The Centers for Medicare and Medicaid Services (CMS) finalized an increase in the relative value of evaluation and management (E/M) service codes effective January 1, 2021, which results in an overall decrease in the payment for procedural services in the Medicare program. (Due to the mandate for budget neutrality, an increase in relative value units [RVUs] for E/M resulted in a large decrease in the conversion factor—the number of dollars per RVU). This has increased payments for endocrinologists, rheumatologists, and family medicine clinicians and decreased payments for radiologists, pathologists, and surgeons.

In a major win for physicians, CMS proposes to simplify documentation requirements for billing and focus on the complexity of the medical decision making (MDM) or the total time needed to care for the patient on the date of the service as the foundation for determining the relative value of the service. Therefore, there is no more counting bullets—ie, we don’t have to perform a comprehensive physical exam or review of systems to achieve a high level code! Prior to this change, time was only available for coding purposes when counseling and coordination of care was the predominant service (>50%), and only face-to-face time with the patient was considered. Effective January 1, for office and other outpatient services, total time on the calendar date of the encounter will be used. This acknowledges the intensity and value of non–face-to-face work.

Acting through CMS, the federal government influences greatly the US health care system. CMS is an agency in the Department of Health and Human Services that administers the Medicare program and partners with state governments to administer the Health Insurance Exchanges, Medicaid, and the Children’s Health Insurance programs (CHIP).¹ In addition, CMS is responsible for enforcing quality care standards in long-term care facilities and clinical laboratories and the implementation of the Health Insurance Portability and Accountability Act.¹

In January, CMS plans the following major changes to coding and documentation^2,3:

1. Selection of the level of E/M service will no longer require documentation of bullet points in the history, physical exam, and MDM. The simplified system allows physicians and qualified health care professionals to code either by total time (both face-to-face and non–face-to-face) on the date of the encounter or by level of MDM.
2. For established office patients, 5 levels of office-based evaluation and management services will be retained. CMS had initially proposed to reduce the number of office-based E/M codes from 5 to 3, combining code levels 2, 3, and 4 into 1 code.⁴ However, after receiving feedback from professional societies and the public, CMS abandoned the plan for radical simplification of coding levels.^2,3 Implementation of their proposal would have resulted in the same payment for treatment of a hang nail as for a complex gyn patient with multiple medical problems. Both patient advocacy groups and professional societies argued that incentives originally were misaligned.
3. For new office patients, since both 99201 and 99202 require straightforward MDM, the level 1 code (99201) has been eliminated, reducing the number of code levels from 5 to 4.
4. History and physical exam will no longer be used to determine code level for office E/M codes. These elements will be required only as medically appropriate. This means that documentation review will no longer focus on “bean counting” the elements in the history and physical exam.
5. Following a reassessment of the actual time required to provide E/M services in real-life practice, CMS plans to markedly increase the relative value of office visits for established patients and modestly increase the relative value of office visits for new patients. CMS operates under the principle of “neutral budgeting,” meaning that an increase of the relative value of E/M codes will result in a decrease in the payment for procedural codes. The actual RVUs for procedural services do not change; however, budget neutrality requires a decrease in the dollar conversion factor. The proposed changes will increase the payment for E/M services and decrease payments for procedural services.

Continue to: Refocusing practice on MDM complexity...

Refocusing practice on MDM complexity

The practice of medicine is a calling with great rewards. Prominent among those rewards are improving the health of women, children, and the community, developing deep and trusting relationships with patients, families, and clinical colleagues. The practice of medicine is also replete with a host of punishing administrative burdens, including prior authorizations, clunky electronic medical records, poorly designed quality metrics that are applied to clinicians, and billing compliance rules that emphasize the repetitive documentation of clinical information with minimal value.

Some of the most irritating aspects of medical practice are the CMS rules governing medical record documentation required for billing ambulatory office visits. Current coding compliance focuses on counting the number of systems reviewed in the review of systems; the documentation of past history, social history, and family history; the number of organs and organ elements examined during the physical examination; and the complexity of MDM.

In January 2021, CMS plans to adopt new Current Procedural Terminology (CPT) code descriptors for the office and other outpatient E/M services that sunset most of the “bean-counting” metrics and emphasize the importance of the complexity of MDM in guiding selection of a correct code.² Beginning in January 2021, clinicians will have the option of selecting an E/M code level based on the total amount of time required to provide the office visit service or the complexity of MDM. When selecting a code level based on MDM the new guidance emphasizes the importance of reviewing notes from other clinicians, reviewing test results, ordering of tests, and discussing and coordinating the care of the patient with other treating physicians. These changes reflect a better understanding of what is most important in good medical practice, promoting better patient care. TABLES 1 and 2 provide the initial guidance from CMS concerning selection of E/M code level based on time and MDM, respectively.² The guidance for using MDM to select an E/M code level is likely to evolve following implementation, so stay tuned. When using MDM to select a code, 2 of the 3 general categories are required to select that level of service.

Increase in the valuation of office-based E/M services

The Medicare Physician Fee Schedule uses a resource-based relative value system to determine time and intensity of the work of clinical practice. This system recognizes 3 major factors that influence the resources required to provide a service:

• work of the clinician
• practice expense for technical components
• cost of professional liability insurance.

Many primary care professional associations have long contended that CMS has undervalued office-based E/M services relative to procedures, resulting in the devaluing of primary care practice. After the CPT code descriptors were updated by the CPT editorial panel, 52 specialty societies surveyed their members to provide inputs to CMS on the time and intensity of the office and other outpatient E/M codes as currently practiced. The American Medical Association’s Specialty Society Resource-Based Relative Value Scale Update Committee (RUC) reviewed the surveys and provided new inputs via open comment to CMS. CMS has responded to this feedback with a review of the intensity of clinical work required to provide an ambulatory visit service. In response to the review, CMS proposes to accept the recommendations of the RUC representing the house of medicine and increase the work and practice expense relative value assigned to new and established office visit codes. Overall, the combination of changes in relative values assigned for the work of the clinician and the expense of practice, increases the total value of office-based E/M codes for new patients by 7% to 14% and for established patients from 28% to 46% (see supplemental table in the sidebar at the end of this article).

Continue to: Decreased payments for procedural services...

Decreased payments for procedural services

Medicare is required to offset increased payment in one arena of health care delivery with decreased payment in other arenas of care, thereby achieving “budget-neutrality.” As detailed above, CMS plans to increase Medicare payments for office-based E/M services. Payment for services is calculated by multiplying the total RVUs for a particular service by a “conversion factor” (ie, number of dollars per RVU). To achieve budget-neutrality, CMS has proposed substantially reducing the conversion factor for 2021 (from $36.09 to $32.26), which will effectively decrease Medicare payments for procedural services since their RVUs have not changed. While the AMA RUC and many specialty societies continue to strongly advocate for the E/M work RVU increases to be included in the E/M components of 10- and 90-day global services, CMS has proposed to implement them only for “stand alone” E/M services.

Organizations are lobbying to delay or prevent the planned decrease in conversion factor, which results in substantial declines in payment for procedural services. (See "What do the Medicare billing changes mean for the Obstetrical Bundled services?" at the end of this article.) Due to the economic and clinical practice challenges caused by the corona­virus disease 2019 (COVID-19) pandemic it would be best if CMS did not reduce payments to physicians who are experts in procedural health care, thereby avoiding the risk of reduced access to these vital services.

If the current CMS changes in payment are implemented, endocrinologists, rheumatologists, and family physicians will have an increase in payment, and radiologists, pathologists, and surgeons will have a decrease in payment (TABLE 3).⁶ Obstetrics and gynecology is projected to have an 8% increase in Medicare payment. However, if an obstetrician-gynecologist derives most of their Medicare payments from surgical procedures, they are likely to have a decrease in payment from Medicare. Other payers will be incorporating the new coding structure for 2021; however, their payment structures and conversion factors are likely to vary. It is important to note that the RVUs for procedures have not changed. The budget neutrality adjustment resulted in a much lower conversion factor and therefore a decrease in payment for those specialties whose RVUs did not increase.

Bottom line

Working through the Medicare, Medicaid, and CHIP programs, CMS can influence greatly the practice of medicine including medical record documentation practices and payment rates for every clinical service. CMS proposes to end the onerous “bean counting” approach to billing compliance and refocus on the complexity of MDM as the foundation for selecting a billing code level. This change is long overdue, valuing the effective management of complex patients in office practice. Hopefully, CMS will reverse the planned reduction in the payment for procedural services, preserving patient access to important health care services. ●

What do the Medicare billing changes mean for the Obstetrical Bundled services?

---

The CY 2020 Medicare Physician Fee Schedule Final Rule was published electronically in the Federal Register on November 1, 2019. This final rule aligns the evaluation and management (E/M) coding and payment with changes recommended by the Current Procedural Terminology (CPT) Editorial Panel and American Medical Association’s (AMA) Specialty Society Resource-Based Relative Value Scale Update Committee (RUC) for office/outpatient E/M visits. Unfortunately, the Centers for Medicare and Medicaid Services (CMS) did not agree with the RUC, AMA, and specialty societies that the E/M payment changes should be applicable across all global services that incorporate E/M visits—despite the fact that the values proposed by the RUC incorporated survey data from 52 specialties, representing most of medicine (including those specialties that predominantly perform procedures). Specifically, CMS expressed the view that the number of E/M visits within the 10- and 90-day global codes, as well as the maternity care bundle, were difficult to validate; therefore, the increased values would not be distributed to those procedural services.

Many professional societies expressed significant concerns about the resulting budget neutrality adjustments that would occur effective January 2021. The great news for ObGyns is that the American College of Obstetricians and Gynecologists (ACOG) was able to respond directly to CMS’s concerns with data to support the number of prenatal visits within the Obstetrical Bundle. Tapping into a de-identified, cloud-based data set of prenatal records—representing more than 1,100 obstetric providers with close to 30,000 recently completed pregnancies—ACOG was able to document both a mean and median number of prenatal visits across a broad geographic, payer, and patient demographic that supported the 13 prenatal visits in the Obstetrical Bundle.

With ACOG’s advocacy and ability to provide data to CMS, the proposed physician fee schedule rule for 2021 has proposed to incorporate the E/M increased reimbursement into the prenatal care codes. Now we urge the CMS to finalize this proposal. Although Medicare pays for a tiny number of pregnancies annually, we hope that all payers, including Medicaid and managed care plans, will agree with this acknowledgement of the increased work of evaluation and management that obstetricians provide during prenatal care. Join ACOG in telling CMS to finalize their proposal to increase the values of the global obstetric codes: https://acog.quorum.us/campaign/28579/.

The Centers for Medicare and Medicaid Services (CMS) finalized an increase in the relative value of evaluation and management (E/M) service codes effective January 1, 2021, which results in an overall decrease in the payment for procedural services in the Medicare program. (Due to the mandate for budget neutrality, an increase in relative value units [RVUs] for E/M resulted in a large decrease in the conversion factor—the number of dollars per RVU). This has increased payments for endocrinologists, rheumatologists, and family medicine clinicians and decreased payments for radiologists, pathologists, and surgeons.

