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Is there a (robotic) doctor in the house?
In the 2012 movie “Robot and Frank,” an aging ex-jewel thief named Frank receives a robotic home assistant from his well-meaning son. Frank lives alone and suffers from dementia, and his son hopes that the friendly electronic companion will help keep his father safe, assisting him with housework and improving his cognitive health. Frank initially rejects the idea but changes his mind when he realizes the robot’s talents aren’t limited to domestic chores. He begins teaching the robot new skills, and an unlikely partnership develops. With Frank’s penchant for pilfering and the robot’s digital dexterity, the two of them pull off a multimillion-dollar jewelry heist – and Frank’s outlook improves in ways his son never dreamed possible!
“Robot and Frank” takes place “in the near future,” and while we don’t yet have robotic home companions as capable as the one in the movie, we need not look very far to realize that robotics and artificial intelligence may revolutionize the delivery of health care.
With an aging population and an industry shift toward value-based care, new research has focused on novel ways of avoiding hospitalization and reducing hospital readmission. We have seen a resurgence of home visits and the development of telemedicine and remote monitoring.
To stay healthy, patients need to be safe in their home environment and at a minimum need to be able to navigate their activities of daily living. Research published last year by Washington University’s Center for Advanced Studies in Adaptive Systems (CASAS) describes a technology that aims to help patients in their own homes.
The Robot Activity Support system, or RAS, interacts with intelligent sensors in a home environment “to detect and assist with activity errors that may occur in everyday settings.”1 If sensors in the home indicate that a person is experiencing difficulty completing a certain task such as taking a medication or finding a bathroom, a robot can navigate to the person in need and show an instructional video, or lead the patient to the next step in the process.
Another manufacturer is taking a ‘softer’ approach to activity support in the elderly. Toymaker Hasbro has developed a line of robotic cats that provide companionship and comfort. While currently limited to tactile stimulation and simple responses, the manufacturer is working in collaboration with researchers at Brown University to add artificial intelligence capabilities. The goal of the program – Project ARIES (Affordable Robotic Intelligence for Elderly Support) – is to give the cats useful skills such as being able to provide medication and safety reminders while keeping their price point accessible to all.
Other organizations are attempting to take the robotic home health aide idea to the next level. “RUDY,” a robotic companion developed by INF Robotics, is capable of much more than just educating patients and leading them around the house. About the size of small child and wearing a huge smile, Rudy can detect falls, ensure medication adherence, provide social interaction, and even offer remote patient monitoring. According to the manufacturer, it uses natural language processing, machine learning, and a smart social interface to “facilitate trusting relationships between RUDY and older adults.” The idea is to promote acceptance from patients and offer peace of mind to their loved ones. This can be particularly valuable in assisting those with dementia, as a heavy emphasis is placed on socialization and maintaining cognitive stimulation.
Instead of developing novel artificial intelligence platforms, many groups are attempting to leverage existing technologies to assist patients in their homes. One such technology is Amazon’s Echo smart speakers, which became more attractive to health care providers on April 4 of this year with the launch of the Alexa Healthcare Skills Kit. This is Amazon’s HIPAA-compliant application programming interface (API) that allows developers to create ‘skills’ (apps for Echo devices) that can securely handle protected health information.
At launch, Amazon announced six partner organizations who have already written skills for patients. One organization, Boston Children’s Hospital, developed a skill called My Children’s Enhanced Recovery After Surgery (ERAS). According to John Brownstein, the hospital’s Chief Innovation Officer, it “allows patients and caregivers to easily share recovery progress with their care team post surgery ... it is just one example of how voice technology can extend the care and support of our patients beyond the four walls of the hospital.”
Some companies, such as HealthTap, have been working on artificial intelligence to build a platform to allow physicians and patients to interact online. HealthTap is leveraging the wisdom of those interactions to power a deep learning system called Dr. A.I. Available for Alexa and mobile devices, it attempts to assess patients’ symptoms and provide personalized medical explanations and health recommendations. In the developer’s own words: “Dr. A.I. engages with you in an empathetic conversation about your symptoms and overall health ... then gives you appropriate doctor-recommended insights as well as the best possible courses of action you can take on the road to feeling good.”
Some physicians may find this movement troubling, but we believe it represents an early glimpse of what is to come. with no shortage of companies stepping up to meet the demand. While it’s doubtful the robots they create can be easily reprogrammed to steal jewelry, it won’t stop them from trying to steal our jobs. We as physicians will need to continue to hone our skills in compassion and empathy to provide something a computer never can: true care for our patients.
Dr. Notte is a family physician and associate chief medical information officer for Abington (Pa.) Jefferson Health. Follow him on twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.
Reference
1. Robot-enabled support of daily activities in smart home environments. Cogn Syst Res. 2019 May. doi: 10.1016/j.cogsys.2018.10.032.
In the 2012 movie “Robot and Frank,” an aging ex-jewel thief named Frank receives a robotic home assistant from his well-meaning son. Frank lives alone and suffers from dementia, and his son hopes that the friendly electronic companion will help keep his father safe, assisting him with housework and improving his cognitive health. Frank initially rejects the idea but changes his mind when he realizes the robot’s talents aren’t limited to domestic chores. He begins teaching the robot new skills, and an unlikely partnership develops. With Frank’s penchant for pilfering and the robot’s digital dexterity, the two of them pull off a multimillion-dollar jewelry heist – and Frank’s outlook improves in ways his son never dreamed possible!
“Robot and Frank” takes place “in the near future,” and while we don’t yet have robotic home companions as capable as the one in the movie, we need not look very far to realize that robotics and artificial intelligence may revolutionize the delivery of health care.
With an aging population and an industry shift toward value-based care, new research has focused on novel ways of avoiding hospitalization and reducing hospital readmission. We have seen a resurgence of home visits and the development of telemedicine and remote monitoring.
To stay healthy, patients need to be safe in their home environment and at a minimum need to be able to navigate their activities of daily living. Research published last year by Washington University’s Center for Advanced Studies in Adaptive Systems (CASAS) describes a technology that aims to help patients in their own homes.
The Robot Activity Support system, or RAS, interacts with intelligent sensors in a home environment “to detect and assist with activity errors that may occur in everyday settings.”1 If sensors in the home indicate that a person is experiencing difficulty completing a certain task such as taking a medication or finding a bathroom, a robot can navigate to the person in need and show an instructional video, or lead the patient to the next step in the process.
Another manufacturer is taking a ‘softer’ approach to activity support in the elderly. Toymaker Hasbro has developed a line of robotic cats that provide companionship and comfort. While currently limited to tactile stimulation and simple responses, the manufacturer is working in collaboration with researchers at Brown University to add artificial intelligence capabilities. The goal of the program – Project ARIES (Affordable Robotic Intelligence for Elderly Support) – is to give the cats useful skills such as being able to provide medication and safety reminders while keeping their price point accessible to all.
Other organizations are attempting to take the robotic home health aide idea to the next level. “RUDY,” a robotic companion developed by INF Robotics, is capable of much more than just educating patients and leading them around the house. About the size of small child and wearing a huge smile, Rudy can detect falls, ensure medication adherence, provide social interaction, and even offer remote patient monitoring. According to the manufacturer, it uses natural language processing, machine learning, and a smart social interface to “facilitate trusting relationships between RUDY and older adults.” The idea is to promote acceptance from patients and offer peace of mind to their loved ones. This can be particularly valuable in assisting those with dementia, as a heavy emphasis is placed on socialization and maintaining cognitive stimulation.
Instead of developing novel artificial intelligence platforms, many groups are attempting to leverage existing technologies to assist patients in their homes. One such technology is Amazon’s Echo smart speakers, which became more attractive to health care providers on April 4 of this year with the launch of the Alexa Healthcare Skills Kit. This is Amazon’s HIPAA-compliant application programming interface (API) that allows developers to create ‘skills’ (apps for Echo devices) that can securely handle protected health information.
At launch, Amazon announced six partner organizations who have already written skills for patients. One organization, Boston Children’s Hospital, developed a skill called My Children’s Enhanced Recovery After Surgery (ERAS). According to John Brownstein, the hospital’s Chief Innovation Officer, it “allows patients and caregivers to easily share recovery progress with their care team post surgery ... it is just one example of how voice technology can extend the care and support of our patients beyond the four walls of the hospital.”
Some companies, such as HealthTap, have been working on artificial intelligence to build a platform to allow physicians and patients to interact online. HealthTap is leveraging the wisdom of those interactions to power a deep learning system called Dr. A.I. Available for Alexa and mobile devices, it attempts to assess patients’ symptoms and provide personalized medical explanations and health recommendations. In the developer’s own words: “Dr. A.I. engages with you in an empathetic conversation about your symptoms and overall health ... then gives you appropriate doctor-recommended insights as well as the best possible courses of action you can take on the road to feeling good.”
Some physicians may find this movement troubling, but we believe it represents an early glimpse of what is to come. with no shortage of companies stepping up to meet the demand. While it’s doubtful the robots they create can be easily reprogrammed to steal jewelry, it won’t stop them from trying to steal our jobs. We as physicians will need to continue to hone our skills in compassion and empathy to provide something a computer never can: true care for our patients.
Dr. Notte is a family physician and associate chief medical information officer for Abington (Pa.) Jefferson Health. Follow him on twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.
Reference
1. Robot-enabled support of daily activities in smart home environments. Cogn Syst Res. 2019 May. doi: 10.1016/j.cogsys.2018.10.032.
In the 2012 movie “Robot and Frank,” an aging ex-jewel thief named Frank receives a robotic home assistant from his well-meaning son. Frank lives alone and suffers from dementia, and his son hopes that the friendly electronic companion will help keep his father safe, assisting him with housework and improving his cognitive health. Frank initially rejects the idea but changes his mind when he realizes the robot’s talents aren’t limited to domestic chores. He begins teaching the robot new skills, and an unlikely partnership develops. With Frank’s penchant for pilfering and the robot’s digital dexterity, the two of them pull off a multimillion-dollar jewelry heist – and Frank’s outlook improves in ways his son never dreamed possible!
“Robot and Frank” takes place “in the near future,” and while we don’t yet have robotic home companions as capable as the one in the movie, we need not look very far to realize that robotics and artificial intelligence may revolutionize the delivery of health care.
With an aging population and an industry shift toward value-based care, new research has focused on novel ways of avoiding hospitalization and reducing hospital readmission. We have seen a resurgence of home visits and the development of telemedicine and remote monitoring.
To stay healthy, patients need to be safe in their home environment and at a minimum need to be able to navigate their activities of daily living. Research published last year by Washington University’s Center for Advanced Studies in Adaptive Systems (CASAS) describes a technology that aims to help patients in their own homes.
The Robot Activity Support system, or RAS, interacts with intelligent sensors in a home environment “to detect and assist with activity errors that may occur in everyday settings.”1 If sensors in the home indicate that a person is experiencing difficulty completing a certain task such as taking a medication or finding a bathroom, a robot can navigate to the person in need and show an instructional video, or lead the patient to the next step in the process.
Another manufacturer is taking a ‘softer’ approach to activity support in the elderly. Toymaker Hasbro has developed a line of robotic cats that provide companionship and comfort. While currently limited to tactile stimulation and simple responses, the manufacturer is working in collaboration with researchers at Brown University to add artificial intelligence capabilities. The goal of the program – Project ARIES (Affordable Robotic Intelligence for Elderly Support) – is to give the cats useful skills such as being able to provide medication and safety reminders while keeping their price point accessible to all.
Other organizations are attempting to take the robotic home health aide idea to the next level. “RUDY,” a robotic companion developed by INF Robotics, is capable of much more than just educating patients and leading them around the house. About the size of small child and wearing a huge smile, Rudy can detect falls, ensure medication adherence, provide social interaction, and even offer remote patient monitoring. According to the manufacturer, it uses natural language processing, machine learning, and a smart social interface to “facilitate trusting relationships between RUDY and older adults.” The idea is to promote acceptance from patients and offer peace of mind to their loved ones. This can be particularly valuable in assisting those with dementia, as a heavy emphasis is placed on socialization and maintaining cognitive stimulation.
Instead of developing novel artificial intelligence platforms, many groups are attempting to leverage existing technologies to assist patients in their homes. One such technology is Amazon’s Echo smart speakers, which became more attractive to health care providers on April 4 of this year with the launch of the Alexa Healthcare Skills Kit. This is Amazon’s HIPAA-compliant application programming interface (API) that allows developers to create ‘skills’ (apps for Echo devices) that can securely handle protected health information.
At launch, Amazon announced six partner organizations who have already written skills for patients. One organization, Boston Children’s Hospital, developed a skill called My Children’s Enhanced Recovery After Surgery (ERAS). According to John Brownstein, the hospital’s Chief Innovation Officer, it “allows patients and caregivers to easily share recovery progress with their care team post surgery ... it is just one example of how voice technology can extend the care and support of our patients beyond the four walls of the hospital.”
Some companies, such as HealthTap, have been working on artificial intelligence to build a platform to allow physicians and patients to interact online. HealthTap is leveraging the wisdom of those interactions to power a deep learning system called Dr. A.I. Available for Alexa and mobile devices, it attempts to assess patients’ symptoms and provide personalized medical explanations and health recommendations. In the developer’s own words: “Dr. A.I. engages with you in an empathetic conversation about your symptoms and overall health ... then gives you appropriate doctor-recommended insights as well as the best possible courses of action you can take on the road to feeling good.”
Some physicians may find this movement troubling, but we believe it represents an early glimpse of what is to come. with no shortage of companies stepping up to meet the demand. While it’s doubtful the robots they create can be easily reprogrammed to steal jewelry, it won’t stop them from trying to steal our jobs. We as physicians will need to continue to hone our skills in compassion and empathy to provide something a computer never can: true care for our patients.
Dr. Notte is a family physician and associate chief medical information officer for Abington (Pa.) Jefferson Health. Follow him on twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.
Reference
1. Robot-enabled support of daily activities in smart home environments. Cogn Syst Res. 2019 May. doi: 10.1016/j.cogsys.2018.10.032.
How should we monitor for ovarian cancer recurrence?
Several practice-changing developments in the treatment of ovarian cancer were seen in 2019, including the results of the pivotal trial Gynecologic Oncology Group (GOG)-213, which were published in November in the New England Journal of Medicine.1 This trial randomly assigned women with ovarian cancer who had achieved a remission of more than 6 months after primary therapy (“platinum sensitive”) to either a repeat surgical cytoreduction followed by chemotherapy versus chemotherapy alone. It found that the addition of surgery provided no benefit in overall survival, challenging the notion that repeat surgical “debulking” should be routinely considered for the treatment of women with platinum-sensitive ovarian cancer.
