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Inpatient telemedicine can help address hospitalist pain points
COVID-19 has increased confidence in the technology
Since the advent of COVID-19, health care has seen an unprecedented rise in virtual health. Telemedicine has come to the forefront of our conversations, and there are many speculations around its future state. One such discussion is around the sustainability and expansion of inpatient telemedicine programs post COVID, and if – and how – it is going to be helpful for health care.
Consider the following scenarios:
Scenario 1
A patient presents to an emergency department of a small community hospital. He needs to be seen by a specialist, but (s)he is not available, so patient gets transferred out to the ED of a different hospital several miles away from his hometown.
He is evaluated in the second ED by the specialist, has repeat testing done – some of those tests were already completed at the first hospital. After evaluating him, the specialist recommends that he does not need to be admitted to the hospital and can be safely followed up as an outpatient. The patient does not require any further intervention and is discharged from the ED.
Scenario 2
Dr. N is a hospitalist in a rural hospital that does not have intensivist support at night. She works 7 on/7 off and is on call 24/7 during her “on” week. Dr. N cannot be physically present in the hospital 24/7. She receives messages from the hospital around the clock and feels that this call schedule is no longer sustainable. She doesn’t feel comfortable admitting patients in the ICU who come to the hospital at night without physically seeing them and without ICU backup. Therefore, some of the patients who are sick enough to be admitted in ICU for closer monitoring but can be potentially handled in this rural hospital get transferred out to a different hospital.
Dr. N has been asking the hospital to provide her intensivist back up at night and to give her some flexibility in the call schedule. However, from hospital’s perspective, the volume isn’t high enough to hire a dedicated nocturnist, and because the hospital is in the small rural area, it is having a hard time attracting more intensivists. After multiple conversations between both parties, Dr. N finally resigns.
Scenario 3
Dr. A is a specialist who is on call covering different hospitals and seeing patients in clinic. His call is getting busier. He has received many new consults and also has to follow up on his other patients in hospital who he saw a day prior.
Dr. A started receiving many pages from the hospitals – some of his patients and their families are anxiously waiting on him so that he can let them go home once he sees them, while some are waiting to know what the next steps and plan of action are. He ends up canceling some of his clinic patients who had scheduled an appointment with him 3, 4, or even 5 months ago. It’s already afternoon.
Dr. A now drives to one hospital, sees his new consults, orders tests which may or may not get results the same day, follows up on other patients, reviews their test results, modifies treatment plans for some while clearing other patients for discharge. He then drives to the other hospital and follows the same process. Some of the patients aren’t happy because of the long wait, a few couldn’t arrange for the ride to go home and ended up staying in hospital 1 extra night, while the ER is getting backlogged waiting on discharges.
These scenarios highlight some of the important and prevalent pain points in health care as shown in Figure 1.
Scenario 1 and part of scenario 2 describe what is called potentially avoidable interfacility transfers. One study showed that around 8% of transferred patients (transferred from one ED to another) were discharged after ED evaluation in the second hospital, meaning they could have been retained locally without necessarily getting transferred if they could have been evaluated by the specialist.1
Transferring a patient from one hospital to another isn’t as simple as picking up a person from point A and dropping him off at point B. Rather it’s a very complicated, high-risk, capital-intensive, and time-consuming process that leads not only to excessive cost involved around transfer but also adds additional stress and burden on the patient and family. In these scenarios, having a specialist available via teleconsult could have eliminated much of this hassle and cost, allowing the patient to stay locally close to family and get access to necessary medical expertise from any part of the country in a timely manner.
Scenario 2 talks about the recruitment and retention challenges in low-volume, low-resourced locations because of call schedule and the lack of specialty support. It is reported in one study that 19% of common hospitalist admissions happen between 7:00 p.m. and 7:00 a.m. Eighty percent of admissions occurred prior to midnight. Nonrural facilities averaged 6.69 hospitalist admissions per night in that study, whereas rural facilities averaged 1.35 admissions.2 It’s like a double-edged sword for such facilities. While having a dedicated nocturnist is not a sustainable model for these hospitals, not having adequate support at night impacts physician wellness, which is already costing hospitals billions of dollars as well as leading to physician turnover: It could cost a hospital somewhere between $500,000 and $1 million to replace just one physician.3 Hence, the potential exists for a telehospitalist program in these settings to address this dilemma.
Scenario 3 sheds light on the operational issues resulting in reduced patient satisfaction and lost revenues, both on the outpatient and inpatient sides by cancellation of office visits and ED backlog. Telemedicine use in these situations can improve the turnaround time of physicians who can see some of those patients while staying at one location as they wait on other patients to show up in the clinic or wait on the operation room crew, or the procedure kit etcetera, hence improving the length of stay, ED throughput, patient satisfaction, and quality of care. This also can improve overall workflow and the wellness of physicians.
One common outcome in all these scenarios is emergency department overcrowding. There have been multiple studies that suggest that ED overcrowding can result in increased costs, lost revenues, and poor clinical outcomes, including delayed administration of antibiotics, delayed administration of analgesics to suffering patients, increased hospital length of stay, and even increased mortality.4-6 A crowded ED limits the ability of an institution to accept referrals and increases medicolegal risks. (See Figure 2.)
Another study showed that a 1-hour reduction in ED boarding time would result in over $9,000 of additional revenue by reducing ambulance diversion and the number of patients who left without being seen.7 Another found that using tele-emergency services can potentially result in net savings of $3,823 per avoided transfer, while accounting for the costs related to tele-emergency technology, hospital revenues, and patient-associated savings.8
There are other instances where gaps in staffing and cracks in workflow can have a negative impact on hospital operations. For example, the busier hospitals that do have a dedicated nocturnist also struggle with physician retention, since such hospitals have higher volumes and higher cross-coverage needs, and are therefore hard to manage by just one single physician at night. Since these are temporary surges, hiring another full-time nocturnist is not a viable option for the hospitals and is considered an expense in many places.
Similarly, during day shift, if a physician goes on vacation or there are surges in patient volumes, hiring a locum tenens hospitalist can be an expensive option, since the cost also includes travel and lodging. In many instances, hiring locum tenens in a given time frame is also not possible, and it leaves the physicians short staffed, fueling both physicians’ and patients’ dissatisfaction and leading to other operational and safety challenges, which I highlighted above.
Telemedicine services in these situations can provide cross-coverage while nocturnists can focus on admissions and other acute issues. Also, when physicians are on vacation or there is surge capacity (that can be forecast by using various predictive analytics models), hospitals can make plans accordingly and make use of telemedicine services. For example, Providence St. Joseph Health reported improvement in timeliness and efficiency of care after implementation of a telehospitalist program. Their 2-year study at a partner site showed a 59% improvement in patients admitted prior to midnight, about $547,000 improvement in first-day revenue capture, an increase in total revenue days and comparable patient experience scores, and a substantial increase in inpatient census and case mix index.9
Other institutions have successfully implemented some inpatient telemedicine programs – such as telepsych, telestroke, and tele-ICU – and some have also reported positive outcomes in terms of patient satisfaction, improved access, reduced length of stay in the ED, and improved quality metrics. Emory Healthcare in Atlanta reported $4.6 million savings in Medicare costs over a 15-month period from adopting a telemedicine model in the ICU, and a reduction in 60-day readmissions by 2.1%.10 Similarly, another study showed that one large health care center improved its direct contribution margins by 376% (from $7.9 million to $37.7 million) because of increased case volume, shorter lengths of stay, and higher case revenue relative to direct costs. When combined with a logistics center, they reported improved contribution margins by 665% (from $7.9 million to $60.6 million).11
There are barriers to the integration and implementation of inpatient telemedicine, including regulations, reimbursement, physician licensing, adoption of technology, and trust among staff and patients. However, I am cautiously optimistic that increased use of telehealth during the COVID-19 pandemic has allowed patients, physicians, nurses, and health care workers and leaders to gain experience with this technology, which will help them gain confidence and reduce hesitation in adapting to this new digital platform. Ultimately, the extent to which telemedicine is able to positively impact patient care will revolve around overcoming these barriers, likely through an evolution of both the technology itself and the attitudes and regulations surrounding it.
I do not suggest that telemedicine should replace the in-person encounter, but it can be implemented and used successfully in addressing the pain points in U.S. health care. (See Figure 3.)
To that end, the purpose of this article is to spark discussion around different ways of implementing telemedicine in inpatient settings to solve many of the challenges that health care faces today.
Dr. Zia is an internal medicine board-certified physician, serving as a hospitalist and physician adviser in a medically underserved area. She has also served as interim medical director of the department of hospital medicine, and medical staff president, at SIH Herrin Hospital, in Herrin, Ill., part of Southern Illinois Healthcare. She has a special interest in improving access to health care in physician shortage areas.
References
1. Kindermann DR et al. Emergency department transfers and transfer relationships in United States hospitals. Acad Emerg Med. 2015 Feb;22(2):157-65.
2. Sanders RB et al. New hospital telemedicine services: Potential market for a nighttime hospitalist service. Telemed J E Health. 2014 Oct 1;20(10):902-8.
3. Shanafelt T et al. The business case for investing in physician well-being. JAMA Intern Med. 2017;177(12):1826-32.
4. Pines JM et al. The impact of emergency department crowding measures on time to antibiotics for patients with community-acquired pneumonia. Ann Emerg Med. 2007 Nov;50(5):510-6.
5. Pines JM and Hollander JE. Emergency department crowding is associated with poor care for patients with severe pain. Ann Emerg Med. 2008 Jan;51(1):1-5.
6. Chalfin DB et al. Impact of delayed transfer of critically ill patients from the emergency department to the intensive care unit. Crit Care Med. 2007 Jun;35(6):1477-83.
7. Pines JM et al. The financial consequences of lost demand and reducing boarding in hospital emergency departments. Ann Emerg Med. 2011 Oct;58(4):331-40.
8. Natafgi N et al. Using tele-emergency to avoid patient transfers in rural emergency. J Telemed Telecare. 2018 Apri;24(3):193-201.
9. Providence.org/telehealthhospitalistcasestudy.
10. Woodruff Health Sciences Center. CMS report: eICU program reduced hospital stays, saved millions, eased provider shortage. 2017 Apr 5.
11. Lilly CM et al. ICU telemedicine program financial outcomes. Chest. 2017 Feb;151(2):286-97.
COVID-19 has increased confidence in the technology
COVID-19 has increased confidence in the technology
Since the advent of COVID-19, health care has seen an unprecedented rise in virtual health. Telemedicine has come to the forefront of our conversations, and there are many speculations around its future state. One such discussion is around the sustainability and expansion of inpatient telemedicine programs post COVID, and if – and how – it is going to be helpful for health care.
Consider the following scenarios:
Scenario 1
A patient presents to an emergency department of a small community hospital. He needs to be seen by a specialist, but (s)he is not available, so patient gets transferred out to the ED of a different hospital several miles away from his hometown.
He is evaluated in the second ED by the specialist, has repeat testing done – some of those tests were already completed at the first hospital. After evaluating him, the specialist recommends that he does not need to be admitted to the hospital and can be safely followed up as an outpatient. The patient does not require any further intervention and is discharged from the ED.
Scenario 2
Dr. N is a hospitalist in a rural hospital that does not have intensivist support at night. She works 7 on/7 off and is on call 24/7 during her “on” week. Dr. N cannot be physically present in the hospital 24/7. She receives messages from the hospital around the clock and feels that this call schedule is no longer sustainable. She doesn’t feel comfortable admitting patients in the ICU who come to the hospital at night without physically seeing them and without ICU backup. Therefore, some of the patients who are sick enough to be admitted in ICU for closer monitoring but can be potentially handled in this rural hospital get transferred out to a different hospital.
Dr. N has been asking the hospital to provide her intensivist back up at night and to give her some flexibility in the call schedule. However, from hospital’s perspective, the volume isn’t high enough to hire a dedicated nocturnist, and because the hospital is in the small rural area, it is having a hard time attracting more intensivists. After multiple conversations between both parties, Dr. N finally resigns.
Scenario 3
Dr. A is a specialist who is on call covering different hospitals and seeing patients in clinic. His call is getting busier. He has received many new consults and also has to follow up on his other patients in hospital who he saw a day prior.
Dr. A started receiving many pages from the hospitals – some of his patients and their families are anxiously waiting on him so that he can let them go home once he sees them, while some are waiting to know what the next steps and plan of action are. He ends up canceling some of his clinic patients who had scheduled an appointment with him 3, 4, or even 5 months ago. It’s already afternoon.
Dr. A now drives to one hospital, sees his new consults, orders tests which may or may not get results the same day, follows up on other patients, reviews their test results, modifies treatment plans for some while clearing other patients for discharge. He then drives to the other hospital and follows the same process. Some of the patients aren’t happy because of the long wait, a few couldn’t arrange for the ride to go home and ended up staying in hospital 1 extra night, while the ER is getting backlogged waiting on discharges.
These scenarios highlight some of the important and prevalent pain points in health care as shown in Figure 1.
Scenario 1 and part of scenario 2 describe what is called potentially avoidable interfacility transfers. One study showed that around 8% of transferred patients (transferred from one ED to another) were discharged after ED evaluation in the second hospital, meaning they could have been retained locally without necessarily getting transferred if they could have been evaluated by the specialist.1
Transferring a patient from one hospital to another isn’t as simple as picking up a person from point A and dropping him off at point B. Rather it’s a very complicated, high-risk, capital-intensive, and time-consuming process that leads not only to excessive cost involved around transfer but also adds additional stress and burden on the patient and family. In these scenarios, having a specialist available via teleconsult could have eliminated much of this hassle and cost, allowing the patient to stay locally close to family and get access to necessary medical expertise from any part of the country in a timely manner.
Scenario 2 talks about the recruitment and retention challenges in low-volume, low-resourced locations because of call schedule and the lack of specialty support. It is reported in one study that 19% of common hospitalist admissions happen between 7:00 p.m. and 7:00 a.m. Eighty percent of admissions occurred prior to midnight. Nonrural facilities averaged 6.69 hospitalist admissions per night in that study, whereas rural facilities averaged 1.35 admissions.2 It’s like a double-edged sword for such facilities. While having a dedicated nocturnist is not a sustainable model for these hospitals, not having adequate support at night impacts physician wellness, which is already costing hospitals billions of dollars as well as leading to physician turnover: It could cost a hospital somewhere between $500,000 and $1 million to replace just one physician.3 Hence, the potential exists for a telehospitalist program in these settings to address this dilemma.
Scenario 3 sheds light on the operational issues resulting in reduced patient satisfaction and lost revenues, both on the outpatient and inpatient sides by cancellation of office visits and ED backlog. Telemedicine use in these situations can improve the turnaround time of physicians who can see some of those patients while staying at one location as they wait on other patients to show up in the clinic or wait on the operation room crew, or the procedure kit etcetera, hence improving the length of stay, ED throughput, patient satisfaction, and quality of care. This also can improve overall workflow and the wellness of physicians.
One common outcome in all these scenarios is emergency department overcrowding. There have been multiple studies that suggest that ED overcrowding can result in increased costs, lost revenues, and poor clinical outcomes, including delayed administration of antibiotics, delayed administration of analgesics to suffering patients, increased hospital length of stay, and even increased mortality.4-6 A crowded ED limits the ability of an institution to accept referrals and increases medicolegal risks. (See Figure 2.)
Another study showed that a 1-hour reduction in ED boarding time would result in over $9,000 of additional revenue by reducing ambulance diversion and the number of patients who left without being seen.7 Another found that using tele-emergency services can potentially result in net savings of $3,823 per avoided transfer, while accounting for the costs related to tele-emergency technology, hospital revenues, and patient-associated savings.8
There are other instances where gaps in staffing and cracks in workflow can have a negative impact on hospital operations. For example, the busier hospitals that do have a dedicated nocturnist also struggle with physician retention, since such hospitals have higher volumes and higher cross-coverage needs, and are therefore hard to manage by just one single physician at night. Since these are temporary surges, hiring another full-time nocturnist is not a viable option for the hospitals and is considered an expense in many places.
Similarly, during day shift, if a physician goes on vacation or there are surges in patient volumes, hiring a locum tenens hospitalist can be an expensive option, since the cost also includes travel and lodging. In many instances, hiring locum tenens in a given time frame is also not possible, and it leaves the physicians short staffed, fueling both physicians’ and patients’ dissatisfaction and leading to other operational and safety challenges, which I highlighted above.
Telemedicine services in these situations can provide cross-coverage while nocturnists can focus on admissions and other acute issues. Also, when physicians are on vacation or there is surge capacity (that can be forecast by using various predictive analytics models), hospitals can make plans accordingly and make use of telemedicine services. For example, Providence St. Joseph Health reported improvement in timeliness and efficiency of care after implementation of a telehospitalist program. Their 2-year study at a partner site showed a 59% improvement in patients admitted prior to midnight, about $547,000 improvement in first-day revenue capture, an increase in total revenue days and comparable patient experience scores, and a substantial increase in inpatient census and case mix index.9
Other institutions have successfully implemented some inpatient telemedicine programs – such as telepsych, telestroke, and tele-ICU – and some have also reported positive outcomes in terms of patient satisfaction, improved access, reduced length of stay in the ED, and improved quality metrics. Emory Healthcare in Atlanta reported $4.6 million savings in Medicare costs over a 15-month period from adopting a telemedicine model in the ICU, and a reduction in 60-day readmissions by 2.1%.10 Similarly, another study showed that one large health care center improved its direct contribution margins by 376% (from $7.9 million to $37.7 million) because of increased case volume, shorter lengths of stay, and higher case revenue relative to direct costs. When combined with a logistics center, they reported improved contribution margins by 665% (from $7.9 million to $60.6 million).11
There are barriers to the integration and implementation of inpatient telemedicine, including regulations, reimbursement, physician licensing, adoption of technology, and trust among staff and patients. However, I am cautiously optimistic that increased use of telehealth during the COVID-19 pandemic has allowed patients, physicians, nurses, and health care workers and leaders to gain experience with this technology, which will help them gain confidence and reduce hesitation in adapting to this new digital platform. Ultimately, the extent to which telemedicine is able to positively impact patient care will revolve around overcoming these barriers, likely through an evolution of both the technology itself and the attitudes and regulations surrounding it.
I do not suggest that telemedicine should replace the in-person encounter, but it can be implemented and used successfully in addressing the pain points in U.S. health care. (See Figure 3.)
To that end, the purpose of this article is to spark discussion around different ways of implementing telemedicine in inpatient settings to solve many of the challenges that health care faces today.
Dr. Zia is an internal medicine board-certified physician, serving as a hospitalist and physician adviser in a medically underserved area. She has also served as interim medical director of the department of hospital medicine, and medical staff president, at SIH Herrin Hospital, in Herrin, Ill., part of Southern Illinois Healthcare. She has a special interest in improving access to health care in physician shortage areas.
References
1. Kindermann DR et al. Emergency department transfers and transfer relationships in United States hospitals. Acad Emerg Med. 2015 Feb;22(2):157-65.
2. Sanders RB et al. New hospital telemedicine services: Potential market for a nighttime hospitalist service. Telemed J E Health. 2014 Oct 1;20(10):902-8.
3. Shanafelt T et al. The business case for investing in physician well-being. JAMA Intern Med. 2017;177(12):1826-32.
4. Pines JM et al. The impact of emergency department crowding measures on time to antibiotics for patients with community-acquired pneumonia. Ann Emerg Med. 2007 Nov;50(5):510-6.
5. Pines JM and Hollander JE. Emergency department crowding is associated with poor care for patients with severe pain. Ann Emerg Med. 2008 Jan;51(1):1-5.
6. Chalfin DB et al. Impact of delayed transfer of critically ill patients from the emergency department to the intensive care unit. Crit Care Med. 2007 Jun;35(6):1477-83.
7. Pines JM et al. The financial consequences of lost demand and reducing boarding in hospital emergency departments. Ann Emerg Med. 2011 Oct;58(4):331-40.
8. Natafgi N et al. Using tele-emergency to avoid patient transfers in rural emergency. J Telemed Telecare. 2018 Apri;24(3):193-201.
9. Providence.org/telehealthhospitalistcasestudy.
10. Woodruff Health Sciences Center. CMS report: eICU program reduced hospital stays, saved millions, eased provider shortage. 2017 Apr 5.
11. Lilly CM et al. ICU telemedicine program financial outcomes. Chest. 2017 Feb;151(2):286-97.
Since the advent of COVID-19, health care has seen an unprecedented rise in virtual health. Telemedicine has come to the forefront of our conversations, and there are many speculations around its future state. One such discussion is around the sustainability and expansion of inpatient telemedicine programs post COVID, and if – and how – it is going to be helpful for health care.
Consider the following scenarios:
Scenario 1
A patient presents to an emergency department of a small community hospital. He needs to be seen by a specialist, but (s)he is not available, so patient gets transferred out to the ED of a different hospital several miles away from his hometown.
He is evaluated in the second ED by the specialist, has repeat testing done – some of those tests were already completed at the first hospital. After evaluating him, the specialist recommends that he does not need to be admitted to the hospital and can be safely followed up as an outpatient. The patient does not require any further intervention and is discharged from the ED.
Scenario 2
Dr. N is a hospitalist in a rural hospital that does not have intensivist support at night. She works 7 on/7 off and is on call 24/7 during her “on” week. Dr. N cannot be physically present in the hospital 24/7. She receives messages from the hospital around the clock and feels that this call schedule is no longer sustainable. She doesn’t feel comfortable admitting patients in the ICU who come to the hospital at night without physically seeing them and without ICU backup. Therefore, some of the patients who are sick enough to be admitted in ICU for closer monitoring but can be potentially handled in this rural hospital get transferred out to a different hospital.
Dr. N has been asking the hospital to provide her intensivist back up at night and to give her some flexibility in the call schedule. However, from hospital’s perspective, the volume isn’t high enough to hire a dedicated nocturnist, and because the hospital is in the small rural area, it is having a hard time attracting more intensivists. After multiple conversations between both parties, Dr. N finally resigns.
Scenario 3
Dr. A is a specialist who is on call covering different hospitals and seeing patients in clinic. His call is getting busier. He has received many new consults and also has to follow up on his other patients in hospital who he saw a day prior.
Dr. A started receiving many pages from the hospitals – some of his patients and their families are anxiously waiting on him so that he can let them go home once he sees them, while some are waiting to know what the next steps and plan of action are. He ends up canceling some of his clinic patients who had scheduled an appointment with him 3, 4, or even 5 months ago. It’s already afternoon.
Dr. A now drives to one hospital, sees his new consults, orders tests which may or may not get results the same day, follows up on other patients, reviews their test results, modifies treatment plans for some while clearing other patients for discharge. He then drives to the other hospital and follows the same process. Some of the patients aren’t happy because of the long wait, a few couldn’t arrange for the ride to go home and ended up staying in hospital 1 extra night, while the ER is getting backlogged waiting on discharges.
These scenarios highlight some of the important and prevalent pain points in health care as shown in Figure 1.
Scenario 1 and part of scenario 2 describe what is called potentially avoidable interfacility transfers. One study showed that around 8% of transferred patients (transferred from one ED to another) were discharged after ED evaluation in the second hospital, meaning they could have been retained locally without necessarily getting transferred if they could have been evaluated by the specialist.1
Transferring a patient from one hospital to another isn’t as simple as picking up a person from point A and dropping him off at point B. Rather it’s a very complicated, high-risk, capital-intensive, and time-consuming process that leads not only to excessive cost involved around transfer but also adds additional stress and burden on the patient and family. In these scenarios, having a specialist available via teleconsult could have eliminated much of this hassle and cost, allowing the patient to stay locally close to family and get access to necessary medical expertise from any part of the country in a timely manner.
Scenario 2 talks about the recruitment and retention challenges in low-volume, low-resourced locations because of call schedule and the lack of specialty support. It is reported in one study that 19% of common hospitalist admissions happen between 7:00 p.m. and 7:00 a.m. Eighty percent of admissions occurred prior to midnight. Nonrural facilities averaged 6.69 hospitalist admissions per night in that study, whereas rural facilities averaged 1.35 admissions.2 It’s like a double-edged sword for such facilities. While having a dedicated nocturnist is not a sustainable model for these hospitals, not having adequate support at night impacts physician wellness, which is already costing hospitals billions of dollars as well as leading to physician turnover: It could cost a hospital somewhere between $500,000 and $1 million to replace just one physician.3 Hence, the potential exists for a telehospitalist program in these settings to address this dilemma.
Scenario 3 sheds light on the operational issues resulting in reduced patient satisfaction and lost revenues, both on the outpatient and inpatient sides by cancellation of office visits and ED backlog. Telemedicine use in these situations can improve the turnaround time of physicians who can see some of those patients while staying at one location as they wait on other patients to show up in the clinic or wait on the operation room crew, or the procedure kit etcetera, hence improving the length of stay, ED throughput, patient satisfaction, and quality of care. This also can improve overall workflow and the wellness of physicians.