In a major win for physicians, CMS proposes to simplify documentation requirements for billing and focus on the complexity of the medical decision making (MDM) or the total time needed to care for the patient on the date of the service as the foundation for determining the relative value of the service. Therefore, there is no more counting bullets—ie, we don’t have to perform a comprehensive physical exam or review of systems to achieve a high level code! Prior to this change, time was only available for coding purposes when counseling and coordination of care was the predominant service (>50%), and only face-to-face time with the patient was considered. Effective January 1, for office and other outpatient services, total time on the calendar date of the encounter will be used. This acknowledges the intensity and value of non–face-to-face work.

Acting through CMS, the federal government influences greatly the US health care system. CMS is an agency in the Department of Health and Human Services that administers the Medicare program and partners with state governments to administer the Health Insurance Exchanges, Medicaid, and the Children’s Health Insurance programs (CHIP).¹ In addition, CMS is responsible for enforcing quality care standards in long-term care facilities and clinical laboratories and the implementation of the Health Insurance Portability and Accountability Act.¹

In January, CMS plans the following major changes to coding and documentation^2,3:

1. Selection of the level of E/M service will no longer require documentation of bullet points in the history, physical exam, and MDM. The simplified system allows physicians and qualified health care professionals to code either by total time (both face-to-face and non–face-to-face) on the date of the encounter or by level of MDM.
2. For established office patients, 5 levels of office-based evaluation and management services will be retained. CMS had initially proposed to reduce the number of office-based E/M codes from 5 to 3, combining code levels 2, 3, and 4 into 1 code.⁴ However, after receiving feedback from professional societies and the public, CMS abandoned the plan for radical simplification of coding levels.^2,3 Implementation of their proposal would have resulted in the same payment for treatment of a hang nail as for a complex gyn patient with multiple medical problems. Both patient advocacy groups and professional societies argued that incentives originally were misaligned.
3. For new office patients, since both 99201 and 99202 require straightforward MDM, the level 1 code (99201) has been eliminated, reducing the number of code levels from 5 to 4.
4. History and physical exam will no longer be used to determine code level for office E/M codes. These elements will be required only as medically appropriate. This means that documentation review will no longer focus on “bean counting” the elements in the history and physical exam.
5. Following a reassessment of the actual time required to provide E/M services in real-life practice, CMS plans to markedly increase the relative value of office visits for established patients and modestly increase the relative value of office visits for new patients. CMS operates under the principle of “neutral budgeting,” meaning that an increase of the relative value of E/M codes will result in a decrease in the payment for procedural codes. The actual RVUs for procedural services do not change; however, budget neutrality requires a decrease in the dollar conversion factor. The proposed changes will increase the payment for E/M services and decrease payments for procedural services.

Continue to: Refocusing practice on MDM complexity...

Refocusing practice on MDM complexity

The practice of medicine is a calling with great rewards. Prominent among those rewards are improving the health of women, children, and the community, developing deep and trusting relationships with patients, families, and clinical colleagues. The practice of medicine is also replete with a host of punishing administrative burdens, including prior authorizations, clunky electronic medical records, poorly designed quality metrics that are applied to clinicians, and billing compliance rules that emphasize the repetitive documentation of clinical information with minimal value.

Some of the most irritating aspects of medical practice are the CMS rules governing medical record documentation required for billing ambulatory office visits. Current coding compliance focuses on counting the number of systems reviewed in the review of systems; the documentation of past history, social history, and family history; the number of organs and organ elements examined during the physical examination; and the complexity of MDM.

In January 2021, CMS plans to adopt new Current Procedural Terminology (CPT) code descriptors for the office and other outpatient E/M services that sunset most of the “bean-counting” metrics and emphasize the importance of the complexity of MDM in guiding selection of a correct code.² Beginning in January 2021, clinicians will have the option of selecting an E/M code level based on the total amount of time required to provide the office visit service or the complexity of MDM. When selecting a code level based on MDM the new guidance emphasizes the importance of reviewing notes from other clinicians, reviewing test results, ordering of tests, and discussing and coordinating the care of the patient with other treating physicians. These changes reflect a better understanding of what is most important in good medical practice, promoting better patient care. TABLES 1 and 2 provide the initial guidance from CMS concerning selection of E/M code level based on time and MDM, respectively.² The guidance for using MDM to select an E/M code level is likely to evolve following implementation, so stay tuned. When using MDM to select a code, 2 of the 3 general categories are required to select that level of service.

Increase in the valuation of office-based E/M services

The Medicare Physician Fee Schedule uses a resource-based relative value system to determine time and intensity of the work of clinical practice. This system recognizes 3 major factors that influence the resources required to provide a service:

• work of the clinician
• practice expense for technical components
• cost of professional liability insurance.

Many primary care professional associations have long contended that CMS has undervalued office-based E/M services relative to procedures, resulting in the devaluing of primary care practice. After the CPT code descriptors were updated by the CPT editorial panel, 52 specialty societies surveyed their members to provide inputs to CMS on the time and intensity of the office and other outpatient E/M codes as currently practiced. The American Medical Association’s Specialty Society Resource-Based Relative Value Scale Update Committee (RUC) reviewed the surveys and provided new inputs via open comment to CMS. CMS has responded to this feedback with a review of the intensity of clinical work required to provide an ambulatory visit service. In response to the review, CMS proposes to accept the recommendations of the RUC representing the house of medicine and increase the work and practice expense relative value assigned to new and established office visit codes. Overall, the combination of changes in relative values assigned for the work of the clinician and the expense of practice, increases the total value of office-based E/M codes for new patients by 7% to 14% and for established patients from 28% to 46% (see supplemental table in the sidebar at the end of this article).

Continue to: Decreased payments for procedural services...

Decreased payments for procedural services

Medicare is required to offset increased payment in one arena of health care delivery with decreased payment in other arenas of care, thereby achieving “budget-neutrality.” As detailed above, CMS plans to increase Medicare payments for office-based E/M services. Payment for services is calculated by multiplying the total RVUs for a particular service by a “conversion factor” (ie, number of dollars per RVU). To achieve budget-neutrality, CMS has proposed substantially reducing the conversion factor for 2021 (from $36.09 to $32.26), which will effectively decrease Medicare payments for procedural services since their RVUs have not changed. While the AMA RUC and many specialty societies continue to strongly advocate for the E/M work RVU increases to be included in the E/M components of 10- and 90-day global services, CMS has proposed to implement them only for “stand alone” E/M services.

Organizations are lobbying to delay or prevent the planned decrease in conversion factor, which results in substantial declines in payment for procedural services. (See "What do the Medicare billing changes mean for the Obstetrical Bundled services?" at the end of this article.) Due to the economic and clinical practice challenges caused by the corona­virus disease 2019 (COVID-19) pandemic it would be best if CMS did not reduce payments to physicians who are experts in procedural health care, thereby avoiding the risk of reduced access to these vital services.

If the current CMS changes in payment are implemented, endocrinologists, rheumatologists, and family physicians will have an increase in payment, and radiologists, pathologists, and surgeons will have a decrease in payment (TABLE 3).⁶ Obstetrics and gynecology is projected to have an 8% increase in Medicare payment. However, if an obstetrician-gynecologist derives most of their Medicare payments from surgical procedures, they are likely to have a decrease in payment from Medicare. Other payers will be incorporating the new coding structure for 2021; however, their payment structures and conversion factors are likely to vary. It is important to note that the RVUs for procedures have not changed. The budget neutrality adjustment resulted in a much lower conversion factor and therefore a decrease in payment for those specialties whose RVUs did not increase.

Bottom line

Working through the Medicare, Medicaid, and CHIP programs, CMS can influence greatly the practice of medicine including medical record documentation practices and payment rates for every clinical service. CMS proposes to end the onerous “bean counting” approach to billing compliance and refocus on the complexity of MDM as the foundation for selecting a billing code level. This change is long overdue, valuing the effective management of complex patients in office practice. Hopefully, CMS will reverse the planned reduction in the payment for procedural services, preserving patient access to important health care services. ●

What do the Medicare billing changes mean for the Obstetrical Bundled services?

---

The CY 2020 Medicare Physician Fee Schedule Final Rule was published electronically in the Federal Register on November 1, 2019. This final rule aligns the evaluation and management (E/M) coding and payment with changes recommended by the Current Procedural Terminology (CPT) Editorial Panel and American Medical Association’s (AMA) Specialty Society Resource-Based Relative Value Scale Update Committee (RUC) for office/outpatient E/M visits. Unfortunately, the Centers for Medicare and Medicaid Services (CMS) did not agree with the RUC, AMA, and specialty societies that the E/M payment changes should be applicable across all global services that incorporate E/M visits—despite the fact that the values proposed by the RUC incorporated survey data from 52 specialties, representing most of medicine (including those specialties that predominantly perform procedures). Specifically, CMS expressed the view that the number of E/M visits within the 10- and 90-day global codes, as well as the maternity care bundle, were difficult to validate; therefore, the increased values would not be distributed to those procedural services.

Many professional societies expressed significant concerns about the resulting budget neutrality adjustments that would occur effective January 2021. The great news for ObGyns is that the American College of Obstetricians and Gynecologists (ACOG) was able to respond directly to CMS’s concerns with data to support the number of prenatal visits within the Obstetrical Bundle. Tapping into a de-identified, cloud-based data set of prenatal records—representing more than 1,100 obstetric providers with close to 30,000 recently completed pregnancies—ACOG was able to document both a mean and median number of prenatal visits across a broad geographic, payer, and patient demographic that supported the 13 prenatal visits in the Obstetrical Bundle.

With ACOG’s advocacy and ability to provide data to CMS, the proposed physician fee schedule rule for 2021 has proposed to incorporate the E/M increased reimbursement into the prenatal care codes. Now we urge the CMS to finalize this proposal. Although Medicare pays for a tiny number of pregnancies annually, we hope that all payers, including Medicaid and managed care plans, will agree with this acknowledgement of the increased work of evaluation and management that obstetricians provide during prenatal care. Join ACOG in telling CMS to finalize their proposal to increase the values of the global obstetric codes: https://acog.quorum.us/campaign/28579/.

The Centers for Medicare and Medicaid Services (CMS) finalized an increase in the relative value of evaluation and management (E/M) service codes effective January 1, 2021, which results in an overall decrease in the payment for procedural services in the Medicare program. (Due to the mandate for budget neutrality, an increase in relative value units [RVUs] for E/M resulted in a large decrease in the conversion factor—the number of dollars per RVU). This has increased payments for endocrinologists, rheumatologists, and family medicine clinicians and decreased payments for radiologists, pathologists, and surgeons.

In a major win for physicians, CMS proposes to simplify documentation requirements for billing and focus on the complexity of the medical decision making (MDM) or the total time needed to care for the patient on the date of the service as the foundation for determining the relative value of the service. Therefore, there is no more counting bullets—ie, we don’t have to perform a comprehensive physical exam or review of systems to achieve a high level code! Prior to this change, time was only available for coding purposes when counseling and coordination of care was the predominant service (>50%), and only face-to-face time with the patient was considered. Effective January 1, for office and other outpatient services, total time on the calendar date of the encounter will be used. This acknowledges the intensity and value of non–face-to-face work.