The primary treatment of ovarian cancer includes a combination of surgery and chemotherapy, after which the vast majority of patients will experience a complete clinical response, a so-called “remission.” At that time patients enter surveillance care, in which their providers evaluate them, typically every 3 months in the first 2-3 years. These visits are designed to address ongoing toxicities of therapy in addition to evaluation for recurrence. At these visits, it is common for providers to assess tumor markers, such as CA 125 (cancer antigen 125), if they had been elevated at original diagnosis. As a gynecologic oncologist, I can vouch for the fact that patients “sweat” on this lab result the most. No matter how reassuring my physical exams or their symptom profiles are, there is nothing more comforting as a normal, stable CA 125 value in black and white. However, and may, in fact, be harmful.
Providers have drawn tumor markers at surveillance exams under the working premise that abnormal or rising values signal the onset of asymptomatic recurrence, and that earlier treatment will be associated with better responses to salvage therapy. However, this has not been shown to be the case in randomized, controlled trials. In a large European cooperative-group trial, more than 500 patients with a history of completely treated ovarian cancer were randomized to either reinitiation of chemotherapy (salvage therapy) when CA 125 values first doubled or to reinitiation of therapy when they became symptomatic without knowledge of their CA 125 values.2 In this trial the mean survival of both groups was the same (26 months for the early initiation of chemotherapy vs. 27 for late initiation). However, what did differ were the quality of life scores, which were lower for the group who initiated chemotherapy earlier, likely because they received toxic therapies for longer periods of time.
The results of this trial were challenged by those who felt that this study did not evaluate the role that surgery might play. Their argument was that surgery in the recurrent setting would improve the outcomes from chemotherapy for certain patients with long platinum-free intervals (duration of remission since last receiving a platinum-containing drug), oligometastatic disease, and good performance status, just as it had in the primary setting. Retrospective series seemed to confirm this phenomenon, particularly if surgeons were able to achieve a complete resection (no residual measurable disease).3,4 By detecting asymptomatic patients with early elevations in CA 125, they proposed they might identify patients with lower disease burden in whom complete debulking would be more feasible. Whereas, in waiting for symptoms alone, they might “miss the boat,” and discover recurrence when it was too advanced to be completely resected.
The results of the GOG-213 study significantly challenge this line of thought, although with some caveats. Because this new trial showed no survival benefit for women with secondary debulking prior to chemotherapy, one could question whether there is any benefit in screening for asymptomatic, early recurrence. The authors of the study looked in subgroup analyses to attempt to identify groups who might benefit over others, such as women who had complete surgical cytoreduction (no residual disease) but still did not find a benefit to surgery. The trial population as a whole included women who had very favorable prognostic factors, including very long disease-free intervals (median, 20.4 months), and most women had only one or two sites of measurable recurrence. Yet it is remarkable that, in this group of patients who were predisposed to optimal outcomes, no benefit from surgery was observed.
However, it is important to recognize that the equivalent results of single-modality chemotherapy were achieved with the majority of women receiving bevacizumab with their chemotherapy regimen. An additional consideration is that the chemotherapy for platinum-sensitive, recurrent ovarian cancer has changed in recent years as we have learned the benefit of poly (ADP-ribose) polymerase (PARP) inhibitor drugs as maintenance therapy following complete or partial response to chemotherapy.5 It is unclear how the addition of PARP inhibitor maintenance therapy might have influenced the results of GOG-213. Further advancements in targeted therapies and consideration of hyperthermic intraperitoneal chemotherapy at the time of surgery also are being developed, and so, the answer of optimal therapy for platinum-sensitive ovarian cancer is a fluid one and might include a role for surgery for some of these patients.
However, in the meantime, before routinely ordering that tumor marker assessment in the surveillance period, it is important to remember that, if secondary cytoreduction is not beneficial and early initiation of chemotherapy is not helpful either, then these tumor marker results might provide more hindrance than help. Why search for recurrence at an earlier time point with CA 125 elevations if there isn’t a benefit to the patient in doing so? There certainly appears to be worse quality of life in doing so, and most likely also additional cost. Perhaps we should wait for clinical symptoms to confirm recurrence?
In the meantime, we will continue to have discussions with patients after primary therapy regarding how to best monitor them in the surveillance period. We will educate them about the limitations of early initiation of chemotherapy and the potentially limited role for surgery. Hopefully with individualized care and shared decision making, patients can guide us as to how they best be evaluated. While receiving a normal CA 125 result is powerfully reassuring, it is just as powerfully confusing and difficult for a patient to receive an abnormal one followed by a period of “doing nothing,” otherwise known as expectant management, if immediate treatment is not beneficial.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She had no relevant financial disclosures. Email her at obnews@mdedge.com.
References
1. N Engl J Med. 2019 Nov 14;381(20):1929-39.
2. Lancet. 2010 Oct 2;376(9747):1155-63.
3. Gynecol Oncol. 2009 Jan;112(1):265-74.
4. Br J Cancer. 2011 Sep 27;105(7):890-6.
5. N Engl J Med. 2016 Dec 1;375(22):2154-64.
Several practice-changing developments in the treatment of ovarian cancer were seen in 2019, including the results of the pivotal trial Gynecologic Oncology Group (GOG)-213, which were published in November in the New England Journal of Medicine.1 This trial randomly assigned women with ovarian cancer who had achieved a remission of more than 6 months after primary therapy (“platinum sensitive”) to either a repeat surgical cytoreduction followed by chemotherapy versus chemotherapy alone. It found that the addition of surgery provided no benefit in overall survival, challenging the notion that repeat surgical “debulking” should be routinely considered for the treatment of women with platinum-sensitive ovarian cancer.
The primary treatment of ovarian cancer includes a combination of surgery and chemotherapy, after which the vast majority of patients will experience a complete clinical response, a so-called “remission.” At that time patients enter surveillance care, in which their providers evaluate them, typically every 3 months in the first 2-3 years. These visits are designed to address ongoing toxicities of therapy in addition to evaluation for recurrence. At these visits, it is common for providers to assess tumor markers, such as CA 125 (cancer antigen 125), if they had been elevated at original diagnosis. As a gynecologic oncologist, I can vouch for the fact that patients “sweat” on this lab result the most. No matter how reassuring my physical exams or their symptom profiles are, there is nothing more comforting as a normal, stable CA 125 value in black and white. However, and may, in fact, be harmful.
Providers have drawn tumor markers at surveillance exams under the working premise that abnormal or rising values signal the onset of asymptomatic recurrence, and that earlier treatment will be associated with better responses to salvage therapy. However, this has not been shown to be the case in randomized, controlled trials. In a large European cooperative-group trial, more than 500 patients with a history of completely treated ovarian cancer were randomized to either reinitiation of chemotherapy (salvage therapy) when CA 125 values first doubled or to reinitiation of therapy when they became symptomatic without knowledge of their CA 125 values.2 In this trial the mean survival of both groups was the same (26 months for the early initiation of chemotherapy vs. 27 for late initiation). However, what did differ were the quality of life scores, which were lower for the group who initiated chemotherapy earlier, likely because they received toxic therapies for longer periods of time.
The results of this trial were challenged by those who felt that this study did not evaluate the role that surgery might play. Their argument was that surgery in the recurrent setting would improve the outcomes from chemotherapy for certain patients with long platinum-free intervals (duration of remission since last receiving a platinum-containing drug), oligometastatic disease, and good performance status, just as it had in the primary setting. Retrospective series seemed to confirm this phenomenon, particularly if surgeons were able to achieve a complete resection (no residual measurable disease).3,4 By detecting asymptomatic patients with early elevations in CA 125, they proposed they might identify patients with lower disease burden in whom complete debulking would be more feasible. Whereas, in waiting for symptoms alone, they might “miss the boat,” and discover recurrence when it was too advanced to be completely resected.
The results of the GOG-213 study significantly challenge this line of thought, although with some caveats. Because this new trial showed no survival benefit for women with secondary debulking prior to chemotherapy, one could question whether there is any benefit in screening for asymptomatic, early recurrence. The authors of the study looked in subgroup analyses to attempt to identify groups who might benefit over others, such as women who had complete surgical cytoreduction (no residual disease) but still did not find a benefit to surgery. The trial population as a whole included women who had very favorable prognostic factors, including very long disease-free intervals (median, 20.4 months), and most women had only one or two sites of measurable recurrence. Yet it is remarkable that, in this group of patients who were predisposed to optimal outcomes, no benefit from surgery was observed.
However, it is important to recognize that the equivalent results of single-modality chemotherapy were achieved with the majority of women receiving bevacizumab with their chemotherapy regimen. An additional consideration is that the chemotherapy for platinum-sensitive, recurrent ovarian cancer has changed in recent years as we have learned the benefit of poly (ADP-ribose) polymerase (PARP) inhibitor drugs as maintenance therapy following complete or partial response to chemotherapy.5 It is unclear how the addition of PARP inhibitor maintenance therapy might have influenced the results of GOG-213. Further advancements in targeted therapies and consideration of hyperthermic intraperitoneal chemotherapy at the time of surgery also are being developed, and so, the answer of optimal therapy for platinum-sensitive ovarian cancer is a fluid one and might include a role for surgery for some of these patients.
However, in the meantime, before routinely ordering that tumor marker assessment in the surveillance period, it is important to remember that, if secondary cytoreduction is not beneficial and early initiation of chemotherapy is not helpful either, then these tumor marker results might provide more hindrance than help. Why search for recurrence at an earlier time point with CA 125 elevations if there isn’t a benefit to the patient in doing so? There certainly appears to be worse quality of life in doing so, and most likely also additional cost. Perhaps we should wait for clinical symptoms to confirm recurrence?
In the meantime, we will continue to have discussions with patients after primary therapy regarding how to best monitor them in the surveillance period. We will educate them about the limitations of early initiation of chemotherapy and the potentially limited role for surgery. Hopefully with individualized care and shared decision making, patients can guide us as to how they best be evaluated. While receiving a normal CA 125 result is powerfully reassuring, it is just as powerfully confusing and difficult for a patient to receive an abnormal one followed by a period of “doing nothing,” otherwise known as expectant management, if immediate treatment is not beneficial.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She had no relevant financial disclosures. Email her at obnews@mdedge.com.
References
1. N Engl J Med. 2019 Nov 14;381(20):1929-39.
2. Lancet. 2010 Oct 2;376(9747):1155-63.
3. Gynecol Oncol. 2009 Jan;112(1):265-74.
4. Br J Cancer. 2011 Sep 27;105(7):890-6.
5. N Engl J Med. 2016 Dec 1;375(22):2154-64.
Several practice-changing developments in the treatment of ovarian cancer were seen in 2019, including the results of the pivotal trial Gynecologic Oncology Group (GOG)-213, which were published in November in the New England Journal of Medicine.1 This trial randomly assigned women with ovarian cancer who had achieved a remission of more than 6 months after primary therapy (“platinum sensitive”) to either a repeat surgical cytoreduction followed by chemotherapy versus chemotherapy alone. It found that the addition of surgery provided no benefit in overall survival, challenging the notion that repeat surgical “debulking” should be routinely considered for the treatment of women with platinum-sensitive ovarian cancer.
The primary treatment of ovarian cancer includes a combination of surgery and chemotherapy, after which the vast majority of patients will experience a complete clinical response, a so-called “remission.” At that time patients enter surveillance care, in which their providers evaluate them, typically every 3 months in the first 2-3 years. These visits are designed to address ongoing toxicities of therapy in addition to evaluation for recurrence. At these visits, it is common for providers to assess tumor markers, such as CA 125 (cancer antigen 125), if they had been elevated at original diagnosis. As a gynecologic oncologist, I can vouch for the fact that patients “sweat” on this lab result the most. No matter how reassuring my physical exams or their symptom profiles are, there is nothing more comforting as a normal, stable CA 125 value in black and white. However, and may, in fact, be harmful.
Providers have drawn tumor markers at surveillance exams under the working premise that abnormal or rising values signal the onset of asymptomatic recurrence, and that earlier treatment will be associated with better responses to salvage therapy. However, this has not been shown to be the case in randomized, controlled trials. In a large European cooperative-group trial, more than 500 patients with a history of completely treated ovarian cancer were randomized to either reinitiation of chemotherapy (salvage therapy) when CA 125 values first doubled or to reinitiation of therapy when they became symptomatic without knowledge of their CA 125 values.2 In this trial the mean survival of both groups was the same (26 months for the early initiation of chemotherapy vs. 27 for late initiation). However, what did differ were the quality of life scores, which were lower for the group who initiated chemotherapy earlier, likely because they received toxic therapies for longer periods of time.
The results of this trial were challenged by those who felt that this study did not evaluate the role that surgery might play. Their argument was that surgery in the recurrent setting would improve the outcomes from chemotherapy for certain patients with long platinum-free intervals (duration of remission since last receiving a platinum-containing drug), oligometastatic disease, and good performance status, just as it had in the primary setting. Retrospective series seemed to confirm this phenomenon, particularly if surgeons were able to achieve a complete resection (no residual measurable disease).3,4 By detecting asymptomatic patients with early elevations in CA 125, they proposed they might identify patients with lower disease burden in whom complete debulking would be more feasible. Whereas, in waiting for symptoms alone, they might “miss the boat,” and discover recurrence when it was too advanced to be completely resected.
The results of the GOG-213 study significantly challenge this line of thought, although with some caveats. Because this new trial showed no survival benefit for women with secondary debulking prior to chemotherapy, one could question whether there is any benefit in screening for asymptomatic, early recurrence. The authors of the study looked in subgroup analyses to attempt to identify groups who might benefit over others, such as women who had complete surgical cytoreduction (no residual disease) but still did not find a benefit to surgery. The trial population as a whole included women who had very favorable prognostic factors, including very long disease-free intervals (median, 20.4 months), and most women had only one or two sites of measurable recurrence. Yet it is remarkable that, in this group of patients who were predisposed to optimal outcomes, no benefit from surgery was observed.
However, it is important to recognize that the equivalent results of single-modality chemotherapy were achieved with the majority of women receiving bevacizumab with their chemotherapy regimen. An additional consideration is that the chemotherapy for platinum-sensitive, recurrent ovarian cancer has changed in recent years as we have learned the benefit of poly (ADP-ribose) polymerase (PARP) inhibitor drugs as maintenance therapy following complete or partial response to chemotherapy.5 It is unclear how the addition of PARP inhibitor maintenance therapy might have influenced the results of GOG-213. Further advancements in targeted therapies and consideration of hyperthermic intraperitoneal chemotherapy at the time of surgery also are being developed, and so, the answer of optimal therapy for platinum-sensitive ovarian cancer is a fluid one and might include a role for surgery for some of these patients.