One common outcome in all these scenarios is emergency department overcrowding. There have been multiple studies that suggest that ED overcrowding can result in increased costs, lost revenues, and poor clinical outcomes, including delayed administration of antibiotics, delayed administration of analgesics to suffering patients, increased hospital length of stay, and even increased mortality.4-6 A crowded ED limits the ability of an institution to accept referrals and increases medicolegal risks. (See Figure 2.)
Another study showed that a 1-hour reduction in ED boarding time would result in over $9,000 of additional revenue by reducing ambulance diversion and the number of patients who left without being seen.7 Another found that using tele-emergency services can potentially result in net savings of $3,823 per avoided transfer, while accounting for the costs related to tele-emergency technology, hospital revenues, and patient-associated savings.8
There are other instances where gaps in staffing and cracks in workflow can have a negative impact on hospital operations. For example, the busier hospitals that do have a dedicated nocturnist also struggle with physician retention, since such hospitals have higher volumes and higher cross-coverage needs, and are therefore hard to manage by just one single physician at night. Since these are temporary surges, hiring another full-time nocturnist is not a viable option for the hospitals and is considered an expense in many places.
Similarly, during day shift, if a physician goes on vacation or there are surges in patient volumes, hiring a locum tenens hospitalist can be an expensive option, since the cost also includes travel and lodging. In many instances, hiring locum tenens in a given time frame is also not possible, and it leaves the physicians short staffed, fueling both physicians’ and patients’ dissatisfaction and leading to other operational and safety challenges, which I highlighted above.
Telemedicine services in these situations can provide cross-coverage while nocturnists can focus on admissions and other acute issues. Also, when physicians are on vacation or there is surge capacity (that can be forecast by using various predictive analytics models), hospitals can make plans accordingly and make use of telemedicine services. For example, Providence St. Joseph Health reported improvement in timeliness and efficiency of care after implementation of a telehospitalist program. Their 2-year study at a partner site showed a 59% improvement in patients admitted prior to midnight, about $547,000 improvement in first-day revenue capture, an increase in total revenue days and comparable patient experience scores, and a substantial increase in inpatient census and case mix index.9
Other institutions have successfully implemented some inpatient telemedicine programs – such as telepsych, telestroke, and tele-ICU – and some have also reported positive outcomes in terms of patient satisfaction, improved access, reduced length of stay in the ED, and improved quality metrics. Emory Healthcare in Atlanta reported $4.6 million savings in Medicare costs over a 15-month period from adopting a telemedicine model in the ICU, and a reduction in 60-day readmissions by 2.1%.10 Similarly, another study showed that one large health care center improved its direct contribution margins by 376% (from $7.9 million to $37.7 million) because of increased case volume, shorter lengths of stay, and higher case revenue relative to direct costs. When combined with a logistics center, they reported improved contribution margins by 665% (from $7.9 million to $60.6 million).11
There are barriers to the integration and implementation of inpatient telemedicine, including regulations, reimbursement, physician licensing, adoption of technology, and trust among staff and patients. However, I am cautiously optimistic that increased use of telehealth during the COVID-19 pandemic has allowed patients, physicians, nurses, and health care workers and leaders to gain experience with this technology, which will help them gain confidence and reduce hesitation in adapting to this new digital platform. Ultimately, the extent to which telemedicine is able to positively impact patient care will revolve around overcoming these barriers, likely through an evolution of both the technology itself and the attitudes and regulations surrounding it.
I do not suggest that telemedicine should replace the in-person encounter, but it can be implemented and used successfully in addressing the pain points in U.S. health care. (See Figure 3.)
To that end, the purpose of this article is to spark discussion around different ways of implementing telemedicine in inpatient settings to solve many of the challenges that health care faces today.
Dr. Zia is an internal medicine board-certified physician, serving as a hospitalist and physician adviser in a medically underserved area. She has also served as interim medical director of the department of hospital medicine, and medical staff president, at SIH Herrin Hospital, in Herrin, Ill., part of Southern Illinois Healthcare. She has a special interest in improving access to health care in physician shortage areas.
References
1. Kindermann DR et al. Emergency department transfers and transfer relationships in United States hospitals. Acad Emerg Med. 2015 Feb;22(2):157-65.
2. Sanders RB et al. New hospital telemedicine services: Potential market for a nighttime hospitalist service. Telemed J E Health. 2014 Oct 1;20(10):902-8.
3. Shanafelt T et al. The business case for investing in physician well-being. JAMA Intern Med. 2017;177(12):1826-32.
4. Pines JM et al. The impact of emergency department crowding measures on time to antibiotics for patients with community-acquired pneumonia. Ann Emerg Med. 2007 Nov;50(5):510-6.
5. Pines JM and Hollander JE. Emergency department crowding is associated with poor care for patients with severe pain. Ann Emerg Med. 2008 Jan;51(1):1-5.
6. Chalfin DB et al. Impact of delayed transfer of critically ill patients from the emergency department to the intensive care unit. Crit Care Med. 2007 Jun;35(6):1477-83.
7. Pines JM et al. The financial consequences of lost demand and reducing boarding in hospital emergency departments. Ann Emerg Med. 2011 Oct;58(4):331-40.
8. Natafgi N et al. Using tele-emergency to avoid patient transfers in rural emergency. J Telemed Telecare. 2018 Apri;24(3):193-201.
9. Providence.org/telehealthhospitalistcasestudy.
10. Woodruff Health Sciences Center. CMS report: eICU program reduced hospital stays, saved millions, eased provider shortage. 2017 Apr 5.
11. Lilly CM et al. ICU telemedicine program financial outcomes. Chest. 2017 Feb;151(2):286-97.
Late-window stroke thrombolysis not linked to clot migration
In patients with acute ischemic stroke, the use of thrombolysis in the late window of 4.5-9 hours after symptom onset was not associated with an increase in clot migration that would cause reduced clot accessibility to endovascular therapy, a new analysis from the EXTEND trial shows.
“There was no significant difference in the incidence of clot migration leading to clot inaccessibility in patients who received placebo or (intravenous) thrombolysis,” the authors report.
“Our results found no convincing evidence against the use of bridging thrombolysis before endovascular therapy in patients with acute ischemic stroke who present outside the 4.5-hour window,” they conclude.
“This information is important because it provides some comfort for neurointerventionists that IV thrombolysis does not unduly increase the risk of clot migration,” senior author, Bernard Yan, DMedSci, FRACP, told this news organization.
The study was published online in Stroke on Feb. 16.
The Australian researchers explain that endovascular thrombectomy is the standard of care in patients presenting with acute ischemic stroke caused by large-vessel occlusion, and current treatment guidelines recommend bridging thrombolysis for all patients receiving thrombectomy within the 4.5-hour time window.
While thrombectomy is also recommended in selected patients up to 24 hours after onset of symptoms, it remains unclear whether thrombolysis pretreatment should be administered in this setting.
One of the issues that might affect use of thrombolysis is distal clot migration. As proximal clot location is a crucial factor determining suitability for endovascular clot retrieval, distal migration may prevent successful thrombectomy, they note.
“Clot migration can happen any time and makes life more difficult for the neurointerventionist who performs the endovascular clot retrieval,” added Dr. Yan, who is a neurologist and neurointerventionist at the Royal Melbourne Hospital, Australia.
In the current paper, the researchers report a retrospective analysis of data from the EXTEND trial of late thrombolysis, defined as 4.5-9 hours after symptom onset, to investigate the association between thrombolysis and clot migration leading to clot irretrievability.
The analysis included a total of 220 patients (109 patients in the placebo group and 111 in the thrombolysis group).
Results showed that retrievable clot was seen on baseline imaging in 69% of patients in the placebo group and 61% in the thrombolysis group. Clot resolution occurred in 28% of patients in the placebo group and 50% in the thrombolysis group.
No significant difference was observed in the incidence of clot migration leading to inaccessibility between groups. Clot migration from a retrievable to nonretrievable location occurred in 19% of the placebo group and 14% of the thrombolysis group, with an odds ratio for clot migration in the thrombolysis group of 0.70 (95% confidence interval, 0.35-1.44). This outcome was consistent across subgroups.
The researchers note that, to their knowledge, this is the first randomized controlled study to assess the effect of thrombolysis on clot migration and accessibility in an extended time window.
They acknowledge that a limitation of this study is that they only assessed clot migration from a retrievable to a nonretrievable location; therefore, the true frequency of any clot migration occurring was likely to be higher, and this could explain why other reports have found higher odds ratios of clot migration.
But they point out that they chose to limit their analysis in this way specifically to guide decision-making regarding bridging thrombolysis incorporating endovascular therapy in the extended time window.
“The findings of this study are highly relevant in the current clinical environment, where there are multiple ongoing trials looking at removing thrombolysis pretreatment within the 4.5-hour time window in thrombectomy patients,” the authors write.
“We have demonstrated that thrombolysis in the 4.5- to 9-hour window is not associated with reduced clot accessibility, and this information will be useful in future trial designs incorporating this extended time window,” they add.
Commenting on the study for this news organization, Michael Hill, MD, University of Calgary (Alta.), said: “Thrombus migration does happen and is likely part of the natural history of ischemic stroke, which may be influenced by therapeutics such as thrombolysis. This paper’s top-line result is that thrombus migration occurs in both treated and untreated groups – and therefore that this is really an observation of natural history.”
Dr. Hill says that, at present, patients should be treated with thrombolysis before endovascular therapy if they are eligible, and these results do not change that recommendation.
“The results of the ongoing trials comparing direct thrombectomy with thrombolysis plus thrombectomy will help to understand the potential clinical outcome relevance of this phenomenon,” he added.
The EXTEND trial was supported by grants from the Australian National Health and Medical Research Council of Australia and the Commonwealth Scientific and Industrial Research Organization Flagship Program. Dr. Yan reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In patients with acute ischemic stroke, the use of thrombolysis in the late window of 4.5-9 hours after symptom onset was not associated with an increase in clot migration that would cause reduced clot accessibility to endovascular therapy, a new analysis from the EXTEND trial shows.
“There was no significant difference in the incidence of clot migration leading to clot inaccessibility in patients who received placebo or (intravenous) thrombolysis,” the authors report.
“Our results found no convincing evidence against the use of bridging thrombolysis before endovascular therapy in patients with acute ischemic stroke who present outside the 4.5-hour window,” they conclude.
“This information is important because it provides some comfort for neurointerventionists that IV thrombolysis does not unduly increase the risk of clot migration,” senior author, Bernard Yan, DMedSci, FRACP, told this news organization.
The study was published online in Stroke on Feb. 16.
The Australian researchers explain that endovascular thrombectomy is the standard of care in patients presenting with acute ischemic stroke caused by large-vessel occlusion, and current treatment guidelines recommend bridging thrombolysis for all patients receiving thrombectomy within the 4.5-hour time window.
While thrombectomy is also recommended in selected patients up to 24 hours after onset of symptoms, it remains unclear whether thrombolysis pretreatment should be administered in this setting.
One of the issues that might affect use of thrombolysis is distal clot migration. As proximal clot location is a crucial factor determining suitability for endovascular clot retrieval, distal migration may prevent successful thrombectomy, they note.
“Clot migration can happen any time and makes life more difficult for the neurointerventionist who performs the endovascular clot retrieval,” added Dr. Yan, who is a neurologist and neurointerventionist at the Royal Melbourne Hospital, Australia.
In the current paper, the researchers report a retrospective analysis of data from the EXTEND trial of late thrombolysis, defined as 4.5-9 hours after symptom onset, to investigate the association between thrombolysis and clot migration leading to clot irretrievability.
The analysis included a total of 220 patients (109 patients in the placebo group and 111 in the thrombolysis group).
Results showed that retrievable clot was seen on baseline imaging in 69% of patients in the placebo group and 61% in the thrombolysis group. Clot resolution occurred in 28% of patients in the placebo group and 50% in the thrombolysis group.
No significant difference was observed in the incidence of clot migration leading to inaccessibility between groups. Clot migration from a retrievable to nonretrievable location occurred in 19% of the placebo group and 14% of the thrombolysis group, with an odds ratio for clot migration in the thrombolysis group of 0.70 (95% confidence interval, 0.35-1.44). This outcome was consistent across subgroups.
The researchers note that, to their knowledge, this is the first randomized controlled study to assess the effect of thrombolysis on clot migration and accessibility in an extended time window.
They acknowledge that a limitation of this study is that they only assessed clot migration from a retrievable to a nonretrievable location; therefore, the true frequency of any clot migration occurring was likely to be higher, and this could explain why other reports have found higher odds ratios of clot migration.
But they point out that they chose to limit their analysis in this way specifically to guide decision-making regarding bridging thrombolysis incorporating endovascular therapy in the extended time window.
“The findings of this study are highly relevant in the current clinical environment, where there are multiple ongoing trials looking at removing thrombolysis pretreatment within the 4.5-hour time window in thrombectomy patients,” the authors write.
“We have demonstrated that thrombolysis in the 4.5- to 9-hour window is not associated with reduced clot accessibility, and this information will be useful in future trial designs incorporating this extended time window,” they add.
Commenting on the study for this news organization, Michael Hill, MD, University of Calgary (Alta.), said: “Thrombus migration does happen and is likely part of the natural history of ischemic stroke, which may be influenced by therapeutics such as thrombolysis. This paper’s top-line result is that thrombus migration occurs in both treated and untreated groups – and therefore that this is really an observation of natural history.”
Dr. Hill says that, at present, patients should be treated with thrombolysis before endovascular therapy if they are eligible, and these results do not change that recommendation.
“The results of the ongoing trials comparing direct thrombectomy with thrombolysis plus thrombectomy will help to understand the potential clinical outcome relevance of this phenomenon,” he added.
The EXTEND trial was supported by grants from the Australian National Health and Medical Research Council of Australia and the Commonwealth Scientific and Industrial Research Organization Flagship Program. Dr. Yan reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In patients with acute ischemic stroke, the use of thrombolysis in the late window of 4.5-9 hours after symptom onset was not associated with an increase in clot migration that would cause reduced clot accessibility to endovascular therapy, a new analysis from the EXTEND trial shows.
“There was no significant difference in the incidence of clot migration leading to clot inaccessibility in patients who received placebo or (intravenous) thrombolysis,” the authors report.
“Our results found no convincing evidence against the use of bridging thrombolysis before endovascular therapy in patients with acute ischemic stroke who present outside the 4.5-hour window,” they conclude.
“This information is important because it provides some comfort for neurointerventionists that IV thrombolysis does not unduly increase the risk of clot migration,” senior author, Bernard Yan, DMedSci, FRACP, told this news organization.
The study was published online in Stroke on Feb. 16.
The Australian researchers explain that endovascular thrombectomy is the standard of care in patients presenting with acute ischemic stroke caused by large-vessel occlusion, and current treatment guidelines recommend bridging thrombolysis for all patients receiving thrombectomy within the 4.5-hour time window.
While thrombectomy is also recommended in selected patients up to 24 hours after onset of symptoms, it remains unclear whether thrombolysis pretreatment should be administered in this setting.
One of the issues that might affect use of thrombolysis is distal clot migration. As proximal clot location is a crucial factor determining suitability for endovascular clot retrieval, distal migration may prevent successful thrombectomy, they note.
“Clot migration can happen any time and makes life more difficult for the neurointerventionist who performs the endovascular clot retrieval,” added Dr. Yan, who is a neurologist and neurointerventionist at the Royal Melbourne Hospital, Australia.
In the current paper, the researchers report a retrospective analysis of data from the EXTEND trial of late thrombolysis, defined as 4.5-9 hours after symptom onset, to investigate the association between thrombolysis and clot migration leading to clot irretrievability.
The analysis included a total of 220 patients (109 patients in the placebo group and 111 in the thrombolysis group).
Results showed that retrievable clot was seen on baseline imaging in 69% of patients in the placebo group and 61% in the thrombolysis group. Clot resolution occurred in 28% of patients in the placebo group and 50% in the thrombolysis group.
No significant difference was observed in the incidence of clot migration leading to inaccessibility between groups. Clot migration from a retrievable to nonretrievable location occurred in 19% of the placebo group and 14% of the thrombolysis group, with an odds ratio for clot migration in the thrombolysis group of 0.70 (95% confidence interval, 0.35-1.44). This outcome was consistent across subgroups.
The researchers note that, to their knowledge, this is the first randomized controlled study to assess the effect of thrombolysis on clot migration and accessibility in an extended time window.
They acknowledge that a limitation of this study is that they only assessed clot migration from a retrievable to a nonretrievable location; therefore, the true frequency of any clot migration occurring was likely to be higher, and this could explain why other reports have found higher odds ratios of clot migration.
But they point out that they chose to limit their analysis in this way specifically to guide decision-making regarding bridging thrombolysis incorporating endovascular therapy in the extended time window.
“The findings of this study are highly relevant in the current clinical environment, where there are multiple ongoing trials looking at removing thrombolysis pretreatment within the 4.5-hour time window in thrombectomy patients,” the authors write.
“We have demonstrated that thrombolysis in the 4.5- to 9-hour window is not associated with reduced clot accessibility, and this information will be useful in future trial designs incorporating this extended time window,” they add.
Commenting on the study for this news organization, Michael Hill, MD, University of Calgary (Alta.), said: “Thrombus migration does happen and is likely part of the natural history of ischemic stroke, which may be influenced by therapeutics such as thrombolysis. This paper’s top-line result is that thrombus migration occurs in both treated and untreated groups – and therefore that this is really an observation of natural history.”
Dr. Hill says that, at present, patients should be treated with thrombolysis before endovascular therapy if they are eligible, and these results do not change that recommendation.
“The results of the ongoing trials comparing direct thrombectomy with thrombolysis plus thrombectomy will help to understand the potential clinical outcome relevance of this phenomenon,” he added.
The EXTEND trial was supported by grants from the Australian National Health and Medical Research Council of Australia and the Commonwealth Scientific and Industrial Research Organization Flagship Program. Dr. Yan reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Big data ‘clinch’ link between high glycemic index diets and CVD
People who mostly ate foods with a low glycemic index had a lower likelihood of premature death and major cardiovascular disease (CVD) events, compared with those whose diet included more “poor-quality” food with a high glycemic index.
The results from the global PURE study of nearly 120,000 people provide evidence that helps cement glycemic index as a key measure of dietary health.
This new analysis from PURE (Prospective Urban and Rural Epidemiological Study) – a massive prospective epidemiologic study – shows people with a diet in the highest quintile of glycemic index had a significant 25% higher rate of combined total deaths and major CVD events during a median follow-up of nearly 10 years, compared with those with a diet in the lowest glycemic index quintile, in the report published online on Feb. 24, 2021, in the New England Journal of Medicine.
David J.A. Jenkins, MD, PhD, DSc, lead author, said people do not necessarily need to closely track the glycemic index of what they eat to follow the guidance that lower is better.
The link between lower glycemic load and fewer CVD events was even stronger among people with an established history of CVD at study entry. In this subset, which included 9% of the total cohort, people in the highest quintile for glycemic index consumption had a 51% higher rate of the composite primary endpoint, compared with those in the lowest quintile, in an analysis that adjusted for several potential confounders.
A simple but accurate and effective public health message is to follow existing dietary recommendations to eat better-quality food – more unprocessed fruits, vegetables, legumes, and whole grains – Dr. Jenkins advised. Those who prefer a more detailed approach could use the comprehensive glycemic index tables compiled by researchers at the University of Sydney.
‘All carbohydrates are not the same’
“What we’re saying is that all carbohydrates are not the same. Some seem to increase the risk for CVD, and others seem protective. This is not new, but worth restating in an era of low-carb and no-carb diets,” said Dr. Jenkins.
Low-glycemic-index foods are generally unprocessed foods in their native state, including fruits, vegetables, legumes, and unrefined whole grains. High-glycemic-index foods contain processed and refined carbohydrates that deliver jolts of glucose soon after eating, as the sugar in these carbohydrates quickly moves from the gut to the bloodstream.
An association between a diet with a lower glycemic index and better outcomes had appeared in prior reports from other studies, but not as unambiguously as in the new data from PURE, likely because of fewer study participants in previous studies.
Another feature of PURE that adds to the generalizability of the findings is the diversity of adults included in the study, from 20 countries on five continents.
“This clinches it,” Dr. Jenkins declared in an interview.
New PURE data tip the evidence balance
The NEJM article includes a new meta-analysis that adds the PURE findings to data from two large prior reports that were each less conclusive. The new calculation with the PURE numbers helps establish a clearer association between a diet with a higher glycemic index and the endpoint of CVD death, showing an overall 26% increase in the outcome.
The PURE data are especially informative because the investigators collected additional information on a range of potential confounders they incorporated into their analyses.
“We were able to include a lot of documentation on many potential confounders. That’s a strength of our data,” noted Dr. Jenkins, a professor of nutritional science and medicine at the University of Toronto.
“The present data, along with prior publications from PURE and several other studies, emphasize that consumption of poor quality carbohydrates is likely to be more adverse than the consumption of most fats in the diet,” said senior author Salim Yusuf, MD, DPhil, professor of medicine and executive director of the Population Health Research Institute at McMaster University, Hamilton, Ont.
“This calls for a fundamental shift in our thinking of what types of diet are likely to be harmful and what types neutral or beneficial,” Dr. Yusuf said in a statement from his institution.
Higher BMI associated with greater glycemic index effect
Another important analysis in the new report calculated the impact of a higher glycemic index diet among people with a body mass index (BMI) of less than 25 kg/m2 as well as higher BMIs.
Among people in the lower BMI subgroup, greater intake of high-glycemic-index foods showed slightly more incident primary outcome events. In contrast, people with a BMI of 25 or greater showed a steady increment in primary outcome events as the glycemic index of their diet increased.
People with higher BMIs in the quartile that ate the greatest amount of high-glycemic =-index foods had a significant 38% higher rate of primary outcome events, compared with people with similar BMIs in the lowest quartile for high-glycemic-index intake.
However, the study showed no impact on the primary association of high glycemic index and increased adverse outcomes by exercise habits, smoking, use of blood pressure medications, or use of statins.
The new report complements a separate analysis from PURE published just a few weeks earlier in the BMJ that established a significant association between increased consumption of whole grains and fewer CVD events, compared with people who had more refined grains in their diet, as reported by this news organization.
This prior report on whole versus refined grains, which Dr. Jenkins coauthored, looked at carbohydrate quality using a two-pronged approach, while glycemic index is a continuous variable that provides more nuance and takes into account carbohydrates from sources other than grains, Dr. Jenkins said.
PURE enrolled roughly 225,000 people aged 35-70 years at entry. The glycemic index analysis focused on 119,575 people who had data available for the primary outcome. During a median follow-up of 9.5 years, these people had 14,075 primary outcome events, including 8,780 deaths.
Analyses that looked at the individual outcomes that comprised the composite endpoint showed significant associations between a high-glycemic-index diet and total mortality, CVD death, non-CVD death, and stroke, but showed no significant link with myocardial infarction or heart failure. These findings are consistent with prior results of other studies that showed a stronger link between stroke and a high glycemic index diet, compared with other nonfatal CVD events.
Dr. Jenkins suggested that the significant excess of non-CVD deaths linked with a high-glycemic-index diet may stem from the impact of this type of diet on cancer-associated mortality.
PURE received partial funding through unrestricted grants from several drug companies. Dr. Jenkins has reported receiving gifts from several food-related trade associations and food companies, as well as research grants from two legume-oriented trade associations.
A version of this article first appeared on Medscape.com.
People who mostly ate foods with a low glycemic index had a lower likelihood of premature death and major cardiovascular disease (CVD) events, compared with those whose diet included more “poor-quality” food with a high glycemic index.
The results from the global PURE study of nearly 120,000 people provide evidence that helps cement glycemic index as a key measure of dietary health.
This new analysis from PURE (Prospective Urban and Rural Epidemiological Study) – a massive prospective epidemiologic study – shows people with a diet in the highest quintile of glycemic index had a significant 25% higher rate of combined total deaths and major CVD events during a median follow-up of nearly 10 years, compared with those with a diet in the lowest glycemic index quintile, in the report published online on Feb. 24, 2021, in the New England Journal of Medicine.
David J.A. Jenkins, MD, PhD, DSc, lead author, said people do not necessarily need to closely track the glycemic index of what they eat to follow the guidance that lower is better.
The link between lower glycemic load and fewer CVD events was even stronger among people with an established history of CVD at study entry. In this subset, which included 9% of the total cohort, people in the highest quintile for glycemic index consumption had a 51% higher rate of the composite primary endpoint, compared with those in the lowest quintile, in an analysis that adjusted for several potential confounders.
A simple but accurate and effective public health message is to follow existing dietary recommendations to eat better-quality food – more unprocessed fruits, vegetables, legumes, and whole grains – Dr. Jenkins advised. Those who prefer a more detailed approach could use the comprehensive glycemic index tables compiled by researchers at the University of Sydney.