Acting through CMS, the federal government influences greatly the US health care system. CMS is an agency in the Department of Health and Human Services that administers the Medicare program and partners with state governments to administer the Health Insurance Exchanges, Medicaid, and the Children’s Health Insurance programs (CHIP).¹ In addition, CMS is responsible for enforcing quality care standards in long-term care facilities and clinical laboratories and the implementation of the Health Insurance Portability and Accountability Act.¹

In January, CMS plans the following major changes to coding and documentation^2,3:

1. Selection of the level of E/M service will no longer require documentation of bullet points in the history, physical exam, and MDM. The simplified system allows physicians and qualified health care professionals to code either by total time (both face-to-face and non–face-to-face) on the date of the encounter or by level of MDM.
2. For established office patients, 5 levels of office-based evaluation and management services will be retained. CMS had initially proposed to reduce the number of office-based E/M codes from 5 to 3, combining code levels 2, 3, and 4 into 1 code.⁴ However, after receiving feedback from professional societies and the public, CMS abandoned the plan for radical simplification of coding levels.^2,3 Implementation of their proposal would have resulted in the same payment for treatment of a hang nail as for a complex gyn patient with multiple medical problems. Both patient advocacy groups and professional societies argued that incentives originally were misaligned.
3. For new office patients, since both 99201 and 99202 require straightforward MDM, the level 1 code (99201) has been eliminated, reducing the number of code levels from 5 to 4.
4. History and physical exam will no longer be used to determine code level for office E/M codes. These elements will be required only as medically appropriate. This means that documentation review will no longer focus on “bean counting” the elements in the history and physical exam.
5. Following a reassessment of the actual time required to provide E/M services in real-life practice, CMS plans to markedly increase the relative value of office visits for established patients and modestly increase the relative value of office visits for new patients. CMS operates under the principle of “neutral budgeting,” meaning that an increase of the relative value of E/M codes will result in a decrease in the payment for procedural codes. The actual RVUs for procedural services do not change; however, budget neutrality requires a decrease in the dollar conversion factor. The proposed changes will increase the payment for E/M services and decrease payments for procedural services.

Continue to: Refocusing practice on MDM complexity...

Refocusing practice on MDM complexity

The practice of medicine is a calling with great rewards. Prominent among those rewards are improving the health of women, children, and the community, developing deep and trusting relationships with patients, families, and clinical colleagues. The practice of medicine is also replete with a host of punishing administrative burdens, including prior authorizations, clunky electronic medical records, poorly designed quality metrics that are applied to clinicians, and billing compliance rules that emphasize the repetitive documentation of clinical information with minimal value.

Some of the most irritating aspects of medical practice are the CMS rules governing medical record documentation required for billing ambulatory office visits. Current coding compliance focuses on counting the number of systems reviewed in the review of systems; the documentation of past history, social history, and family history; the number of organs and organ elements examined during the physical examination; and the complexity of MDM.

In January 2021, CMS plans to adopt new Current Procedural Terminology (CPT) code descriptors for the office and other outpatient E/M services that sunset most of the “bean-counting” metrics and emphasize the importance of the complexity of MDM in guiding selection of a correct code.² Beginning in January 2021, clinicians will have the option of selecting an E/M code level based on the total amount of time required to provide the office visit service or the complexity of MDM. When selecting a code level based on MDM the new guidance emphasizes the importance of reviewing notes from other clinicians, reviewing test results, ordering of tests, and discussing and coordinating the care of the patient with other treating physicians. These changes reflect a better understanding of what is most important in good medical practice, promoting better patient care. TABLES 1 and 2 provide the initial guidance from CMS concerning selection of E/M code level based on time and MDM, respectively.² The guidance for using MDM to select an E/M code level is likely to evolve following implementation, so stay tuned. When using MDM to select a code, 2 of the 3 general categories are required to select that level of service.

Increase in the valuation of office-based E/M services

The Medicare Physician Fee Schedule uses a resource-based relative value system to determine time and intensity of the work of clinical practice. This system recognizes 3 major factors that influence the resources required to provide a service:

• work of the clinician
• practice expense for technical components
• cost of professional liability insurance.

Many primary care professional associations have long contended that CMS has undervalued office-based E/M services relative to procedures, resulting in the devaluing of primary care practice. After the CPT code descriptors were updated by the CPT editorial panel, 52 specialty societies surveyed their members to provide inputs to CMS on the time and intensity of the office and other outpatient E/M codes as currently practiced. The American Medical Association’s Specialty Society Resource-Based Relative Value Scale Update Committee (RUC) reviewed the surveys and provided new inputs via open comment to CMS. CMS has responded to this feedback with a review of the intensity of clinical work required to provide an ambulatory visit service. In response to the review, CMS proposes to accept the recommendations of the RUC representing the house of medicine and increase the work and practice expense relative value assigned to new and established office visit codes. Overall, the combination of changes in relative values assigned for the work of the clinician and the expense of practice, increases the total value of office-based E/M codes for new patients by 7% to 14% and for established patients from 28% to 46% (see supplemental table in the sidebar at the end of this article).

Continue to: Decreased payments for procedural services...

Decreased payments for procedural services

Medicare is required to offset increased payment in one arena of health care delivery with decreased payment in other arenas of care, thereby achieving “budget-neutrality.” As detailed above, CMS plans to increase Medicare payments for office-based E/M services. Payment for services is calculated by multiplying the total RVUs for a particular service by a “conversion factor” (ie, number of dollars per RVU). To achieve budget-neutrality, CMS has proposed substantially reducing the conversion factor for 2021 (from $36.09 to $32.26), which will effectively decrease Medicare payments for procedural services since their RVUs have not changed. While the AMA RUC and many specialty societies continue to strongly advocate for the E/M work RVU increases to be included in the E/M components of 10- and 90-day global services, CMS has proposed to implement them only for “stand alone” E/M services.

Organizations are lobbying to delay or prevent the planned decrease in conversion factor, which results in substantial declines in payment for procedural services. (See "What do the Medicare billing changes mean for the Obstetrical Bundled services?" at the end of this article.) Due to the economic and clinical practice challenges caused by the corona­virus disease 2019 (COVID-19) pandemic it would be best if CMS did not reduce payments to physicians who are experts in procedural health care, thereby avoiding the risk of reduced access to these vital services.

If the current CMS changes in payment are implemented, endocrinologists, rheumatologists, and family physicians will have an increase in payment, and radiologists, pathologists, and surgeons will have a decrease in payment (TABLE 3).⁶ Obstetrics and gynecology is projected to have an 8% increase in Medicare payment. However, if an obstetrician-gynecologist derives most of their Medicare payments from surgical procedures, they are likely to have a decrease in payment from Medicare. Other payers will be incorporating the new coding structure for 2021; however, their payment structures and conversion factors are likely to vary. It is important to note that the RVUs for procedures have not changed. The budget neutrality adjustment resulted in a much lower conversion factor and therefore a decrease in payment for those specialties whose RVUs did not increase.

Bottom line

Working through the Medicare, Medicaid, and CHIP programs, CMS can influence greatly the practice of medicine including medical record documentation practices and payment rates for every clinical service. CMS proposes to end the onerous “bean counting” approach to billing compliance and refocus on the complexity of MDM as the foundation for selecting a billing code level. This change is long overdue, valuing the effective management of complex patients in office practice. Hopefully, CMS will reverse the planned reduction in the payment for procedural services, preserving patient access to important health care services. ●

What do the Medicare billing changes mean for the Obstetrical Bundled services?

---

The CY 2020 Medicare Physician Fee Schedule Final Rule was published electronically in the Federal Register on November 1, 2019. This final rule aligns the evaluation and management (E/M) coding and payment with changes recommended by the Current Procedural Terminology (CPT) Editorial Panel and American Medical Association’s (AMA) Specialty Society Resource-Based Relative Value Scale Update Committee (RUC) for office/outpatient E/M visits. Unfortunately, the Centers for Medicare and Medicaid Services (CMS) did not agree with the RUC, AMA, and specialty societies that the E/M payment changes should be applicable across all global services that incorporate E/M visits—despite the fact that the values proposed by the RUC incorporated survey data from 52 specialties, representing most of medicine (including those specialties that predominantly perform procedures). Specifically, CMS expressed the view that the number of E/M visits within the 10- and 90-day global codes, as well as the maternity care bundle, were difficult to validate; therefore, the increased values would not be distributed to those procedural services.

Many professional societies expressed significant concerns about the resulting budget neutrality adjustments that would occur effective January 2021. The great news for ObGyns is that the American College of Obstetricians and Gynecologists (ACOG) was able to respond directly to CMS’s concerns with data to support the number of prenatal visits within the Obstetrical Bundle. Tapping into a de-identified, cloud-based data set of prenatal records—representing more than 1,100 obstetric providers with close to 30,000 recently completed pregnancies—ACOG was able to document both a mean and median number of prenatal visits across a broad geographic, payer, and patient demographic that supported the 13 prenatal visits in the Obstetrical Bundle.

With ACOG’s advocacy and ability to provide data to CMS, the proposed physician fee schedule rule for 2021 has proposed to incorporate the E/M increased reimbursement into the prenatal care codes. Now we urge the CMS to finalize this proposal. Although Medicare pays for a tiny number of pregnancies annually, we hope that all payers, including Medicaid and managed care plans, will agree with this acknowledgement of the increased work of evaluation and management that obstetricians provide during prenatal care. Join ACOG in telling CMS to finalize their proposal to increase the values of the global obstetric codes: https://acog.quorum.us/campaign/28579/.

In contrast to findings of previous research, low levels of von Willebrand Factor (VWF) and blood group O were not associated with a first-ever intracerebral hemorrhage (ICH), according to a study published in Thrombosis Research.

The researchers compared 176 cases of ICH with 349 age- and sex-matched controls. The mean patient age was 57 years, and 50% were women. The median time from baseline blood sampling to the first ICH was 5.6 years, according to the study reported by Kristina Johansson of Umeå (Sweden) University and her colleagues.
 

Complicated picture

The level of VWF differed significantly among blood groups: In individuals with blood group O, the mean VWF level was 1.29 kIU/L; for blood group A, it was 1.52 kIU/L; for blood group AB, 1.59 kIU/L; and in blood group B, 1.76 kIU/L. However, there was no difference in VWF concentration between cases and controls.

The researchers found no association between blood group O and the risk of ICH, a finding previously seen in other studies. They did, however, find that, in the limited number of patients with blood group B there was an association with a lower risk of ICH, compared with blood group A (odds ratio, 0.47; 95% confidence interval, 0.23-0.95).

“To our knowledge this is the largest prospective study investigating the association between VWF, ABO blood group and ICH. We found no association between VWF or blood group O and risk of future ICH,” the researchers concluded.

The study was funded by public institutions in Sweden. The authors declared that they had no conflicts.
 

mlesney@mdedge.com

SOURCE: Johansson K et al. Thromb Res. 2020 Jul 5;195:77-80.

In contrast to findings of previous research, low levels of von Willebrand Factor (VWF) and blood group O were not associated with a first-ever intracerebral hemorrhage (ICH), according to a study published in Thrombosis Research.

The researchers compared 176 cases of ICH with 349 age- and sex-matched controls. The mean patient age was 57 years, and 50% were women. The median time from baseline blood sampling to the first ICH was 5.6 years, according to the study reported by Kristina Johansson of Umeå (Sweden) University and her colleagues.
 

Complicated picture

The level of VWF differed significantly among blood groups: In individuals with blood group O, the mean VWF level was 1.29 kIU/L; for blood group A, it was 1.52 kIU/L; for blood group AB, 1.59 kIU/L; and in blood group B, 1.76 kIU/L. However, there was no difference in VWF concentration between cases and controls.