However, in the meantime, before routinely ordering that tumor marker assessment in the surveillance period, it is important to remember that, if secondary cytoreduction is not beneficial and early initiation of chemotherapy is not helpful either, then these tumor marker results might provide more hindrance than help. Why search for recurrence at an earlier time point with CA 125 elevations if there isn’t a benefit to the patient in doing so? There certainly appears to be worse quality of life in doing so, and most likely also additional cost. Perhaps we should wait for clinical symptoms to confirm recurrence?
In the meantime, we will continue to have discussions with patients after primary therapy regarding how to best monitor them in the surveillance period. We will educate them about the limitations of early initiation of chemotherapy and the potentially limited role for surgery. Hopefully with individualized care and shared decision making, patients can guide us as to how they best be evaluated. While receiving a normal CA 125 result is powerfully reassuring, it is just as powerfully confusing and difficult for a patient to receive an abnormal one followed by a period of “doing nothing,” otherwise known as expectant management, if immediate treatment is not beneficial.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She had no relevant financial disclosures. Email her at obnews@mdedge.com.
References
1. N Engl J Med. 2019 Nov 14;381(20):1929-39.
2. Lancet. 2010 Oct 2;376(9747):1155-63.
3. Gynecol Oncol. 2009 Jan;112(1):265-74.
4. Br J Cancer. 2011 Sep 27;105(7):890-6.
5. N Engl J Med. 2016 Dec 1;375(22):2154-64.
Have earlier diagnosis and treatment advances cut deaths from systemic sclerosis?
This abstract highlights a promising result for our younger patients diagnosed with systemic sclerosis. The fact that patients aged 44 years and younger with systemic sclerosis now have a death rate similar to that of the general population should be celebrated. Practicing clinicians can speculate why this trend has occurred. It is well known that these patients many times suffer from cardiopulmonary involvement.
Thus, the advances in the treatment of interstitial lung disease and pulmonary hypertension may account for the decreased mortality in this population.
Earlier detection has certainly helped this group. In addition, using immune modulators earlier at disease onset is likely another contributor to this positive trend. We are entering a decade and beyond filled with hope to change the course of this particular autoimmune disease.
Dr. Oberstein is a practicing rheumatologist at the University of Miami Health System and is senior medical director of musculoskeletal at Modernizing Medicine in Boca Raton, Fla. She has no relevant disclosures to report.
This abstract highlights a promising result for our younger patients diagnosed with systemic sclerosis. The fact that patients aged 44 years and younger with systemic sclerosis now have a death rate similar to that of the general population should be celebrated. Practicing clinicians can speculate why this trend has occurred. It is well known that these patients many times suffer from cardiopulmonary involvement.
Thus, the advances in the treatment of interstitial lung disease and pulmonary hypertension may account for the decreased mortality in this population.
Earlier detection has certainly helped this group. In addition, using immune modulators earlier at disease onset is likely another contributor to this positive trend. We are entering a decade and beyond filled with hope to change the course of this particular autoimmune disease.
Dr. Oberstein is a practicing rheumatologist at the University of Miami Health System and is senior medical director of musculoskeletal at Modernizing Medicine in Boca Raton, Fla. She has no relevant disclosures to report.
This abstract highlights a promising result for our younger patients diagnosed with systemic sclerosis. The fact that patients aged 44 years and younger with systemic sclerosis now have a death rate similar to that of the general population should be celebrated. Practicing clinicians can speculate why this trend has occurred. It is well known that these patients many times suffer from cardiopulmonary involvement.
Thus, the advances in the treatment of interstitial lung disease and pulmonary hypertension may account for the decreased mortality in this population.
Earlier detection has certainly helped this group. In addition, using immune modulators earlier at disease onset is likely another contributor to this positive trend. We are entering a decade and beyond filled with hope to change the course of this particular autoimmune disease.
Dr. Oberstein is a practicing rheumatologist at the University of Miami Health System and is senior medical director of musculoskeletal at Modernizing Medicine in Boca Raton, Fla. She has no relevant disclosures to report.
More studies like VERVE needed to test live vaccines in special populations
The VERVE study highlights a crucial topic for rheumatologists treating patients in clinical practice. The traditional thinking is to inform patients never to receive live vaccines when they are using TNF (tumor necrosis factor) inhibitors to treat their autoimmune disease. The VERVE study indicates that in the case of the Zostavax vaccine, patients on this form of biologic therapy for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis can safely receive this preventive measure. This study scratches the surface on an important topic, and other studies need to follow.
Many patients on biologic therapy want to travel. Many times, international travel requires vaccination that is only in the form of a live vaccine – for example, the yellow fever vaccine. It would be useful for us to better understand whether other live vaccines can safely be administered and better inform our patients who want to travel. In addition, many times mothers with young infants are nervous if they are on biologic therapy and their children need to receive a live vaccine. They are concerned that their children will shed the live virus and they will be in jeopardy. This study highlights that this may be more of an antiquated way of thinking. We need more studies of this kind to better understand and advise our patients properly without instilling unwarranted fear.
Dr. Oberstein is a practicing rheumatologist at the University of Miami Health System and is senior medical director of musculoskeletal at Modernizing Medicine in Boca Raton, Fla. She has no relevant disclosures to report.
The VERVE study highlights a crucial topic for rheumatologists treating patients in clinical practice. The traditional thinking is to inform patients never to receive live vaccines when they are using TNF (tumor necrosis factor) inhibitors to treat their autoimmune disease. The VERVE study indicates that in the case of the Zostavax vaccine, patients on this form of biologic therapy for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis can safely receive this preventive measure. This study scratches the surface on an important topic, and other studies need to follow.
Many patients on biologic therapy want to travel. Many times, international travel requires vaccination that is only in the form of a live vaccine – for example, the yellow fever vaccine. It would be useful for us to better understand whether other live vaccines can safely be administered and better inform our patients who want to travel. In addition, many times mothers with young infants are nervous if they are on biologic therapy and their children need to receive a live vaccine. They are concerned that their children will shed the live virus and they will be in jeopardy. This study highlights that this may be more of an antiquated way of thinking. We need more studies of this kind to better understand and advise our patients properly without instilling unwarranted fear.
Dr. Oberstein is a practicing rheumatologist at the University of Miami Health System and is senior medical director of musculoskeletal at Modernizing Medicine in Boca Raton, Fla. She has no relevant disclosures to report.
The VERVE study highlights a crucial topic for rheumatologists treating patients in clinical practice. The traditional thinking is to inform patients never to receive live vaccines when they are using TNF (tumor necrosis factor) inhibitors to treat their autoimmune disease. The VERVE study indicates that in the case of the Zostavax vaccine, patients on this form of biologic therapy for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis can safely receive this preventive measure. This study scratches the surface on an important topic, and other studies need to follow.
Many patients on biologic therapy want to travel. Many times, international travel requires vaccination that is only in the form of a live vaccine – for example, the yellow fever vaccine. It would be useful for us to better understand whether other live vaccines can safely be administered and better inform our patients who want to travel. In addition, many times mothers with young infants are nervous if they are on biologic therapy and their children need to receive a live vaccine. They are concerned that their children will shed the live virus and they will be in jeopardy. This study highlights that this may be more of an antiquated way of thinking. We need more studies of this kind to better understand and advise our patients properly without instilling unwarranted fear.
Dr. Oberstein is a practicing rheumatologist at the University of Miami Health System and is senior medical director of musculoskeletal at Modernizing Medicine in Boca Raton, Fla. She has no relevant disclosures to report.
Expanding the reach of available cancer therapies
In this edition of “How I Will Treat My Next Patient,” I highlight two articles that demonstrate the safety of established treatments – nephrectomy and stereotactic ablative body radiotherapy (SABR) – in patient populations that previously may have been excluded from those treatments at many centers.
Nephrectomy in advanced RCC
Nirmish Singla, MD, and colleagues reported a single-center retrospective cohort study, assessing outcomes of 11 nephrectomies (10 radical, 1 partial) in 10 patients with advanced renal cell carcinoma (RCC) who had received front- or later-line immune checkpoint inhibitor therapy (ICIs). Half had received nivolumab alone; the others received nivolumab plus ipilimumab. Surgery was performed laparoscopically in five cases (Urol Oncol. 2019 Dec;37[12]:924-31).
No patient experienced a major intraoperative complication. Four experienced postoperative complications, the majority of which were addressed with interventional radiology procedures. The median hospital stay was 4 days. One patient died of progressive disease more than 3 months after surgery, and another died of pulmonary embolism and sepsis. Six of the 10 patients did not have any complications or readmissions. There were no immune-related toxicities and no wound-healing issues. ICI therapy was resumed postoperatively in six patients.
At nephrectomy (plus or minus metastatectomy), one patient achieved a response to immunotherapy in the primary tumor, and three of four patients who underwent resection of hepatic, pulmonary, or adrenal metastases had no detectable cancer. All surgical margins were negative.
During a median postoperative follow-up of 180 days, nephrectomy following ICI was safe. Pathologic response in both the primary tumor and metastatic sites was encouraging.
What this means in clinical practice
In medical school, all of us are admonished not to be afraid to unlearn something and to learn something new. Historically, nephrectomy was felt to be helpful in improving overall survival in patients with advanced RCC. Effective targeted therapies and ICIs have caused us to question the role of nephrectomy and its timing, since 20%-40% of patients who have apparently localized RCC at the time of nephrectomy develop recurrences within 3 years. Preoperative therapy could mitigate potentially aggressive tumor biology, treat micrometastatic disease, and help select patients who should not be treated surgically.
In the CARMENA trial of the treatment of advanced RCC patients with the tyrosine kinase inhibitor sunitinib versus nephrectomy followed by sunitinib, most patients could avoid nephrectomy without compromising survival (N Engl J Med. 2018; 379:417-27). Results were updated at the 2019 annual meeting of the American Society of Clinical Oncology. Overall, nephrectomy was not beneficial. However, delayed nephrectomy (after sunitinib) appeared be beneficial for good responders with only one IMDC (International Metastatic RCC Database Consortium) risk factor and only one metastatic site.
The small study by Dr. Singla and colleagues illustrates that nephrectomy is feasible after ICI, plus or minus anti-CTLA4-targeted treatment, and that favorable histologic results can be achieved. With ICI plus or minus anti-CTLA4-targeted treatment, no patient had progressive disease prior to surgery. This experience is germane in view of recently updated results of the CheckMate 214 trial, showing superior overall survival, response rates, and response duration for nivolumab plus ipilimumab, in comparison with sunitinib.
There are still unresolved questions, including whether these favorable outcomes can be achieved in community practice and whether there are genomic or immunohistochemistry expression profiles to select patients who can benefit from this approach. It’s unclear whether there are practical issues that influence outcome, such as type of ICI, number of preoperative treatment cycles, and additional systemic therapies including postoperative treatment. However, the current series rings the starting bell for the study of those questions and a promising era for patients with this deadly disease.
SABR in moderately central NSCLC
SABR to peripheral, small non–small cell lung cancers (NSCLCs) produces high local control rates, with low grade 3-4 toxicity, and is an alternative to resection in patients who are unfit for surgery. In a pragmatic, community-based, prospective cohort experience in Scotland, Robert Rulach, MBChB, and colleagues, treated 50 T1-2N0M0 NSCLC patients with SABR 50-Gy in five fractions (Clin Oncol. 2019 Oct 10. doi: 10.1016/j.clon.2019.09.055). The dose and fractionation schedule was safe and effective in the phase 1/2 RTOG 0813 trial and is concordant with guidelines from the National Comprehensive Cancer Network (NCCN).
All of the tumors were moderately central, as in the RTOG trial. One patient had an additional tumor that was ultracentral. Notably, 84% of patients were deemed medically unfit for surgery.
All patients completed radiotherapy without treatment delays. Two patients died within 90 days of treatment. There were no grade 4 or grade 5 toxicities and the overall rate of grade 3 toxicity was 4%. With a median follow-up of 25.2 months, 34 patients died: 18 from causes unrelated to cancer and 16 from cancer recurrence. The median overall survival was 27 months. The 2-year overall survival rate was 67.6%, commensurate with the rate seen in RTOG 0813.
The researchers concluded that, for frail patients with centrally-located NSCLC treated uniformly in a community practice, SABR with the RTOG 0813 treatment protocol produced acceptable toxicity and overall survival comparable with the published literature.
What this means in clinical practice
The results and conclusions of the study by Dr. Rulach and colleagues are straightforward: SABR can be used for centrally-located NSCLC without producing massive hemoptysis, bronchial stricture, and fistula formation. Since the majority of patients had no histologic diagnosis, T1N0 lesions, and no routine follow-up CT scans beyond 3 months post treatment, conclusions beyond that are unjustified.
In a community-based practice, NCCN guideline–concordant SABR treatment in moderately centrally-located NSCLC was safely delivered. For the burgeoning population of medically inoperable and/or elderly NSCLC patients, this alone is reassuring for clinicians and is helpful information for patients who require and/or desire nonsurgical treatment.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
In this edition of “How I Will Treat My Next Patient,” I highlight two articles that demonstrate the safety of established treatments – nephrectomy and stereotactic ablative body radiotherapy (SABR) – in patient populations that previously may have been excluded from those treatments at many centers.
Nephrectomy in advanced RCC
Nirmish Singla, MD, and colleagues reported a single-center retrospective cohort study, assessing outcomes of 11 nephrectomies (10 radical, 1 partial) in 10 patients with advanced renal cell carcinoma (RCC) who had received front- or later-line immune checkpoint inhibitor therapy (ICIs). Half had received nivolumab alone; the others received nivolumab plus ipilimumab. Surgery was performed laparoscopically in five cases (Urol Oncol. 2019 Dec;37[12]:924-31).
No patient experienced a major intraoperative complication. Four experienced postoperative complications, the majority of which were addressed with interventional radiology procedures. The median hospital stay was 4 days. One patient died of progressive disease more than 3 months after surgery, and another died of pulmonary embolism and sepsis. Six of the 10 patients did not have any complications or readmissions. There were no immune-related toxicities and no wound-healing issues. ICI therapy was resumed postoperatively in six patients.
At nephrectomy (plus or minus metastatectomy), one patient achieved a response to immunotherapy in the primary tumor, and three of four patients who underwent resection of hepatic, pulmonary, or adrenal metastases had no detectable cancer. All surgical margins were negative.
During a median postoperative follow-up of 180 days, nephrectomy following ICI was safe. Pathologic response in both the primary tumor and metastatic sites was encouraging.