‘All carbohydrates are not the same’
“What we’re saying is that all carbohydrates are not the same. Some seem to increase the risk for CVD, and others seem protective. This is not new, but worth restating in an era of low-carb and no-carb diets,” said Dr. Jenkins.
Low-glycemic-index foods are generally unprocessed foods in their native state, including fruits, vegetables, legumes, and unrefined whole grains. High-glycemic-index foods contain processed and refined carbohydrates that deliver jolts of glucose soon after eating, as the sugar in these carbohydrates quickly moves from the gut to the bloodstream.
An association between a diet with a lower glycemic index and better outcomes had appeared in prior reports from other studies, but not as unambiguously as in the new data from PURE, likely because of fewer study participants in previous studies.
Another feature of PURE that adds to the generalizability of the findings is the diversity of adults included in the study, from 20 countries on five continents.
“This clinches it,” Dr. Jenkins declared in an interview.
New PURE data tip the evidence balance
The NEJM article includes a new meta-analysis that adds the PURE findings to data from two large prior reports that were each less conclusive. The new calculation with the PURE numbers helps establish a clearer association between a diet with a higher glycemic index and the endpoint of CVD death, showing an overall 26% increase in the outcome.
The PURE data are especially informative because the investigators collected additional information on a range of potential confounders they incorporated into their analyses.
“We were able to include a lot of documentation on many potential confounders. That’s a strength of our data,” noted Dr. Jenkins, a professor of nutritional science and medicine at the University of Toronto.
“The present data, along with prior publications from PURE and several other studies, emphasize that consumption of poor quality carbohydrates is likely to be more adverse than the consumption of most fats in the diet,” said senior author Salim Yusuf, MD, DPhil, professor of medicine and executive director of the Population Health Research Institute at McMaster University, Hamilton, Ont.
“This calls for a fundamental shift in our thinking of what types of diet are likely to be harmful and what types neutral or beneficial,” Dr. Yusuf said in a statement from his institution.
Higher BMI associated with greater glycemic index effect
Another important analysis in the new report calculated the impact of a higher glycemic index diet among people with a body mass index (BMI) of less than 25 kg/m2 as well as higher BMIs.
Among people in the lower BMI subgroup, greater intake of high-glycemic-index foods showed slightly more incident primary outcome events. In contrast, people with a BMI of 25 or greater showed a steady increment in primary outcome events as the glycemic index of their diet increased.
People with higher BMIs in the quartile that ate the greatest amount of high-glycemic =-index foods had a significant 38% higher rate of primary outcome events, compared with people with similar BMIs in the lowest quartile for high-glycemic-index intake.
However, the study showed no impact on the primary association of high glycemic index and increased adverse outcomes by exercise habits, smoking, use of blood pressure medications, or use of statins.
The new report complements a separate analysis from PURE published just a few weeks earlier in the BMJ that established a significant association between increased consumption of whole grains and fewer CVD events, compared with people who had more refined grains in their diet, as reported by this news organization.
This prior report on whole versus refined grains, which Dr. Jenkins coauthored, looked at carbohydrate quality using a two-pronged approach, while glycemic index is a continuous variable that provides more nuance and takes into account carbohydrates from sources other than grains, Dr. Jenkins said.
PURE enrolled roughly 225,000 people aged 35-70 years at entry. The glycemic index analysis focused on 119,575 people who had data available for the primary outcome. During a median follow-up of 9.5 years, these people had 14,075 primary outcome events, including 8,780 deaths.
Analyses that looked at the individual outcomes that comprised the composite endpoint showed significant associations between a high-glycemic-index diet and total mortality, CVD death, non-CVD death, and stroke, but showed no significant link with myocardial infarction or heart failure. These findings are consistent with prior results of other studies that showed a stronger link between stroke and a high glycemic index diet, compared with other nonfatal CVD events.
Dr. Jenkins suggested that the significant excess of non-CVD deaths linked with a high-glycemic-index diet may stem from the impact of this type of diet on cancer-associated mortality.
PURE received partial funding through unrestricted grants from several drug companies. Dr. Jenkins has reported receiving gifts from several food-related trade associations and food companies, as well as research grants from two legume-oriented trade associations.
A version of this article first appeared on Medscape.com.
People who mostly ate foods with a low glycemic index had a lower likelihood of premature death and major cardiovascular disease (CVD) events, compared with those whose diet included more “poor-quality” food with a high glycemic index.
The results from the global PURE study of nearly 120,000 people provide evidence that helps cement glycemic index as a key measure of dietary health.
This new analysis from PURE (Prospective Urban and Rural Epidemiological Study) – a massive prospective epidemiologic study – shows people with a diet in the highest quintile of glycemic index had a significant 25% higher rate of combined total deaths and major CVD events during a median follow-up of nearly 10 years, compared with those with a diet in the lowest glycemic index quintile, in the report published online on Feb. 24, 2021, in the New England Journal of Medicine.
David J.A. Jenkins, MD, PhD, DSc, lead author, said people do not necessarily need to closely track the glycemic index of what they eat to follow the guidance that lower is better.
The link between lower glycemic load and fewer CVD events was even stronger among people with an established history of CVD at study entry. In this subset, which included 9% of the total cohort, people in the highest quintile for glycemic index consumption had a 51% higher rate of the composite primary endpoint, compared with those in the lowest quintile, in an analysis that adjusted for several potential confounders.
A simple but accurate and effective public health message is to follow existing dietary recommendations to eat better-quality food – more unprocessed fruits, vegetables, legumes, and whole grains – Dr. Jenkins advised. Those who prefer a more detailed approach could use the comprehensive glycemic index tables compiled by researchers at the University of Sydney.
‘All carbohydrates are not the same’
“What we’re saying is that all carbohydrates are not the same. Some seem to increase the risk for CVD, and others seem protective. This is not new, but worth restating in an era of low-carb and no-carb diets,” said Dr. Jenkins.
Low-glycemic-index foods are generally unprocessed foods in their native state, including fruits, vegetables, legumes, and unrefined whole grains. High-glycemic-index foods contain processed and refined carbohydrates that deliver jolts of glucose soon after eating, as the sugar in these carbohydrates quickly moves from the gut to the bloodstream.
An association between a diet with a lower glycemic index and better outcomes had appeared in prior reports from other studies, but not as unambiguously as in the new data from PURE, likely because of fewer study participants in previous studies.
Another feature of PURE that adds to the generalizability of the findings is the diversity of adults included in the study, from 20 countries on five continents.
“This clinches it,” Dr. Jenkins declared in an interview.
New PURE data tip the evidence balance
The NEJM article includes a new meta-analysis that adds the PURE findings to data from two large prior reports that were each less conclusive. The new calculation with the PURE numbers helps establish a clearer association between a diet with a higher glycemic index and the endpoint of CVD death, showing an overall 26% increase in the outcome.
The PURE data are especially informative because the investigators collected additional information on a range of potential confounders they incorporated into their analyses.
“We were able to include a lot of documentation on many potential confounders. That’s a strength of our data,” noted Dr. Jenkins, a professor of nutritional science and medicine at the University of Toronto.
“The present data, along with prior publications from PURE and several other studies, emphasize that consumption of poor quality carbohydrates is likely to be more adverse than the consumption of most fats in the diet,” said senior author Salim Yusuf, MD, DPhil, professor of medicine and executive director of the Population Health Research Institute at McMaster University, Hamilton, Ont.
“This calls for a fundamental shift in our thinking of what types of diet are likely to be harmful and what types neutral or beneficial,” Dr. Yusuf said in a statement from his institution.
Higher BMI associated with greater glycemic index effect
Another important analysis in the new report calculated the impact of a higher glycemic index diet among people with a body mass index (BMI) of less than 25 kg/m2 as well as higher BMIs.
Among people in the lower BMI subgroup, greater intake of high-glycemic-index foods showed slightly more incident primary outcome events. In contrast, people with a BMI of 25 or greater showed a steady increment in primary outcome events as the glycemic index of their diet increased.
People with higher BMIs in the quartile that ate the greatest amount of high-glycemic =-index foods had a significant 38% higher rate of primary outcome events, compared with people with similar BMIs in the lowest quartile for high-glycemic-index intake.
However, the study showed no impact on the primary association of high glycemic index and increased adverse outcomes by exercise habits, smoking, use of blood pressure medications, or use of statins.
The new report complements a separate analysis from PURE published just a few weeks earlier in the BMJ that established a significant association between increased consumption of whole grains and fewer CVD events, compared with people who had more refined grains in their diet, as reported by this news organization.
This prior report on whole versus refined grains, which Dr. Jenkins coauthored, looked at carbohydrate quality using a two-pronged approach, while glycemic index is a continuous variable that provides more nuance and takes into account carbohydrates from sources other than grains, Dr. Jenkins said.
PURE enrolled roughly 225,000 people aged 35-70 years at entry. The glycemic index analysis focused on 119,575 people who had data available for the primary outcome. During a median follow-up of 9.5 years, these people had 14,075 primary outcome events, including 8,780 deaths.
Analyses that looked at the individual outcomes that comprised the composite endpoint showed significant associations between a high-glycemic-index diet and total mortality, CVD death, non-CVD death, and stroke, but showed no significant link with myocardial infarction or heart failure. These findings are consistent with prior results of other studies that showed a stronger link between stroke and a high glycemic index diet, compared with other nonfatal CVD events.
Dr. Jenkins suggested that the significant excess of non-CVD deaths linked with a high-glycemic-index diet may stem from the impact of this type of diet on cancer-associated mortality.
PURE received partial funding through unrestricted grants from several drug companies. Dr. Jenkins has reported receiving gifts from several food-related trade associations and food companies, as well as research grants from two legume-oriented trade associations.
A version of this article first appeared on Medscape.com.
No benefit seen with everolimus in early breast cancer
At a median follow-up of almost 3 years, rates of disease-free survival, distant metastasis-free survival, and overall survival were similar in the everolimus and hormone therapy-alone arms.
These findings were presented at the inaugural ESMO Virtual Plenary and published in Annals of Oncology.
The UNIRAD results contrast results from prior studies of everolimus in the advanced breast cancer setting. In the BOLERO-2 and BOLERO-4 studies, the mTOR inhibitor provided a progression-free survival benefit when added to hormone therapy.
“There clearly is rationale for targeted therapy in early ER+, HER2- breast cancer,” said Rebecca Dent, MD, of the National Cancer Center in Singapore, who chaired the ESMO Virtual Plenary in which the UNIRAD findings were presented.
“Patients with high-risk luminal breast cancer clearly have an unmet need. We probably still underestimate the risk of early and late recurrences, and chemotherapy is not necessarily the answer,” Dr. Dent said.
She observed that a lot has been learned about the mTOR pathway, including how complicated it is and its role in endocrine resistance. Since mTOR inhibition was standard care in the metastatic setting, “it really is appropriate now to test in early breast cancer,” she added.
Study details
The aim of the UNIRAD study was to compare the efficacy and safety of everolimus plus standard adjuvant hormone therapy to hormone therapy alone in women with ER+, HER2- early breast cancer who had a high risk of recurrence. High risk was defined as having more than four positive nodes, having one or more positive nodes after neoadjuvant chemotherapy or hormone therapy, or having one or more positive nodes and an EPclin score of 3.3 or higher.
The trial enrolled 1,278 patients. At baseline, their median age was 54 years (range, 48-63), 65.8% were postmenopausal, and 52.7% had four or more positive nodes.
The patients were randomized 1:1 to receive 2 years of everolimus plus hormone therapy or placebo plus hormone therapy. The type of hormone therapy was investigor’s choice.
Investigator Thomas Bachelot, MD, PhD, of Centre Leon Berard in Lyon, France, noted that the study started in 2013 and underwent several protocol amendments, first for accrual problems and then because of toxicity. This led to dropping the starting dose of everolimus from 10 mg to 5 mg.
“Acceptability was a concern; 50% of our patients stopped everolimus before study completion for toxicity or personal decision,” Dr. Bachelot acknowledged.
Grade 3 or higher adverse events were more frequent in patients taking everolimus (29.9%) than placebo (15.9%) in combination with hormone therapy. The rates of serious adverse events were a respective 11.8% and 9.3%.
Mucositis was one of the main adverse events, occurring in more than half of all patients treated with everolimus (33.8% grade 1, 25.4% grade 2, and 7.4% grade 3/4). The success of managing this side effect with a dexamethasone mouthwash was not known at the time of the UNIRAD trial design.
The study also showed no benefit of everolimus over placebo for the following efficacy outcomes:
- Disease-free survival – 88% and 89%, respectively (hazard ratio, 0.95; 95% confidence interval, 0.69-1.32; P = .78)
- Distant metastasis-free survival – 91% and 90%, respectively (HR, 0.88; 95% CI, 0.62-1.25)
- Overall survival – both 96% (HR, 1.09; 95% CI, 0.62-1.92).
With the exception of patients who had received tamoxifen rather than an aromatase inhibitor, a preplanned subgroup analysis suggested there was no population of patients who benefited from the addition of everolimus.
Problems interpreting data
There are several problems in interpreting the UNIRAD data, observed study discussant Peter Schmid, MD, PhD, of St. Bartholomew’s Hospital & Barts Cancer Institute in London.
For one, “whether we like it or not,” the trial was underpowered, he said. This was because the trial had been halted early for futility at the first interim analysis when about two-thirds of the intended study cohort had been accrued.
In addition, Dr. Schmid said, this is clearly not a trial that included patients with primary endocrine resistance. In all, 43% of patients had received less than 1 year of endocrine treatment, 42% had received 2-3 years, and 15% had received more than 3 years of endocrine treatment.
Dr. Schmid said that the starting dose of everolimus had to be lowered because of toxicity or poor acceptance. “As a result, two-thirds of patients received a 5-mg dose, and we don’t know whether that had an impact on efficacy,” he said.
Furthermore, the median time on treatment was less than half of what was initially planned, and 53% of patients had to stop everolimus before the end of the study.
Dr. Schmid noted that this discontinuation rate is higher than that seen in trials of CDK4/6 inhibitors added to endocrine treatment. Dropout rates were 19% in the negative Penelope-B trial with palbociclib, 42% in the negative PALLAS trial with palbociclib, and 27% in the positive monarchE trial with abemaciclib.
With such a high discontinuation rate in the UNIRAD trial, “we’re not sure whether we can ultimately evaluate really whether this trial did work,” Dr. Schmid said.
“Could the results change over time?” he asked. “I personally think it is unlikely, as the trial clearly has already an adequate follow-up for what it was supposed to show.”
Looking at whether the trial’s hypothesis is still valid, he added: “I think that is unclear to all of us, and we need to work out whether these compounds are cytostatic in nature, or cytotoxic. And that is something we need to learn over time.”
Commending the study overall, Dr. Schmid observed: “I think it was an excellent trial design based on what we knew at that time,” and the design “was changed in a pragmatic way because of recruitment challenges.”
Something for the future would be to select patients for such trials based on the tumor biology rather than risk status, Dr. Schmid suggested. “That is something we may have to take into consideration with our increasing knowledge around primary and secondary resistance and what treatments we want to introduce to target-resistant clones,” he said.
The UNIRAD study was sponsored by UNICANCER, with funding and support from the French Ministry of Health, Cancer Research UK, Myriad Genetics (which provided Endopredict tests), and Novartis (which provided everolimus and placebo). Dr. Bachelot, Dr. Schmid, and Dr. Dent disclosed relationships with Novartis and several other pharmaceutical companies.
At a median follow-up of almost 3 years, rates of disease-free survival, distant metastasis-free survival, and overall survival were similar in the everolimus and hormone therapy-alone arms.
These findings were presented at the inaugural ESMO Virtual Plenary and published in Annals of Oncology.
The UNIRAD results contrast results from prior studies of everolimus in the advanced breast cancer setting. In the BOLERO-2 and BOLERO-4 studies, the mTOR inhibitor provided a progression-free survival benefit when added to hormone therapy.
“There clearly is rationale for targeted therapy in early ER+, HER2- breast cancer,” said Rebecca Dent, MD, of the National Cancer Center in Singapore, who chaired the ESMO Virtual Plenary in which the UNIRAD findings were presented.
“Patients with high-risk luminal breast cancer clearly have an unmet need. We probably still underestimate the risk of early and late recurrences, and chemotherapy is not necessarily the answer,” Dr. Dent said.
She observed that a lot has been learned about the mTOR pathway, including how complicated it is and its role in endocrine resistance. Since mTOR inhibition was standard care in the metastatic setting, “it really is appropriate now to test in early breast cancer,” she added.
Study details
The aim of the UNIRAD study was to compare the efficacy and safety of everolimus plus standard adjuvant hormone therapy to hormone therapy alone in women with ER+, HER2- early breast cancer who had a high risk of recurrence. High risk was defined as having more than four positive nodes, having one or more positive nodes after neoadjuvant chemotherapy or hormone therapy, or having one or more positive nodes and an EPclin score of 3.3 or higher.
The trial enrolled 1,278 patients. At baseline, their median age was 54 years (range, 48-63), 65.8% were postmenopausal, and 52.7% had four or more positive nodes.
The patients were randomized 1:1 to receive 2 years of everolimus plus hormone therapy or placebo plus hormone therapy. The type of hormone therapy was investigor’s choice.
Investigator Thomas Bachelot, MD, PhD, of Centre Leon Berard in Lyon, France, noted that the study started in 2013 and underwent several protocol amendments, first for accrual problems and then because of toxicity. This led to dropping the starting dose of everolimus from 10 mg to 5 mg.
“Acceptability was a concern; 50% of our patients stopped everolimus before study completion for toxicity or personal decision,” Dr. Bachelot acknowledged.
Grade 3 or higher adverse events were more frequent in patients taking everolimus (29.9%) than placebo (15.9%) in combination with hormone therapy. The rates of serious adverse events were a respective 11.8% and 9.3%.
Mucositis was one of the main adverse events, occurring in more than half of all patients treated with everolimus (33.8% grade 1, 25.4% grade 2, and 7.4% grade 3/4). The success of managing this side effect with a dexamethasone mouthwash was not known at the time of the UNIRAD trial design.
The study also showed no benefit of everolimus over placebo for the following efficacy outcomes:
- Disease-free survival – 88% and 89%, respectively (hazard ratio, 0.95; 95% confidence interval, 0.69-1.32; P = .78)
- Distant metastasis-free survival – 91% and 90%, respectively (HR, 0.88; 95% CI, 0.62-1.25)
- Overall survival – both 96% (HR, 1.09; 95% CI, 0.62-1.92).
With the exception of patients who had received tamoxifen rather than an aromatase inhibitor, a preplanned subgroup analysis suggested there was no population of patients who benefited from the addition of everolimus.
Problems interpreting data
There are several problems in interpreting the UNIRAD data, observed study discussant Peter Schmid, MD, PhD, of St. Bartholomew’s Hospital & Barts Cancer Institute in London.
For one, “whether we like it or not,” the trial was underpowered, he said. This was because the trial had been halted early for futility at the first interim analysis when about two-thirds of the intended study cohort had been accrued.
In addition, Dr. Schmid said, this is clearly not a trial that included patients with primary endocrine resistance. In all, 43% of patients had received less than 1 year of endocrine treatment, 42% had received 2-3 years, and 15% had received more than 3 years of endocrine treatment.
Dr. Schmid said that the starting dose of everolimus had to be lowered because of toxicity or poor acceptance. “As a result, two-thirds of patients received a 5-mg dose, and we don’t know whether that had an impact on efficacy,” he said.
Furthermore, the median time on treatment was less than half of what was initially planned, and 53% of patients had to stop everolimus before the end of the study.
Dr. Schmid noted that this discontinuation rate is higher than that seen in trials of CDK4/6 inhibitors added to endocrine treatment. Dropout rates were 19% in the negative Penelope-B trial with palbociclib, 42% in the negative PALLAS trial with palbociclib, and 27% in the positive monarchE trial with abemaciclib.
With such a high discontinuation rate in the UNIRAD trial, “we’re not sure whether we can ultimately evaluate really whether this trial did work,” Dr. Schmid said.
“Could the results change over time?” he asked. “I personally think it is unlikely, as the trial clearly has already an adequate follow-up for what it was supposed to show.”
Looking at whether the trial’s hypothesis is still valid, he added: “I think that is unclear to all of us, and we need to work out whether these compounds are cytostatic in nature, or cytotoxic. And that is something we need to learn over time.”
Commending the study overall, Dr. Schmid observed: “I think it was an excellent trial design based on what we knew at that time,” and the design “was changed in a pragmatic way because of recruitment challenges.”
Something for the future would be to select patients for such trials based on the tumor biology rather than risk status, Dr. Schmid suggested. “That is something we may have to take into consideration with our increasing knowledge around primary and secondary resistance and what treatments we want to introduce to target-resistant clones,” he said.
The UNIRAD study was sponsored by UNICANCER, with funding and support from the French Ministry of Health, Cancer Research UK, Myriad Genetics (which provided Endopredict tests), and Novartis (which provided everolimus and placebo). Dr. Bachelot, Dr. Schmid, and Dr. Dent disclosed relationships with Novartis and several other pharmaceutical companies.
At a median follow-up of almost 3 years, rates of disease-free survival, distant metastasis-free survival, and overall survival were similar in the everolimus and hormone therapy-alone arms.
These findings were presented at the inaugural ESMO Virtual Plenary and published in Annals of Oncology.
The UNIRAD results contrast results from prior studies of everolimus in the advanced breast cancer setting. In the BOLERO-2 and BOLERO-4 studies, the mTOR inhibitor provided a progression-free survival benefit when added to hormone therapy.
“There clearly is rationale for targeted therapy in early ER+, HER2- breast cancer,” said Rebecca Dent, MD, of the National Cancer Center in Singapore, who chaired the ESMO Virtual Plenary in which the UNIRAD findings were presented.
“Patients with high-risk luminal breast cancer clearly have an unmet need. We probably still underestimate the risk of early and late recurrences, and chemotherapy is not necessarily the answer,” Dr. Dent said.
She observed that a lot has been learned about the mTOR pathway, including how complicated it is and its role in endocrine resistance. Since mTOR inhibition was standard care in the metastatic setting, “it really is appropriate now to test in early breast cancer,” she added.
Study details
The aim of the UNIRAD study was to compare the efficacy and safety of everolimus plus standard adjuvant hormone therapy to hormone therapy alone in women with ER+, HER2- early breast cancer who had a high risk of recurrence. High risk was defined as having more than four positive nodes, having one or more positive nodes after neoadjuvant chemotherapy or hormone therapy, or having one or more positive nodes and an EPclin score of 3.3 or higher.
The trial enrolled 1,278 patients. At baseline, their median age was 54 years (range, 48-63), 65.8% were postmenopausal, and 52.7% had four or more positive nodes.
The patients were randomized 1:1 to receive 2 years of everolimus plus hormone therapy or placebo plus hormone therapy. The type of hormone therapy was investigor’s choice.
Investigator Thomas Bachelot, MD, PhD, of Centre Leon Berard in Lyon, France, noted that the study started in 2013 and underwent several protocol amendments, first for accrual problems and then because of toxicity. This led to dropping the starting dose of everolimus from 10 mg to 5 mg.
“Acceptability was a concern; 50% of our patients stopped everolimus before study completion for toxicity or personal decision,” Dr. Bachelot acknowledged.
Grade 3 or higher adverse events were more frequent in patients taking everolimus (29.9%) than placebo (15.9%) in combination with hormone therapy. The rates of serious adverse events were a respective 11.8% and 9.3%.
Mucositis was one of the main adverse events, occurring in more than half of all patients treated with everolimus (33.8% grade 1, 25.4% grade 2, and 7.4% grade 3/4). The success of managing this side effect with a dexamethasone mouthwash was not known at the time of the UNIRAD trial design.
The study also showed no benefit of everolimus over placebo for the following efficacy outcomes:
- Disease-free survival – 88% and 89%, respectively (hazard ratio, 0.95; 95% confidence interval, 0.69-1.32; P = .78)
- Distant metastasis-free survival – 91% and 90%, respectively (HR, 0.88; 95% CI, 0.62-1.25)
- Overall survival – both 96% (HR, 1.09; 95% CI, 0.62-1.92).
With the exception of patients who had received tamoxifen rather than an aromatase inhibitor, a preplanned subgroup analysis suggested there was no population of patients who benefited from the addition of everolimus.
Problems interpreting data
There are several problems in interpreting the UNIRAD data, observed study discussant Peter Schmid, MD, PhD, of St. Bartholomew’s Hospital & Barts Cancer Institute in London.
For one, “whether we like it or not,” the trial was underpowered, he said. This was because the trial had been halted early for futility at the first interim analysis when about two-thirds of the intended study cohort had been accrued.
In addition, Dr. Schmid said, this is clearly not a trial that included patients with primary endocrine resistance. In all, 43% of patients had received less than 1 year of endocrine treatment, 42% had received 2-3 years, and 15% had received more than 3 years of endocrine treatment.