The researchers found no association between blood group O and the risk of ICH, a finding previously seen in other studies. They did, however, find that, in the limited number of patients with blood group B there was an association with a lower risk of ICH, compared with blood group A (odds ratio, 0.47; 95% confidence interval, 0.23-0.95).

“To our knowledge this is the largest prospective study investigating the association between VWF, ABO blood group and ICH. We found no association between VWF or blood group O and risk of future ICH,” the researchers concluded.

The study was funded by public institutions in Sweden. The authors declared that they had no conflicts.
 

mlesney@mdedge.com

SOURCE: Johansson K et al. Thromb Res. 2020 Jul 5;195:77-80.

In contrast to findings of previous research, low levels of von Willebrand Factor (VWF) and blood group O were not associated with a first-ever intracerebral hemorrhage (ICH), according to a study published in Thrombosis Research.

The researchers compared 176 cases of ICH with 349 age- and sex-matched controls. The mean patient age was 57 years, and 50% were women. The median time from baseline blood sampling to the first ICH was 5.6 years, according to the study reported by Kristina Johansson of Umeå (Sweden) University and her colleagues.
 

Complicated picture

The level of VWF differed significantly among blood groups: In individuals with blood group O, the mean VWF level was 1.29 kIU/L; for blood group A, it was 1.52 kIU/L; for blood group AB, 1.59 kIU/L; and in blood group B, 1.76 kIU/L. However, there was no difference in VWF concentration between cases and controls.

The researchers found no association between blood group O and the risk of ICH, a finding previously seen in other studies. They did, however, find that, in the limited number of patients with blood group B there was an association with a lower risk of ICH, compared with blood group A (odds ratio, 0.47; 95% confidence interval, 0.23-0.95).

“To our knowledge this is the largest prospective study investigating the association between VWF, ABO blood group and ICH. We found no association between VWF or blood group O and risk of future ICH,” the researchers concluded.

The study was funded by public institutions in Sweden. The authors declared that they had no conflicts.
 

mlesney@mdedge.com

SOURCE: Johansson K et al. Thromb Res. 2020 Jul 5;195:77-80.

Mifepristone is a safe, effective, and well-tolerated medication for managing miscarriage and for medical abortion when combined with misoprostol.^1,2 Since the US Food and Drug Administration (FDA) approved its use in 2000, more than 4 million women have used this medication.³ The combination of mifepristone with misoprostol was used for 39% of all US abortions in 2017.⁴ Approximately 10% of all clinically recognized pregnancies end in miscarriages, and many are safely managed with either misoprostol alone or with the combination of mifepristone and misoprostol.⁵
 

The issue

The prescription and distribution of mifepristone is highly regulated by the FDA via requirements outlined in the Risk Evaluation and Mitigation Strategies (REMS) drug safety program. The FDA may determine a REMS is necessary for a specific drug to ensure the benefits of a drug outweigh the potential risks. A REMS may include an informative package insert for patients, follow-up communication to prescribers—including letters, safety protocols or recommended laboratory tests, or Elements to Assure Safe Use (ETASU). ETASU are types of REMS that are placed on medications that have significant potential for serious adverse effects, and without such restrictions FDA approval would be rescinded.

Are mifepristone requirements fairly applied?

The 3 ETASU restrictions on the distribution of mifepristone are in-person dispensation, prescriber certification, and patient signatures on special forms.⁶ The in-person dispensing requirement is applied to only 16 other medications (one of which is Mifeprex, the brand version of mifepristone), and Mifeprex/mifepristone are the only ones deemed safe for self-administration—meaning that patients receive the drug from a clinic but then may take it at a site of their choosing. The prescriber certification requirement places expectations on providers to account for distribution of doses and keep records of serial numbers (in effect, having clinicians act as both physician and pharmacist, as most medications are distributed and recorded in pharmacies). The patient form was recommended for elimination in 2016 due to its duplicative information and burden on patients—a recommendation that was then overruled by the FDA commissioner.⁷

These 3 requirements placed on mifepristone specifically target dosages for use related to abortions and miscarriages. Mifepristone is used to treat other medical conditions, with much higher doses, without the same restrictions—in fact, the FDA has allowed much higher doses of mifepristone to be mailed directly to a patient when prescribed for different disorders. The American College of Obstetricians and Gynecologists (ACOG) has long opposed the burdensome REMS requirements on mifepristone for reproductive health indications.⁸

Arguments regarding the safety of mifepristone must be understood in the context of how the medication is taken, and the unique difference with other medications that must be administered by physicians or in health care facilities. Mifepristone is self-administered, and the desired effect—evacuation of uterine contents—typically occurs after a patient takes the accompanying medication misoprostol, which is some 24 to 72 hours later. This timeframe makes it highly unlikely that any patient would be in the presence of their provider at the time of medication effect, thus an in-person dispensing requirement has no medical bearing on the outcome of the health of the patient. 

REMS changes during the COVID-19 pandemic

The coronavirus disease 2019 (COVID-19) pandemic has necessarily changed the structure of REMS and ETASU requirements for many medications, with changes made in order to mitigate viral transmission through the limitation of unnecessary visits to clinics or hospitals. The FDA announced in March of 2020 that it would not enforce pre-prescription requirements, such as laboratory or magnetic resonance imaging results, for many medications (including those more toxic than mifepristone), and that it would lift the requirement for in-person dispensation of several medications.⁹ Also in March 2020 the Department of Health and Human Services Secretary (HHS) and the Drug Enforcement Agency (DEA) activated a “telemedicine exception” to allow physicians to use telemedicine to satisfy mandatory requirements for prescribing controlled substances, including opioids.¹⁰

Despite repeated pleas from organizations, individuals, and physician groups, the FDA continued to enforce the REMS/ETASU for mifepristone as the pandemic decimated communities. Importantly, the pandemic has not had an equal effect on all communities, and the disparities highlighted in outcomes as related to COVID-19 are also reflected in disparities to access to reproductive choices.¹¹ By enforcing REMS/ETASU for mifepristone during a global pandemic, the FDA has placed additional burden on women and people who menstruate. As offices and clinics have closed, and as many jobs have evaporated, additional barriers have emerged, such as lack of childcare, fewer transportation options, and decreased clinic appointments. 

As the pandemic continues to affect communities in the United States, ACOG has issued guidance recommending assessment for eligibility for medical abortion remotely, and has encouraged the use of telemedicine and other remote interactions for its members and patients to limit transmission of the virus. 

The lawsuit

On May 27, 2020, the American Civil Liberties Union (ACLU) (on behalf of ACOG, the Council of University Chairs of Obstetrics and Gynecology, New York State Academy of Family Physicians, SisterSong, and Honor MacNaughton, MD) filed a civil action against the FDA and HHS challenging the requirement for in-person dispensing of mifepristone and associated ETASU requirements during the COVID-19 pandemic. The plaintiffs sought this injunction based on the claim that these restrictions during the pandemic infringe on the constitutional rights to patients’ privacy and liberty and to equal protection of the law as protected by the Due Process Clause of the Fifth Amendment. Additionally, the ACLU and other organizations said these unnecessary restrictions place patients, providers, and staff at unnecessary risk of viral exposure amidst a global pandemic.

The verdict

On July 13, 2020, a federal court granted the preliminary injunction to suspend FDA’s enforcement of the in-person requirements of mifepristone for abortion during the COVID-19 pandemic. The court denied the motion for suspension of in-person restrictions as applied to miscarriage management. The preliminary injunction applies nationwide without geographic limitation. It will remain in effect until the end of the litigation or for 30 days following the expiration of the public health emergency.

What the outcome means

This injunction is a step in the right direction for patients and providers to allow for autonomy and clinical practice guided by clinician expertise. However, this ruling remains narrow. Patients must be counseled about mifepristone via telemedicine and sign a Patient Agreement Form, which must be returned electronically or by mail.  Patients must receive a copy of the mifepristone medication guide, and dispensing of mifepristone must still be conducted by or under the supervision of a certified provider. The medication may not be dispensed by retail pharmacies, thus requiring providers to arrange for mailing of prescriptions to patients. Given state-based legal statutes regarding mailing of medications, this injunction may not lead to an immediate increase in access to care. In addition, patients seeking management for miscarriage must go to clinic to have mifepristone dispensed and thus risk exposure to viral transmission. 

What now?

The regulation of mifepristone—in spite of excellent safety and specifically for the narrow purpose of administration in the setting of abortion and miscarriage care—is by definition a discriminatory practice against patients and providers. As clinicians, we are duty-bound to speak out against injustices to our practices and our patients. At a local level, we can work to implement safe practices in the setting of this injunction and continue to work on a national level to ensure this injunction becomes permanent and with more broad scope to eliminate all of the REMS requirements for mifepristone.

ACTION ITEMS

• Act locally! Are you an abortion provider? Contact your local ACLU (find them here) or lawyer in your area for assistance navigating the legal landscape to prescribe after this injunction. 
• Act statewide! Press candidates in your state to stand up for science and data. Support legislative acts and bills that address combating discriminatory regulations.
• Act nationally! The President is responsible for appointing the Commissioner of the FDA and the Secretary of Health and Human Services (with Senate advice and consent). Who we elect matters. Seek out opportunities to become involved in increasing access to and awareness of voter registration and Election Day, and speak out against voter suppression. Make sure you are registered to vote here and check your area to review new recommendations amidst the pandemic.

Mifepristone is a safe, effective, and well-tolerated medication for managing miscarriage and for medical abortion when combined with misoprostol.^1,2 Since the US Food and Drug Administration (FDA) approved its use in 2000, more than 4 million women have used this medication.³ The combination of mifepristone with misoprostol was used for 39% of all US abortions in 2017.⁴ Approximately 10% of all clinically recognized pregnancies end in miscarriages, and many are safely managed with either misoprostol alone or with the combination of mifepristone and misoprostol.⁵
 

The issue

The prescription and distribution of mifepristone is highly regulated by the FDA via requirements outlined in the Risk Evaluation and Mitigation Strategies (REMS) drug safety program. The FDA may determine a REMS is necessary for a specific drug to ensure the benefits of a drug outweigh the potential risks. A REMS may include an informative package insert for patients, follow-up communication to prescribers—including letters, safety protocols or recommended laboratory tests, or Elements to Assure Safe Use (ETASU). ETASU are types of REMS that are placed on medications that have significant potential for serious adverse effects, and without such restrictions FDA approval would be rescinded.

Are mifepristone requirements fairly applied?

The 3 ETASU restrictions on the distribution of mifepristone are in-person dispensation, prescriber certification, and patient signatures on special forms.⁶ The in-person dispensing requirement is applied to only 16 other medications (one of which is Mifeprex, the brand version of mifepristone), and Mifeprex/mifepristone are the only ones deemed safe for self-administration—meaning that patients receive the drug from a clinic but then may take it at a site of their choosing. The prescriber certification requirement places expectations on providers to account for distribution of doses and keep records of serial numbers (in effect, having clinicians act as both physician and pharmacist, as most medications are distributed and recorded in pharmacies). The patient form was recommended for elimination in 2016 due to its duplicative information and burden on patients—a recommendation that was then overruled by the FDA commissioner.⁷

These 3 requirements placed on mifepristone specifically target dosages for use related to abortions and miscarriages. Mifepristone is used to treat other medical conditions, with much higher doses, without the same restrictions—in fact, the FDA has allowed much higher doses of mifepristone to be mailed directly to a patient when prescribed for different disorders. The American College of Obstetricians and Gynecologists (ACOG) has long opposed the burdensome REMS requirements on mifepristone for reproductive health indications.⁸

Arguments regarding the safety of mifepristone must be understood in the context of how the medication is taken, and the unique difference with other medications that must be administered by physicians or in health care facilities. Mifepristone is self-administered, and the desired effect—evacuation of uterine contents—typically occurs after a patient takes the accompanying medication misoprostol, which is some 24 to 72 hours later. This timeframe makes it highly unlikely that any patient would be in the presence of their provider at the time of medication effect, thus an in-person dispensing requirement has no medical bearing on the outcome of the health of the patient. 