What this means in clinical practice
In medical school, all of us are admonished not to be afraid to unlearn something and to learn something new. Historically, nephrectomy was felt to be helpful in improving overall survival in patients with advanced RCC. Effective targeted therapies and ICIs have caused us to question the role of nephrectomy and its timing, since 20%-40% of patients who have apparently localized RCC at the time of nephrectomy develop recurrences within 3 years. Preoperative therapy could mitigate potentially aggressive tumor biology, treat micrometastatic disease, and help select patients who should not be treated surgically.
In the CARMENA trial of the treatment of advanced RCC patients with the tyrosine kinase inhibitor sunitinib versus nephrectomy followed by sunitinib, most patients could avoid nephrectomy without compromising survival (N Engl J Med. 2018; 379:417-27). Results were updated at the 2019 annual meeting of the American Society of Clinical Oncology. Overall, nephrectomy was not beneficial. However, delayed nephrectomy (after sunitinib) appeared be beneficial for good responders with only one IMDC (International Metastatic RCC Database Consortium) risk factor and only one metastatic site.
The small study by Dr. Singla and colleagues illustrates that nephrectomy is feasible after ICI, plus or minus anti-CTLA4-targeted treatment, and that favorable histologic results can be achieved. With ICI plus or minus anti-CTLA4-targeted treatment, no patient had progressive disease prior to surgery. This experience is germane in view of recently updated results of the CheckMate 214 trial, showing superior overall survival, response rates, and response duration for nivolumab plus ipilimumab, in comparison with sunitinib.
There are still unresolved questions, including whether these favorable outcomes can be achieved in community practice and whether there are genomic or immunohistochemistry expression profiles to select patients who can benefit from this approach. It’s unclear whether there are practical issues that influence outcome, such as type of ICI, number of preoperative treatment cycles, and additional systemic therapies including postoperative treatment. However, the current series rings the starting bell for the study of those questions and a promising era for patients with this deadly disease.
SABR in moderately central NSCLC
SABR to peripheral, small non–small cell lung cancers (NSCLCs) produces high local control rates, with low grade 3-4 toxicity, and is an alternative to resection in patients who are unfit for surgery. In a pragmatic, community-based, prospective cohort experience in Scotland, Robert Rulach, MBChB, and colleagues, treated 50 T1-2N0M0 NSCLC patients with SABR 50-Gy in five fractions (Clin Oncol. 2019 Oct 10. doi: 10.1016/j.clon.2019.09.055). The dose and fractionation schedule was safe and effective in the phase 1/2 RTOG 0813 trial and is concordant with guidelines from the National Comprehensive Cancer Network (NCCN).
All of the tumors were moderately central, as in the RTOG trial. One patient had an additional tumor that was ultracentral. Notably, 84% of patients were deemed medically unfit for surgery.
All patients completed radiotherapy without treatment delays. Two patients died within 90 days of treatment. There were no grade 4 or grade 5 toxicities and the overall rate of grade 3 toxicity was 4%. With a median follow-up of 25.2 months, 34 patients died: 18 from causes unrelated to cancer and 16 from cancer recurrence. The median overall survival was 27 months. The 2-year overall survival rate was 67.6%, commensurate with the rate seen in RTOG 0813.
The researchers concluded that, for frail patients with centrally-located NSCLC treated uniformly in a community practice, SABR with the RTOG 0813 treatment protocol produced acceptable toxicity and overall survival comparable with the published literature.
What this means in clinical practice
The results and conclusions of the study by Dr. Rulach and colleagues are straightforward: SABR can be used for centrally-located NSCLC without producing massive hemoptysis, bronchial stricture, and fistula formation. Since the majority of patients had no histologic diagnosis, T1N0 lesions, and no routine follow-up CT scans beyond 3 months post treatment, conclusions beyond that are unjustified.
In a community-based practice, NCCN guideline–concordant SABR treatment in moderately centrally-located NSCLC was safely delivered. For the burgeoning population of medically inoperable and/or elderly NSCLC patients, this alone is reassuring for clinicians and is helpful information for patients who require and/or desire nonsurgical treatment.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
In this edition of “How I Will Treat My Next Patient,” I highlight two articles that demonstrate the safety of established treatments – nephrectomy and stereotactic ablative body radiotherapy (SABR) – in patient populations that previously may have been excluded from those treatments at many centers.
Nephrectomy in advanced RCC
Nirmish Singla, MD, and colleagues reported a single-center retrospective cohort study, assessing outcomes of 11 nephrectomies (10 radical, 1 partial) in 10 patients with advanced renal cell carcinoma (RCC) who had received front- or later-line immune checkpoint inhibitor therapy (ICIs). Half had received nivolumab alone; the others received nivolumab plus ipilimumab. Surgery was performed laparoscopically in five cases (Urol Oncol. 2019 Dec;37[12]:924-31).
No patient experienced a major intraoperative complication. Four experienced postoperative complications, the majority of which were addressed with interventional radiology procedures. The median hospital stay was 4 days. One patient died of progressive disease more than 3 months after surgery, and another died of pulmonary embolism and sepsis. Six of the 10 patients did not have any complications or readmissions. There were no immune-related toxicities and no wound-healing issues. ICI therapy was resumed postoperatively in six patients.
At nephrectomy (plus or minus metastatectomy), one patient achieved a response to immunotherapy in the primary tumor, and three of four patients who underwent resection of hepatic, pulmonary, or adrenal metastases had no detectable cancer. All surgical margins were negative.
During a median postoperative follow-up of 180 days, nephrectomy following ICI was safe. Pathologic response in both the primary tumor and metastatic sites was encouraging.
What this means in clinical practice
In medical school, all of us are admonished not to be afraid to unlearn something and to learn something new. Historically, nephrectomy was felt to be helpful in improving overall survival in patients with advanced RCC. Effective targeted therapies and ICIs have caused us to question the role of nephrectomy and its timing, since 20%-40% of patients who have apparently localized RCC at the time of nephrectomy develop recurrences within 3 years. Preoperative therapy could mitigate potentially aggressive tumor biology, treat micrometastatic disease, and help select patients who should not be treated surgically.
In the CARMENA trial of the treatment of advanced RCC patients with the tyrosine kinase inhibitor sunitinib versus nephrectomy followed by sunitinib, most patients could avoid nephrectomy without compromising survival (N Engl J Med. 2018; 379:417-27). Results were updated at the 2019 annual meeting of the American Society of Clinical Oncology. Overall, nephrectomy was not beneficial. However, delayed nephrectomy (after sunitinib) appeared be beneficial for good responders with only one IMDC (International Metastatic RCC Database Consortium) risk factor and only one metastatic site.
The small study by Dr. Singla and colleagues illustrates that nephrectomy is feasible after ICI, plus or minus anti-CTLA4-targeted treatment, and that favorable histologic results can be achieved. With ICI plus or minus anti-CTLA4-targeted treatment, no patient had progressive disease prior to surgery. This experience is germane in view of recently updated results of the CheckMate 214 trial, showing superior overall survival, response rates, and response duration for nivolumab plus ipilimumab, in comparison with sunitinib.
There are still unresolved questions, including whether these favorable outcomes can be achieved in community practice and whether there are genomic or immunohistochemistry expression profiles to select patients who can benefit from this approach. It’s unclear whether there are practical issues that influence outcome, such as type of ICI, number of preoperative treatment cycles, and additional systemic therapies including postoperative treatment. However, the current series rings the starting bell for the study of those questions and a promising era for patients with this deadly disease.
SABR in moderately central NSCLC
SABR to peripheral, small non–small cell lung cancers (NSCLCs) produces high local control rates, with low grade 3-4 toxicity, and is an alternative to resection in patients who are unfit for surgery. In a pragmatic, community-based, prospective cohort experience in Scotland, Robert Rulach, MBChB, and colleagues, treated 50 T1-2N0M0 NSCLC patients with SABR 50-Gy in five fractions (Clin Oncol. 2019 Oct 10. doi: 10.1016/j.clon.2019.09.055). The dose and fractionation schedule was safe and effective in the phase 1/2 RTOG 0813 trial and is concordant with guidelines from the National Comprehensive Cancer Network (NCCN).
All of the tumors were moderately central, as in the RTOG trial. One patient had an additional tumor that was ultracentral. Notably, 84% of patients were deemed medically unfit for surgery.
All patients completed radiotherapy without treatment delays. Two patients died within 90 days of treatment. There were no grade 4 or grade 5 toxicities and the overall rate of grade 3 toxicity was 4%. With a median follow-up of 25.2 months, 34 patients died: 18 from causes unrelated to cancer and 16 from cancer recurrence. The median overall survival was 27 months. The 2-year overall survival rate was 67.6%, commensurate with the rate seen in RTOG 0813.
The researchers concluded that, for frail patients with centrally-located NSCLC treated uniformly in a community practice, SABR with the RTOG 0813 treatment protocol produced acceptable toxicity and overall survival comparable with the published literature.
What this means in clinical practice
The results and conclusions of the study by Dr. Rulach and colleagues are straightforward: SABR can be used for centrally-located NSCLC without producing massive hemoptysis, bronchial stricture, and fistula formation. Since the majority of patients had no histologic diagnosis, T1N0 lesions, and no routine follow-up CT scans beyond 3 months post treatment, conclusions beyond that are unjustified.
In a community-based practice, NCCN guideline–concordant SABR treatment in moderately centrally-located NSCLC was safely delivered. For the burgeoning population of medically inoperable and/or elderly NSCLC patients, this alone is reassuring for clinicians and is helpful information for patients who require and/or desire nonsurgical treatment.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
Learning about and prescribing emergency contraception
As health care providers to children, we always are learning. And with new knowledge we sometimes can be taken out of our comfort zone. One of those areas are teenagers, contraception, safe-sex counseling, and now emergency contraception (EC). In residency you have your 1-month adolescent medicine rotation to try and absorb every bit of information like a sponge, but there also will be a level of discomfort and uncertainty. However, as medical providers we cannot let the above prevent us from giving well-rounded and informed care.
When our teens disclose the most private moment of their life, we have to be armed and ready to not only comfort them, but advise and guide them to making a decision so that they can ensure their safety. The answers regarding sexual activity are becoming more and more alarming, especially in our younger patients. Therefore, this is an important discussion to have at every visit (not just well-child checks), so that education opportunities are not missed and our patients feel a sense of normalcy about discussing reproductive health with their health care provider and or parents.
We all have our personal beliefs, but we cannot let that guide our decision on what care or education we give our patients. Unfortunately, I have heard many health care providers judge our patients for their promiscuity, when we need to educate them – not be their judge and jury. Our teens go through different stages of growth and development, and with these stages come experimentation and risk taking. So as their health care providers, we need to be up to date on the information out there.
With regards with EC, some of our patients think that they can get it only after having unprotected sex. However, they should know that the oral ECs can be given to them at any time, so should they be in the situation above, they have an immediate remedy. With the different options come different counseling and different instructions on administration and follow-up. In residency, we might not have learned the skill of inserting an IUD, which is another form of EC; that is why there are many resources available. These resources include hands-on workshops, videos on counseling, and your friendly neighborhood adolescent medicine physician or ob.gyn.
EC can give our patients that sense of relief, especially when they have unprotected sex. However, they also need to have a sense of responsibility for their actions because you do not want them to engage in high-risk behaviors. Just as we are responsible to provide up-to-date care, our patients must take ownership of their health and well-being. Also If they are engaging in unprotected sex, they are just as responsible; therefore, they should know everything about contraception as well as EC. They should feel comfortable talking to their partners about contraception. Health care providers should make them feel comfortable receiving EC that they can give to their female partner.
We need to become knowledgeable and comfortable prescribing EC, as well as incorporating it in our routine care. This is a policy that I strongly believe should be part of every pediatrician’s and family physician’s office, especially when there is a lack of resources. Of the different options that are available, the oral forms of EC – especially Ella or Plan B step 1 (levonorgestrel) – would be the easiest to prescribe and counsel on. I would not recommend the options where multiple pills need to be taken more than once a day, because compliance becomes a factor. Also knowing that these options are available over the counter also is helpful because our community pharmacist also can help with medication administration and counseling.
In summary, I strongly recommend the discussion of EC in the office, especially the general pediatrician’s office. I recommend that, for those physicians’ who may be uncomfortable, that they should start with the “easier” options of oral progestins (Ella or Plan B step 1). As you become more comfortable with the information and counseling, you can learn skills such as IUD insertions, so you then can offer more options.
As health care providers to children, we always are learning. And with new knowledge we sometimes can be taken out of our comfort zone. One of those areas are teenagers, contraception, safe-sex counseling, and now emergency contraception (EC). In residency you have your 1-month adolescent medicine rotation to try and absorb every bit of information like a sponge, but there also will be a level of discomfort and uncertainty. However, as medical providers we cannot let the above prevent us from giving well-rounded and informed care.
When our teens disclose the most private moment of their life, we have to be armed and ready to not only comfort them, but advise and guide them to making a decision so that they can ensure their safety. The answers regarding sexual activity are becoming more and more alarming, especially in our younger patients. Therefore, this is an important discussion to have at every visit (not just well-child checks), so that education opportunities are not missed and our patients feel a sense of normalcy about discussing reproductive health with their health care provider and or parents.
We all have our personal beliefs, but we cannot let that guide our decision on what care or education we give our patients. Unfortunately, I have heard many health care providers judge our patients for their promiscuity, when we need to educate them – not be their judge and jury. Our teens go through different stages of growth and development, and with these stages come experimentation and risk taking. So as their health care providers, we need to be up to date on the information out there.
With regards with EC, some of our patients think that they can get it only after having unprotected sex. However, they should know that the oral ECs can be given to them at any time, so should they be in the situation above, they have an immediate remedy. With the different options come different counseling and different instructions on administration and follow-up. In residency, we might not have learned the skill of inserting an IUD, which is another form of EC; that is why there are many resources available. These resources include hands-on workshops, videos on counseling, and your friendly neighborhood adolescent medicine physician or ob.gyn.
EC can give our patients that sense of relief, especially when they have unprotected sex. However, they also need to have a sense of responsibility for their actions because you do not want them to engage in high-risk behaviors. Just as we are responsible to provide up-to-date care, our patients must take ownership of their health and well-being. Also If they are engaging in unprotected sex, they are just as responsible; therefore, they should know everything about contraception as well as EC. They should feel comfortable talking to their partners about contraception. Health care providers should make them feel comfortable receiving EC that they can give to their female partner.