Dr. Schmid said that the starting dose of everolimus had to be lowered because of toxicity or poor acceptance. “As a result, two-thirds of patients received a 5-mg dose, and we don’t know whether that had an impact on efficacy,” he said.
Furthermore, the median time on treatment was less than half of what was initially planned, and 53% of patients had to stop everolimus before the end of the study.
Dr. Schmid noted that this discontinuation rate is higher than that seen in trials of CDK4/6 inhibitors added to endocrine treatment. Dropout rates were 19% in the negative Penelope-B trial with palbociclib, 42% in the negative PALLAS trial with palbociclib, and 27% in the positive monarchE trial with abemaciclib.
With such a high discontinuation rate in the UNIRAD trial, “we’re not sure whether we can ultimately evaluate really whether this trial did work,” Dr. Schmid said.
“Could the results change over time?” he asked. “I personally think it is unlikely, as the trial clearly has already an adequate follow-up for what it was supposed to show.”
Looking at whether the trial’s hypothesis is still valid, he added: “I think that is unclear to all of us, and we need to work out whether these compounds are cytostatic in nature, or cytotoxic. And that is something we need to learn over time.”
Commending the study overall, Dr. Schmid observed: “I think it was an excellent trial design based on what we knew at that time,” and the design “was changed in a pragmatic way because of recruitment challenges.”
Something for the future would be to select patients for such trials based on the tumor biology rather than risk status, Dr. Schmid suggested. “That is something we may have to take into consideration with our increasing knowledge around primary and secondary resistance and what treatments we want to introduce to target-resistant clones,” he said.
The UNIRAD study was sponsored by UNICANCER, with funding and support from the French Ministry of Health, Cancer Research UK, Myriad Genetics (which provided Endopredict tests), and Novartis (which provided everolimus and placebo). Dr. Bachelot, Dr. Schmid, and Dr. Dent disclosed relationships with Novartis and several other pharmaceutical companies.
FROM ESMO VIRTUAL PLENARY
The Genital Examination in Dermatologic Practice
A casual survey of my dermatology co-residents yielded overwhelmingly unanimous results: A complete skin check goes from head to toe but does not routinely include an examination of the genital area. This observation contrasts starkly with the American Academy of Dermatology’s Basic Dermatology Curriculum, which recommends inspection of the entire skin surface including the mucous membranes (ie, eyes, mouth, anus, genital area) as part of the total-body skin examination (TBSE).1 It even draws attention to so-called hidden areas where lesions easily can be missed, such as the perianal skin. My observation seems far from anecdotal; even a recent attempt at optimizing movements in the TBSE neglected to include examination of the genitalia in the proposed method,2-4 and many practicing dermatologists seem to agree. A survey of international dermatologists at high-risk skin cancer clinics found male and female genitalia were the least frequently examined anatomy sites during the TBSE. Additionally, female genitalia were examined less frequently than male genitalia (labia majora, 28%; penis, 52%; P=.003).5 Another survey of US academic dermatologists (23 dermatologists, 1 nurse practitioner) found that only 4% always visually inspected the vulva during routine annual examinations, and 50% did not think that vulvar examination was the dermatologist’s responsibility.6 Similar findings were reported in a survey of US dermatology residents.7
Why is the genital area routinely omitted from the dermatologic TBSE? Based on the surveys of dermatologists and dermatology residents, the most common reason cited for not examining these sites was patient discomfort, but there also was a dominant belief that other specialties, such as gynecologists, urologists, or primary care providers, routinely examine these areas.5,7 Time constraints also were a concern.
Although examination of sensitive areas can be uncomfortable,8 most patients still expect these locations to be examined during the TBSE. In a survey of 500 adults presenting for TBSE at an academic dermatology clinic, 84% of respondents expected the dermatologist to examine the genital area.9 Similarly, another survey of patient preferences (N=443) for the TBSE found that only 31.3% of women and 12.5% of men preferred not to have their genital area examined.10 As providers, we may be uncomfortable examining the genital area; however, our patients mostly expect it as part of routine practice. There are a number of barriers that may prevent incorporating the genital examination into daily dermatologic practice.
Training in Genital Examinations
Adequate training may be an issue for provider comfort when examining the genital skin. In a survey of dermatology residency program directors (n=38) and residents (n=91), 61.7% reported receiving formal instruction on TBSE technique and 38.3% reported being self-taught. Examination of the genital skin was included only 40% of the time.11 Even vulvar disorder experts have admitted to receiving their training by self-teaching, with only 19% receiving vulvar training during residency and 11% during fellowship.12 Improving this training appears to be an ongoing effort.2
Passing the Buck
It may be easier to think that another provider is routinely examining genital skin based on the relative absence of this area in dermatologic training; however, that does not appear to be the case. In a 1999 survey of primary care providers, only 31% reported performing skin cancer screenings on their adult patients, citing lack of confidence in this clinical skill as the biggest hurdle.13 Similarly, changes in recommendations for the utility of the screening pelvic examination in asymptomatic, average-risk, nonpregnant adult women have decreased the performance of this examination in actual practice.14 Reviews of resident training in vulvovaginal disease also have shown that although dermatology residents receive slightly less formal training hours on vulvar skin disease, they see more than double the number of patients with vulvar disease per year when compared to obstetrics and gynecology residents.15 In practice, dermatologists generally are more confident when evaluating vulvar pigmented lesions than gynecologists.6
The Importance of the Genital Examination
Looking past these barriers seems essential to providing the best dermatologic care, as there are a multitude of neoplastic and inflammatory dermatoses that can affect the genital skin. Furthermore, early diagnosis and treatment of these conditions potentially can limit morbidity and mortality as well as improve quality of life. Genital melanomas are a good example. Although they may be rare, it is well known that genital melanomas are associated with an aggressive disease course and have worse outcomes than melanomas found elsewhere on the body.16,17 Increasing rates of genital and perianal keratinocyte carcinomas make including this as part of the TBSE even more important.18
We also should not forget that inflammatory conditions can routinely involve the genitals.19-21 Although robust data are lacking, chronic vulvar concerns frequently are seen in the primary care setting. In one study in the United Kingdom, 52% of general practitioners surveyed saw more than 3 patients per month with vulvar concerns.22 Even in common dermatologic conditions such as psoriasis and lichen planus, genital involvement often is overlooked despite its relative frequency.23-27 In one study, 60% of psoriasis patients with genital involvement had not had these lesions examined by a physician.28
Theoretically, TBSEs that include genital examination would yield higher and earlier detection rates of neoplasms as well as inflammatory dermatoses.29-32 Thus, there is real value in diagnosing ailments of the genital skin, and dermatologists are well prepared to manage these conditions. Consistently incorporating a genital examination within the TBSE is the first step.
An Approach to the Genital Skin Examination
As with the TBSE, no standardized protocol for the genital skin examination exists, and there is no consensus for how best to perform this evaluation. Ideally, both male and female patients should remove all clothing, including undergarments, though one study found patients preferred to keep undergarments on during the genital examination.10,33,34
In general, adult female genital anatomy is best viewed with the patient in the supine position.6,33,35 There is no clear agreement on the use of stirrups, and the decision to use these may be left to the discretion of the patient. One randomized clinical trial found that women undergoing routine gynecologic examination without stirrups reported less physical discomfort and had a reduced sense of vulnerability than women examined in stirrups.36 During the female genital examination, the head of the bed ideally should be positioned at a 30° to 45° angle to allow the provider to maintain eye contact and face-to-face communication with the patient.33 This positioning also facilitates the use of a handheld mirror to instruct patients on techniques for medication application as well as to point out sites of disease.
For adult males, the genital examination can be performed with the patient standing facing a seated examiner.35 The patient’s gown should be raised to the level of the umbilicus to expose the entire genital region. Good lighting is essential. These recommendations apply mainly to adults, but helpful tips on how to approach evaluating prepubertal children in the dermatology clinic are available.37
The presence of a chaperone also is optional for maximizing patient comfort but also may be helpful for providing medicolegal protection for the provider. It always should be offered regardless of patient gender. A dermatology study found that when patients were examined by a same-gender physician, women and men were more comfortable without a chaperone than with a chaperone, and patients generally preferred fewer bodies in the room during sensitive examinations.9
Educating Patients About the TBSE
The most helpful recommendation for successfully incorporating and performing the genital skin examination as part of the TBSE appears to be patient education. In a randomized double-arm study, patients who received pre-education consisting of written information explaining the need for a TBSE were less likely to be concerned about a genital examination compared to patients who received no information.38 Discussing that skin diseases, including melanoma, can arise in all areas of the body including the genital skin and encouraging patients to perform genital self-examinations is critical.35 In the age of the electronic health record and virtual communication, disseminating this information has become even easier.39 It may be beneficial to explore patients’ TBSE expectations at the outset through these varied avenues to help establish a trusted physician-patient relationship.40
Final Thoughts
Dermatologists should consistently offer a genital examination to all patients who present for a routine TBSE. Patients should be provided with adequate education to assess their comfort level for the skin examination. If a patient declines this examination, the dermatologist should ensure that another physician—be it a gynecologist, primary care provider, or other specialist—is routinely examining the area.6,7
- The skin exam. American Academy of Dermatology. https://digital-catalog.aad.org/diweb/catalog/launch/package/4/did/327974/iid/327974
- Helm MF, Hallock KK, Bisbee E, et al. Optimizing the total-body skin exam: an observational cohort study. J Am Acad Dermatol. 2019;81:1115-1119.
- Nielson CB, Grant-Kels JM. Commentary on “optimizing the total-body skin exam: an observational cohort study.” J Am Acad Dermatol. 2019;81:E131.
- Helm MF, Hallock KK, Bisbee E, et al. Reply to: “commentary on ‘optimizing the total-body skin exam: an observational cohort study.’” J Am Acad Dermatol. 2019;81:E133.
- Bajaj S, Wolner ZJ, Dusza SW, et al. Total body skin examination practices: a survey study amongst dermatologists at high-risk skin cancer clinics. Dermatol Pract Concept. 2019;9:132-138.
- Krathen MS, Liu CL, Loo DS. Vulvar melanoma: a missed opportunity for early intervention? J Am Acad Dermatol. 2012;66:697-698.
- Hosking AM, Chapman L, Zachary CB, et al. Anogenital examination practices among U.S. dermatology residents [published online January 9, 2020]. J Am Acad Dermatol. doi:10.1016/j.jaad.2019.12.061
- Grundström H, Wallin K, Berterö C. ‘You expose yourself in so many ways’: young women’s experiences of pelvic examination. J Psychosom Obstet Gynaecol. 2011;32:59-64.
- McClatchey Connors T, Reddy P, Weiss E, et al. Patient comfort and expectations for total body skin examinations: a cross-sectional study. J Am Acad Dermatol. 2019;81:615-617.
- Houston NA, Secrest AM, Harris RJ, et al. Patient preferences during skin cancer screening examination. JAMA Dermatol. 2016;152:1052-1054.
- Milchak M, Miller J, Dellasega C, et al. Education on total body skin examination in dermatology residency. Poster presented at: Association of Professors of Dermatology Annual Meeting; September 25-26, 2015; Chicago, IL.
- Venkatesan A, Farsani T, O’Sullivan P, et al. Identifying competencies in vulvar disorder management for medical students and residents: a survey of US vulvar disorder experts. J Low Genit Tract Dis. 2012;16:398-402.
- Kirsner RS, Muhkerjee S, Federman DG. Skin cancer screening in primary care: prevalence and barriers. J Am Acad Dermatol. 1999;41:564-566.
- Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Screening for gynecologic conditions with pelvic examination: US Preventive Services Task Force recommendation statement. JAMA. 2017;317:947-953.
- Comstock JR, Endo JO, Kornik RI. Adequacy of dermatology and ob-gyn graduate medical education for inflammatory vulvovaginal skin disease: a nationwide needs assessment survey. Int J Womens Dermatol. 2020;6:182-185.
- Sanchez A, Rodríguez D, Allard CB, et al. Primary genitourinary melanoma: epidemiology and disease-specific survival in a large population-based cohort. Urol Oncol. 2016;34:E7-E14.
- Vyas R, Thompson CL, Zargar H, et al. Epidemiology of genitourinary melanoma in the United States: 1992 through 2012. J Am Acad Dermatol. 2016;75:144-150.
- Misitzis A, Beatson M, Weinstock MA. Keratinocyte carcinoma mortality in the United States as reported in death certificates, 2011-2017. Dermatol Surg. 2020;46:1135-1140.
- Sullivan AK, Straughair GJ, Marwood RP, et al. A multidisciplinary vulva clinic: the role of genito-urinary medicine. J Eur Acad Dermatol Venereol. 1999;13:36-40.
- Goncalves DLM, Romero RL, Ferreira PL, et al. Clinical and epidemiological profile of patients attended in a vulvar clinic of the dermatology outpatient unit of a tertiary hospital during a 4-year period. Int J Dermatol. 2019;58:1311-1316.
- Bauer A, Greif C, Vollandt R, et al. Vulval diseases need an interdisciplinary approach. Dermatology. 1999;199:223-226.
- Nunns D, Mandal D. The chronically symptomatic vulva: prevalence in primary health care. Genitourin Med. 1996;72:343-344.
- Meeuwis KA, de Hullu JA, de Jager ME, et al. Genital psoriasis: a questionnaire-based survey on a concealed skin disease in the Netherlands. J Eur Acad Dermatol Venereol. 2010;24:1425-1430.
- Ryan C, Sadlier M, De Vol E, et al. Genital psoriasis is associated with significant impairment in quality of life and sexual functioning. J Am Acad Dermatol. 2015;72:978-983.
- Fouéré S, Adjadj L, Pawin H. How patients experience psoriasis: results from a European survey. J Eur Acad Dermatol Venereol. 2005;(19 suppl 3):2-6.
- Eisen D. The evaluation of cutaneous, genital, scalp, nail, esophageal, and ocular involvement in patients with oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;88:431-436.
- Meeuwis KAP, Potts Bleakman A, van de Kerkhof PCM, et al. Prevalence of genital psoriasis in patients with psoriasis. J Dermatolog Treat. 2018;29:754-760.
- Larsabal M, Ly S, Sbidian E, et al. GENIPSO: a French prospective study assessing instantaneous prevalence, clinical features and impact on quality of life of genital psoriasis among patients consulting for psoriasis. Br J Dermatol. 2019;180:647-656.
- Rigel DS, Friedman RJ, Kopf AW, et al. Importance of complete cutaneous examination for the detection of malignant melanoma. J Am Acad Dermatol. 1986;14(5 pt 1):857-860.
- De Rooij MJ, Rampen FH, Schouten LJ, et al. Total skin examination during screening for malignant melanoma does not increase the detection rate. Br J Dermatol. 1996;135:42-45.
- Johansson M, Brodersen J, Gøtzsche PC, et al. Screening for reducing morbidity and mortality in malignant melanoma. Cochrane Database Syst Rev. 2019;6:CD012352.
- Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Screening for skin cancer: US Preventive Services Task Force recommendation statement. JAMA. 2016;316:429-435.
- Mauskar MM, Marathe K, Venkatesan A, et al. Vulvar diseases: approach to the patient. J Am Acad Dermatol. 2020;82:1277-1284.
- Chen C. How full is a full body skin exam? investigation into the practice of the full body skin exam as conducted by board-certified and board-eligibile dermatologists. Michigan State University. Published April 24, 2015. Accessed February 4, 2021. https://cdn.ymaws.com/www.aocd.org/resource/resmgr/2015SpringMeeting/ChenSpr15.pdf
- Zikry J, Chapman LW, Korta DZ, et al. Genital melanoma: are we adequately screening our patients? Dermatol Online J. 2017;23:13030/qt7zk476vn.
- Seehusen DA, Johnson DR, Earwood JS, et al. Improving women’s experience during speculum examinations at routine gynaecological visits: randomised clinical trial [published online June 27, 2006]. BMJ. 2006;333:171.
- Habeshian K, Fowler K, Gomez-Lobo V, et al. Guidelines for pediatric anogenital examination: insights from our vulvar dermatology clinic. Pediatr Dermatol. 2018;35:693-695.
- Leffell DJ, Berwick M, Bolognia J. The effect of pre-education on patient compliance with full-body examination in a public skin cancer screening. J Dermatol Surg Oncol. 1993;19:660-663.
- Hong J, Nguyen TV, Prose NS. Compassionate care: enhancing physician-patient communication and education in dermatology: part II: patient education. J Am Acad Dermatol. 2013;68:364.e361-310.
- Rosamilia LL. The naked truth about total body skin examination: a lesson from Goldilocks and the Three Bears. American Academy of Dermatology. Published November 13, 2019. Accessed February 4, 2021. https://www.aad.org/dw/dw-insights-and-inquiries/2019-archive/november/dwii-11-13-19-the-naked-truth-about-total-body-skin-examination-a-lesson-from-goldilocks-and-the-three-bears
A casual survey of my dermatology co-residents yielded overwhelmingly unanimous results: A complete skin check goes from head to toe but does not routinely include an examination of the genital area. This observation contrasts starkly with the American Academy of Dermatology’s Basic Dermatology Curriculum, which recommends inspection of the entire skin surface including the mucous membranes (ie, eyes, mouth, anus, genital area) as part of the total-body skin examination (TBSE).1 It even draws attention to so-called hidden areas where lesions easily can be missed, such as the perianal skin. My observation seems far from anecdotal; even a recent attempt at optimizing movements in the TBSE neglected to include examination of the genitalia in the proposed method,2-4 and many practicing dermatologists seem to agree. A survey of international dermatologists at high-risk skin cancer clinics found male and female genitalia were the least frequently examined anatomy sites during the TBSE. Additionally, female genitalia were examined less frequently than male genitalia (labia majora, 28%; penis, 52%; P=.003).5 Another survey of US academic dermatologists (23 dermatologists, 1 nurse practitioner) found that only 4% always visually inspected the vulva during routine annual examinations, and 50% did not think that vulvar examination was the dermatologist’s responsibility.6 Similar findings were reported in a survey of US dermatology residents.7
Why is the genital area routinely omitted from the dermatologic TBSE? Based on the surveys of dermatologists and dermatology residents, the most common reason cited for not examining these sites was patient discomfort, but there also was a dominant belief that other specialties, such as gynecologists, urologists, or primary care providers, routinely examine these areas.5,7 Time constraints also were a concern.
Although examination of sensitive areas can be uncomfortable,8 most patients still expect these locations to be examined during the TBSE. In a survey of 500 adults presenting for TBSE at an academic dermatology clinic, 84% of respondents expected the dermatologist to examine the genital area.9 Similarly, another survey of patient preferences (N=443) for the TBSE found that only 31.3% of women and 12.5% of men preferred not to have their genital area examined.10 As providers, we may be uncomfortable examining the genital area; however, our patients mostly expect it as part of routine practice. There are a number of barriers that may prevent incorporating the genital examination into daily dermatologic practice.
Training in Genital Examinations
Adequate training may be an issue for provider comfort when examining the genital skin. In a survey of dermatology residency program directors (n=38) and residents (n=91), 61.7% reported receiving formal instruction on TBSE technique and 38.3% reported being self-taught. Examination of the genital skin was included only 40% of the time.11 Even vulvar disorder experts have admitted to receiving their training by self-teaching, with only 19% receiving vulvar training during residency and 11% during fellowship.12 Improving this training appears to be an ongoing effort.2
Passing the Buck
It may be easier to think that another provider is routinely examining genital skin based on the relative absence of this area in dermatologic training; however, that does not appear to be the case. In a 1999 survey of primary care providers, only 31% reported performing skin cancer screenings on their adult patients, citing lack of confidence in this clinical skill as the biggest hurdle.13 Similarly, changes in recommendations for the utility of the screening pelvic examination in asymptomatic, average-risk, nonpregnant adult women have decreased the performance of this examination in actual practice.14 Reviews of resident training in vulvovaginal disease also have shown that although dermatology residents receive slightly less formal training hours on vulvar skin disease, they see more than double the number of patients with vulvar disease per year when compared to obstetrics and gynecology residents.15 In practice, dermatologists generally are more confident when evaluating vulvar pigmented lesions than gynecologists.6
The Importance of the Genital Examination
Looking past these barriers seems essential to providing the best dermatologic care, as there are a multitude of neoplastic and inflammatory dermatoses that can affect the genital skin. Furthermore, early diagnosis and treatment of these conditions potentially can limit morbidity and mortality as well as improve quality of life. Genital melanomas are a good example. Although they may be rare, it is well known that genital melanomas are associated with an aggressive disease course and have worse outcomes than melanomas found elsewhere on the body.16,17 Increasing rates of genital and perianal keratinocyte carcinomas make including this as part of the TBSE even more important.18
We also should not forget that inflammatory conditions can routinely involve the genitals.19-21 Although robust data are lacking, chronic vulvar concerns frequently are seen in the primary care setting. In one study in the United Kingdom, 52% of general practitioners surveyed saw more than 3 patients per month with vulvar concerns.22 Even in common dermatologic conditions such as psoriasis and lichen planus, genital involvement often is overlooked despite its relative frequency.23-27 In one study, 60% of psoriasis patients with genital involvement had not had these lesions examined by a physician.28
Theoretically, TBSEs that include genital examination would yield higher and earlier detection rates of neoplasms as well as inflammatory dermatoses.29-32 Thus, there is real value in diagnosing ailments of the genital skin, and dermatologists are well prepared to manage these conditions. Consistently incorporating a genital examination within the TBSE is the first step.
An Approach to the Genital Skin Examination
As with the TBSE, no standardized protocol for the genital skin examination exists, and there is no consensus for how best to perform this evaluation. Ideally, both male and female patients should remove all clothing, including undergarments, though one study found patients preferred to keep undergarments on during the genital examination.10,33,34
In general, adult female genital anatomy is best viewed with the patient in the supine position.6,33,35 There is no clear agreement on the use of stirrups, and the decision to use these may be left to the discretion of the patient. One randomized clinical trial found that women undergoing routine gynecologic examination without stirrups reported less physical discomfort and had a reduced sense of vulnerability than women examined in stirrups.36 During the female genital examination, the head of the bed ideally should be positioned at a 30° to 45° angle to allow the provider to maintain eye contact and face-to-face communication with the patient.33 This positioning also facilitates the use of a handheld mirror to instruct patients on techniques for medication application as well as to point out sites of disease.
For adult males, the genital examination can be performed with the patient standing facing a seated examiner.35 The patient’s gown should be raised to the level of the umbilicus to expose the entire genital region. Good lighting is essential. These recommendations apply mainly to adults, but helpful tips on how to approach evaluating prepubertal children in the dermatology clinic are available.37
The presence of a chaperone also is optional for maximizing patient comfort but also may be helpful for providing medicolegal protection for the provider. It always should be offered regardless of patient gender. A dermatology study found that when patients were examined by a same-gender physician, women and men were more comfortable without a chaperone than with a chaperone, and patients generally preferred fewer bodies in the room during sensitive examinations.9
Educating Patients About the TBSE
The most helpful recommendation for successfully incorporating and performing the genital skin examination as part of the TBSE appears to be patient education. In a randomized double-arm study, patients who received pre-education consisting of written information explaining the need for a TBSE were less likely to be concerned about a genital examination compared to patients who received no information.38 Discussing that skin diseases, including melanoma, can arise in all areas of the body including the genital skin and encouraging patients to perform genital self-examinations is critical.35 In the age of the electronic health record and virtual communication, disseminating this information has become even easier.39 It may be beneficial to explore patients’ TBSE expectations at the outset through these varied avenues to help establish a trusted physician-patient relationship.40
Final Thoughts
Dermatologists should consistently offer a genital examination to all patients who present for a routine TBSE. Patients should be provided with adequate education to assess their comfort level for the skin examination. If a patient declines this examination, the dermatologist should ensure that another physician—be it a gynecologist, primary care provider, or other specialist—is routinely examining the area.6,7
A casual survey of my dermatology co-residents yielded overwhelmingly unanimous results: A complete skin check goes from head to toe but does not routinely include an examination of the genital area. This observation contrasts starkly with the American Academy of Dermatology’s Basic Dermatology Curriculum, which recommends inspection of the entire skin surface including the mucous membranes (ie, eyes, mouth, anus, genital area) as part of the total-body skin examination (TBSE).1 It even draws attention to so-called hidden areas where lesions easily can be missed, such as the perianal skin. My observation seems far from anecdotal; even a recent attempt at optimizing movements in the TBSE neglected to include examination of the genitalia in the proposed method,2-4 and many practicing dermatologists seem to agree. A survey of international dermatologists at high-risk skin cancer clinics found male and female genitalia were the least frequently examined anatomy sites during the TBSE. Additionally, female genitalia were examined less frequently than male genitalia (labia majora, 28%; penis, 52%; P=.003).5 Another survey of US academic dermatologists (23 dermatologists, 1 nurse practitioner) found that only 4% always visually inspected the vulva during routine annual examinations, and 50% did not think that vulvar examination was the dermatologist’s responsibility.6 Similar findings were reported in a survey of US dermatology residents.7
Why is the genital area routinely omitted from the dermatologic TBSE? Based on the surveys of dermatologists and dermatology residents, the most common reason cited for not examining these sites was patient discomfort, but there also was a dominant belief that other specialties, such as gynecologists, urologists, or primary care providers, routinely examine these areas.5,7 Time constraints also were a concern.
