. For the publications in which the first author was not the presenting author, the presenting author was the senior author in 2 of the publications and the second or third author on the remaining 8. Of the abstracts accepted for presentation, 70 (38.3%) were subsequently published. Abstracts accepted for oral presentation had almost 7-fold greater odds of subsequent publication than those that were rejected (Table 1; OR 6.8; 95% confidence interval [CI], 2.4-19.4). Differences in the odds of publication for rejected abstracts compared with those accepted for poster presentation were not statistically significant (OR 1.2; 95% CI, 0.5-2.5).
DISCUSSION
About one-third of abstracts submitted to the 2014 PHM conference were subsequently published in peer-reviewed journals within 30 months of the conference. Compared with rejected abstracts, the rate of publication was significantly higher for abstracts selected for oral presentation but not for those selected for poster presentation. For abstracts ultimately published in journals, selection for oral presentation was significantly associated with both a shorter time to publication and a higher median journal impact factor compared with rejected abstracts. Time to publication and median journal impact factor were similar between rejected abstracts and those accepted for poster presentation. Our findings suggest that abstract reviewers may be able to identify which abstracts will ultimately withstand more stringent peer review in the publication process when accepting abstracts for oral presentation. However, the selection for poster presentation versus rejection may not be indicative of future publication or the impact factor of the subsequent publication journal.
Previous studies have reviewed publication rates after meetings of the European Society for Pediatric Urology (publication rate of 47%),11 the Ambulatory Pediatric Association (now the Academic Pediatric Association; publication rate of 47%), the American Pediatric Society/Society for Pediatric Research (publication rate of 54%), and the PAS (publication rate of 45%).19,20 Our lower publication rate of 36.3% may be attributed to the shorter follow-up time in our study (30 months from the PHM conference), whereas prior studies monitored for publication up to 60 months after the PAS conference.20 Factors associated with subsequent publication include statistically significant results, a large sample size, and a randomized controlled trial study design.15,16 The primary reason for nonpublication for up to 80% of abstracts is failure to submit a manuscript for publication.23 A lack of time and fear of rejection after peer review are commonly cited explanations.18,23,24 Individuals may view acceptance for an oral presentation as positive reinforcement and be more motivated to pursue subsequent manuscript publication than individuals whose abstracts are offered poster presentations or are rejected. Trainees frequently present abstracts at scientific meetings, representing 40.3% of primary authors submitting abstracts to PHM in 2014, but may not have sufficient time or mentorship to develop a complete manuscript.18 To our knowledge, there have been no publications that assess the impact of trainee status on subsequent publication after conference submission.
Our study demonstrated that selection for oral presentation was associated with subsequent publication, shorter time to publication, and publication in journals with higher impact factors. A 2005 Cochrane review also demonstrated that selection for oral presentation was associated with subsequent journal publication.16 Abstracts accepted for oral publication may represent work further along in the research process, with more developed methodology and results. The shorter time to publication for abstracts accepted for oral presentation could also reflect feedback provided by conference attendees after the presentation, whereas poster sessions frequently lack a formalized process for critique.
Carroll et al. found no difference in time to publication between abstracts accepted for presentation at the PAS and rejected abstracts.20 Previous studies demonstrate that most abstracts presented at scientific meetings that are subsequently accepted for publication are published within 2 to 3 years of the meeting,12 with publication rates as high as 98% within 3 years of presentation.17 In contrast to Carroll et al., we found that abstracts accepted for oral presentation had a 4-fold greater likelihood of publication at each month than rejected abstracts. However, abstracts accepted for poster presentation did not have a significant difference in the proportional hazard ratio models for publication compared with rejected abstracts. Because space considerations limit the number of abstracts that can be accepted for presentation at a conference, some abstracts that are suitable for future publication may have been rejected due to a lack of space. Because researchers often use scientific meetings as a forum to receive peer feedback,12 authors who present at conferences may take more time to write a manuscript in order to incorporate this feedback.
The most common journal in which submitted abstracts were subsequently published was Hospital Pediatrics, representing twice as many published manuscripts as the second most frequent journal, Pediatrics. Hospital Pediatrics, which was first published in 2011, did not have an impact factor assigned during the study period. Yet, as a peer-reviewed journal dedicated to the field of PHM, it is well aligned with the research presented at the PHM meeting. It is unclear if Hospital Pediatrics is a journal to which pediatric hospitalists tend to submit manuscripts initially or if manuscripts are frequently submitted elsewhere prior to their publication in Hospital Pediatrics. Submission to other journals first likely extends the time to publication, especially for abstracts accepted for poster presentation, which may describe studies with less developed methods or results.
This study has several limitations. Previous studies have demonstrated mean time to publication of 12 to 32 months following abstract presentation with a median time of 19.6 months.16 Because we only have a 30-month follow-up, there may be abstracts still in the review process that are yet to be published, especially because the length of the review process varies by journal. We based our literature search on the first author of each PHM conference abstract submission, assuming that this presenting author would be one of the publishing authors even if not remaining first author; if this was not the case, we may have missed some abstracts that were subsequently published in full. Likewise, if a presenting author’s last name changed prior to the publication of a manuscript, a publication may have been missed. This limitation would cause us to underestimate the overall publication rate. It is not clear whether this would differentially affect the method of presentation. However, in this study, there was concordance between the presenting author and the publication’s first author in 87.8% of the abstracts subsequently published in full. Presenting authors who did not remain the first author on the published manuscript maintained authorship as either the senior author or second or third author, which may represent changes in the degree of involvement or a division of responsibilities for individuals working on a project together. While our search methods were comprehensive, there is a possibility that abstracts may have been published in a venue that was not searched. Additionally, we only reviewed abstracts submitted to PHM for 1 year. As the field matures and the number of fellowship programs increases, the quality of submitted abstracts may increase, leading to higher publication rates or shorter times to publication. It is also possible that the publication rate may not be reflective of PHM as a field because hospitalists may submit their work to conferences other than the PHM. Lastly, it may be more challenging to interpret any differences in impact factor because some journals, including Hospital Pediatrics (which represented a plurality of poster presentation abstracts that were subsequently published and is a relatively new journal), did not have an impact factor assigned during the study period. Assigning a 0 to journals without an impact factor may artificially lower the average impact factor reported. Furthermore, an impact factor, which is based on the frequency with which an individual journal’s articles are cited in scientific or medical publications, may not necessarily reflect a journal’s quality.
CONCLUSIONS
Of the 226 abstracts submitted to the 2014 PHM conference, approximately one-third were published in peer-reviewed journals within 30 months of the conference. Selection for oral presentation was found to be associated with subsequent publication as well as publication in journals with higher impact factors. The overall low publication rate may indicate a need for increased mentorship and resources for research development in this growing specialty. Improved mechanisms for author feedback at poster sessions may provide constructive suggestions for further development of these projects into full manuscripts or opportunities for trainees and early-career hospitalists to network with more experienced researchers in the field.
Disclosure
Drs. Herrmann, Hall, Kyler, Andrews, Williams, and Shah and Mr. Cochran have nothing to disclose. Dr. Wilson reports personal fees from the American Academy of Pediatrics during the conduct of the study. The authors have no financial relationships relevant to this article to disclose.
1. Stucky ER, Ottolini MC, Maniscalco J. Pediatric hospital medicine core competencies: development and methodology. J Hosp Med. 2010;5(6):339-343. PubMed
2. Freed GL, McGuinness GA, Althouse LA, Moran LM, Spera L. Long-term plans for those selecting hospital medicine as an initial career choice. Hosp Pediatr. 2015;5(4):169-174. PubMed
3. Rauch D. Pediatric Hospital Medicine Subspecialty. 2016; https://www.aap.org/en-us/about-the-aap/Committees-Councils-Sections/Section-on-Hospital-Medicine/Pages/Pediatric-Hospital-Medicine-Subspecialty.aspx. Accessed November 28, 2016.
4. Bekmezian A, Teufel RJ, Wilson KM. Research needs of pediatric hospitalists. Hosp Pediatr. 2011;1(1):38-44. PubMed
5. Teufel RJ, Bekmezian A, Wilson K. Pediatric hospitalist research productivity: predictors of success at presenting abstracts and publishing peer-reviewed manuscripts among pediatric hospitalists. Hosp Pediatr. 2012;2(3):149-160. PubMed
6. Wilson KM, Shah SS, Simon TD, Srivastava R, Tieder JS. The challenge of pediatric hospital medicine research. Hosp Pediatr. 2012;2(1):8-9. PubMed
7. Froom P, Froom J. Presentation Deficiencies in structured medical abstracts. J Clin Epidemiol. 1993;46(7):591-594. PubMed
8. Relman AS. News reports of medical meetings: how reliable are abstracts? N Engl J Med. 1980;303(5):277-278. PubMed
9. Soffer A. Beware the 200-word abstract! Arch Intern Med. 1976;136(11):1232-1233. PubMed
10. Bhandari M, Devereaux P, Guyatt GH, et al. An observational study of orthopaedic abstracts and subsequent full-text publications. J Bone Joint Surg Am. 2002;84(4):615-621. PubMed
11. Castagnetti M, Subramaniam R, El-Ghoneimi A. Abstracts presented at the European Society for Pediatric Urology (ESPU) meetings (2003–2010): Characteristics and outcome. J Pediatr Urol. 2014;10(2):355-360. PubMed
12. Halikman R, Scolnik D, Rimon A, Glatstein MM. Peer-Reviewed Journal Publication of Abstracts Presented at an International Emergency Medicine Scientific Meeting: Outcomes and Comparison With the Previous Meeting. Pediatr Emerg Care. 2016. PubMed
13. Relman AS. Peer review in scientific journals--what good is it? West J Med. 1990;153(5):520. PubMed
14. Riordan F. Do presenters to paediatric meetings get their work published? Arch Dis Child. 2000;83(6):524-526. PubMed
15. Scherer RW, Dickersin K, Langenberg P. Full publication of results initially presented in abstracts: a meta-analysis. JAMA. 1994;272(2):158-162. PubMed
16. Scherer RW, Langenberg P, Elm E. Full publication of results initially presented in abstracts. Cochrane Database Syst Rev. 2005. PubMed
17. Marx WF, Cloft HJ, Do HM, Kallmes DF. The fate of neuroradiologic abstracts presented at national meetings in 1993: rate of subsequent publication in peer-reviewed, indexed journals. Am J Neuroradiol. 1999;20(6):1173-1177. PubMed
18. Roy D, Sankar V, Hughes J, Jones A, Fenton J. Publication rates of scientific papers presented at the Otorhinolarygological Research Society meetings. Clin Otolaryngol Allied Sci. 2001;26(3):253-256. PubMed
19. McCormick MC, Holmes JH. Publication of research presented at the pediatric meetings: change in selection. Am J Dis Child. 1985;139(2):122-126. PubMed
20. Carroll AE, Sox CM, Tarini BA, Ringold S, Christakis DA. Does presentation format at the Pediatric Academic Societies’ annual meeting predict subsequent publication? Pediatrics. 2003;112(6):1238-1241. PubMed
21. Saha S, Saint S, Christakis DA. Impact factor: a valid measure of journal quality? J Med Libr Assoc. 2003;91(1):42. PubMed
22. Office for Human Research Protections. Code of Federal Regulations, Title 45 Public Welfare: Part 46, Protection of Human Subjects, §46.102(f ). http://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr-46/index.html#46.102. Accessed October 21, 2016.
23. Weber EJ, Callaham ML, Wears RL, Barton C, Young G. Unpublished research from a medical specialty meeting: why investigators fail to publish. JAMA. 1998;280(3):257-259. PubMed
24. Timmer A, Hilsden RJ, Cole J, Hailey D, Sutherland LR. Publication bias in gastroenterological research–a retrospective cohort study based on abstracts submitted to a scientific meeting. BMC Med Res Methodol. 2002;2(1):1. PubMed
1. Stucky ER, Ottolini MC, Maniscalco J. Pediatric hospital medicine core competencies: development and methodology. J Hosp Med. 2010;5(6):339-343. PubMed
2. Freed GL, McGuinness GA, Althouse LA, Moran LM, Spera L. Long-term plans for those selecting hospital medicine as an initial career choice. Hosp Pediatr. 2015;5(4):169-174. PubMed
3. Rauch D. Pediatric Hospital Medicine Subspecialty. 2016; https://www.aap.org/en-us/about-the-aap/Committees-Councils-Sections/Section-on-Hospital-Medicine/Pages/Pediatric-Hospital-Medicine-Subspecialty.aspx. Accessed November 28, 2016.
4. Bekmezian A, Teufel RJ, Wilson KM. Research needs of pediatric hospitalists. Hosp Pediatr. 2011;1(1):38-44. PubMed
5. Teufel RJ, Bekmezian A, Wilson K. Pediatric hospitalist research productivity: predictors of success at presenting abstracts and publishing peer-reviewed manuscripts among pediatric hospitalists. Hosp Pediatr. 2012;2(3):149-160. PubMed
6. Wilson KM, Shah SS, Simon TD, Srivastava R, Tieder JS. The challenge of pediatric hospital medicine research. Hosp Pediatr. 2012;2(1):8-9. PubMed
7. Froom P, Froom J. Presentation Deficiencies in structured medical abstracts. J Clin Epidemiol. 1993;46(7):591-594. PubMed
8. Relman AS. News reports of medical meetings: how reliable are abstracts? N Engl J Med. 1980;303(5):277-278. PubMed
9. Soffer A. Beware the 200-word abstract! Arch Intern Med. 1976;136(11):1232-1233. PubMed
10. Bhandari M, Devereaux P, Guyatt GH, et al. An observational study of orthopaedic abstracts and subsequent full-text publications. J Bone Joint Surg Am. 2002;84(4):615-621. PubMed
11. Castagnetti M, Subramaniam R, El-Ghoneimi A. Abstracts presented at the European Society for Pediatric Urology (ESPU) meetings (2003–2010): Characteristics and outcome. J Pediatr Urol. 2014;10(2):355-360. PubMed
12. Halikman R, Scolnik D, Rimon A, Glatstein MM. Peer-Reviewed Journal Publication of Abstracts Presented at an International Emergency Medicine Scientific Meeting: Outcomes and Comparison With the Previous Meeting. Pediatr Emerg Care. 2016. PubMed
13. Relman AS. Peer review in scientific journals--what good is it? West J Med. 1990;153(5):520. PubMed
14. Riordan F. Do presenters to paediatric meetings get their work published? Arch Dis Child. 2000;83(6):524-526. PubMed
15. Scherer RW, Dickersin K, Langenberg P. Full publication of results initially presented in abstracts: a meta-analysis. JAMA. 1994;272(2):158-162. PubMed
16. Scherer RW, Langenberg P, Elm E. Full publication of results initially presented in abstracts. Cochrane Database Syst Rev. 2005. PubMed
17. Marx WF, Cloft HJ, Do HM, Kallmes DF. The fate of neuroradiologic abstracts presented at national meetings in 1993: rate of subsequent publication in peer-reviewed, indexed journals. Am J Neuroradiol. 1999;20(6):1173-1177. PubMed
18. Roy D, Sankar V, Hughes J, Jones A, Fenton J. Publication rates of scientific papers presented at the Otorhinolarygological Research Society meetings. Clin Otolaryngol Allied Sci. 2001;26(3):253-256. PubMed
19. McCormick MC, Holmes JH. Publication of research presented at the pediatric meetings: change in selection. Am J Dis Child. 1985;139(2):122-126. PubMed
20. Carroll AE, Sox CM, Tarini BA, Ringold S, Christakis DA. Does presentation format at the Pediatric Academic Societies’ annual meeting predict subsequent publication? Pediatrics. 2003;112(6):1238-1241. PubMed
21. Saha S, Saint S, Christakis DA. Impact factor: a valid measure of journal quality? J Med Libr Assoc. 2003;91(1):42. PubMed
22. Office for Human Research Protections. Code of Federal Regulations, Title 45 Public Welfare: Part 46, Protection of Human Subjects, §46.102(f ). http://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr-46/index.html#46.102. Accessed October 21, 2016.
23. Weber EJ, Callaham ML, Wears RL, Barton C, Young G. Unpublished research from a medical specialty meeting: why investigators fail to publish. JAMA. 1998;280(3):257-259. PubMed
24. Timmer A, Hilsden RJ, Cole J, Hailey D, Sutherland LR. Publication bias in gastroenterological research–a retrospective cohort study based on abstracts submitted to a scientific meeting. BMC Med Res Methodol. 2002;2(1):1. PubMed
© 2018 Society of Hospital Medicine
Do Combined Pharmacist and Prescriber Efforts on Medication Reconciliation Reduce Postdischarge Patient Emergency Department Visits and Hospital Readmissions?
Healthcare systems are targeting effective strategies to improve patient safety and reduce hospital readmissions. Hospital readmissions can be detrimental to patients’ health, a source of avoidable healthcare costs, and are frequently a reflection of the quality of patient care during transitions of care. Medication reconciliation (Med Rec) was identified as 1 of 12 interventions that may reduce 30-day readmissions; however, rigorously designed studies are scarce.1,2 Published systematic reviews and meta-analyses have produced mixed conclusions regarding the impact of Med Rec on unplanned 30-day readmissions.2-4
In several studies, researchers have established the positive impact of Med Rec on reducing patient medication discrepancies and potential adverse drug events.4-8 Pharmacy-led Med Rec interventions have been shown to easily identify more clinically relevant and higher impact medication discrepancies when compared to usual care.8 In a systematic review, Mueller et al.2 suggest that there are several interrelated elements that determine if a Med Rec intervention will influence hospital readmissions. These elements form a multicomponent “bundle” of interventions, including a systematic medication history process, admission reconciliation, patient education on discharge, discharge reconciliation, and communication to outpatient providers.9 Several prospective randomized controlled studies have demonstrated lower readmission rates and fewer visits to the emergency department (ED) after implementing a comprehensive, interprofessional, bundled intervention (including Med Rec) from admission to discharge.10-13 A 2016 systematic review and meta-analysis specifically evaluated pharmacy-led Med Rec programs (the majority of which included interventions involving multicomponent bundles) and demonstrated a significant reduction in posthospital healthcare utilization.14
Although comprehensive, interprofessional, bundled interventions have been shown to reduce readmission rates and ED visits in randomized controlled trials (RCTs), limited resources often prevent hospitals from consistently implementing all aspects of these multicomponent interventions. In practice, clinicians may provide varying components of the bundle, such as the combination of admission medication history by the pharmacist and discharge Med Rec completed by the physician alone. The unique impact of combined pharmacist and prescriber Med Rec interventions from admission to discharge on readmissions remains inconclusive. Further, it is unclear which high-risk patient groups will benefit the most from these interventions. We set out to evaluate the impact of an enhanced, interprofessional Med Rec process from admission to discharge (characterized within the context of a novel taxonomy continuum that specifies clinician involvement and intensity of services) on readmissions to hospital and ED visits within 30 days of discharge.
METHODS
We conducted a retrospective, observational, analytical cohort study using QuadraMed’s Computerized Patient Record and the EMITT (Electronic Medication Information Transfer Tool)15 to collect data from 2007 to 2011.
Setting
The study was conducted at a 417-bed tertiary care teaching hospital in Toronto, Ontario, Canada.
Med Rec Process and Description of Exposure (Intervention)
The targeted clinical areas had sustained interprofessional models of patient care in place from admission to discharge. They also were actively using an in-house EMITT to facilitate the documentation and tracking of Med Rec efforts throughout patient admission, transfer, and discharge.15 On admission, the pharmacist conducted a best possible medication history (BPMH). A BPMH provides the cornerstone for Med Rec. It differs from a routine medication history in that it involves (1) a systematic process for interviewing the patient (or family) and (2) a review of at least one other reliable source of information (eg, a provincial medication database, an inspection of medication vials, or contact with the community pharmacy) to obtain and verify patient medications (prescribed and nonprescribed). The pharmacist recorded the BPMH in the electronic patient record. The application supported admission and discharge Med Rec. On discharge, there were 2 options: (1) the prescriber alone would review and complete the discharge Med Rec and generate electronic prescriptions (Table 1, Silver level care) or (2) the pharmacist would collaborate with the prescriber to complete the discharge reconciliation and the prescriber would electronically generate prescriptions (Table 1, Gold level care). All clinical areas had a combined pharmacist and prescriber Med Rec model in place at admission, but the proportion of patients receiving discharge reconciliation completed by pharmacist and prescriber versus the prescriber-alone varied based on the individual clinician’s practices.
Patient Selection
All consecutive hospitalized patients admitted and discharged by the general internal medicine [GIM] service from March 2007 to December 2011 were included. The GIM service was chosen for the main analysis because they had been performing the intervention for the longest period of time and had the largest population of patients. Patients were identified via their hospital-specific medical record identification number and specific hospital-visit number. Patients were excluded if any of the following occurred: (1) the length of stay of their index admission was less than 24 hours; (2) they died during the visit; (3) they were transferred to a separate acute care inpatient facility; or (4) they left hospital against medical advice. Patient visits were excluded as index cases from the analysis if they were returning within 90 days of a previous discharge.
Outcomes
The primary study outcome was the occurrence of an inpatient readmission or ED visit within 30 days of discharge. In our secondary analyses, we examined the impact of the intervention on high-risk patient populations, such as those ≥65 years of age, with a length of stay, acuity of admission, Charlson comorbidity index, and emergency department visits in past 6 months (LACE) index score ≥10 (see supplementary Appendix 1 for LACE score description), on high-alert medications (1 or more of warfarin, insulin, digoxin, and opioids), and on ≥10 medications.
Data Collection
Identification of Exposure of Interest
We used the electronic database to capture all patients who received pharmacist and prescriber supported admission-to-discharge reconciliation. We explicitly defined increasing intensity of Med Rec care in categories of Bronze, Silver, and Gold care levels (Table 1). The exposed (intervention) group received an enhanced Med Rec bundle (patients receiving Gold level care). The control group was made of patients receiving a partial Med Rec Bundle (patients receiving Silver or Bronze level of care or below).
Determination of Hospital Visits
A search of administrative databases was used to determine if patients admitted to the targeted services had an ED visit or urgent inpatient admission to the study hospital within 30 days.
Statistical Analysis
A logistic regression for outcomes was performed. This yielded an adjusted odds ratio with a 95% confidence interval (CI) between the intervention and control groups. Statistical significance was determined with a 2-sided α level of 0.05. In the analysis, we used Statistical Analysis Software version 9.2.
In our multivariate logistic regression model, we adjusted for confounding factors that might influence the patients’ risk of readmission or the type of Med Rec they received upon discharge. By using administrative databases, patient level demographics, and the Charlson comorbidity index, the most responsible diagnosis and disease burden were collected. Medication-related factors collected included the number of medications on discharge and the presence of predefined high-alert medications. The number of medications on the medication discharge list was determined by using the electronic database. The final adjustment model included age, gender, the number of medications on discharge, and the LACE index score (supplementary Appendix 1). The LACE index score has been validated in Ontario, Canada, populations to quantify the risk of death or unplanned readmission within 30 days of discharge.24
Propensity Score Adjustment
Propensity scoring (probability of treatment assignment conditional on observed baseline characteristics) was planned a priori to account for possible factors that would impact whether a patient received the intervention or control care levels. The propensity score for receiving Med Rec was computed from a logistic model using Med Rec as the outcome. A structured iterative approach was used to refine this model to achieve covariate balance within the matched pairs. Covariate balance was measured by the standardized difference, in which an absolute standardized difference >10% represents meaningful imbalance.25 From the original cohort, we attempted to match patients who had the intervention to patients from the control by means of a matching algorithm using the logit of the propensity score for receiving the intervention.26
Subgroup Analysis
We also examined the impact of the intervention on high-risk patient populations such as those ≥65 years of age, with a LACE index score ≥10, on high-alert medications, and on ≥10 medications. A univariate analysis was conducted to identify patient-related risk predictors that may be independently correlated with a higher risk of hospital visits.
RESULTS
Baseline Characteristics
A total of 8678 patients representing 9931 unique visits met the inclusion criteria for analysis. There were 2541 unique visits (approximately 26% of visits) in the intervention group that received Gold level care and 7390 unique visits in the control group. The patients in the control group were largely patients who received the original standard of care at the institution, Silver level care (67% of the control group). Patients who received Bronze level care or less comprised 33% of the control group.
Patients in the intervention group were significantly older (average of 68 years old versus 64 years old) and on more medications. They also notably had a longer duration of stay in hospital, an increased percentage of visits with a LACE index score ≥10, and were more likely to be discharged home on a high-alert medication and with supports (Table 2).
Main Analysis
The main unadjusted analysis of GIM patients (n = 9931 visits) did not detect a difference in 30-day ED visits and readmissions between the intervention group (540 out of 2541; 21.2%) and control (1423 out of 7390; 19.3%; Table 3). By using a multivariate logistic regression model to account for age, sex, LACE index, and number of medications on discharge, the adjusted odds ratio was 1.06 (95% CI, 0.95-1.19; P = 0.33). After propensity score adjustment, the relative risk of readmission was 0.88 (16.7% vs 18.9%; 95% CI, 0.59-1.32; P = 0.54).
Secondary Analyses
In each predefined high-risk patient subgroup (age ≥65, LACE index score ≥10, number of discharge medications ≥10, and the presence of high-alert medications), analyses of our primary endpoint did not detect significant adjusted odds ratios (Table 4). In our univariate analysis, increasing number of medications, LACE index score, and male gender were independently correlated with a higher risk of hospital visits (supplementary Appendix 2).
DISCUSSION
Med Rec is widely recommended as a patient safety strategy to prevent clinically significant medication discrepancies at transitions in care.4-9 However, Med Rec varies widely in terms of what it entails and who delivers it, with the preponderance of evidence suggesting an impact on clinically significant medication discrepancies only when interprofessional care delivered includes a central role for pharmacists.27 Furthermore, Med Rec appears to impact short term readmissions only when embedded in a broader, multifaceted, bundled intervention in which pharmacists or other team members educate patients about their medications and deliver postdischarge follow-up phone calls.10-13
As very few hospitals have the resources to sustainably deliver intensive care bundles that are represented in RCTs (characterized by Platinum and Diamond levels of care in Table 1), in our observational study, we sought to explore whether a resource-attainable, enhanced Med Rec care bundle (Gold level) had an impact on hospital utilization compared to partial Med Rec care bundles (Bronze and Silver levels). In our findings, we did not detect a significant difference on ED visits and readmissions within 30 days between enhanced and partial care bundles. In a secondary analysis of the influence of the intervention on prespecified high-risk patient subgroups, we also did not detect a difference.
As far as we are aware, our long-term, observational study is the largest to date to explore a real-life, enhanced Med Rec intervention and examine its impact on meaningful patient outcomes. We extrapolated that our intervention group received several critical attributes of a successful bundle as discussed by Mueller in a systematic review.2 Our intervention included the following: (1) a systematic BPMH process on admission; (2) integrated admission-to-discharge reconciliation processes; (3) discharge delineation of medication changes since admission; (4) pharmacist involvement in reconciliation from admission to discharge; (5) an electronic platform; and (6) formal discharge reconciliation with interprofessional collaboration. Additional components in the bundle described by Mueller included the following: patient education at discharge, postdischarge communication with the patient, and communication with outpatient providers and medication management.
In our results, we did not find a difference in outcomes between the intervention and control groups. Therefore, it is possible that the enhanced bundle’s focus on interprofessional involvement in discharge reconciliation (Gold care level) has no impact on hospital utilization compared to partial care bundles (Silver and Bronze levels). Kwan et al.3 describe similar findings in their systematic review, in which they evaluated the effects of hospital-based Med Rec on unintentional discrepancies with nontrivial risks for harm to patients on 30-day postdischarge hospital visits. Kwan et al.3 concluded that larger well-designed studies are required to further evaluate this outcome, but authors of current published studies suggest that Med Rec alone probably does not reduce postdischarge hospital utilization within 30 days. Med Rec may have a more significant impact on utilization when bundled with other interventions that improve discharge coordination.3
There may be several reasons why we were unable to detect a significant difference between the intervention and control groups. One limitation is that our nonrandomized, retrospective design may have led to unmeasured confounders that impacted allocation into the intervention group versus the control group. It was notable that patients in the intervention group had an increased age, longer duration of hospital stay, more medications, and high-alert medications on discharge compared to the control group and that may have biased our results towards the null hypothesis. Although the propensity score analysis attempted to adjust for this, it also did not detect a significant difference between groups.
In addition, the existing standard of care during the study period allowed for patients in the control group to receive varying levels of Med Rec. Ideally, we would have compared the intervention to a placebo group that did not receive any Med Rec-related care elements. However, as this was a real-life observational study, the majority of patients received some Med Rec services as a part of the standard of care. As a result, 67% of patients in the control group received Silver level Med Rec with a BPMH, admission reconciliation, and prescriber-only discharge reconciliation. This may have made it more difficult to show an incremental benefit on readmissions between the intervention and control.
Also, our primary outcome of all-cause ED or hospital readmissions within 30 days may not have been sensitive enough to detect the effect of Med Rec interventions alone. Only a small proportion of readmissions within 30 days of discharge are preventable and many patient and community level factors responsible for readmissions cannot be controlled by the hospital’s actions.28 Comprehensive pharmacy interventions have demonstrated decreased hospitalizations and emergency visits at 12 months; however, the largest impact was seen on the more specific outcome of medication-related hospitalizations (80% reduction).29 Lastly, another limitation was that we were unable to capture hospital visits to other centres. However, in our region, almost 75% of readmissions are to the same site as the initial hospitalization.30
Overall, our findings in this study and novel characterization of Med Rec services are relevant to many hospital sites that are striving to implement integrated Med Rec with limited healthcare resources. Although interprofessional Med Rec likely reduces clinically significant medication discrepancies, enhanced interprofessional Med Rec on discharge (Gold Med Rec) alone may not be enough to impact hospital utilization compared to partial Med Rec services (Silver and Bronze Med Rec). Further research into practical, targeted Med Rec bundles on more specific outcomes (such as preventable postdischarge adverse events, “avoidable” hospital readmissions, and medication-related readmissions) may detect a significant benefit.
CONCLUSION
A long-term observational evaluation of interprofessional Med Rec did not detect a difference in 30-day postdischarge patient hospital visits between patients who received enhanced versus partial Med Rec patient care bundles. Researchers of future prospective studies could focus on evaluating high-risk populations or specific elements of Med Rec services on avoidable medication-related hospital admissions and postdischarge adverse drug events.
Acknowledgments
The authors thank Nita Dhir, MBA.
Presented as a poster and oral presentation at the 2012 American College of Clinical Pharmacy Annual Meeting, Hollywood, Florida, October 21-24, 2012, and as an encore poster presentation at the Canadian Society of Hospital Pharmacists Professional Practice Conference, Toronto, Canada, Feb 3, 2013.
Disclosure
The authors declare no conflicts of interest related to the manuscript submitted. All monies used for the research came from the University Health Network Department of Pharmacy Budget, including the pharmacy residency program.
1. Hansen LO, Young RS, Hinami K, Leung A, Williams MV. Interventions to reduce 30-day rehospitalization: a systematic review. Ann Intern Med. 2011;155:520-528. PubMed
2. Mueller SK, Sponsler KC, Kripalani S, Schnipper JL. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069. PubMed
3. Kwan JL, Lo L, Sampson M, Shojania KG. Medication reconciliation during transitions of care as a patient safety strategy: a systematic review. Ann Intern Med. 2013;158:397-403. PubMed
4. Safer Health Care Now. Medication Reconciliation in Home Care Getting Started Kit. March 2015. www.ismp-canada.org/download/MedRec/Medrec_HC_English_GSK_v2.pdf. Accessed August 22, 2017.
5. Karapinar-Çarkit F, Borgsteede SD, Zoer J, Smit HJ, Egberts AC, van den Bemt PM. Effect of medication reconciliation with and without patient counseling on the number of pharmaceutical interventions among patients discharged from the hospital. Ann Pharmacother. 2009;43(6):1001-1010. PubMed
6. Wong JD, Bajcar JM, Wong GG, et al. Medication reconciliation at hospital discharge: evaluating discrepancies. Ann Pharmacother. 2008;42(10):1373-1379. PubMed
7. Schnipper JL, Hamann C, Ndumele CD, et al. Effect of an electronic medication reconciliation application and process redesign on potential adverse drug events: a cluster-randomized trial. Arch Intern Med. 2009;169(8):771-780. PubMed
8. Mekonnen AB, McLachlan AJ, Brien JA. Pharmacy-led medication reconciliation programmes at hospital transitions: a systematic review and meta-analysis. J Clin Pharm Ther. 2016;41(2):128-144. PubMed
9. Kaboli PJ, Fernandes O. Medication reconciliation: moving forward. Arch Intern Med. 2012;172(14):1069-1070. PubMed
10. Koehler BE, Richter KM, Youngblood L, et al. Reduction of 30-day postdischarge hospital readmission or emergency department (ED) visit rates in high-risk elderly medical patients through delivery of a targeted care bundle. J Hosp Med. 2009;4:211-218. PubMed
11. Jack BW, Chetty VK, Anthony D, et al. A reengineered hospital discharge program to decrease rehospitalization: a randomized trial. Ann Intern Med. 2009;150:178-187. PubMed
12. Gillespie U, Alassaad A, Henrohn D, et al. A comprehensive pharmacist intervention to reduce morbidity in patients 80 years or older. Arch Intern Med. 2009:169(9):894-900. PubMed
13. Makowsky MJ, Koshman SL, Midodzi WK, Tsuyuki RT. Capturing outcomes of clinical activities performed by a rounding pharmacist practicing in a team environment: the COLLABORATE study [NCT00351676]. Med Care. 2009;47(6):642-650. PubMed
14. Mekonnen AB, McLachlan AJ, Brien JA. Effectiveness of pharmacist-led medication reconciliation programmes on clinical outcomes at hospital transitions: a systematic review and meta-analysis. BMJ Open. 2016;6(2):e010003. PubMed
15. Cesta A, Bajcar JM, Ong SW, Fernandes OA. The EMITT study: development and evaluation of a medication information transfer tool. Ann Pharmacother. 2006:40(6):1074-1081 PubMed
16. Cornish P, et al. Unintended medication discrepancies at the time of hospital admission. Arch Internal Medicine, 2005, Feb: 165: 424-29. PubMed
17. Kwan Y, Fernandes OA, Nagge JJ, et al. Pharmacist medication assessments in a surgical preadmission clinic. Arch Intern Med. 2007;167(10):1034-1040 PubMed
18. Dedhia P, Kravet S, Bulger J, et al. A quality improvement intervention to facilitate the transition of older adults from three hospitals back to their homes. J Am Geriatr Soc. 2009;57:1540–1546. PubMed
19. Murphy EM, Oxencis CJ, Klauck JA, et al. Medication reconciliation at an academic medical center: implementation of a comprehensive program from admission to discharge. Am J Health Syst Pharm. 2009;66:2126–31 PubMed
20. , , , , , . A pharmacy discharge plan for hospitalized elderly patients - a randomized controlled trial. Age and Ageing. 2001;30(1):33-40. PubMed
21. Al-Rashed SA, Wright DJ, Roebuck N, et al. The value of inpatient pharmaceutical counselling to elderly patients prior to discharge. Br J Clin Pharmacol. 2002 Dec;54(6):657–64. PubMed
22. Schnipper JL, Kirwin JL, Cotugno MC, et al. Role of pharmacist counseling in preventing adverse drug events after hospitalization. Arch Intern Med. 2006 Mar 13;166(5):565–71. PubMed
23. Walker PC, Bernstein SJ, Jones JN, et al. Impact of a pharmacist-facilitated hospital discharge program: a quasi-experimental study. Arch Intern Med. 2009 Nov 23;169(21):2003–10. PubMed
24. van Walraven C, Dhalla IA, Bell C, et al. Derivation and validation of an index to predict early death or unplanned readmission after discharge from hospital to the community. CMAJ. 2010;182(6):551-557. PubMed
25. Normand ST, Landrum MB, Guadagnoli E, et al. Validating recommendations for coronary angiography following an acute myocardial infarction in the elderly: a matched analysis using propensity scores. J Clin Epidemiol. 2001;54(4):387-398. PubMed
26. Rosenbaum PR., Donald BR. Constructing a control group using multivariate matched sampling methods that incorporate the propensity score. Am Stat. 1985;39(1):33-38.