We need to become knowledgeable and comfortable prescribing EC, as well as incorporating it in our routine care. This is a policy that I strongly believe should be part of every pediatrician’s and family physician’s office, especially when there is a lack of resources. Of the different options that are available, the oral forms of EC – especially Ella or Plan B step 1 (levonorgestrel) – would be the easiest to prescribe and counsel on. I would not recommend the options where multiple pills need to be taken more than once a day, because compliance becomes a factor. Also knowing that these options are available over the counter also is helpful because our community pharmacist also can help with medication administration and counseling.
In summary, I strongly recommend the discussion of EC in the office, especially the general pediatrician’s office. I recommend that, for those physicians’ who may be uncomfortable, that they should start with the “easier” options of oral progestins (Ella or Plan B step 1). As you become more comfortable with the information and counseling, you can learn skills such as IUD insertions, so you then can offer more options.
As health care providers to children, we always are learning. And with new knowledge we sometimes can be taken out of our comfort zone. One of those areas are teenagers, contraception, safe-sex counseling, and now emergency contraception (EC). In residency you have your 1-month adolescent medicine rotation to try and absorb every bit of information like a sponge, but there also will be a level of discomfort and uncertainty. However, as medical providers we cannot let the above prevent us from giving well-rounded and informed care.
When our teens disclose the most private moment of their life, we have to be armed and ready to not only comfort them, but advise and guide them to making a decision so that they can ensure their safety. The answers regarding sexual activity are becoming more and more alarming, especially in our younger patients. Therefore, this is an important discussion to have at every visit (not just well-child checks), so that education opportunities are not missed and our patients feel a sense of normalcy about discussing reproductive health with their health care provider and or parents.
We all have our personal beliefs, but we cannot let that guide our decision on what care or education we give our patients. Unfortunately, I have heard many health care providers judge our patients for their promiscuity, when we need to educate them – not be their judge and jury. Our teens go through different stages of growth and development, and with these stages come experimentation and risk taking. So as their health care providers, we need to be up to date on the information out there.
With regards with EC, some of our patients think that they can get it only after having unprotected sex. However, they should know that the oral ECs can be given to them at any time, so should they be in the situation above, they have an immediate remedy. With the different options come different counseling and different instructions on administration and follow-up. In residency, we might not have learned the skill of inserting an IUD, which is another form of EC; that is why there are many resources available. These resources include hands-on workshops, videos on counseling, and your friendly neighborhood adolescent medicine physician or ob.gyn.
EC can give our patients that sense of relief, especially when they have unprotected sex. However, they also need to have a sense of responsibility for their actions because you do not want them to engage in high-risk behaviors. Just as we are responsible to provide up-to-date care, our patients must take ownership of their health and well-being. Also If they are engaging in unprotected sex, they are just as responsible; therefore, they should know everything about contraception as well as EC. They should feel comfortable talking to their partners about contraception. Health care providers should make them feel comfortable receiving EC that they can give to their female partner.
We need to become knowledgeable and comfortable prescribing EC, as well as incorporating it in our routine care. This is a policy that I strongly believe should be part of every pediatrician’s and family physician’s office, especially when there is a lack of resources. Of the different options that are available, the oral forms of EC – especially Ella or Plan B step 1 (levonorgestrel) – would be the easiest to prescribe and counsel on. I would not recommend the options where multiple pills need to be taken more than once a day, because compliance becomes a factor. Also knowing that these options are available over the counter also is helpful because our community pharmacist also can help with medication administration and counseling.
In summary, I strongly recommend the discussion of EC in the office, especially the general pediatrician’s office. I recommend that, for those physicians’ who may be uncomfortable, that they should start with the “easier” options of oral progestins (Ella or Plan B step 1). As you become more comfortable with the information and counseling, you can learn skills such as IUD insertions, so you then can offer more options.
Guideline: Diagnosis and treatment of adults with community-acquired pneumonia
A new guideline has been published to update the 2007 guidelines for the management of adults with community-acquired pneumonia (CAP).
The practice guideline was jointly written by an ad hoc committee of the American Thoracic Society and Infectious Diseases Society of America. CAP refers to a pneumonia infection that was acquired by a patient in his or her community. Decisions about which antibiotics to use to treat this kind of infection are based on risk factors for resistant organisms and the severity of illness.
Pathogens
Traditionally, CAP is caused by common bacterial pathogens that include Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Staphylococcus aureus, Legionella species, Chlamydia pneumonia, and Moraxella catarrhalis. Risk factors for multidrug resistant pathogens such as methicillin-resistant S. aureus (MRSA) and Pseudomonas aeruginosa include previous infection with MRSA or P. aeruginosa, recent hospitalization, and requiring parenteral antibiotics in the last 90 days.
Defining severe community-acquired pneumonia
The health care–associated pneumonia, or HCAP, classification should no longer be used to determine empiric treatment. The recommendations for which antibiotics to use are linked to the severity of illness. Previously the site of treatment drove antibiotic selection, but since decision about the site of care can be affected by many considerations, the guidelines recommend using the CAP severity criteria. Severe CAP includes either one major or at least three minor criteria.
Major criteria are:
- Septic shock requiring vasopressors.
- Respiratory failure requiring mechanical ventilation.
Minor criteria are:
- Respiratory rate greater than or equal to 30 breaths/min.
- Ratio of arterial O2 partial pressure to fractional inspired O2 less than or equal to 250.
- Multilobar infiltrates.
- Confusion/disorientation.
- Uremia (blood urea nitrogen level greater than or equal to 20 mg/dL).
- Leukopenia (white blood cell count less than 4,000 cells/mcL).
- Thrombocytopenia (platelet count less than 100,000 mcL)
- Hypothermia (core temperature less than 36º C).
- Hypotension requiring aggressive fluid resuscitation.
Management and diagnostic testing
Clinicians should use the Pneumonia Severity Index (PSI) and clinical judgment to guide the site of treatment for patients. Gram stain, sputum, and blood culture should not be routinely obtained in an outpatient setting. Legionella antigen should not be routinely obtained unless indicated by epidemiological factors. During influenza season, a rapid influenza assay, preferably a nucleic acid amplification test, should be obtained to help guide treatment.
For patients with severe CAP or risk factors for MRSA or P. aeruginosa, gram stain and culture and Legionella antigen should be obtained to manage antibiotic choices. Also, blood cultures should be obtained for these patients.
Empiric antibiotic therapy should be initiated based on clinical judgment and radiographic confirmation of CAP. Serum procalcitonin should not be used to assess initiation of antibiotic therapy.
Empiric antibiotic therapy
Healthy adults without comorbidities should be treated with monotherapy of either:
- Amoxicillin 1 g three times daily.
- OR doxycycline 100 mg twice daily.
- OR a macrolide (azithromycin 500 mg on first day then 250 mg daily or clarithromycin 500 mg twice daily or clarithromycin extended release 1,000 mg daily) only in areas with pneumococcal resistance to macrolides less than 25%.
Adults with comorbidities such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; or asplenia should be treated with:
- Amoxicillin/clavulanate 500 mg/125 mg three times daily, or amoxicillin/ clavulanate 875 mg/125 mg twice daily, or 2,000 mg/125 mg twice daily, or a cephalosporin (cefpodoxime 200 mg twice daily or cefuroxime 500 mg twice daily); and a macrolide (azithromycin 500 mg on first day then 250 mg daily, clarithromycin [500 mg twice daily or extended release 1,000 mg once daily]), or doxycycline 100 mg twice daily. (Some experts recommend that the first dose of doxycycline should be 200 mg.)
- OR monotherapy with respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily).
Inpatient pneumonia that is not severe, without risk factors for resistant organisms should be treated with:
- Beta-lactam (ampicillin 1 sulbactam 1.5-3 g every 6 h, cefotaxime 1-2 g every 8 h, ceftriaxone 1-2 g daily, or ceftaroline 600 mg every 12 h) and a macrolide (azithromycin 500 mg daily or clarithromycin 500 mg twice daily).
- OR monotherapy with a respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily).
If there is a contraindication for the use of both a macrolide and a fluoroquinolone, then doxycycline can be used instead.
Severe inpatient pneumonia without risk factors for resistant organisms should be treated with combination therapy of either (agents and doses the same as above):
- Beta-lactam and macrolide.
- OR fluoroquinolone and beta-lactam.
It is recommended to not routinely add anaerobic coverage for suspected aspiration pneumonia unless lung abscess or empyema is suspected. Clinicians should identify risk factors for MRSA or P. aeruginosa before adding additional agents.
Duration of antibiotic therapy is determined by the patient achieving clinical stability with no less than 5 days of antibiotics. In adults with symptom resolution within 5-7 days, no additional follow-up chest imaging is recommended. If patients test positive for influenza, then anti-influenza treatment such as oseltamivir should be used in addition to antibiotics regardless of length of influenza symptoms before presentation.
The bottom line
CAP treatment should be based on severity of illness and risk factors for resistant organisms. Blood and sputum cultures are recommended only for patients with severe pneumonia. There have been important changes in the recommendations for antibiotic treatment of CAP, with high-dose amoxicillin recommended for most patients with CAP who are treated as outpatients. Patients who exhibit clinical stability should be treated for at least 5 days and do not require follow up imaging studies.
For a podcast of this guideline, go to iTunes and download the Infectious Diseases Society of America guideline podcast.
Reference
Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67.
Tina Chuong, DO, is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.
A new guideline has been published to update the 2007 guidelines for the management of adults with community-acquired pneumonia (CAP).
The practice guideline was jointly written by an ad hoc committee of the American Thoracic Society and Infectious Diseases Society of America. CAP refers to a pneumonia infection that was acquired by a patient in his or her community. Decisions about which antibiotics to use to treat this kind of infection are based on risk factors for resistant organisms and the severity of illness.
Pathogens
Traditionally, CAP is caused by common bacterial pathogens that include Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Staphylococcus aureus, Legionella species, Chlamydia pneumonia, and Moraxella catarrhalis. Risk factors for multidrug resistant pathogens such as methicillin-resistant S. aureus (MRSA) and Pseudomonas aeruginosa include previous infection with MRSA or P. aeruginosa, recent hospitalization, and requiring parenteral antibiotics in the last 90 days.
Defining severe community-acquired pneumonia
The health care–associated pneumonia, or HCAP, classification should no longer be used to determine empiric treatment. The recommendations for which antibiotics to use are linked to the severity of illness. Previously the site of treatment drove antibiotic selection, but since decision about the site of care can be affected by many considerations, the guidelines recommend using the CAP severity criteria. Severe CAP includes either one major or at least three minor criteria.
Major criteria are:
- Septic shock requiring vasopressors.
- Respiratory failure requiring mechanical ventilation.
Minor criteria are:
- Respiratory rate greater than or equal to 30 breaths/min.
- Ratio of arterial O2 partial pressure to fractional inspired O2 less than or equal to 250.
- Multilobar infiltrates.
- Confusion/disorientation.
- Uremia (blood urea nitrogen level greater than or equal to 20 mg/dL).
- Leukopenia (white blood cell count less than 4,000 cells/mcL).
- Thrombocytopenia (platelet count less than 100,000 mcL)
- Hypothermia (core temperature less than 36º C).
- Hypotension requiring aggressive fluid resuscitation.
Management and diagnostic testing
Clinicians should use the Pneumonia Severity Index (PSI) and clinical judgment to guide the site of treatment for patients. Gram stain, sputum, and blood culture should not be routinely obtained in an outpatient setting. Legionella antigen should not be routinely obtained unless indicated by epidemiological factors. During influenza season, a rapid influenza assay, preferably a nucleic acid amplification test, should be obtained to help guide treatment.
For patients with severe CAP or risk factors for MRSA or P. aeruginosa, gram stain and culture and Legionella antigen should be obtained to manage antibiotic choices. Also, blood cultures should be obtained for these patients.
Empiric antibiotic therapy should be initiated based on clinical judgment and radiographic confirmation of CAP. Serum procalcitonin should not be used to assess initiation of antibiotic therapy.
Empiric antibiotic therapy
Healthy adults without comorbidities should be treated with monotherapy of either:
- Amoxicillin 1 g three times daily.
- OR doxycycline 100 mg twice daily.
- OR a macrolide (azithromycin 500 mg on first day then 250 mg daily or clarithromycin 500 mg twice daily or clarithromycin extended release 1,000 mg daily) only in areas with pneumococcal resistance to macrolides less than 25%.
Adults with comorbidities such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; or asplenia should be treated with:
- Amoxicillin/clavulanate 500 mg/125 mg three times daily, or amoxicillin/ clavulanate 875 mg/125 mg twice daily, or 2,000 mg/125 mg twice daily, or a cephalosporin (cefpodoxime 200 mg twice daily or cefuroxime 500 mg twice daily); and a macrolide (azithromycin 500 mg on first day then 250 mg daily, clarithromycin [500 mg twice daily or extended release 1,000 mg once daily]), or doxycycline 100 mg twice daily. (Some experts recommend that the first dose of doxycycline should be 200 mg.)
- OR monotherapy with respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily).
Inpatient pneumonia that is not severe, without risk factors for resistant organisms should be treated with:
- Beta-lactam (ampicillin 1 sulbactam 1.5-3 g every 6 h, cefotaxime 1-2 g every 8 h, ceftriaxone 1-2 g daily, or ceftaroline 600 mg every 12 h) and a macrolide (azithromycin 500 mg daily or clarithromycin 500 mg twice daily).
- OR monotherapy with a respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily).
If there is a contraindication for the use of both a macrolide and a fluoroquinolone, then doxycycline can be used instead.
Severe inpatient pneumonia without risk factors for resistant organisms should be treated with combination therapy of either (agents and doses the same as above):
- Beta-lactam and macrolide.
- OR fluoroquinolone and beta-lactam.
It is recommended to not routinely add anaerobic coverage for suspected aspiration pneumonia unless lung abscess or empyema is suspected. Clinicians should identify risk factors for MRSA or P. aeruginosa before adding additional agents.
Duration of antibiotic therapy is determined by the patient achieving clinical stability with no less than 5 days of antibiotics. In adults with symptom resolution within 5-7 days, no additional follow-up chest imaging is recommended. If patients test positive for influenza, then anti-influenza treatment such as oseltamivir should be used in addition to antibiotics regardless of length of influenza symptoms before presentation.
The bottom line
CAP treatment should be based on severity of illness and risk factors for resistant organisms. Blood and sputum cultures are recommended only for patients with severe pneumonia. There have been important changes in the recommendations for antibiotic treatment of CAP, with high-dose amoxicillin recommended for most patients with CAP who are treated as outpatients. Patients who exhibit clinical stability should be treated for at least 5 days and do not require follow up imaging studies.
For a podcast of this guideline, go to iTunes and download the Infectious Diseases Society of America guideline podcast.
Reference
Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67.
Tina Chuong, DO, is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.