Although examination of sensitive areas can be uncomfortable,8 most patients still expect these locations to be examined during the TBSE. In a survey of 500 adults presenting for TBSE at an academic dermatology clinic, 84% of respondents expected the dermatologist to examine the genital area.9 Similarly, another survey of patient preferences (N=443) for the TBSE found that only 31.3% of women and 12.5% of men preferred not to have their genital area examined.10 As providers, we may be uncomfortable examining the genital area; however, our patients mostly expect it as part of routine practice. There are a number of barriers that may prevent incorporating the genital examination into daily dermatologic practice.
Training in Genital Examinations
Adequate training may be an issue for provider comfort when examining the genital skin. In a survey of dermatology residency program directors (n=38) and residents (n=91), 61.7% reported receiving formal instruction on TBSE technique and 38.3% reported being self-taught. Examination of the genital skin was included only 40% of the time.11 Even vulvar disorder experts have admitted to receiving their training by self-teaching, with only 19% receiving vulvar training during residency and 11% during fellowship.12 Improving this training appears to be an ongoing effort.2
Passing the Buck
It may be easier to think that another provider is routinely examining genital skin based on the relative absence of this area in dermatologic training; however, that does not appear to be the case. In a 1999 survey of primary care providers, only 31% reported performing skin cancer screenings on their adult patients, citing lack of confidence in this clinical skill as the biggest hurdle.13 Similarly, changes in recommendations for the utility of the screening pelvic examination in asymptomatic, average-risk, nonpregnant adult women have decreased the performance of this examination in actual practice.14 Reviews of resident training in vulvovaginal disease also have shown that although dermatology residents receive slightly less formal training hours on vulvar skin disease, they see more than double the number of patients with vulvar disease per year when compared to obstetrics and gynecology residents.15 In practice, dermatologists generally are more confident when evaluating vulvar pigmented lesions than gynecologists.6
The Importance of the Genital Examination
Looking past these barriers seems essential to providing the best dermatologic care, as there are a multitude of neoplastic and inflammatory dermatoses that can affect the genital skin. Furthermore, early diagnosis and treatment of these conditions potentially can limit morbidity and mortality as well as improve quality of life. Genital melanomas are a good example. Although they may be rare, it is well known that genital melanomas are associated with an aggressive disease course and have worse outcomes than melanomas found elsewhere on the body.16,17 Increasing rates of genital and perianal keratinocyte carcinomas make including this as part of the TBSE even more important.18
We also should not forget that inflammatory conditions can routinely involve the genitals.19-21 Although robust data are lacking, chronic vulvar concerns frequently are seen in the primary care setting. In one study in the United Kingdom, 52% of general practitioners surveyed saw more than 3 patients per month with vulvar concerns.22 Even in common dermatologic conditions such as psoriasis and lichen planus, genital involvement often is overlooked despite its relative frequency.23-27 In one study, 60% of psoriasis patients with genital involvement had not had these lesions examined by a physician.28
Theoretically, TBSEs that include genital examination would yield higher and earlier detection rates of neoplasms as well as inflammatory dermatoses.29-32 Thus, there is real value in diagnosing ailments of the genital skin, and dermatologists are well prepared to manage these conditions. Consistently incorporating a genital examination within the TBSE is the first step.
An Approach to the Genital Skin Examination
As with the TBSE, no standardized protocol for the genital skin examination exists, and there is no consensus for how best to perform this evaluation. Ideally, both male and female patients should remove all clothing, including undergarments, though one study found patients preferred to keep undergarments on during the genital examination.10,33,34
In general, adult female genital anatomy is best viewed with the patient in the supine position.6,33,35 There is no clear agreement on the use of stirrups, and the decision to use these may be left to the discretion of the patient. One randomized clinical trial found that women undergoing routine gynecologic examination without stirrups reported less physical discomfort and had a reduced sense of vulnerability than women examined in stirrups.36 During the female genital examination, the head of the bed ideally should be positioned at a 30° to 45° angle to allow the provider to maintain eye contact and face-to-face communication with the patient.33 This positioning also facilitates the use of a handheld mirror to instruct patients on techniques for medication application as well as to point out sites of disease.
For adult males, the genital examination can be performed with the patient standing facing a seated examiner.35 The patient’s gown should be raised to the level of the umbilicus to expose the entire genital region. Good lighting is essential. These recommendations apply mainly to adults, but helpful tips on how to approach evaluating prepubertal children in the dermatology clinic are available.37
The presence of a chaperone also is optional for maximizing patient comfort but also may be helpful for providing medicolegal protection for the provider. It always should be offered regardless of patient gender. A dermatology study found that when patients were examined by a same-gender physician, women and men were more comfortable without a chaperone than with a chaperone, and patients generally preferred fewer bodies in the room during sensitive examinations.9
Educating Patients About the TBSE
The most helpful recommendation for successfully incorporating and performing the genital skin examination as part of the TBSE appears to be patient education. In a randomized double-arm study, patients who received pre-education consisting of written information explaining the need for a TBSE were less likely to be concerned about a genital examination compared to patients who received no information.38 Discussing that skin diseases, including melanoma, can arise in all areas of the body including the genital skin and encouraging patients to perform genital self-examinations is critical.35 In the age of the electronic health record and virtual communication, disseminating this information has become even easier.39 It may be beneficial to explore patients’ TBSE expectations at the outset through these varied avenues to help establish a trusted physician-patient relationship.40
Final Thoughts
Dermatologists should consistently offer a genital examination to all patients who present for a routine TBSE. Patients should be provided with adequate education to assess their comfort level for the skin examination. If a patient declines this examination, the dermatologist should ensure that another physician—be it a gynecologist, primary care provider, or other specialist—is routinely examining the area.6,7
- The skin exam. American Academy of Dermatology. https://digital-catalog.aad.org/diweb/catalog/launch/package/4/did/327974/iid/327974
- Helm MF, Hallock KK, Bisbee E, et al. Optimizing the total-body skin exam: an observational cohort study. J Am Acad Dermatol. 2019;81:1115-1119.
- Nielson CB, Grant-Kels JM. Commentary on “optimizing the total-body skin exam: an observational cohort study.” J Am Acad Dermatol. 2019;81:E131.
- Helm MF, Hallock KK, Bisbee E, et al. Reply to: “commentary on ‘optimizing the total-body skin exam: an observational cohort study.’” J Am Acad Dermatol. 2019;81:E133.
- Bajaj S, Wolner ZJ, Dusza SW, et al. Total body skin examination practices: a survey study amongst dermatologists at high-risk skin cancer clinics. Dermatol Pract Concept. 2019;9:132-138.
- Krathen MS, Liu CL, Loo DS. Vulvar melanoma: a missed opportunity for early intervention? J Am Acad Dermatol. 2012;66:697-698.
- Hosking AM, Chapman L, Zachary CB, et al. Anogenital examination practices among U.S. dermatology residents [published online January 9, 2020]. J Am Acad Dermatol. doi:10.1016/j.jaad.2019.12.061
- Grundström H, Wallin K, Berterö C. ‘You expose yourself in so many ways’: young women’s experiences of pelvic examination. J Psychosom Obstet Gynaecol. 2011;32:59-64.
- McClatchey Connors T, Reddy P, Weiss E, et al. Patient comfort and expectations for total body skin examinations: a cross-sectional study. J Am Acad Dermatol. 2019;81:615-617.
- Houston NA, Secrest AM, Harris RJ, et al. Patient preferences during skin cancer screening examination. JAMA Dermatol. 2016;152:1052-1054.
- Milchak M, Miller J, Dellasega C, et al. Education on total body skin examination in dermatology residency. Poster presented at: Association of Professors of Dermatology Annual Meeting; September 25-26, 2015; Chicago, IL.
- Venkatesan A, Farsani T, O’Sullivan P, et al. Identifying competencies in vulvar disorder management for medical students and residents: a survey of US vulvar disorder experts. J Low Genit Tract Dis. 2012;16:398-402.
- Kirsner RS, Muhkerjee S, Federman DG. Skin cancer screening in primary care: prevalence and barriers. J Am Acad Dermatol. 1999;41:564-566.
- Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Screening for gynecologic conditions with pelvic examination: US Preventive Services Task Force recommendation statement. JAMA. 2017;317:947-953.
- Comstock JR, Endo JO, Kornik RI. Adequacy of dermatology and ob-gyn graduate medical education for inflammatory vulvovaginal skin disease: a nationwide needs assessment survey. Int J Womens Dermatol. 2020;6:182-185.
- Sanchez A, Rodríguez D, Allard CB, et al. Primary genitourinary melanoma: epidemiology and disease-specific survival in a large population-based cohort. Urol Oncol. 2016;34:E7-E14.
- Vyas R, Thompson CL, Zargar H, et al. Epidemiology of genitourinary melanoma in the United States: 1992 through 2012. J Am Acad Dermatol. 2016;75:144-150.
- Misitzis A, Beatson M, Weinstock MA. Keratinocyte carcinoma mortality in the United States as reported in death certificates, 2011-2017. Dermatol Surg. 2020;46:1135-1140.
- Sullivan AK, Straughair GJ, Marwood RP, et al. A multidisciplinary vulva clinic: the role of genito-urinary medicine. J Eur Acad Dermatol Venereol. 1999;13:36-40.
- Goncalves DLM, Romero RL, Ferreira PL, et al. Clinical and epidemiological profile of patients attended in a vulvar clinic of the dermatology outpatient unit of a tertiary hospital during a 4-year period. Int J Dermatol. 2019;58:1311-1316.
- Bauer A, Greif C, Vollandt R, et al. Vulval diseases need an interdisciplinary approach. Dermatology. 1999;199:223-226.
- Nunns D, Mandal D. The chronically symptomatic vulva: prevalence in primary health care. Genitourin Med. 1996;72:343-344.
- Meeuwis KA, de Hullu JA, de Jager ME, et al. Genital psoriasis: a questionnaire-based survey on a concealed skin disease in the Netherlands. J Eur Acad Dermatol Venereol. 2010;24:1425-1430.
- Ryan C, Sadlier M, De Vol E, et al. Genital psoriasis is associated with significant impairment in quality of life and sexual functioning. J Am Acad Dermatol. 2015;72:978-983.
- Fouéré S, Adjadj L, Pawin H. How patients experience psoriasis: results from a European survey. J Eur Acad Dermatol Venereol. 2005;(19 suppl 3):2-6.
- Eisen D. The evaluation of cutaneous, genital, scalp, nail, esophageal, and ocular involvement in patients with oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;88:431-436.
- Meeuwis KAP, Potts Bleakman A, van de Kerkhof PCM, et al. Prevalence of genital psoriasis in patients with psoriasis. J Dermatolog Treat. 2018;29:754-760.
- Larsabal M, Ly S, Sbidian E, et al. GENIPSO: a French prospective study assessing instantaneous prevalence, clinical features and impact on quality of life of genital psoriasis among patients consulting for psoriasis. Br J Dermatol. 2019;180:647-656.
- Rigel DS, Friedman RJ, Kopf AW, et al. Importance of complete cutaneous examination for the detection of malignant melanoma. J Am Acad Dermatol. 1986;14(5 pt 1):857-860.
- De Rooij MJ, Rampen FH, Schouten LJ, et al. Total skin examination during screening for malignant melanoma does not increase the detection rate. Br J Dermatol. 1996;135:42-45.
- Johansson M, Brodersen J, Gøtzsche PC, et al. Screening for reducing morbidity and mortality in malignant melanoma. Cochrane Database Syst Rev. 2019;6:CD012352.
- Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Screening for skin cancer: US Preventive Services Task Force recommendation statement. JAMA. 2016;316:429-435.
- Mauskar MM, Marathe K, Venkatesan A, et al. Vulvar diseases: approach to the patient. J Am Acad Dermatol. 2020;82:1277-1284.
- Chen C. How full is a full body skin exam? investigation into the practice of the full body skin exam as conducted by board-certified and board-eligibile dermatologists. Michigan State University. Published April 24, 2015. Accessed February 4, 2021. https://cdn.ymaws.com/www.aocd.org/resource/resmgr/2015SpringMeeting/ChenSpr15.pdf
- Zikry J, Chapman LW, Korta DZ, et al. Genital melanoma: are we adequately screening our patients? Dermatol Online J. 2017;23:13030/qt7zk476vn.
- Seehusen DA, Johnson DR, Earwood JS, et al. Improving women’s experience during speculum examinations at routine gynaecological visits: randomised clinical trial [published online June 27, 2006]. BMJ. 2006;333:171.
- Habeshian K, Fowler K, Gomez-Lobo V, et al. Guidelines for pediatric anogenital examination: insights from our vulvar dermatology clinic. Pediatr Dermatol. 2018;35:693-695.
- Leffell DJ, Berwick M, Bolognia J. The effect of pre-education on patient compliance with full-body examination in a public skin cancer screening. J Dermatol Surg Oncol. 1993;19:660-663.
- Hong J, Nguyen TV, Prose NS. Compassionate care: enhancing physician-patient communication and education in dermatology: part II: patient education. J Am Acad Dermatol. 2013;68:364.e361-310.
- Rosamilia LL. The naked truth about total body skin examination: a lesson from Goldilocks and the Three Bears. American Academy of Dermatology. Published November 13, 2019. Accessed February 4, 2021. https://www.aad.org/dw/dw-insights-and-inquiries/2019-archive/november/dwii-11-13-19-the-naked-truth-about-total-body-skin-examination-a-lesson-from-goldilocks-and-the-three-bears
- The skin exam. American Academy of Dermatology. https://digital-catalog.aad.org/diweb/catalog/launch/package/4/did/327974/iid/327974
- Helm MF, Hallock KK, Bisbee E, et al. Optimizing the total-body skin exam: an observational cohort study. J Am Acad Dermatol. 2019;81:1115-1119.
- Nielson CB, Grant-Kels JM. Commentary on “optimizing the total-body skin exam: an observational cohort study.” J Am Acad Dermatol. 2019;81:E131.
- Helm MF, Hallock KK, Bisbee E, et al. Reply to: “commentary on ‘optimizing the total-body skin exam: an observational cohort study.’” J Am Acad Dermatol. 2019;81:E133.
- Bajaj S, Wolner ZJ, Dusza SW, et al. Total body skin examination practices: a survey study amongst dermatologists at high-risk skin cancer clinics. Dermatol Pract Concept. 2019;9:132-138.
- Krathen MS, Liu CL, Loo DS. Vulvar melanoma: a missed opportunity for early intervention? J Am Acad Dermatol. 2012;66:697-698.
- Hosking AM, Chapman L, Zachary CB, et al. Anogenital examination practices among U.S. dermatology residents [published online January 9, 2020]. J Am Acad Dermatol. doi:10.1016/j.jaad.2019.12.061
- Grundström H, Wallin K, Berterö C. ‘You expose yourself in so many ways’: young women’s experiences of pelvic examination. J Psychosom Obstet Gynaecol. 2011;32:59-64.
- McClatchey Connors T, Reddy P, Weiss E, et al. Patient comfort and expectations for total body skin examinations: a cross-sectional study. J Am Acad Dermatol. 2019;81:615-617.
- Houston NA, Secrest AM, Harris RJ, et al. Patient preferences during skin cancer screening examination. JAMA Dermatol. 2016;152:1052-1054.
- Milchak M, Miller J, Dellasega C, et al. Education on total body skin examination in dermatology residency. Poster presented at: Association of Professors of Dermatology Annual Meeting; September 25-26, 2015; Chicago, IL.
- Venkatesan A, Farsani T, O’Sullivan P, et al. Identifying competencies in vulvar disorder management for medical students and residents: a survey of US vulvar disorder experts. J Low Genit Tract Dis. 2012;16:398-402.
- Kirsner RS, Muhkerjee S, Federman DG. Skin cancer screening in primary care: prevalence and barriers. J Am Acad Dermatol. 1999;41:564-566.
- Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Screening for gynecologic conditions with pelvic examination: US Preventive Services Task Force recommendation statement. JAMA. 2017;317:947-953.
- Comstock JR, Endo JO, Kornik RI. Adequacy of dermatology and ob-gyn graduate medical education for inflammatory vulvovaginal skin disease: a nationwide needs assessment survey. Int J Womens Dermatol. 2020;6:182-185.
- Sanchez A, Rodríguez D, Allard CB, et al. Primary genitourinary melanoma: epidemiology and disease-specific survival in a large population-based cohort. Urol Oncol. 2016;34:E7-E14.
- Vyas R, Thompson CL, Zargar H, et al. Epidemiology of genitourinary melanoma in the United States: 1992 through 2012. J Am Acad Dermatol. 2016;75:144-150.
- Misitzis A, Beatson M, Weinstock MA. Keratinocyte carcinoma mortality in the United States as reported in death certificates, 2011-2017. Dermatol Surg. 2020;46:1135-1140.
- Sullivan AK, Straughair GJ, Marwood RP, et al. A multidisciplinary vulva clinic: the role of genito-urinary medicine. J Eur Acad Dermatol Venereol. 1999;13:36-40.
- Goncalves DLM, Romero RL, Ferreira PL, et al. Clinical and epidemiological profile of patients attended in a vulvar clinic of the dermatology outpatient unit of a tertiary hospital during a 4-year period. Int J Dermatol. 2019;58:1311-1316.
- Bauer A, Greif C, Vollandt R, et al. Vulval diseases need an interdisciplinary approach. Dermatology. 1999;199:223-226.
- Nunns D, Mandal D. The chronically symptomatic vulva: prevalence in primary health care. Genitourin Med. 1996;72:343-344.
- Meeuwis KA, de Hullu JA, de Jager ME, et al. Genital psoriasis: a questionnaire-based survey on a concealed skin disease in the Netherlands. J Eur Acad Dermatol Venereol. 2010;24:1425-1430.
- Ryan C, Sadlier M, De Vol E, et al. Genital psoriasis is associated with significant impairment in quality of life and sexual functioning. J Am Acad Dermatol. 2015;72:978-983.
- Fouéré S, Adjadj L, Pawin H. How patients experience psoriasis: results from a European survey. J Eur Acad Dermatol Venereol. 2005;(19 suppl 3):2-6.
- Eisen D. The evaluation of cutaneous, genital, scalp, nail, esophageal, and ocular involvement in patients with oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;88:431-436.
- Meeuwis KAP, Potts Bleakman A, van de Kerkhof PCM, et al. Prevalence of genital psoriasis in patients with psoriasis. J Dermatolog Treat. 2018;29:754-760.
- Larsabal M, Ly S, Sbidian E, et al. GENIPSO: a French prospective study assessing instantaneous prevalence, clinical features and impact on quality of life of genital psoriasis among patients consulting for psoriasis. Br J Dermatol. 2019;180:647-656.
- Rigel DS, Friedman RJ, Kopf AW, et al. Importance of complete cutaneous examination for the detection of malignant melanoma. J Am Acad Dermatol. 1986;14(5 pt 1):857-860.
- De Rooij MJ, Rampen FH, Schouten LJ, et al. Total skin examination during screening for malignant melanoma does not increase the detection rate. Br J Dermatol. 1996;135:42-45.
- Johansson M, Brodersen J, Gøtzsche PC, et al. Screening for reducing morbidity and mortality in malignant melanoma. Cochrane Database Syst Rev. 2019;6:CD012352.
- Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Screening for skin cancer: US Preventive Services Task Force recommendation statement. JAMA. 2016;316:429-435.
- Mauskar MM, Marathe K, Venkatesan A, et al. Vulvar diseases: approach to the patient. J Am Acad Dermatol. 2020;82:1277-1284.
- Chen C. How full is a full body skin exam? investigation into the practice of the full body skin exam as conducted by board-certified and board-eligibile dermatologists. Michigan State University. Published April 24, 2015. Accessed February 4, 2021. https://cdn.ymaws.com/www.aocd.org/resource/resmgr/2015SpringMeeting/ChenSpr15.pdf
- Zikry J, Chapman LW, Korta DZ, et al. Genital melanoma: are we adequately screening our patients? Dermatol Online J. 2017;23:13030/qt7zk476vn.
- Seehusen DA, Johnson DR, Earwood JS, et al. Improving women’s experience during speculum examinations at routine gynaecological visits: randomised clinical trial [published online June 27, 2006]. BMJ. 2006;333:171.
- Habeshian K, Fowler K, Gomez-Lobo V, et al. Guidelines for pediatric anogenital examination: insights from our vulvar dermatology clinic. Pediatr Dermatol. 2018;35:693-695.
- Leffell DJ, Berwick M, Bolognia J. The effect of pre-education on patient compliance with full-body examination in a public skin cancer screening. J Dermatol Surg Oncol. 1993;19:660-663.
- Hong J, Nguyen TV, Prose NS. Compassionate care: enhancing physician-patient communication and education in dermatology: part II: patient education. J Am Acad Dermatol. 2013;68:364.e361-310.
- Rosamilia LL. The naked truth about total body skin examination: a lesson from Goldilocks and the Three Bears. American Academy of Dermatology. Published November 13, 2019. Accessed February 4, 2021. https://www.aad.org/dw/dw-insights-and-inquiries/2019-archive/november/dwii-11-13-19-the-naked-truth-about-total-body-skin-examination-a-lesson-from-goldilocks-and-the-three-bears
Resident Pearls
- Dermatologists should offer a genital examination to all patients who present for a routine total-body skin examination.
- It is critical to educate patients about the importance of examining the genital skin by discussing that skin diseases can arise in all areas of the body including the genital area. Encouraging genital self-examination also is helpful.
- If a patient declines, the dermatologist should strive to ensure that another provider is examining the genital skin.
Acquired Unilateral Nevoid Telangiectasia With Pruritus and Unknown Etiology
To the Editor:
Unilateral nevoid telangiectasia (UNT) is a rare cutaneous disease characterized by superficial telangiectases arranged in a unilateral linear pattern. First described by Alfred Blaschko in 1899, this rare disease has been reported in higher frequency in recent years, with approximately 100 cases published in the literature according to a PubMed search of articles indexed for MEDLINE using the term unilateral nevoid telangiectasia.1 Unilateral nevoid telangiectasia can be congenital or acquired; occurs more commonly in women; and typically involves the dermatomal distributions of the trigeminal, cervical, and upper thoracic nerves. Although the pathogenesis of the disease remains unknown, the currently proposed etiology involves hyperestrogenic states, including puberty, pregnancy, and chronic liver disease.2 We report a case of progressively worsening, pruritic, unilateral telangiectases of unknown etiology.
A 55-year-old woman presented to our dermatology clinic with progressive red spots involving the right side of the upper body of 3 years’ duration. She noted pruritus, and the rash was otherwise asymptomatic. Her medical history was notable for hypertension, dyspepsia, sciatica, uterine fibroids, and a hysterectomy. Her medications included lisinopril, hydrochlorothiazide, tramadol, aspirin, and a multivitamin. The patient did not report the use of oral contraceptive pills or hormone replacement therapy. She also denied the use of cigarettes or illicit drugs but reported occasional alcohol consumption. A review of systems was negative for any constitutional symptoms or symptoms of liver disease. Her family history also was noncontributory.
Physical examination revealed multiple, 1- to 3-mm, telangiectatic macules and patches in a blaschkoid distribution on the right side of the upper chest, back, shoulder, and arm (Figure, A–C). Darier sign was negative. There was no evidence of palmar erythema, hepatosplenomegaly, ascites, thyromegaly, or thyroid nodules. Dermoscopy confirmed the presence of telangiectasia (Figure, D). More specifically, dermoscopy revealed plump telangiectasia with faint pigment in the background, consistent with UNT. Additionally, there was no pink-white, shiny, scarlike background, and vessels were not thin or arborized, further supporting our diagnosis vs other entities included in the differential diagnosis.
Laboratory testing for estrogen levels was within normal postmenopausal limits. A complete blood cell count, basic metabolic panel, hepatic panel, and thyroid stimulating hormone levels all were within reference range. Hepatitis B and C virus testing was nonreactive. The diagnosis of UNT was made based on clinical characteristics. The patient then was referred for pulsed dye laser treatment.