27. Fernandes O, Shojania KG. Medication reconciliation in the hospital: what, why, where, when, who and how? Healthc Q. 2012;15(Special Issue):42-49. PubMed
28. Joynt KE, Jha AK. Thirty-day readmissions—truth and consequences. N Engl J Med. 2012;366(15):1366-1369. PubMed
29. Zed PJ, Abu-Laban RB, Balen RM, et al. Incidence, severity and preventability of medication-related visits to the emergency department: a prospective study. CMAJ. 2008;178(12):1563-1569. PubMed
30. Gruneir A, Dhalla IA, van Walraven C, et al. Unplanned readmissions after hospital discharge among patients identified as being at high risk for readmission using a validated predictive algorithm. Open Med. 2011;5(2):e104-e111. PubMed
Healthcare systems are targeting effective strategies to improve patient safety and reduce hospital readmissions. Hospital readmissions can be detrimental to patients’ health, a source of avoidable healthcare costs, and are frequently a reflection of the quality of patient care during transitions of care. Medication reconciliation (Med Rec) was identified as 1 of 12 interventions that may reduce 30-day readmissions; however, rigorously designed studies are scarce.1,2 Published systematic reviews and meta-analyses have produced mixed conclusions regarding the impact of Med Rec on unplanned 30-day readmissions.2-4
In several studies, researchers have established the positive impact of Med Rec on reducing patient medication discrepancies and potential adverse drug events.4-8 Pharmacy-led Med Rec interventions have been shown to easily identify more clinically relevant and higher impact medication discrepancies when compared to usual care.8 In a systematic review, Mueller et al.2 suggest that there are several interrelated elements that determine if a Med Rec intervention will influence hospital readmissions. These elements form a multicomponent “bundle” of interventions, including a systematic medication history process, admission reconciliation, patient education on discharge, discharge reconciliation, and communication to outpatient providers.9 Several prospective randomized controlled studies have demonstrated lower readmission rates and fewer visits to the emergency department (ED) after implementing a comprehensive, interprofessional, bundled intervention (including Med Rec) from admission to discharge.10-13 A 2016 systematic review and meta-analysis specifically evaluated pharmacy-led Med Rec programs (the majority of which included interventions involving multicomponent bundles) and demonstrated a significant reduction in posthospital healthcare utilization.14
Although comprehensive, interprofessional, bundled interventions have been shown to reduce readmission rates and ED visits in randomized controlled trials (RCTs), limited resources often prevent hospitals from consistently implementing all aspects of these multicomponent interventions. In practice, clinicians may provide varying components of the bundle, such as the combination of admission medication history by the pharmacist and discharge Med Rec completed by the physician alone. The unique impact of combined pharmacist and prescriber Med Rec interventions from admission to discharge on readmissions remains inconclusive. Further, it is unclear which high-risk patient groups will benefit the most from these interventions. We set out to evaluate the impact of an enhanced, interprofessional Med Rec process from admission to discharge (characterized within the context of a novel taxonomy continuum that specifies clinician involvement and intensity of services) on readmissions to hospital and ED visits within 30 days of discharge.
METHODS
We conducted a retrospective, observational, analytical cohort study using QuadraMed’s Computerized Patient Record and the EMITT (Electronic Medication Information Transfer Tool)15 to collect data from 2007 to 2011.
Setting
The study was conducted at a 417-bed tertiary care teaching hospital in Toronto, Ontario, Canada.
Med Rec Process and Description of Exposure (Intervention)
The targeted clinical areas had sustained interprofessional models of patient care in place from admission to discharge. They also were actively using an in-house EMITT to facilitate the documentation and tracking of Med Rec efforts throughout patient admission, transfer, and discharge.15 On admission, the pharmacist conducted a best possible medication history (BPMH). A BPMH provides the cornerstone for Med Rec. It differs from a routine medication history in that it involves (1) a systematic process for interviewing the patient (or family) and (2) a review of at least one other reliable source of information (eg, a provincial medication database, an inspection of medication vials, or contact with the community pharmacy) to obtain and verify patient medications (prescribed and nonprescribed). The pharmacist recorded the BPMH in the electronic patient record. The application supported admission and discharge Med Rec. On discharge, there were 2 options: (1) the prescriber alone would review and complete the discharge Med Rec and generate electronic prescriptions (Table 1, Silver level care) or (2) the pharmacist would collaborate with the prescriber to complete the discharge reconciliation and the prescriber would electronically generate prescriptions (Table 1, Gold level care). All clinical areas had a combined pharmacist and prescriber Med Rec model in place at admission, but the proportion of patients receiving discharge reconciliation completed by pharmacist and prescriber versus the prescriber-alone varied based on the individual clinician’s practices.
Patient Selection
All consecutive hospitalized patients admitted and discharged by the general internal medicine [GIM] service from March 2007 to December 2011 were included. The GIM service was chosen for the main analysis because they had been performing the intervention for the longest period of time and had the largest population of patients. Patients were identified via their hospital-specific medical record identification number and specific hospital-visit number. Patients were excluded if any of the following occurred: (1) the length of stay of their index admission was less than 24 hours; (2) they died during the visit; (3) they were transferred to a separate acute care inpatient facility; or (4) they left hospital against medical advice. Patient visits were excluded as index cases from the analysis if they were returning within 90 days of a previous discharge.
Outcomes
The primary study outcome was the occurrence of an inpatient readmission or ED visit within 30 days of discharge. In our secondary analyses, we examined the impact of the intervention on high-risk patient populations, such as those ≥65 years of age, with a length of stay, acuity of admission, Charlson comorbidity index, and emergency department visits in past 6 months (LACE) index score ≥10 (see supplementary Appendix 1 for LACE score description), on high-alert medications (1 or more of warfarin, insulin, digoxin, and opioids), and on ≥10 medications.
Data Collection
Identification of Exposure of Interest
We used the electronic database to capture all patients who received pharmacist and prescriber supported admission-to-discharge reconciliation. We explicitly defined increasing intensity of Med Rec care in categories of Bronze, Silver, and Gold care levels (Table 1). The exposed (intervention) group received an enhanced Med Rec bundle (patients receiving Gold level care). The control group was made of patients receiving a partial Med Rec Bundle (patients receiving Silver or Bronze level of care or below).
Determination of Hospital Visits
A search of administrative databases was used to determine if patients admitted to the targeted services had an ED visit or urgent inpatient admission to the study hospital within 30 days.
Statistical Analysis
A logistic regression for outcomes was performed. This yielded an adjusted odds ratio with a 95% confidence interval (CI) between the intervention and control groups. Statistical significance was determined with a 2-sided α level of 0.05. In the analysis, we used Statistical Analysis Software version 9.2.
In our multivariate logistic regression model, we adjusted for confounding factors that might influence the patients’ risk of readmission or the type of Med Rec they received upon discharge. By using administrative databases, patient level demographics, and the Charlson comorbidity index, the most responsible diagnosis and disease burden were collected. Medication-related factors collected included the number of medications on discharge and the presence of predefined high-alert medications. The number of medications on the medication discharge list was determined by using the electronic database. The final adjustment model included age, gender, the number of medications on discharge, and the LACE index score (supplementary Appendix 1). The LACE index score has been validated in Ontario, Canada, populations to quantify the risk of death or unplanned readmission within 30 days of discharge.24
Propensity Score Adjustment
Propensity scoring (probability of treatment assignment conditional on observed baseline characteristics) was planned a priori to account for possible factors that would impact whether a patient received the intervention or control care levels. The propensity score for receiving Med Rec was computed from a logistic model using Med Rec as the outcome. A structured iterative approach was used to refine this model to achieve covariate balance within the matched pairs. Covariate balance was measured by the standardized difference, in which an absolute standardized difference >10% represents meaningful imbalance.25 From the original cohort, we attempted to match patients who had the intervention to patients from the control by means of a matching algorithm using the logit of the propensity score for receiving the intervention.26
Subgroup Analysis
We also examined the impact of the intervention on high-risk patient populations such as those ≥65 years of age, with a LACE index score ≥10, on high-alert medications, and on ≥10 medications. A univariate analysis was conducted to identify patient-related risk predictors that may be independently correlated with a higher risk of hospital visits.
RESULTS
Baseline Characteristics
A total of 8678 patients representing 9931 unique visits met the inclusion criteria for analysis. There were 2541 unique visits (approximately 26% of visits) in the intervention group that received Gold level care and 7390 unique visits in the control group. The patients in the control group were largely patients who received the original standard of care at the institution, Silver level care (67% of the control group). Patients who received Bronze level care or less comprised 33% of the control group.
Patients in the intervention group were significantly older (average of 68 years old versus 64 years old) and on more medications. They also notably had a longer duration of stay in hospital, an increased percentage of visits with a LACE index score ≥10, and were more likely to be discharged home on a high-alert medication and with supports (Table 2).
Main Analysis
The main unadjusted analysis of GIM patients (n = 9931 visits) did not detect a difference in 30-day ED visits and readmissions between the intervention group (540 out of 2541; 21.2%) and control (1423 out of 7390; 19.3%; Table 3). By using a multivariate logistic regression model to account for age, sex, LACE index, and number of medications on discharge, the adjusted odds ratio was 1.06 (95% CI, 0.95-1.19; P = 0.33). After propensity score adjustment, the relative risk of readmission was 0.88 (16.7% vs 18.9%; 95% CI, 0.59-1.32; P = 0.54).
Secondary Analyses
In each predefined high-risk patient subgroup (age ≥65, LACE index score ≥10, number of discharge medications ≥10, and the presence of high-alert medications), analyses of our primary endpoint did not detect significant adjusted odds ratios (Table 4). In our univariate analysis, increasing number of medications, LACE index score, and male gender were independently correlated with a higher risk of hospital visits (supplementary Appendix 2).
DISCUSSION
Med Rec is widely recommended as a patient safety strategy to prevent clinically significant medication discrepancies at transitions in care.4-9 However, Med Rec varies widely in terms of what it entails and who delivers it, with the preponderance of evidence suggesting an impact on clinically significant medication discrepancies only when interprofessional care delivered includes a central role for pharmacists.27 Furthermore, Med Rec appears to impact short term readmissions only when embedded in a broader, multifaceted, bundled intervention in which pharmacists or other team members educate patients about their medications and deliver postdischarge follow-up phone calls.10-13
As very few hospitals have the resources to sustainably deliver intensive care bundles that are represented in RCTs (characterized by Platinum and Diamond levels of care in Table 1), in our observational study, we sought to explore whether a resource-attainable, enhanced Med Rec care bundle (Gold level) had an impact on hospital utilization compared to partial Med Rec care bundles (Bronze and Silver levels). In our findings, we did not detect a significant difference on ED visits and readmissions within 30 days between enhanced and partial care bundles. In a secondary analysis of the influence of the intervention on prespecified high-risk patient subgroups, we also did not detect a difference.
As far as we are aware, our long-term, observational study is the largest to date to explore a real-life, enhanced Med Rec intervention and examine its impact on meaningful patient outcomes. We extrapolated that our intervention group received several critical attributes of a successful bundle as discussed by Mueller in a systematic review.2 Our intervention included the following: (1) a systematic BPMH process on admission; (2) integrated admission-to-discharge reconciliation processes; (3) discharge delineation of medication changes since admission; (4) pharmacist involvement in reconciliation from admission to discharge; (5) an electronic platform; and (6) formal discharge reconciliation with interprofessional collaboration. Additional components in the bundle described by Mueller included the following: patient education at discharge, postdischarge communication with the patient, and communication with outpatient providers and medication management.
In our results, we did not find a difference in outcomes between the intervention and control groups. Therefore, it is possible that the enhanced bundle’s focus on interprofessional involvement in discharge reconciliation (Gold care level) has no impact on hospital utilization compared to partial care bundles (Silver and Bronze levels). Kwan et al.3 describe similar findings in their systematic review, in which they evaluated the effects of hospital-based Med Rec on unintentional discrepancies with nontrivial risks for harm to patients on 30-day postdischarge hospital visits. Kwan et al.3 concluded that larger well-designed studies are required to further evaluate this outcome, but authors of current published studies suggest that Med Rec alone probably does not reduce postdischarge hospital utilization within 30 days. Med Rec may have a more significant impact on utilization when bundled with other interventions that improve discharge coordination.3
There may be several reasons why we were unable to detect a significant difference between the intervention and control groups. One limitation is that our nonrandomized, retrospective design may have led to unmeasured confounders that impacted allocation into the intervention group versus the control group. It was notable that patients in the intervention group had an increased age, longer duration of hospital stay, more medications, and high-alert medications on discharge compared to the control group and that may have biased our results towards the null hypothesis. Although the propensity score analysis attempted to adjust for this, it also did not detect a significant difference between groups.
In addition, the existing standard of care during the study period allowed for patients in the control group to receive varying levels of Med Rec. Ideally, we would have compared the intervention to a placebo group that did not receive any Med Rec-related care elements. However, as this was a real-life observational study, the majority of patients received some Med Rec services as a part of the standard of care. As a result, 67% of patients in the control group received Silver level Med Rec with a BPMH, admission reconciliation, and prescriber-only discharge reconciliation. This may have made it more difficult to show an incremental benefit on readmissions between the intervention and control.
Also, our primary outcome of all-cause ED or hospital readmissions within 30 days may not have been sensitive enough to detect the effect of Med Rec interventions alone. Only a small proportion of readmissions within 30 days of discharge are preventable and many patient and community level factors responsible for readmissions cannot be controlled by the hospital’s actions.28 Comprehensive pharmacy interventions have demonstrated decreased hospitalizations and emergency visits at 12 months; however, the largest impact was seen on the more specific outcome of medication-related hospitalizations (80% reduction).29 Lastly, another limitation was that we were unable to capture hospital visits to other centres. However, in our region, almost 75% of readmissions are to the same site as the initial hospitalization.30
Overall, our findings in this study and novel characterization of Med Rec services are relevant to many hospital sites that are striving to implement integrated Med Rec with limited healthcare resources. Although interprofessional Med Rec likely reduces clinically significant medication discrepancies, enhanced interprofessional Med Rec on discharge (Gold Med Rec) alone may not be enough to impact hospital utilization compared to partial Med Rec services (Silver and Bronze Med Rec). Further research into practical, targeted Med Rec bundles on more specific outcomes (such as preventable postdischarge adverse events, “avoidable” hospital readmissions, and medication-related readmissions) may detect a significant benefit.
CONCLUSION
A long-term observational evaluation of interprofessional Med Rec did not detect a difference in 30-day postdischarge patient hospital visits between patients who received enhanced versus partial Med Rec patient care bundles. Researchers of future prospective studies could focus on evaluating high-risk populations or specific elements of Med Rec services on avoidable medication-related hospital admissions and postdischarge adverse drug events.
Acknowledgments
The authors thank Nita Dhir, MBA.
Presented as a poster and oral presentation at the 2012 American College of Clinical Pharmacy Annual Meeting, Hollywood, Florida, October 21-24, 2012, and as an encore poster presentation at the Canadian Society of Hospital Pharmacists Professional Practice Conference, Toronto, Canada, Feb 3, 2013.
Disclosure
The authors declare no conflicts of interest related to the manuscript submitted. All monies used for the research came from the University Health Network Department of Pharmacy Budget, including the pharmacy residency program.
Healthcare systems are targeting effective strategies to improve patient safety and reduce hospital readmissions. Hospital readmissions can be detrimental to patients’ health, a source of avoidable healthcare costs, and are frequently a reflection of the quality of patient care during transitions of care. Medication reconciliation (Med Rec) was identified as 1 of 12 interventions that may reduce 30-day readmissions; however, rigorously designed studies are scarce.1,2 Published systematic reviews and meta-analyses have produced mixed conclusions regarding the impact of Med Rec on unplanned 30-day readmissions.2-4
In several studies, researchers have established the positive impact of Med Rec on reducing patient medication discrepancies and potential adverse drug events.4-8 Pharmacy-led Med Rec interventions have been shown to easily identify more clinically relevant and higher impact medication discrepancies when compared to usual care.8 In a systematic review, Mueller et al.2 suggest that there are several interrelated elements that determine if a Med Rec intervention will influence hospital readmissions. These elements form a multicomponent “bundle” of interventions, including a systematic medication history process, admission reconciliation, patient education on discharge, discharge reconciliation, and communication to outpatient providers.9 Several prospective randomized controlled studies have demonstrated lower readmission rates and fewer visits to the emergency department (ED) after implementing a comprehensive, interprofessional, bundled intervention (including Med Rec) from admission to discharge.10-13 A 2016 systematic review and meta-analysis specifically evaluated pharmacy-led Med Rec programs (the majority of which included interventions involving multicomponent bundles) and demonstrated a significant reduction in posthospital healthcare utilization.14
Although comprehensive, interprofessional, bundled interventions have been shown to reduce readmission rates and ED visits in randomized controlled trials (RCTs), limited resources often prevent hospitals from consistently implementing all aspects of these multicomponent interventions. In practice, clinicians may provide varying components of the bundle, such as the combination of admission medication history by the pharmacist and discharge Med Rec completed by the physician alone. The unique impact of combined pharmacist and prescriber Med Rec interventions from admission to discharge on readmissions remains inconclusive. Further, it is unclear which high-risk patient groups will benefit the most from these interventions. We set out to evaluate the impact of an enhanced, interprofessional Med Rec process from admission to discharge (characterized within the context of a novel taxonomy continuum that specifies clinician involvement and intensity of services) on readmissions to hospital and ED visits within 30 days of discharge.
METHODS
We conducted a retrospective, observational, analytical cohort study using QuadraMed’s Computerized Patient Record and the EMITT (Electronic Medication Information Transfer Tool)15 to collect data from 2007 to 2011.
Setting
The study was conducted at a 417-bed tertiary care teaching hospital in Toronto, Ontario, Canada.
Med Rec Process and Description of Exposure (Intervention)
The targeted clinical areas had sustained interprofessional models of patient care in place from admission to discharge. They also were actively using an in-house EMITT to facilitate the documentation and tracking of Med Rec efforts throughout patient admission, transfer, and discharge.15 On admission, the pharmacist conducted a best possible medication history (BPMH). A BPMH provides the cornerstone for Med Rec. It differs from a routine medication history in that it involves (1) a systematic process for interviewing the patient (or family) and (2) a review of at least one other reliable source of information (eg, a provincial medication database, an inspection of medication vials, or contact with the community pharmacy) to obtain and verify patient medications (prescribed and nonprescribed). The pharmacist recorded the BPMH in the electronic patient record. The application supported admission and discharge Med Rec. On discharge, there were 2 options: (1) the prescriber alone would review and complete the discharge Med Rec and generate electronic prescriptions (Table 1, Silver level care) or (2) the pharmacist would collaborate with the prescriber to complete the discharge reconciliation and the prescriber would electronically generate prescriptions (Table 1, Gold level care). All clinical areas had a combined pharmacist and prescriber Med Rec model in place at admission, but the proportion of patients receiving discharge reconciliation completed by pharmacist and prescriber versus the prescriber-alone varied based on the individual clinician’s practices.
Patient Selection
All consecutive hospitalized patients admitted and discharged by the general internal medicine [GIM] service from March 2007 to December 2011 were included. The GIM service was chosen for the main analysis because they had been performing the intervention for the longest period of time and had the largest population of patients. Patients were identified via their hospital-specific medical record identification number and specific hospital-visit number. Patients were excluded if any of the following occurred: (1) the length of stay of their index admission was less than 24 hours; (2) they died during the visit; (3) they were transferred to a separate acute care inpatient facility; or (4) they left hospital against medical advice. Patient visits were excluded as index cases from the analysis if they were returning within 90 days of a previous discharge.
Outcomes
The primary study outcome was the occurrence of an inpatient readmission or ED visit within 30 days of discharge. In our secondary analyses, we examined the impact of the intervention on high-risk patient populations, such as those ≥65 years of age, with a length of stay, acuity of admission, Charlson comorbidity index, and emergency department visits in past 6 months (LACE) index score ≥10 (see supplementary Appendix 1 for LACE score description), on high-alert medications (1 or more of warfarin, insulin, digoxin, and opioids), and on ≥10 medications.
Data Collection
Identification of Exposure of Interest
We used the electronic database to capture all patients who received pharmacist and prescriber supported admission-to-discharge reconciliation. We explicitly defined increasing intensity of Med Rec care in categories of Bronze, Silver, and Gold care levels (Table 1). The exposed (intervention) group received an enhanced Med Rec bundle (patients receiving Gold level care). The control group was made of patients receiving a partial Med Rec Bundle (patients receiving Silver or Bronze level of care or below).
Determination of Hospital Visits
A search of administrative databases was used to determine if patients admitted to the targeted services had an ED visit or urgent inpatient admission to the study hospital within 30 days.
Statistical Analysis
A logistic regression for outcomes was performed. This yielded an adjusted odds ratio with a 95% confidence interval (CI) between the intervention and control groups. Statistical significance was determined with a 2-sided α level of 0.05. In the analysis, we used Statistical Analysis Software version 9.2.
In our multivariate logistic regression model, we adjusted for confounding factors that might influence the patients’ risk of readmission or the type of Med Rec they received upon discharge. By using administrative databases, patient level demographics, and the Charlson comorbidity index, the most responsible diagnosis and disease burden were collected. Medication-related factors collected included the number of medications on discharge and the presence of predefined high-alert medications. The number of medications on the medication discharge list was determined by using the electronic database. The final adjustment model included age, gender, the number of medications on discharge, and the LACE index score (supplementary Appendix 1). The LACE index score has been validated in Ontario, Canada, populations to quantify the risk of death or unplanned readmission within 30 days of discharge.24
Propensity Score Adjustment
Propensity scoring (probability of treatment assignment conditional on observed baseline characteristics) was planned a priori to account for possible factors that would impact whether a patient received the intervention or control care levels. The propensity score for receiving Med Rec was computed from a logistic model using Med Rec as the outcome. A structured iterative approach was used to refine this model to achieve covariate balance within the matched pairs. Covariate balance was measured by the standardized difference, in which an absolute standardized difference >10% represents meaningful imbalance.25 From the original cohort, we attempted to match patients who had the intervention to patients from the control by means of a matching algorithm using the logit of the propensity score for receiving the intervention.26
Subgroup Analysis
We also examined the impact of the intervention on high-risk patient populations such as those ≥65 years of age, with a LACE index score ≥10, on high-alert medications, and on ≥10 medications. A univariate analysis was conducted to identify patient-related risk predictors that may be independently correlated with a higher risk of hospital visits.
RESULTS
Baseline Characteristics
A total of 8678 patients representing 9931 unique visits met the inclusion criteria for analysis. There were 2541 unique visits (approximately 26% of visits) in the intervention group that received Gold level care and 7390 unique visits in the control group. The patients in the control group were largely patients who received the original standard of care at the institution, Silver level care (67% of the control group). Patients who received Bronze level care or less comprised 33% of the control group.
Patients in the intervention group were significantly older (average of 68 years old versus 64 years old) and on more medications. They also notably had a longer duration of stay in hospital, an increased percentage of visits with a LACE index score ≥10, and were more likely to be discharged home on a high-alert medication and with supports (Table 2).
Main Analysis
The main unadjusted analysis of GIM patients (n = 9931 visits) did not detect a difference in 30-day ED visits and readmissions between the intervention group (540 out of 2541; 21.2%) and control (1423 out of 7390; 19.3%; Table 3). By using a multivariate logistic regression model to account for age, sex, LACE index, and number of medications on discharge, the adjusted odds ratio was 1.06 (95% CI, 0.95-1.19; P = 0.33). After propensity score adjustment, the relative risk of readmission was 0.88 (16.7% vs 18.9%; 95% CI, 0.59-1.32; P = 0.54).
Secondary Analyses
In each predefined high-risk patient subgroup (age ≥65, LACE index score ≥10, number of discharge medications ≥10, and the presence of high-alert medications), analyses of our primary endpoint did not detect significant adjusted odds ratios (Table 4). In our univariate analysis, increasing number of medications, LACE index score, and male gender were independently correlated with a higher risk of hospital visits (supplementary Appendix 2).
DISCUSSION
Med Rec is widely recommended as a patient safety strategy to prevent clinically significant medication discrepancies at transitions in care.4-9 However, Med Rec varies widely in terms of what it entails and who delivers it, with the preponderance of evidence suggesting an impact on clinically significant medication discrepancies only when interprofessional care delivered includes a central role for pharmacists.27 Furthermore, Med Rec appears to impact short term readmissions only when embedded in a broader, multifaceted, bundled intervention in which pharmacists or other team members educate patients about their medications and deliver postdischarge follow-up phone calls.10-13
As very few hospitals have the resources to sustainably deliver intensive care bundles that are represented in RCTs (characterized by Platinum and Diamond levels of care in Table 1), in our observational study, we sought to explore whether a resource-attainable, enhanced Med Rec care bundle (Gold level) had an impact on hospital utilization compared to partial Med Rec care bundles (Bronze and Silver levels). In our findings, we did not detect a significant difference on ED visits and readmissions within 30 days between enhanced and partial care bundles. In a secondary analysis of the influence of the intervention on prespecified high-risk patient subgroups, we also did not detect a difference.
As far as we are aware, our long-term, observational study is the largest to date to explore a real-life, enhanced Med Rec intervention and examine its impact on meaningful patient outcomes. We extrapolated that our intervention group received several critical attributes of a successful bundle as discussed by Mueller in a systematic review.2 Our intervention included the following: (1) a systematic BPMH process on admission; (2) integrated admission-to-discharge reconciliation processes; (3) discharge delineation of medication changes since admission; (4) pharmacist involvement in reconciliation from admission to discharge; (5) an electronic platform; and (6) formal discharge reconciliation with interprofessional collaboration. Additional components in the bundle described by Mueller included the following: patient education at discharge, postdischarge communication with the patient, and communication with outpatient providers and medication management.
In our results, we did not find a difference in outcomes between the intervention and control groups. Therefore, it is possible that the enhanced bundle’s focus on interprofessional involvement in discharge reconciliation (Gold care level) has no impact on hospital utilization compared to partial care bundles (Silver and Bronze levels). Kwan et al.3 describe similar findings in their systematic review, in which they evaluated the effects of hospital-based Med Rec on unintentional discrepancies with nontrivial risks for harm to patients on 30-day postdischarge hospital visits. Kwan et al.3 concluded that larger well-designed studies are required to further evaluate this outcome, but authors of current published studies suggest that Med Rec alone probably does not reduce postdischarge hospital utilization within 30 days. Med Rec may have a more significant impact on utilization when bundled with other interventions that improve discharge coordination.3
There may be several reasons why we were unable to detect a significant difference between the intervention and control groups. One limitation is that our nonrandomized, retrospective design may have led to unmeasured confounders that impacted allocation into the intervention group versus the control group. It was notable that patients in the intervention group had an increased age, longer duration of hospital stay, more medications, and high-alert medications on discharge compared to the control group and that may have biased our results towards the null hypothesis. Although the propensity score analysis attempted to adjust for this, it also did not detect a significant difference between groups.
In addition, the existing standard of care during the study period allowed for patients in the control group to receive varying levels of Med Rec. Ideally, we would have compared the intervention to a placebo group that did not receive any Med Rec-related care elements. However, as this was a real-life observational study, the majority of patients received some Med Rec services as a part of the standard of care. As a result, 67% of patients in the control group received Silver level Med Rec with a BPMH, admission reconciliation, and prescriber-only discharge reconciliation. This may have made it more difficult to show an incremental benefit on readmissions between the intervention and control.
Also, our primary outcome of all-cause ED or hospital readmissions within 30 days may not have been sensitive enough to detect the effect of Med Rec interventions alone. Only a small proportion of readmissions within 30 days of discharge are preventable and many patient and community level factors responsible for readmissions cannot be controlled by the hospital’s actions.28 Comprehensive pharmacy interventions have demonstrated decreased hospitalizations and emergency visits at 12 months; however, the largest impact was seen on the more specific outcome of medication-related hospitalizations (80% reduction).29 Lastly, another limitation was that we were unable to capture hospital visits to other centres. However, in our region, almost 75% of readmissions are to the same site as the initial hospitalization.30
Overall, our findings in this study and novel characterization of Med Rec services are relevant to many hospital sites that are striving to implement integrated Med Rec with limited healthcare resources. Although interprofessional Med Rec likely reduces clinically significant medication discrepancies, enhanced interprofessional Med Rec on discharge (Gold Med Rec) alone may not be enough to impact hospital utilization compared to partial Med Rec services (Silver and Bronze Med Rec). Further research into practical, targeted Med Rec bundles on more specific outcomes (such as preventable postdischarge adverse events, “avoidable” hospital readmissions, and medication-related readmissions) may detect a significant benefit.
CONCLUSION
A long-term observational evaluation of interprofessional Med Rec did not detect a difference in 30-day postdischarge patient hospital visits between patients who received enhanced versus partial Med Rec patient care bundles. Researchers of future prospective studies could focus on evaluating high-risk populations or specific elements of Med Rec services on avoidable medication-related hospital admissions and postdischarge adverse drug events.
Acknowledgments
The authors thank Nita Dhir, MBA.
Presented as a poster and oral presentation at the 2012 American College of Clinical Pharmacy Annual Meeting, Hollywood, Florida, October 21-24, 2012, and as an encore poster presentation at the Canadian Society of Hospital Pharmacists Professional Practice Conference, Toronto, Canada, Feb 3, 2013.
Disclosure
The authors declare no conflicts of interest related to the manuscript submitted. All monies used for the research came from the University Health Network Department of Pharmacy Budget, including the pharmacy residency program.
1. Hansen LO, Young RS, Hinami K, Leung A, Williams MV. Interventions to reduce 30-day rehospitalization: a systematic review. Ann Intern Med. 2011;155:520-528. PubMed
2. Mueller SK, Sponsler KC, Kripalani S, Schnipper JL. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069. PubMed
3. Kwan JL, Lo L, Sampson M, Shojania KG. Medication reconciliation during transitions of care as a patient safety strategy: a systematic review. Ann Intern Med. 2013;158:397-403. PubMed
4. Safer Health Care Now. Medication Reconciliation in Home Care Getting Started Kit. March 2015. www.ismp-canada.org/download/MedRec/Medrec_HC_English_GSK_v2.pdf. Accessed August 22, 2017.
5. Karapinar-Çarkit F, Borgsteede SD, Zoer J, Smit HJ, Egberts AC, van den Bemt PM. Effect of medication reconciliation with and without patient counseling on the number of pharmaceutical interventions among patients discharged from the hospital. Ann Pharmacother. 2009;43(6):1001-1010. PubMed
6. Wong JD, Bajcar JM, Wong GG, et al. Medication reconciliation at hospital discharge: evaluating discrepancies. Ann Pharmacother. 2008;42(10):1373-1379. PubMed
7. Schnipper JL, Hamann C, Ndumele CD, et al. Effect of an electronic medication reconciliation application and process redesign on potential adverse drug events: a cluster-randomized trial. Arch Intern Med. 2009;169(8):771-780. PubMed
8. Mekonnen AB, McLachlan AJ, Brien JA. Pharmacy-led medication reconciliation programmes at hospital transitions: a systematic review and meta-analysis. J Clin Pharm Ther. 2016;41(2):128-144. PubMed
9. Kaboli PJ, Fernandes O. Medication reconciliation: moving forward. Arch Intern Med. 2012;172(14):1069-1070. PubMed
10. Koehler BE, Richter KM, Youngblood L, et al. Reduction of 30-day postdischarge hospital readmission or emergency department (ED) visit rates in high-risk elderly medical patients through delivery of a targeted care bundle. J Hosp Med. 2009;4:211-218. PubMed
11. Jack BW, Chetty VK, Anthony D, et al. A reengineered hospital discharge program to decrease rehospitalization: a randomized trial. Ann Intern Med. 2009;150:178-187. PubMed
12. Gillespie U, Alassaad A, Henrohn D, et al. A comprehensive pharmacist intervention to reduce morbidity in patients 80 years or older. Arch Intern Med. 2009:169(9):894-900. PubMed
13. Makowsky MJ, Koshman SL, Midodzi WK, Tsuyuki RT. Capturing outcomes of clinical activities performed by a rounding pharmacist practicing in a team environment: the COLLABORATE study [NCT00351676]. Med Care. 2009;47(6):642-650. PubMed
14. Mekonnen AB, McLachlan AJ, Brien JA. Effectiveness of pharmacist-led medication reconciliation programmes on clinical outcomes at hospital transitions: a systematic review and meta-analysis. BMJ Open. 2016;6(2):e010003. PubMed
15. Cesta A, Bajcar JM, Ong SW, Fernandes OA. The EMITT study: development and evaluation of a medication information transfer tool. Ann Pharmacother. 2006:40(6):1074-1081 PubMed
16. Cornish P, et al. Unintended medication discrepancies at the time of hospital admission. Arch Internal Medicine, 2005, Feb: 165: 424-29. PubMed
17. Kwan Y, Fernandes OA, Nagge JJ, et al. Pharmacist medication assessments in a surgical preadmission clinic. Arch Intern Med. 2007;167(10):1034-1040 PubMed
18. Dedhia P, Kravet S, Bulger J, et al. A quality improvement intervention to facilitate the transition of older adults from three hospitals back to their homes. J Am Geriatr Soc. 2009;57:1540–1546. PubMed
19. Murphy EM, Oxencis CJ, Klauck JA, et al. Medication reconciliation at an academic medical center: implementation of a comprehensive program from admission to discharge. Am J Health Syst Pharm. 2009;66:2126–31 PubMed
20. , , , , , . A pharmacy discharge plan for hospitalized elderly patients - a randomized controlled trial. Age and Ageing. 2001;30(1):33-40. PubMed
21. Al-Rashed SA, Wright DJ, Roebuck N, et al. The value of inpatient pharmaceutical counselling to elderly patients prior to discharge. Br J Clin Pharmacol. 2002 Dec;54(6):657–64. PubMed
22. Schnipper JL, Kirwin JL, Cotugno MC, et al. Role of pharmacist counseling in preventing adverse drug events after hospitalization. Arch Intern Med. 2006 Mar 13;166(5):565–71. PubMed
23. Walker PC, Bernstein SJ, Jones JN, et al. Impact of a pharmacist-facilitated hospital discharge program: a quasi-experimental study. Arch Intern Med. 2009 Nov 23;169(21):2003–10. PubMed
24. van Walraven C, Dhalla IA, Bell C, et al. Derivation and validation of an index to predict early death or unplanned readmission after discharge from hospital to the community. CMAJ. 2010;182(6):551-557. PubMed
25. Normand ST, Landrum MB, Guadagnoli E, et al. Validating recommendations for coronary angiography following an acute myocardial infarction in the elderly: a matched analysis using propensity scores. J Clin Epidemiol. 2001;54(4):387-398. PubMed
26. Rosenbaum PR., Donald BR. Constructing a control group using multivariate matched sampling methods that incorporate the propensity score. Am Stat. 1985;39(1):33-38.
27. Fernandes O, Shojania KG. Medication reconciliation in the hospital: what, why, where, when, who and how? Healthc Q. 2012;15(Special Issue):42-49. PubMed
28. Joynt KE, Jha AK. Thirty-day readmissions—truth and consequences. N Engl J Med. 2012;366(15):1366-1369. PubMed
29. Zed PJ, Abu-Laban RB, Balen RM, et al. Incidence, severity and preventability of medication-related visits to the emergency department: a prospective study. CMAJ. 2008;178(12):1563-1569. PubMed
30. Gruneir A, Dhalla IA, van Walraven C, et al. Unplanned readmissions after hospital discharge among patients identified as being at high risk for readmission using a validated predictive algorithm. Open Med. 2011;5(2):e104-e111. PubMed
1. Hansen LO, Young RS, Hinami K, Leung A, Williams MV. Interventions to reduce 30-day rehospitalization: a systematic review. Ann Intern Med. 2011;155:520-528. PubMed
2. Mueller SK, Sponsler KC, Kripalani S, Schnipper JL. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069. PubMed
3. Kwan JL, Lo L, Sampson M, Shojania KG. Medication reconciliation during transitions of care as a patient safety strategy: a systematic review. Ann Intern Med. 2013;158:397-403. PubMed
4. Safer Health Care Now. Medication Reconciliation in Home Care Getting Started Kit. March 2015. www.ismp-canada.org/download/MedRec/Medrec_HC_English_GSK_v2.pdf. Accessed August 22, 2017.
5. Karapinar-Çarkit F, Borgsteede SD, Zoer J, Smit HJ, Egberts AC, van den Bemt PM. Effect of medication reconciliation with and without patient counseling on the number of pharmaceutical interventions among patients discharged from the hospital. Ann Pharmacother. 2009;43(6):1001-1010. PubMed
6. Wong JD, Bajcar JM, Wong GG, et al. Medication reconciliation at hospital discharge: evaluating discrepancies. Ann Pharmacother. 2008;42(10):1373-1379. PubMed
7. Schnipper JL, Hamann C, Ndumele CD, et al. Effect of an electronic medication reconciliation application and process redesign on potential adverse drug events: a cluster-randomized trial. Arch Intern Med. 2009;169(8):771-780. PubMed
8. Mekonnen AB, McLachlan AJ, Brien JA. Pharmacy-led medication reconciliation programmes at hospital transitions: a systematic review and meta-analysis. J Clin Pharm Ther. 2016;41(2):128-144. PubMed
9. Kaboli PJ, Fernandes O. Medication reconciliation: moving forward. Arch Intern Med. 2012;172(14):1069-1070. PubMed
10. Koehler BE, Richter KM, Youngblood L, et al. Reduction of 30-day postdischarge hospital readmission or emergency department (ED) visit rates in high-risk elderly medical patients through delivery of a targeted care bundle. J Hosp Med. 2009;4:211-218. PubMed
11. Jack BW, Chetty VK, Anthony D, et al. A reengineered hospital discharge program to decrease rehospitalization: a randomized trial. Ann Intern Med. 2009;150:178-187. PubMed
12. Gillespie U, Alassaad A, Henrohn D, et al. A comprehensive pharmacist intervention to reduce morbidity in patients 80 years or older. Arch Intern Med. 2009:169(9):894-900. PubMed
13. Makowsky MJ, Koshman SL, Midodzi WK, Tsuyuki RT. Capturing outcomes of clinical activities performed by a rounding pharmacist practicing in a team environment: the COLLABORATE study [NCT00351676]. Med Care. 2009;47(6):642-650. PubMed
14. Mekonnen AB, McLachlan AJ, Brien JA. Effectiveness of pharmacist-led medication reconciliation programmes on clinical outcomes at hospital transitions: a systematic review and meta-analysis. BMJ Open. 2016;6(2):e010003. PubMed
15. Cesta A, Bajcar JM, Ong SW, Fernandes OA. The EMITT study: development and evaluation of a medication information transfer tool. Ann Pharmacother. 2006:40(6):1074-1081 PubMed
16. Cornish P, et al. Unintended medication discrepancies at the time of hospital admission. Arch Internal Medicine, 2005, Feb: 165: 424-29. PubMed
17. Kwan Y, Fernandes OA, Nagge JJ, et al. Pharmacist medication assessments in a surgical preadmission clinic. Arch Intern Med. 2007;167(10):1034-1040 PubMed
18. Dedhia P, Kravet S, Bulger J, et al. A quality improvement intervention to facilitate the transition of older adults from three hospitals back to their homes. J Am Geriatr Soc. 2009;57:1540–1546. PubMed
19. Murphy EM, Oxencis CJ, Klauck JA, et al. Medication reconciliation at an academic medical center: implementation of a comprehensive program from admission to discharge. Am J Health Syst Pharm. 2009;66:2126–31 PubMed
20. , , , , , . A pharmacy discharge plan for hospitalized elderly patients - a randomized controlled trial. Age and Ageing. 2001;30(1):33-40. PubMed
21. Al-Rashed SA, Wright DJ, Roebuck N, et al. The value of inpatient pharmaceutical counselling to elderly patients prior to discharge. Br J Clin Pharmacol. 2002 Dec;54(6):657–64. PubMed
22. Schnipper JL, Kirwin JL, Cotugno MC, et al. Role of pharmacist counseling in preventing adverse drug events after hospitalization. Arch Intern Med. 2006 Mar 13;166(5):565–71. PubMed
23. Walker PC, Bernstein SJ, Jones JN, et al. Impact of a pharmacist-facilitated hospital discharge program: a quasi-experimental study. Arch Intern Med. 2009 Nov 23;169(21):2003–10. PubMed
24. van Walraven C, Dhalla IA, Bell C, et al. Derivation and validation of an index to predict early death or unplanned readmission after discharge from hospital to the community. CMAJ. 2010;182(6):551-557. PubMed
25. Normand ST, Landrum MB, Guadagnoli E, et al. Validating recommendations for coronary angiography following an acute myocardial infarction in the elderly: a matched analysis using propensity scores. J Clin Epidemiol. 2001;54(4):387-398. PubMed
26. Rosenbaum PR., Donald BR. Constructing a control group using multivariate matched sampling methods that incorporate the propensity score. Am Stat. 1985;39(1):33-38.