A new guideline has been published to update the 2007 guidelines for the management of adults with community-acquired pneumonia (CAP).
The practice guideline was jointly written by an ad hoc committee of the American Thoracic Society and Infectious Diseases Society of America. CAP refers to a pneumonia infection that was acquired by a patient in his or her community. Decisions about which antibiotics to use to treat this kind of infection are based on risk factors for resistant organisms and the severity of illness.
Pathogens
Traditionally, CAP is caused by common bacterial pathogens that include Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Staphylococcus aureus, Legionella species, Chlamydia pneumonia, and Moraxella catarrhalis. Risk factors for multidrug resistant pathogens such as methicillin-resistant S. aureus (MRSA) and Pseudomonas aeruginosa include previous infection with MRSA or P. aeruginosa, recent hospitalization, and requiring parenteral antibiotics in the last 90 days.
Defining severe community-acquired pneumonia
The health care–associated pneumonia, or HCAP, classification should no longer be used to determine empiric treatment. The recommendations for which antibiotics to use are linked to the severity of illness. Previously the site of treatment drove antibiotic selection, but since decision about the site of care can be affected by many considerations, the guidelines recommend using the CAP severity criteria. Severe CAP includes either one major or at least three minor criteria.
Major criteria are:
- Septic shock requiring vasopressors.
- Respiratory failure requiring mechanical ventilation.
Minor criteria are:
- Respiratory rate greater than or equal to 30 breaths/min.
- Ratio of arterial O2 partial pressure to fractional inspired O2 less than or equal to 250.
- Multilobar infiltrates.
- Confusion/disorientation.
- Uremia (blood urea nitrogen level greater than or equal to 20 mg/dL).
- Leukopenia (white blood cell count less than 4,000 cells/mcL).
- Thrombocytopenia (platelet count less than 100,000 mcL)
- Hypothermia (core temperature less than 36º C).
- Hypotension requiring aggressive fluid resuscitation.
Management and diagnostic testing
Clinicians should use the Pneumonia Severity Index (PSI) and clinical judgment to guide the site of treatment for patients. Gram stain, sputum, and blood culture should not be routinely obtained in an outpatient setting. Legionella antigen should not be routinely obtained unless indicated by epidemiological factors. During influenza season, a rapid influenza assay, preferably a nucleic acid amplification test, should be obtained to help guide treatment.
For patients with severe CAP or risk factors for MRSA or P. aeruginosa, gram stain and culture and Legionella antigen should be obtained to manage antibiotic choices. Also, blood cultures should be obtained for these patients.
Empiric antibiotic therapy should be initiated based on clinical judgment and radiographic confirmation of CAP. Serum procalcitonin should not be used to assess initiation of antibiotic therapy.
Empiric antibiotic therapy
Healthy adults without comorbidities should be treated with monotherapy of either:
- Amoxicillin 1 g three times daily.
- OR doxycycline 100 mg twice daily.
- OR a macrolide (azithromycin 500 mg on first day then 250 mg daily or clarithromycin 500 mg twice daily or clarithromycin extended release 1,000 mg daily) only in areas with pneumococcal resistance to macrolides less than 25%.
Adults with comorbidities such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; or asplenia should be treated with:
- Amoxicillin/clavulanate 500 mg/125 mg three times daily, or amoxicillin/ clavulanate 875 mg/125 mg twice daily, or 2,000 mg/125 mg twice daily, or a cephalosporin (cefpodoxime 200 mg twice daily or cefuroxime 500 mg twice daily); and a macrolide (azithromycin 500 mg on first day then 250 mg daily, clarithromycin [500 mg twice daily or extended release 1,000 mg once daily]), or doxycycline 100 mg twice daily. (Some experts recommend that the first dose of doxycycline should be 200 mg.)
- OR monotherapy with respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily).
Inpatient pneumonia that is not severe, without risk factors for resistant organisms should be treated with:
- Beta-lactam (ampicillin 1 sulbactam 1.5-3 g every 6 h, cefotaxime 1-2 g every 8 h, ceftriaxone 1-2 g daily, or ceftaroline 600 mg every 12 h) and a macrolide (azithromycin 500 mg daily or clarithromycin 500 mg twice daily).
- OR monotherapy with a respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily).
If there is a contraindication for the use of both a macrolide and a fluoroquinolone, then doxycycline can be used instead.
Severe inpatient pneumonia without risk factors for resistant organisms should be treated with combination therapy of either (agents and doses the same as above):
- Beta-lactam and macrolide.
- OR fluoroquinolone and beta-lactam.
It is recommended to not routinely add anaerobic coverage for suspected aspiration pneumonia unless lung abscess or empyema is suspected. Clinicians should identify risk factors for MRSA or P. aeruginosa before adding additional agents.
Duration of antibiotic therapy is determined by the patient achieving clinical stability with no less than 5 days of antibiotics. In adults with symptom resolution within 5-7 days, no additional follow-up chest imaging is recommended. If patients test positive for influenza, then anti-influenza treatment such as oseltamivir should be used in addition to antibiotics regardless of length of influenza symptoms before presentation.
The bottom line
CAP treatment should be based on severity of illness and risk factors for resistant organisms. Blood and sputum cultures are recommended only for patients with severe pneumonia. There have been important changes in the recommendations for antibiotic treatment of CAP, with high-dose amoxicillin recommended for most patients with CAP who are treated as outpatients. Patients who exhibit clinical stability should be treated for at least 5 days and do not require follow up imaging studies.
For a podcast of this guideline, go to iTunes and download the Infectious Diseases Society of America guideline podcast.
Reference
Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67.
Tina Chuong, DO, is a second-year resident in the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.
Newer IL-17 inhibitors make their case in phase 3 nonradiographic axial spondyloarthritis trials
A major gap in interleukin-17 inhibitor (IL-17i) therapy for axial spondyloarthritis (axSpA) was evidence of efficacy in nonradiographic axSpA. At ACR 2019, we saw two different IL-17i studies showing efficacy in nr-axSpA patients. Now we know that both secukinumab and ixekizumab are effective in the full spectrum of axSpA patients (ankylosing spondylitis [AS] and nr-axSpA).
The majority of clinicians would consider both AS and nr-axSpA to be driven by common processes and so drugs that are effective on one should have the same effect in the other as well. Hence the results are not a big surprise. In certain places, an approved indication for use may be important especially for reimbursement purposes. These results are likely to have maximal impact there.
The COAST-X study on ixekizumab was designed in a way similar to that of the C-axSpAnd study with certolizumab pegol. There was an extended 52-week placebo arm to study the natural history of nr-axSpA patients who are not actively treated with biologics. This design was necessary to respond to the Food and Drug Administration’s concern that, in the absence of this prolonged observation on placebo, we cannot be sure that nr-axSpA patients are not spontaneously remitting (not due to biologics).
However, the results here did surprise me. Unlike in the C-axSpAnd trial where only 13% of actively treated patients (on certolizumab pegol) switched to open-label treatment, in the COAST-X study 40% of patients on both doses of ixekizumab opted for open-label treatment. The number of patients moving out of the placebo arm was around 60% (similar in both studies). There are no straightforward factors evidently explaining this discrepancy. Between 15% and 25% of patients who switched had achieved the primary endpoint of ASAS40. Does this reflect that ASAS40 is not acceptable to patients? As the results show responses plateaued after week 16, it could be that the patients who switched might have done so well into the 52-week observation period.
Patients in the COAST-X study had slightly longer disease duration and marginally lower HLA-B27 prevalence (both factors may indicate lower chance of treatment response).
The primary endpoint of ASAS40 was met at weeks 16 and 52 with significantly higher rates seen with ixekizumab than with placebo. Again the response seems to plateau around 16 weeks with minimal gain up to week 52.
The results from the secukinumab PREVENT study are very similar to those of the COAST-X study showing the superiority of secukinumab over placebo in treating nr-axSpA patients. Interestingly, if we do not use the loading dose for secukinumab, there does not seem to be any difference from standard treatment with loading. This may have economic and administrative implications on the decision to use loading doses of secukinumab. We should carefully consider the MEASURE 4 trial results before making decisions on the utility of loading doses. In the MEASURE 4 study on AS patients, although there was no difference between load and no load arms of secukinumab (around 60% ASAS20 response in both arms), there was no significant gain above placebo with both doses. (The primary endpoint was not met.) This is likely due to the high placebo response (47% ASAS20 response). Similarly, we see a high placebo response in the COAST-X study as well, with an ASAS40 response rate of about 40% in active secukinumab arms vs. 30% in the placebo arm.
The number of patients dropping out over the 52-week follow-up period was not discussed in the PREVENT trial presentation.
There is not much here to favor one IL-17i over the other.
Dr. Haroon is codirector of the Spondylitis Program at University Health Network and associate professor of medicine and rheumatology at the University of Toronto. He is chair of the scientific committee of the Spondyloarthritis Research and Treatment Network. He disclosed serving as a consultant for Amgen, AbbVie, Janssen, Lilly, Novartis, and UCB.
A major gap in interleukin-17 inhibitor (IL-17i) therapy for axial spondyloarthritis (axSpA) was evidence of efficacy in nonradiographic axSpA. At ACR 2019, we saw two different IL-17i studies showing efficacy in nr-axSpA patients. Now we know that both secukinumab and ixekizumab are effective in the full spectrum of axSpA patients (ankylosing spondylitis [AS] and nr-axSpA).
The majority of clinicians would consider both AS and nr-axSpA to be driven by common processes and so drugs that are effective on one should have the same effect in the other as well. Hence the results are not a big surprise. In certain places, an approved indication for use may be important especially for reimbursement purposes. These results are likely to have maximal impact there.
The COAST-X study on ixekizumab was designed in a way similar to that of the C-axSpAnd study with certolizumab pegol. There was an extended 52-week placebo arm to study the natural history of nr-axSpA patients who are not actively treated with biologics. This design was necessary to respond to the Food and Drug Administration’s concern that, in the absence of this prolonged observation on placebo, we cannot be sure that nr-axSpA patients are not spontaneously remitting (not due to biologics).
However, the results here did surprise me. Unlike in the C-axSpAnd trial where only 13% of actively treated patients (on certolizumab pegol) switched to open-label treatment, in the COAST-X study 40% of patients on both doses of ixekizumab opted for open-label treatment. The number of patients moving out of the placebo arm was around 60% (similar in both studies). There are no straightforward factors evidently explaining this discrepancy. Between 15% and 25% of patients who switched had achieved the primary endpoint of ASAS40. Does this reflect that ASAS40 is not acceptable to patients? As the results show responses plateaued after week 16, it could be that the patients who switched might have done so well into the 52-week observation period.
Patients in the COAST-X study had slightly longer disease duration and marginally lower HLA-B27 prevalence (both factors may indicate lower chance of treatment response).
The primary endpoint of ASAS40 was met at weeks 16 and 52 with significantly higher rates seen with ixekizumab than with placebo. Again the response seems to plateau around 16 weeks with minimal gain up to week 52.
The results from the secukinumab PREVENT study are very similar to those of the COAST-X study showing the superiority of secukinumab over placebo in treating nr-axSpA patients. Interestingly, if we do not use the loading dose for secukinumab, there does not seem to be any difference from standard treatment with loading. This may have economic and administrative implications on the decision to use loading doses of secukinumab. We should carefully consider the MEASURE 4 trial results before making decisions on the utility of loading doses. In the MEASURE 4 study on AS patients, although there was no difference between load and no load arms of secukinumab (around 60% ASAS20 response in both arms), there was no significant gain above placebo with both doses. (The primary endpoint was not met.) This is likely due to the high placebo response (47% ASAS20 response). Similarly, we see a high placebo response in the COAST-X study as well, with an ASAS40 response rate of about 40% in active secukinumab arms vs. 30% in the placebo arm.
The number of patients dropping out over the 52-week follow-up period was not discussed in the PREVENT trial presentation.
There is not much here to favor one IL-17i over the other.
Dr. Haroon is codirector of the Spondylitis Program at University Health Network and associate professor of medicine and rheumatology at the University of Toronto. He is chair of the scientific committee of the Spondyloarthritis Research and Treatment Network. He disclosed serving as a consultant for Amgen, AbbVie, Janssen, Lilly, Novartis, and UCB.
A major gap in interleukin-17 inhibitor (IL-17i) therapy for axial spondyloarthritis (axSpA) was evidence of efficacy in nonradiographic axSpA. At ACR 2019, we saw two different IL-17i studies showing efficacy in nr-axSpA patients. Now we know that both secukinumab and ixekizumab are effective in the full spectrum of axSpA patients (ankylosing spondylitis [AS] and nr-axSpA).
The majority of clinicians would consider both AS and nr-axSpA to be driven by common processes and so drugs that are effective on one should have the same effect in the other as well. Hence the results are not a big surprise. In certain places, an approved indication for use may be important especially for reimbursement purposes. These results are likely to have maximal impact there.
The COAST-X study on ixekizumab was designed in a way similar to that of the C-axSpAnd study with certolizumab pegol. There was an extended 52-week placebo arm to study the natural history of nr-axSpA patients who are not actively treated with biologics. This design was necessary to respond to the Food and Drug Administration’s concern that, in the absence of this prolonged observation on placebo, we cannot be sure that nr-axSpA patients are not spontaneously remitting (not due to biologics).
However, the results here did surprise me. Unlike in the C-axSpAnd trial where only 13% of actively treated patients (on certolizumab pegol) switched to open-label treatment, in the COAST-X study 40% of patients on both doses of ixekizumab opted for open-label treatment. The number of patients moving out of the placebo arm was around 60% (similar in both studies). There are no straightforward factors evidently explaining this discrepancy. Between 15% and 25% of patients who switched had achieved the primary endpoint of ASAS40. Does this reflect that ASAS40 is not acceptable to patients? As the results show responses plateaued after week 16, it could be that the patients who switched might have done so well into the 52-week observation period.
Patients in the COAST-X study had slightly longer disease duration and marginally lower HLA-B27 prevalence (both factors may indicate lower chance of treatment response).
The primary endpoint of ASAS40 was met at weeks 16 and 52 with significantly higher rates seen with ixekizumab than with placebo. Again the response seems to plateau around 16 weeks with minimal gain up to week 52.