Since the first reports of UNT in 1899, it has been described in multiple individually reported cases. The typical description of UNT involves linearly arranged telangiectasia of one side of the body, following either dermatomal or blaschkoid distribution, most commonly along the C3 and C4 dermatome. In 1970, Selmanowitz3 divided the diagnosis into 2 categories: congenital and acquired. The congenital form is less common overall, seen more frequently in males, and occurs in direct relation to the neonatal period.4 The acquired form that is more common overall and seen more frequently in females is suggested to be due to hyperestrogenic states. Most reports of the acquired form involve some underlying pathology that may lead to higher estrogen states. In a review article published in 2011, Wenson et al1 summarized the reported cases to date. The authors found that out of close to 100 cases reported, 26 acquired cases were associated with pregnancy and 23 with puberty. They further found 10 cases associated with hepatic disease, 2 associated with hormonal contraceptive pills, 1 associated with hyperthyroidism, and 1 associated with carcinoid syndrome.1Interestingly, a more varied presentation of disease has been reported, as cases are now being reported in healthy patients with no comorbidities or reasons for hyperestrogenism.5 In fact, presentations in healthy adult men have led some authors to believe that estrogen may not play a major role in the pathogenesis of the disease.5-8 Reports of 16 cases of UNT have indicated no association with hyperestrogenic states.1 Because the etiology remains unknown, individual cases both supporting and refuting the hypothesis of estrogen-driven vessel inflammation may drive the investigation of further explanations.
Because UNT usually is asymptomatic, treatment options are largely based on improvement in appearance of the lesions. The pulsed dye laser (PDL) has shown success in treatment of lesions, as Sharma et al,9 reported resolution of lesions in 9 cases. These cases were not without side effects, as some patients did experience reversible pigmentary changes. Other studies have validated the use of PDL for cosmetic improvement of UNT; however, some studies have noted the recurrence of lesions after treatment.10
Our case provides another unique presentation of UNT. Our patient was a healthy adult woman with no hyperestrogen-based etiology for disease. Importantly, our patient also represented a rare instance of UNT presenting with symptoms such as pruritus, though UNT classically is described as an asymptomatic phenomenon. In our patient, treatment with PDL was suggested and believed to be warranted not only for cosmetic improvement but also in light of the fact that her lesions were symptomatic.
- Wenson SF, Jan F, Sepehr A. Unilateral nevoid telangiectasia syndrome: a case report and review of the literature. Dermatol Online J. 2011;17:2.
- Wilkin JK. Unilateral nevoid telangiectasia: three new cases and the role of estrogen. Arch Dermatol. 1977;113:486-488.
- Selmanowitz VJ. Unilateral nevoid telangiectasia. Ann Intern Med. 1970;73:87-90.
- Karakas¸ M, Durdu M, Sönmezog˘lu S, et al. Unilateral nevoid telangiectasia. J Dermatol. 2004;31:109-112.
- Jordão JM, Haendchen LC, Berestinas TC, et al. Acquired unilateral nevoid telangiectasia in a healthy men. An Bras Dermatol. 2010;85:912-914.
- Tas¸kapan O, Harmanyeri Y, Sener O, et al. Acquired unilateral nevoid telangiectasia syndrome. Acta Derm Venereol. 1997;77:62-63.
- Karabudak O, Dogan B, Taskapan O, et al. Acquired unilateral nevoid telangiectasia syndrome. J Dermatol. 2006;33:825-826.
- Jucas JJ, Rietschel RL, Lewis CW. Unilateral nevoid telangiectasia. Arch Dermatol. 1979;115:359-360.
- Sharma VK, Khandpur S. Unilateral nevoid telangiectasia—response to pulsed dye laser. Int J Dermatol. 2006;45:960-964.
- Cliff S, Harland CC. Recurrence of unilateral naevoid telangiectatic syndrome following treatment with the pulsed dye laser. J Cutan Laser Ther. 1999;1:105-107.
To the Editor:
Unilateral nevoid telangiectasia (UNT) is a rare cutaneous disease characterized by superficial telangiectases arranged in a unilateral linear pattern. First described by Alfred Blaschko in 1899, this rare disease has been reported in higher frequency in recent years, with approximately 100 cases published in the literature according to a PubMed search of articles indexed for MEDLINE using the term unilateral nevoid telangiectasia.1 Unilateral nevoid telangiectasia can be congenital or acquired; occurs more commonly in women; and typically involves the dermatomal distributions of the trigeminal, cervical, and upper thoracic nerves. Although the pathogenesis of the disease remains unknown, the currently proposed etiology involves hyperestrogenic states, including puberty, pregnancy, and chronic liver disease.2 We report a case of progressively worsening, pruritic, unilateral telangiectases of unknown etiology.
A 55-year-old woman presented to our dermatology clinic with progressive red spots involving the right side of the upper body of 3 years’ duration. She noted pruritus, and the rash was otherwise asymptomatic. Her medical history was notable for hypertension, dyspepsia, sciatica, uterine fibroids, and a hysterectomy. Her medications included lisinopril, hydrochlorothiazide, tramadol, aspirin, and a multivitamin. The patient did not report the use of oral contraceptive pills or hormone replacement therapy. She also denied the use of cigarettes or illicit drugs but reported occasional alcohol consumption. A review of systems was negative for any constitutional symptoms or symptoms of liver disease. Her family history also was noncontributory.
Physical examination revealed multiple, 1- to 3-mm, telangiectatic macules and patches in a blaschkoid distribution on the right side of the upper chest, back, shoulder, and arm (Figure, A–C). Darier sign was negative. There was no evidence of palmar erythema, hepatosplenomegaly, ascites, thyromegaly, or thyroid nodules. Dermoscopy confirmed the presence of telangiectasia (Figure, D). More specifically, dermoscopy revealed plump telangiectasia with faint pigment in the background, consistent with UNT. Additionally, there was no pink-white, shiny, scarlike background, and vessels were not thin or arborized, further supporting our diagnosis vs other entities included in the differential diagnosis.
Laboratory testing for estrogen levels was within normal postmenopausal limits. A complete blood cell count, basic metabolic panel, hepatic panel, and thyroid stimulating hormone levels all were within reference range. Hepatitis B and C virus testing was nonreactive. The diagnosis of UNT was made based on clinical characteristics. The patient then was referred for pulsed dye laser treatment.
Since the first reports of UNT in 1899, it has been described in multiple individually reported cases. The typical description of UNT involves linearly arranged telangiectasia of one side of the body, following either dermatomal or blaschkoid distribution, most commonly along the C3 and C4 dermatome. In 1970, Selmanowitz3 divided the diagnosis into 2 categories: congenital and acquired. The congenital form is less common overall, seen more frequently in males, and occurs in direct relation to the neonatal period.4 The acquired form that is more common overall and seen more frequently in females is suggested to be due to hyperestrogenic states. Most reports of the acquired form involve some underlying pathology that may lead to higher estrogen states. In a review article published in 2011, Wenson et al1 summarized the reported cases to date. The authors found that out of close to 100 cases reported, 26 acquired cases were associated with pregnancy and 23 with puberty. They further found 10 cases associated with hepatic disease, 2 associated with hormonal contraceptive pills, 1 associated with hyperthyroidism, and 1 associated with carcinoid syndrome.1Interestingly, a more varied presentation of disease has been reported, as cases are now being reported in healthy patients with no comorbidities or reasons for hyperestrogenism.5 In fact, presentations in healthy adult men have led some authors to believe that estrogen may not play a major role in the pathogenesis of the disease.5-8 Reports of 16 cases of UNT have indicated no association with hyperestrogenic states.1 Because the etiology remains unknown, individual cases both supporting and refuting the hypothesis of estrogen-driven vessel inflammation may drive the investigation of further explanations.
Because UNT usually is asymptomatic, treatment options are largely based on improvement in appearance of the lesions. The pulsed dye laser (PDL) has shown success in treatment of lesions, as Sharma et al,9 reported resolution of lesions in 9 cases. These cases were not without side effects, as some patients did experience reversible pigmentary changes. Other studies have validated the use of PDL for cosmetic improvement of UNT; however, some studies have noted the recurrence of lesions after treatment.10
Our case provides another unique presentation of UNT. Our patient was a healthy adult woman with no hyperestrogen-based etiology for disease. Importantly, our patient also represented a rare instance of UNT presenting with symptoms such as pruritus, though UNT classically is described as an asymptomatic phenomenon. In our patient, treatment with PDL was suggested and believed to be warranted not only for cosmetic improvement but also in light of the fact that her lesions were symptomatic.
To the Editor:
Unilateral nevoid telangiectasia (UNT) is a rare cutaneous disease characterized by superficial telangiectases arranged in a unilateral linear pattern. First described by Alfred Blaschko in 1899, this rare disease has been reported in higher frequency in recent years, with approximately 100 cases published in the literature according to a PubMed search of articles indexed for MEDLINE using the term unilateral nevoid telangiectasia.1 Unilateral nevoid telangiectasia can be congenital or acquired; occurs more commonly in women; and typically involves the dermatomal distributions of the trigeminal, cervical, and upper thoracic nerves. Although the pathogenesis of the disease remains unknown, the currently proposed etiology involves hyperestrogenic states, including puberty, pregnancy, and chronic liver disease.2 We report a case of progressively worsening, pruritic, unilateral telangiectases of unknown etiology.
A 55-year-old woman presented to our dermatology clinic with progressive red spots involving the right side of the upper body of 3 years’ duration. She noted pruritus, and the rash was otherwise asymptomatic. Her medical history was notable for hypertension, dyspepsia, sciatica, uterine fibroids, and a hysterectomy. Her medications included lisinopril, hydrochlorothiazide, tramadol, aspirin, and a multivitamin. The patient did not report the use of oral contraceptive pills or hormone replacement therapy. She also denied the use of cigarettes or illicit drugs but reported occasional alcohol consumption. A review of systems was negative for any constitutional symptoms or symptoms of liver disease. Her family history also was noncontributory.
Physical examination revealed multiple, 1- to 3-mm, telangiectatic macules and patches in a blaschkoid distribution on the right side of the upper chest, back, shoulder, and arm (Figure, A–C). Darier sign was negative. There was no evidence of palmar erythema, hepatosplenomegaly, ascites, thyromegaly, or thyroid nodules. Dermoscopy confirmed the presence of telangiectasia (Figure, D). More specifically, dermoscopy revealed plump telangiectasia with faint pigment in the background, consistent with UNT. Additionally, there was no pink-white, shiny, scarlike background, and vessels were not thin or arborized, further supporting our diagnosis vs other entities included in the differential diagnosis.
Laboratory testing for estrogen levels was within normal postmenopausal limits. A complete blood cell count, basic metabolic panel, hepatic panel, and thyroid stimulating hormone levels all were within reference range. Hepatitis B and C virus testing was nonreactive. The diagnosis of UNT was made based on clinical characteristics. The patient then was referred for pulsed dye laser treatment.
Since the first reports of UNT in 1899, it has been described in multiple individually reported cases. The typical description of UNT involves linearly arranged telangiectasia of one side of the body, following either dermatomal or blaschkoid distribution, most commonly along the C3 and C4 dermatome. In 1970, Selmanowitz3 divided the diagnosis into 2 categories: congenital and acquired. The congenital form is less common overall, seen more frequently in males, and occurs in direct relation to the neonatal period.4 The acquired form that is more common overall and seen more frequently in females is suggested to be due to hyperestrogenic states. Most reports of the acquired form involve some underlying pathology that may lead to higher estrogen states. In a review article published in 2011, Wenson et al1 summarized the reported cases to date. The authors found that out of close to 100 cases reported, 26 acquired cases were associated with pregnancy and 23 with puberty. They further found 10 cases associated with hepatic disease, 2 associated with hormonal contraceptive pills, 1 associated with hyperthyroidism, and 1 associated with carcinoid syndrome.1Interestingly, a more varied presentation of disease has been reported, as cases are now being reported in healthy patients with no comorbidities or reasons for hyperestrogenism.5 In fact, presentations in healthy adult men have led some authors to believe that estrogen may not play a major role in the pathogenesis of the disease.5-8 Reports of 16 cases of UNT have indicated no association with hyperestrogenic states.1 Because the etiology remains unknown, individual cases both supporting and refuting the hypothesis of estrogen-driven vessel inflammation may drive the investigation of further explanations.
Because UNT usually is asymptomatic, treatment options are largely based on improvement in appearance of the lesions. The pulsed dye laser (PDL) has shown success in treatment of lesions, as Sharma et al,9 reported resolution of lesions in 9 cases. These cases were not without side effects, as some patients did experience reversible pigmentary changes. Other studies have validated the use of PDL for cosmetic improvement of UNT; however, some studies have noted the recurrence of lesions after treatment.10
Our case provides another unique presentation of UNT. Our patient was a healthy adult woman with no hyperestrogen-based etiology for disease. Importantly, our patient also represented a rare instance of UNT presenting with symptoms such as pruritus, though UNT classically is described as an asymptomatic phenomenon. In our patient, treatment with PDL was suggested and believed to be warranted not only for cosmetic improvement but also in light of the fact that her lesions were symptomatic.
- Wenson SF, Jan F, Sepehr A. Unilateral nevoid telangiectasia syndrome: a case report and review of the literature. Dermatol Online J. 2011;17:2.
- Wilkin JK. Unilateral nevoid telangiectasia: three new cases and the role of estrogen. Arch Dermatol. 1977;113:486-488.
- Selmanowitz VJ. Unilateral nevoid telangiectasia. Ann Intern Med. 1970;73:87-90.
- Karakas¸ M, Durdu M, Sönmezog˘lu S, et al. Unilateral nevoid telangiectasia. J Dermatol. 2004;31:109-112.
- Jordão JM, Haendchen LC, Berestinas TC, et al. Acquired unilateral nevoid telangiectasia in a healthy men. An Bras Dermatol. 2010;85:912-914.
- Tas¸kapan O, Harmanyeri Y, Sener O, et al. Acquired unilateral nevoid telangiectasia syndrome. Acta Derm Venereol. 1997;77:62-63.
- Karabudak O, Dogan B, Taskapan O, et al. Acquired unilateral nevoid telangiectasia syndrome. J Dermatol. 2006;33:825-826.
- Jucas JJ, Rietschel RL, Lewis CW. Unilateral nevoid telangiectasia. Arch Dermatol. 1979;115:359-360.
- Sharma VK, Khandpur S. Unilateral nevoid telangiectasia—response to pulsed dye laser. Int J Dermatol. 2006;45:960-964.
- Cliff S, Harland CC. Recurrence of unilateral naevoid telangiectatic syndrome following treatment with the pulsed dye laser. J Cutan Laser Ther. 1999;1:105-107.
- Wenson SF, Jan F, Sepehr A. Unilateral nevoid telangiectasia syndrome: a case report and review of the literature. Dermatol Online J. 2011;17:2.
- Wilkin JK. Unilateral nevoid telangiectasia: three new cases and the role of estrogen. Arch Dermatol. 1977;113:486-488.
- Selmanowitz VJ. Unilateral nevoid telangiectasia. Ann Intern Med. 1970;73:87-90.
- Karakas¸ M, Durdu M, Sönmezog˘lu S, et al. Unilateral nevoid telangiectasia. J Dermatol. 2004;31:109-112.
- Jordão JM, Haendchen LC, Berestinas TC, et al. Acquired unilateral nevoid telangiectasia in a healthy men. An Bras Dermatol. 2010;85:912-914.
- Tas¸kapan O, Harmanyeri Y, Sener O, et al. Acquired unilateral nevoid telangiectasia syndrome. Acta Derm Venereol. 1997;77:62-63.
- Karabudak O, Dogan B, Taskapan O, et al. Acquired unilateral nevoid telangiectasia syndrome. J Dermatol. 2006;33:825-826.
- Jucas JJ, Rietschel RL, Lewis CW. Unilateral nevoid telangiectasia. Arch Dermatol. 1979;115:359-360.
- Sharma VK, Khandpur S. Unilateral nevoid telangiectasia—response to pulsed dye laser. Int J Dermatol. 2006;45:960-964.
- Cliff S, Harland CC. Recurrence of unilateral naevoid telangiectatic syndrome following treatment with the pulsed dye laser. J Cutan Laser Ther. 1999;1:105-107.
Practice Points
- Unilateral nevoid telangiectasia may present in patients without an underlying hyperestrogenic state.
- Unilateral nevoid telangiectasia may present with symptoms including pruritus.
Maternal chronic conditions predict cerebral palsy in offspring
Several maternal chronic conditions increase the risk of giving birth to a child with cerebral palsy, based on data from more than 1.3 million Norwegian children.
Mothers with autoimmune disorders, such as diabetes and lupus, had the greatest risks, reported lead author Marianne S. Strøm, MD, of the University of Bergen (Norway) and colleagues.
“The etiologies of cerebral palsy are complex, and only a few prenatal risk factors have been identified,” the investigators wrote in Pediatrics. “Among these possible risk factors are maternal chronic conditions, although studies are typically underpowered and limited to one or two conditions.”
According to Dr. Strøm and colleagues, several components of maternal chronic conditions have been linked with cerebral palsy, including placental abnormalities, altered thrombotic state, and inflammation. Furthermore, mothers with chronic conditions are more likely to give birth prematurely and have children with congenital malformations, both of which have also been associated with cerebral palsy.
To date, however, “there has been no systematic description of maternal chronic conditions and risk of cerebral palsy in offspring,” the investigators noted.
The present, prospective cohort study aimed to meet this need with a population of 1,360,149 children born in Norway from 1990 to 2012, among whom 3,575 had cerebral palsy. Case data were extracted from the Norwegian Patient Registry and the National Insurance Scheme. Information about maternal chronic conditions was extracted from the Medical Birth Registry of Norway and the Norwegian Patient Registry, with the latter also providing information about paternal chronic conditions.
Using log binomial regression models, the investigators determined relative risks of having children with cerebral palsy among parents with chronic conditions versus parents from the general population. This revealed that chronic conditions in fathers had no correlation with cerebral palsy. In contrast, mothers with chronic conditions had a 30% increased risk (relative risk, 1.3; 95% confidence interval, 1.2-1.5), which could be further stratified by number of chronic conditions; mothers with one chronic condition, for instance, had a 20% increased risk (RR, 1.2; 95% CI, 1.1-1.4), while those with two chronic conditions had a 60% increased risk (RR, 1.6; 95% CI, 1.1-2.2), and those with more than two chronic conditions had triple the risk (RR, 3.1; 95% CI, 1.4-6.8)
“The lack of associations between the father’s chronic illness and cerebral palsy risk supports the interpretation that cerebral palsy risk in offspring is the direct result of the mother’s condition and not genetic predisposition or unmeasured situational factors,” the investigators wrote.
Maternal autoimmune conditions were particularly relevant, as they were associated with a 40% increased risk of cerebral palsy (RR, 1.4; 95% CI, 1.1-1.7), a rate that climbed dramatically, to 270%, among mothers with more than one autoimmune condition (RR, 2.7; 95% CI, 1.1-6.6).
“The role of autoimmune diseases in cerebral palsy risk (and maternal inflammation specifically) deserves closer attention,” the investigators wrote. “Using studies with larger sample sizes and a more clinical focus, including measures of placental structure and perinatal blood assays, researchers may be able to explore these possible connections between maternal autoimmune diseases and fetal neurodevelopment.”
Specifically, cerebral palsy in offspring was most strongly associated with maternal Crohn’s disease (RR, 2.1; 95% CI, 1.0-4.1), type 1 diabetes (RR, 2.2; 95% CI, 1.4-3.4), lupus erythematosus (RR, 2.7; 95% CI, 0.9-8.3), and type 2 diabetes (RR, 3.2; 95% CI, 1.8-5.4). Associations were also found for migraine (RR, 1.6; 95% CI, 1.2-2.2), multiple sclerosis (RR, 1.8; 95% CI, 0.8-4.4), and rheumatoid arthritis (RR, 2.0; 95% CI, 1.3-2.9). Several “weaker and less convincing associations” were detected for ulcerative colitis, thyroid disorder, epilepsy, asthma, anemia, and hypertension. Adjusting for parental education level, age, smoking status, and single-mother status did not significantly alter findings. Poisson and logistic regression models generated similar results.
In an accompanying editorial, Sandra Julsen Hollung, PhD, of the Cerebral Palsy Registry of Norway, Vestfold Hospital Trust, Tønsberg, and colleagues, advised that clinicians maintain perspective when discussing these findings with the general public.
“As the authors state, the absolute risk of cerebral palsy associated with at least one chronic maternal condition is low,” wrote Dr. Hollung and colleagues. “Among 1,000 pregnant women with any chronic and/or autoimmune disorder, more than 990 will deliver an infant who will not be diagnosed with cerebral palsy.”
They went on to emphasize that the study findings should not be viewed as firm evidence of causal relationships.
“Thus, the study cannot give clues to any specific preventive treatment,” wrote Dr. Hollung and colleagues. “However, if these disorders are part of a causal pathway, optimal treatment might reduce the risk of cerebral palsy.”
Although Dr. Hollung and colleagues advised that such efforts “would hardly affect the birth prevalence of cerebral palsy,” they also cited the Royal College of Obstetricians and Gynaecologists in the United Kingdom, noting that “each baby counts.”
Emeritus Professor Alastair MacLennan, AO, MB ChB, FRCOG, FRANZCOG, head of the Australian Collaborative Cerebral Palsy Research Group at the University of Adelaide (Australia) suggested that the findings may guide future research.
“An increasing proportion of cerebral palsy cases are being diagnosed by genome sequencing and other genetic techniques to have causative genetic variations,” Dr. MacLennan said. “The possibility of epigenetic interactions are also likely and are still to be investigated. Maternal disorders such as diabetes, lupus, or Crohn’s disease are possible epigenetic factors and this study helps to target these in future genetic and environmental studies of cerebral palsy causation. The days of attributing cerebral palsy to ‘birth asphyxia’ are over.”
The study was supported by the National Institutes of Health and the Western Norwegian Regional Health Authorities. The investigators reported no conflicts of interest.
Several maternal chronic conditions increase the risk of giving birth to a child with cerebral palsy, based on data from more than 1.3 million Norwegian children.
Mothers with autoimmune disorders, such as diabetes and lupus, had the greatest risks, reported lead author Marianne S. Strøm, MD, of the University of Bergen (Norway) and colleagues.
“The etiologies of cerebral palsy are complex, and only a few prenatal risk factors have been identified,” the investigators wrote in Pediatrics. “Among these possible risk factors are maternal chronic conditions, although studies are typically underpowered and limited to one or two conditions.”
According to Dr. Strøm and colleagues, several components of maternal chronic conditions have been linked with cerebral palsy, including placental abnormalities, altered thrombotic state, and inflammation. Furthermore, mothers with chronic conditions are more likely to give birth prematurely and have children with congenital malformations, both of which have also been associated with cerebral palsy.
To date, however, “there has been no systematic description of maternal chronic conditions and risk of cerebral palsy in offspring,” the investigators noted.
The present, prospective cohort study aimed to meet this need with a population of 1,360,149 children born in Norway from 1990 to 2012, among whom 3,575 had cerebral palsy. Case data were extracted from the Norwegian Patient Registry and the National Insurance Scheme. Information about maternal chronic conditions was extracted from the Medical Birth Registry of Norway and the Norwegian Patient Registry, with the latter also providing information about paternal chronic conditions.
Using log binomial regression models, the investigators determined relative risks of having children with cerebral palsy among parents with chronic conditions versus parents from the general population. This revealed that chronic conditions in fathers had no correlation with cerebral palsy. In contrast, mothers with chronic conditions had a 30% increased risk (relative risk, 1.3; 95% confidence interval, 1.2-1.5), which could be further stratified by number of chronic conditions; mothers with one chronic condition, for instance, had a 20% increased risk (RR, 1.2; 95% CI, 1.1-1.4), while those with two chronic conditions had a 60% increased risk (RR, 1.6; 95% CI, 1.1-2.2), and those with more than two chronic conditions had triple the risk (RR, 3.1; 95% CI, 1.4-6.8)
“The lack of associations between the father’s chronic illness and cerebral palsy risk supports the interpretation that cerebral palsy risk in offspring is the direct result of the mother’s condition and not genetic predisposition or unmeasured situational factors,” the investigators wrote.
Maternal autoimmune conditions were particularly relevant, as they were associated with a 40% increased risk of cerebral palsy (RR, 1.4; 95% CI, 1.1-1.7), a rate that climbed dramatically, to 270%, among mothers with more than one autoimmune condition (RR, 2.7; 95% CI, 1.1-6.6).
“The role of autoimmune diseases in cerebral palsy risk (and maternal inflammation specifically) deserves closer attention,” the investigators wrote. “Using studies with larger sample sizes and a more clinical focus, including measures of placental structure and perinatal blood assays, researchers may be able to explore these possible connections between maternal autoimmune diseases and fetal neurodevelopment.”
Specifically, cerebral palsy in offspring was most strongly associated with maternal Crohn’s disease (RR, 2.1; 95% CI, 1.0-4.1), type 1 diabetes (RR, 2.2; 95% CI, 1.4-3.4), lupus erythematosus (RR, 2.7; 95% CI, 0.9-8.3), and type 2 diabetes (RR, 3.2; 95% CI, 1.8-5.4). Associations were also found for migraine (RR, 1.6; 95% CI, 1.2-2.2), multiple sclerosis (RR, 1.8; 95% CI, 0.8-4.4), and rheumatoid arthritis (RR, 2.0; 95% CI, 1.3-2.9). Several “weaker and less convincing associations” were detected for ulcerative colitis, thyroid disorder, epilepsy, asthma, anemia, and hypertension. Adjusting for parental education level, age, smoking status, and single-mother status did not significantly alter findings. Poisson and logistic regression models generated similar results.