27. Fernandes O, Shojania KG. Medication reconciliation in the hospital: what, why, where, when, who and how? Healthc Q. 2012;15(Special Issue):42-49. PubMed
28. Joynt KE, Jha AK. Thirty-day readmissions—truth and consequences. N Engl J Med. 2012;366(15):1366-1369. PubMed
29. Zed PJ, Abu-Laban RB, Balen RM, et al. Incidence, severity and preventability of medication-related visits to the emergency department: a prospective study. CMAJ. 2008;178(12):1563-1569. PubMed
30. Gruneir A, Dhalla IA, van Walraven C, et al. Unplanned readmissions after hospital discharge among patients identified as being at high risk for readmission using a validated predictive algorithm. Open Med. 2011;5(2):e104-e111. PubMed
© 2018 Society of Hospital Medicine
Supporting Faculty Development in Hospital Medicine: Design and Implementation of a Personalized Structured Mentoring Program
The lack of mentorship in hospital medicine has been previously documented,1-3 but there is scant literature about solutions to the problem.4 In other disciplines, data suggest that the guidance of a mentor has a positive influence on academic productivity and professional satisfaction. Mentored faculty at all levels in their careers are more successful at producing peer-reviewed publications, procuring grant support, and maintaining confidence in their career trajectory.
METHODS
The mentorship program was implemented from October 2015 to June 2016 in the Hospital Medicine Unit (HMU) of the Massachusetts General Hospital (MGH), a teaching affiliate of Harvard Medical School.
Program Goals, Design, and Development
Participants
Mentees had to be hired at >0.5 full-time equivalent and have 3 years or fewer of hospitalist experience.
Mentor–Mentee Matching
Mentors were paired with 1 or 2 mentees. Participant information such as history of mentorship and areas of interest for mentorship was collected. Two authors matched mentors and mentees to maximize similarities in these areas. Four mentors were paired with 2 mentees each, and 12 mentors were paired with 1 mentee each.
Mentorship Training Sessions
The program provided 3 mentorship-training lunch sessions for both mentees and mentors during the 9-month program. To enrich attendance, mentees were provided coverage for their clinical duties. The initial training session provided an opportunity to meet, articulate expectations and challenges, and develop action plans with individualized goals for the mentoring relationship. The second training session occurred at the midpoint. Pairs considered their mentorship status, evaluated their progress, and discussed strategies for optimizing their experience. At the final training session, participants reflected on their mentoring relationships, identified their extended network of mentoring support, and set expectations regarding whether the mentoring relationship would continue.
Mentorship Meetings
In addition to the training sessions, mentee–mentor pairs were expected to meet a minimum of 2 times during the formal mentorship program. CFD experts performed participant outreach via e-mail to assess progress. Mentees were given dining facility gift cards to support meetings with their mentors.
Program Evaluation
Statistical Analysis
RESULTS
Program Participation and Response Rate
Of the 25 eligible mentees, 16 (64%) participated in the mentorship program. Of the 20 eligible mentors, 12 (60%) participated. One participating mentee and 1 mentor left the institution during the intervention period. Fourteen mentees (response rate: 88%) and 9 mentors (response rate: 75%) completed the preintervention survey. Ten mentees (response rate: 63%) and 8 mentors (response rate: 67%) completed the postintervention survey.
Mentor Characteristics
Mentorship Meetings and the Mentorship Network
All participants attended at least 2 of the 3 trainings. For the mentees who completed the postintervention survey, 9 (90%) met with their mentors 3 or more additional times, and 8 (80%) were connected by their mentor to at least 1 additional faculty mentor.
Perceptions and Overall Satisfaction with Mentorship
Prior to starting the mentoring relationship, 86% of mentees and 78% of mentors anticipated that differing career goals would be a challenge to a successful mentor–mentee relationship. At the end of the program, only 30% of mentees and 38% of mentors felt that such differences were a challenge. Ninety percent of mentees and 88% of mentors were satisfied or very satisfied with their mentorship match. Forty-three percent of mentees felt supported by the HMU prior to the mentorship program, while 90% felt supported after the program. All the mentees agreed that future HMU faculty should participate in a similar program.
Impact of Mentorship on Critical Domains
At baseline, the following domains were most commonly rated as very important by mentees: career planning, professional connectedness, producing scholarly work, finding an area of expertise, balancing work and family life, and job satisfaction (Figure 1). There was a significant improvement in composite satisfaction scores after completion of the mentorship program (54.5 ± 6.2 vs 65 ± 14.9, P = 0.02). The influence of the mentorship program on all domains is shown in Figure 2.
DISCUSSION
Our pilot structured mentorship program for junior hospitalists was feasible and led to improved satisfaction in select key career domains. Other mentoring or faculty coaching programs have been studied in several fields of medicine10-12; however, to our knowledge, there have not been published data studying a structured mentorship program for junior faculty in hospital medicine. Our intervention prioritized not only optimizing mentorship matches but also formalizing training sessions led by content experts.
After experiencing a structured mentoring relationship, most mentees felt a greater sense of support, were satisfied with their mentoring experiences, were connected to additional faculty, and had significant improvement in satisfaction in key career domains. Satisfaction with other self-identified “very important” domains, including scholarly activity, finding an area of expertise, job satisfaction, and work and family-life balance, did not significantly improve by the end of the program.
Perceived challenges to mentoring did not persist to the same degree with the implementation of a structured program. This highlights the importance of building mentorship skill sets (such as mentoring across differences and goal setting) through expert-led training sessions and perhaps also the importance of matching based on career goals.
CONCLUSION
Effective and sustainable career development requires mentorship.
Acknowledgments
The authors would like to thank each of the participants in the HMU Mentorship Program and the MGH CFD and Division of General Internal Medicine for supporting this effort.
Disclosure
Funding was provided by the MGH DGIM and CFD. Dr. Regina O’Neill reports the following relevant financial relationship: Massachusetts General Hospital Center for Faculty Development (consultant). All other authors report no other financial or other conflicts of interest to disclose.
1. Harrison R, Hunter AJ, Sharpe B, Auerbach AD. Survey of US academic hospitalist leaders about mentorship and academic activities in hospitalist groups. J Hosp Med. 2011;6:5-9. PubMed
2. Reid MB, Misky GJ, Harrison RA, Sharpe B, Auerbach A, Glasheen JJ. Mentorship, productivity, and promotion among academic hospitalists. J Gen Intern Med. 2012;27:23-27. PubMed
3. Wiese J, Centor R. The need for mentors in the odyssey of the academic hospitalist. J Hosp Med. 2011;6:1-2. PubMed
4. Howell E, Kravet S, Kisuule F, Wright SM. An innovative approach to supporting hospitalist physicians towards academic success. J Hosp Med. 2008;3:314-318. PubMed
5. Berk RA, Berg J, Mortimer R, Walton-Moss B, Yeo TP. Measuring the effectiveness of faculty mentoring relationships. Acad Med. 2005;80:66-71. PubMed
6. Jackson VA, Palepu A, Szalacha L, Caswell C, Carr PL, Inui T. “Having the right chemistry”: a qualitative study of mentoring in academic medicine. Acad Med. 2003;78:328-334. PubMed
7. Ramanan RA, Phillips RS, Davis RB, Silen W, Reede JY. Mentoring in medicine: keys to satisfaction. Am J Med. 2002;112:336-341. PubMed
8. Steven A, Oxley J, Fleming WG. Mentoring for NHS doctors: perceived benefits across the personal-professional interface. J R Soc Med. 2008;101:552-557. PubMed
9. Jha AK, Orav EJ, Zheng J, Epstein AM. Patients’ perception of hospital care in the United States. N Engl J Med. 2008;359:1921-1931. PubMed
10. Pololi LH, Knight SM, Dennis K, Frankel RM. Helping medical school faculty realize their dreams: an innovative, collaborative mentoring program. Acad Med. 2002;77:377-384. PubMed
11. Sambunjak D, Straus SE, Marusic A. Mentoring in academic medicine: a systematic review. JAMA. 2006;296:1103-1115. PubMed
12. Sehgal NL, Sharpe BA, Auerbach AA, Wachter RM. Investing in the future: building an academic hospitalist faculty development program. J Hosp Med. 2011;6:161-166. PubMed
The lack of mentorship in hospital medicine has been previously documented,1-3 but there is scant literature about solutions to the problem.4 In other disciplines, data suggest that the guidance of a mentor has a positive influence on academic productivity and professional satisfaction. Mentored faculty at all levels in their careers are more successful at producing peer-reviewed publications, procuring grant support, and maintaining confidence in their career trajectory.
METHODS
The mentorship program was implemented from October 2015 to June 2016 in the Hospital Medicine Unit (HMU) of the Massachusetts General Hospital (MGH), a teaching affiliate of Harvard Medical School.
Program Goals, Design, and Development
Participants
Mentees had to be hired at >0.5 full-time equivalent and have 3 years or fewer of hospitalist experience.
Mentor–Mentee Matching
Mentors were paired with 1 or 2 mentees. Participant information such as history of mentorship and areas of interest for mentorship was collected. Two authors matched mentors and mentees to maximize similarities in these areas. Four mentors were paired with 2 mentees each, and 12 mentors were paired with 1 mentee each.
Mentorship Training Sessions
The program provided 3 mentorship-training lunch sessions for both mentees and mentors during the 9-month program. To enrich attendance, mentees were provided coverage for their clinical duties. The initial training session provided an opportunity to meet, articulate expectations and challenges, and develop action plans with individualized goals for the mentoring relationship. The second training session occurred at the midpoint. Pairs considered their mentorship status, evaluated their progress, and discussed strategies for optimizing their experience. At the final training session, participants reflected on their mentoring relationships, identified their extended network of mentoring support, and set expectations regarding whether the mentoring relationship would continue.
Mentorship Meetings
In addition to the training sessions, mentee–mentor pairs were expected to meet a minimum of 2 times during the formal mentorship program. CFD experts performed participant outreach via e-mail to assess progress. Mentees were given dining facility gift cards to support meetings with their mentors.
Program Evaluation
Statistical Analysis
RESULTS
Program Participation and Response Rate
Of the 25 eligible mentees, 16 (64%) participated in the mentorship program. Of the 20 eligible mentors, 12 (60%) participated. One participating mentee and 1 mentor left the institution during the intervention period. Fourteen mentees (response rate: 88%) and 9 mentors (response rate: 75%) completed the preintervention survey. Ten mentees (response rate: 63%) and 8 mentors (response rate: 67%) completed the postintervention survey.
Mentor Characteristics
Mentorship Meetings and the Mentorship Network
All participants attended at least 2 of the 3 trainings. For the mentees who completed the postintervention survey, 9 (90%) met with their mentors 3 or more additional times, and 8 (80%) were connected by their mentor to at least 1 additional faculty mentor.
Perceptions and Overall Satisfaction with Mentorship
Prior to starting the mentoring relationship, 86% of mentees and 78% of mentors anticipated that differing career goals would be a challenge to a successful mentor–mentee relationship. At the end of the program, only 30% of mentees and 38% of mentors felt that such differences were a challenge. Ninety percent of mentees and 88% of mentors were satisfied or very satisfied with their mentorship match. Forty-three percent of mentees felt supported by the HMU prior to the mentorship program, while 90% felt supported after the program. All the mentees agreed that future HMU faculty should participate in a similar program.
Impact of Mentorship on Critical Domains
At baseline, the following domains were most commonly rated as very important by mentees: career planning, professional connectedness, producing scholarly work, finding an area of expertise, balancing work and family life, and job satisfaction (Figure 1). There was a significant improvement in composite satisfaction scores after completion of the mentorship program (54.5 ± 6.2 vs 65 ± 14.9, P = 0.02). The influence of the mentorship program on all domains is shown in Figure 2.
DISCUSSION
Our pilot structured mentorship program for junior hospitalists was feasible and led to improved satisfaction in select key career domains. Other mentoring or faculty coaching programs have been studied in several fields of medicine10-12; however, to our knowledge, there have not been published data studying a structured mentorship program for junior faculty in hospital medicine. Our intervention prioritized not only optimizing mentorship matches but also formalizing training sessions led by content experts.
After experiencing a structured mentoring relationship, most mentees felt a greater sense of support, were satisfied with their mentoring experiences, were connected to additional faculty, and had significant improvement in satisfaction in key career domains. Satisfaction with other self-identified “very important” domains, including scholarly activity, finding an area of expertise, job satisfaction, and work and family-life balance, did not significantly improve by the end of the program.
Perceived challenges to mentoring did not persist to the same degree with the implementation of a structured program. This highlights the importance of building mentorship skill sets (such as mentoring across differences and goal setting) through expert-led training sessions and perhaps also the importance of matching based on career goals.
CONCLUSION
Effective and sustainable career development requires mentorship.
Acknowledgments
The authors would like to thank each of the participants in the HMU Mentorship Program and the MGH CFD and Division of General Internal Medicine for supporting this effort.
Disclosure
Funding was provided by the MGH DGIM and CFD. Dr. Regina O’Neill reports the following relevant financial relationship: Massachusetts General Hospital Center for Faculty Development (consultant). All other authors report no other financial or other conflicts of interest to disclose.
The lack of mentorship in hospital medicine has been previously documented,1-3 but there is scant literature about solutions to the problem.4 In other disciplines, data suggest that the guidance of a mentor has a positive influence on academic productivity and professional satisfaction. Mentored faculty at all levels in their careers are more successful at producing peer-reviewed publications, procuring grant support, and maintaining confidence in their career trajectory.
METHODS
The mentorship program was implemented from October 2015 to June 2016 in the Hospital Medicine Unit (HMU) of the Massachusetts General Hospital (MGH), a teaching affiliate of Harvard Medical School.
Program Goals, Design, and Development
Participants
Mentees had to be hired at >0.5 full-time equivalent and have 3 years or fewer of hospitalist experience.
Mentor–Mentee Matching
Mentors were paired with 1 or 2 mentees. Participant information such as history of mentorship and areas of interest for mentorship was collected. Two authors matched mentors and mentees to maximize similarities in these areas. Four mentors were paired with 2 mentees each, and 12 mentors were paired with 1 mentee each.
Mentorship Training Sessions
The program provided 3 mentorship-training lunch sessions for both mentees and mentors during the 9-month program. To enrich attendance, mentees were provided coverage for their clinical duties. The initial training session provided an opportunity to meet, articulate expectations and challenges, and develop action plans with individualized goals for the mentoring relationship. The second training session occurred at the midpoint. Pairs considered their mentorship status, evaluated their progress, and discussed strategies for optimizing their experience. At the final training session, participants reflected on their mentoring relationships, identified their extended network of mentoring support, and set expectations regarding whether the mentoring relationship would continue.
Mentorship Meetings
In addition to the training sessions, mentee–mentor pairs were expected to meet a minimum of 2 times during the formal mentorship program. CFD experts performed participant outreach via e-mail to assess progress. Mentees were given dining facility gift cards to support meetings with their mentors.
Program Evaluation
Statistical Analysis
RESULTS
Program Participation and Response Rate
Of the 25 eligible mentees, 16 (64%) participated in the mentorship program. Of the 20 eligible mentors, 12 (60%) participated. One participating mentee and 1 mentor left the institution during the intervention period. Fourteen mentees (response rate: 88%) and 9 mentors (response rate: 75%) completed the preintervention survey. Ten mentees (response rate: 63%) and 8 mentors (response rate: 67%) completed the postintervention survey.
Mentor Characteristics
Mentorship Meetings and the Mentorship Network
All participants attended at least 2 of the 3 trainings. For the mentees who completed the postintervention survey, 9 (90%) met with their mentors 3 or more additional times, and 8 (80%) were connected by their mentor to at least 1 additional faculty mentor.
Perceptions and Overall Satisfaction with Mentorship
Prior to starting the mentoring relationship, 86% of mentees and 78% of mentors anticipated that differing career goals would be a challenge to a successful mentor–mentee relationship. At the end of the program, only 30% of mentees and 38% of mentors felt that such differences were a challenge. Ninety percent of mentees and 88% of mentors were satisfied or very satisfied with their mentorship match. Forty-three percent of mentees felt supported by the HMU prior to the mentorship program, while 90% felt supported after the program. All the mentees agreed that future HMU faculty should participate in a similar program.
Impact of Mentorship on Critical Domains
At baseline, the following domains were most commonly rated as very important by mentees: career planning, professional connectedness, producing scholarly work, finding an area of expertise, balancing work and family life, and job satisfaction (Figure 1). There was a significant improvement in composite satisfaction scores after completion of the mentorship program (54.5 ± 6.2 vs 65 ± 14.9, P = 0.02). The influence of the mentorship program on all domains is shown in Figure 2.
DISCUSSION
Our pilot structured mentorship program for junior hospitalists was feasible and led to improved satisfaction in select key career domains. Other mentoring or faculty coaching programs have been studied in several fields of medicine10-12; however, to our knowledge, there have not been published data studying a structured mentorship program for junior faculty in hospital medicine. Our intervention prioritized not only optimizing mentorship matches but also formalizing training sessions led by content experts.
After experiencing a structured mentoring relationship, most mentees felt a greater sense of support, were satisfied with their mentoring experiences, were connected to additional faculty, and had significant improvement in satisfaction in key career domains. Satisfaction with other self-identified “very important” domains, including scholarly activity, finding an area of expertise, job satisfaction, and work and family-life balance, did not significantly improve by the end of the program.
Perceived challenges to mentoring did not persist to the same degree with the implementation of a structured program. This highlights the importance of building mentorship skill sets (such as mentoring across differences and goal setting) through expert-led training sessions and perhaps also the importance of matching based on career goals.
CONCLUSION
Effective and sustainable career development requires mentorship.
Acknowledgments
The authors would like to thank each of the participants in the HMU Mentorship Program and the MGH CFD and Division of General Internal Medicine for supporting this effort.
Disclosure
Funding was provided by the MGH DGIM and CFD. Dr. Regina O’Neill reports the following relevant financial relationship: Massachusetts General Hospital Center for Faculty Development (consultant). All other authors report no other financial or other conflicts of interest to disclose.
1. Harrison R, Hunter AJ, Sharpe B, Auerbach AD. Survey of US academic hospitalist leaders about mentorship and academic activities in hospitalist groups. J Hosp Med. 2011;6:5-9. PubMed
2. Reid MB, Misky GJ, Harrison RA, Sharpe B, Auerbach A, Glasheen JJ. Mentorship, productivity, and promotion among academic hospitalists. J Gen Intern Med. 2012;27:23-27. PubMed
3. Wiese J, Centor R. The need for mentors in the odyssey of the academic hospitalist. J Hosp Med. 2011;6:1-2. PubMed
4. Howell E, Kravet S, Kisuule F, Wright SM. An innovative approach to supporting hospitalist physicians towards academic success. J Hosp Med. 2008;3:314-318. PubMed
5. Berk RA, Berg J, Mortimer R, Walton-Moss B, Yeo TP. Measuring the effectiveness of faculty mentoring relationships. Acad Med. 2005;80:66-71. PubMed
6. Jackson VA, Palepu A, Szalacha L, Caswell C, Carr PL, Inui T. “Having the right chemistry”: a qualitative study of mentoring in academic medicine. Acad Med. 2003;78:328-334. PubMed
7. Ramanan RA, Phillips RS, Davis RB, Silen W, Reede JY. Mentoring in medicine: keys to satisfaction. Am J Med. 2002;112:336-341. PubMed
8. Steven A, Oxley J, Fleming WG. Mentoring for NHS doctors: perceived benefits across the personal-professional interface. J R Soc Med. 2008;101:552-557. PubMed
9. Jha AK, Orav EJ, Zheng J, Epstein AM. Patients’ perception of hospital care in the United States. N Engl J Med. 2008;359:1921-1931. PubMed
10. Pololi LH, Knight SM, Dennis K, Frankel RM. Helping medical school faculty realize their dreams: an innovative, collaborative mentoring program. Acad Med. 2002;77:377-384. PubMed
11. Sambunjak D, Straus SE, Marusic A. Mentoring in academic medicine: a systematic review. JAMA. 2006;296:1103-1115. PubMed
12. Sehgal NL, Sharpe BA, Auerbach AA, Wachter RM. Investing in the future: building an academic hospitalist faculty development program. J Hosp Med. 2011;6:161-166. PubMed
1. Harrison R, Hunter AJ, Sharpe B, Auerbach AD. Survey of US academic hospitalist leaders about mentorship and academic activities in hospitalist groups. J Hosp Med. 2011;6:5-9. PubMed
2. Reid MB, Misky GJ, Harrison RA, Sharpe B, Auerbach A, Glasheen JJ. Mentorship, productivity, and promotion among academic hospitalists. J Gen Intern Med. 2012;27:23-27. PubMed
3. Wiese J, Centor R. The need for mentors in the odyssey of the academic hospitalist. J Hosp Med. 2011;6:1-2. PubMed
4. Howell E, Kravet S, Kisuule F, Wright SM. An innovative approach to supporting hospitalist physicians towards academic success. J Hosp Med. 2008;3:314-318. PubMed
5. Berk RA, Berg J, Mortimer R, Walton-Moss B, Yeo TP. Measuring the effectiveness of faculty mentoring relationships. Acad Med. 2005;80:66-71. PubMed
6. Jackson VA, Palepu A, Szalacha L, Caswell C, Carr PL, Inui T. “Having the right chemistry”: a qualitative study of mentoring in academic medicine. Acad Med. 2003;78:328-334. PubMed
7. Ramanan RA, Phillips RS, Davis RB, Silen W, Reede JY. Mentoring in medicine: keys to satisfaction. Am J Med. 2002;112:336-341. PubMed
8. Steven A, Oxley J, Fleming WG. Mentoring for NHS doctors: perceived benefits across the personal-professional interface. J R Soc Med. 2008;101:552-557. PubMed
9. Jha AK, Orav EJ, Zheng J, Epstein AM. Patients’ perception of hospital care in the United States. N Engl J Med. 2008;359:1921-1931. PubMed
10. Pololi LH, Knight SM, Dennis K, Frankel RM. Helping medical school faculty realize their dreams: an innovative, collaborative mentoring program. Acad Med. 2002;77:377-384. PubMed
11. Sambunjak D, Straus SE, Marusic A. Mentoring in academic medicine: a systematic review. JAMA. 2006;296:1103-1115. PubMed
12. Sehgal NL, Sharpe BA, Auerbach AA, Wachter RM. Investing in the future: building an academic hospitalist faculty development program. J Hosp Med. 2011;6:161-166. PubMed
© 2018 Society of Hospital Medicine
The Enhanced Care Program: Impact of a Care Transition Program on 30-Day Hospital Readmissions for Patients Discharged From an Acute Care Facility to Skilled Nursing Facilities
Public reporting of readmission rates on the Nursing Home Compare website is mandated to begin on October 1, 2017, with skilled nursing facilities (SNFs) set to receive a Medicare bonus or penalty beginning a year later.1 The Centers for Medicare & Medicaid Services (CMS) began public reporting of hospitals’ 30-day readmission rates for selected conditions in 2009, and the Patient Protection and Affordable Care Act of 2010 mandated financial penalties for excess readmissions through the Hospital Readmission Reduction Program.2 In response, most hospitals have focused on patients who return home following discharge. Innovative interventions have proven successful, such as the Transitional Care model developed by Naylor and Coleman’s Care Transitions Intervention.3-5 Approximately 20% of Medicare beneficiaries are discharged from hospitals to SNFs, and these patients have higher readmission rates than those discharged home. CMS reported that in 2010, 23.3% of those with an SNF stay were readmitted within 30 days, compared with 18.8% for those with other discharge dispositions.6
Some work has been undertaken in this arena. In 2012, the Center for Medicare and Medicaid Innovation (CMMI) and the Medicare-Medicaid Coordination Office jointly launched the Initiative to Reduce Avoidable Hospitalizations among Nursing Facility Residents.7 This partnership established 7 Enhanced Care and Coordination Provider organizations and was designed to improve care by reducing hospitalizations among long-stay, dual-eligible nursing facility residents at 143 nursing homes in 7 states.8 At the time of the most recent project report, there were mixed results regarding program effects on hospitalizations and spending, with 2 states showing strongly positive patterns, 3 states with reductions that were consistent though not statistically strong, and mixed results in the remaining states. Quality measures did not show any pattern suggesting a program effect.9 Interventions to Reduce Acute Care Transfers (INTERACT) II was a 6-month, collaborative, quality-improvement project implemented in 2009 at 30 nursing homes in 3 states.10 The project evaluation found a statistically significant, 17% decrease in self-reported hospital admissions among the 25 SNFs that completed the intervention, compared with the same 6 months in the prior year. The Cleveland Clinic recently reported favorable results implementing its Connected Care model, which relied on staff physicians and advanced practice professionals to visit patients 4 to 5 times per week and be on call 24/7 at 7 intervention SNFs.11 Through this intervention, it successfully reduced its 30-day hospital readmission rate from SNFs from 28.1% to 21.7% (P < 0.001), and the authors posed the question as to whether its model and results were reproducible in other healthcare systems.
Herein, we report on the results of a collaborative initiative named the Enhanced Care Program (ECP), which offers the services of clinical providers and administrative staff to assist with the care of patients at 8 partner SNFs. The 3 components of ECP (described below) were specifically designed to address commonly recognized gaps and opportunities in routine SNF care. In contrast to the Cleveland Clinic’s Connected Care model (which involved hospital-employed physicians serving as the SNF attendings and excluded patients followed by their own physicians), ECP was designed to integrate into a pluralistic, community model whereby independent physicians continued to follow their own patients at the SNFs. The Connected Care analysis compared participating versus nonparticipating SNFs; both the Connected Care model and the INTERACT II evaluation relied on pre–post comparisons; the CMMI evaluation used a difference-in-differences model to compare the outcomes of the program SNFs with those of a matched comparison group of nonparticipating SNFs. The evaluation of ECP differs from these other initiatives, using a concurrent comparison group of patients discharged to the same SNFs but who were not enrolled in ECP.
METHODS
Setting
Cedars-Sinai Medical Center (CSMC) is an 850-bed, acute care facility located in an urban area of Los Angeles. Eight SNFs, ranging in size from 49 to 150 beds and located between 0.6 and 2.2 miles from CSMC, were invited to partner with the ECP. The physician community encompasses more than 2000 physicians on the medical staff, including private practitioners, nonteaching hospitalists, full-time faculty hospitalists, and faculty specialists.
Study Design and Patients
This was an observational, retrospective cohort analysis of 30-day same-hospital readmissions among 3951 patients discharged from CSMC to 8 SNFs between January 1, 2014, and June 30, 2015. A total of 2394 patients were enrolled in the ECP, and 1557 patients were not enrolled.
ECP Enrollment Protocol
Every patient discharged from CSMC to 1 of the 8 partner SNFs was eligible to participate in the program. To respect the autonomy of the SNF attending physicians and to facilitate a collaborative relationship, the decision to enroll a patient in the ECP rested with the SNF attending physician. The ECP team maintained a database that tracked whether each SNF attending physician (1) opted to automatically enroll all his or her patients in the ECP, (2) opted to enroll patients on a case-by-case basis (in which case an ECP nurse practitioner [N
Program Description
Patients enrolled in the ECP experienced the standard care provided by the SNF staff and attending physicians plus a clinical care program delivered by 9 full-time NPs, 1 full-time pharmacist, 1 pharmacy technician, 1 full-time nurse educator, a program administrator, and a medical director.
The program included the following 3 major components:
1. Direct patient care and 24/7 NP availability: Program enrollment began with an on-site, bedside evaluation by an ECP NP at the SNF within 24 hours of arrival and continued with weekly NP rounding (or more frequently, if clinically indicated) on the patient. Each encounter included a review of the medical record; a dialogue with the patient’s SNF attending physician to formulate treatment plans and place orders; discussions with nurses, family members, and other caregivers; and documentation in the medical record. The ECP team was on-site at the SNFs 7 days a week and on call 24/7 to address questions and concerns. Patients remained enrolled in the ECP from SNF admission to discharge even if their stay extended beyond 30 days.
2. Medication reconciliation: The ECP pharmacy team completed a review of a patient’s SNF medication administration record (MAR) within 72 hours of SNF admission. This process involved the pharmacy technician gathering medication lists from the SNFs and CSMC and providing this information to the pharmacist for a medication reconciliation and clinical evaluation. Discrepancies and pharmacist recommendations were communicated to the ECP NPs, and all identified issues were resolved.
3. Educational in-services: Building upon the INTERACT II model, the ECP team identified high-yield, clinically relevant topics, which the ECP nurse educator turned into monthly educational sessions for the SNF nursing staff at each of the participating SNFs.10
Primary Outcome Measure
An inpatient readmission to CSMC within 30 days of the hospital discharge date was counted as a readmission, whether the patient returned directly from an SNF or was readmitted from home after an SNF discharge.
Data
ECP patients were identified using a log maintained by the ECP program manager. Non-ECP patients discharged to the same SNFs during the study period were identified from CSMC’s electronic registry of SNF discharges. Covariates known to be associated with increased risk of 30-day readmission were obtained from CSMC’s electronic data warehouse, including demographic information, length of stay (LOS) of index hospitalization, and payer.12 Eleven clinical service lines represented patients’ clinical conditions based on Medicare-Severity Diagnosis-Related groupings. The discharge severity of illness score was calculated using 3M All Patients Refined Diagnosis Related Group software, version 33.13
Analysis
Characteristics of the ECP and non-ECP patients were compared using the χ2 test. A multivariable logistic regression model with fixed effects for SNF was created to determine the program’s impact on 30-day hospital readmission, adjusting for patient characteristics. The Pearson χ2 goodness-of-fit test and the link test for model specification were used to evaluate model specification. The sensitivity of the results to differences in patient characteristics was assessed in 2 ways. First, the ECP and non-ECP populations were stratified based on race and/or ethnicity and payer, and the multivariable regression model was run within the strata associated with the highest readmission rates. Second, a propensity analysis using inverse probability of treatment weighting (IPTW) was performed to control for group differences. Results of all comparisons were considered statistically significant when P < 0.05. Stata version 13 was used to perform the main analyses.14 The propensity analysis was conducted using R version 3.2.3. The CSMC Institutional Review Board (IRB) determined that this study qualified as a quality-improvement activity and did not require IRB approval or exemption.
RESULTS
The average unadjusted 30-day readmission rate for ECP patients over the 18-month study period was 17.2%, compared to 23.0% for patients not enrolled in ECP (P < 0.001) (Figure 1). After adjusting for patient characteristics, ECP patients had 29% lower odds (95% confidence interval [CI], 0.60-0.85) of being readmitted to the medical center within 30 days than non-ECP patients at the same SNFs. The characteristics of the ECP and comparison patient cohorts are shown in Table 1. There were significant differences in sociodemographic characteristics: The ECP group had a higher proportion of non-Hispanic white patients, while the comparison group had a higher proportion of patients who were African American or Hispanic. ECP patients were more likely to prefer speaking English, while Russian, Farsi, and Spanish were preferred more frequently in the comparison group. There were also differences in payer mix, with the ECP group including proportionately more Medicare fee-for-service (52.9% vs 35.0%, P < 0.001), while the comparison group had a correspondingly larger proportion of dual-eligible (Medicare and Medicaid) patients (55.0% vs 35.1%, P < 0.001).
The largest clinical differences observed between the ECP and non-ECP groups were the proportions of patients in the clinical service lines of orthopedic surgery (28.7% vs 21.1%, P < 0.001), medical cardiology (7.4% vs 9.7%, P < 0.001), and surgery other than general surgery (5.8% vs 9.2%, P < 0.001). Despite these differences in case mix, no differences were seen between the 2 groups in discharge severity of illness or LOS of the index hospitalization. The distribution of index hospital LOS by quartile was the same, with the exception that the ECP group had a higher proportion of patients with longer LOS.
Sensitivity Analyses
The results were robust when tested within strata of the study population, including analyses limited to dual-eligible patients, African American patients, patients admitted to all except the highest volume facility, and patients admitted to any service line other than orthopedic surgery. Similar results were obtained when the study population was restricted to patients living within the medical center’s primary service area and to patients living in zip codes in which the proportion of adults living in households with income below 100% of the poverty level was 15% or greater (see Supplementary Material for results).
The effect of the program on readmission was also consistent when the full logistic regression model was run with IPTW using the propensity score. The evaluation of standardized cluster differences between the ECP and non-ECP groups before and after IPTW showed that the differences were reduced to <10% for being African American; speaking Russian or Farsi; having dual-eligible insurance coverage; having orthopedic surgery; being discharged from the clinical service lines of gastroenterology, pulmonary, other surgery, and other services; and having an index hospital LOS of 4 to 5 days or 10 or more days (results are provided in the Supplementary Material).
DISCUSSION
Hospitals continue to experience significant pressure to manage LOS, and SNFs and hospitals are being held accountable for readmission rates. The setting of this study is representative of many large, urban hospitals in the United States whose communities include a heterogeneous mix of hospitalists, primary care physicians who follow their patients in SNFs, and independent SNFs.15 The current regulations have not kept up with the increasing acuity and complexity of SNF patients. Specifically, Medicare guidelines allow the SNF attending physician up to 72 hours to complete a history and physical (or 7 days if he or she was the hospital attending physician for the index hospitalization) and only require monthly follow-up visits. It is the opinion of the ECP designers that these relatively lax requirements present unnecessary risk for vulnerable patients. While the INTERACT II model was focused largely on educational initiatives (with an advanced practice nurse available in a consultative role, as needed), the central tenet of ECP was similar to the Connected Care model in that the focus was on adding an extra layer of direct clinical support. Protocols that provided timely initial assessments by an NP (within 24 hours), weekly NP rounding (at a minimum), and 24/7 on-call availability all contributed to helping patients stay on track. Although the ECP had patients visited less frequently than the Connected Care model, and the Cleveland Clinic started with a higher baseline 30-day readmission rate from SNFs, similar overall reductions in 30-day readmissions were observed. The key point from both initiatives is that an increase in clinical touchpoints and ease of access to clinicians generates myriad opportunities to identify and address small issues before they become clinical emergencies requiring hospital transfers and readmissions.
Correcting medication discrepancies between hospital discharge summaries and SNF admission orders through a systematic medication reconciliation using a clinical pharmacist has previously been shown to improve outcomes.16-18 The ECP pharmacy technician and ECP clinical pharmacist discovered and corrected errors on a daily basis that ranged from incidental to potentially life-threatening. If the SNF staff does not provide the patient’s MAR within 48 hours of arrival, the pharmacy technician contacts the facility to obtain the information. As a result, all patients enrolled in the ECP during the study period received this intervention (unless they were rehospitalized or left the SNF before the process was completed), and 54% of ECP patients required some form of intervention after medication reconciliation was completed (data not shown).
This type of program requires hospital leadership and SNF administrators to be fully committed to developing strong working relationships, and in fact, there is evidence that SNF baseline readmission rates have a greater influence on patients’ risk of rehospitalization than the discharging hospital itself.19-21 Monthly educational in-services are delivered at the partner SNFs to enhance SNF nursing staff knowledge and clinical acumen. High-impact topics identified by the ECP team include the following: fall prevention, hand hygiene, venous thromboembolism, cardiovascular health, how to report change in condition, and advanced care planning, among others. While no formal pre–post assessments of the SNF nurses’ knowledge were conducted, a log of in-services was kept, subjective feedback was collected for performance improvement purposes, and continuing educational units were provided to the SNF nurses who attended.
This study has limitations. As a single-hospital study, generalizability may be limited. While adherence to the program components was closely monitored daily, service gaps may have occurred that were not captured. The program design makes it difficult to quantify the relative impact of the 3 program components on the outcome. Furthermore, the study was observational, so the differences in readmission rates may have been due to unmeasured variables. The decision to enroll patients in the ECP was made by each patient’s SNF attending physician, and those who chose to (or not to) participate in the program may manifest other, unmeasured practice patterns that made readmissions more or less likely. Participating physicians also had the option to enroll their patients on a case-by-case basis, introducing further potential bias in patient selection; however, <5% of physicians exercised this option. Patients may have also been readmitted to hospitals other than CSMC, producing an observed readmission rate for 1 or both groups that underrepresents the true outcome. On this point, while we did not systematically track these other-hospital readmissions for both groups, there is no reason to believe that this occurred preferentially for ECP or non-ECP patients.