The results from the secukinumab PREVENT study are very similar to those of the COAST-X study showing the superiority of secukinumab over placebo in treating nr-axSpA patients. Interestingly, if we do not use the loading dose for secukinumab, there does not seem to be any difference from standard treatment with loading. This may have economic and administrative implications on the decision to use loading doses of secukinumab. We should carefully consider the MEASURE 4 trial results before making decisions on the utility of loading doses. In the MEASURE 4 study on AS patients, although there was no difference between load and no load arms of secukinumab (around 60% ASAS20 response in both arms), there was no significant gain above placebo with both doses. (The primary endpoint was not met.) This is likely due to the high placebo response (47% ASAS20 response). Similarly, we see a high placebo response in the COAST-X study as well, with an ASAS40 response rate of about 40% in active secukinumab arms vs. 30% in the placebo arm.
The number of patients dropping out over the 52-week follow-up period was not discussed in the PREVENT trial presentation.
There is not much here to favor one IL-17i over the other.
Dr. Haroon is codirector of the Spondylitis Program at University Health Network and associate professor of medicine and rheumatology at the University of Toronto. He is chair of the scientific committee of the Spondyloarthritis Research and Treatment Network. He disclosed serving as a consultant for Amgen, AbbVie, Janssen, Lilly, Novartis, and UCB.
An alarming number of bipolar disorder diagnoses or something else?
During a particularly busy day in my inpatient and outpatient practice, I realized that nearly every one of the patients had been given the diagnosis of bipolar disorder at one point or another. The interesting thing is this wasn’t an unusual day.
Nearly all of my patients and their family members have been given the diagnosis of bipolar disorder. Because prevalence of bipolar affective disorders is a little over 2%, this seemed a little odd. Could there be an epidemic of bipolar disorder in the area? Should someone sound the alarm on this unique cluster and get Julia Roberts ready? Unfortunately, the story behind this mystery is a little less sexy but nevertheless interesting.
When I probe more into what symptoms might have led to the diagnosis of bipolar disorder, I most often get some sort of answer about being easily angered (“I’m fine 1 minute and the next minute I’m yelling at my mom”) or mood changing from 1 minute to the next. Rarely do they tell me about sleeping less, increased energy, change in mood (elation, anger, irritability), increase in activity level, and increased pleasurable though dangerous activities all happening around the same time(s). So what is going on?
Beginning in the 1990s, a debate about the phenotypic presentation of pediatric bipolar disorder polarized the field. It was theorized that mania could present with severe nonepisodic irritability with extended periods of very rapid mood cycling within the day as opposed to discrete episodic mood cycles in children and adolescents. With this broader conceptualization in the United States, the rate of bipolar diagnosis increased by over 40 times in less than a decade.1 Similarly, the use of mood stabilizers and atypical antipsychotics in children also rose substantially.2
To help assess if severe nonepisodic irritability belongs in the spectrum of bipolar disorders, the National Institutes of Mental Health proposed a syndrome called “Severe Mood Dysregulation” or SMD, to promote the study of children with this phenotype. In longitudinal studies, Stringaris et al. compared rates of manic episodes in youth with SMD versus bipolar disorder over 2 years and found only one youth (1%) with SMD who presented with manic, hypomanic, or mixed episodes, compared with 58 (62%) with bipolar disorder.3 Leibenluft et al.showed that chronic irritability during early adolescence predicted ADHD at late adolescence and major depressive disorder in early adulthood whereas episodic irritability predicted mania.4 Twenty-year follow-up of the same sample showed chronic irritability in adolescence predicted dysthymia, generalized anxiety disorders, and major depressive disorder.5 Other longitudinal studies essentially have shown the same results.6
At this point, the question of whether chronic irritability is a part of the bipolar spectrum disorder is largely resolved – 7 The diagnosis emphasizes the episodic nature of the illness, and that irritability would wax and wane with other manic symptoms such as changes in energy and sleep. And the ultrarapid mood changes (mood changes within the day) appear to describe mood fluctuations within a manic episode as opposed to each change being a separate episode.
So, most likely, my patients were caught in a time of uncertainty before data were able to clarify their phenotype.
Dr. Chung is a child and adolescent psychiatrist at the University of Vermont Medical Center, Burlington, and practices at Champlain Valley Physician’s Hospital in Plattsburgh, N.Y. Email him at pdnews@mdedge.com.
References
1. Biol Psychiatry. 2007 Jul 15;62(2):107–14.
2. JAMA Psychiatry. 2015 Sep;72(9):859-60.
3. J Am Acad Child Adolesc Psychiatry. 2010 Apr;49(4):397-405.
4. J Child Adolesc Psychopharmacol 2006;16(4):456-66.
5. Am J Psychiatry. 2009 Sep;166(9):1048-54.
6. Biol Psychiatry. 2006 Nov 1;60(9):991-7.
7. Bipolar Disord. 2017 Nov;19(7):524-43.
During a particularly busy day in my inpatient and outpatient practice, I realized that nearly every one of the patients had been given the diagnosis of bipolar disorder at one point or another. The interesting thing is this wasn’t an unusual day.
Nearly all of my patients and their family members have been given the diagnosis of bipolar disorder. Because prevalence of bipolar affective disorders is a little over 2%, this seemed a little odd. Could there be an epidemic of bipolar disorder in the area? Should someone sound the alarm on this unique cluster and get Julia Roberts ready? Unfortunately, the story behind this mystery is a little less sexy but nevertheless interesting.
When I probe more into what symptoms might have led to the diagnosis of bipolar disorder, I most often get some sort of answer about being easily angered (“I’m fine 1 minute and the next minute I’m yelling at my mom”) or mood changing from 1 minute to the next. Rarely do they tell me about sleeping less, increased energy, change in mood (elation, anger, irritability), increase in activity level, and increased pleasurable though dangerous activities all happening around the same time(s). So what is going on?
Beginning in the 1990s, a debate about the phenotypic presentation of pediatric bipolar disorder polarized the field. It was theorized that mania could present with severe nonepisodic irritability with extended periods of very rapid mood cycling within the day as opposed to discrete episodic mood cycles in children and adolescents. With this broader conceptualization in the United States, the rate of bipolar diagnosis increased by over 40 times in less than a decade.1 Similarly, the use of mood stabilizers and atypical antipsychotics in children also rose substantially.2
To help assess if severe nonepisodic irritability belongs in the spectrum of bipolar disorders, the National Institutes of Mental Health proposed a syndrome called “Severe Mood Dysregulation” or SMD, to promote the study of children with this phenotype. In longitudinal studies, Stringaris et al. compared rates of manic episodes in youth with SMD versus bipolar disorder over 2 years and found only one youth (1%) with SMD who presented with manic, hypomanic, or mixed episodes, compared with 58 (62%) with bipolar disorder.3 Leibenluft et al.showed that chronic irritability during early adolescence predicted ADHD at late adolescence and major depressive disorder in early adulthood whereas episodic irritability predicted mania.4 Twenty-year follow-up of the same sample showed chronic irritability in adolescence predicted dysthymia, generalized anxiety disorders, and major depressive disorder.5 Other longitudinal studies essentially have shown the same results.6
At this point, the question of whether chronic irritability is a part of the bipolar spectrum disorder is largely resolved – 7 The diagnosis emphasizes the episodic nature of the illness, and that irritability would wax and wane with other manic symptoms such as changes in energy and sleep. And the ultrarapid mood changes (mood changes within the day) appear to describe mood fluctuations within a manic episode as opposed to each change being a separate episode.
So, most likely, my patients were caught in a time of uncertainty before data were able to clarify their phenotype.
Dr. Chung is a child and adolescent psychiatrist at the University of Vermont Medical Center, Burlington, and practices at Champlain Valley Physician’s Hospital in Plattsburgh, N.Y. Email him at pdnews@mdedge.com.
References
1. Biol Psychiatry. 2007 Jul 15;62(2):107–14.
2. JAMA Psychiatry. 2015 Sep;72(9):859-60.
3. J Am Acad Child Adolesc Psychiatry. 2010 Apr;49(4):397-405.
4. J Child Adolesc Psychopharmacol 2006;16(4):456-66.
5. Am J Psychiatry. 2009 Sep;166(9):1048-54.
6. Biol Psychiatry. 2006 Nov 1;60(9):991-7.
7. Bipolar Disord. 2017 Nov;19(7):524-43.
During a particularly busy day in my inpatient and outpatient practice, I realized that nearly every one of the patients had been given the diagnosis of bipolar disorder at one point or another. The interesting thing is this wasn’t an unusual day.
Nearly all of my patients and their family members have been given the diagnosis of bipolar disorder. Because prevalence of bipolar affective disorders is a little over 2%, this seemed a little odd. Could there be an epidemic of bipolar disorder in the area? Should someone sound the alarm on this unique cluster and get Julia Roberts ready? Unfortunately, the story behind this mystery is a little less sexy but nevertheless interesting.
When I probe more into what symptoms might have led to the diagnosis of bipolar disorder, I most often get some sort of answer about being easily angered (“I’m fine 1 minute and the next minute I’m yelling at my mom”) or mood changing from 1 minute to the next. Rarely do they tell me about sleeping less, increased energy, change in mood (elation, anger, irritability), increase in activity level, and increased pleasurable though dangerous activities all happening around the same time(s). So what is going on?
Beginning in the 1990s, a debate about the phenotypic presentation of pediatric bipolar disorder polarized the field. It was theorized that mania could present with severe nonepisodic irritability with extended periods of very rapid mood cycling within the day as opposed to discrete episodic mood cycles in children and adolescents. With this broader conceptualization in the United States, the rate of bipolar diagnosis increased by over 40 times in less than a decade.1 Similarly, the use of mood stabilizers and atypical antipsychotics in children also rose substantially.2
To help assess if severe nonepisodic irritability belongs in the spectrum of bipolar disorders, the National Institutes of Mental Health proposed a syndrome called “Severe Mood Dysregulation” or SMD, to promote the study of children with this phenotype. In longitudinal studies, Stringaris et al. compared rates of manic episodes in youth with SMD versus bipolar disorder over 2 years and found only one youth (1%) with SMD who presented with manic, hypomanic, or mixed episodes, compared with 58 (62%) with bipolar disorder.3 Leibenluft et al.showed that chronic irritability during early adolescence predicted ADHD at late adolescence and major depressive disorder in early adulthood whereas episodic irritability predicted mania.4 Twenty-year follow-up of the same sample showed chronic irritability in adolescence predicted dysthymia, generalized anxiety disorders, and major depressive disorder.5 Other longitudinal studies essentially have shown the same results.6
At this point, the question of whether chronic irritability is a part of the bipolar spectrum disorder is largely resolved – 7 The diagnosis emphasizes the episodic nature of the illness, and that irritability would wax and wane with other manic symptoms such as changes in energy and sleep. And the ultrarapid mood changes (mood changes within the day) appear to describe mood fluctuations within a manic episode as opposed to each change being a separate episode.
So, most likely, my patients were caught in a time of uncertainty before data were able to clarify their phenotype.
Dr. Chung is a child and adolescent psychiatrist at the University of Vermont Medical Center, Burlington, and practices at Champlain Valley Physician’s Hospital in Plattsburgh, N.Y. Email him at pdnews@mdedge.com.
References
1. Biol Psychiatry. 2007 Jul 15;62(2):107–14.
2. JAMA Psychiatry. 2015 Sep;72(9):859-60.
3. J Am Acad Child Adolesc Psychiatry. 2010 Apr;49(4):397-405.
4. J Child Adolesc Psychopharmacol 2006;16(4):456-66.
5. Am J Psychiatry. 2009 Sep;166(9):1048-54.
6. Biol Psychiatry. 2006 Nov 1;60(9):991-7.
7. Bipolar Disord. 2017 Nov;19(7):524-43.
Proposed RESPONSE Act targets potential shooters
As I’m writing, my Twitter feed announces yet another public shooting, this one at a Walmart in Oklahoma. It’s a problem that gets worse as it gets more attention and the argument over how to approach the issue of mass shootings still continues down two separate and distinct pathways: Is this the result of too-easy access to firearms or is it one of untreated mental illness?
Sen. John Cornyn (R-Tex.) spoke on the Senate floor on Oct. 23, 2019, about new legislation he is cosponsoring in the aftermath of two mass shootings in Texas this past August. The Restoring, Enhancing, Strengthening, and Promoting Our Nation’s Safety Efforts Act of 2019 (S. 2690), or the RESPONSE Act, is designed to “reduce mass violence, strengthen mental health collaboration in communities, improve school safety, and for other purposes.” Sen. Cornyn notes that in the aftermath of those shootings he met with his constituents and he heard a common refrain: Please do something.
“Unfortunately, there is no quick fix, no simple answer, instead we are left to look at the factors that led to these attacks and to try to do something to prevent the sequence of events from playing out again in the future,” Sen. Cornyn said.
“While mental illness is not the prevailing cause of mass violence, enhanced mental health resources are critical to saving lives,” he said, adding that most gun deaths are from suicide. In his speech, he outlined the issues it would address – and despite his statement that mental illness is not the cause of mass violence – he went on to elaborate on the issues that the bill would address.
“First, this legislation takes aim at unlicensed firearms dealers who are breaking the law,” he said. This legislation would create a task force to prosecute those who buy and sell firearms through unlicensed dealers, and he notes that one of the Texas shooters was denied a gun by a licensed firearms dealer before purchasing one from an unlicensed dealer. That Sen. Cornyn’s proposed legislation would not create any new gun legislation is not a surprise: he has an A+ rating from the National Rifle Association and his website’s fun facts include the statement: “Sen. Cornyn owns several firearms and hunts as often as he can.”
The rest of the RESPONSE Act takes aim at those who have or might have psychiatric disorders or a tendency toward violence. Sen. Cornyn noted that the act would expand assisted outpatient treatment (AOT, or outpatient civil commitment). He referenced this as a way for families to get care for their loved ones in the community rather than in a hospital and did not allude to the involuntary nature of the treatment.
Marvin Swartz, MD, is professor of psychiatry at Duke University, Durham, N.C., and lead investigator on outcome studies following the implementation of outpatient civil commitment legislation.
“AOT may be justified in improving treatment adherence and service provision,” Dr. Swartz noted, “but there is no direct line to serious violence. The violence we documented as reduced were mainly minor acts of interpersonal violence – pushing and shoving – what we call minor acts of violence. There is no evidence that AOT is a remedy to serious acts of violence – mass shootings included.”
In addition, Sen. Cornyn noted there would be expanded crisis intervention teams and increased coordination between mental health providers and law enforcement. Furthermore, the bill would make schools safer by identifying students whose behavior indicated a threat of violence and providing those students with the services they need. This would be done “by promoting best practices within our schools and promoting Internet safety.”
Finally, Sen. Cornyn talked about using social media as a means to identify those who might be a danger. “Because so often these shooters advertise on social media ... this legislation includes provisions to [ensure] that law enforcement can receive timely information about threats made online.”