REMS changes during the COVID-19 pandemic

The coronavirus disease 2019 (COVID-19) pandemic has necessarily changed the structure of REMS and ETASU requirements for many medications, with changes made in order to mitigate viral transmission through the limitation of unnecessary visits to clinics or hospitals. The FDA announced in March of 2020 that it would not enforce pre-prescription requirements, such as laboratory or magnetic resonance imaging results, for many medications (including those more toxic than mifepristone), and that it would lift the requirement for in-person dispensation of several medications.⁹ Also in March 2020 the Department of Health and Human Services Secretary (HHS) and the Drug Enforcement Agency (DEA) activated a “telemedicine exception” to allow physicians to use telemedicine to satisfy mandatory requirements for prescribing controlled substances, including opioids.¹⁰

Despite repeated pleas from organizations, individuals, and physician groups, the FDA continued to enforce the REMS/ETASU for mifepristone as the pandemic decimated communities. Importantly, the pandemic has not had an equal effect on all communities, and the disparities highlighted in outcomes as related to COVID-19 are also reflected in disparities to access to reproductive choices.¹¹ By enforcing REMS/ETASU for mifepristone during a global pandemic, the FDA has placed additional burden on women and people who menstruate. As offices and clinics have closed, and as many jobs have evaporated, additional barriers have emerged, such as lack of childcare, fewer transportation options, and decreased clinic appointments. 

As the pandemic continues to affect communities in the United States, ACOG has issued guidance recommending assessment for eligibility for medical abortion remotely, and has encouraged the use of telemedicine and other remote interactions for its members and patients to limit transmission of the virus. 

The lawsuit

On May 27, 2020, the American Civil Liberties Union (ACLU) (on behalf of ACOG, the Council of University Chairs of Obstetrics and Gynecology, New York State Academy of Family Physicians, SisterSong, and Honor MacNaughton, MD) filed a civil action against the FDA and HHS challenging the requirement for in-person dispensing of mifepristone and associated ETASU requirements during the COVID-19 pandemic. The plaintiffs sought this injunction based on the claim that these restrictions during the pandemic infringe on the constitutional rights to patients’ privacy and liberty and to equal protection of the law as protected by the Due Process Clause of the Fifth Amendment. Additionally, the ACLU and other organizations said these unnecessary restrictions place patients, providers, and staff at unnecessary risk of viral exposure amidst a global pandemic.

The verdict

On July 13, 2020, a federal court granted the preliminary injunction to suspend FDA’s enforcement of the in-person requirements of mifepristone for abortion during the COVID-19 pandemic. The court denied the motion for suspension of in-person restrictions as applied to miscarriage management. The preliminary injunction applies nationwide without geographic limitation. It will remain in effect until the end of the litigation or for 30 days following the expiration of the public health emergency.

What the outcome means

This injunction is a step in the right direction for patients and providers to allow for autonomy and clinical practice guided by clinician expertise. However, this ruling remains narrow. Patients must be counseled about mifepristone via telemedicine and sign a Patient Agreement Form, which must be returned electronically or by mail.  Patients must receive a copy of the mifepristone medication guide, and dispensing of mifepristone must still be conducted by or under the supervision of a certified provider. The medication may not be dispensed by retail pharmacies, thus requiring providers to arrange for mailing of prescriptions to patients. Given state-based legal statutes regarding mailing of medications, this injunction may not lead to an immediate increase in access to care. In addition, patients seeking management for miscarriage must go to clinic to have mifepristone dispensed and thus risk exposure to viral transmission. 

What now?

The regulation of mifepristone—in spite of excellent safety and specifically for the narrow purpose of administration in the setting of abortion and miscarriage care—is by definition a discriminatory practice against patients and providers. As clinicians, we are duty-bound to speak out against injustices to our practices and our patients. At a local level, we can work to implement safe practices in the setting of this injunction and continue to work on a national level to ensure this injunction becomes permanent and with more broad scope to eliminate all of the REMS requirements for mifepristone.

ACTION ITEMS

• Act locally! Are you an abortion provider? Contact your local ACLU (find them here) or lawyer in your area for assistance navigating the legal landscape to prescribe after this injunction. 
• Act statewide! Press candidates in your state to stand up for science and data. Support legislative acts and bills that address combating discriminatory regulations.
• Act nationally! The President is responsible for appointing the Commissioner of the FDA and the Secretary of Health and Human Services (with Senate advice and consent). Who we elect matters. Seek out opportunities to become involved in increasing access to and awareness of voter registration and Election Day, and speak out against voter suppression. Make sure you are registered to vote here and check your area to review new recommendations amidst the pandemic.

Mifepristone is a safe, effective, and well-tolerated medication for managing miscarriage and for medical abortion when combined with misoprostol.^1,2 Since the US Food and Drug Administration (FDA) approved its use in 2000, more than 4 million women have used this medication.³ The combination of mifepristone with misoprostol was used for 39% of all US abortions in 2017.⁴ Approximately 10% of all clinically recognized pregnancies end in miscarriages, and many are safely managed with either misoprostol alone or with the combination of mifepristone and misoprostol.⁵
 

The issue

The prescription and distribution of mifepristone is highly regulated by the FDA via requirements outlined in the Risk Evaluation and Mitigation Strategies (REMS) drug safety program. The FDA may determine a REMS is necessary for a specific drug to ensure the benefits of a drug outweigh the potential risks. A REMS may include an informative package insert for patients, follow-up communication to prescribers—including letters, safety protocols or recommended laboratory tests, or Elements to Assure Safe Use (ETASU). ETASU are types of REMS that are placed on medications that have significant potential for serious adverse effects, and without such restrictions FDA approval would be rescinded.

Are mifepristone requirements fairly applied?

The 3 ETASU restrictions on the distribution of mifepristone are in-person dispensation, prescriber certification, and patient signatures on special forms.⁶ The in-person dispensing requirement is applied to only 16 other medications (one of which is Mifeprex, the brand version of mifepristone), and Mifeprex/mifepristone are the only ones deemed safe for self-administration—meaning that patients receive the drug from a clinic but then may take it at a site of their choosing. The prescriber certification requirement places expectations on providers to account for distribution of doses and keep records of serial numbers (in effect, having clinicians act as both physician and pharmacist, as most medications are distributed and recorded in pharmacies). The patient form was recommended for elimination in 2016 due to its duplicative information and burden on patients—a recommendation that was then overruled by the FDA commissioner.⁷

These 3 requirements placed on mifepristone specifically target dosages for use related to abortions and miscarriages. Mifepristone is used to treat other medical conditions, with much higher doses, without the same restrictions—in fact, the FDA has allowed much higher doses of mifepristone to be mailed directly to a patient when prescribed for different disorders. The American College of Obstetricians and Gynecologists (ACOG) has long opposed the burdensome REMS requirements on mifepristone for reproductive health indications.⁸

Arguments regarding the safety of mifepristone must be understood in the context of how the medication is taken, and the unique difference with other medications that must be administered by physicians or in health care facilities. Mifepristone is self-administered, and the desired effect—evacuation of uterine contents—typically occurs after a patient takes the accompanying medication misoprostol, which is some 24 to 72 hours later. This timeframe makes it highly unlikely that any patient would be in the presence of their provider at the time of medication effect, thus an in-person dispensing requirement has no medical bearing on the outcome of the health of the patient. 

REMS changes during the COVID-19 pandemic

The coronavirus disease 2019 (COVID-19) pandemic has necessarily changed the structure of REMS and ETASU requirements for many medications, with changes made in order to mitigate viral transmission through the limitation of unnecessary visits to clinics or hospitals. The FDA announced in March of 2020 that it would not enforce pre-prescription requirements, such as laboratory or magnetic resonance imaging results, for many medications (including those more toxic than mifepristone), and that it would lift the requirement for in-person dispensation of several medications.⁹ Also in March 2020 the Department of Health and Human Services Secretary (HHS) and the Drug Enforcement Agency (DEA) activated a “telemedicine exception” to allow physicians to use telemedicine to satisfy mandatory requirements for prescribing controlled substances, including opioids.¹⁰

Despite repeated pleas from organizations, individuals, and physician groups, the FDA continued to enforce the REMS/ETASU for mifepristone as the pandemic decimated communities. Importantly, the pandemic has not had an equal effect on all communities, and the disparities highlighted in outcomes as related to COVID-19 are also reflected in disparities to access to reproductive choices.¹¹ By enforcing REMS/ETASU for mifepristone during a global pandemic, the FDA has placed additional burden on women and people who menstruate. As offices and clinics have closed, and as many jobs have evaporated, additional barriers have emerged, such as lack of childcare, fewer transportation options, and decreased clinic appointments. 

As the pandemic continues to affect communities in the United States, ACOG has issued guidance recommending assessment for eligibility for medical abortion remotely, and has encouraged the use of telemedicine and other remote interactions for its members and patients to limit transmission of the virus. 

The lawsuit

On May 27, 2020, the American Civil Liberties Union (ACLU) (on behalf of ACOG, the Council of University Chairs of Obstetrics and Gynecology, New York State Academy of Family Physicians, SisterSong, and Honor MacNaughton, MD) filed a civil action against the FDA and HHS challenging the requirement for in-person dispensing of mifepristone and associated ETASU requirements during the COVID-19 pandemic. The plaintiffs sought this injunction based on the claim that these restrictions during the pandemic infringe on the constitutional rights to patients’ privacy and liberty and to equal protection of the law as protected by the Due Process Clause of the Fifth Amendment. Additionally, the ACLU and other organizations said these unnecessary restrictions place patients, providers, and staff at unnecessary risk of viral exposure amidst a global pandemic.

The verdict

On July 13, 2020, a federal court granted the preliminary injunction to suspend FDA’s enforcement of the in-person requirements of mifepristone for abortion during the COVID-19 pandemic. The court denied the motion for suspension of in-person restrictions as applied to miscarriage management. The preliminary injunction applies nationwide without geographic limitation. It will remain in effect until the end of the litigation or for 30 days following the expiration of the public health emergency.

What the outcome means

This injunction is a step in the right direction for patients and providers to allow for autonomy and clinical practice guided by clinician expertise. However, this ruling remains narrow. Patients must be counseled about mifepristone via telemedicine and sign a Patient Agreement Form, which must be returned electronically or by mail.  Patients must receive a copy of the mifepristone medication guide, and dispensing of mifepristone must still be conducted by or under the supervision of a certified provider. The medication may not be dispensed by retail pharmacies, thus requiring providers to arrange for mailing of prescriptions to patients. Given state-based legal statutes regarding mailing of medications, this injunction may not lead to an immediate increase in access to care. In addition, patients seeking management for miscarriage must go to clinic to have mifepristone dispensed and thus risk exposure to viral transmission. 