Multiple sensitivity analyses were performed to address the observed differences between ECP and non-ECP patients. These included stratified examinations of variables differing between populations, examination of clustering effects between SNFs, and an analysis adjusted for the propensity to be included in the ECP. The calculated effect of the intervention on readmission remained robust, although we acknowledge that differences in the populations may persist and have influenced the outcomes even after controlling for multiple variables.22-25
In conclusion, the results of this intervention are compelling and add to the growing body of literature suggesting that a comprehensive, multipronged effort to enhance clinical oversight and coordination of care for SNF patients can improve outcomes. Given CMS’s plans to report SNF readmission rates in 2017 followed by the application of financial incentives in 2018, a favorable climate currently exists for greater coordination between hospitals and SNFs.26 We are currently undertaking an economic evaluation of the program.
Acknowledgments
The authors would like to thank the following people for their contributions: Mae Saunders, Rita Shane, Dr. Jon Kea, Miranda Li, the ECP NPs, the ECP pharmacy team, CSMC’s performance improvement team, and Alan Matus.
Disclosure
No conflicts of interest or disclosures.
1. Centers for Medicare & Medicaid Services (CMS), HHS. Medicare Program; Prospective Payment System and Consolidated Billing for Skilled Nursing Facilities (SNFs) for FY 2016, SNF Value-Based Purchasing Program, SNF Quality Reporting Program, and Staffing Data Collection. Final Rule. Fed Regist. 2015;80(149):46389-46477. PubMed
2. “Readmissions Reduction Program,” Centers for Medicare & Medicaid Services. http://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/AcuteInpatientPPS/Readmissions-Reduction-Program.html. Accessed November 5, 2015.
3. Naylor MD, Brooten D, Campbell R, et al. Comprehensive discharge planning and home follow-up of hospitalized elders: a randomized clinical trial. JAMA. 1999;281:613-620. PubMed
4. Naylor MD, Brooten DA, Campbell RL, Maislin G, McCauley KM, Schwartz JS. Transitional care of older adults hospitalized with heart failure: a randomized, controlled trial. J Am Geriatr Soc. 2004;52:675-684. PubMed
5. Coleman EA, Parry C, Chalmers S, Min SJ. The care transitions intervention: results of a randomized controlled trial. Arch Intern Med. 2006;166:1822-1828. PubMed
6. CMS Office of Information Products and Data Analytics. National Medicare Readmission Findings: Recent Data and Trends. 2012. http://www.academyhealth.org/files/2012/sunday/brennan.pdf. Accessed on September 21, 2015.
7. Centers for Medicare & Medicaid Services, CMS Innovation Center. Initiative to Reduce Avoidable Hospitalizations among Nursing Facility Residents. https://innovation.cms.gov/initiatives/rahnfr/. Accessed on November 5, 2015.
8. Unroe KT, Nazir A, Holtz LR, et al. The Optimizing Patient Transfers, Impacting Medical Quality and Improving Symptoms: Transforming Institutional Care Approach: Preliminary data from the implementation of a Centers for Medicare and Medicaid Services nursing facility demonstration project. J Am Geriatr Soc. 2015;65:165-169. PubMed
9. Ingber MJ, Feng Z, Khatstsky G, et al. Evaluation of the Initiative to Reduce Avoidable Hospitalizations among Nursing Facility Residents: Final Annual Report Project Year 3. Waltham, MA: RTI International, RTI Project Number 0212790.006, January 2016.
10. Ouslander JG, Lamb G, Tappen R, et al. Interventions to reduce hospitalizations from nursing homes: Evaluation of the INTERACT II collaborative quality improvement project. J Am Geriatr Soc. 2011:59:745-753. PubMed
11. Kim L, Kou L, Hu B, Gorodeski EZ, Rothberg M. Impact of a Connected Care Model on 30-Day Readmission Rates from Skilled Nursing Facilities. J Hosp Med. 2017;12:238-244. PubMed
12. Kansagara D, Englander H, Salanitro A, et al. Risk Prediction Models for Hospital Readmission: A Systematic Review. JAMA. 2011;306(15):1688-1698. PubMed
13. Averill RF, Goldfield N, Hughes JS, et al. All Patient Refined Diagnosis Related Groups (APR-DRGs): Methodology Overview. 3M Health Information Systems Document GRP-041 (2003). https://www.hcup-us.ahrq.gov/db/nation/nis/APR-DRGsV20MethodologyOverviewandBibliography.pdf. Accessed on November 5, 2015.
14. StataCorp. 2013. Stata Statistical Software: Release 13. College Station, TX: StataCorp LP.
15. Cebul RD, Rebitzer JB, Taylor LJ, Votruba ME. Organizational fragmentation and care quality in the U.S. healthcare system. J Econ Perspect. 2008;22(4):93-113. PubMed
16. Tjia J, Bonner A, Briesacher BA, McGee S, Terrill E, Miller K. Medication discrepancies upon hospital to skilled nursing facility transitions. J Gen Intern Med. 2009;24:630-635. PubMed
17. Desai R, Williams CE, Greene SB, Pierson S, Hansen RA. Medication errors during patient transitions into nursing homes: characteristics and association with patient harm. Am J Geriatr Pharmacother. 2011;9:413-422. PubMed
18. Chhabra PT, Rattinger GB, Dutcher SK, Hare ME, Parsons KL, Zuckerman IH. Medication reconciliation during the transition to and from long-term care settings: a systematic review. Res Social Adm Pharm. 2012;8(1):60-75. PubMed
19. Rahman M, Foster AD, Grabowski DC, Zinn JS, Mor V. Effect of hospital-SNF referral linkages on rehospitalization. Health Serv Res. 2013;48(6, pt 1):1898-1919. PubMed
20. Schoenfeld AJ, Zhang X, Grabowski DC, Mor V, Weissman JS, Rahman M. Hospital-skilled nursing facility referral linkage reduces readmission rates among Medicare patients receiving major surgery. Surgery. 2016;159(5):1461-1468. PubMed
21. Rahman M, McHugh J, Gozalo P, Ackerly DC, Mor V. The Contribution of Skilled Nursing Facilities to Hospitals’ Readmission Rate. HSR: Health Services Research. 2017;52(2):656-675. PubMed
22. Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients in the Medicare fee-for-service program. New Engl J Med. 2009;360(14):1418-1428. PubMed
23. Hasan O, Meltzer DO, Shaykevich SA, et al. Hospital readmission in general medicine patients: a prediction model. J Hosp Med. 2010;25(3)211-219. PubMed
24. Allaudeen N, Vidyarhi A, Masella J, Auerbach A. Redefining readmission risk factors for general medicine patients. J Hosp Med. 2011;6(2):54-60. PubMed
25. Van Walraven C, Wong J, Forster AJ. LACE+ index: extension of a validated index to predict early death or urgent readmission after discharge using administrative data. Open Med. 2012;6(3):e80-e90. PubMed
26. Protecting Access to Medicare Act of 2014, Pub. L. No. 113-93, 128 Stat. 1040 (April 1, 2014). https://www.congress.gov/113/plaws/publ93/PLAW-113publ93.pdf. Accessed on October 3, 2015.
Public reporting of readmission rates on the Nursing Home Compare website is mandated to begin on October 1, 2017, with skilled nursing facilities (SNFs) set to receive a Medicare bonus or penalty beginning a year later.1 The Centers for Medicare & Medicaid Services (CMS) began public reporting of hospitals’ 30-day readmission rates for selected conditions in 2009, and the Patient Protection and Affordable Care Act of 2010 mandated financial penalties for excess readmissions through the Hospital Readmission Reduction Program.2 In response, most hospitals have focused on patients who return home following discharge. Innovative interventions have proven successful, such as the Transitional Care model developed by Naylor and Coleman’s Care Transitions Intervention.3-5 Approximately 20% of Medicare beneficiaries are discharged from hospitals to SNFs, and these patients have higher readmission rates than those discharged home. CMS reported that in 2010, 23.3% of those with an SNF stay were readmitted within 30 days, compared with 18.8% for those with other discharge dispositions.6
Some work has been undertaken in this arena. In 2012, the Center for Medicare and Medicaid Innovation (CMMI) and the Medicare-Medicaid Coordination Office jointly launched the Initiative to Reduce Avoidable Hospitalizations among Nursing Facility Residents.7 This partnership established 7 Enhanced Care and Coordination Provider organizations and was designed to improve care by reducing hospitalizations among long-stay, dual-eligible nursing facility residents at 143 nursing homes in 7 states.8 At the time of the most recent project report, there were mixed results regarding program effects on hospitalizations and spending, with 2 states showing strongly positive patterns, 3 states with reductions that were consistent though not statistically strong, and mixed results in the remaining states. Quality measures did not show any pattern suggesting a program effect.9 Interventions to Reduce Acute Care Transfers (INTERACT) II was a 6-month, collaborative, quality-improvement project implemented in 2009 at 30 nursing homes in 3 states.10 The project evaluation found a statistically significant, 17% decrease in self-reported hospital admissions among the 25 SNFs that completed the intervention, compared with the same 6 months in the prior year. The Cleveland Clinic recently reported favorable results implementing its Connected Care model, which relied on staff physicians and advanced practice professionals to visit patients 4 to 5 times per week and be on call 24/7 at 7 intervention SNFs.11 Through this intervention, it successfully reduced its 30-day hospital readmission rate from SNFs from 28.1% to 21.7% (P < 0.001), and the authors posed the question as to whether its model and results were reproducible in other healthcare systems.
Herein, we report on the results of a collaborative initiative named the Enhanced Care Program (ECP), which offers the services of clinical providers and administrative staff to assist with the care of patients at 8 partner SNFs. The 3 components of ECP (described below) were specifically designed to address commonly recognized gaps and opportunities in routine SNF care. In contrast to the Cleveland Clinic’s Connected Care model (which involved hospital-employed physicians serving as the SNF attendings and excluded patients followed by their own physicians), ECP was designed to integrate into a pluralistic, community model whereby independent physicians continued to follow their own patients at the SNFs. The Connected Care analysis compared participating versus nonparticipating SNFs; both the Connected Care model and the INTERACT II evaluation relied on pre–post comparisons; the CMMI evaluation used a difference-in-differences model to compare the outcomes of the program SNFs with those of a matched comparison group of nonparticipating SNFs. The evaluation of ECP differs from these other initiatives, using a concurrent comparison group of patients discharged to the same SNFs but who were not enrolled in ECP.
METHODS
Setting
Cedars-Sinai Medical Center (CSMC) is an 850-bed, acute care facility located in an urban area of Los Angeles. Eight SNFs, ranging in size from 49 to 150 beds and located between 0.6 and 2.2 miles from CSMC, were invited to partner with the ECP. The physician community encompasses more than 2000 physicians on the medical staff, including private practitioners, nonteaching hospitalists, full-time faculty hospitalists, and faculty specialists.
Study Design and Patients
This was an observational, retrospective cohort analysis of 30-day same-hospital readmissions among 3951 patients discharged from CSMC to 8 SNFs between January 1, 2014, and June 30, 2015. A total of 2394 patients were enrolled in the ECP, and 1557 patients were not enrolled.
ECP Enrollment Protocol
Every patient discharged from CSMC to 1 of the 8 partner SNFs was eligible to participate in the program. To respect the autonomy of the SNF attending physicians and to facilitate a collaborative relationship, the decision to enroll a patient in the ECP rested with the SNF attending physician. The ECP team maintained a database that tracked whether each SNF attending physician (1) opted to automatically enroll all his or her patients in the ECP, (2) opted to enroll patients on a case-by-case basis (in which case an ECP nurse practitioner [N
Program Description
Patients enrolled in the ECP experienced the standard care provided by the SNF staff and attending physicians plus a clinical care program delivered by 9 full-time NPs, 1 full-time pharmacist, 1 pharmacy technician, 1 full-time nurse educator, a program administrator, and a medical director.
The program included the following 3 major components:
1. Direct patient care and 24/7 NP availability: Program enrollment began with an on-site, bedside evaluation by an ECP NP at the SNF within 24 hours of arrival and continued with weekly NP rounding (or more frequently, if clinically indicated) on the patient. Each encounter included a review of the medical record; a dialogue with the patient’s SNF attending physician to formulate treatment plans and place orders; discussions with nurses, family members, and other caregivers; and documentation in the medical record. The ECP team was on-site at the SNFs 7 days a week and on call 24/7 to address questions and concerns. Patients remained enrolled in the ECP from SNF admission to discharge even if their stay extended beyond 30 days.
2. Medication reconciliation: The ECP pharmacy team completed a review of a patient’s SNF medication administration record (MAR) within 72 hours of SNF admission. This process involved the pharmacy technician gathering medication lists from the SNFs and CSMC and providing this information to the pharmacist for a medication reconciliation and clinical evaluation. Discrepancies and pharmacist recommendations were communicated to the ECP NPs, and all identified issues were resolved.
3. Educational in-services: Building upon the INTERACT II model, the ECP team identified high-yield, clinically relevant topics, which the ECP nurse educator turned into monthly educational sessions for the SNF nursing staff at each of the participating SNFs.10
Primary Outcome Measure
An inpatient readmission to CSMC within 30 days of the hospital discharge date was counted as a readmission, whether the patient returned directly from an SNF or was readmitted from home after an SNF discharge.
Data
ECP patients were identified using a log maintained by the ECP program manager. Non-ECP patients discharged to the same SNFs during the study period were identified from CSMC’s electronic registry of SNF discharges. Covariates known to be associated with increased risk of 30-day readmission were obtained from CSMC’s electronic data warehouse, including demographic information, length of stay (LOS) of index hospitalization, and payer.12 Eleven clinical service lines represented patients’ clinical conditions based on Medicare-Severity Diagnosis-Related groupings. The discharge severity of illness score was calculated using 3M All Patients Refined Diagnosis Related Group software, version 33.13
Analysis
Characteristics of the ECP and non-ECP patients were compared using the χ2 test. A multivariable logistic regression model with fixed effects for SNF was created to determine the program’s impact on 30-day hospital readmission, adjusting for patient characteristics. The Pearson χ2 goodness-of-fit test and the link test for model specification were used to evaluate model specification. The sensitivity of the results to differences in patient characteristics was assessed in 2 ways. First, the ECP and non-ECP populations were stratified based on race and/or ethnicity and payer, and the multivariable regression model was run within the strata associated with the highest readmission rates. Second, a propensity analysis using inverse probability of treatment weighting (IPTW) was performed to control for group differences. Results of all comparisons were considered statistically significant when P < 0.05. Stata version 13 was used to perform the main analyses.14 The propensity analysis was conducted using R version 3.2.3. The CSMC Institutional Review Board (IRB) determined that this study qualified as a quality-improvement activity and did not require IRB approval or exemption.
RESULTS
The average unadjusted 30-day readmission rate for ECP patients over the 18-month study period was 17.2%, compared to 23.0% for patients not enrolled in ECP (P < 0.001) (Figure 1). After adjusting for patient characteristics, ECP patients had 29% lower odds (95% confidence interval [CI], 0.60-0.85) of being readmitted to the medical center within 30 days than non-ECP patients at the same SNFs. The characteristics of the ECP and comparison patient cohorts are shown in Table 1. There were significant differences in sociodemographic characteristics: The ECP group had a higher proportion of non-Hispanic white patients, while the comparison group had a higher proportion of patients who were African American or Hispanic. ECP patients were more likely to prefer speaking English, while Russian, Farsi, and Spanish were preferred more frequently in the comparison group. There were also differences in payer mix, with the ECP group including proportionately more Medicare fee-for-service (52.9% vs 35.0%, P < 0.001), while the comparison group had a correspondingly larger proportion of dual-eligible (Medicare and Medicaid) patients (55.0% vs 35.1%, P < 0.001).
The largest clinical differences observed between the ECP and non-ECP groups were the proportions of patients in the clinical service lines of orthopedic surgery (28.7% vs 21.1%, P < 0.001), medical cardiology (7.4% vs 9.7%, P < 0.001), and surgery other than general surgery (5.8% vs 9.2%, P < 0.001). Despite these differences in case mix, no differences were seen between the 2 groups in discharge severity of illness or LOS of the index hospitalization. The distribution of index hospital LOS by quartile was the same, with the exception that the ECP group had a higher proportion of patients with longer LOS.
Sensitivity Analyses
The results were robust when tested within strata of the study population, including analyses limited to dual-eligible patients, African American patients, patients admitted to all except the highest volume facility, and patients admitted to any service line other than orthopedic surgery. Similar results were obtained when the study population was restricted to patients living within the medical center’s primary service area and to patients living in zip codes in which the proportion of adults living in households with income below 100% of the poverty level was 15% or greater (see Supplementary Material for results).
The effect of the program on readmission was also consistent when the full logistic regression model was run with IPTW using the propensity score. The evaluation of standardized cluster differences between the ECP and non-ECP groups before and after IPTW showed that the differences were reduced to <10% for being African American; speaking Russian or Farsi; having dual-eligible insurance coverage; having orthopedic surgery; being discharged from the clinical service lines of gastroenterology, pulmonary, other surgery, and other services; and having an index hospital LOS of 4 to 5 days or 10 or more days (results are provided in the Supplementary Material).
DISCUSSION
Hospitals continue to experience significant pressure to manage LOS, and SNFs and hospitals are being held accountable for readmission rates. The setting of this study is representative of many large, urban hospitals in the United States whose communities include a heterogeneous mix of hospitalists, primary care physicians who follow their patients in SNFs, and independent SNFs.15 The current regulations have not kept up with the increasing acuity and complexity of SNF patients. Specifically, Medicare guidelines allow the SNF attending physician up to 72 hours to complete a history and physical (or 7 days if he or she was the hospital attending physician for the index hospitalization) and only require monthly follow-up visits. It is the opinion of the ECP designers that these relatively lax requirements present unnecessary risk for vulnerable patients. While the INTERACT II model was focused largely on educational initiatives (with an advanced practice nurse available in a consultative role, as needed), the central tenet of ECP was similar to the Connected Care model in that the focus was on adding an extra layer of direct clinical support. Protocols that provided timely initial assessments by an NP (within 24 hours), weekly NP rounding (at a minimum), and 24/7 on-call availability all contributed to helping patients stay on track. Although the ECP had patients visited less frequently than the Connected Care model, and the Cleveland Clinic started with a higher baseline 30-day readmission rate from SNFs, similar overall reductions in 30-day readmissions were observed. The key point from both initiatives is that an increase in clinical touchpoints and ease of access to clinicians generates myriad opportunities to identify and address small issues before they become clinical emergencies requiring hospital transfers and readmissions.
Correcting medication discrepancies between hospital discharge summaries and SNF admission orders through a systematic medication reconciliation using a clinical pharmacist has previously been shown to improve outcomes.16-18 The ECP pharmacy technician and ECP clinical pharmacist discovered and corrected errors on a daily basis that ranged from incidental to potentially life-threatening. If the SNF staff does not provide the patient’s MAR within 48 hours of arrival, the pharmacy technician contacts the facility to obtain the information. As a result, all patients enrolled in the ECP during the study period received this intervention (unless they were rehospitalized or left the SNF before the process was completed), and 54% of ECP patients required some form of intervention after medication reconciliation was completed (data not shown).
This type of program requires hospital leadership and SNF administrators to be fully committed to developing strong working relationships, and in fact, there is evidence that SNF baseline readmission rates have a greater influence on patients’ risk of rehospitalization than the discharging hospital itself.19-21 Monthly educational in-services are delivered at the partner SNFs to enhance SNF nursing staff knowledge and clinical acumen. High-impact topics identified by the ECP team include the following: fall prevention, hand hygiene, venous thromboembolism, cardiovascular health, how to report change in condition, and advanced care planning, among others. While no formal pre–post assessments of the SNF nurses’ knowledge were conducted, a log of in-services was kept, subjective feedback was collected for performance improvement purposes, and continuing educational units were provided to the SNF nurses who attended.
This study has limitations. As a single-hospital study, generalizability may be limited. While adherence to the program components was closely monitored daily, service gaps may have occurred that were not captured. The program design makes it difficult to quantify the relative impact of the 3 program components on the outcome. Furthermore, the study was observational, so the differences in readmission rates may have been due to unmeasured variables. The decision to enroll patients in the ECP was made by each patient’s SNF attending physician, and those who chose to (or not to) participate in the program may manifest other, unmeasured practice patterns that made readmissions more or less likely. Participating physicians also had the option to enroll their patients on a case-by-case basis, introducing further potential bias in patient selection; however, <5% of physicians exercised this option. Patients may have also been readmitted to hospitals other than CSMC, producing an observed readmission rate for 1 or both groups that underrepresents the true outcome. On this point, while we did not systematically track these other-hospital readmissions for both groups, there is no reason to believe that this occurred preferentially for ECP or non-ECP patients.
Multiple sensitivity analyses were performed to address the observed differences between ECP and non-ECP patients. These included stratified examinations of variables differing between populations, examination of clustering effects between SNFs, and an analysis adjusted for the propensity to be included in the ECP. The calculated effect of the intervention on readmission remained robust, although we acknowledge that differences in the populations may persist and have influenced the outcomes even after controlling for multiple variables.22-25
In conclusion, the results of this intervention are compelling and add to the growing body of literature suggesting that a comprehensive, multipronged effort to enhance clinical oversight and coordination of care for SNF patients can improve outcomes. Given CMS’s plans to report SNF readmission rates in 2017 followed by the application of financial incentives in 2018, a favorable climate currently exists for greater coordination between hospitals and SNFs.26 We are currently undertaking an economic evaluation of the program.
Acknowledgments
The authors would like to thank the following people for their contributions: Mae Saunders, Rita Shane, Dr. Jon Kea, Miranda Li, the ECP NPs, the ECP pharmacy team, CSMC’s performance improvement team, and Alan Matus.
Disclosure
No conflicts of interest or disclosures.
Public reporting of readmission rates on the Nursing Home Compare website is mandated to begin on October 1, 2017, with skilled nursing facilities (SNFs) set to receive a Medicare bonus or penalty beginning a year later.1 The Centers for Medicare & Medicaid Services (CMS) began public reporting of hospitals’ 30-day readmission rates for selected conditions in 2009, and the Patient Protection and Affordable Care Act of 2010 mandated financial penalties for excess readmissions through the Hospital Readmission Reduction Program.2 In response, most hospitals have focused on patients who return home following discharge. Innovative interventions have proven successful, such as the Transitional Care model developed by Naylor and Coleman’s Care Transitions Intervention.3-5 Approximately 20% of Medicare beneficiaries are discharged from hospitals to SNFs, and these patients have higher readmission rates than those discharged home. CMS reported that in 2010, 23.3% of those with an SNF stay were readmitted within 30 days, compared with 18.8% for those with other discharge dispositions.6
Some work has been undertaken in this arena. In 2012, the Center for Medicare and Medicaid Innovation (CMMI) and the Medicare-Medicaid Coordination Office jointly launched the Initiative to Reduce Avoidable Hospitalizations among Nursing Facility Residents.7 This partnership established 7 Enhanced Care and Coordination Provider organizations and was designed to improve care by reducing hospitalizations among long-stay, dual-eligible nursing facility residents at 143 nursing homes in 7 states.8 At the time of the most recent project report, there were mixed results regarding program effects on hospitalizations and spending, with 2 states showing strongly positive patterns, 3 states with reductions that were consistent though not statistically strong, and mixed results in the remaining states. Quality measures did not show any pattern suggesting a program effect.9 Interventions to Reduce Acute Care Transfers (INTERACT) II was a 6-month, collaborative, quality-improvement project implemented in 2009 at 30 nursing homes in 3 states.10 The project evaluation found a statistically significant, 17% decrease in self-reported hospital admissions among the 25 SNFs that completed the intervention, compared with the same 6 months in the prior year. The Cleveland Clinic recently reported favorable results implementing its Connected Care model, which relied on staff physicians and advanced practice professionals to visit patients 4 to 5 times per week and be on call 24/7 at 7 intervention SNFs.11 Through this intervention, it successfully reduced its 30-day hospital readmission rate from SNFs from 28.1% to 21.7% (P < 0.001), and the authors posed the question as to whether its model and results were reproducible in other healthcare systems.
Herein, we report on the results of a collaborative initiative named the Enhanced Care Program (ECP), which offers the services of clinical providers and administrative staff to assist with the care of patients at 8 partner SNFs. The 3 components of ECP (described below) were specifically designed to address commonly recognized gaps and opportunities in routine SNF care. In contrast to the Cleveland Clinic’s Connected Care model (which involved hospital-employed physicians serving as the SNF attendings and excluded patients followed by their own physicians), ECP was designed to integrate into a pluralistic, community model whereby independent physicians continued to follow their own patients at the SNFs. The Connected Care analysis compared participating versus nonparticipating SNFs; both the Connected Care model and the INTERACT II evaluation relied on pre–post comparisons; the CMMI evaluation used a difference-in-differences model to compare the outcomes of the program SNFs with those of a matched comparison group of nonparticipating SNFs. The evaluation of ECP differs from these other initiatives, using a concurrent comparison group of patients discharged to the same SNFs but who were not enrolled in ECP.
METHODS
Setting
Cedars-Sinai Medical Center (CSMC) is an 850-bed, acute care facility located in an urban area of Los Angeles. Eight SNFs, ranging in size from 49 to 150 beds and located between 0.6 and 2.2 miles from CSMC, were invited to partner with the ECP. The physician community encompasses more than 2000 physicians on the medical staff, including private practitioners, nonteaching hospitalists, full-time faculty hospitalists, and faculty specialists.
Study Design and Patients
This was an observational, retrospective cohort analysis of 30-day same-hospital readmissions among 3951 patients discharged from CSMC to 8 SNFs between January 1, 2014, and June 30, 2015. A total of 2394 patients were enrolled in the ECP, and 1557 patients were not enrolled.
ECP Enrollment Protocol
Every patient discharged from CSMC to 1 of the 8 partner SNFs was eligible to participate in the program. To respect the autonomy of the SNF attending physicians and to facilitate a collaborative relationship, the decision to enroll a patient in the ECP rested with the SNF attending physician. The ECP team maintained a database that tracked whether each SNF attending physician (1) opted to automatically enroll all his or her patients in the ECP, (2) opted to enroll patients on a case-by-case basis (in which case an ECP nurse practitioner [N
Program Description
Patients enrolled in the ECP experienced the standard care provided by the SNF staff and attending physicians plus a clinical care program delivered by 9 full-time NPs, 1 full-time pharmacist, 1 pharmacy technician, 1 full-time nurse educator, a program administrator, and a medical director.
The program included the following 3 major components:
1. Direct patient care and 24/7 NP availability: Program enrollment began with an on-site, bedside evaluation by an ECP NP at the SNF within 24 hours of arrival and continued with weekly NP rounding (or more frequently, if clinically indicated) on the patient. Each encounter included a review of the medical record; a dialogue with the patient’s SNF attending physician to formulate treatment plans and place orders; discussions with nurses, family members, and other caregivers; and documentation in the medical record. The ECP team was on-site at the SNFs 7 days a week and on call 24/7 to address questions and concerns. Patients remained enrolled in the ECP from SNF admission to discharge even if their stay extended beyond 30 days.
2. Medication reconciliation: The ECP pharmacy team completed a review of a patient’s SNF medication administration record (MAR) within 72 hours of SNF admission. This process involved the pharmacy technician gathering medication lists from the SNFs and CSMC and providing this information to the pharmacist for a medication reconciliation and clinical evaluation. Discrepancies and pharmacist recommendations were communicated to the ECP NPs, and all identified issues were resolved.
3. Educational in-services: Building upon the INTERACT II model, the ECP team identified high-yield, clinically relevant topics, which the ECP nurse educator turned into monthly educational sessions for the SNF nursing staff at each of the participating SNFs.10
Primary Outcome Measure
An inpatient readmission to CSMC within 30 days of the hospital discharge date was counted as a readmission, whether the patient returned directly from an SNF or was readmitted from home after an SNF discharge.
Data
ECP patients were identified using a log maintained by the ECP program manager. Non-ECP patients discharged to the same SNFs during the study period were identified from CSMC’s electronic registry of SNF discharges. Covariates known to be associated with increased risk of 30-day readmission were obtained from CSMC’s electronic data warehouse, including demographic information, length of stay (LOS) of index hospitalization, and payer.12 Eleven clinical service lines represented patients’ clinical conditions based on Medicare-Severity Diagnosis-Related groupings. The discharge severity of illness score was calculated using 3M All Patients Refined Diagnosis Related Group software, version 33.13
Analysis
Characteristics of the ECP and non-ECP patients were compared using the χ2 test. A multivariable logistic regression model with fixed effects for SNF was created to determine the program’s impact on 30-day hospital readmission, adjusting for patient characteristics. The Pearson χ2 goodness-of-fit test and the link test for model specification were used to evaluate model specification. The sensitivity of the results to differences in patient characteristics was assessed in 2 ways. First, the ECP and non-ECP populations were stratified based on race and/or ethnicity and payer, and the multivariable regression model was run within the strata associated with the highest readmission rates. Second, a propensity analysis using inverse probability of treatment weighting (IPTW) was performed to control for group differences. Results of all comparisons were considered statistically significant when P < 0.05. Stata version 13 was used to perform the main analyses.14 The propensity analysis was conducted using R version 3.2.3. The CSMC Institutional Review Board (IRB) determined that this study qualified as a quality-improvement activity and did not require IRB approval or exemption.
RESULTS
The average unadjusted 30-day readmission rate for ECP patients over the 18-month study period was 17.2%, compared to 23.0% for patients not enrolled in ECP (P < 0.001) (Figure 1). After adjusting for patient characteristics, ECP patients had 29% lower odds (95% confidence interval [CI], 0.60-0.85) of being readmitted to the medical center within 30 days than non-ECP patients at the same SNFs. The characteristics of the ECP and comparison patient cohorts are shown in Table 1. There were significant differences in sociodemographic characteristics: The ECP group had a higher proportion of non-Hispanic white patients, while the comparison group had a higher proportion of patients who were African American or Hispanic. ECP patients were more likely to prefer speaking English, while Russian, Farsi, and Spanish were preferred more frequently in the comparison group. There were also differences in payer mix, with the ECP group including proportionately more Medicare fee-for-service (52.9% vs 35.0%, P < 0.001), while the comparison group had a correspondingly larger proportion of dual-eligible (Medicare and Medicaid) patients (55.0% vs 35.1%, P < 0.001).
The largest clinical differences observed between the ECP and non-ECP groups were the proportions of patients in the clinical service lines of orthopedic surgery (28.7% vs 21.1%, P < 0.001), medical cardiology (7.4% vs 9.7%, P < 0.001), and surgery other than general surgery (5.8% vs 9.2%, P < 0.001). Despite these differences in case mix, no differences were seen between the 2 groups in discharge severity of illness or LOS of the index hospitalization. The distribution of index hospital LOS by quartile was the same, with the exception that the ECP group had a higher proportion of patients with longer LOS.
Sensitivity Analyses
The results were robust when tested within strata of the study population, including analyses limited to dual-eligible patients, African American patients, patients admitted to all except the highest volume facility, and patients admitted to any service line other than orthopedic surgery. Similar results were obtained when the study population was restricted to patients living within the medical center’s primary service area and to patients living in zip codes in which the proportion of adults living in households with income below 100% of the poverty level was 15% or greater (see Supplementary Material for results).
The effect of the program on readmission was also consistent when the full logistic regression model was run with IPTW using the propensity score. The evaluation of standardized cluster differences between the ECP and non-ECP groups before and after IPTW showed that the differences were reduced to <10% for being African American; speaking Russian or Farsi; having dual-eligible insurance coverage; having orthopedic surgery; being discharged from the clinical service lines of gastroenterology, pulmonary, other surgery, and other services; and having an index hospital LOS of 4 to 5 days or 10 or more days (results are provided in the Supplementary Material).
DISCUSSION
Hospitals continue to experience significant pressure to manage LOS, and SNFs and hospitals are being held accountable for readmission rates. The setting of this study is representative of many large, urban hospitals in the United States whose communities include a heterogeneous mix of hospitalists, primary care physicians who follow their patients in SNFs, and independent SNFs.15 The current regulations have not kept up with the increasing acuity and complexity of SNF patients. Specifically, Medicare guidelines allow the SNF attending physician up to 72 hours to complete a history and physical (or 7 days if he or she was the hospital attending physician for the index hospitalization) and only require monthly follow-up visits. It is the opinion of the ECP designers that these relatively lax requirements present unnecessary risk for vulnerable patients. While the INTERACT II model was focused largely on educational initiatives (with an advanced practice nurse available in a consultative role, as needed), the central tenet of ECP was similar to the Connected Care model in that the focus was on adding an extra layer of direct clinical support. Protocols that provided timely initial assessments by an NP (within 24 hours), weekly NP rounding (at a minimum), and 24/7 on-call availability all contributed to helping patients stay on track. Although the ECP had patients visited less frequently than the Connected Care model, and the Cleveland Clinic started with a higher baseline 30-day readmission rate from SNFs, similar overall reductions in 30-day readmissions were observed. The key point from both initiatives is that an increase in clinical touchpoints and ease of access to clinicians generates myriad opportunities to identify and address small issues before they become clinical emergencies requiring hospital transfers and readmissions.
Correcting medication discrepancies between hospital discharge summaries and SNF admission orders through a systematic medication reconciliation using a clinical pharmacist has previously been shown to improve outcomes.16-18 The ECP pharmacy technician and ECP clinical pharmacist discovered and corrected errors on a daily basis that ranged from incidental to potentially life-threatening. If the SNF staff does not provide the patient’s MAR within 48 hours of arrival, the pharmacy technician contacts the facility to obtain the information. As a result, all patients enrolled in the ECP during the study period received this intervention (unless they were rehospitalized or left the SNF before the process was completed), and 54% of ECP patients required some form of intervention after medication reconciliation was completed (data not shown).
This type of program requires hospital leadership and SNF administrators to be fully committed to developing strong working relationships, and in fact, there is evidence that SNF baseline readmission rates have a greater influence on patients’ risk of rehospitalization than the discharging hospital itself.19-21 Monthly educational in-services are delivered at the partner SNFs to enhance SNF nursing staff knowledge and clinical acumen. High-impact topics identified by the ECP team include the following: fall prevention, hand hygiene, venous thromboembolism, cardiovascular health, how to report change in condition, and advanced care planning, among others. While no formal pre–post assessments of the SNF nurses’ knowledge were conducted, a log of in-services was kept, subjective feedback was collected for performance improvement purposes, and continuing educational units were provided to the SNF nurses who attended.
This study has limitations. As a single-hospital study, generalizability may be limited. While adherence to the program components was closely monitored daily, service gaps may have occurred that were not captured. The program design makes it difficult to quantify the relative impact of the 3 program components on the outcome. Furthermore, the study was observational, so the differences in readmission rates may have been due to unmeasured variables. The decision to enroll patients in the ECP was made by each patient’s SNF attending physician, and those who chose to (or not to) participate in the program may manifest other, unmeasured practice patterns that made readmissions more or less likely. Participating physicians also had the option to enroll their patients on a case-by-case basis, introducing further potential bias in patient selection; however, <5% of physicians exercised this option. Patients may have also been readmitted to hospitals other than CSMC, producing an observed readmission rate for 1 or both groups that underrepresents the true outcome. On this point, while we did not systematically track these other-hospital readmissions for both groups, there is no reason to believe that this occurred preferentially for ECP or non-ECP patients.
Multiple sensitivity analyses were performed to address the observed differences between ECP and non-ECP patients. These included stratified examinations of variables differing between populations, examination of clustering effects between SNFs, and an analysis adjusted for the propensity to be included in the ECP. The calculated effect of the intervention on readmission remained robust, although we acknowledge that differences in the populations may persist and have influenced the outcomes even after controlling for multiple variables.22-25
In conclusion, the results of this intervention are compelling and add to the growing body of literature suggesting that a comprehensive, multipronged effort to enhance clinical oversight and coordination of care for SNF patients can improve outcomes. Given CMS’s plans to report SNF readmission rates in 2017 followed by the application of financial incentives in 2018, a favorable climate currently exists for greater coordination between hospitals and SNFs.26 We are currently undertaking an economic evaluation of the program.
Acknowledgments
The authors would like to thank the following people for their contributions: Mae Saunders, Rita Shane, Dr. Jon Kea, Miranda Li, the ECP NPs, the ECP pharmacy team, CSMC’s performance improvement team, and Alan Matus.
Disclosure
No conflicts of interest or disclosures.
1. Centers for Medicare & Medicaid Services (CMS), HHS. Medicare Program; Prospective Payment System and Consolidated Billing for Skilled Nursing Facilities (SNFs) for FY 2016, SNF Value-Based Purchasing Program, SNF Quality Reporting Program, and Staffing Data Collection. Final Rule. Fed Regist. 2015;80(149):46389-46477. PubMed
2. “Readmissions Reduction Program,” Centers for Medicare & Medicaid Services. http://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/AcuteInpatientPPS/Readmissions-Reduction-Program.html. Accessed November 5, 2015.
3. Naylor MD, Brooten D, Campbell R, et al. Comprehensive discharge planning and home follow-up of hospitalized elders: a randomized clinical trial. JAMA. 1999;281:613-620. PubMed
4. Naylor MD, Brooten DA, Campbell RL, Maislin G, McCauley KM, Schwartz JS. Transitional care of older adults hospitalized with heart failure: a randomized, controlled trial. J Am Geriatr Soc. 2004;52:675-684. PubMed
5. Coleman EA, Parry C, Chalmers S, Min SJ. The care transitions intervention: results of a randomized controlled trial. Arch Intern Med. 2006;166:1822-1828. PubMed
6. CMS Office of Information Products and Data Analytics. National Medicare Readmission Findings: Recent Data and Trends. 2012. http://www.academyhealth.org/files/2012/sunday/brennan.pdf. Accessed on September 21, 2015.