The bill already has garnered both support and opposition. It has been supported by the National Council for Behavioral Health, the National Alliance on Mental Illness (NAMI), and the Treatment Advocacy Center. Those opposed to the legislation include the National Disability Rights Network, the American Association of People with Disabilities, the National Council on Independent Living, the Disability Rights Education & Defense Fund, the Bazelon Center for Mental Health Law, and the Autistic Self Advocacy Network. The American Psychiatric Association has not made a statement on the proposed legislation as of this writing.
The National Council for Behavioral Health posted an endorsement on its website. It notes: “The RESPONSE Act authorizes up to $10 million of existing funds in the Department of Justice for partnership between law enforcement and mental health providers to increase access to long-acting medically assisted treatment. Additionally, it requires the Department of Health and Human Services (HHS) to develop and disseminate guidance for states to fund mental health programs and crisis intervention teams through Medicaid as well as to issue a report to Congress on best practices to expand the mental health workforce. These provisions aim to divert more individuals from incarceration and will create more opportunities for community-based treatment and recovery.”
There is no question that psychiatric treatment for those with mental illness is underfunded and often inaccessible. But while it is true that some individuals become violent when they are ill, most do not, and targeting those one in five Americans who suffer from a psychiatric disorder each year in an effort to identify, then thwart, the rare mass murderer among us makes no sense.
Acts of mass violence remain rare. In 2018, the year we had a record-breaking number of mass shootings, there were 12 mass murders in the United States, according to the criteria used by Mother Jones, and 27 active shooter incidents using the FBI’s criteria. Approximately half of all mass shooters showed signs of mental illness prior to the shooting and of those, some had never come to the attention of mental health professionals in a way that would have predicted violence. While linking mass violence to mental illness may seem reasonable, the numbers just don’t make sense and targeting this presumed link between mental illness and mass violence is stigmatizing.
The text of the RESPONSE Act reveals proposed legislation that is perhaps more thoughtful than Sen. Cornyn’s speech suggested; the bill starts with funding services for those with psychiatric disorders who are being released from the correctional system, a population that may be at higher risk for acts of violence. The funding for outpatient civil commitment is worded in such a way that it is hard to know exactly what is required. The bill starts by mandating that each state must use 10% of the funding it gets from this bill for court-ordered treatment (AOT), but then lists alternative ways states may use that 10%, including “otherwise support evidence-based programs that address the needs of eligible patients.” In all, the proposed legislation is long and complex and attempts to address issues related to terrorism, the Internet, mental health, and the educational system. It’s an ambitious use of $10 million a year for our entire country.
At a time when mental health care is desperately underfunded and many are unable to access treatment, it is tempting to endorse any legislation that improves funding. But does it serve society to endorse legislation that suggests psychiatrists can prevent mass shootings? Does that ultimately serve our patients?
Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle of Inpatient Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016), and has a private practice in Baltimore.
As I’m writing, my Twitter feed announces yet another public shooting, this one at a Walmart in Oklahoma. It’s a problem that gets worse as it gets more attention and the argument over how to approach the issue of mass shootings still continues down two separate and distinct pathways: Is this the result of too-easy access to firearms or is it one of untreated mental illness?
Sen. John Cornyn (R-Tex.) spoke on the Senate floor on Oct. 23, 2019, about new legislation he is cosponsoring in the aftermath of two mass shootings in Texas this past August. The Restoring, Enhancing, Strengthening, and Promoting Our Nation’s Safety Efforts Act of 2019 (S. 2690), or the RESPONSE Act, is designed to “reduce mass violence, strengthen mental health collaboration in communities, improve school safety, and for other purposes.” Sen. Cornyn notes that in the aftermath of those shootings he met with his constituents and he heard a common refrain: Please do something.
“Unfortunately, there is no quick fix, no simple answer, instead we are left to look at the factors that led to these attacks and to try to do something to prevent the sequence of events from playing out again in the future,” Sen. Cornyn said.
“While mental illness is not the prevailing cause of mass violence, enhanced mental health resources are critical to saving lives,” he said, adding that most gun deaths are from suicide. In his speech, he outlined the issues it would address – and despite his statement that mental illness is not the cause of mass violence – he went on to elaborate on the issues that the bill would address.
“First, this legislation takes aim at unlicensed firearms dealers who are breaking the law,” he said. This legislation would create a task force to prosecute those who buy and sell firearms through unlicensed dealers, and he notes that one of the Texas shooters was denied a gun by a licensed firearms dealer before purchasing one from an unlicensed dealer. That Sen. Cornyn’s proposed legislation would not create any new gun legislation is not a surprise: he has an A+ rating from the National Rifle Association and his website’s fun facts include the statement: “Sen. Cornyn owns several firearms and hunts as often as he can.”
The rest of the RESPONSE Act takes aim at those who have or might have psychiatric disorders or a tendency toward violence. Sen. Cornyn noted that the act would expand assisted outpatient treatment (AOT, or outpatient civil commitment). He referenced this as a way for families to get care for their loved ones in the community rather than in a hospital and did not allude to the involuntary nature of the treatment.
Marvin Swartz, MD, is professor of psychiatry at Duke University, Durham, N.C., and lead investigator on outcome studies following the implementation of outpatient civil commitment legislation.
“AOT may be justified in improving treatment adherence and service provision,” Dr. Swartz noted, “but there is no direct line to serious violence. The violence we documented as reduced were mainly minor acts of interpersonal violence – pushing and shoving – what we call minor acts of violence. There is no evidence that AOT is a remedy to serious acts of violence – mass shootings included.”
In addition, Sen. Cornyn noted there would be expanded crisis intervention teams and increased coordination between mental health providers and law enforcement. Furthermore, the bill would make schools safer by identifying students whose behavior indicated a threat of violence and providing those students with the services they need. This would be done “by promoting best practices within our schools and promoting Internet safety.”
Finally, Sen. Cornyn talked about using social media as a means to identify those who might be a danger. “Because so often these shooters advertise on social media ... this legislation includes provisions to [ensure] that law enforcement can receive timely information about threats made online.”
The bill already has garnered both support and opposition. It has been supported by the National Council for Behavioral Health, the National Alliance on Mental Illness (NAMI), and the Treatment Advocacy Center. Those opposed to the legislation include the National Disability Rights Network, the American Association of People with Disabilities, the National Council on Independent Living, the Disability Rights Education & Defense Fund, the Bazelon Center for Mental Health Law, and the Autistic Self Advocacy Network. The American Psychiatric Association has not made a statement on the proposed legislation as of this writing.
The National Council for Behavioral Health posted an endorsement on its website. It notes: “The RESPONSE Act authorizes up to $10 million of existing funds in the Department of Justice for partnership between law enforcement and mental health providers to increase access to long-acting medically assisted treatment. Additionally, it requires the Department of Health and Human Services (HHS) to develop and disseminate guidance for states to fund mental health programs and crisis intervention teams through Medicaid as well as to issue a report to Congress on best practices to expand the mental health workforce. These provisions aim to divert more individuals from incarceration and will create more opportunities for community-based treatment and recovery.”
There is no question that psychiatric treatment for those with mental illness is underfunded and often inaccessible. But while it is true that some individuals become violent when they are ill, most do not, and targeting those one in five Americans who suffer from a psychiatric disorder each year in an effort to identify, then thwart, the rare mass murderer among us makes no sense.
Acts of mass violence remain rare. In 2018, the year we had a record-breaking number of mass shootings, there were 12 mass murders in the United States, according to the criteria used by Mother Jones, and 27 active shooter incidents using the FBI’s criteria. Approximately half of all mass shooters showed signs of mental illness prior to the shooting and of those, some had never come to the attention of mental health professionals in a way that would have predicted violence. While linking mass violence to mental illness may seem reasonable, the numbers just don’t make sense and targeting this presumed link between mental illness and mass violence is stigmatizing.
The text of the RESPONSE Act reveals proposed legislation that is perhaps more thoughtful than Sen. Cornyn’s speech suggested; the bill starts with funding services for those with psychiatric disorders who are being released from the correctional system, a population that may be at higher risk for acts of violence. The funding for outpatient civil commitment is worded in such a way that it is hard to know exactly what is required. The bill starts by mandating that each state must use 10% of the funding it gets from this bill for court-ordered treatment (AOT), but then lists alternative ways states may use that 10%, including “otherwise support evidence-based programs that address the needs of eligible patients.” In all, the proposed legislation is long and complex and attempts to address issues related to terrorism, the Internet, mental health, and the educational system. It’s an ambitious use of $10 million a year for our entire country.
At a time when mental health care is desperately underfunded and many are unable to access treatment, it is tempting to endorse any legislation that improves funding. But does it serve society to endorse legislation that suggests psychiatrists can prevent mass shootings? Does that ultimately serve our patients?
Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle of Inpatient Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016), and has a private practice in Baltimore.
As I’m writing, my Twitter feed announces yet another public shooting, this one at a Walmart in Oklahoma. It’s a problem that gets worse as it gets more attention and the argument over how to approach the issue of mass shootings still continues down two separate and distinct pathways: Is this the result of too-easy access to firearms or is it one of untreated mental illness?
Sen. John Cornyn (R-Tex.) spoke on the Senate floor on Oct. 23, 2019, about new legislation he is cosponsoring in the aftermath of two mass shootings in Texas this past August. The Restoring, Enhancing, Strengthening, and Promoting Our Nation’s Safety Efforts Act of 2019 (S. 2690), or the RESPONSE Act, is designed to “reduce mass violence, strengthen mental health collaboration in communities, improve school safety, and for other purposes.” Sen. Cornyn notes that in the aftermath of those shootings he met with his constituents and he heard a common refrain: Please do something.
“Unfortunately, there is no quick fix, no simple answer, instead we are left to look at the factors that led to these attacks and to try to do something to prevent the sequence of events from playing out again in the future,” Sen. Cornyn said.
“While mental illness is not the prevailing cause of mass violence, enhanced mental health resources are critical to saving lives,” he said, adding that most gun deaths are from suicide. In his speech, he outlined the issues it would address – and despite his statement that mental illness is not the cause of mass violence – he went on to elaborate on the issues that the bill would address.
“First, this legislation takes aim at unlicensed firearms dealers who are breaking the law,” he said. This legislation would create a task force to prosecute those who buy and sell firearms through unlicensed dealers, and he notes that one of the Texas shooters was denied a gun by a licensed firearms dealer before purchasing one from an unlicensed dealer. That Sen. Cornyn’s proposed legislation would not create any new gun legislation is not a surprise: he has an A+ rating from the National Rifle Association and his website’s fun facts include the statement: “Sen. Cornyn owns several firearms and hunts as often as he can.”
The rest of the RESPONSE Act takes aim at those who have or might have psychiatric disorders or a tendency toward violence. Sen. Cornyn noted that the act would expand assisted outpatient treatment (AOT, or outpatient civil commitment). He referenced this as a way for families to get care for their loved ones in the community rather than in a hospital and did not allude to the involuntary nature of the treatment.
Marvin Swartz, MD, is professor of psychiatry at Duke University, Durham, N.C., and lead investigator on outcome studies following the implementation of outpatient civil commitment legislation.
“AOT may be justified in improving treatment adherence and service provision,” Dr. Swartz noted, “but there is no direct line to serious violence. The violence we documented as reduced were mainly minor acts of interpersonal violence – pushing and shoving – what we call minor acts of violence. There is no evidence that AOT is a remedy to serious acts of violence – mass shootings included.”
In addition, Sen. Cornyn noted there would be expanded crisis intervention teams and increased coordination between mental health providers and law enforcement. Furthermore, the bill would make schools safer by identifying students whose behavior indicated a threat of violence and providing those students with the services they need. This would be done “by promoting best practices within our schools and promoting Internet safety.”
Finally, Sen. Cornyn talked about using social media as a means to identify those who might be a danger. “Because so often these shooters advertise on social media ... this legislation includes provisions to [ensure] that law enforcement can receive timely information about threats made online.”
The bill already has garnered both support and opposition. It has been supported by the National Council for Behavioral Health, the National Alliance on Mental Illness (NAMI), and the Treatment Advocacy Center. Those opposed to the legislation include the National Disability Rights Network, the American Association of People with Disabilities, the National Council on Independent Living, the Disability Rights Education & Defense Fund, the Bazelon Center for Mental Health Law, and the Autistic Self Advocacy Network. The American Psychiatric Association has not made a statement on the proposed legislation as of this writing.
The National Council for Behavioral Health posted an endorsement on its website. It notes: “The RESPONSE Act authorizes up to $10 million of existing funds in the Department of Justice for partnership between law enforcement and mental health providers to increase access to long-acting medically assisted treatment. Additionally, it requires the Department of Health and Human Services (HHS) to develop and disseminate guidance for states to fund mental health programs and crisis intervention teams through Medicaid as well as to issue a report to Congress on best practices to expand the mental health workforce. These provisions aim to divert more individuals from incarceration and will create more opportunities for community-based treatment and recovery.”
There is no question that psychiatric treatment for those with mental illness is underfunded and often inaccessible. But while it is true that some individuals become violent when they are ill, most do not, and targeting those one in five Americans who suffer from a psychiatric disorder each year in an effort to identify, then thwart, the rare mass murderer among us makes no sense.
Acts of mass violence remain rare. In 2018, the year we had a record-breaking number of mass shootings, there were 12 mass murders in the United States, according to the criteria used by Mother Jones, and 27 active shooter incidents using the FBI’s criteria. Approximately half of all mass shooters showed signs of mental illness prior to the shooting and of those, some had never come to the attention of mental health professionals in a way that would have predicted violence. While linking mass violence to mental illness may seem reasonable, the numbers just don’t make sense and targeting this presumed link between mental illness and mass violence is stigmatizing.
The text of the RESPONSE Act reveals proposed legislation that is perhaps more thoughtful than Sen. Cornyn’s speech suggested; the bill starts with funding services for those with psychiatric disorders who are being released from the correctional system, a population that may be at higher risk for acts of violence. The funding for outpatient civil commitment is worded in such a way that it is hard to know exactly what is required. The bill starts by mandating that each state must use 10% of the funding it gets from this bill for court-ordered treatment (AOT), but then lists alternative ways states may use that 10%, including “otherwise support evidence-based programs that address the needs of eligible patients.” In all, the proposed legislation is long and complex and attempts to address issues related to terrorism, the Internet, mental health, and the educational system. It’s an ambitious use of $10 million a year for our entire country.
At a time when mental health care is desperately underfunded and many are unable to access treatment, it is tempting to endorse any legislation that improves funding. But does it serve society to endorse legislation that suggests psychiatrists can prevent mass shootings? Does that ultimately serve our patients?
Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle of Inpatient Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016), and has a private practice in Baltimore.