What now?

The regulation of mifepristone—in spite of excellent safety and specifically for the narrow purpose of administration in the setting of abortion and miscarriage care—is by definition a discriminatory practice against patients and providers. As clinicians, we are duty-bound to speak out against injustices to our practices and our patients. At a local level, we can work to implement safe practices in the setting of this injunction and continue to work on a national level to ensure this injunction becomes permanent and with more broad scope to eliminate all of the REMS requirements for mifepristone.

ACTION ITEMS

• Act locally! Are you an abortion provider? Contact your local ACLU (find them here) or lawyer in your area for assistance navigating the legal landscape to prescribe after this injunction. 
• Act statewide! Press candidates in your state to stand up for science and data. Support legislative acts and bills that address combating discriminatory regulations.
• Act nationally! The President is responsible for appointing the Commissioner of the FDA and the Secretary of Health and Human Services (with Senate advice and consent). Who we elect matters. Seek out opportunities to become involved in increasing access to and awareness of voter registration and Election Day, and speak out against voter suppression. Make sure you are registered to vote here and check your area to review new recommendations amidst the pandemic.

THE CASE

A 4-year-old girl was triaged to the Pediatric Emergency Department (PED) Fast Track, complaining of pain and limited movement in both arms. For an unknown reason, she had attempted to lift a heavy, 3-person sofa several hours earlier.

Her prior medical history included left nursemaid elbow (NME) at both 15 months and 33 months of age. Neither event had a known mechanism of injury. In both episodes, it was noted in the medical record that the child was not using her arm, “was holding it funny,” and was complaining of pain. Each time, she presented about 24 hours after symptom onset.

During the physical exam in the PED, the patient showed no signs of acute distress. She held both arms close to her body, with a slight flexion at the elbows, and her hands were pronated. She could not pinpoint the location of her discomfort and described diffuse pain in her forearms, elbows, and upper arms. Examination revealed no localized pain or tenderness in her hands, wrists, or clavicles. Radial pulses were easily palpated, and capillary refill was less than 2 seconds. There was no swelling or bruising. The rest of her physical exam was normal.

DIAGNOSIS

The patient was given a diagnosis of self-inflicted bilateral nursemaid elbows (BNME). Reductions were performed by individually stabilizing the elbows and hyper-pronating the forearms, with palpable clicks felt at the proximal radius. Even though a palpable click was felt, this motion was immediately followed by supination of the forearm and flexion at the elbow. The patient tolerated the procedures well and was using both arms normally within 10 minutes. She was discharged home shortly thereafter.

DISCUSSION

BNME is an uncommon diagnosis; a literature review of reported cases indicates none were self-inflicted.^1-4 However, NME is a common injury and is easily reduced. The classic mechanism of injury for NME involves the elbow in extension, while the forearm is pronated, and a sudden brisk axial traction is applied. This combination of motions causes the annular ligament to slip over the head of the radius and become displaced downward into the radiohumeral joint, where it becomes entrapped. In this case, the patient apparently exerted enough longitudinal traction while trying to lift the couch to produce the injury.

NME occurs most commonly in the left arm of girls between the ages of 4 months and 7 years and peaks at around the age of 2 years.⁵ A 2014 study by Irie et al⁶ corroborated the findings on left-side predominance and increased incidence with age, noting that frequency of injury peaked at 6 months in those younger than 1 year of age and at 2 years for those 1 year or older. However, the researchers found no significant sex difference.⁶

NME is radiographically indistinguishable from a healthy elbow.⁷ To prevent unnecessary expense and radiation exposure in young children, prereduction radiographs should only be used to rule out the possibility of fracture or other injury.⁷ Krul et al⁸ recommend restricting x-ray use to cases with an unclear history or those that are due to trauma other than an arm pull.

Continue to: Methods of reduction

Methods of reduction. Once NME is diagnosed, there are 2 methods of reduction: hyper-pronation and supination-flexion. Reduction is best performed with the child sitting in the parent’s lap with the injured arm facing the examiner.

Nursemaid’s elbow is radiographically indistinguishable from a healthy elbow.

Success rates for both methods of NME reduction are statistically similar; however, first-attempt success rates are significantly higher with the hyper-pronation method than with supination-flexion.⁹ Furthermore, physicians have deemed the hyper-­pronation method significantly easier to perform than supination-flexion.⁹ A Cochrane review by Krul et al¹⁰ concluded that the hyper-­pronation method may result in lower failure rates than supination-flexion, but due to limited evidence, the researchers were unable to draw any conclusions on other outcomes, such as pain. Green et al¹¹ noted that hyper-pronation is perceived by parents of children with NME as being less painful. For these reasons, hyper-pronation should be utilized as the first method of reduction, followed by supination-flexion if the former does not work.¹²

Additional management. In a limited study of 50 children with pulled-elbow injuries, ultrasound revealed that 78% had an intact yet interposed radial annular ligament and 22% had a tear in the radial annular ligament.¹³ The authors propose that if, after appropriate reduction methods are attempted, no pop is felt, or there is no prompt clinical improvement, and ultrasound is not available to assess the integrity of the annular ligament, the child should be placed in a splint for 7 days and referred for orthopedic intervention.¹³

Our patient returned to the PED 3 days later, complaining of pain and an inability to move her left arm after her older sibling pulled her by her outstretched arms. She was once again diagnosed with NME, the injury was reduced, and she was using the arm within minutes. She has not presented to either the PED or the pediatric clinic with a similar complaint since. Discarding outliers, NME recurrence rates fall within a range of 23.7% to 32.9%.^14,15

THE TAKEAWAY

Pre-reduction x-rays are not warranted in cases of NME unless there is suspicion for fracture or another injury. The 2 reduction methods, hyper-pronation and supination-flexion, are easily mastered. Any reduction should be quick, easy, and as painless as possible. Hyper-pronation should be utilized first, as this maneuver seems to be the more successful and is perceived by parents as being less painful. However, it is always most helpful to be proficient in both methods. If, after appropriate attempts at reduction, the child has not regained the use of the arm, 7 days of splinting is recommended, along with an orthopedic referral.

CORRESPONDENCE
Robert N. Anderson, DNP, APRN, (F)NP-C, ENP-BC, Vanderbilt Health, 512 Autumn Springs Court, Suite 100 C, Franklin, TN 37067; bob.anderson@vumc.org

THE CASE

A 4-year-old girl was triaged to the Pediatric Emergency Department (PED) Fast Track, complaining of pain and limited movement in both arms. For an unknown reason, she had attempted to lift a heavy, 3-person sofa several hours earlier.

Her prior medical history included left nursemaid elbow (NME) at both 15 months and 33 months of age. Neither event had a known mechanism of injury. In both episodes, it was noted in the medical record that the child was not using her arm, “was holding it funny,” and was complaining of pain. Each time, she presented about 24 hours after symptom onset.

During the physical exam in the PED, the patient showed no signs of acute distress. She held both arms close to her body, with a slight flexion at the elbows, and her hands were pronated. She could not pinpoint the location of her discomfort and described diffuse pain in her forearms, elbows, and upper arms. Examination revealed no localized pain or tenderness in her hands, wrists, or clavicles. Radial pulses were easily palpated, and capillary refill was less than 2 seconds. There was no swelling or bruising. The rest of her physical exam was normal.

DIAGNOSIS

The patient was given a diagnosis of self-inflicted bilateral nursemaid elbows (BNME). Reductions were performed by individually stabilizing the elbows and hyper-pronating the forearms, with palpable clicks felt at the proximal radius. Even though a palpable click was felt, this motion was immediately followed by supination of the forearm and flexion at the elbow. The patient tolerated the procedures well and was using both arms normally within 10 minutes. She was discharged home shortly thereafter.

DISCUSSION

BNME is an uncommon diagnosis; a literature review of reported cases indicates none were self-inflicted.^1-4 However, NME is a common injury and is easily reduced. The classic mechanism of injury for NME involves the elbow in extension, while the forearm is pronated, and a sudden brisk axial traction is applied. This combination of motions causes the annular ligament to slip over the head of the radius and become displaced downward into the radiohumeral joint, where it becomes entrapped. In this case, the patient apparently exerted enough longitudinal traction while trying to lift the couch to produce the injury.

NME occurs most commonly in the left arm of girls between the ages of 4 months and 7 years and peaks at around the age of 2 years.⁵ A 2014 study by Irie et al⁶ corroborated the findings on left-side predominance and increased incidence with age, noting that frequency of injury peaked at 6 months in those younger than 1 year of age and at 2 years for those 1 year or older. However, the researchers found no significant sex difference.⁶

NME is radiographically indistinguishable from a healthy elbow.⁷ To prevent unnecessary expense and radiation exposure in young children, prereduction radiographs should only be used to rule out the possibility of fracture or other injury.⁷ Krul et al⁸ recommend restricting x-ray use to cases with an unclear history or those that are due to trauma other than an arm pull.

Continue to: Methods of reduction

Methods of reduction. Once NME is diagnosed, there are 2 methods of reduction: hyper-pronation and supination-flexion. Reduction is best performed with the child sitting in the parent’s lap with the injured arm facing the examiner.

Nursemaid’s elbow is radiographically indistinguishable from a healthy elbow.

Success rates for both methods of NME reduction are statistically similar; however, first-attempt success rates are significantly higher with the hyper-pronation method than with supination-flexion.⁹ Furthermore, physicians have deemed the hyper-­pronation method significantly easier to perform than supination-flexion.⁹ A Cochrane review by Krul et al¹⁰ concluded that the hyper-­pronation method may result in lower failure rates than supination-flexion, but due to limited evidence, the researchers were unable to draw any conclusions on other outcomes, such as pain. Green et al¹¹ noted that hyper-pronation is perceived by parents of children with NME as being less painful. For these reasons, hyper-pronation should be utilized as the first method of reduction, followed by supination-flexion if the former does not work.¹²

Additional management. In a limited study of 50 children with pulled-elbow injuries, ultrasound revealed that 78% had an intact yet interposed radial annular ligament and 22% had a tear in the radial annular ligament.¹³ The authors propose that if, after appropriate reduction methods are attempted, no pop is felt, or there is no prompt clinical improvement, and ultrasound is not available to assess the integrity of the annular ligament, the child should be placed in a splint for 7 days and referred for orthopedic intervention.¹³

Our patient returned to the PED 3 days later, complaining of pain and an inability to move her left arm after her older sibling pulled her by her outstretched arms. She was once again diagnosed with NME, the injury was reduced, and she was using the arm within minutes. She has not presented to either the PED or the pediatric clinic with a similar complaint since. Discarding outliers, NME recurrence rates fall within a range of 23.7% to 32.9%.^14,15

THE TAKEAWAY

Pre-reduction x-rays are not warranted in cases of NME unless there is suspicion for fracture or another injury. The 2 reduction methods, hyper-pronation and supination-flexion, are easily mastered. Any reduction should be quick, easy, and as painless as possible. Hyper-pronation should be utilized first, as this maneuver seems to be the more successful and is perceived by parents as being less painful. However, it is always most helpful to be proficient in both methods. If, after appropriate attempts at reduction, the child has not regained the use of the arm, 7 days of splinting is recommended, along with an orthopedic referral.