7. Centers for Medicare & Medicaid Services, CMS Innovation Center. Initiative to Reduce Avoidable Hospitalizations among Nursing Facility Residents. https://innovation.cms.gov/initiatives/rahnfr/. Accessed on November 5, 2015.
8. Unroe KT, Nazir A, Holtz LR, et al. The Optimizing Patient Transfers, Impacting Medical Quality and Improving Symptoms: Transforming Institutional Care Approach: Preliminary data from the implementation of a Centers for Medicare and Medicaid Services nursing facility demonstration project. J Am Geriatr Soc. 2015;65:165-169. PubMed
9. Ingber MJ, Feng Z, Khatstsky G, et al. Evaluation of the Initiative to Reduce Avoidable Hospitalizations among Nursing Facility Residents: Final Annual Report Project Year 3. Waltham, MA: RTI International, RTI Project Number 0212790.006, January 2016.
10. Ouslander JG, Lamb G, Tappen R, et al. Interventions to reduce hospitalizations from nursing homes: Evaluation of the INTERACT II collaborative quality improvement project. J Am Geriatr Soc. 2011:59:745-753. PubMed
11. Kim L, Kou L, Hu B, Gorodeski EZ, Rothberg M. Impact of a Connected Care Model on 30-Day Readmission Rates from Skilled Nursing Facilities. J Hosp Med. 2017;12:238-244. PubMed
12. Kansagara D, Englander H, Salanitro A, et al. Risk Prediction Models for Hospital Readmission: A Systematic Review. JAMA. 2011;306(15):1688-1698. PubMed
13. Averill RF, Goldfield N, Hughes JS, et al. All Patient Refined Diagnosis Related Groups (APR-DRGs): Methodology Overview. 3M Health Information Systems Document GRP-041 (2003). https://www.hcup-us.ahrq.gov/db/nation/nis/APR-DRGsV20MethodologyOverviewandBibliography.pdf. Accessed on November 5, 2015.
14. StataCorp. 2013. Stata Statistical Software: Release 13. College Station, TX: StataCorp LP.
15. Cebul RD, Rebitzer JB, Taylor LJ, Votruba ME. Organizational fragmentation and care quality in the U.S. healthcare system. J Econ Perspect. 2008;22(4):93-113. PubMed
16. Tjia J, Bonner A, Briesacher BA, McGee S, Terrill E, Miller K. Medication discrepancies upon hospital to skilled nursing facility transitions. J Gen Intern Med. 2009;24:630-635. PubMed
17. Desai R, Williams CE, Greene SB, Pierson S, Hansen RA. Medication errors during patient transitions into nursing homes: characteristics and association with patient harm. Am J Geriatr Pharmacother. 2011;9:413-422. PubMed
18. Chhabra PT, Rattinger GB, Dutcher SK, Hare ME, Parsons KL, Zuckerman IH. Medication reconciliation during the transition to and from long-term care settings: a systematic review. Res Social Adm Pharm. 2012;8(1):60-75. PubMed
19. Rahman M, Foster AD, Grabowski DC, Zinn JS, Mor V. Effect of hospital-SNF referral linkages on rehospitalization. Health Serv Res. 2013;48(6, pt 1):1898-1919. PubMed
20. Schoenfeld AJ, Zhang X, Grabowski DC, Mor V, Weissman JS, Rahman M. Hospital-skilled nursing facility referral linkage reduces readmission rates among Medicare patients receiving major surgery. Surgery. 2016;159(5):1461-1468. PubMed
21. Rahman M, McHugh J, Gozalo P, Ackerly DC, Mor V. The Contribution of Skilled Nursing Facilities to Hospitals’ Readmission Rate. HSR: Health Services Research. 2017;52(2):656-675. PubMed
22. Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients in the Medicare fee-for-service program. New Engl J Med. 2009;360(14):1418-1428. PubMed
23. Hasan O, Meltzer DO, Shaykevich SA, et al. Hospital readmission in general medicine patients: a prediction model. J Hosp Med. 2010;25(3)211-219. PubMed
24. Allaudeen N, Vidyarhi A, Masella J, Auerbach A. Redefining readmission risk factors for general medicine patients. J Hosp Med. 2011;6(2):54-60. PubMed
25. Van Walraven C, Wong J, Forster AJ. LACE+ index: extension of a validated index to predict early death or urgent readmission after discharge using administrative data. Open Med. 2012;6(3):e80-e90. PubMed
26. Protecting Access to Medicare Act of 2014, Pub. L. No. 113-93, 128 Stat. 1040 (April 1, 2014). https://www.congress.gov/113/plaws/publ93/PLAW-113publ93.pdf. Accessed on October 3, 2015.
1. Centers for Medicare & Medicaid Services (CMS), HHS. Medicare Program; Prospective Payment System and Consolidated Billing for Skilled Nursing Facilities (SNFs) for FY 2016, SNF Value-Based Purchasing Program, SNF Quality Reporting Program, and Staffing Data Collection. Final Rule. Fed Regist. 2015;80(149):46389-46477. PubMed
2. “Readmissions Reduction Program,” Centers for Medicare & Medicaid Services. http://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/AcuteInpatientPPS/Readmissions-Reduction-Program.html. Accessed November 5, 2015.
3. Naylor MD, Brooten D, Campbell R, et al. Comprehensive discharge planning and home follow-up of hospitalized elders: a randomized clinical trial. JAMA. 1999;281:613-620. PubMed
4. Naylor MD, Brooten DA, Campbell RL, Maislin G, McCauley KM, Schwartz JS. Transitional care of older adults hospitalized with heart failure: a randomized, controlled trial. J Am Geriatr Soc. 2004;52:675-684. PubMed
5. Coleman EA, Parry C, Chalmers S, Min SJ. The care transitions intervention: results of a randomized controlled trial. Arch Intern Med. 2006;166:1822-1828. PubMed
6. CMS Office of Information Products and Data Analytics. National Medicare Readmission Findings: Recent Data and Trends. 2012. http://www.academyhealth.org/files/2012/sunday/brennan.pdf. Accessed on September 21, 2015.
7. Centers for Medicare & Medicaid Services, CMS Innovation Center. Initiative to Reduce Avoidable Hospitalizations among Nursing Facility Residents. https://innovation.cms.gov/initiatives/rahnfr/. Accessed on November 5, 2015.
8. Unroe KT, Nazir A, Holtz LR, et al. The Optimizing Patient Transfers, Impacting Medical Quality and Improving Symptoms: Transforming Institutional Care Approach: Preliminary data from the implementation of a Centers for Medicare and Medicaid Services nursing facility demonstration project. J Am Geriatr Soc. 2015;65:165-169. PubMed
9. Ingber MJ, Feng Z, Khatstsky G, et al. Evaluation of the Initiative to Reduce Avoidable Hospitalizations among Nursing Facility Residents: Final Annual Report Project Year 3. Waltham, MA: RTI International, RTI Project Number 0212790.006, January 2016.
10. Ouslander JG, Lamb G, Tappen R, et al. Interventions to reduce hospitalizations from nursing homes: Evaluation of the INTERACT II collaborative quality improvement project. J Am Geriatr Soc. 2011:59:745-753. PubMed
11. Kim L, Kou L, Hu B, Gorodeski EZ, Rothberg M. Impact of a Connected Care Model on 30-Day Readmission Rates from Skilled Nursing Facilities. J Hosp Med. 2017;12:238-244. PubMed
12. Kansagara D, Englander H, Salanitro A, et al. Risk Prediction Models for Hospital Readmission: A Systematic Review. JAMA. 2011;306(15):1688-1698. PubMed
13. Averill RF, Goldfield N, Hughes JS, et al. All Patient Refined Diagnosis Related Groups (APR-DRGs): Methodology Overview. 3M Health Information Systems Document GRP-041 (2003). https://www.hcup-us.ahrq.gov/db/nation/nis/APR-DRGsV20MethodologyOverviewandBibliography.pdf. Accessed on November 5, 2015.
14. StataCorp. 2013. Stata Statistical Software: Release 13. College Station, TX: StataCorp LP.
15. Cebul RD, Rebitzer JB, Taylor LJ, Votruba ME. Organizational fragmentation and care quality in the U.S. healthcare system. J Econ Perspect. 2008;22(4):93-113. PubMed
16. Tjia J, Bonner A, Briesacher BA, McGee S, Terrill E, Miller K. Medication discrepancies upon hospital to skilled nursing facility transitions. J Gen Intern Med. 2009;24:630-635. PubMed
17. Desai R, Williams CE, Greene SB, Pierson S, Hansen RA. Medication errors during patient transitions into nursing homes: characteristics and association with patient harm. Am J Geriatr Pharmacother. 2011;9:413-422. PubMed
18. Chhabra PT, Rattinger GB, Dutcher SK, Hare ME, Parsons KL, Zuckerman IH. Medication reconciliation during the transition to and from long-term care settings: a systematic review. Res Social Adm Pharm. 2012;8(1):60-75. PubMed
19. Rahman M, Foster AD, Grabowski DC, Zinn JS, Mor V. Effect of hospital-SNF referral linkages on rehospitalization. Health Serv Res. 2013;48(6, pt 1):1898-1919. PubMed
20. Schoenfeld AJ, Zhang X, Grabowski DC, Mor V, Weissman JS, Rahman M. Hospital-skilled nursing facility referral linkage reduces readmission rates among Medicare patients receiving major surgery. Surgery. 2016;159(5):1461-1468. PubMed
21. Rahman M, McHugh J, Gozalo P, Ackerly DC, Mor V. The Contribution of Skilled Nursing Facilities to Hospitals’ Readmission Rate. HSR: Health Services Research. 2017;52(2):656-675. PubMed
22. Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients in the Medicare fee-for-service program. New Engl J Med. 2009;360(14):1418-1428. PubMed
23. Hasan O, Meltzer DO, Shaykevich SA, et al. Hospital readmission in general medicine patients: a prediction model. J Hosp Med. 2010;25(3)211-219. PubMed
24. Allaudeen N, Vidyarhi A, Masella J, Auerbach A. Redefining readmission risk factors for general medicine patients. J Hosp Med. 2011;6(2):54-60. PubMed
25. Van Walraven C, Wong J, Forster AJ. LACE+ index: extension of a validated index to predict early death or urgent readmission after discharge using administrative data. Open Med. 2012;6(3):e80-e90. PubMed
26. Protecting Access to Medicare Act of 2014, Pub. L. No. 113-93, 128 Stat. 1040 (April 1, 2014). https://www.congress.gov/113/plaws/publ93/PLAW-113publ93.pdf. Accessed on October 3, 2015.
© 2018 Society of Hospital Medicine
Paraskiing Crash and Knee Dislocation With Multiligament Reconstruction and Iliotibial Band Repair
Take-Home Points
- Reconstruction of a torn ITB is important in restoration of native anatomy and function given its properties in anterolateral stabilization and resistance to varus stress and internal tibial rotation.
- Restoration of posterolateral instability primarily involves reconstructing the FCL, PLT, and popliteofibular ligament.
- For combined PLC injuries, concurrent reconstruction of the cruciate ligaments in one stage is highly recommended.
- Post-surgery, a 6-week non-weight-bearing, limited flexion rehab protocol utilizing a dynamic PCL brace, such as the PCL Rebound brace, is recommended to prevent posterior tibial sag.
- Arthrofibrosis and decreased ROM can be seen following a violent knee injury which requires extensive multiligament reconstruction surgeries, occasionally requiring a secondary surgery for further restoration of knee motion.
Tibiofemoral knee dislocations are uncommon injuries that have devastating complications and potentially result in complex surgeries.1 Knee dislocations (KDs) can be classified with the Schenck system.2 KD-I is a multiligament injury involving the anterior cruciate ligament (ACL) or the posterior cruciate ligament (PCL), and the scale increases in severity/number of ligaments involved, with KD-V being a multiligament injury with periarticular fracture.2
In this article, we report the case of a complex multiligament knee reconstruction performed with a midsubstance iliotibial band (ITB) repair. The patient provided written informed consent for print and electronic publication of this case report.
Case Report
A 27-year-old man presented 12 days after a paraskiing crash in which he collided with a tree at 45 mph and fell 40 feet before hitting snow. Physical examination revealed a large hemarthrosis of the left lower extremity and ecchymosis about the posterolateral aspect of the knee and popliteal fossa. Range of motion (ROM) was limited from 5° of hyperextension to 90° of flexion. Additional motion was deferred secondary to pain. Varus stress testing at 0° and 30° of knee flexion demonstrated significant side-to-side differences. The Lachman test, posterior drawer test, and posterolateral drawer test were all 3+. The dial test was 3 to 4+ compared with the contralateral knee. Valgus stress testing at 0° and 30° of flexion did not reveal any side-to-side laxity. The calf was nontender, and all compartments were soft. The patient reported no neurovascular symptoms and had no neuromotor deficits other than mild common peroneal nerve dysesthesias.
Varus stress radiographs showed increased side-to-side gapping (8 mm) of the lateral compartment of the injured knee. Kneeling posterior stress radiographs, limited because of the patient’s inability to apply full stress on the injured knee secondary to pain, showed a difference of 6 mm in increased posterior translation on the uninjured leg (Figures 1A-1D). 
First Surgery
1. PLC Approach. A lateral hockey-stick skin incision was made along the ITB and extended distally between the fibular head and the Gerdy tubercle. The subcutaneous tissue was then dissected, and a posteriorly based flap was developed for preservation of vascular support to the superficial tissues. The ITB and the lateral capsule had completely torn off of the femur, allowing exposure directly into the joint. The long and short heads of the biceps femoris were exposed, with about 50% of the biceps attachment torn. The FCL was torn midsubstance, and the PLT had no remnant attachment left on the femur.
2. ITB and Lateral Capsule Tag Stitched. The torn ends of the ITB were dissected and tag stitches placed in each end. Tag stitches were also placed in the lateral capsule in preparation for a direct repair.
3. Neurolysis. The common peroneal nerve was found encased in a significant amount of scar tissue, and extensive neurolysis was required. Slow, methodical dissection was performed under the partially torn long head of the biceps femoris and was continued through the scar tissue and adhesions. Distally, 5 mm to 7 mm of the peroneus longus fascia was incised as part of the neurolysis in order to prevent nerve irritation or foot drop caused by postoperative swelling.
4. PLC Tunnels. The margin between the lateral gastrocnemius tendon and the soleus muscle was identified by blunt dissection that allowed palpation of the posteromedial aspect of the fibular styloid and the popliteus musculotendinous junction. The underlying biceps bursa was incised in order to locate the midportion of the FCL remnant, which typically is tag-stitched with No. 2 FiberWire to help identify the femoral attachment (this was not done because of the complete tear at the midsubstance of the FCL).
Subperiosteal dissection of the lateral aspect of the fibular head was performed anterior to posterior and distally extended to the champagne-glass drop-off of the fibular head. Continuing the dissection distally beyond this point can endanger the common peroneal nerve. A small sulcus can be palpated where the distal FCL inserts on the fibular head. Posteriorly, a small elevator was used to dissect the soleus muscle off of the posteromedial aspect of the fibular head, where the fibular tunnel would later be created.
A Chandler retractor was placed posterior to the fibular head to protect the neurovascular bundle. With the aid of a collateral ligament aiming device, a guide pin was drilled from the lateral aspect of the fibular head (FCL attachment) to the posteromedial downslope of the fibular styloid (popliteofibular ligament attachment). The entry point of the guide pin was immediately above the champagne- glass drop-off, at the distal insertion site of the FCL, which was described as being 28.4 mm from the styloid tip and 8.2 mm posterior to the anterior margin of the fibular head.3 Care should be taken not to ream the tunnel too proximal, as doing so increases the risk of iatrogenic fracture. A 7-mm reamer was then used to drill the fibular tunnel. To facilitate later passage of the graft, a passing suture was placed through the tunnel, leaving the loop anterolateral.
Next, the starting point for the tibial tunnel was located on the flat spot of the anterolateral tibia distal and medial to the Gerdy tubercle, just lateral to the tibial tubercle. The tibial popliteal sulcus was identified by palpation of the posterolateral tibial plateau to localize the site of the popliteus musculotendinous junction, which is the ideal location of the posterior aperture of the tibial tunnel. This point is 1 cm proximal and 1 cm medial to the posteromedial exit of the fibular tunnel. A Chandler retractor was placed anterior to the lateral gastrocnemius to protect the neurovascular bundle. In the locations described earlier, a cruciate aiming device was used to place a guide pin anterior to posterior. A 9-mm tunnel was overreamed and a passing suture placed, leaving the loop posterior to facilitate graft passage.
The femoral insertions of the FCL and the PLT were then identified. ITB splitting was not necessary, given the complete midsubstance tear of this structure. The FCL attachment was identified 1.4 mm proximal and 3.1 mm posterior to the lateral epicondyle.3 Sharp dissection was performed in this location, proximal to distal, exposing the lateral epicondyle and the small sulcus at the FCL attachment site. A collateral ligament reconstruction aiming sleeve was used to drill a guide pin over the FCL femoral attachment site and out the medial aspect of the distal thigh, about 5 cm proximal and anterior to the adductor tubercle.
The femoral attachment of the PLT was reported located 18.5 mm anterior to the FCL insertion, in the anterior fifth of the popliteal sulcus.3 Although arthrotomy is usually required in order to access the PLT attachment, it was not necessary in this case, given the lateral capsule tear. A guide pin was inserted at the PLT attachment site, parallel to the FCL pin. After proper placement was verified, a 9-mm reamer was used to drill the FCL and PLT tunnels to a depth of 25 mm (socket), and a passing suture was placed into each tunnel to facilitate graft passage.
5. ACL Graft Harvest. The central third of the ipsilateral patellar tendon was harvested for use in the ACL reconstruction. Included were a 10-mm × 20-mm bone plug from the patella and a 10-mm × 25-mm bone plug from the tibial tubercle. The patella defect was then bone-grafted, and the patellar tendon closed side-to-side.
6. Graft Preparation. For the PLC, we used a split Achilles tendon allograft that had two 9-mm × 25-mm bone plugs proximally and were tubularized distally. For the PCL, we used an anterolateral bundle (ALB), which consisted of an Achilles tendon allograft that had an 11-mm × 25-mm bone plug proximally and was tubularized distally, and a posteromedial bundle (PMB), which consisted of a tibialis anterior allograft that was tubularized at both ends. For the ACL, we used a bone–patellar tendon–bone autograft 10 mm in diameter with a 20-mm femoral bone plug and a 25-mm tibial bone plug distally.
7. Arthroscopy. We created standard anterolateral and anteromedial parapatellar portals and performed arthroscopy, including lysis of adhesions. Cartilage and menisci were lesion-free.
8. PCL Femoral Tunnels. The ALB attachment was identified and outlined with a coagulator between the trochlear point and the medial arch point, adjacent to the edge of the articular cartilage. Similarly, the PMB attachment was marked about 8 mm or 9 mm posterior to the edge of the articular cartilage of the medial femoral condyle and slightly posterior to the ALB tunnel.4
In the anterolateral tunnel, an acorn reamer 11 mm in diameter was used to score the entry point of the ALB femoral tunnel. An eyelet pin was then drilled through the reamer anteromedially out the knee. Then a closed socket tunnel was reamed over the eyelet pin to a depth of 25 mm. A passing suture was pulled through the tunnel in preparation for graft passage.
With use of the same technique, a 7-mm reamer was placed against the outline of the PMB attachment site, and an eyelet pin was drilled through this reamer and out the anteromedial aspect of the knee. Again, a 25-mm deep closed socket was reamed. A bone bridge distance of 2 mm was maintained between the 2 femoral PCL bundle tunnels.
9. ACL Femoral Tunnel. The femoral ACL attachment was identified and outlined. An over-the-top guide was used to determine proper placement of the 10-mm low-profile reamer. A guide pin was drilled through the center of the reamer. The reamer was used to create a 25-mm deep closed socket tunnel, and a passing stitch was placed.
10. PCL Tibial Tunnel. With use of a 70° arthroscope for visualization, a posteromedial arthroscopic portal was created, and a shaver and a coagulator were used to identify the tibial PCL attachment, located distally along the PCL facet, until the proximal aspect of the popliteus muscle fibers were visualized. A guide pin was drilled starting at the anteromedial aspect of the tibia, about 6 cm distal to the joint line and centered between the anterior tibial crest and the medial tibial border. The pin exited posteriorly at the center of the PCL tibial attachment along the PCL bundle ridge, which was reported located between the ALB and the PMB on the tibia.5 Pin placement was verified with intraoperative lateral and anteroposterior radiographs. On the lateral radiograph, the pin should be about 6 mm or 7 mm proximal to the champagne-glass drop-off at the PCL facet on the posterior aspect of the tibia. On the anteroposterior radiograph, the pin should be 1 mm to 2 mm distal to the joint line and at the medial aspect of the lateral tibial eminence. A large curette was passed through the posteromedial arthroscopic portal both to retract the posterior tissues away from the reamer and to protect against guide-pin protrusion The guide pin was then overreamed with a 12-mm acorn reamer.
A large smoother was passed proximally up the tibial tunnel and then pulled out the anteromedial portal with a grasper. The smoother was gently cycled to smooth the intra-articular tibial tunnel aperture to remove any bony spicules that could interfere with graft passage. The smoother was then pulled back into the joint, passed out the anterolateral arthroscopic portal, and secured with a small clamp.4
11. ACL Tibial Tunnel. The ACL tibial attachment site was identified and cleaned of soft tissue. A guide pin was placed and then overreamed with a 10-mm acorn reamer.
12. PCL Femoral Fixation. The PMB graft was passed into its tunnel and secured with a 7-mm × 23-mm titanium screw. Next, the ALB was secured to the femur with a 7-mm × 20-mm titanium screw. The smoother was used to pull both grafts down through the tibial tunnel.
13. ACL Femoral Fixation. A 7-mm × 20-mm titanium screw was then used to fix the ACL autograft inside the femur. Traction was applied to the 3 cruciate grafts. There was no sign of impingement.
14. PLC Femoral Fixation. The FCL and the popliteus bone plugs were passed into their respective femoral sockets and secured with 7-mm × 20-mm titanium screws.
15. Lateral Capsule Femoral Anchors. Two suture anchors were placed into the femur, and the sutures were passed through the femoral portion of the lateral capsule for later repair.
16. PCL Tibial Fixation. Both grafts were fixed with a fully threaded bicortical 6.5-mm × 40-mm cannulated cancellous screw and an 18-mm spiked washer. The ALB was fixed first, with the knee flexed to 90°, traction on the graft, and the tibia in neutral rotation. Restoration of the normal tibiofemoral step-off was verified. The PMB was then fixed with the knee in full extension. A posterior drawer test was performed to verify restoration of stability.
17. PLC Fibula Fixation. The PLT graft was passed down the popliteal hiatus, and the FCL graft was passed under the remnant of the biceps bursa on the fibular head and then through the fibular head, anterolateral to posteromedial. The FCL graft was fixed in the fibular tunnel with the knee in 20° of flexion, a slight valgus reduction force, the tibia in neutral rotation, and traction on the graft. A 7-mm × 23-mm bioabsorbable screw was used.
18. Lateral Capsular Repair. The lateral capsule was directly repaired with the previously placed sutures. The sutures were tied with the knee in 20° of flexion.
19. PLC Tibial Fixation. The grafts were passed together, posterior to anterior, through the tibial tunnel. The knee was cycled several times through complete flexion/extension ROM. A 9-mm × 23-mm bioabsorbable screw was then used to fix the grafts to the tibia. During this fixation, the knee was kept in 60° of flexion and neutral rotation while traction was being applied to the distal end of both grafts.
20. ACL Tibial Fixation. A 9-mm × 20-mm titanium screw was used to fix the ACL graft with the knee in full extension. The graft was then viewed intra-articularly to confirm there was no impingement. The Lachman, posterior drawer, posterolateral drawer, dial, and varus stress tests were performed to ensure restoration of stability.
21. ITB Repair. A portion of the remaining Achilles tendon allograft was used to perform ITB reconstruction (reconstitution of the gaped portion of the ITB). Orthocord (DePuy Synthes) and Vicryl (Ethicon) sutures were used for this reconstruction. Knee stability was deemed restored, and the incisions were closed in standard layered fashion.
First Surgery: Postoperative Management
The patient remained non-weight-bearing the first 6 weeks after surgery, with prone knee flexion limited (0°-90°) the first 2 weeks. In addition, a PCL Jack brace (Albrecht) was placed 1 week after surgery and was to be worn at all times to decrease stress on the PCL grafts.
As ROM was not progressing as expected, the patient was instructed to use a continuous passive motion (CPM) machine 2 hours 3 times a day. About 4 weeks after surgery, with ROM still not progressing, the frequency of use of this machine was increased.
Despite continued physical therapy, use of the CPM machine, and pain management, ROM was limited (11°-90° of flexion) 5.5 months after left knee multiligament reconstruction. However, stress radiographs showed excellent stability. Varus stress radiographs showed a side-to-side difference of 0.3 mm less on the left (injured) knee, and kneeling PCL stress radiographs showed a side-to-side difference of 1.3 mm more on the left knee (Figures 3A-3D). 
Second Surgery and Postoperative Management
As gentle manipulation under anesthesia was unsuccessful, the patient underwent knee arthroscopy, including 4-compartment lysis of adhesions, arthroscopically assisted posteromedial capsular release, and post-débridement manipulation under anesthesia. During manipulation, full extension and knee flexion up to 135° were achieved. ACL, PCL, and popliteus grafts were visualized and confirmed to be intact.
After this second surgery, the patient was to resume physical therapy and begin weight- bearing as tolerated. Active ROM was prioritized in an attempt to reach full ROM. In addition, a CPM machine was to be used from 0° to 135° of knee flexion 4 hours 3 times a day for 6 weeks.
Two weeks after surgery, the patient had continued pain, and extracapsular swelling in the left knee. However, ROM (0°-115° of flexion) was improved relative to before surgery (11°-90° of flexion), though it remained below the range on the contralateral side. Of note, the patient reported having a flexion contracture (~10°) in the immediate postoperative period. He had woken up with it after sleeping with the CPM machine the night before. The contracture delayed his physical therapy for several hours and resulted in a redesign of his therapy protocol to emphasize full, active knee extension and patellar mobilization, as well as discontinuation of use of the CPM machine. Corticosteroids were initiated to help with the extracapsular swelling, and the new therapy regimen brought adequate progress in ROM. Four months after the second surgery, the patient had full extension and 135° of flexion and was transitioned into wearing the PCL Rebound brace.
Discussion
This case was unique because of the midsubstance ITB tear and simultaneous multiligament injury caused by a KD-IIIL, a KD involving the ACL, the PCL, and the PLC with the medial side intact. There is limited research on ITB repair generally, with or without KD involvement. In a retrospective review of acute knee trauma cases, ITB pathologies were seen on 45% of reviewed MRI scans, and only 3% of the injuries were grade III; in addition, only 9 (5%) of the 200 cases involved both ITB and multiligament (ACL, PCL) knee injuries.6
After our patient’s ACL, PCL, and PLC were reconstructed, a fan piece of the Achilles tendon allograft from the PLC reconstruction was used to repair the ITB. The graft was used to reconstitute the torn gapped portion of the band in multiple locations, and this repair helped restore stability. The literature has reported numerous surgical uses for a portion of the ITB but few studies on repairing this anatomical structure. Preservation of the ITB is important to restoration of native anatomy and function. The ITB helps with anterolateral stabilization of the knee and with resistance of varus stress and internal tibial rotation.
The PLC reconstruction used in this case has been biomechanically validated as restoring the knee to near native stability through anatomical reconstruction of the PLC’s 3 main static stabilizers: the FCL, the PLT, and the popliteofibular ligament.7-9 First described in 2004,7 this anatomical PLC reconstruction technique has improved subjective and objective patient outcomes.10,11 For combined PLC injuries (eg, our patient’s injuries), Geeslin and LaPrade10 recommended concurrent reconstruction of the cruciate ligaments. In addition to the PLC reconstruction, the anatomical double-bundle PCL reconstruction used in this case has demonstrated significant improvements in subjective and objective outcome scores and objective knee stability.12
Although the stability and anatomy of this patient’s injured knee were reestablished, his development of arthrofibrosis is important. Many have discussed the commonality of arthrofibrosis or decreased ROM after extensive multiligament reconstruction surgeries.13,14 One study involving surgical management and outcomes of multiligament knee injuries found that, in more than half of its cases, restoration of full ROM required at least one operation after the initial one.13 Therefore, it is not unusual that our patient required a second operation for decreased ROM.
Conclusion
After surgery, excellent stabilization was achieved. Although the patient had setbacks related to pain and decreased ROM, his second surgery and continued physical therapy likely will help him return to his preoperative recreational activity levels.
1. Delos D, Warren RF, Marx RG. Multiligament knee injuries and their treatment. Oper Tech Sports Med. 2010;18(4):219-226.
2. Hobby B, Treme G, Wascher DC, Schenck RC. How I manage knee dislocations. Oper Tech Sports Med. 2010;18(4):227-234.
3. LaPrade RF, Ly TV, Wentorf FA, Engebretsen L. The posterolateral attachments of the knee: a qualitative and quantitative morphologic analysis of the fibular collateral ligament, popliteus tendon, popliteofibular ligament, and lateral gastrocnemius tendon. Am J Sports Med. 2003;31(6):854-860.
4. Chahla J, Nitri M, Civitarese D, Dean CS, Moulton SG, LaPrade RF. Anatomic double-bundle posterior cruciate ligament reconstruction. Arthrosc Tech. 2016;5(1):e149-e156.
5. Anderson CJ, Ziegler CG, Wijdicks CA, Engebretsen L, LaPrade RF. Arthroscopically pertinent anatomy of the anterolateral and posteromedial bundles of the posterior cruciate ligament. J Bone Joint Surg Am. 2012;94(21):1936-1945.
6. Mansour R, Yoong P, McKean D, Teh JL. The iliotibial band in acute knee trauma: patterns of injury on MR imaging. Skeletal Radiol. 2014;43(10):1369-1375.
7. LaPrade RF, Johansen S, Wentorf FA, Engebretsen L, Esterberg JL, Tso A. An analysis of an anatomical posterolateral knee reconstruction: an in vitro biomechanical study and development of a surgical technique. Am J Sports Med. 2004;32(6):1405-1414.
8. McCarthy M, Camarda L, Wijdicks CA, Johansen S, Engebretsen L, LaPrade RF. Anatomic posterolateral knee reconstructions require a popliteofibular ligament reconstruction through a tibial tunnel. Am J Sports Med. 2010;38(8):1674-1681.
9. LaPrade RF, Wozniczka JK, Stellmaker MP, Wijdicks CA. Analysis of the static function of the popliteus tendon and evaluation of an anatomic reconstruction: the “fifth ligament” of the knee. Am J Sports Med. 2010;38(3):543-549.
10. Geeslin AG, LaPrade RF. Outcomes of treatment of acute grade-III isolated and combined posterolateral knee injuries: a prospective case series and surgical technique. J Bone Joint Surg Am. 2011;93(18):1672-1683.
11. LaPrade RF, Johansen S, Agel J, Risberg MA, Moksnes H, Engebretsen L. Outcomes of an anatomic posterolateral knee reconstruction. J Bone Joint Surg Am. 2010;92(1):16-22.
12. Spiridonov SI, Slinkard NJ, LaPrade RF. Isolated and combined grade-III posterior cruciate ligament tears treated with double-bundle reconstruction with use of endoscopically placed femoral tunnels and grafts: operative technique and clinical outcomes. J Bone Joint Surg Am. 2011;93(19):1773-1780.
13. Noyes FR, Barber-Westin SD. Reconstruction of the anterior and posterior cruciate ligaments after knee dislocation. Use of early protected postoperative motion to decrease arthrofibrosis. Am J Sports Med. 1997;25(6):769-778.
14. Yenchak AJ, Wilk KE, Arrigo CA, Simpson CD, Andrews JR. Criteria-based management of an acute multistructure knee injury in a professional football player: a case report. J Orthop Sports Phys Ther. 2011;41(9):675-686.
Take-Home Points
- Reconstruction of a torn ITB is important in restoration of native anatomy and function given its properties in anterolateral stabilization and resistance to varus stress and internal tibial rotation.
- Restoration of posterolateral instability primarily involves reconstructing the FCL, PLT, and popliteofibular ligament.
- For combined PLC injuries, concurrent reconstruction of the cruciate ligaments in one stage is highly recommended.
- Post-surgery, a 6-week non-weight-bearing, limited flexion rehab protocol utilizing a dynamic PCL brace, such as the PCL Rebound brace, is recommended to prevent posterior tibial sag.
- Arthrofibrosis and decreased ROM can be seen following a violent knee injury which requires extensive multiligament reconstruction surgeries, occasionally requiring a secondary surgery for further restoration of knee motion.
Tibiofemoral knee dislocations are uncommon injuries that have devastating complications and potentially result in complex surgeries.1 Knee dislocations (KDs) can be classified with the Schenck system.2 KD-I is a multiligament injury involving the anterior cruciate ligament (ACL) or the posterior cruciate ligament (PCL), and the scale increases in severity/number of ligaments involved, with KD-V being a multiligament injury with periarticular fracture.2
In this article, we report the case of a complex multiligament knee reconstruction performed with a midsubstance iliotibial band (ITB) repair. The patient provided written informed consent for print and electronic publication of this case report.
Case Report
A 27-year-old man presented 12 days after a paraskiing crash in which he collided with a tree at 45 mph and fell 40 feet before hitting snow. Physical examination revealed a large hemarthrosis of the left lower extremity and ecchymosis about the posterolateral aspect of the knee and popliteal fossa. Range of motion (ROM) was limited from 5° of hyperextension to 90° of flexion. Additional motion was deferred secondary to pain. Varus stress testing at 0° and 30° of knee flexion demonstrated significant side-to-side differences. The Lachman test, posterior drawer test, and posterolateral drawer test were all 3+. The dial test was 3 to 4+ compared with the contralateral knee. Valgus stress testing at 0° and 30° of flexion did not reveal any side-to-side laxity. The calf was nontender, and all compartments were soft. The patient reported no neurovascular symptoms and had no neuromotor deficits other than mild common peroneal nerve dysesthesias.
Varus stress radiographs showed increased side-to-side gapping (8 mm) of the lateral compartment of the injured knee. Kneeling posterior stress radiographs, limited because of the patient’s inability to apply full stress on the injured knee secondary to pain, showed a difference of 6 mm in increased posterior translation on the uninjured leg (Figures 1A-1D).
First Surgery
1. PLC Approach. A lateral hockey-stick skin incision was made along the ITB and extended distally between the fibular head and the Gerdy tubercle. The subcutaneous tissue was then dissected, and a posteriorly based flap was developed for preservation of vascular support to the superficial tissues. The ITB and the lateral capsule had completely torn off of the femur, allowing exposure directly into the joint. The long and short heads of the biceps femoris were exposed, with about 50% of the biceps attachment torn. The FCL was torn midsubstance, and the PLT had no remnant attachment left on the femur.
2. ITB and Lateral Capsule Tag Stitched. The torn ends of the ITB were dissected and tag stitches placed in each end. Tag stitches were also placed in the lateral capsule in preparation for a direct repair.
3. Neurolysis. The common peroneal nerve was found encased in a significant amount of scar tissue, and extensive neurolysis was required. Slow, methodical dissection was performed under the partially torn long head of the biceps femoris and was continued through the scar tissue and adhesions. Distally, 5 mm to 7 mm of the peroneus longus fascia was incised as part of the neurolysis in order to prevent nerve irritation or foot drop caused by postoperative swelling.
4. PLC Tunnels. The margin between the lateral gastrocnemius tendon and the soleus muscle was identified by blunt dissection that allowed palpation of the posteromedial aspect of the fibular styloid and the popliteus musculotendinous junction. The underlying biceps bursa was incised in order to locate the midportion of the FCL remnant, which typically is tag-stitched with No. 2 FiberWire to help identify the femoral attachment (this was not done because of the complete tear at the midsubstance of the FCL).
Subperiosteal dissection of the lateral aspect of the fibular head was performed anterior to posterior and distally extended to the champagne-glass drop-off of the fibular head. Continuing the dissection distally beyond this point can endanger the common peroneal nerve. A small sulcus can be palpated where the distal FCL inserts on the fibular head. Posteriorly, a small elevator was used to dissect the soleus muscle off of the posteromedial aspect of the fibular head, where the fibular tunnel would later be created.
A Chandler retractor was placed posterior to the fibular head to protect the neurovascular bundle. With the aid of a collateral ligament aiming device, a guide pin was drilled from the lateral aspect of the fibular head (FCL attachment) to the posteromedial downslope of the fibular styloid (popliteofibular ligament attachment). The entry point of the guide pin was immediately above the champagne- glass drop-off, at the distal insertion site of the FCL, which was described as being 28.4 mm from the styloid tip and 8.2 mm posterior to the anterior margin of the fibular head.3 Care should be taken not to ream the tunnel too proximal, as doing so increases the risk of iatrogenic fracture. A 7-mm reamer was then used to drill the fibular tunnel. To facilitate later passage of the graft, a passing suture was placed through the tunnel, leaving the loop anterolateral.