In an accompanying editorial, Sandra Julsen Hollung, PhD, of the Cerebral Palsy Registry of Norway, Vestfold Hospital Trust, Tønsberg, and colleagues, advised that clinicians maintain perspective when discussing these findings with the general public.
“As the authors state, the absolute risk of cerebral palsy associated with at least one chronic maternal condition is low,” wrote Dr. Hollung and colleagues. “Among 1,000 pregnant women with any chronic and/or autoimmune disorder, more than 990 will deliver an infant who will not be diagnosed with cerebral palsy.”
They went on to emphasize that the study findings should not be viewed as firm evidence of causal relationships.
“Thus, the study cannot give clues to any specific preventive treatment,” wrote Dr. Hollung and colleagues. “However, if these disorders are part of a causal pathway, optimal treatment might reduce the risk of cerebral palsy.”
Although Dr. Hollung and colleagues advised that such efforts “would hardly affect the birth prevalence of cerebral palsy,” they also cited the Royal College of Obstetricians and Gynaecologists in the United Kingdom, noting that “each baby counts.”
Emeritus Professor Alastair MacLennan, AO, MB ChB, FRCOG, FRANZCOG, head of the Australian Collaborative Cerebral Palsy Research Group at the University of Adelaide (Australia) suggested that the findings may guide future research.
“An increasing proportion of cerebral palsy cases are being diagnosed by genome sequencing and other genetic techniques to have causative genetic variations,” Dr. MacLennan said. “The possibility of epigenetic interactions are also likely and are still to be investigated. Maternal disorders such as diabetes, lupus, or Crohn’s disease are possible epigenetic factors and this study helps to target these in future genetic and environmental studies of cerebral palsy causation. The days of attributing cerebral palsy to ‘birth asphyxia’ are over.”
The study was supported by the National Institutes of Health and the Western Norwegian Regional Health Authorities. The investigators reported no conflicts of interest.
Several maternal chronic conditions increase the risk of giving birth to a child with cerebral palsy, based on data from more than 1.3 million Norwegian children.
Mothers with autoimmune disorders, such as diabetes and lupus, had the greatest risks, reported lead author Marianne S. Strøm, MD, of the University of Bergen (Norway) and colleagues.
“The etiologies of cerebral palsy are complex, and only a few prenatal risk factors have been identified,” the investigators wrote in Pediatrics. “Among these possible risk factors are maternal chronic conditions, although studies are typically underpowered and limited to one or two conditions.”
According to Dr. Strøm and colleagues, several components of maternal chronic conditions have been linked with cerebral palsy, including placental abnormalities, altered thrombotic state, and inflammation. Furthermore, mothers with chronic conditions are more likely to give birth prematurely and have children with congenital malformations, both of which have also been associated with cerebral palsy.
To date, however, “there has been no systematic description of maternal chronic conditions and risk of cerebral palsy in offspring,” the investigators noted.
The present, prospective cohort study aimed to meet this need with a population of 1,360,149 children born in Norway from 1990 to 2012, among whom 3,575 had cerebral palsy. Case data were extracted from the Norwegian Patient Registry and the National Insurance Scheme. Information about maternal chronic conditions was extracted from the Medical Birth Registry of Norway and the Norwegian Patient Registry, with the latter also providing information about paternal chronic conditions.
Using log binomial regression models, the investigators determined relative risks of having children with cerebral palsy among parents with chronic conditions versus parents from the general population. This revealed that chronic conditions in fathers had no correlation with cerebral palsy. In contrast, mothers with chronic conditions had a 30% increased risk (relative risk, 1.3; 95% confidence interval, 1.2-1.5), which could be further stratified by number of chronic conditions; mothers with one chronic condition, for instance, had a 20% increased risk (RR, 1.2; 95% CI, 1.1-1.4), while those with two chronic conditions had a 60% increased risk (RR, 1.6; 95% CI, 1.1-2.2), and those with more than two chronic conditions had triple the risk (RR, 3.1; 95% CI, 1.4-6.8)
“The lack of associations between the father’s chronic illness and cerebral palsy risk supports the interpretation that cerebral palsy risk in offspring is the direct result of the mother’s condition and not genetic predisposition or unmeasured situational factors,” the investigators wrote.
Maternal autoimmune conditions were particularly relevant, as they were associated with a 40% increased risk of cerebral palsy (RR, 1.4; 95% CI, 1.1-1.7), a rate that climbed dramatically, to 270%, among mothers with more than one autoimmune condition (RR, 2.7; 95% CI, 1.1-6.6).
“The role of autoimmune diseases in cerebral palsy risk (and maternal inflammation specifically) deserves closer attention,” the investigators wrote. “Using studies with larger sample sizes and a more clinical focus, including measures of placental structure and perinatal blood assays, researchers may be able to explore these possible connections between maternal autoimmune diseases and fetal neurodevelopment.”
Specifically, cerebral palsy in offspring was most strongly associated with maternal Crohn’s disease (RR, 2.1; 95% CI, 1.0-4.1), type 1 diabetes (RR, 2.2; 95% CI, 1.4-3.4), lupus erythematosus (RR, 2.7; 95% CI, 0.9-8.3), and type 2 diabetes (RR, 3.2; 95% CI, 1.8-5.4). Associations were also found for migraine (RR, 1.6; 95% CI, 1.2-2.2), multiple sclerosis (RR, 1.8; 95% CI, 0.8-4.4), and rheumatoid arthritis (RR, 2.0; 95% CI, 1.3-2.9). Several “weaker and less convincing associations” were detected for ulcerative colitis, thyroid disorder, epilepsy, asthma, anemia, and hypertension. Adjusting for parental education level, age, smoking status, and single-mother status did not significantly alter findings. Poisson and logistic regression models generated similar results.
In an accompanying editorial, Sandra Julsen Hollung, PhD, of the Cerebral Palsy Registry of Norway, Vestfold Hospital Trust, Tønsberg, and colleagues, advised that clinicians maintain perspective when discussing these findings with the general public.
“As the authors state, the absolute risk of cerebral palsy associated with at least one chronic maternal condition is low,” wrote Dr. Hollung and colleagues. “Among 1,000 pregnant women with any chronic and/or autoimmune disorder, more than 990 will deliver an infant who will not be diagnosed with cerebral palsy.”
They went on to emphasize that the study findings should not be viewed as firm evidence of causal relationships.
“Thus, the study cannot give clues to any specific preventive treatment,” wrote Dr. Hollung and colleagues. “However, if these disorders are part of a causal pathway, optimal treatment might reduce the risk of cerebral palsy.”
Although Dr. Hollung and colleagues advised that such efforts “would hardly affect the birth prevalence of cerebral palsy,” they also cited the Royal College of Obstetricians and Gynaecologists in the United Kingdom, noting that “each baby counts.”
Emeritus Professor Alastair MacLennan, AO, MB ChB, FRCOG, FRANZCOG, head of the Australian Collaborative Cerebral Palsy Research Group at the University of Adelaide (Australia) suggested that the findings may guide future research.
“An increasing proportion of cerebral palsy cases are being diagnosed by genome sequencing and other genetic techniques to have causative genetic variations,” Dr. MacLennan said. “The possibility of epigenetic interactions are also likely and are still to be investigated. Maternal disorders such as diabetes, lupus, or Crohn’s disease are possible epigenetic factors and this study helps to target these in future genetic and environmental studies of cerebral palsy causation. The days of attributing cerebral palsy to ‘birth asphyxia’ are over.”
The study was supported by the National Institutes of Health and the Western Norwegian Regional Health Authorities. The investigators reported no conflicts of interest.
FROM PEDIATRICS
Severe atopic dermatitis often puts a dent in quality of life
In his role as head of the division of pediatric behavioral health at National Jewish Health, Denver, Bruce G. Bender, PhD, helps children and adults navigate the adverse effects of severe atopic dermatitis (AD) on their quality of life.
“There have been many surveys of adults with AD who report impairment of their sleep, reduced activity level, increased work absence, financial burden, emotional distress, and social avoidance,” he said at the Revolutionizing Atopic Dermatitis virtual symposium. “Similarly, children with AD or their parents report emotional distress, reduced activity, and increased school absence, social avoidance, and sleep disturbance. Families report financial burdens, conflict, particularly among the adults, social avoidance, sleep disturbance in the parents, and reduction of well-being in the siblings.”
In an effort to objectively measure sleep change in this population, Dr. Bender and colleagues recruited 14 adults with AD and 14 healthy controls who wore an ActiGraph for 1 week and completed questionnaires about sleep, itch, and quality of life. Patients with AD were awake almost twice as many minutes each night as the healthy controls (a mean of 57.3 vs. 32.3 minutes, respectively; P = .0480). Consequently, their sleep efficiency was significantly reduced based on the Pittsburgh sleep quality index (a mean of 90.6 vs. 95; P = .0305).
In another study, Dr. Bender and colleagues enrolled 20 adults with AD who underwent 2 nights of polysomnography and actigraphy. The lab was set up to measure a scratching event, which was recorded when a burst of electromyographic activity of at least 3 seconds was accompanied by a visible scratching motion. “We learned that sleep efficiency as measured by both PSG and actigraphy correlated with total body surface area and scratching index,” he said. “As we might assume, the more skin involved, the more patients scratch, the less well they sleep.”
Behavioral, neurocognitive effects
In a separate study of AD, sleep, and behavior, the researchers studied 1,041 children with asthma who were enrolled in the Childhood Asthma Management Program at eight North American sites. They used baseline parent ratings on standardized sleep and behavior rating scales and found that increased awakenings were associated with increased school absence and daytime behavior problems. “So, not only do children with AD sleep less well, but this shows up to impair their functioning during the day,” said Dr. Bender, professor of psychiatry at the University of Colorado, Denver.
In a report from Australia, researchers set out to explore the association between sleep and neurocognitive function in 21 children with eczema and 20 healthy controls. Participants underwent cognitive testing and polysomnography. The authors found that the children with eczema demonstrated lower test scores. Reduced scores were correlated with parental reports of sleep problems but not polysomnography.
In a much larger study funded by the Agency for Healthcare Research and Quality, investigators analyzed data on 354,416 children and 34,613 adults from 19 U.S. population surveys including the National Health Interview Survey 1997-2013 and the National Survey of Children’s Health 2003/4 and 2007/8. They found that AD was associated with ADHD in children (adjusted odds ratio, 1.14) and adults (aOR, 1.61). Higher odds of ADHD were found in children who had significant sleep disturbance (aOR, 16.83) and other allergic disease and asthma (aOR, 1.61).
“All of these findings show that AD can impact quality of life, especially sleep, with the result of poorer daytime functioning,” Dr. Bender said. “But those studies don’t answer this question: Are patients with AD at increased risk for psychological disorders such as depression and anxiety?”
Impact on depression, anxiety
Two systematic reviews on the topic suggest that patients with AD are twice as likely to experience depression. One was published in 2018 and the other in 2019. The 2018 review reported a little more than a twofold increase (OR, 2.19), the 2019 review a little bit less (OR, 1.71).
“At the more severe end of the depression continuum, we sometimes see suicidal ideation and suicide attempts,” Dr. Bender said. “A number of studies have asked whether these are increased in patients with AD. Quite a few studies collectively show an increased incidence of suicidal ideation. The question of suicide attempts is reflected in fewer studies. And while the result is small, it is significant. There is a significant increase reported of suicide attempts in AD patients.”
The 2018 review also found an increased incidence of anxiety in AD patients: a little more than twofold in adults (OR, 2.19) and a little less than twofold in children (OR, 1.81).
“It’s a two-way relationship between AD and psychological factors,” Dr. Bender said. “We generally think about AD – the stress that it brings, the burden that it puts on children, adults, and families. But it can work the other way around,” he said, referring to patients who have psychological problems, experience a great deal of stress, have trouble being adherent to their treatment regimen, and find it difficult to resist scratching. “The behavioral/psychological characteristics of the patient also drive the AD. It is well established that acute and chronic stress can result in a worsening of skin conditions in AD patients.”
Behavioral health interventions that have been described in the literature include cognitive therapy, stress management, biofeedback, hypnotherapy, relaxation training, mindfulness, habit reversal, and patient education – some of which have been tested in randomized trials. “All of them report a decrease in scratching as a consequence of the behavioral intervention,” Dr. Bender said.
“Other studies have been reported that look at the impact of behavioral interventions on the severity of the skin condition. Most report an improvement in the skin condition from these behavioral interventions but it’s not a perfect literature.” Critiques of these studies include the fact that there is often not enough detail about the intervention or the framework for the intervention that would allow a clinician to test an intervention in another study or actually pull that intervention into clinical practice (Cochrane Database Syst Rev. 2014 Jan 7;2014[1]:CD004054), (Int Arch Allergy Immunol.2007;144[1]:1-9).
“Some of the studies lack rigorous designs, some have sampling bias, and some have inadequate outcome measurements,” he said. “We really need additional, high-quality studies to look at what is helpful for patients with AD.”
Dr. Bender reported having no financial disclosures.
In his role as head of the division of pediatric behavioral health at National Jewish Health, Denver, Bruce G. Bender, PhD, helps children and adults navigate the adverse effects of severe atopic dermatitis (AD) on their quality of life.
“There have been many surveys of adults with AD who report impairment of their sleep, reduced activity level, increased work absence, financial burden, emotional distress, and social avoidance,” he said at the Revolutionizing Atopic Dermatitis virtual symposium. “Similarly, children with AD or their parents report emotional distress, reduced activity, and increased school absence, social avoidance, and sleep disturbance. Families report financial burdens, conflict, particularly among the adults, social avoidance, sleep disturbance in the parents, and reduction of well-being in the siblings.”
In an effort to objectively measure sleep change in this population, Dr. Bender and colleagues recruited 14 adults with AD and 14 healthy controls who wore an ActiGraph for 1 week and completed questionnaires about sleep, itch, and quality of life. Patients with AD were awake almost twice as many minutes each night as the healthy controls (a mean of 57.3 vs. 32.3 minutes, respectively; P = .0480). Consequently, their sleep efficiency was significantly reduced based on the Pittsburgh sleep quality index (a mean of 90.6 vs. 95; P = .0305).
In another study, Dr. Bender and colleagues enrolled 20 adults with AD who underwent 2 nights of polysomnography and actigraphy. The lab was set up to measure a scratching event, which was recorded when a burst of electromyographic activity of at least 3 seconds was accompanied by a visible scratching motion. “We learned that sleep efficiency as measured by both PSG and actigraphy correlated with total body surface area and scratching index,” he said. “As we might assume, the more skin involved, the more patients scratch, the less well they sleep.”
Behavioral, neurocognitive effects
In a separate study of AD, sleep, and behavior, the researchers studied 1,041 children with asthma who were enrolled in the Childhood Asthma Management Program at eight North American sites. They used baseline parent ratings on standardized sleep and behavior rating scales and found that increased awakenings were associated with increased school absence and daytime behavior problems. “So, not only do children with AD sleep less well, but this shows up to impair their functioning during the day,” said Dr. Bender, professor of psychiatry at the University of Colorado, Denver.
In a report from Australia, researchers set out to explore the association between sleep and neurocognitive function in 21 children with eczema and 20 healthy controls. Participants underwent cognitive testing and polysomnography. The authors found that the children with eczema demonstrated lower test scores. Reduced scores were correlated with parental reports of sleep problems but not polysomnography.
In a much larger study funded by the Agency for Healthcare Research and Quality, investigators analyzed data on 354,416 children and 34,613 adults from 19 U.S. population surveys including the National Health Interview Survey 1997-2013 and the National Survey of Children’s Health 2003/4 and 2007/8. They found that AD was associated with ADHD in children (adjusted odds ratio, 1.14) and adults (aOR, 1.61). Higher odds of ADHD were found in children who had significant sleep disturbance (aOR, 16.83) and other allergic disease and asthma (aOR, 1.61).
“All of these findings show that AD can impact quality of life, especially sleep, with the result of poorer daytime functioning,” Dr. Bender said. “But those studies don’t answer this question: Are patients with AD at increased risk for psychological disorders such as depression and anxiety?”
Impact on depression, anxiety
Two systematic reviews on the topic suggest that patients with AD are twice as likely to experience depression. One was published in 2018 and the other in 2019. The 2018 review reported a little more than a twofold increase (OR, 2.19), the 2019 review a little bit less (OR, 1.71).
“At the more severe end of the depression continuum, we sometimes see suicidal ideation and suicide attempts,” Dr. Bender said. “A number of studies have asked whether these are increased in patients with AD. Quite a few studies collectively show an increased incidence of suicidal ideation. The question of suicide attempts is reflected in fewer studies. And while the result is small, it is significant. There is a significant increase reported of suicide attempts in AD patients.”
The 2018 review also found an increased incidence of anxiety in AD patients: a little more than twofold in adults (OR, 2.19) and a little less than twofold in children (OR, 1.81).
“It’s a two-way relationship between AD and psychological factors,” Dr. Bender said. “We generally think about AD – the stress that it brings, the burden that it puts on children, adults, and families. But it can work the other way around,” he said, referring to patients who have psychological problems, experience a great deal of stress, have trouble being adherent to their treatment regimen, and find it difficult to resist scratching. “The behavioral/psychological characteristics of the patient also drive the AD. It is well established that acute and chronic stress can result in a worsening of skin conditions in AD patients.”
Behavioral health interventions that have been described in the literature include cognitive therapy, stress management, biofeedback, hypnotherapy, relaxation training, mindfulness, habit reversal, and patient education – some of which have been tested in randomized trials. “All of them report a decrease in scratching as a consequence of the behavioral intervention,” Dr. Bender said.
“Other studies have been reported that look at the impact of behavioral interventions on the severity of the skin condition. Most report an improvement in the skin condition from these behavioral interventions but it’s not a perfect literature.” Critiques of these studies include the fact that there is often not enough detail about the intervention or the framework for the intervention that would allow a clinician to test an intervention in another study or actually pull that intervention into clinical practice (Cochrane Database Syst Rev. 2014 Jan 7;2014[1]:CD004054), (Int Arch Allergy Immunol.2007;144[1]:1-9).
“Some of the studies lack rigorous designs, some have sampling bias, and some have inadequate outcome measurements,” he said. “We really need additional, high-quality studies to look at what is helpful for patients with AD.”
Dr. Bender reported having no financial disclosures.
In his role as head of the division of pediatric behavioral health at National Jewish Health, Denver, Bruce G. Bender, PhD, helps children and adults navigate the adverse effects of severe atopic dermatitis (AD) on their quality of life.
“There have been many surveys of adults with AD who report impairment of their sleep, reduced activity level, increased work absence, financial burden, emotional distress, and social avoidance,” he said at the Revolutionizing Atopic Dermatitis virtual symposium. “Similarly, children with AD or their parents report emotional distress, reduced activity, and increased school absence, social avoidance, and sleep disturbance. Families report financial burdens, conflict, particularly among the adults, social avoidance, sleep disturbance in the parents, and reduction of well-being in the siblings.”
In an effort to objectively measure sleep change in this population, Dr. Bender and colleagues recruited 14 adults with AD and 14 healthy controls who wore an ActiGraph for 1 week and completed questionnaires about sleep, itch, and quality of life. Patients with AD were awake almost twice as many minutes each night as the healthy controls (a mean of 57.3 vs. 32.3 minutes, respectively; P = .0480). Consequently, their sleep efficiency was significantly reduced based on the Pittsburgh sleep quality index (a mean of 90.6 vs. 95; P = .0305).
In another study, Dr. Bender and colleagues enrolled 20 adults with AD who underwent 2 nights of polysomnography and actigraphy. The lab was set up to measure a scratching event, which was recorded when a burst of electromyographic activity of at least 3 seconds was accompanied by a visible scratching motion. “We learned that sleep efficiency as measured by both PSG and actigraphy correlated with total body surface area and scratching index,” he said. “As we might assume, the more skin involved, the more patients scratch, the less well they sleep.”
Behavioral, neurocognitive effects
In a separate study of AD, sleep, and behavior, the researchers studied 1,041 children with asthma who were enrolled in the Childhood Asthma Management Program at eight North American sites. They used baseline parent ratings on standardized sleep and behavior rating scales and found that increased awakenings were associated with increased school absence and daytime behavior problems. “So, not only do children with AD sleep less well, but this shows up to impair their functioning during the day,” said Dr. Bender, professor of psychiatry at the University of Colorado, Denver.
In a report from Australia, researchers set out to explore the association between sleep and neurocognitive function in 21 children with eczema and 20 healthy controls. Participants underwent cognitive testing and polysomnography. The authors found that the children with eczema demonstrated lower test scores. Reduced scores were correlated with parental reports of sleep problems but not polysomnography.
In a much larger study funded by the Agency for Healthcare Research and Quality, investigators analyzed data on 354,416 children and 34,613 adults from 19 U.S. population surveys including the National Health Interview Survey 1997-2013 and the National Survey of Children’s Health 2003/4 and 2007/8. They found that AD was associated with ADHD in children (adjusted odds ratio, 1.14) and adults (aOR, 1.61). Higher odds of ADHD were found in children who had significant sleep disturbance (aOR, 16.83) and other allergic disease and asthma (aOR, 1.61).
“All of these findings show that AD can impact quality of life, especially sleep, with the result of poorer daytime functioning,” Dr. Bender said. “But those studies don’t answer this question: Are patients with AD at increased risk for psychological disorders such as depression and anxiety?”
Impact on depression, anxiety
Two systematic reviews on the topic suggest that patients with AD are twice as likely to experience depression. One was published in 2018 and the other in 2019. The 2018 review reported a little more than a twofold increase (OR, 2.19), the 2019 review a little bit less (OR, 1.71).
“At the more severe end of the depression continuum, we sometimes see suicidal ideation and suicide attempts,” Dr. Bender said. “A number of studies have asked whether these are increased in patients with AD. Quite a few studies collectively show an increased incidence of suicidal ideation. The question of suicide attempts is reflected in fewer studies. And while the result is small, it is significant. There is a significant increase reported of suicide attempts in AD patients.”
The 2018 review also found an increased incidence of anxiety in AD patients: a little more than twofold in adults (OR, 2.19) and a little less than twofold in children (OR, 1.81).
“It’s a two-way relationship between AD and psychological factors,” Dr. Bender said. “We generally think about AD – the stress that it brings, the burden that it puts on children, adults, and families. But it can work the other way around,” he said, referring to patients who have psychological problems, experience a great deal of stress, have trouble being adherent to their treatment regimen, and find it difficult to resist scratching. “The behavioral/psychological characteristics of the patient also drive the AD. It is well established that acute and chronic stress can result in a worsening of skin conditions in AD patients.”
Behavioral health interventions that have been described in the literature include cognitive therapy, stress management, biofeedback, hypnotherapy, relaxation training, mindfulness, habit reversal, and patient education – some of which have been tested in randomized trials. “All of them report a decrease in scratching as a consequence of the behavioral intervention,” Dr. Bender said.
“Other studies have been reported that look at the impact of behavioral interventions on the severity of the skin condition. Most report an improvement in the skin condition from these behavioral interventions but it’s not a perfect literature.” Critiques of these studies include the fact that there is often not enough detail about the intervention or the framework for the intervention that would allow a clinician to test an intervention in another study or actually pull that intervention into clinical practice (Cochrane Database Syst Rev. 2014 Jan 7;2014[1]:CD004054), (Int Arch Allergy Immunol.2007;144[1]:1-9).
“Some of the studies lack rigorous designs, some have sampling bias, and some have inadequate outcome measurements,” he said. “We really need additional, high-quality studies to look at what is helpful for patients with AD.”
Dr. Bender reported having no financial disclosures.
FROM REVOLUTIONIZING AD 2020
NfL levels linked to worse disability in real-world MS
according to new findings from a large, diverse population of patients with MS. “This is one of the largest studies to evaluate serum neurofilament light chain levels in people with MS,” said lead author Elias S. Sotirchos, MD, an assistant professor of neurology at Johns Hopkins University, Baltimore.
“An important strength of this cohort is that it is a real-world cohort of patients followed in U.S. and European MS centers,” he said. “The study captures the diversity of the MS population, including demographics, comorbidities, lifestyle factors, and clinical characteristics that may otherwise not be captured in a clinical trial population.”
The research was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Scrutinizing serum neurofilament light chain levels in a real-world cohort
Neurofilaments – neuron-specific proteins that release in response to neuroaxonal injury – have been observed to be elevated in a variety of neurologic disorders, and with a need for biomarkers in MS, there is high interest of their role in the disease. But studies involving real-world, heterogeneous MS populations are lacking, the researchers noted.
To take a broader look at the issue, Dr. Sotirchos and colleagues conducted a cross-sectional evaluation of 6,968 people with MS in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS), a large network of MS centers in the United States and Europe.