CORRESPONDENCE
Robert N. Anderson, DNP, APRN, (F)NP-C, ENP-BC, Vanderbilt Health, 512 Autumn Springs Court, Suite 100 C, Franklin, TN 37067; bob.anderson@vumc.org

THE CASE

A 4-year-old girl was triaged to the Pediatric Emergency Department (PED) Fast Track, complaining of pain and limited movement in both arms. For an unknown reason, she had attempted to lift a heavy, 3-person sofa several hours earlier.

Her prior medical history included left nursemaid elbow (NME) at both 15 months and 33 months of age. Neither event had a known mechanism of injury. In both episodes, it was noted in the medical record that the child was not using her arm, “was holding it funny,” and was complaining of pain. Each time, she presented about 24 hours after symptom onset.

During the physical exam in the PED, the patient showed no signs of acute distress. She held both arms close to her body, with a slight flexion at the elbows, and her hands were pronated. She could not pinpoint the location of her discomfort and described diffuse pain in her forearms, elbows, and upper arms. Examination revealed no localized pain or tenderness in her hands, wrists, or clavicles. Radial pulses were easily palpated, and capillary refill was less than 2 seconds. There was no swelling or bruising. The rest of her physical exam was normal.

DIAGNOSIS

The patient was given a diagnosis of self-inflicted bilateral nursemaid elbows (BNME). Reductions were performed by individually stabilizing the elbows and hyper-pronating the forearms, with palpable clicks felt at the proximal radius. Even though a palpable click was felt, this motion was immediately followed by supination of the forearm and flexion at the elbow. The patient tolerated the procedures well and was using both arms normally within 10 minutes. She was discharged home shortly thereafter.

DISCUSSION

BNME is an uncommon diagnosis; a literature review of reported cases indicates none were self-inflicted.^1-4 However, NME is a common injury and is easily reduced. The classic mechanism of injury for NME involves the elbow in extension, while the forearm is pronated, and a sudden brisk axial traction is applied. This combination of motions causes the annular ligament to slip over the head of the radius and become displaced downward into the radiohumeral joint, where it becomes entrapped. In this case, the patient apparently exerted enough longitudinal traction while trying to lift the couch to produce the injury.

NME occurs most commonly in the left arm of girls between the ages of 4 months and 7 years and peaks at around the age of 2 years.⁵ A 2014 study by Irie et al⁶ corroborated the findings on left-side predominance and increased incidence with age, noting that frequency of injury peaked at 6 months in those younger than 1 year of age and at 2 years for those 1 year or older. However, the researchers found no significant sex difference.⁶

NME is radiographically indistinguishable from a healthy elbow.⁷ To prevent unnecessary expense and radiation exposure in young children, prereduction radiographs should only be used to rule out the possibility of fracture or other injury.⁷ Krul et al⁸ recommend restricting x-ray use to cases with an unclear history or those that are due to trauma other than an arm pull.

Continue to: Methods of reduction

Methods of reduction. Once NME is diagnosed, there are 2 methods of reduction: hyper-pronation and supination-flexion. Reduction is best performed with the child sitting in the parent’s lap with the injured arm facing the examiner.

Nursemaid’s elbow is radiographically indistinguishable from a healthy elbow.

Success rates for both methods of NME reduction are statistically similar; however, first-attempt success rates are significantly higher with the hyper-pronation method than with supination-flexion.⁹ Furthermore, physicians have deemed the hyper-­pronation method significantly easier to perform than supination-flexion.⁹ A Cochrane review by Krul et al¹⁰ concluded that the hyper-­pronation method may result in lower failure rates than supination-flexion, but due to limited evidence, the researchers were unable to draw any conclusions on other outcomes, such as pain. Green et al¹¹ noted that hyper-pronation is perceived by parents of children with NME as being less painful. For these reasons, hyper-pronation should be utilized as the first method of reduction, followed by supination-flexion if the former does not work.¹²

Additional management. In a limited study of 50 children with pulled-elbow injuries, ultrasound revealed that 78% had an intact yet interposed radial annular ligament and 22% had a tear in the radial annular ligament.¹³ The authors propose that if, after appropriate reduction methods are attempted, no pop is felt, or there is no prompt clinical improvement, and ultrasound is not available to assess the integrity of the annular ligament, the child should be placed in a splint for 7 days and referred for orthopedic intervention.¹³

Our patient returned to the PED 3 days later, complaining of pain and an inability to move her left arm after her older sibling pulled her by her outstretched arms. She was once again diagnosed with NME, the injury was reduced, and she was using the arm within minutes. She has not presented to either the PED or the pediatric clinic with a similar complaint since. Discarding outliers, NME recurrence rates fall within a range of 23.7% to 32.9%.^14,15

THE TAKEAWAY

Pre-reduction x-rays are not warranted in cases of NME unless there is suspicion for fracture or another injury. The 2 reduction methods, hyper-pronation and supination-flexion, are easily mastered. Any reduction should be quick, easy, and as painless as possible. Hyper-pronation should be utilized first, as this maneuver seems to be the more successful and is perceived by parents as being less painful. However, it is always most helpful to be proficient in both methods. If, after appropriate attempts at reduction, the child has not regained the use of the arm, 7 days of splinting is recommended, along with an orthopedic referral.

CORRESPONDENCE
Robert N. Anderson, DNP, APRN, (F)NP-C, ENP-BC, Vanderbilt Health, 512 Autumn Springs Court, Suite 100 C, Franklin, TN 37067; bob.anderson@vumc.org

Since the early 1990s, modern treatments have steadily reduced overall cancer mortality from primary tumors.¹ Consequently, more people are at risk of metastatic bone disease, with subsequent pain and pathologic fractures^1,2 and death from metastasis.³ Patients who have bone metastases present with a variety of signs and symptoms including pain, fractures, and metabolic derangements. The primary care approach to work-up and diagnosis described in this article enables prompt treatment, either surgical or nonsurgical, to maintain a high quality of life for patients.

Primary tumors determine types of metastases and prognosis

Metastasis, a complex pathologic process in which cancerous cells migrate to distant organs, implant, and grow,³ is a poor prognostic indicator in cancer patients. Bone is the third most common site of metastasis, behind the liver and lungs.⁴ While the true prevalence of metastatic bone cancer is unknown, studies have estimated it to be > 280,000 cases in the United States.⁵

Bone metastases interfere with normal bone metabolism and turnover in several different characteristic patterns. These changes—radiographically defined as osteoblastic, osteolytic, or mixed lesions—are determined by the primary tumor type.

• Osteoblastic lesions, comprised of new, disorganized bone formation, often occur secondary to prostate cancer, small cell lung cancer, and carcinoid malignancies, among others.
• Osteolytic lesions, in which bone is destroyed, are more common with breast cancer, renal cell carcinoma, melanoma, and multiple myeloma.
• Mixed lesions, in which areas of bone destruction and growth are simultaneously found, occur with some GI cancers and a few breast cancers.^6,7

Most bone metastases result from carcinomas, of which up to 50% eventually spread to bone, although this process can take 10 to 15 years.^8,9 The likelihood of bone metastasis depends on the primary tumor and its stage. Breast and prostate cancer account for most skeletal metastases, although these lesions are often asymptomatic.^6,9 Other malignancies, such as ovarian and gastrointestinal, metastasize to bone much less frequently.^7,10 Virtually any cancer at an advanced stage can spread to bone. These metastases are usually multifocal and incurable, with the patient’s prognosis varying from a few months to years.^6,11,12

Factors that influence prognosis. Metastatic bone disease arising from melanoma and lung cancers has the shortest life expectancy of roughly 6 months from initial diagnosis; metastasis following prostate, breast, and thyroid cancers has the longest, usually 2 to 4 years.¹¹TABLE 1¹³ shows survival estimates from a large Danish population at various time points following bone metastasis diagnosis for several primary cancer types.

When a patient presents with signs and symptoms suggestive of metastatic bone disease, inquire about a history of cancer—even if such a history is remote. It’s important.

When surgical intervention for bony metastasis is required, prognosis is generally poorer, likely due to more advanced disease. The overall 1-year survival following surgery varies, but several large studies have found a rate of around 40% when considering all primary tumors.^14,15 The most common metastases, from breast and prostate cancers, have 1-year survivals of around 50% and 30%, respectively, following surgical intervention.^16-18

What you’re likely to see on presentation

Bone metastases are one of the leading causes of morbidity in cancer patients from resultant pain, pathologic fractures, metabolic derangements, and reduced activities of daily living.^8,19 The most common cause of cancer pain is bone involvement.⁶ Patients report pain that is usually worse at night, poorly localized, and not alleviated with rest. They often mistakenly relate the pain to an injury.²⁰ The pathophysiology of bone pain is not completely understood but is likely multifactorial and includes inflammatory and mechanical processes.^7,21 Spine involvement can lead to stenosis or nerve root compression, with symptoms dependent on level and severity of nerve or cord compromise.²⁰ Overall, the most common site of bone metastasis is the thoracic spine, followed by the ribs, pelvis, and proximal long bones.²⁰

Continue to: Pathologic fractures

Pathologic fractures occur frequently in cancer patients. Bone destruction leads to a loss of mechanical support which, in turn, causes microfractures and pain. These microfractures can proliferate and coalesce, causing a pathologic fracture, often in weight-bearing bones.⁶ Breast cancer with lytic lesions is the single leading cause of all pathologic fractures.²² Lung cancer with its short survival time and prostate cancer with blastic lesions are less common causes.²³ In the appendicular skeleton, the vast majority of these fractures occur in the femur and humerus.¹¹

Symptomatic metabolic derangements. The most common metabolic disorder is hypercalcemia, found predominantly in patients with hematologic malignancies, squamous cell lung cancer, renal cell cancer, and breast cancer.^6,7,12,24 The clinical presentation is nonspecific and can include polyuria, polydipsia, fatigue, constipation, and confusion. The prevalence is estimated to be 13% in breast cancer, 4% in lung cancers, and 1% in prostate cancer, although results in individual studies vary.¹² The pathophysiology is multifactorial and often includes osteolytic lesions and an increased circulating level of parathyroid hormone–related peptide, although other mechanisms contribute.^25,26 Ultimately, severe hypercalcemia may be fatal secondary to renal failure and cardiac arrhythmias.^6,7,12 Paraneoplastic hypercalcemia independently decreases survival; 1 study found the median survival to be 10 to 12 weeks.¹¹

Primary care work-up and diagnosis

When a patient presents with signs and symptoms suggestive of metastatic bone disease, inquire about a history of cancer. Even if such a history is remote, it is important—­particularly so if the patient received chemotherapy or radiation, which can lead to secondary cancers such as leukemia or sarcoma.²⁰ If a primary site of malignancy is unknown, pursue a general review of systems. Clues to the primary site of disease could be a history of chest pain, shortness of breath, hemoptysis, heat/cold intolerance, or changes in bowel/bladder habits. Also ask about risk factors such as smoking, chemical exposure, and sun exposure.