Next, the starting point for the tibial tunnel was located on the flat spot of the anterolateral tibia distal and medial to the Gerdy tubercle, just lateral to the tibial tubercle. The tibial popliteal sulcus was identified by palpation of the posterolateral tibial plateau to localize the site of the popliteus musculotendinous junction, which is the ideal location of the posterior aperture of the tibial tunnel. This point is 1 cm proximal and 1 cm medial to the posteromedial exit of the fibular tunnel. A Chandler retractor was placed anterior to the lateral gastrocnemius to protect the neurovascular bundle. In the locations described earlier, a cruciate aiming device was used to place a guide pin anterior to posterior. A 9-mm tunnel was overreamed and a passing suture placed, leaving the loop posterior to facilitate graft passage.
The femoral insertions of the FCL and the PLT were then identified. ITB splitting was not necessary, given the complete midsubstance tear of this structure. The FCL attachment was identified 1.4 mm proximal and 3.1 mm posterior to the lateral epicondyle.3 Sharp dissection was performed in this location, proximal to distal, exposing the lateral epicondyle and the small sulcus at the FCL attachment site. A collateral ligament reconstruction aiming sleeve was used to drill a guide pin over the FCL femoral attachment site and out the medial aspect of the distal thigh, about 5 cm proximal and anterior to the adductor tubercle.
The femoral attachment of the PLT was reported located 18.5 mm anterior to the FCL insertion, in the anterior fifth of the popliteal sulcus.3 Although arthrotomy is usually required in order to access the PLT attachment, it was not necessary in this case, given the lateral capsule tear. A guide pin was inserted at the PLT attachment site, parallel to the FCL pin. After proper placement was verified, a 9-mm reamer was used to drill the FCL and PLT tunnels to a depth of 25 mm (socket), and a passing suture was placed into each tunnel to facilitate graft passage.
5. ACL Graft Harvest. The central third of the ipsilateral patellar tendon was harvested for use in the ACL reconstruction. Included were a 10-mm × 20-mm bone plug from the patella and a 10-mm × 25-mm bone plug from the tibial tubercle. The patella defect was then bone-grafted, and the patellar tendon closed side-to-side.
6. Graft Preparation. For the PLC, we used a split Achilles tendon allograft that had two 9-mm × 25-mm bone plugs proximally and were tubularized distally. For the PCL, we used an anterolateral bundle (ALB), which consisted of an Achilles tendon allograft that had an 11-mm × 25-mm bone plug proximally and was tubularized distally, and a posteromedial bundle (PMB), which consisted of a tibialis anterior allograft that was tubularized at both ends. For the ACL, we used a bone–patellar tendon–bone autograft 10 mm in diameter with a 20-mm femoral bone plug and a 25-mm tibial bone plug distally.
7. Arthroscopy. We created standard anterolateral and anteromedial parapatellar portals and performed arthroscopy, including lysis of adhesions. Cartilage and menisci were lesion-free.
8. PCL Femoral Tunnels. The ALB attachment was identified and outlined with a coagulator between the trochlear point and the medial arch point, adjacent to the edge of the articular cartilage. Similarly, the PMB attachment was marked about 8 mm or 9 mm posterior to the edge of the articular cartilage of the medial femoral condyle and slightly posterior to the ALB tunnel.4
In the anterolateral tunnel, an acorn reamer 11 mm in diameter was used to score the entry point of the ALB femoral tunnel. An eyelet pin was then drilled through the reamer anteromedially out the knee. Then a closed socket tunnel was reamed over the eyelet pin to a depth of 25 mm. A passing suture was pulled through the tunnel in preparation for graft passage.
With use of the same technique, a 7-mm reamer was placed against the outline of the PMB attachment site, and an eyelet pin was drilled through this reamer and out the anteromedial aspect of the knee. Again, a 25-mm deep closed socket was reamed. A bone bridge distance of 2 mm was maintained between the 2 femoral PCL bundle tunnels.
9. ACL Femoral Tunnel. The femoral ACL attachment was identified and outlined. An over-the-top guide was used to determine proper placement of the 10-mm low-profile reamer. A guide pin was drilled through the center of the reamer. The reamer was used to create a 25-mm deep closed socket tunnel, and a passing stitch was placed.
10. PCL Tibial Tunnel. With use of a 70° arthroscope for visualization, a posteromedial arthroscopic portal was created, and a shaver and a coagulator were used to identify the tibial PCL attachment, located distally along the PCL facet, until the proximal aspect of the popliteus muscle fibers were visualized. A guide pin was drilled starting at the anteromedial aspect of the tibia, about 6 cm distal to the joint line and centered between the anterior tibial crest and the medial tibial border. The pin exited posteriorly at the center of the PCL tibial attachment along the PCL bundle ridge, which was reported located between the ALB and the PMB on the tibia.5 Pin placement was verified with intraoperative lateral and anteroposterior radiographs. On the lateral radiograph, the pin should be about 6 mm or 7 mm proximal to the champagne-glass drop-off at the PCL facet on the posterior aspect of the tibia. On the anteroposterior radiograph, the pin should be 1 mm to 2 mm distal to the joint line and at the medial aspect of the lateral tibial eminence. A large curette was passed through the posteromedial arthroscopic portal both to retract the posterior tissues away from the reamer and to protect against guide-pin protrusion The guide pin was then overreamed with a 12-mm acorn reamer.
A large smoother was passed proximally up the tibial tunnel and then pulled out the anteromedial portal with a grasper. The smoother was gently cycled to smooth the intra-articular tibial tunnel aperture to remove any bony spicules that could interfere with graft passage. The smoother was then pulled back into the joint, passed out the anterolateral arthroscopic portal, and secured with a small clamp.4
11. ACL Tibial Tunnel. The ACL tibial attachment site was identified and cleaned of soft tissue. A guide pin was placed and then overreamed with a 10-mm acorn reamer.
12. PCL Femoral Fixation. The PMB graft was passed into its tunnel and secured with a 7-mm × 23-mm titanium screw. Next, the ALB was secured to the femur with a 7-mm × 20-mm titanium screw. The smoother was used to pull both grafts down through the tibial tunnel.
13. ACL Femoral Fixation. A 7-mm × 20-mm titanium screw was then used to fix the ACL autograft inside the femur. Traction was applied to the 3 cruciate grafts. There was no sign of impingement.
14. PLC Femoral Fixation. The FCL and the popliteus bone plugs were passed into their respective femoral sockets and secured with 7-mm × 20-mm titanium screws.
15. Lateral Capsule Femoral Anchors. Two suture anchors were placed into the femur, and the sutures were passed through the femoral portion of the lateral capsule for later repair.
16. PCL Tibial Fixation. Both grafts were fixed with a fully threaded bicortical 6.5-mm × 40-mm cannulated cancellous screw and an 18-mm spiked washer. The ALB was fixed first, with the knee flexed to 90°, traction on the graft, and the tibia in neutral rotation. Restoration of the normal tibiofemoral step-off was verified. The PMB was then fixed with the knee in full extension. A posterior drawer test was performed to verify restoration of stability.
17. PLC Fibula Fixation. The PLT graft was passed down the popliteal hiatus, and the FCL graft was passed under the remnant of the biceps bursa on the fibular head and then through the fibular head, anterolateral to posteromedial. The FCL graft was fixed in the fibular tunnel with the knee in 20° of flexion, a slight valgus reduction force, the tibia in neutral rotation, and traction on the graft. A 7-mm × 23-mm bioabsorbable screw was used.
18. Lateral Capsular Repair. The lateral capsule was directly repaired with the previously placed sutures. The sutures were tied with the knee in 20° of flexion.
19. PLC Tibial Fixation. The grafts were passed together, posterior to anterior, through the tibial tunnel. The knee was cycled several times through complete flexion/extension ROM. A 9-mm × 23-mm bioabsorbable screw was then used to fix the grafts to the tibia. During this fixation, the knee was kept in 60° of flexion and neutral rotation while traction was being applied to the distal end of both grafts.
20. ACL Tibial Fixation. A 9-mm × 20-mm titanium screw was used to fix the ACL graft with the knee in full extension. The graft was then viewed intra-articularly to confirm there was no impingement. The Lachman, posterior drawer, posterolateral drawer, dial, and varus stress tests were performed to ensure restoration of stability.
21. ITB Repair. A portion of the remaining Achilles tendon allograft was used to perform ITB reconstruction (reconstitution of the gaped portion of the ITB). Orthocord (DePuy Synthes) and Vicryl (Ethicon) sutures were used for this reconstruction. Knee stability was deemed restored, and the incisions were closed in standard layered fashion.
First Surgery: Postoperative Management
The patient remained non-weight-bearing the first 6 weeks after surgery, with prone knee flexion limited (0°-90°) the first 2 weeks. In addition, a PCL Jack brace (Albrecht) was placed 1 week after surgery and was to be worn at all times to decrease stress on the PCL grafts.
As ROM was not progressing as expected, the patient was instructed to use a continuous passive motion (CPM) machine 2 hours 3 times a day. About 4 weeks after surgery, with ROM still not progressing, the frequency of use of this machine was increased.
Despite continued physical therapy, use of the CPM machine, and pain management, ROM was limited (11°-90° of flexion) 5.5 months after left knee multiligament reconstruction. However, stress radiographs showed excellent stability. Varus stress radiographs showed a side-to-side difference of 0.3 mm less on the left (injured) knee, and kneeling PCL stress radiographs showed a side-to-side difference of 1.3 mm more on the left knee (Figures 3A-3D).
Second Surgery and Postoperative Management
As gentle manipulation under anesthesia was unsuccessful, the patient underwent knee arthroscopy, including 4-compartment lysis of adhesions, arthroscopically assisted posteromedial capsular release, and post-débridement manipulation under anesthesia. During manipulation, full extension and knee flexion up to 135° were achieved. ACL, PCL, and popliteus grafts were visualized and confirmed to be intact.
After this second surgery, the patient was to resume physical therapy and begin weight- bearing as tolerated. Active ROM was prioritized in an attempt to reach full ROM. In addition, a CPM machine was to be used from 0° to 135° of knee flexion 4 hours 3 times a day for 6 weeks.
Two weeks after surgery, the patient had continued pain, and extracapsular swelling in the left knee. However, ROM (0°-115° of flexion) was improved relative to before surgery (11°-90° of flexion), though it remained below the range on the contralateral side. Of note, the patient reported having a flexion contracture (~10°) in the immediate postoperative period. He had woken up with it after sleeping with the CPM machine the night before. The contracture delayed his physical therapy for several hours and resulted in a redesign of his therapy protocol to emphasize full, active knee extension and patellar mobilization, as well as discontinuation of use of the CPM machine. Corticosteroids were initiated to help with the extracapsular swelling, and the new therapy regimen brought adequate progress in ROM. Four months after the second surgery, the patient had full extension and 135° of flexion and was transitioned into wearing the PCL Rebound brace.
Discussion
This case was unique because of the midsubstance ITB tear and simultaneous multiligament injury caused by a KD-IIIL, a KD involving the ACL, the PCL, and the PLC with the medial side intact. There is limited research on ITB repair generally, with or without KD involvement. In a retrospective review of acute knee trauma cases, ITB pathologies were seen on 45% of reviewed MRI scans, and only 3% of the injuries were grade III; in addition, only 9 (5%) of the 200 cases involved both ITB and multiligament (ACL, PCL) knee injuries.6
After our patient’s ACL, PCL, and PLC were reconstructed, a fan piece of the Achilles tendon allograft from the PLC reconstruction was used to repair the ITB. The graft was used to reconstitute the torn gapped portion of the band in multiple locations, and this repair helped restore stability. The literature has reported numerous surgical uses for a portion of the ITB but few studies on repairing this anatomical structure. Preservation of the ITB is important to restoration of native anatomy and function. The ITB helps with anterolateral stabilization of the knee and with resistance of varus stress and internal tibial rotation.
The PLC reconstruction used in this case has been biomechanically validated as restoring the knee to near native stability through anatomical reconstruction of the PLC’s 3 main static stabilizers: the FCL, the PLT, and the popliteofibular ligament.7-9 First described in 2004,7 this anatomical PLC reconstruction technique has improved subjective and objective patient outcomes.10,11 For combined PLC injuries (eg, our patient’s injuries), Geeslin and LaPrade10 recommended concurrent reconstruction of the cruciate ligaments. In addition to the PLC reconstruction, the anatomical double-bundle PCL reconstruction used in this case has demonstrated significant improvements in subjective and objective outcome scores and objective knee stability.12
Although the stability and anatomy of this patient’s injured knee were reestablished, his development of arthrofibrosis is important. Many have discussed the commonality of arthrofibrosis or decreased ROM after extensive multiligament reconstruction surgeries.13,14 One study involving surgical management and outcomes of multiligament knee injuries found that, in more than half of its cases, restoration of full ROM required at least one operation after the initial one.13 Therefore, it is not unusual that our patient required a second operation for decreased ROM.
Conclusion
After surgery, excellent stabilization was achieved. Although the patient had setbacks related to pain and decreased ROM, his second surgery and continued physical therapy likely will help him return to his preoperative recreational activity levels.
Take-Home Points
- Reconstruction of a torn ITB is important in restoration of native anatomy and function given its properties in anterolateral stabilization and resistance to varus stress and internal tibial rotation.
- Restoration of posterolateral instability primarily involves reconstructing the FCL, PLT, and popliteofibular ligament.
- For combined PLC injuries, concurrent reconstruction of the cruciate ligaments in one stage is highly recommended.
- Post-surgery, a 6-week non-weight-bearing, limited flexion rehab protocol utilizing a dynamic PCL brace, such as the PCL Rebound brace, is recommended to prevent posterior tibial sag.
- Arthrofibrosis and decreased ROM can be seen following a violent knee injury which requires extensive multiligament reconstruction surgeries, occasionally requiring a secondary surgery for further restoration of knee motion.
Tibiofemoral knee dislocations are uncommon injuries that have devastating complications and potentially result in complex surgeries.1 Knee dislocations (KDs) can be classified with the Schenck system.2 KD-I is a multiligament injury involving the anterior cruciate ligament (ACL) or the posterior cruciate ligament (PCL), and the scale increases in severity/number of ligaments involved, with KD-V being a multiligament injury with periarticular fracture.2
In this article, we report the case of a complex multiligament knee reconstruction performed with a midsubstance iliotibial band (ITB) repair. The patient provided written informed consent for print and electronic publication of this case report.
Case Report
A 27-year-old man presented 12 days after a paraskiing crash in which he collided with a tree at 45 mph and fell 40 feet before hitting snow. Physical examination revealed a large hemarthrosis of the left lower extremity and ecchymosis about the posterolateral aspect of the knee and popliteal fossa. Range of motion (ROM) was limited from 5° of hyperextension to 90° of flexion. Additional motion was deferred secondary to pain. Varus stress testing at 0° and 30° of knee flexion demonstrated significant side-to-side differences. The Lachman test, posterior drawer test, and posterolateral drawer test were all 3+. The dial test was 3 to 4+ compared with the contralateral knee. Valgus stress testing at 0° and 30° of flexion did not reveal any side-to-side laxity. The calf was nontender, and all compartments were soft. The patient reported no neurovascular symptoms and had no neuromotor deficits other than mild common peroneal nerve dysesthesias.
Varus stress radiographs showed increased side-to-side gapping (8 mm) of the lateral compartment of the injured knee. Kneeling posterior stress radiographs, limited because of the patient’s inability to apply full stress on the injured knee secondary to pain, showed a difference of 6 mm in increased posterior translation on the uninjured leg (Figures 1A-1D).
First Surgery
1. PLC Approach. A lateral hockey-stick skin incision was made along the ITB and extended distally between the fibular head and the Gerdy tubercle. The subcutaneous tissue was then dissected, and a posteriorly based flap was developed for preservation of vascular support to the superficial tissues. The ITB and the lateral capsule had completely torn off of the femur, allowing exposure directly into the joint. The long and short heads of the biceps femoris were exposed, with about 50% of the biceps attachment torn. The FCL was torn midsubstance, and the PLT had no remnant attachment left on the femur.
2. ITB and Lateral Capsule Tag Stitched. The torn ends of the ITB were dissected and tag stitches placed in each end. Tag stitches were also placed in the lateral capsule in preparation for a direct repair.
3. Neurolysis. The common peroneal nerve was found encased in a significant amount of scar tissue, and extensive neurolysis was required. Slow, methodical dissection was performed under the partially torn long head of the biceps femoris and was continued through the scar tissue and adhesions. Distally, 5 mm to 7 mm of the peroneus longus fascia was incised as part of the neurolysis in order to prevent nerve irritation or foot drop caused by postoperative swelling.
4. PLC Tunnels. The margin between the lateral gastrocnemius tendon and the soleus muscle was identified by blunt dissection that allowed palpation of the posteromedial aspect of the fibular styloid and the popliteus musculotendinous junction. The underlying biceps bursa was incised in order to locate the midportion of the FCL remnant, which typically is tag-stitched with No. 2 FiberWire to help identify the femoral attachment (this was not done because of the complete tear at the midsubstance of the FCL).
Subperiosteal dissection of the lateral aspect of the fibular head was performed anterior to posterior and distally extended to the champagne-glass drop-off of the fibular head. Continuing the dissection distally beyond this point can endanger the common peroneal nerve. A small sulcus can be palpated where the distal FCL inserts on the fibular head. Posteriorly, a small elevator was used to dissect the soleus muscle off of the posteromedial aspect of the fibular head, where the fibular tunnel would later be created.
A Chandler retractor was placed posterior to the fibular head to protect the neurovascular bundle. With the aid of a collateral ligament aiming device, a guide pin was drilled from the lateral aspect of the fibular head (FCL attachment) to the posteromedial downslope of the fibular styloid (popliteofibular ligament attachment). The entry point of the guide pin was immediately above the champagne- glass drop-off, at the distal insertion site of the FCL, which was described as being 28.4 mm from the styloid tip and 8.2 mm posterior to the anterior margin of the fibular head.3 Care should be taken not to ream the tunnel too proximal, as doing so increases the risk of iatrogenic fracture. A 7-mm reamer was then used to drill the fibular tunnel. To facilitate later passage of the graft, a passing suture was placed through the tunnel, leaving the loop anterolateral.
Next, the starting point for the tibial tunnel was located on the flat spot of the anterolateral tibia distal and medial to the Gerdy tubercle, just lateral to the tibial tubercle. The tibial popliteal sulcus was identified by palpation of the posterolateral tibial plateau to localize the site of the popliteus musculotendinous junction, which is the ideal location of the posterior aperture of the tibial tunnel. This point is 1 cm proximal and 1 cm medial to the posteromedial exit of the fibular tunnel. A Chandler retractor was placed anterior to the lateral gastrocnemius to protect the neurovascular bundle. In the locations described earlier, a cruciate aiming device was used to place a guide pin anterior to posterior. A 9-mm tunnel was overreamed and a passing suture placed, leaving the loop posterior to facilitate graft passage.
The femoral insertions of the FCL and the PLT were then identified. ITB splitting was not necessary, given the complete midsubstance tear of this structure. The FCL attachment was identified 1.4 mm proximal and 3.1 mm posterior to the lateral epicondyle.3 Sharp dissection was performed in this location, proximal to distal, exposing the lateral epicondyle and the small sulcus at the FCL attachment site. A collateral ligament reconstruction aiming sleeve was used to drill a guide pin over the FCL femoral attachment site and out the medial aspect of the distal thigh, about 5 cm proximal and anterior to the adductor tubercle.
The femoral attachment of the PLT was reported located 18.5 mm anterior to the FCL insertion, in the anterior fifth of the popliteal sulcus.3 Although arthrotomy is usually required in order to access the PLT attachment, it was not necessary in this case, given the lateral capsule tear. A guide pin was inserted at the PLT attachment site, parallel to the FCL pin. After proper placement was verified, a 9-mm reamer was used to drill the FCL and PLT tunnels to a depth of 25 mm (socket), and a passing suture was placed into each tunnel to facilitate graft passage.
5. ACL Graft Harvest. The central third of the ipsilateral patellar tendon was harvested for use in the ACL reconstruction. Included were a 10-mm × 20-mm bone plug from the patella and a 10-mm × 25-mm bone plug from the tibial tubercle. The patella defect was then bone-grafted, and the patellar tendon closed side-to-side.
6. Graft Preparation. For the PLC, we used a split Achilles tendon allograft that had two 9-mm × 25-mm bone plugs proximally and were tubularized distally. For the PCL, we used an anterolateral bundle (ALB), which consisted of an Achilles tendon allograft that had an 11-mm × 25-mm bone plug proximally and was tubularized distally, and a posteromedial bundle (PMB), which consisted of a tibialis anterior allograft that was tubularized at both ends. For the ACL, we used a bone–patellar tendon–bone autograft 10 mm in diameter with a 20-mm femoral bone plug and a 25-mm tibial bone plug distally.
7. Arthroscopy. We created standard anterolateral and anteromedial parapatellar portals and performed arthroscopy, including lysis of adhesions. Cartilage and menisci were lesion-free.
8. PCL Femoral Tunnels. The ALB attachment was identified and outlined with a coagulator between the trochlear point and the medial arch point, adjacent to the edge of the articular cartilage. Similarly, the PMB attachment was marked about 8 mm or 9 mm posterior to the edge of the articular cartilage of the medial femoral condyle and slightly posterior to the ALB tunnel.4
In the anterolateral tunnel, an acorn reamer 11 mm in diameter was used to score the entry point of the ALB femoral tunnel. An eyelet pin was then drilled through the reamer anteromedially out the knee. Then a closed socket tunnel was reamed over the eyelet pin to a depth of 25 mm. A passing suture was pulled through the tunnel in preparation for graft passage.
With use of the same technique, a 7-mm reamer was placed against the outline of the PMB attachment site, and an eyelet pin was drilled through this reamer and out the anteromedial aspect of the knee. Again, a 25-mm deep closed socket was reamed. A bone bridge distance of 2 mm was maintained between the 2 femoral PCL bundle tunnels.
9. ACL Femoral Tunnel. The femoral ACL attachment was identified and outlined. An over-the-top guide was used to determine proper placement of the 10-mm low-profile reamer. A guide pin was drilled through the center of the reamer. The reamer was used to create a 25-mm deep closed socket tunnel, and a passing stitch was placed.
10. PCL Tibial Tunnel. With use of a 70° arthroscope for visualization, a posteromedial arthroscopic portal was created, and a shaver and a coagulator were used to identify the tibial PCL attachment, located distally along the PCL facet, until the proximal aspect of the popliteus muscle fibers were visualized. A guide pin was drilled starting at the anteromedial aspect of the tibia, about 6 cm distal to the joint line and centered between the anterior tibial crest and the medial tibial border. The pin exited posteriorly at the center of the PCL tibial attachment along the PCL bundle ridge, which was reported located between the ALB and the PMB on the tibia.5 Pin placement was verified with intraoperative lateral and anteroposterior radiographs. On the lateral radiograph, the pin should be about 6 mm or 7 mm proximal to the champagne-glass drop-off at the PCL facet on the posterior aspect of the tibia. On the anteroposterior radiograph, the pin should be 1 mm to 2 mm distal to the joint line and at the medial aspect of the lateral tibial eminence. A large curette was passed through the posteromedial arthroscopic portal both to retract the posterior tissues away from the reamer and to protect against guide-pin protrusion The guide pin was then overreamed with a 12-mm acorn reamer.
A large smoother was passed proximally up the tibial tunnel and then pulled out the anteromedial portal with a grasper. The smoother was gently cycled to smooth the intra-articular tibial tunnel aperture to remove any bony spicules that could interfere with graft passage. The smoother was then pulled back into the joint, passed out the anterolateral arthroscopic portal, and secured with a small clamp.4
11. ACL Tibial Tunnel. The ACL tibial attachment site was identified and cleaned of soft tissue. A guide pin was placed and then overreamed with a 10-mm acorn reamer.
12. PCL Femoral Fixation. The PMB graft was passed into its tunnel and secured with a 7-mm × 23-mm titanium screw. Next, the ALB was secured to the femur with a 7-mm × 20-mm titanium screw. The smoother was used to pull both grafts down through the tibial tunnel.
13. ACL Femoral Fixation. A 7-mm × 20-mm titanium screw was then used to fix the ACL autograft inside the femur. Traction was applied to the 3 cruciate grafts. There was no sign of impingement.
14. PLC Femoral Fixation. The FCL and the popliteus bone plugs were passed into their respective femoral sockets and secured with 7-mm × 20-mm titanium screws.
15. Lateral Capsule Femoral Anchors. Two suture anchors were placed into the femur, and the sutures were passed through the femoral portion of the lateral capsule for later repair.
16. PCL Tibial Fixation. Both grafts were fixed with a fully threaded bicortical 6.5-mm × 40-mm cannulated cancellous screw and an 18-mm spiked washer. The ALB was fixed first, with the knee flexed to 90°, traction on the graft, and the tibia in neutral rotation. Restoration of the normal tibiofemoral step-off was verified. The PMB was then fixed with the knee in full extension. A posterior drawer test was performed to verify restoration of stability.
17. PLC Fibula Fixation. The PLT graft was passed down the popliteal hiatus, and the FCL graft was passed under the remnant of the biceps bursa on the fibular head and then through the fibular head, anterolateral to posteromedial. The FCL graft was fixed in the fibular tunnel with the knee in 20° of flexion, a slight valgus reduction force, the tibia in neutral rotation, and traction on the graft. A 7-mm × 23-mm bioabsorbable screw was used.
18. Lateral Capsular Repair. The lateral capsule was directly repaired with the previously placed sutures. The sutures were tied with the knee in 20° of flexion.
19. PLC Tibial Fixation. The grafts were passed together, posterior to anterior, through the tibial tunnel. The knee was cycled several times through complete flexion/extension ROM. A 9-mm × 23-mm bioabsorbable screw was then used to fix the grafts to the tibia. During this fixation, the knee was kept in 60° of flexion and neutral rotation while traction was being applied to the distal end of both grafts.
20. ACL Tibial Fixation. A 9-mm × 20-mm titanium screw was used to fix the ACL graft with the knee in full extension. The graft was then viewed intra-articularly to confirm there was no impingement. The Lachman, posterior drawer, posterolateral drawer, dial, and varus stress tests were performed to ensure restoration of stability.
21. ITB Repair. A portion of the remaining Achilles tendon allograft was used to perform ITB reconstruction (reconstitution of the gaped portion of the ITB). Orthocord (DePuy Synthes) and Vicryl (Ethicon) sutures were used for this reconstruction. Knee stability was deemed restored, and the incisions were closed in standard layered fashion.
First Surgery: Postoperative Management
The patient remained non-weight-bearing the first 6 weeks after surgery, with prone knee flexion limited (0°-90°) the first 2 weeks. In addition, a PCL Jack brace (Albrecht) was placed 1 week after surgery and was to be worn at all times to decrease stress on the PCL grafts.
As ROM was not progressing as expected, the patient was instructed to use a continuous passive motion (CPM) machine 2 hours 3 times a day. About 4 weeks after surgery, with ROM still not progressing, the frequency of use of this machine was increased.
Despite continued physical therapy, use of the CPM machine, and pain management, ROM was limited (11°-90° of flexion) 5.5 months after left knee multiligament reconstruction. However, stress radiographs showed excellent stability. Varus stress radiographs showed a side-to-side difference of 0.3 mm less on the left (injured) knee, and kneeling PCL stress radiographs showed a side-to-side difference of 1.3 mm more on the left knee (Figures 3A-3D).
Second Surgery and Postoperative Management
As gentle manipulation under anesthesia was unsuccessful, the patient underwent knee arthroscopy, including 4-compartment lysis of adhesions, arthroscopically assisted posteromedial capsular release, and post-débridement manipulation under anesthesia. During manipulation, full extension and knee flexion up to 135° were achieved. ACL, PCL, and popliteus grafts were visualized and confirmed to be intact.
After this second surgery, the patient was to resume physical therapy and begin weight- bearing as tolerated. Active ROM was prioritized in an attempt to reach full ROM. In addition, a CPM machine was to be used from 0° to 135° of knee flexion 4 hours 3 times a day for 6 weeks.
Two weeks after surgery, the patient had continued pain, and extracapsular swelling in the left knee. However, ROM (0°-115° of flexion) was improved relative to before surgery (11°-90° of flexion), though it remained below the range on the contralateral side. Of note, the patient reported having a flexion contracture (~10°) in the immediate postoperative period. He had woken up with it after sleeping with the CPM machine the night before. The contracture delayed his physical therapy for several hours and resulted in a redesign of his therapy protocol to emphasize full, active knee extension and patellar mobilization, as well as discontinuation of use of the CPM machine. Corticosteroids were initiated to help with the extracapsular swelling, and the new therapy regimen brought adequate progress in ROM. Four months after the second surgery, the patient had full extension and 135° of flexion and was transitioned into wearing the PCL Rebound brace.
Discussion
This case was unique because of the midsubstance ITB tear and simultaneous multiligament injury caused by a KD-IIIL, a KD involving the ACL, the PCL, and the PLC with the medial side intact. There is limited research on ITB repair generally, with or without KD involvement. In a retrospective review of acute knee trauma cases, ITB pathologies were seen on 45% of reviewed MRI scans, and only 3% of the injuries were grade III; in addition, only 9 (5%) of the 200 cases involved both ITB and multiligament (ACL, PCL) knee injuries.6
After our patient’s ACL, PCL, and PLC were reconstructed, a fan piece of the Achilles tendon allograft from the PLC reconstruction was used to repair the ITB. The graft was used to reconstitute the torn gapped portion of the band in multiple locations, and this repair helped restore stability. The literature has reported numerous surgical uses for a portion of the ITB but few studies on repairing this anatomical structure. Preservation of the ITB is important to restoration of native anatomy and function. The ITB helps with anterolateral stabilization of the knee and with resistance of varus stress and internal tibial rotation.
The PLC reconstruction used in this case has been biomechanically validated as restoring the knee to near native stability through anatomical reconstruction of the PLC’s 3 main static stabilizers: the FCL, the PLT, and the popliteofibular ligament.7-9 First described in 2004,7 this anatomical PLC reconstruction technique has improved subjective and objective patient outcomes.10,11 For combined PLC injuries (eg, our patient’s injuries), Geeslin and LaPrade10 recommended concurrent reconstruction of the cruciate ligaments. In addition to the PLC reconstruction, the anatomical double-bundle PCL reconstruction used in this case has demonstrated significant improvements in subjective and objective outcome scores and objective knee stability.12
Although the stability and anatomy of this patient’s injured knee were reestablished, his development of arthrofibrosis is important. Many have discussed the commonality of arthrofibrosis or decreased ROM after extensive multiligament reconstruction surgeries.13,14 One study involving surgical management and outcomes of multiligament knee injuries found that, in more than half of its cases, restoration of full ROM required at least one operation after the initial one.13 Therefore, it is not unusual that our patient required a second operation for decreased ROM.
Conclusion
After surgery, excellent stabilization was achieved. Although the patient had setbacks related to pain and decreased ROM, his second surgery and continued physical therapy likely will help him return to his preoperative recreational activity levels.
1. Delos D, Warren RF, Marx RG. Multiligament knee injuries and their treatment. Oper Tech Sports Med. 2010;18(4):219-226.
2. Hobby B, Treme G, Wascher DC, Schenck RC. How I manage knee dislocations. Oper Tech Sports Med. 2010;18(4):227-234.
3. LaPrade RF, Ly TV, Wentorf FA, Engebretsen L. The posterolateral attachments of the knee: a qualitative and quantitative morphologic analysis of the fibular collateral ligament, popliteus tendon, popliteofibular ligament, and lateral gastrocnemius tendon. Am J Sports Med. 2003;31(6):854-860.
4. Chahla J, Nitri M, Civitarese D, Dean CS, Moulton SG, LaPrade RF. Anatomic double-bundle posterior cruciate ligament reconstruction. Arthrosc Tech. 2016;5(1):e149-e156.
5. Anderson CJ, Ziegler CG, Wijdicks CA, Engebretsen L, LaPrade RF. Arthroscopically pertinent anatomy of the anterolateral and posteromedial bundles of the posterior cruciate ligament. J Bone Joint Surg Am. 2012;94(21):1936-1945.
6. Mansour R, Yoong P, McKean D, Teh JL. The iliotibial band in acute knee trauma: patterns of injury on MR imaging. Skeletal Radiol. 2014;43(10):1369-1375.
7. LaPrade RF, Johansen S, Wentorf FA, Engebretsen L, Esterberg JL, Tso A. An analysis of an anatomical posterolateral knee reconstruction: an in vitro biomechanical study and development of a surgical technique. Am J Sports Med. 2004;32(6):1405-1414.
8. McCarthy M, Camarda L, Wijdicks CA, Johansen S, Engebretsen L, LaPrade RF. Anatomic posterolateral knee reconstructions require a popliteofibular ligament reconstruction through a tibial tunnel. Am J Sports Med. 2010;38(8):1674-1681.
9. LaPrade RF, Wozniczka JK, Stellmaker MP, Wijdicks CA. Analysis of the static function of the popliteus tendon and evaluation of an anatomic reconstruction: the “fifth ligament” of the knee. Am J Sports Med. 2010;38(3):543-549.
10. Geeslin AG, LaPrade RF. Outcomes of treatment of acute grade-III isolated and combined posterolateral knee injuries: a prospective case series and surgical technique. J Bone Joint Surg Am. 2011;93(18):1672-1683.
11. LaPrade RF, Johansen S, Agel J, Risberg MA, Moksnes H, Engebretsen L. Outcomes of an anatomic posterolateral knee reconstruction. J Bone Joint Surg Am. 2010;92(1):16-22.
12. Spiridonov SI, Slinkard NJ, LaPrade RF. Isolated and combined grade-III posterior cruciate ligament tears treated with double-bundle reconstruction with use of endoscopically placed femoral tunnels and grafts: operative technique and clinical outcomes. J Bone Joint Surg Am. 2011;93(19):1773-1780.
13. Noyes FR, Barber-Westin SD. Reconstruction of the anterior and posterior cruciate ligaments after knee dislocation. Use of early protected postoperative motion to decrease arthrofibrosis. Am J Sports Med. 1997;25(6):769-778.
14. Yenchak AJ, Wilk KE, Arrigo CA, Simpson CD, Andrews JR. Criteria-based management of an acute multistructure knee injury in a professional football player: a case report. J Orthop Sports Phys Ther. 2011;41(9):675-686.
1. Delos D, Warren RF, Marx RG. Multiligament knee injuries and their treatment. Oper Tech Sports Med. 2010;18(4):219-226.
2. Hobby B, Treme G, Wascher DC, Schenck RC. How I manage knee dislocations. Oper Tech Sports Med. 2010;18(4):227-234.
3. LaPrade RF, Ly TV, Wentorf FA, Engebretsen L. The posterolateral attachments of the knee: a qualitative and quantitative morphologic analysis of the fibular collateral ligament, popliteus tendon, popliteofibular ligament, and lateral gastrocnemius tendon. Am J Sports Med. 2003;31(6):854-860.
4. Chahla J, Nitri M, Civitarese D, Dean CS, Moulton SG, LaPrade RF. Anatomic double-bundle posterior cruciate ligament reconstruction. Arthrosc Tech. 2016;5(1):e149-e156.
5. Anderson CJ, Ziegler CG, Wijdicks CA, Engebretsen L, LaPrade RF. Arthroscopically pertinent anatomy of the anterolateral and posteromedial bundles of the posterior cruciate ligament. J Bone Joint Surg Am. 2012;94(21):1936-1945.
6. Mansour R, Yoong P, McKean D, Teh JL. The iliotibial band in acute knee trauma: patterns of injury on MR imaging. Skeletal Radiol. 2014;43(10):1369-1375.
7. LaPrade RF, Johansen S, Wentorf FA, Engebretsen L, Esterberg JL, Tso A. An analysis of an anatomical posterolateral knee reconstruction: an in vitro biomechanical study and development of a surgical technique. Am J Sports Med. 2004;32(6):1405-1414.
8. McCarthy M, Camarda L, Wijdicks CA, Johansen S, Engebretsen L, LaPrade RF. Anatomic posterolateral knee reconstructions require a popliteofibular ligament reconstruction through a tibial tunnel. Am J Sports Med. 2010;38(8):1674-1681.
9. LaPrade RF, Wozniczka JK, Stellmaker MP, Wijdicks CA. Analysis of the static function of the popliteus tendon and evaluation of an anatomic reconstruction: the “fifth ligament” of the knee. Am J Sports Med. 2010;38(3):543-549.
10. Geeslin AG, LaPrade RF. Outcomes of treatment of acute grade-III isolated and combined posterolateral knee injuries: a prospective case series and surgical technique. J Bone Joint Surg Am. 2011;93(18):1672-1683.
11. LaPrade RF, Johansen S, Agel J, Risberg MA, Moksnes H, Engebretsen L. Outcomes of an anatomic posterolateral knee reconstruction. J Bone Joint Surg Am. 2010;92(1):16-22.
12. Spiridonov SI, Slinkard NJ, LaPrade RF. Isolated and combined grade-III posterior cruciate ligament tears treated with double-bundle reconstruction with use of endoscopically placed femoral tunnels and grafts: operative technique and clinical outcomes. J Bone Joint Surg Am. 2011;93(19):1773-1780.
13. Noyes FR, Barber-Westin SD. Reconstruction of the anterior and posterior cruciate ligaments after knee dislocation. Use of early protected postoperative motion to decrease arthrofibrosis. Am J Sports Med. 1997;25(6):769-778.
14. Yenchak AJ, Wilk KE, Arrigo CA, Simpson CD, Andrews JR. Criteria-based management of an acute multistructure knee injury in a professional football player: a case report. J Orthop Sports Phys Ther. 2011;41(9):675-686.
Acute monocular vision loss: Don’t lose sight of the differential
An 83-year-old man presented to the emergency department with acute, painless loss of vision in his left eye. His vision in that eye had been normal in the middle of the night when he woke to use the restroom, but on awakening 6 hours later he could perceive only light or darkness.