Participants’ baseline serum neurofilament light chain levels were compared with those of 201 healthy controls in the cohort using a novel, high-throughput immunoassay (Siemens Healthineers).
Of those with MS, 1,202 (17.2%) showed elevated serum neurofilament light chain levels, above the age-specific 97.5th percentile derived from the healthy controls.
A look at key factors associated with elevations showed significant links to having progressive MS (odds ratio, 1.63), non-White race (OR, 1.43), type 2 diabetes (OR, 1.89), and smoking (current vs. never smoker; OR, 1.49).
Associations with age and symptom duration were somewhat complex, but overall, younger patients and those with shorter disease duration had the highest frequency of elevated serum neurofilament light chain levels.
Interestingly, those with a higher body mass index (BMI) showed a reduced odds of having elevated serum neurofilament light chain levels (OR, 0.83 per 5 kg/m2 increase in BMI).
Evaluation of neuroperformance measures – including walking speed, manual dexterity and processing speed, and MRI data – showed that those with elevated serum neurofilament light chain levels had worse neurologic function, lower brain parenchymal fraction, lower thalamic volume, and higher T2 lesion volume (P < .001 for all).
Dr. Sotirchos noted that the higher rates of elevations in younger people, also observed in previous clinical trials, may reflect higher early-stage disease activity. “Generally, people who are younger and earlier in the course of disease tend to have more inflammatory disease activity in MS, and that could be what we’re capturing here, but we need to better understand the pathologic correlates of elevated serum neurofilament light chain levels.”
The lower levels of neurofilament light chain with higher BMI, also recently reported in another study, likewise need further investigation, including in healthy controls, Dr. Sotirchos added. “Having lower serum neurofilament light chain levels with increasing BMI could have to do with effects of blood volume and how the serum neurofilament light chain levels is distributed in the body,” he explained.
The findings suggest that interpretation of serum neurofilament light chain levels without accounting for BMI could result in false-negative or false-positive results, Dr. Sotirchos noted. “It will be important to further evaluate this observation in control populations and account for BMI in neurofilament light chain reference ranges.”
Dr. Sotirchos added that the 17% rate of elevated serum neurofilament light chain levels seen in people with MS in the study is likely an underestimate.
“This is a cross-sectional study and represents one sample per patient, so it is a snapshot in time,” he said. “With the nature of MS, we know that people’s levels fluctuate over time.” In addition, most patients were on disease-modifying therapy for MS, so serum neurofilament light chain elevations could have been suppressed.
Applying the findings to individual patients
Commenting on the findings, Jennifer Graves, MD, PhD, director of the neuroimmunology research program at the University of California, San Diego, said the study is an important addition to the ongoing evidence on serum neurofilament light chain in MS.
“The current presented research importantly addresses the gaps we have in understanding how best to apply serum filament light chain levels to individual patients and not just using them to assess group level means of outcome measures,” she said.
“The MS PATHS collaborative is looking at multiple factors (in addition to MS activity) that drive serum neurofilament light chain levels so meaningful and practical cutoffs for what’s abnormal can be created,” said Dr. Graves, who also directs the Rady Children’s Pediatric MS Clinic in San Diego.
Dr. Graves noted that the findings on BMI were unexpected. “Elevated BMI has been shown to be associated with greater brain atrophy and greater relapses and disability in MS participants, so to have an opposite effect with serum neurofilament light chain is interesting.
“My thoughts would be that obesity is somehow affecting measurable blood levels of this marker. I think it less likely BMI has a protective effect against neurodegeneration given the observations with other MS outcome measures,” she added.
Future research
In terms of future directions, Dr. Sotirchos noted that the researchers are following the group longitudinally to further assess changes in neurofilament light chain over time, and will be looking at associations with longitudinal, clinical, and radiologic outcomes.
The current research, meanwhile, offers important insights in terms of developing precision reference ranges, he noted.
“It appears that reference ranges may need to account for sex, race, BMI, and comorbid/lifestyle factors,” Dr. Sotirchos said, “in order to potentially improve the performance of serum neurofilament light chain as a biomarker in MS and other neurological diseases.”
The study received funding from Biogen and the MS PATHS network receives funding from Biogen. Dr. Sotirchos has served on scientific advisory boards for Alexion, Viela Bio, and Genentech, and has received speaker honoraria from Viela Bio and Biogen. Dr. Graves has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to new findings from a large, diverse population of patients with MS. “This is one of the largest studies to evaluate serum neurofilament light chain levels in people with MS,” said lead author Elias S. Sotirchos, MD, an assistant professor of neurology at Johns Hopkins University, Baltimore.
“An important strength of this cohort is that it is a real-world cohort of patients followed in U.S. and European MS centers,” he said. “The study captures the diversity of the MS population, including demographics, comorbidities, lifestyle factors, and clinical characteristics that may otherwise not be captured in a clinical trial population.”
The research was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Scrutinizing serum neurofilament light chain levels in a real-world cohort
Neurofilaments – neuron-specific proteins that release in response to neuroaxonal injury – have been observed to be elevated in a variety of neurologic disorders, and with a need for biomarkers in MS, there is high interest of their role in the disease. But studies involving real-world, heterogeneous MS populations are lacking, the researchers noted.
To take a broader look at the issue, Dr. Sotirchos and colleagues conducted a cross-sectional evaluation of 6,968 people with MS in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS), a large network of MS centers in the United States and Europe.
Participants’ baseline serum neurofilament light chain levels were compared with those of 201 healthy controls in the cohort using a novel, high-throughput immunoassay (Siemens Healthineers).
Of those with MS, 1,202 (17.2%) showed elevated serum neurofilament light chain levels, above the age-specific 97.5th percentile derived from the healthy controls.
A look at key factors associated with elevations showed significant links to having progressive MS (odds ratio, 1.63), non-White race (OR, 1.43), type 2 diabetes (OR, 1.89), and smoking (current vs. never smoker; OR, 1.49).
Associations with age and symptom duration were somewhat complex, but overall, younger patients and those with shorter disease duration had the highest frequency of elevated serum neurofilament light chain levels.
Interestingly, those with a higher body mass index (BMI) showed a reduced odds of having elevated serum neurofilament light chain levels (OR, 0.83 per 5 kg/m2 increase in BMI).
Evaluation of neuroperformance measures – including walking speed, manual dexterity and processing speed, and MRI data – showed that those with elevated serum neurofilament light chain levels had worse neurologic function, lower brain parenchymal fraction, lower thalamic volume, and higher T2 lesion volume (P < .001 for all).
Dr. Sotirchos noted that the higher rates of elevations in younger people, also observed in previous clinical trials, may reflect higher early-stage disease activity. “Generally, people who are younger and earlier in the course of disease tend to have more inflammatory disease activity in MS, and that could be what we’re capturing here, but we need to better understand the pathologic correlates of elevated serum neurofilament light chain levels.”
The lower levels of neurofilament light chain with higher BMI, also recently reported in another study, likewise need further investigation, including in healthy controls, Dr. Sotirchos added. “Having lower serum neurofilament light chain levels with increasing BMI could have to do with effects of blood volume and how the serum neurofilament light chain levels is distributed in the body,” he explained.
The findings suggest that interpretation of serum neurofilament light chain levels without accounting for BMI could result in false-negative or false-positive results, Dr. Sotirchos noted. “It will be important to further evaluate this observation in control populations and account for BMI in neurofilament light chain reference ranges.”
Dr. Sotirchos added that the 17% rate of elevated serum neurofilament light chain levels seen in people with MS in the study is likely an underestimate.
“This is a cross-sectional study and represents one sample per patient, so it is a snapshot in time,” he said. “With the nature of MS, we know that people’s levels fluctuate over time.” In addition, most patients were on disease-modifying therapy for MS, so serum neurofilament light chain elevations could have been suppressed.
Applying the findings to individual patients
Commenting on the findings, Jennifer Graves, MD, PhD, director of the neuroimmunology research program at the University of California, San Diego, said the study is an important addition to the ongoing evidence on serum neurofilament light chain in MS.
“The current presented research importantly addresses the gaps we have in understanding how best to apply serum filament light chain levels to individual patients and not just using them to assess group level means of outcome measures,” she said.
“The MS PATHS collaborative is looking at multiple factors (in addition to MS activity) that drive serum neurofilament light chain levels so meaningful and practical cutoffs for what’s abnormal can be created,” said Dr. Graves, who also directs the Rady Children’s Pediatric MS Clinic in San Diego.
Dr. Graves noted that the findings on BMI were unexpected. “Elevated BMI has been shown to be associated with greater brain atrophy and greater relapses and disability in MS participants, so to have an opposite effect with serum neurofilament light chain is interesting.
“My thoughts would be that obesity is somehow affecting measurable blood levels of this marker. I think it less likely BMI has a protective effect against neurodegeneration given the observations with other MS outcome measures,” she added.
Future research
In terms of future directions, Dr. Sotirchos noted that the researchers are following the group longitudinally to further assess changes in neurofilament light chain over time, and will be looking at associations with longitudinal, clinical, and radiologic outcomes.
The current research, meanwhile, offers important insights in terms of developing precision reference ranges, he noted.
“It appears that reference ranges may need to account for sex, race, BMI, and comorbid/lifestyle factors,” Dr. Sotirchos said, “in order to potentially improve the performance of serum neurofilament light chain as a biomarker in MS and other neurological diseases.”
The study received funding from Biogen and the MS PATHS network receives funding from Biogen. Dr. Sotirchos has served on scientific advisory boards for Alexion, Viela Bio, and Genentech, and has received speaker honoraria from Viela Bio and Biogen. Dr. Graves has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to new findings from a large, diverse population of patients with MS. “This is one of the largest studies to evaluate serum neurofilament light chain levels in people with MS,” said lead author Elias S. Sotirchos, MD, an assistant professor of neurology at Johns Hopkins University, Baltimore.
“An important strength of this cohort is that it is a real-world cohort of patients followed in U.S. and European MS centers,” he said. “The study captures the diversity of the MS population, including demographics, comorbidities, lifestyle factors, and clinical characteristics that may otherwise not be captured in a clinical trial population.”
The research was presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
Scrutinizing serum neurofilament light chain levels in a real-world cohort
Neurofilaments – neuron-specific proteins that release in response to neuroaxonal injury – have been observed to be elevated in a variety of neurologic disorders, and with a need for biomarkers in MS, there is high interest of their role in the disease. But studies involving real-world, heterogeneous MS populations are lacking, the researchers noted.
To take a broader look at the issue, Dr. Sotirchos and colleagues conducted a cross-sectional evaluation of 6,968 people with MS in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS), a large network of MS centers in the United States and Europe.
Participants’ baseline serum neurofilament light chain levels were compared with those of 201 healthy controls in the cohort using a novel, high-throughput immunoassay (Siemens Healthineers).
Of those with MS, 1,202 (17.2%) showed elevated serum neurofilament light chain levels, above the age-specific 97.5th percentile derived from the healthy controls.
A look at key factors associated with elevations showed significant links to having progressive MS (odds ratio, 1.63), non-White race (OR, 1.43), type 2 diabetes (OR, 1.89), and smoking (current vs. never smoker; OR, 1.49).
Associations with age and symptom duration were somewhat complex, but overall, younger patients and those with shorter disease duration had the highest frequency of elevated serum neurofilament light chain levels.
Interestingly, those with a higher body mass index (BMI) showed a reduced odds of having elevated serum neurofilament light chain levels (OR, 0.83 per 5 kg/m2 increase in BMI).
Evaluation of neuroperformance measures – including walking speed, manual dexterity and processing speed, and MRI data – showed that those with elevated serum neurofilament light chain levels had worse neurologic function, lower brain parenchymal fraction, lower thalamic volume, and higher T2 lesion volume (P < .001 for all).
Dr. Sotirchos noted that the higher rates of elevations in younger people, also observed in previous clinical trials, may reflect higher early-stage disease activity. “Generally, people who are younger and earlier in the course of disease tend to have more inflammatory disease activity in MS, and that could be what we’re capturing here, but we need to better understand the pathologic correlates of elevated serum neurofilament light chain levels.”
The lower levels of neurofilament light chain with higher BMI, also recently reported in another study, likewise need further investigation, including in healthy controls, Dr. Sotirchos added. “Having lower serum neurofilament light chain levels with increasing BMI could have to do with effects of blood volume and how the serum neurofilament light chain levels is distributed in the body,” he explained.
The findings suggest that interpretation of serum neurofilament light chain levels without accounting for BMI could result in false-negative or false-positive results, Dr. Sotirchos noted. “It will be important to further evaluate this observation in control populations and account for BMI in neurofilament light chain reference ranges.”
Dr. Sotirchos added that the 17% rate of elevated serum neurofilament light chain levels seen in people with MS in the study is likely an underestimate.
“This is a cross-sectional study and represents one sample per patient, so it is a snapshot in time,” he said. “With the nature of MS, we know that people’s levels fluctuate over time.” In addition, most patients were on disease-modifying therapy for MS, so serum neurofilament light chain elevations could have been suppressed.
Applying the findings to individual patients
Commenting on the findings, Jennifer Graves, MD, PhD, director of the neuroimmunology research program at the University of California, San Diego, said the study is an important addition to the ongoing evidence on serum neurofilament light chain in MS.
“The current presented research importantly addresses the gaps we have in understanding how best to apply serum filament light chain levels to individual patients and not just using them to assess group level means of outcome measures,” she said.
“The MS PATHS collaborative is looking at multiple factors (in addition to MS activity) that drive serum neurofilament light chain levels so meaningful and practical cutoffs for what’s abnormal can be created,” said Dr. Graves, who also directs the Rady Children’s Pediatric MS Clinic in San Diego.
Dr. Graves noted that the findings on BMI were unexpected. “Elevated BMI has been shown to be associated with greater brain atrophy and greater relapses and disability in MS participants, so to have an opposite effect with serum neurofilament light chain is interesting.
“My thoughts would be that obesity is somehow affecting measurable blood levels of this marker. I think it less likely BMI has a protective effect against neurodegeneration given the observations with other MS outcome measures,” she added.
Future research
In terms of future directions, Dr. Sotirchos noted that the researchers are following the group longitudinally to further assess changes in neurofilament light chain over time, and will be looking at associations with longitudinal, clinical, and radiologic outcomes.
The current research, meanwhile, offers important insights in terms of developing precision reference ranges, he noted.
“It appears that reference ranges may need to account for sex, race, BMI, and comorbid/lifestyle factors,” Dr. Sotirchos said, “in order to potentially improve the performance of serum neurofilament light chain as a biomarker in MS and other neurological diseases.”
The study received funding from Biogen and the MS PATHS network receives funding from Biogen. Dr. Sotirchos has served on scientific advisory boards for Alexion, Viela Bio, and Genentech, and has received speaker honoraria from Viela Bio and Biogen. Dr. Graves has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ACTRIMS 2021
Earlier antibiotic initiation for sepsis did not lead to overuse
There has been a marked increase in the time to antibiotic administration for ICU patients with sepsis across Veterans Affairs (VA) hospitals, but there is no evidence that they are being given inappropriately, according to new findings.
Accelerating time-to-antibiotics in sepsis means that patients will be treated earlier, but it could also result in more patients receiving antibiotics, including those without infection. This in turn may contribute to antimicrobial resistance.
“The time to antibiotics for sepsis accelerated across VA hospitals, and declined from 5.8 to 4.8 hours between 2013 and 2018,” said lead study author Sarah Seelye, PhD, data scientist at the U.S. Department of Veterans Affairs, Ann Arbor, Mich. “Despite this, there was no evidence between hospital level antibiotic acceleration in sepsis and antibiotic use among all patients with potential sepsis.”
The results were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine, which was held virtually this year.
“Many hospitals have initiated programs like this to accelerate the use of antibiotics in patients with severe sepsis, but at the same time, there is growing concern that earlier antibiotic initiation may result in increased antibiotic treatment overall, including those without infection,” said Dr. Seelye. “However, to date, there is little evidence to support this claim.”
The goal of their study was to investigate whether hospital-level acceleration in antibiotic timing for sepsis was associated with increasing antibiotic use among patients hospitalized with potential infection.
They identified 1,101,239 hospitalizations for potential infection in 132 VA hospitals during the period from 2013 to 2018. Of these patients, 608,128 (55.2%) received antibiotics within 48 hours of presentation to the emergency department. A total of 117,435 (10.7%) met the criteria for sepsis.
Hospitals were classified into tertiles of antibiotic acceleration for sepsis: rapid, slow, and flat.
In the VA system, patients with severe sepsis began receiving faster antibiotic treatment in 2017, compared with earlier years. In 2017-2018 more than 20% of sepsis patients had received their first treatment within 2 hours, compared with 14% in 2013-1014.
In 2017-2018, more than 20% of sepsis patients had received their first treatment within 2 hours, compared with 14% in 2013-1014.
Hospitals categorized as rapid accelerators decreased their time to antibiotic initiation from 6.4 hours to 4.5 hours, while slow accelerators went from 5.6 to 4.6 hours from 2013 to 2018, and flat accelerators remained stable during the time period (5.3 hours down to 5.2 hours).
However, statistical analysis showed no real difference between the three groups in antibiotic prescribing.
“Despite this, there was no evidence between hospital-level antibiotic acceleration in sepsis and antibiotic use among all patients with potential sepsis,” said Dr. Seelye.
Weighing in on the study results, Craig M. Coopersmith, MD, professor of surgery at Emory University, Atlanta, noted that these results are very convincing, considering the size of the study and that it encompassed 132 different facilities.
“It’s difficult to say how generalizable these results are but they are definitely generalizable to all hospitals in the VA system,” he said. “In general, there are similarities between large health care systems, and it would be surprising if we found the opposite to be true in non-VA health systems.”
However, he emphasized that there is some possibility that the results would not be identical because different health care systems have different methods of providing care.
“This paper does show that you can get antibiotics into patients faster, which can be life saving, without inappropriately using them on everybody,” Dr. Coopersmith said.
He explained that there is more attention being paid now to antibiotic stewardship, compared with 10 or 15 years ago. “Given the choice of giving someone a single dose of antibiotics who may not need it, as opposed to withholding them from someone who is septic which is life threatening, the risk benefit ratio weighs heavily towards starting them early,” he said. “And then escalate rapidly.”
There has been a marked increase in the time to antibiotic administration for ICU patients with sepsis across Veterans Affairs (VA) hospitals, but there is no evidence that they are being given inappropriately, according to new findings.
Accelerating time-to-antibiotics in sepsis means that patients will be treated earlier, but it could also result in more patients receiving antibiotics, including those without infection. This in turn may contribute to antimicrobial resistance.
“The time to antibiotics for sepsis accelerated across VA hospitals, and declined from 5.8 to 4.8 hours between 2013 and 2018,” said lead study author Sarah Seelye, PhD, data scientist at the U.S. Department of Veterans Affairs, Ann Arbor, Mich. “Despite this, there was no evidence between hospital level antibiotic acceleration in sepsis and antibiotic use among all patients with potential sepsis.”
The results were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine, which was held virtually this year.
“Many hospitals have initiated programs like this to accelerate the use of antibiotics in patients with severe sepsis, but at the same time, there is growing concern that earlier antibiotic initiation may result in increased antibiotic treatment overall, including those without infection,” said Dr. Seelye. “However, to date, there is little evidence to support this claim.”
The goal of their study was to investigate whether hospital-level acceleration in antibiotic timing for sepsis was associated with increasing antibiotic use among patients hospitalized with potential infection.
They identified 1,101,239 hospitalizations for potential infection in 132 VA hospitals during the period from 2013 to 2018. Of these patients, 608,128 (55.2%) received antibiotics within 48 hours of presentation to the emergency department. A total of 117,435 (10.7%) met the criteria for sepsis.
Hospitals were classified into tertiles of antibiotic acceleration for sepsis: rapid, slow, and flat.
In the VA system, patients with severe sepsis began receiving faster antibiotic treatment in 2017, compared with earlier years. In 2017-2018 more than 20% of sepsis patients had received their first treatment within 2 hours, compared with 14% in 2013-1014.
In 2017-2018, more than 20% of sepsis patients had received their first treatment within 2 hours, compared with 14% in 2013-1014.
Hospitals categorized as rapid accelerators decreased their time to antibiotic initiation from 6.4 hours to 4.5 hours, while slow accelerators went from 5.6 to 4.6 hours from 2013 to 2018, and flat accelerators remained stable during the time period (5.3 hours down to 5.2 hours).
However, statistical analysis showed no real difference between the three groups in antibiotic prescribing.
“Despite this, there was no evidence between hospital-level antibiotic acceleration in sepsis and antibiotic use among all patients with potential sepsis,” said Dr. Seelye.
Weighing in on the study results, Craig M. Coopersmith, MD, professor of surgery at Emory University, Atlanta, noted that these results are very convincing, considering the size of the study and that it encompassed 132 different facilities.
“It’s difficult to say how generalizable these results are but they are definitely generalizable to all hospitals in the VA system,” he said. “In general, there are similarities between large health care systems, and it would be surprising if we found the opposite to be true in non-VA health systems.”
However, he emphasized that there is some possibility that the results would not be identical because different health care systems have different methods of providing care.
“This paper does show that you can get antibiotics into patients faster, which can be life saving, without inappropriately using them on everybody,” Dr. Coopersmith said.
He explained that there is more attention being paid now to antibiotic stewardship, compared with 10 or 15 years ago. “Given the choice of giving someone a single dose of antibiotics who may not need it, as opposed to withholding them from someone who is septic which is life threatening, the risk benefit ratio weighs heavily towards starting them early,” he said. “And then escalate rapidly.”
There has been a marked increase in the time to antibiotic administration for ICU patients with sepsis across Veterans Affairs (VA) hospitals, but there is no evidence that they are being given inappropriately, according to new findings.
Accelerating time-to-antibiotics in sepsis means that patients will be treated earlier, but it could also result in more patients receiving antibiotics, including those without infection. This in turn may contribute to antimicrobial resistance.
“The time to antibiotics for sepsis accelerated across VA hospitals, and declined from 5.8 to 4.8 hours between 2013 and 2018,” said lead study author Sarah Seelye, PhD, data scientist at the U.S. Department of Veterans Affairs, Ann Arbor, Mich. “Despite this, there was no evidence between hospital level antibiotic acceleration in sepsis and antibiotic use among all patients with potential sepsis.”
The results were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine, which was held virtually this year.
“Many hospitals have initiated programs like this to accelerate the use of antibiotics in patients with severe sepsis, but at the same time, there is growing concern that earlier antibiotic initiation may result in increased antibiotic treatment overall, including those without infection,” said Dr. Seelye. “However, to date, there is little evidence to support this claim.”
The goal of their study was to investigate whether hospital-level acceleration in antibiotic timing for sepsis was associated with increasing antibiotic use among patients hospitalized with potential infection.
They identified 1,101,239 hospitalizations for potential infection in 132 VA hospitals during the period from 2013 to 2018. Of these patients, 608,128 (55.2%) received antibiotics within 48 hours of presentation to the emergency department. A total of 117,435 (10.7%) met the criteria for sepsis.
Hospitals were classified into tertiles of antibiotic acceleration for sepsis: rapid, slow, and flat.
In the VA system, patients with severe sepsis began receiving faster antibiotic treatment in 2017, compared with earlier years. In 2017-2018 more than 20% of sepsis patients had received their first treatment within 2 hours, compared with 14% in 2013-1014.
In 2017-2018, more than 20% of sepsis patients had received their first treatment within 2 hours, compared with 14% in 2013-1014.
Hospitals categorized as rapid accelerators decreased their time to antibiotic initiation from 6.4 hours to 4.5 hours, while slow accelerators went from 5.6 to 4.6 hours from 2013 to 2018, and flat accelerators remained stable during the time period (5.3 hours down to 5.2 hours).
However, statistical analysis showed no real difference between the three groups in antibiotic prescribing.
“Despite this, there was no evidence between hospital-level antibiotic acceleration in sepsis and antibiotic use among all patients with potential sepsis,” said Dr. Seelye.
Weighing in on the study results, Craig M. Coopersmith, MD, professor of surgery at Emory University, Atlanta, noted that these results are very convincing, considering the size of the study and that it encompassed 132 different facilities.
“It’s difficult to say how generalizable these results are but they are definitely generalizable to all hospitals in the VA system,” he said. “In general, there are similarities between large health care systems, and it would be surprising if we found the opposite to be true in non-VA health systems.”
However, he emphasized that there is some possibility that the results would not be identical because different health care systems have different methods of providing care.
“This paper does show that you can get antibiotics into patients faster, which can be life saving, without inappropriately using them on everybody,” Dr. Coopersmith said.
He explained that there is more attention being paid now to antibiotic stewardship, compared with 10 or 15 years ago. “Given the choice of giving someone a single dose of antibiotics who may not need it, as opposed to withholding them from someone who is septic which is life threatening, the risk benefit ratio weighs heavily towards starting them early,” he said. “And then escalate rapidly.”
FROM CCC50