He denied headache, scalp tenderness, jaw claudication, fever, weight loss, myalgia, or other neurologic symptoms. He had not experienced any recent change in his vision before this presentation, including halos around lights, floaters, eye pain, or redness. However, 6 months ago he had undergone left cataract surgery (left phacoemulsification with intraocular implant) without complications. And he said that when he was 3 years old, he had sustained a serious injury to his right eye.
His medical history included ischemic heart disease and hypertension. His medications included losartan, furosemide, amlodipine, atorvastatin, and aspirin.
CAUSES OF ACUTE MONOCULAR VISION LOSS
1. Which of the following is the least likely cause of this patient’s acute monocular vision loss?
- Optic neuritis
- Retinal vein occlusion
- Retinal artery occlusion
- Pituitary apoplexy
- Retinal detachment
Acute vision loss is often so distressing to the patient that the emergency department may be the first step in evaluation. While its diagnosis and management often require an interdisciplinary effort, early evaluation and triage of this potential medical emergency is often done by clinicians without specialized training in ophthalmology.
The physiology of vision is complex and the list of possible causes of vision loss is long, but the differential diagnosis can be narrowed quickly by considering the time course of vision loss and the anatomic localization.1
The time course (including onset and tempo) of vision loss can classified as:
- Transient (ie, vision returned to normal by the time seen by clinician)
- Acute (instantaneous onset, ie, within seconds to minutes)
- Subacute (progression over days to weeks)
- Chronic (insidious progression over months to years).
Although acute vision loss is usually dramatic, insidious vision loss may occasionally be unnoticed for a surprisingly long time until the normal eye is inadvertently shielded.
Anatomic localization. Lesions anterior to the optic chiasm cause monocular vision loss, whereas lesions at or posterior to the chiasm lead to bilateral visual field defects. Problems leading to monocular blindness can be broadly divided into 3 anatomic categories (Figure 1):
- Ocular medial (including the cornea, anterior chamber, and lens)
- Retinal
- Neurologic (including the optic nerve and chiasm).
Clues from the history
A careful ophthalmic history is an essential initial step in the evaluation (Table 1). In addition, nonvisual symptoms can help narrow the differential diagnosis.
Nausea and vomiting often accompany acute elevation of intraocular pressure.
Focal neurologic deficits or other neurologic symptoms can point to a demyelinating disease such as multiple sclerosis.
Risk factors for vascular atherosclerotic disease such as diabetes, hypertension, and coronary artery disease raise concern for retinal, optic nerve, or cerebral ischemia.
Medications with anticholinergic and adrenergic properties can also precipitate monocular vision loss with acute angle-closure glaucoma.
Can we rule out anything yet?
Our patient presented with painless monocular vision loss. As discussed, causes of monocular vision loss can be localized to ocular abnormalities and prechiasmatic neurologic ones. Retinal detachment, occlusion of a retinal artery or vein, and optic neuritis are all important potential causes of acute monocular vision loss.
Pituitary apoplexy, on the other hand, is characterized by an acute increase in pituitary volume, often leading to compression of the optic chiasm resulting in a visual-field defect. It is most often characterized by binocular deficits (eg, bitemporal hemianopia) but is less likely to cause monocular vision loss.1
CASE CONTINUED: EXAMINATION
On examination, the patient appeared comfortable. His temperature was 97.6°F (36.4°C), pulse 59 beats per minute, respiratory rate 18 per minute, and blood pressure 153/56 mm Hg.
Heart and lung examinations were notable for a grade 3 of 6 midsystolic, low-pitched murmur in the aortic area radiating to the neck, bilateral carotid bruits, and clear lungs. The cardiac impulse was normal in location and character. There was no evidence of aortic insufficiency (including auscultation during exhalation phase while sitting upright).
Eye examination. Visual acuity in the right eye was 20/200 with correction (owing to his eye injury at age 3). With the left eye, he could see only light or darkness. The conjunctiva and sclera were normal.
The right pupil was irregular and measured 3 mm (baseline from his previous eye injury). The left pupil was 3.5 mm. The direct pupillary response was preserved, but a relative afferent pupillary defect was present: on the swinging flashlight test, the left pupil dilated when the flashlight was passed from the right to the left pupil. Extraocular movements were full and intact bilaterally. The rest of the neurologic examination was normal.
An ophthalmologist was urgently consulted. A dilated funduscopic examination of the left eye revealed peripapillary atrophy, tortuous vessels, a cherry red macular spot, and flame hemorrhages, but no disc edema or pallor (Figure 2).
FURTHER WORKUP
2. Which of the following investigations would be least useful and not indicated at this point for this patient?
- Carotid ultrasonography
- Electrocardiography and echocardiography
- Magnetic resonance angiography of the brain
- Computed tomographic (CT) angiography of the head and neck
- Testing for the factor V Leiden and prothrombin gene mutations
A systematic ocular physical examination can offer important diagnostic information (Table 2). Ophthalmoscopy directly examines the optic disc, macula, and retinal vasculature. To interpret the funduscopic examination, we need a basic understanding of the vascular supply to the eye (Figure 3).
For example, the cherry red spot within the macula in our patient is characteristic of central retinal artery occlusion and highlights the relationship between anatomy and pathophysiology. The retina’s blood supply is compromised, leading to an ischemic, white background (secondary to edema of the inner third of the retina), but the macula continues to be nourished by the posterior ciliary arteries. This contrast in color is accentuated by the underlying structures composing the fovea, which lacks the nerve fiber layer and ganglion cell layer, making the vascular bed more visible.2,3
Also in our patient, the marked reduction in visual acuity and relative afferent pupillary defect in the left eye point to unilateral optic nerve (or retinal ganglion cell) dysfunction. The findings on direct funduscopy were consistent with acute central retinal artery ischemia or occlusion. Central retinal artery occlusion can be either arteritic (due to inflammation, most often giant cell arteritis) or nonarteritic (due to atherosclerotic vascular disease).
Thus, carotid ultrasonography, electrocardiography, and transthoracic and transesophageal echocardiography are important components of the further workup. In addition, urgent brain imaging including either CT angiography or magnetic resonance angiography of the head and neck is indicated in all patients with central retinal artery occlusion.
Thrombophilia testing, including tests for the factor V Leiden and prothrombin gene mutations, is indicated in specific cases when a hypercoagulable state is suggested by components of the history, physical examination, and laboratory and radiologic testing. Thrombophilia testing would be low-yield and should not be part of the first-line testing in elderly patients with several atherosclerotic risk factors, such as our patient.
CASE CONTINUED: LABORATORY AND IMAGING EVIDENCE
Initial laboratory work showed:
- Mild microcytic anemia
- Erythrocyte sedimentation rate 77 mm/hour (reference range 1–10)
- C-reactive protein 4.0 mg/dL (reference range < 0.9).
The rest of the complete blood cell count and metabolic profile were unremarkable. His hemoglobin A1c value was 5.3% (reference range 4.8%–6.2%).
A neurologist was urgently consulted.
Magnetic resonance imaging of the brain without contrast revealed nonspecific white-matter disease with no evidence of ischemic stroke.
Magnetic resonance angiography of the head and neck with contrast demonstrated 20% to 40% stenosis in both carotid arteries with otherwise patent anterior and posterior circulation.
Continuous monitoring of the left carotid artery with transcranial Doppler ultrasonography was also ordered, and the study concluded there were no undetected microembolic events.
Transthoracic echocardiography showed aortic sclerosis with no other abnormalities.
Ophthalmic fluorescein angiography was performed and showed patchy choroidal hypoperfusion, severe delayed filling, and extensive pruning of the arterial circulation with no involvement of the posterior ciliary arteries.
Given the elevated inflammatory markers, pulse-dose intravenous methylprednisolone was started, and a temporal artery biopsy was planned.
CENTRAL RETINAL ARTERY OCCLUSION: NONARTERITIC VS ARTERITIC CAUSES
3. Which of the following is least useful to differentiate arteritic from nonarteritic causes of central retinal artery occlusion?
- Finding emboli in the retinal vasculature on funduscopy
- Temporal artery biopsy
- Measuring the C-reactive protein level and the erythrocyte sedimentation rate
- Echocardiography
- Positron-emission tomography (PET)
- Retinal fluorescein angiography
In patients diagnosed with central retinal artery occlusion, the next step is to differentiate between nonarteritic and arteritic causes, since separating them has therapeutic relevance.
The carotid artery is the main culprit for embolic disease affecting the central retinal artery, leading to the nonarteritic subtype. Thus, evaluation of acute retinal ischemia secondary to nonarteritic central retinal artery occlusion is similar to the evaluation of patients with an acute cerebral stroke.4 Studies have shown that 25% of patients diagnosed with central retinal artery occlusion have an additional ischemic insult in the cerebrovascular system, and these patients are at high risk of recurrent ocular or cerebral infarction. Workup includes diffusion-weighted MRI, angiography, echocardiography, and telemetry.5
Arteritic central retinal artery occlusion is most often caused by giant cell arteritis. The American College of Rheumatology classification criteria for giant cell arteritis include 3 of the following 5:
- Age 50 or older
- New onset of localized headache
- Temporal artery tenderness or decreased temporal artery pulse
- Erythrocyte sedimentation rate 50 mm/hour or greater
- Positive biopsy findings.6
Temporal artery biopsy is the gold standard for the diagnosis of giant cell arteritis and should be done whenever the disease is suspected.7,8 However, the test is invasive and imperfect, as a negative result does not completely rule out giant cell arteritis.9
Although a unilateral temporal artery biopsy can be falsely negative, several studies evaluating the efficacy of bilateral biopsies did not show significant improvement in the diagnostic yield.10,11
Ophthalmic fluorescein angiography is another helpful test for distinguishing nonarteritic from arteritic central retinal artery occlusion.12 Involvement of the posterior ciliary arteries usually occurs in giant cell arteritis, and this leads to choroidal malperfusion with or without retinal involvement. The optic nerve may also be infarcted by closure of the paraoptic vessels fed by the posterior ciliary vessels.12,13 Such involvement of multiple vessels would not be typical with nonarteritic central retinal artery occlusion. Thus, this finding is helpful in making the final diagnosis along with supplying possible prognostic information.13
PET-CT is emerging as a test for early inflammation in extracranial disease, but its utility for diagnosing intracranial disease is limited by high uptake of the tracer fluorodeoxyglucose by the brain and low resolution.14 Currently, it has no established role in the evaluation of patients with central retinal artery occlusion and would have no utility in differentiating arteritic vs nonarteritic causes of central retinal artery occlusion.
If giant cell arteritis is suspected, it is essential to start intravenous pulse-dose methylprednisolone early to prevent further vision loss in the contralateral eye. Treatment should not be delayed for invasive testing or temporal artery biopsy. Improvement in headache, jaw claudication, or scalp tenderness once steroids are initiated also helps support the diagnosis of giant cell arteritis.7
Unfortunately, visual symptoms may be irreversible despite treatment.
Our patient’s central retinal artery occlusion
This case highlights how difficult it is in practice to distinguish nonarteritic from arteritic central retinal artery occlusion.
Our patient had numerous cardiovascular risk factors, including known carotid and coronary artery disease, favoring a nonarteritic diagnosis.
On the other hand, his elevated inflammatory markers suggested an underlying inflammatory response. He lacked the characteristic headache and other systemic signs of giant cell arteritis, but this has been described in about 25% of patients.15 If emboli are seen on funduscopy, further workup for arteritic central retinal artery occlusion is not warranted, but emboli are not always present. Then again, absence of posterior ciliary artery involvement on fluorescein angiography pointed away from giant cell arteritis.
CASE CONTINUED: FINAL DIAGNOSIS
Biopsy of the left temporal artery showed intimal thickening with focal destruction of the internal elastic lamina by dystrophic calcification with no evidence of inflammatory infiltrates, giant cells, or granulomata in the adventitia, media, or intima. Based on the results of biopsy study and fluorescein angiography, we concluded that this was nonarteritic central retinal artery occlusion related to atherosclerotic disease.
Methylprednisolone was discontinued. The patient was discharged on aspirin, losartan, furosemide, amlodipine, and high-dose atorvastatin for standard stroke prevention. He was followed by the medical team and the ophthalmology department. At 6 weeks, there was only marginal improvement in the visual acuity of the left eye.
MANAGEMENT
4. Management of nonarteritic central retinal artery occlusion could include all of the following except which one?
- Ocular massage
- Intravenous thrombolysis
- Intra-arterial thrombolysis
- Risk-factor modification
- Intraocular steroid injection
In patients with acute vision loss from nonarteritic central retinal artery occlusion, acute strategies to restore retinal perfusion include noninvasive “standard” therapies and thrombolysis (intravenous or intra-arterial). Unfortunately, consensus and guidelines are lacking.
Traditional therapies include sublingual isosorbide dinitrate, systemic pentoxifylline, inhalation of a carbogen, hyperbaric oxygen, ocular massage, intravenous acetazolamide and mannitol, anterior chamber paracentesis, and systemic steroids. However, none of these have been shown to be more effective than placebo.16
Thrombolytic therapy, analogous to the treatment of patients with ischemic stroke or myocardial infarction, is more controversial in acute central retinal artery occlusion.13 Data from small case-series suggested that intra-arterial or intravenous thrombolysis might improve visual acuity with reasonable safety.17 On the other hand, a randomized study from the United Kingdom that compared intra-arterial thrombolysis within a 24-hour window and conservative measures concluded that thrombolysis should not be used.18
Thrombolysis is thus used only in selected patients on a case-specific basis with involvement of a multispecialty team including stroke neurologists, especially if patients present within hours of onset and have concomitant neurologic symptoms.
Treatment beyond the acute phase focuses on preventing complications of the eye ischemia and aggressively managing systemic atherosclerotic risk factors to decrease the incidence of further ischemic events. Other interventions include endarterectomy for significant carotid stenosis and anticoagulation to prevent cardioembolic embolization (such as atrial fibrillation). Most experts agree on the addition of an antiplatelet agent.13,19
Intraocular steroid injection can be used in the management of some retinal disorders but has no value in nonarteritic central retinal artery occlusion.
Vision recovery in nonarteritic central retinal artery occlusion is variable, but the prognosis is generally poor. The visual acuity on presentation, the onset of the symptoms, and collateral vessels are major factors influencing long-term recovery. Most of the recovery occurs within 7 days and involves peripheral vision rather than central vision. Several studies report some recovery in peripheral vision in approximately 30% to 35% of affected eyes.20–22
PROMPT ACTION MAY SAVE SIGHT
Vision loss is a common presenting symptom in the emergency setting. A meticulous history and systematic physical examination can narrow the differential diagnosis of this neuro-ophthalmologic emergency. Acute retinal ischemia from central retinal artery occlusion is the ocular equivalent of an ischemic stroke, and they share risk factors, diagnostic workup, and management approaches.
Both etiologic subtypes (ie, arteritic and nonarteritic) require prompt intervention by front-line physicians. If giant cell arteritis is suspected, corticosteroid therapy must be initiated to save the contralateral retina from ischemia. Suspicion of central retinal artery occlusion warrants immediate evaluation by a neurologist to consider thrombolysis. Prompt action and interdisciplinary care involving an ophthalmologist, neurologist, and emergency or internal medicine physician may save a patient from permanent visual disability.
KEY POINTS
- Monocular vision loss requires urgent evaluation with a multidisciplinary management approach.
- There are no consensus treatment guidelines for nonarteritic central retinal artery occlusion, but the workup includes a comprehensive stroke evaluation.
- Arteritic central retinal artery occlusion is most often due to giant cell arteritis, and when it is suspected, the patient should be empirically treated with steroids.
- Glezer A, Bronstein MD. Pituitary apoplexy: pathophysiology, diagnosis and management. Arch Endocrinol Metab 2015; 59:259–264.
- Campbell WW. DeJong’s The Neurologic Examination. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2013.
- Biller J. Practical Neurology. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2012.
- Hayreh SS, Podhajsky PA, Zimmerman MB. Retinal artery occlusion: associated systemic and ophthalmic abnormalities. Ophthalmology 2009; 116:1928–1936.
- Biousse V. Acute retinal arterial ischemia: an emergency often ignored. Am J Ophthalmol 2014; 157:1119–1121.
- Hunder GG, Bloch DA, Michel BA, et al. American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum 1990; 33:1122–1128.
- Smith JH, Swanson JW. Giant cell arteritis. Headache 2014; 54:1273–1289.
- Hall S, Persellin S, Lie JT, O’Brien PC, Kurland LT, Hunder GG. The therapeutic impact of temporal artery biopsy. Lancet 1983; 2:1217–1220.
- Gabriel SE, O’Fallon WM, Achkar AA, Lie JT, Hunder GG. The use of clinical characteristics to predict the results of temporal artery biopsy among patients with suspected giant cell arteritis. J Rheumatol 1995; 22:93–96.
- Boyev LR, Miller NR, Green WR. Efficacy of unilateral versus bilateral temporal artery biopsies for the diagnosis of giant cell arteritis. Am J Ophthalmol 1999; 128:211–215.
- Danesh-Meyer HV, Savino PJ, Eagle RC Jr, Kubis KC, Sergott RC. Low diagnostic yield with second biopsies in suspected giant cell arteritis. J Neuroophthalmol 2000; 20:213–215.
- Cavallerano AA. Ophthalmic fluorescein angiography. Optom Clin 1996; 5:1–23.
- Hayreh SS. Acute retinal arterial occlusive disorders. Prog Retin Eye Res 2011; 30:359–394.
- Khan A, Dasgupta B. Imaging in giant cell arteritis. Curr Rheumatol Rep 2015; 17:52.
- Biousse V, Newman N. Retinal and optic nerve ischemia. Continuum (Minneap Minn) 2014; 20:838–856.
- Fraser SG, Adams W. Interventions for acute non-arteritic central retinal artery occlusion. Cochrane Database Syst Rev 2009; 1:CD001989.
- Beatty S, Au Eong KG. Local intra-arterial fibrinolysis for acute occlusion of the central retinal artery: a meta-analysis of the published data. Br J Ophthalmol 2000; 84:914–916.
- Schumacher M, Schmidt D, Jurklies B, et al; EAGLE-Study Group. Central retinal artery occlusion: local intra-arterial fibrinolysis versus conservative treatment, a multicenter randomized trial. Ophthalmology 2010; 117:1367–1375.e1.
- Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324:71–86.
- Hayreh SS, Zimmerman MB. Central retinal artery occlusion: visual outcome. Am J Ophthalmol 2005; 140:376–391.
- Augsburger JJ, Magargal LE. Visual prognosis following treatment of acute central retinal artery obstruction. Br J Ophthalmol 1980; 64:913–917.
- Brown GC, Shields JA. Cilioretinal arteries and retinal arterial occlusion. Arch Ophthalmol 1979; 97:84–92.
An 83-year-old man presented to the emergency department with acute, painless loss of vision in his left eye. His vision in that eye had been normal in the middle of the night when he woke to use the restroom, but on awakening 6 hours later he could perceive only light or darkness.
He denied headache, scalp tenderness, jaw claudication, fever, weight loss, myalgia, or other neurologic symptoms. He had not experienced any recent change in his vision before this presentation, including halos around lights, floaters, eye pain, or redness. However, 6 months ago he had undergone left cataract surgery (left phacoemulsification with intraocular implant) without complications. And he said that when he was 3 years old, he had sustained a serious injury to his right eye.
His medical history included ischemic heart disease and hypertension. His medications included losartan, furosemide, amlodipine, atorvastatin, and aspirin.
CAUSES OF ACUTE MONOCULAR VISION LOSS
1. Which of the following is the least likely cause of this patient’s acute monocular vision loss?
- Optic neuritis
- Retinal vein occlusion
- Retinal artery occlusion
- Pituitary apoplexy
- Retinal detachment
Acute vision loss is often so distressing to the patient that the emergency department may be the first step in evaluation. While its diagnosis and management often require an interdisciplinary effort, early evaluation and triage of this potential medical emergency is often done by clinicians without specialized training in ophthalmology.
The physiology of vision is complex and the list of possible causes of vision loss is long, but the differential diagnosis can be narrowed quickly by considering the time course of vision loss and the anatomic localization.1
The time course (including onset and tempo) of vision loss can classified as:
- Transient (ie, vision returned to normal by the time seen by clinician)
- Acute (instantaneous onset, ie, within seconds to minutes)
- Subacute (progression over days to weeks)
- Chronic (insidious progression over months to years).
Although acute vision loss is usually dramatic, insidious vision loss may occasionally be unnoticed for a surprisingly long time until the normal eye is inadvertently shielded.
Anatomic localization. Lesions anterior to the optic chiasm cause monocular vision loss, whereas lesions at or posterior to the chiasm lead to bilateral visual field defects. Problems leading to monocular blindness can be broadly divided into 3 anatomic categories (Figure 1):
- Ocular medial (including the cornea, anterior chamber, and lens)
- Retinal
- Neurologic (including the optic nerve and chiasm).
Clues from the history
A careful ophthalmic history is an essential initial step in the evaluation (Table 1). In addition, nonvisual symptoms can help narrow the differential diagnosis.
Nausea and vomiting often accompany acute elevation of intraocular pressure.
Focal neurologic deficits or other neurologic symptoms can point to a demyelinating disease such as multiple sclerosis.
Risk factors for vascular atherosclerotic disease such as diabetes, hypertension, and coronary artery disease raise concern for retinal, optic nerve, or cerebral ischemia.
Medications with anticholinergic and adrenergic properties can also precipitate monocular vision loss with acute angle-closure glaucoma.
Can we rule out anything yet?
Our patient presented with painless monocular vision loss. As discussed, causes of monocular vision loss can be localized to ocular abnormalities and prechiasmatic neurologic ones. Retinal detachment, occlusion of a retinal artery or vein, and optic neuritis are all important potential causes of acute monocular vision loss.
Pituitary apoplexy, on the other hand, is characterized by an acute increase in pituitary volume, often leading to compression of the optic chiasm resulting in a visual-field defect. It is most often characterized by binocular deficits (eg, bitemporal hemianopia) but is less likely to cause monocular vision loss.1
CASE CONTINUED: EXAMINATION
On examination, the patient appeared comfortable. His temperature was 97.6°F (36.4°C), pulse 59 beats per minute, respiratory rate 18 per minute, and blood pressure 153/56 mm Hg.
Heart and lung examinations were notable for a grade 3 of 6 midsystolic, low-pitched murmur in the aortic area radiating to the neck, bilateral carotid bruits, and clear lungs. The cardiac impulse was normal in location and character. There was no evidence of aortic insufficiency (including auscultation during exhalation phase while sitting upright).
Eye examination. Visual acuity in the right eye was 20/200 with correction (owing to his eye injury at age 3). With the left eye, he could see only light or darkness. The conjunctiva and sclera were normal.
The right pupil was irregular and measured 3 mm (baseline from his previous eye injury). The left pupil was 3.5 mm. The direct pupillary response was preserved, but a relative afferent pupillary defect was present: on the swinging flashlight test, the left pupil dilated when the flashlight was passed from the right to the left pupil. Extraocular movements were full and intact bilaterally. The rest of the neurologic examination was normal.
An ophthalmologist was urgently consulted. A dilated funduscopic examination of the left eye revealed peripapillary atrophy, tortuous vessels, a cherry red macular spot, and flame hemorrhages, but no disc edema or pallor (Figure 2).
FURTHER WORKUP
2. Which of the following investigations would be least useful and not indicated at this point for this patient?
- Carotid ultrasonography
- Electrocardiography and echocardiography
- Magnetic resonance angiography of the brain
- Computed tomographic (CT) angiography of the head and neck
- Testing for the factor V Leiden and prothrombin gene mutations
A systematic ocular physical examination can offer important diagnostic information (Table 2). Ophthalmoscopy directly examines the optic disc, macula, and retinal vasculature. To interpret the funduscopic examination, we need a basic understanding of the vascular supply to the eye (Figure 3).
For example, the cherry red spot within the macula in our patient is characteristic of central retinal artery occlusion and highlights the relationship between anatomy and pathophysiology. The retina’s blood supply is compromised, leading to an ischemic, white background (secondary to edema of the inner third of the retina), but the macula continues to be nourished by the posterior ciliary arteries. This contrast in color is accentuated by the underlying structures composing the fovea, which lacks the nerve fiber layer and ganglion cell layer, making the vascular bed more visible.2,3
Also in our patient, the marked reduction in visual acuity and relative afferent pupillary defect in the left eye point to unilateral optic nerve (or retinal ganglion cell) dysfunction. The findings on direct funduscopy were consistent with acute central retinal artery ischemia or occlusion. Central retinal artery occlusion can be either arteritic (due to inflammation, most often giant cell arteritis) or nonarteritic (due to atherosclerotic vascular disease).
Thus, carotid ultrasonography, electrocardiography, and transthoracic and transesophageal echocardiography are important components of the further workup. In addition, urgent brain imaging including either CT angiography or magnetic resonance angiography of the head and neck is indicated in all patients with central retinal artery occlusion.
Thrombophilia testing, including tests for the factor V Leiden and prothrombin gene mutations, is indicated in specific cases when a hypercoagulable state is suggested by components of the history, physical examination, and laboratory and radiologic testing. Thrombophilia testing would be low-yield and should not be part of the first-line testing in elderly patients with several atherosclerotic risk factors, such as our patient.
CASE CONTINUED: LABORATORY AND IMAGING EVIDENCE
Initial laboratory work showed:
- Mild microcytic anemia
- Erythrocyte sedimentation rate 77 mm/hour (reference range 1–10)
- C-reactive protein 4.0 mg/dL (reference range < 0.9).
The rest of the complete blood cell count and metabolic profile were unremarkable. His hemoglobin A1c value was 5.3% (reference range 4.8%–6.2%).
A neurologist was urgently consulted.
Magnetic resonance imaging of the brain without contrast revealed nonspecific white-matter disease with no evidence of ischemic stroke.
Magnetic resonance angiography of the head and neck with contrast demonstrated 20% to 40% stenosis in both carotid arteries with otherwise patent anterior and posterior circulation.
Continuous monitoring of the left carotid artery with transcranial Doppler ultrasonography was also ordered, and the study concluded there were no undetected microembolic events.
Transthoracic echocardiography showed aortic sclerosis with no other abnormalities.
Ophthalmic fluorescein angiography was performed and showed patchy choroidal hypoperfusion, severe delayed filling, and extensive pruning of the arterial circulation with no involvement of the posterior ciliary arteries.
Given the elevated inflammatory markers, pulse-dose intravenous methylprednisolone was started, and a temporal artery biopsy was planned.
CENTRAL RETINAL ARTERY OCCLUSION: NONARTERITIC VS ARTERITIC CAUSES
3. Which of the following is least useful to differentiate arteritic from nonarteritic causes of central retinal artery occlusion?
- Finding emboli in the retinal vasculature on funduscopy
- Temporal artery biopsy
- Measuring the C-reactive protein level and the erythrocyte sedimentation rate
- Echocardiography
- Positron-emission tomography (PET)
- Retinal fluorescein angiography
In patients diagnosed with central retinal artery occlusion, the next step is to differentiate between nonarteritic and arteritic causes, since separating them has therapeutic relevance.
The carotid artery is the main culprit for embolic disease affecting the central retinal artery, leading to the nonarteritic subtype. Thus, evaluation of acute retinal ischemia secondary to nonarteritic central retinal artery occlusion is similar to the evaluation of patients with an acute cerebral stroke.4 Studies have shown that 25% of patients diagnosed with central retinal artery occlusion have an additional ischemic insult in the cerebrovascular system, and these patients are at high risk of recurrent ocular or cerebral infarction. Workup includes diffusion-weighted MRI, angiography, echocardiography, and telemetry.5
Arteritic central retinal artery occlusion is most often caused by giant cell arteritis. The American College of Rheumatology classification criteria for giant cell arteritis include 3 of the following 5:
- Age 50 or older
- New onset of localized headache
- Temporal artery tenderness or decreased temporal artery pulse
- Erythrocyte sedimentation rate 50 mm/hour or greater
- Positive biopsy findings.6
Temporal artery biopsy is the gold standard for the diagnosis of giant cell arteritis and should be done whenever the disease is suspected.7,8 However, the test is invasive and imperfect, as a negative result does not completely rule out giant cell arteritis.9
Although a unilateral temporal artery biopsy can be falsely negative, several studies evaluating the efficacy of bilateral biopsies did not show significant improvement in the diagnostic yield.10,11
Ophthalmic fluorescein angiography is another helpful test for distinguishing nonarteritic from arteritic central retinal artery occlusion.12 Involvement of the posterior ciliary arteries usually occurs in giant cell arteritis, and this leads to choroidal malperfusion with or without retinal involvement. The optic nerve may also be infarcted by closure of the paraoptic vessels fed by the posterior ciliary vessels.12,13 Such involvement of multiple vessels would not be typical with nonarteritic central retinal artery occlusion. Thus, this finding is helpful in making the final diagnosis along with supplying possible prognostic information.13
PET-CT is emerging as a test for early inflammation in extracranial disease, but its utility for diagnosing intracranial disease is limited by high uptake of the tracer fluorodeoxyglucose by the brain and low resolution.14 Currently, it has no established role in the evaluation of patients with central retinal artery occlusion and would have no utility in differentiating arteritic vs nonarteritic causes of central retinal artery occlusion.
If giant cell arteritis is suspected, it is essential to start intravenous pulse-dose methylprednisolone early to prevent further vision loss in the contralateral eye. Treatment should not be delayed for invasive testing or temporal artery biopsy. Improvement in headache, jaw claudication, or scalp tenderness once steroids are initiated also helps support the diagnosis of giant cell arteritis.7
Unfortunately, visual symptoms may be irreversible despite treatment.
Our patient’s central retinal artery occlusion
This case highlights how difficult it is in practice to distinguish nonarteritic from arteritic central retinal artery occlusion.
Our patient had numerous cardiovascular risk factors, including known carotid and coronary artery disease, favoring a nonarteritic diagnosis.
On the other hand, his elevated inflammatory markers suggested an underlying inflammatory response. He lacked the characteristic headache and other systemic signs of giant cell arteritis, but this has been described in about 25% of patients.15 If emboli are seen on funduscopy, further workup for arteritic central retinal artery occlusion is not warranted, but emboli are not always present. Then again, absence of posterior ciliary artery involvement on fluorescein angiography pointed away from giant cell arteritis.
CASE CONTINUED: FINAL DIAGNOSIS
Biopsy of the left temporal artery showed intimal thickening with focal destruction of the internal elastic lamina by dystrophic calcification with no evidence of inflammatory infiltrates, giant cells, or granulomata in the adventitia, media, or intima. Based on the results of biopsy study and fluorescein angiography, we concluded that this was nonarteritic central retinal artery occlusion related to atherosclerotic disease.
Methylprednisolone was discontinued. The patient was discharged on aspirin, losartan, furosemide, amlodipine, and high-dose atorvastatin for standard stroke prevention. He was followed by the medical team and the ophthalmology department. At 6 weeks, there was only marginal improvement in the visual acuity of the left eye.
MANAGEMENT
4. Management of nonarteritic central retinal artery occlusion could include all of the following except which one?
- Ocular massage
- Intravenous thrombolysis
- Intra-arterial thrombolysis
- Risk-factor modification
- Intraocular steroid injection
In patients with acute vision loss from nonarteritic central retinal artery occlusion, acute strategies to restore retinal perfusion include noninvasive “standard” therapies and thrombolysis (intravenous or intra-arterial). Unfortunately, consensus and guidelines are lacking.
Traditional therapies include sublingual isosorbide dinitrate, systemic pentoxifylline, inhalation of a carbogen, hyperbaric oxygen, ocular massage, intravenous acetazolamide and mannitol, anterior chamber paracentesis, and systemic steroids. However, none of these have been shown to be more effective than placebo.16
Thrombolytic therapy, analogous to the treatment of patients with ischemic stroke or myocardial infarction, is more controversial in acute central retinal artery occlusion.13 Data from small case-series suggested that intra-arterial or intravenous thrombolysis might improve visual acuity with reasonable safety.17 On the other hand, a randomized study from the United Kingdom that compared intra-arterial thrombolysis within a 24-hour window and conservative measures concluded that thrombolysis should not be used.18
Thrombolysis is thus used only in selected patients on a case-specific basis with involvement of a multispecialty team including stroke neurologists, especially if patients present within hours of onset and have concomitant neurologic symptoms.
Treatment beyond the acute phase focuses on preventing complications of the eye ischemia and aggressively managing systemic atherosclerotic risk factors to decrease the incidence of further ischemic events. Other interventions include endarterectomy for significant carotid stenosis and anticoagulation to prevent cardioembolic embolization (such as atrial fibrillation). Most experts agree on the addition of an antiplatelet agent.13,19
Intraocular steroid injection can be used in the management of some retinal disorders but has no value in nonarteritic central retinal artery occlusion.
Vision recovery in nonarteritic central retinal artery occlusion is variable, but the prognosis is generally poor. The visual acuity on presentation, the onset of the symptoms, and collateral vessels are major factors influencing long-term recovery. Most of the recovery occurs within 7 days and involves peripheral vision rather than central vision. Several studies report some recovery in peripheral vision in approximately 30% to 35% of affected eyes.20–22
PROMPT ACTION MAY SAVE SIGHT
Vision loss is a common presenting symptom in the emergency setting. A meticulous history and systematic physical examination can narrow the differential diagnosis of this neuro-ophthalmologic emergency. Acute retinal ischemia from central retinal artery occlusion is the ocular equivalent of an ischemic stroke, and they share risk factors, diagnostic workup, and management approaches.
Both etiologic subtypes (ie, arteritic and nonarteritic) require prompt intervention by front-line physicians. If giant cell arteritis is suspected, corticosteroid therapy must be initiated to save the contralateral retina from ischemia. Suspicion of central retinal artery occlusion warrants immediate evaluation by a neurologist to consider thrombolysis. Prompt action and interdisciplinary care involving an ophthalmologist, neurologist, and emergency or internal medicine physician may save a patient from permanent visual disability.
KEY POINTS
- Monocular vision loss requires urgent evaluation with a multidisciplinary management approach.
- There are no consensus treatment guidelines for nonarteritic central retinal artery occlusion, but the workup includes a comprehensive stroke evaluation.
- Arteritic central retinal artery occlusion is most often due to giant cell arteritis, and when it is suspected, the patient should be empirically treated with steroids.
An 83-year-old man presented to the emergency department with acute, painless loss of vision in his left eye. His vision in that eye had been normal in the middle of the night when he woke to use the restroom, but on awakening 6 hours later he could perceive only light or darkness.
He denied headache, scalp tenderness, jaw claudication, fever, weight loss, myalgia, or other neurologic symptoms. He had not experienced any recent change in his vision before this presentation, including halos around lights, floaters, eye pain, or redness. However, 6 months ago he had undergone left cataract surgery (left phacoemulsification with intraocular implant) without complications. And he said that when he was 3 years old, he had sustained a serious injury to his right eye.
His medical history included ischemic heart disease and hypertension. His medications included losartan, furosemide, amlodipine, atorvastatin, and aspirin.
CAUSES OF ACUTE MONOCULAR VISION LOSS
1. Which of the following is the least likely cause of this patient’s acute monocular vision loss?
- Optic neuritis
- Retinal vein occlusion
- Retinal artery occlusion
- Pituitary apoplexy
- Retinal detachment
Acute vision loss is often so distressing to the patient that the emergency department may be the first step in evaluation. While its diagnosis and management often require an interdisciplinary effort, early evaluation and triage of this potential medical emergency is often done by clinicians without specialized training in ophthalmology.
The physiology of vision is complex and the list of possible causes of vision loss is long, but the differential diagnosis can be narrowed quickly by considering the time course of vision loss and the anatomic localization.1
The time course (including onset and tempo) of vision loss can classified as:
- Transient (ie, vision returned to normal by the time seen by clinician)
- Acute (instantaneous onset, ie, within seconds to minutes)
- Subacute (progression over days to weeks)
- Chronic (insidious progression over months to years).
Although acute vision loss is usually dramatic, insidious vision loss may occasionally be unnoticed for a surprisingly long time until the normal eye is inadvertently shielded.
Anatomic localization. Lesions anterior to the optic chiasm cause monocular vision loss, whereas lesions at or posterior to the chiasm lead to bilateral visual field defects. Problems leading to monocular blindness can be broadly divided into 3 anatomic categories (Figure 1):
- Ocular medial (including the cornea, anterior chamber, and lens)
- Retinal
- Neurologic (including the optic nerve and chiasm).
Clues from the history
A careful ophthalmic history is an essential initial step in the evaluation (Table 1). In addition, nonvisual symptoms can help narrow the differential diagnosis.
Nausea and vomiting often accompany acute elevation of intraocular pressure.
Focal neurologic deficits or other neurologic symptoms can point to a demyelinating disease such as multiple sclerosis.
Risk factors for vascular atherosclerotic disease such as diabetes, hypertension, and coronary artery disease raise concern for retinal, optic nerve, or cerebral ischemia.
Medications with anticholinergic and adrenergic properties can also precipitate monocular vision loss with acute angle-closure glaucoma.
Can we rule out anything yet?
Our patient presented with painless monocular vision loss. As discussed, causes of monocular vision loss can be localized to ocular abnormalities and prechiasmatic neurologic ones. Retinal detachment, occlusion of a retinal artery or vein, and optic neuritis are all important potential causes of acute monocular vision loss.
Pituitary apoplexy, on the other hand, is characterized by an acute increase in pituitary volume, often leading to compression of the optic chiasm resulting in a visual-field defect. It is most often characterized by binocular deficits (eg, bitemporal hemianopia) but is less likely to cause monocular vision loss.1
CASE CONTINUED: EXAMINATION
On examination, the patient appeared comfortable. His temperature was 97.6°F (36.4°C), pulse 59 beats per minute, respiratory rate 18 per minute, and blood pressure 153/56 mm Hg.
Heart and lung examinations were notable for a grade 3 of 6 midsystolic, low-pitched murmur in the aortic area radiating to the neck, bilateral carotid bruits, and clear lungs. The cardiac impulse was normal in location and character. There was no evidence of aortic insufficiency (including auscultation during exhalation phase while sitting upright).
Eye examination. Visual acuity in the right eye was 20/200 with correction (owing to his eye injury at age 3). With the left eye, he could see only light or darkness. The conjunctiva and sclera were normal.
The right pupil was irregular and measured 3 mm (baseline from his previous eye injury). The left pupil was 3.5 mm. The direct pupillary response was preserved, but a relative afferent pupillary defect was present: on the swinging flashlight test, the left pupil dilated when the flashlight was passed from the right to the left pupil. Extraocular movements were full and intact bilaterally. The rest of the neurologic examination was normal.
An ophthalmologist was urgently consulted. A dilated funduscopic examination of the left eye revealed peripapillary atrophy, tortuous vessels, a cherry red macular spot, and flame hemorrhages, but no disc edema or pallor (Figure 2).
FURTHER WORKUP
2. Which of the following investigations would be least useful and not indicated at this point for this patient?
- Carotid ultrasonography
- Electrocardiography and echocardiography
- Magnetic resonance angiography of the brain
- Computed tomographic (CT) angiography of the head and neck
- Testing for the factor V Leiden and prothrombin gene mutations
A systematic ocular physical examination can offer important diagnostic information (Table 2). Ophthalmoscopy directly examines the optic disc, macula, and retinal vasculature. To interpret the funduscopic examination, we need a basic understanding of the vascular supply to the eye (Figure 3).
For example, the cherry red spot within the macula in our patient is characteristic of central retinal artery occlusion and highlights the relationship between anatomy and pathophysiology. The retina’s blood supply is compromised, leading to an ischemic, white background (secondary to edema of the inner third of the retina), but the macula continues to be nourished by the posterior ciliary arteries. This contrast in color is accentuated by the underlying structures composing the fovea, which lacks the nerve fiber layer and ganglion cell layer, making the vascular bed more visible.2,3
Also in our patient, the marked reduction in visual acuity and relative afferent pupillary defect in the left eye point to unilateral optic nerve (or retinal ganglion cell) dysfunction. The findings on direct funduscopy were consistent with acute central retinal artery ischemia or occlusion. Central retinal artery occlusion can be either arteritic (due to inflammation, most often giant cell arteritis) or nonarteritic (due to atherosclerotic vascular disease).
Thus, carotid ultrasonography, electrocardiography, and transthoracic and transesophageal echocardiography are important components of the further workup. In addition, urgent brain imaging including either CT angiography or magnetic resonance angiography of the head and neck is indicated in all patients with central retinal artery occlusion.
Thrombophilia testing, including tests for the factor V Leiden and prothrombin gene mutations, is indicated in specific cases when a hypercoagulable state is suggested by components of the history, physical examination, and laboratory and radiologic testing. Thrombophilia testing would be low-yield and should not be part of the first-line testing in elderly patients with several atherosclerotic risk factors, such as our patient.
CASE CONTINUED: LABORATORY AND IMAGING EVIDENCE
Initial laboratory work showed:
- Mild microcytic anemia
- Erythrocyte sedimentation rate 77 mm/hour (reference range 1–10)
- C-reactive protein 4.0 mg/dL (reference range < 0.9).
The rest of the complete blood cell count and metabolic profile were unremarkable. His hemoglobin A1c value was 5.3% (reference range 4.8%–6.2%).
A neurologist was urgently consulted.
Magnetic resonance imaging of the brain without contrast revealed nonspecific white-matter disease with no evidence of ischemic stroke.
Magnetic resonance angiography of the head and neck with contrast demonstrated 20% to 40% stenosis in both carotid arteries with otherwise patent anterior and posterior circulation.
Continuous monitoring of the left carotid artery with transcranial Doppler ultrasonography was also ordered, and the study concluded there were no undetected microembolic events.
Transthoracic echocardiography showed aortic sclerosis with no other abnormalities.
Ophthalmic fluorescein angiography was performed and showed patchy choroidal hypoperfusion, severe delayed filling, and extensive pruning of the arterial circulation with no involvement of the posterior ciliary arteries.
Given the elevated inflammatory markers, pulse-dose intravenous methylprednisolone was started, and a temporal artery biopsy was planned.
CENTRAL RETINAL ARTERY OCCLUSION: NONARTERITIC VS ARTERITIC CAUSES
3. Which of the following is least useful to differentiate arteritic from nonarteritic causes of central retinal artery occlusion?
- Finding emboli in the retinal vasculature on funduscopy
- Temporal artery biopsy
- Measuring the C-reactive protein level and the erythrocyte sedimentation rate
- Echocardiography
- Positron-emission tomography (PET)
- Retinal fluorescein angiography
In patients diagnosed with central retinal artery occlusion, the next step is to differentiate between nonarteritic and arteritic causes, since separating them has therapeutic relevance.
The carotid artery is the main culprit for embolic disease affecting the central retinal artery, leading to the nonarteritic subtype. Thus, evaluation of acute retinal ischemia secondary to nonarteritic central retinal artery occlusion is similar to the evaluation of patients with an acute cerebral stroke.4 Studies have shown that 25% of patients diagnosed with central retinal artery occlusion have an additional ischemic insult in the cerebrovascular system, and these patients are at high risk of recurrent ocular or cerebral infarction. Workup includes diffusion-weighted MRI, angiography, echocardiography, and telemetry.5
Arteritic central retinal artery occlusion is most often caused by giant cell arteritis. The American College of Rheumatology classification criteria for giant cell arteritis include 3 of the following 5:
- Age 50 or older
- New onset of localized headache
- Temporal artery tenderness or decreased temporal artery pulse
- Erythrocyte sedimentation rate 50 mm/hour or greater
- Positive biopsy findings.6
Temporal artery biopsy is the gold standard for the diagnosis of giant cell arteritis and should be done whenever the disease is suspected.7,8 However, the test is invasive and imperfect, as a negative result does not completely rule out giant cell arteritis.9
Although a unilateral temporal artery biopsy can be falsely negative, several studies evaluating the efficacy of bilateral biopsies did not show significant improvement in the diagnostic yield.10,11
Ophthalmic fluorescein angiography is another helpful test for distinguishing nonarteritic from arteritic central retinal artery occlusion.12 Involvement of the posterior ciliary arteries usually occurs in giant cell arteritis, and this leads to choroidal malperfusion with or without retinal involvement. The optic nerve may also be infarcted by closure of the paraoptic vessels fed by the posterior ciliary vessels.12,13 Such involvement of multiple vessels would not be typical with nonarteritic central retinal artery occlusion. Thus, this finding is helpful in making the final diagnosis along with supplying possible prognostic information.13
PET-CT is emerging as a test for early inflammation in extracranial disease, but its utility for diagnosing intracranial disease is limited by high uptake of the tracer fluorodeoxyglucose by the brain and low resolution.14 Currently, it has no established role in the evaluation of patients with central retinal artery occlusion and would have no utility in differentiating arteritic vs nonarteritic causes of central retinal artery occlusion.
If giant cell arteritis is suspected, it is essential to start intravenous pulse-dose methylprednisolone early to prevent further vision loss in the contralateral eye. Treatment should not be delayed for invasive testing or temporal artery biopsy. Improvement in headache, jaw claudication, or scalp tenderness once steroids are initiated also helps support the diagnosis of giant cell arteritis.7
Unfortunately, visual symptoms may be irreversible despite treatment.
Our patient’s central retinal artery occlusion
This case highlights how difficult it is in practice to distinguish nonarteritic from arteritic central retinal artery occlusion.
Our patient had numerous cardiovascular risk factors, including known carotid and coronary artery disease, favoring a nonarteritic diagnosis.
On the other hand, his elevated inflammatory markers suggested an underlying inflammatory response. He lacked the characteristic headache and other systemic signs of giant cell arteritis, but this has been described in about 25% of patients.15 If emboli are seen on funduscopy, further workup for arteritic central retinal artery occlusion is not warranted, but emboli are not always present. Then again, absence of posterior ciliary artery involvement on fluorescein angiography pointed away from giant cell arteritis.
CASE CONTINUED: FINAL DIAGNOSIS
Biopsy of the left temporal artery showed intimal thickening with focal destruction of the internal elastic lamina by dystrophic calcification with no evidence of inflammatory infiltrates, giant cells, or granulomata in the adventitia, media, or intima. Based on the results of biopsy study and fluorescein angiography, we concluded that this was nonarteritic central retinal artery occlusion related to atherosclerotic disease.
Methylprednisolone was discontinued. The patient was discharged on aspirin, losartan, furosemide, amlodipine, and high-dose atorvastatin for standard stroke prevention. He was followed by the medical team and the ophthalmology department. At 6 weeks, there was only marginal improvement in the visual acuity of the left eye.
MANAGEMENT
4. Management of nonarteritic central retinal artery occlusion could include all of the following except which one?
- Ocular massage
- Intravenous thrombolysis
- Intra-arterial thrombolysis
- Risk-factor modification
- Intraocular steroid injection
In patients with acute vision loss from nonarteritic central retinal artery occlusion, acute strategies to restore retinal perfusion include noninvasive “standard” therapies and thrombolysis (intravenous or intra-arterial). Unfortunately, consensus and guidelines are lacking.
Traditional therapies include sublingual isosorbide dinitrate, systemic pentoxifylline, inhalation of a carbogen, hyperbaric oxygen, ocular massage, intravenous acetazolamide and mannitol, anterior chamber paracentesis, and systemic steroids. However, none of these have been shown to be more effective than placebo.16
Thrombolytic therapy, analogous to the treatment of patients with ischemic stroke or myocardial infarction, is more controversial in acute central retinal artery occlusion.13 Data from small case-series suggested that intra-arterial or intravenous thrombolysis might improve visual acuity with reasonable safety.17 On the other hand, a randomized study from the United Kingdom that compared intra-arterial thrombolysis within a 24-hour window and conservative measures concluded that thrombolysis should not be used.18
Thrombolysis is thus used only in selected patients on a case-specific basis with involvement of a multispecialty team including stroke neurologists, especially if patients present within hours of onset and have concomitant neurologic symptoms.
Treatment beyond the acute phase focuses on preventing complications of the eye ischemia and aggressively managing systemic atherosclerotic risk factors to decrease the incidence of further ischemic events. Other interventions include endarterectomy for significant carotid stenosis and anticoagulation to prevent cardioembolic embolization (such as atrial fibrillation). Most experts agree on the addition of an antiplatelet agent.13,19
Intraocular steroid injection can be used in the management of some retinal disorders but has no value in nonarteritic central retinal artery occlusion.
Vision recovery in nonarteritic central retinal artery occlusion is variable, but the prognosis is generally poor. The visual acuity on presentation, the onset of the symptoms, and collateral vessels are major factors influencing long-term recovery. Most of the recovery occurs within 7 days and involves peripheral vision rather than central vision. Several studies report some recovery in peripheral vision in approximately 30% to 35% of affected eyes.20–22
PROMPT ACTION MAY SAVE SIGHT
Vision loss is a common presenting symptom in the emergency setting. A meticulous history and systematic physical examination can narrow the differential diagnosis of this neuro-ophthalmologic emergency. Acute retinal ischemia from central retinal artery occlusion is the ocular equivalent of an ischemic stroke, and they share risk factors, diagnostic workup, and management approaches.
Both etiologic subtypes (ie, arteritic and nonarteritic) require prompt intervention by front-line physicians. If giant cell arteritis is suspected, corticosteroid therapy must be initiated to save the contralateral retina from ischemia. Suspicion of central retinal artery occlusion warrants immediate evaluation by a neurologist to consider thrombolysis. Prompt action and interdisciplinary care involving an ophthalmologist, neurologist, and emergency or internal medicine physician may save a patient from permanent visual disability.
KEY POINTS
- Monocular vision loss requires urgent evaluation with a multidisciplinary management approach.
- There are no consensus treatment guidelines for nonarteritic central retinal artery occlusion, but the workup includes a comprehensive stroke evaluation.
- Arteritic central retinal artery occlusion is most often due to giant cell arteritis, and when it is suspected, the patient should be empirically treated with steroids.
- Glezer A, Bronstein MD. Pituitary apoplexy: pathophysiology, diagnosis and management. Arch Endocrinol Metab 2015; 59:259–264.
- Campbell WW. DeJong’s The Neurologic Examination. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2013.
- Biller J. Practical Neurology. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2012.
- Hayreh SS, Podhajsky PA, Zimmerman MB. Retinal artery occlusion: associated systemic and ophthalmic abnormalities. Ophthalmology 2009; 116:1928–1936.
- Biousse V. Acute retinal arterial ischemia: an emergency often ignored. Am J Ophthalmol 2014; 157:1119–1121.
- Hunder GG, Bloch DA, Michel BA, et al. American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum 1990; 33:1122–1128.
- Smith JH, Swanson JW. Giant cell arteritis. Headache 2014; 54:1273–1289.
- Hall S, Persellin S, Lie JT, O’Brien PC, Kurland LT, Hunder GG. The therapeutic impact of temporal artery biopsy. Lancet 1983; 2:1217–1220.
- Gabriel SE, O’Fallon WM, Achkar AA, Lie JT, Hunder GG. The use of clinical characteristics to predict the results of temporal artery biopsy among patients with suspected giant cell arteritis. J Rheumatol 1995; 22:93–96.
- Boyev LR, Miller NR, Green WR. Efficacy of unilateral versus bilateral temporal artery biopsies for the diagnosis of giant cell arteritis. Am J Ophthalmol 1999; 128:211–215.
- Danesh-Meyer HV, Savino PJ, Eagle RC Jr, Kubis KC, Sergott RC. Low diagnostic yield with second biopsies in suspected giant cell arteritis. J Neuroophthalmol 2000; 20:213–215.
- Cavallerano AA. Ophthalmic fluorescein angiography. Optom Clin 1996; 5:1–23.
- Hayreh SS. Acute retinal arterial occlusive disorders. Prog Retin Eye Res 2011; 30:359–394.
- Khan A, Dasgupta B. Imaging in giant cell arteritis. Curr Rheumatol Rep 2015; 17:52.
- Biousse V, Newman N. Retinal and optic nerve ischemia. Continuum (Minneap Minn) 2014; 20:838–856.
- Fraser SG, Adams W. Interventions for acute non-arteritic central retinal artery occlusion. Cochrane Database Syst Rev 2009; 1:CD001989.
- Beatty S, Au Eong KG. Local intra-arterial fibrinolysis for acute occlusion of the central retinal artery: a meta-analysis of the published data. Br J Ophthalmol 2000; 84:914–916.
- Schumacher M, Schmidt D, Jurklies B, et al; EAGLE-Study Group. Central retinal artery occlusion: local intra-arterial fibrinolysis versus conservative treatment, a multicenter randomized trial. Ophthalmology 2010; 117:1367–1375.e1.
- Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324:71–86.
- Hayreh SS, Zimmerman MB. Central retinal artery occlusion: visual outcome. Am J Ophthalmol 2005; 140:376–391.
- Augsburger JJ, Magargal LE. Visual prognosis following treatment of acute central retinal artery obstruction. Br J Ophthalmol 1980; 64:913–917.
- Brown GC, Shields JA. Cilioretinal arteries and retinal arterial occlusion. Arch Ophthalmol 1979; 97:84–92.
- Glezer A, Bronstein MD. Pituitary apoplexy: pathophysiology, diagnosis and management. Arch Endocrinol Metab 2015; 59:259–264.
- Campbell WW. DeJong’s The Neurologic Examination. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2013.
- Biller J. Practical Neurology. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2012.
- Hayreh SS, Podhajsky PA, Zimmerman MB. Retinal artery occlusion: associated systemic and ophthalmic abnormalities. Ophthalmology 2009; 116:1928–1936.
- Biousse V. Acute retinal arterial ischemia: an emergency often ignored. Am J Ophthalmol 2014; 157:1119–1121.
- Hunder GG, Bloch DA, Michel BA, et al. American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum 1990; 33:1122–1128.
- Smith JH, Swanson JW. Giant cell arteritis. Headache 2014; 54:1273–1289.
- Hall S, Persellin S, Lie JT, O’Brien PC, Kurland LT, Hunder GG. The therapeutic impact of temporal artery biopsy. Lancet 1983; 2:1217–1220.
- Gabriel SE, O’Fallon WM, Achkar AA, Lie JT, Hunder GG. The use of clinical characteristics to predict the results of temporal artery biopsy among patients with suspected giant cell arteritis. J Rheumatol 1995; 22:93–96.
- Boyev LR, Miller NR, Green WR. Efficacy of unilateral versus bilateral temporal artery biopsies for the diagnosis of giant cell arteritis. Am J Ophthalmol 1999; 128:211–215.
- Danesh-Meyer HV, Savino PJ, Eagle RC Jr, Kubis KC, Sergott RC. Low diagnostic yield with second biopsies in suspected giant cell arteritis. J Neuroophthalmol 2000; 20:213–215.
- Cavallerano AA. Ophthalmic fluorescein angiography. Optom Clin 1996; 5:1–23.
- Hayreh SS. Acute retinal arterial occlusive disorders. Prog Retin Eye Res 2011; 30:359–394.
- Khan A, Dasgupta B. Imaging in giant cell arteritis. Curr Rheumatol Rep 2015; 17:52.
- Biousse V, Newman N. Retinal and optic nerve ischemia. Continuum (Minneap Minn) 2014; 20:838–856.
- Fraser SG, Adams W. Interventions for acute non-arteritic central retinal artery occlusion. Cochrane Database Syst Rev 2009; 1:CD001989.
- Beatty S, Au Eong KG. Local intra-arterial fibrinolysis for acute occlusion of the central retinal artery: a meta-analysis of the published data. Br J Ophthalmol 2000; 84:914–916.
- Schumacher M, Schmidt D, Jurklies B, et al; EAGLE-Study Group. Central retinal artery occlusion: local intra-arterial fibrinolysis versus conservative treatment, a multicenter randomized trial. Ophthalmology 2010; 117:1367–1375.e1.
- Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324:71–86.
- Hayreh SS, Zimmerman MB. Central retinal artery occlusion: visual outcome. Am J Ophthalmol 2005; 140:376–391.
- Augsburger JJ, Magargal LE. Visual prognosis following treatment of acute central retinal artery obstruction. Br J Ophthalmol 1980; 64:913–917.
- Brown GC, Shields JA. Cilioretinal arteries and retinal arterial occlusion. Arch Ophthalmol 1979; 97:84–92.
Approaching intraoperative bowel injury
Enterotomy can be a serious complication in abdominopelvic surgery, particularly if it is not immediately recognized and treated. Risk of visceral injury increases when complex dissection is required for treatment of cancer, resection of endometriosis, and extensive lysis of adhesions.
In a retrospective review from 1984 to 2003, investigators assessed intestinal injuries at the time of gynecologic operations. Of the 110 cases reported, about 37% occurred during the opening of the peritoneal cavity, 38% during adhesiolysis and pelvic dissection, 9% during laparoscopy, 9% during vaginal surgery, and 8% during dilation and curettage. Of the bowel injuries, more than 75% were minor.1 Mortality from unrecognized bowel injury is significant, and as such, appropriate recognition and management of these injuries is critical.2
Some basic principles are critical when surgeons face a bowel injury:
1. Recognize the extent of the injury, including the size of the breach, the depth (full or partial thickness), and the nature of the injury (thermal or cold).
2. Assess the integrity of the bowel, including adequacy of blood supply, prior bowel damage from radiation, and absence of downstream obstruction.
3. Ensure no other occult injuries exist in other segments.
4. Obtain adequate exposure and mobilization of the bowel beyond the site of injury, including the adjacent bowel. This involves releasing other adhesions so that adequate bowel length is available for a tension-free repair.
Methods of repair
The decision to employ each is influenced by multiple factors. Primary closure is best suited to small lesions (1 cm or less) that are a result of cold or sharp injury. However, thermal injury sustained via electrosurgical devices induces delayed tissue damage beyond the visible edges of the immediate defect, and surgeons should consider a resection of bowel to at least 1 cm beyond the immediately apparent injury site. Additionally, resection and re-anastamosis should also be considered if the damaged segment of bowel has poor blood supply, integrity, or the repair would result in tension along the suture/staple line or luminal narrowing.
Simple small bowel closures
Serosal abrasions need not be repaired; however, small tears of the serosa and muscularis can be managed with a single layer of interrupted 3-0 absorbable or permanent silk suture on a tapered needle. The suture line should be perpendicular to the longitudinal axis of the bowel at 2-mm to 3-mm intervals in order to prevent narrowing of the lumen. The suture should pass through serosal and muscular layers in an imbricating (Lembert) stitch. For smaller defects of less than 6 mm, a single layer closure is typically adequate.
Small bowel resection
Some larger defects, thermal injuries, and segments with multiple enterotomies may be best repaired with resection and re-anastamosis technique. A segment of resectable bowel is chosen such that the afferent and efferent limbs to be re-anastamosed can be reapproximated in a tension-free fashion. A mesenterotomy is made at the proximal and distal portions of the involved bowel. A gastrointestinal anastomotic stapler is then inserted perpendicularly across the bowel. The remaining wedge of connected mesentery can then be efficiently excised with an electrothermal bipolar coagulator device ensuring that maximal mesentery and blood supply are preserved to the remaining limbs of intestine. The proximal and distal segments are then aligned at the antimesenteric sides.
Large bowel repair
Defects in the serosa and small lacerations can be managed with a primary closure, similar to the small intestine. For more extensive injuries that may require resection, diversion, or complicated repair, consultation with a gynecologic oncologist or general or colorectal surgeon may be indicated as colotomy repairs are associated with higher rates of breakdown and fistula. If fecal contamination is present, copious irrigation should be performed and placement of a peritoneal drain to reduce the likelihood of abscess formation should be considered. If appropriate antibiotic prophylaxis for colonic surgery has not been given prior to skin incision, it should be administered once the colotomy is identified.
Standard prophylaxis for hysterectomy (such as a first-generation cephalosporin like cefazolin) is not adequate for large bowel surgery, and either metronidazole should be added or a second-generation cephalosporin such as cefoxitin should be given. For patients with penicillin allergy, clindamycin or vancomycin with either gentamicin or a fluoroquinolone should be administered.6
Postoperative management
The potential for postoperative morbidity must be understood for appropriate management following bowel surgery. Ileus is common and the clinician should understand how to diagnose and manage it. Additionally, intra-abdominal abscess, anastomotic leak, fistula formation, and mechanical obstruction are complications that may require surgical intervention and must be vigilantly managed.
The routine use of postoperative nasogastric tube (NGT) does not hasten return of bowel function or prevent leak from sites of gastrointestinal repair. In fact, early feeding has been associated with reduced perioperative complications and earlier return of bowel function has been observed without the use of NGT.7 In general, for small and large intestinal injuries, early feeding is considered acceptable.8
Prolonged antibiotic prophylaxis, beyond 24 hours, is not recommended.6
Avoiding injury
Gynecologic surgeons should adhere to surgical principles with sharp dissection for adhesions, gentle tissue handling, adequate exposure, and light retraction to prevent bowel injury or minimize their extent. Laparoscopic entry sites should be chosen based on the likelihood of abdominal adhesions. When the patient’s history predicts a high likelihood of intraperitoneal adhesions, the left upper quadrant site should be strongly considered as the entry site. The likelihood of gastrointestinal injury is not influenced by open versus closed laparoscopic entry and surgeons should use the technique with which they have the greatest experience and skill.9 However, in patients who have had prior laparotomies, there is an increased risk of periumbilical adhesions, and consideration should be made for a nonumbilical entry site.10 Methodical sharp dissection and sparing use of thermal energy should be used with adhesiolysis. When injury occurs, prompt recognition, preparation, and methodical management can mitigate the impact.
Dr. Staley is a gynecologic oncology fellow at the University of North Carolina, Chapel Hill. Dr. Rossi is an assistant professor in the division of gynecologic oncology at the university. They reported having no relevant financial disclosures.
References
1. Int Surg. 2006 Nov-Dec;91(6):336-40.
2. J Am Coll Surg. 2001 Jun;192(6):677-83.
3. Doherty, G. Current Diagnosis and Treatment: Surgery. Thirteenth Edition. New York: McGraw Hill, 2010.
4. Hoffman B. Williams Gynecology. Third Edition. New York: McGraw Hill, 2016.
5. Berek J, Hacker N. Berek & Hacker’s Gynecologic Oncology. Sixth Edition. Philadelphia: Wolters Kluwer, 2015.
6. Surg Infect (Larchmt). 2013 Feb;14(1):73-156.
7. Br J Surg. 2005 Jun;92(6):673-80.
8. Am J Obstet Gynecol. 2001 Jul;185(1):1-4.
9. Cochrane Database Syst Rev. 2015 Aug 31;8:CD006583.
10. Br J Obstet Gynaecol. 1997 May;104(5):595-600.
Enterotomy can be a serious complication in abdominopelvic surgery, particularly if it is not immediately recognized and treated. Risk of visceral injury increases when complex dissection is required for treatment of cancer, resection of endometriosis, and extensive lysis of adhesions.
In a retrospective review from 1984 to 2003, investigators assessed intestinal injuries at the time of gynecologic operations. Of the 110 cases reported, about 37% occurred during the opening of the peritoneal cavity, 38% during adhesiolysis and pelvic dissection, 9% during laparoscopy, 9% during vaginal surgery, and 8% during dilation and curettage. Of the bowel injuries, more than 75% were minor.1 Mortality from unrecognized bowel injury is significant, and as such, appropriate recognition and management of these injuries is critical.2
Some basic principles are critical when surgeons face a bowel injury:
1. Recognize the extent of the injury, including the size of the breach, the depth (full or partial thickness), and the nature of the injury (thermal or cold).
2. Assess the integrity of the bowel, including adequacy of blood supply, prior bowel damage from radiation, and absence of downstream obstruction.
3. Ensure no other occult injuries exist in other segments.
4. Obtain adequate exposure and mobilization of the bowel beyond the site of injury, including the adjacent bowel. This involves releasing other adhesions so that adequate bowel length is available for a tension-free repair.
Methods of repair
The decision to employ each is influenced by multiple factors. Primary closure is best suited to small lesions (1 cm or less) that are a result of cold or sharp injury. However, thermal injury sustained via electrosurgical devices induces delayed tissue damage beyond the visible edges of the immediate defect, and surgeons should consider a resection of bowel to at least 1 cm beyond the immediately apparent injury site. Additionally, resection and re-anastamosis should also be considered if the damaged segment of bowel has poor blood supply, integrity, or the repair would result in tension along the suture/staple line or luminal narrowing.
Simple small bowel closures
Serosal abrasions need not be repaired; however, small tears of the serosa and muscularis can be managed with a single layer of interrupted 3-0 absorbable or permanent silk suture on a tapered needle. The suture line should be perpendicular to the longitudinal axis of the bowel at 2-mm to 3-mm intervals in order to prevent narrowing of the lumen. The suture should pass through serosal and muscular layers in an imbricating (Lembert) stitch. For smaller defects of less than 6 mm, a single layer closure is typically adequate.
Small bowel resection
Some larger defects, thermal injuries, and segments with multiple enterotomies may be best repaired with resection and re-anastamosis technique. A segment of resectable bowel is chosen such that the afferent and efferent limbs to be re-anastamosed can be reapproximated in a tension-free fashion. A mesenterotomy is made at the proximal and distal portions of the involved bowel. A gastrointestinal anastomotic stapler is then inserted perpendicularly across the bowel. The remaining wedge of connected mesentery can then be efficiently excised with an electrothermal bipolar coagulator device ensuring that maximal mesentery and blood supply are preserved to the remaining limbs of intestine. The proximal and distal segments are then aligned at the antimesenteric sides.
Large bowel repair
Defects in the serosa and small lacerations can be managed with a primary closure, similar to the small intestine. For more extensive injuries that may require resection, diversion, or complicated repair, consultation with a gynecologic oncologist or general or colorectal surgeon may be indicated as colotomy repairs are associated with higher rates of breakdown and fistula. If fecal contamination is present, copious irrigation should be performed and placement of a peritoneal drain to reduce the likelihood of abscess formation should be considered. If appropriate antibiotic prophylaxis for colonic surgery has not been given prior to skin incision, it should be administered once the colotomy is identified.
Standard prophylaxis for hysterectomy (such as a first-generation cephalosporin like cefazolin) is not adequate for large bowel surgery, and either metronidazole should be added or a second-generation cephalosporin such as cefoxitin should be given. For patients with penicillin allergy, clindamycin or vancomycin with either gentamicin or a fluoroquinolone should be administered.6
Postoperative management
The potential for postoperative morbidity must be understood for appropriate management following bowel surgery. Ileus is common and the clinician should understand how to diagnose and manage it. Additionally, intra-abdominal abscess, anastomotic leak, fistula formation, and mechanical obstruction are complications that may require surgical intervention and must be vigilantly managed.
The routine use of postoperative nasogastric tube (NGT) does not hasten return of bowel function or prevent leak from sites of gastrointestinal repair. In fact, early feeding has been associated with reduced perioperative complications and earlier return of bowel function has been observed without the use of NGT.7 In general, for small and large intestinal injuries, early feeding is considered acceptable.8
Prolonged antibiotic prophylaxis, beyond 24 hours, is not recommended.6
Avoiding injury
Gynecologic surgeons should adhere to surgical principles with sharp dissection for adhesions, gentle tissue handling, adequate exposure, and light retraction to prevent bowel injury or minimize their extent. Laparoscopic entry sites should be chosen based on the likelihood of abdominal adhesions. When the patient’s history predicts a high likelihood of intraperitoneal adhesions, the left upper quadrant site should be strongly considered as the entry site. The likelihood of gastrointestinal injury is not influenced by open versus closed laparoscopic entry and surgeons should use the technique with which they have the greatest experience and skill.9 However, in patients who have had prior laparotomies, there is an increased risk of periumbilical adhesions, and consideration should be made for a nonumbilical entry site.10 Methodical sharp dissection and sparing use of thermal energy should be used with adhesiolysis. When injury occurs, prompt recognition, preparation, and methodical management can mitigate the impact.
Dr. Staley is a gynecologic oncology fellow at the University of North Carolina, Chapel Hill. Dr. Rossi is an assistant professor in the division of gynecologic oncology at the university. They reported having no relevant financial disclosures.
References
1. Int Surg. 2006 Nov-Dec;91(6):336-40.
2. J Am Coll Surg. 2001 Jun;192(6):677-83.
3. Doherty, G. Current Diagnosis and Treatment: Surgery. Thirteenth Edition. New York: McGraw Hill, 2010.
4. Hoffman B. Williams Gynecology. Third Edition. New York: McGraw Hill, 2016.
5. Berek J, Hacker N. Berek & Hacker’s Gynecologic Oncology. Sixth Edition. Philadelphia: Wolters Kluwer, 2015.
6. Surg Infect (Larchmt). 2013 Feb;14(1):73-156.
7. Br J Surg. 2005 Jun;92(6):673-80.
8. Am J Obstet Gynecol. 2001 Jul;185(1):1-4.
9. Cochrane Database Syst Rev. 2015 Aug 31;8:CD006583.
10. Br J Obstet Gynaecol. 1997 May;104(5):595-600.
Enterotomy can be a serious complication in abdominopelvic surgery, particularly if it is not immediately recognized and treated. Risk of visceral injury increases when complex dissection is required for treatment of cancer, resection of endometriosis, and extensive lysis of adhesions.
In a retrospective review from 1984 to 2003, investigators assessed intestinal injuries at the time of gynecologic operations. Of the 110 cases reported, about 37% occurred during the opening of the peritoneal cavity, 38% during adhesiolysis and pelvic dissection, 9% during laparoscopy, 9% during vaginal surgery, and 8% during dilation and curettage. Of the bowel injuries, more than 75% were minor.1 Mortality from unrecognized bowel injury is significant, and as such, appropriate recognition and management of these injuries is critical.2
Some basic principles are critical when surgeons face a bowel injury:
1. Recognize the extent of the injury, including the size of the breach, the depth (full or partial thickness), and the nature of the injury (thermal or cold).
2. Assess the integrity of the bowel, including adequacy of blood supply, prior bowel damage from radiation, and absence of downstream obstruction.
3. Ensure no other occult injuries exist in other segments.
4. Obtain adequate exposure and mobilization of the bowel beyond the site of injury, including the adjacent bowel. This involves releasing other adhesions so that adequate bowel length is available for a tension-free repair.
Methods of repair
The decision to employ each is influenced by multiple factors. Primary closure is best suited to small lesions (1 cm or less) that are a result of cold or sharp injury. However, thermal injury sustained via electrosurgical devices induces delayed tissue damage beyond the visible edges of the immediate defect, and surgeons should consider a resection of bowel to at least 1 cm beyond the immediately apparent injury site. Additionally, resection and re-anastamosis should also be considered if the damaged segment of bowel has poor blood supply, integrity, or the repair would result in tension along the suture/staple line or luminal narrowing.
Simple small bowel closures
Serosal abrasions need not be repaired; however, small tears of the serosa and muscularis can be managed with a single layer of interrupted 3-0 absorbable or permanent silk suture on a tapered needle. The suture line should be perpendicular to the longitudinal axis of the bowel at 2-mm to 3-mm intervals in order to prevent narrowing of the lumen. The suture should pass through serosal and muscular layers in an imbricating (Lembert) stitch. For smaller defects of less than 6 mm, a single layer closure is typically adequate.
Small bowel resection
Some larger defects, thermal injuries, and segments with multiple enterotomies may be best repaired with resection and re-anastamosis technique. A segment of resectable bowel is chosen such that the afferent and efferent limbs to be re-anastamosed can be reapproximated in a tension-free fashion. A mesenterotomy is made at the proximal and distal portions of the involved bowel. A gastrointestinal anastomotic stapler is then inserted perpendicularly across the bowel. The remaining wedge of connected mesentery can then be efficiently excised with an electrothermal bipolar coagulator device ensuring that maximal mesentery and blood supply are preserved to the remaining limbs of intestine. The proximal and distal segments are then aligned at the antimesenteric sides.
Large bowel repair
Defects in the serosa and small lacerations can be managed with a primary closure, similar to the small intestine. For more extensive injuries that may require resection, diversion, or complicated repair, consultation with a gynecologic oncologist or general or colorectal surgeon may be indicated as colotomy repairs are associated with higher rates of breakdown and fistula. If fecal contamination is present, copious irrigation should be performed and placement of a peritoneal drain to reduce the likelihood of abscess formation should be considered. If appropriate antibiotic prophylaxis for colonic surgery has not been given prior to skin incision, it should be administered once the colotomy is identified.
Standard prophylaxis for hysterectomy (such as a first-generation cephalosporin like cefazolin) is not adequate for large bowel surgery, and either metronidazole should be added or a second-generation cephalosporin such as cefoxitin should be given. For patients with penicillin allergy, clindamycin or vancomycin with either gentamicin or a fluoroquinolone should be administered.6
Postoperative management
The potential for postoperative morbidity must be understood for appropriate management following bowel surgery. Ileus is common and the clinician should understand how to diagnose and manage it. Additionally, intra-abdominal abscess, anastomotic leak, fistula formation, and mechanical obstruction are complications that may require surgical intervention and must be vigilantly managed.
The routine use of postoperative nasogastric tube (NGT) does not hasten return of bowel function or prevent leak from sites of gastrointestinal repair. In fact, early feeding has been associated with reduced perioperative complications and earlier return of bowel function has been observed without the use of NGT.7 In general, for small and large intestinal injuries, early feeding is considered acceptable.8
Prolonged antibiotic prophylaxis, beyond 24 hours, is not recommended.6
Avoiding injury
Gynecologic surgeons should adhere to surgical principles with sharp dissection for adhesions, gentle tissue handling, adequate exposure, and light retraction to prevent bowel injury or minimize their extent. Laparoscopic entry sites should be chosen based on the likelihood of abdominal adhesions. When the patient’s history predicts a high likelihood of intraperitoneal adhesions, the left upper quadrant site should be strongly considered as the entry site. The likelihood of gastrointestinal injury is not influenced by open versus closed laparoscopic entry and surgeons should use the technique with which they have the greatest experience and skill.9 However, in patients who have had prior laparotomies, there is an increased risk of periumbilical adhesions, and consideration should be made for a nonumbilical entry site.10 Methodical sharp dissection and sparing use of thermal energy should be used with adhesiolysis. When injury occurs, prompt recognition, preparation, and methodical management can mitigate the impact.
Dr. Staley is a gynecologic oncology fellow at the University of North Carolina, Chapel Hill. Dr. Rossi is an assistant professor in the division of gynecologic oncology at the university. They reported having no relevant financial disclosures.
References
1. Int Surg. 2006 Nov-Dec;91(6):336-40.
2. J Am Coll Surg. 2001 Jun;192(6):677-83.
3. Doherty, G. Current Diagnosis and Treatment: Surgery. Thirteenth Edition. New York: McGraw Hill, 2010.
4. Hoffman B. Williams Gynecology. Third Edition. New York: McGraw Hill, 2016.
5. Berek J, Hacker N. Berek & Hacker’s Gynecologic Oncology. Sixth Edition. Philadelphia: Wolters Kluwer, 2015.
6. Surg Infect (Larchmt). 2013 Feb;14(1):73-156.
7. Br J Surg. 2005 Jun;92(6):673-80.
8. Am J Obstet Gynecol. 2001 Jul;185(1):1-4.
9. Cochrane Database Syst Rev. 2015 Aug 31;8:CD006583.
10. Br J Obstet Gynaecol. 1997 May;104(5):595-600.