Pointers on radiographic imaging. If you suspect a destructive bone lesion, order appropriate radiographic imaging. Arrange for plain radiographs with at least 2 views of the specific area of interest that include the entire bone along with the joints above and below. Importantly, the entire bone must be imaged before any surgical procedure to avoid periprosthetic fractures from undetected bone metastases around hardware.²⁰ Keep in mind that plain films can miss early lesions, and computed tomography (CT) or magnetic resonance imaging (MRI) may be needed if suspicion of a pathologic process is still strong and especially if a primary malignancy is known.²⁷

Working back to a primary diagnosis

If imaging confirms a suspicious lesion and the patient has no known primary tumor, order labs, a CT scan with contrast of the chest, abdomen, and pelvis, and a bone scan, and refer the patient to an oncologist. If the bone lesion is painful, initiate protected weight-bearing and additionally refer the patient to an orthopedic surgeon.

Continue to: Appropriate laboratory evaluation

Appropriate laboratory evaluation entails a complete blood count; metabolic panel that includes serum calcium and phosphorus, vitamin D, alkaline phosphatase, thyroid-stimulating hormone, and parathyroid hormone; and serum protein electrophoresis to rule out multiple myeloma.^7,11 Tumor markers are useful to monitor a patient’s response to cancer treatment or to determine recurrence, but they play only a limited role in the initial work-up of an unknown bone tumor.²⁸

Further imaging. A CT scan with intravenous contrast of the chest, abdomen, and pelvis is done to screen for visceral malignancy; however, 15% of bone lesions in patients with an unknown primary lesion never have a source identified.²⁹ Bone scans can be useful in identifying the extent of a single lesion seen on plain films and to assess for additional asymptomatic lesions. Additional imaging—eg, CT or MRI of the lesion, or positron emission tomography (PET)—can be left to the discretion of the oncologist or surgeon.

Order plain radiographs if you suspect a bone lesion. Request at least 2 views of the area that include the entire bone with the joints above and below.

CT scans have significantly higher sensitivity than radiographs and offer better visualization of bone quality, bone destruction, and soft-tissue extension.³⁰ MRI can be used to assess changes in bone marrow and soft-tissue involvement. PET scans, which detect tumors by quantifying metabolic activity, remain controversial. PET is superior to bone scans in detecting bone metastases from lung and breast cancers, but worse in renal and prostate cancers due to slow growth of metastases.^31-33

Caveat. Do not assume that a bone lesion is metastatic. Delayed diagnosis of a primary bone tumor can lead to significant changes in clinical course and patient outcome.³⁴ If any doubt exists as to the type of lesion, arrange for a biopsy using proper technique and delay bone fixation until a histologic diagnosis is complete.³⁵ Biopsy may be performed via image-guided fine-needle aspiration, core biopsy, or open incisional biopsy.

Treatment options

Metastatic bone disease is typically managed nonsurgically with radiation, chemo- or immunotherapies, hormone suppression, bone-modifying agents, or ablation.³⁶ An overview of the cancer treatment guidelines for bone metastasis from the 2017 National Comprehensive Cancer Network is shown in TABLE 2.³⁶

Continue to: Radiotherapy

Radiotherapy can take the form of external-beam or radioisotope radiation. With localized irradiation, most patients who have painful lesions experience at least partial relief, often within a few weeks.^12,37 It may be used postoperatively, as well, to decrease the chances of disease progession.²⁰

Systemic therapies include chemo- and hormone therapies. Chemotherapy effectiveness is highly dependent on the primary tumor type. For example, renal cell carcinoma and melanoma are often resistant, while lymphoma and germ-cell tumors may be eliminated and sometimes even cured.⁷ Hormone therapy can be highly effective in selective cancers, primarily breast and prostate cancers. Immunotherapy options may also be used to specifically target bone metastasis sites.

Bone-modifying agents include bisphosphonates and denosumab (Prolia, Xgeva). These are generally initiated at the discretion of the oncologist, but primary care physicians should be familiar with their use. Bisphosphonates, which includes zoledronic acid, pamidronate, and other agents, are analogues of pyrophosphate that inhibit bone demineralization.³⁸ These agents target bone resorption through incorporation into osteoclasts and have been effective in the treatment of hypercalcemia and bone lesions.^6,12,39 Not only do they reduce the incidence of all skeleton-related events, including pathologic fractures and pain, they also appear to have antitumor activity with prolonged survival in certain cancers.^7,12

Denosumab, which has a much shorter half-life than bisphosphonates, is a monoclonal antibody that targets the gene RANKL, a key activator of osteoclasts, and thereby prevents the development of osteoclasts and related bone resorption.⁴⁰

Radiofrequency ablation or cryoablation, using image-guided needle placement, specifically targets individual bone lesions, destroying tumor cells with extreme heat or cold, respectively. This has been shown to reduce pain and opioid consumption.⁴¹

Continue to: Managing pain

 

 

Managing pain

Pain management can be difficult, especially as patients live longer and undergo additional treatments such as surgery, radiation, and chemotherapy, each with the potential to produce chronic pain.⁴² A multidisciplinary team with a stepwise and multimodal approach can improve the patient’s function and comfort while decreasing drug adverse effects.⁴³

For mild-to-moderate pain, nonsteroidal anti-inflammatory drugs, acetaminophen, and tramadol may provide effective relief. For more severe pain, narcotics are often required on a fixed-dose schedule along with breakthrough options such as short-acting hydromorphone, oxycodone, or transmucosal fentanyl.^42-44 Opioid adverse effects such as constipation and nausea/vomiting must be managed with laxatives and metoclopramide/antidopaminergics, respectively.

Other important non-narcotic therapies are corticosteroids, tricyclic antidepressants, gabapentin, neuroleptics, and nerve blocks.⁴⁵ Physical therapy and acupuncture may also be useful, depending on the patient’s needs and desires. Despite the wide range of options, most patients continue to have a significant amount of pain that can impact daily activities and even cause them to feel that their quality of life was not an important factor in physician decision making.⁴⁶

Surgery options

Surgical intervention for metastatic bone disease differs from its use in primary bone tumors in that clinical indications are not clearly defined. In general, surgery for metastatic disease is used in patients who have pathologic fractures, a risk of pathologic fracture, or uncontrolled cancer-induced bone pain. Keep in mind that the overarching goal of surgery is to reduce morbidity, not mortality, although exceptions exist. Metastatic renal cell carcinoma is one such exception: improved survival may be achieved via aggressive surgical resection for solitary or oligometastatic lesions.⁴⁷

Before deciding on surgery, engage the patient in goals-of-care discussions and take into account factors specific to the individual, as operative complications can be devasting. Risk of postoperative infection is high, given that these patients are often immunocompromised and that irradiated tissue is prone to wound healing issues.⁸ Complications may require a pause in chemotherapy and a subsequent decrease in life expectancy.

Continue to: Another factor in surgical decision making...

Another factor in surgical decision making is that newer systemic therapies are leading to longer survival for those with various types of metastatic cancer.⁴⁸ Older methods of fixation designed to last a few years may now fail during the patient’s prolonged ­lifespan. As novel therapies continue to improve survival and complicate surgical indications, it may be prudent for the surgical management of metastatic bone disease to be handled by fellowship-trained orthopedic oncologists.

Factors that affect timing. Surgical intervention ideally occurs before the development of a pathologic fracture. Outcomes research has shown that intervention before fracture leads to reduced blood loss and length of hospital stay with improved functional recovery and survival.^12,49 Despite these improved outcomes, an adequate scoring system to guide surgical intervention has yet to be developed. Mirels’ criteria are cited most often, yet this scoring system fails to account for many important considerations such as primary tumor type, life expectancy, and other factors.^50,51

If a patient with no known primary tumor has a confirmed bone lesion, order labs, a CT scan with contrast of the chest, abdomen, and pelvis, and a bone scan.

Given the deleterious effects of fractures in cancer patients and the inadequacy of closed reduction and immobilization, surgical intervention is often warranted.⁵² Surgical technology has continued to progress; however, intramedullary nailing, plating, and endoprostheses are still the most commonly used methods.⁵³

Intramedullary nailing is commonly used in the prophylactic treatment of pathologic lesions and fractures of long bones in patients whose expected survival is as little as 6 to 12 weeks.⁵⁴ Plate and screw fixation is a viable alternative to intramedullary nailing when tumor resection is desired. Endoprostheses replacement is used when a tumor involves joint surfaces or if biological reconstruction cannot be achieved by nailing or plating.

Explicit communication with patients is critical

Of vital importance is your participation with patients and families in shared decision making throughout the diagnostic and treatment process, ensuring clear communication. Misunderstandings about cancer stages and prognoses are not uncommon and are sometimes due to insufficient explanation.^55,56 Additionally, expectations of survival and adverse effects of treatment often differ greatly between physicians and patients, which can lead to patient dissatisfaction.⁵⁷

Continue to: Finally, the long-term care...

Finally, the long-term care of patients with metastatic cancers necessarily involves multidisciplinary teams, which further complicates communication. To ensure that patients are receiving an appropriate course of treatment, evaluate their health literacy, confirm their understanding of the disease, and acknowledge their desires.

CORRESPONDENCE
Kyle Sweeney, MD, University of Kansas Medical Center, Department of Orthopedic Surgery, 3901 Rainbow Boulevard, MS 3017, Kansas City, KS 66160; ksweeney2@kumc.edu.

Since the early 1990s, modern treatments have steadily reduced overall cancer mortality from primary tumors.¹ Consequently, more people are at risk of metastatic bone disease, with subsequent pain and pathologic fractures^1,2 and death from metastasis.³ Patients who have bone metastases present with a variety of signs and symptoms including pain, fractures, and metabolic derangements. The primary care approach to work-up and diagnosis described in this article enables prompt treatment, either surgical or nonsurgical, to maintain a high quality of life for patients.

Primary tumors determine types of metastases and prognosis

Metastasis, a complex pathologic process in which cancerous cells migrate to distant organs, implant, and grow,³ is a poor prognostic indicator in cancer patients. Bone is the third most common site of metastasis, behind the liver and lungs.⁴ While the true prevalence of metastatic bone cancer is unknown, studies have estimated it to be > 280,000 cases in the United States.⁵

Bone metastases interfere with normal bone metabolism and turnover in several different characteristic patterns. These changes—radiographically defined as osteoblastic, osteolytic, or mixed lesions—are determined by the primary tumor type.

• Osteoblastic lesions, comprised of new, disorganized bone formation, often occur secondary to prostate cancer, small cell lung cancer, and carcinoid malignancies, among others.
• Osteolytic lesions, in which bone is destroyed, are more common with breast cancer, renal cell carcinoma, melanoma, and multiple myeloma.
• Mixed lesions, in which areas of bone destruction and growth are simultaneously found, occur with some GI cancers and a few breast cancers.^6,7

Most bone metastases result from carcinomas, of which up to 50% eventually spread to bone, although this process can take 10 to 15 years.^8,9 The likelihood of bone metastasis depends on the primary tumor and its stage. Breast and prostate cancer account for most skeletal metastases, although these lesions are often asymptomatic.^6,9 Other malignancies, such as ovarian and gastrointestinal, metastasize to bone much less frequently.^7,10 Virtually any cancer at an advanced stage can spread to bone. These metastases are usually multifocal and incurable, with the patient’s prognosis varying from a few months to years.^6,11,12

Factors that influence prognosis. Metastatic bone disease arising from melanoma and lung cancers has the shortest life expectancy of roughly 6 months from initial diagnosis; metastasis following prostate, breast, and thyroid cancers has the longest, usually 2 to 4 years.¹¹TABLE 1¹³ shows survival estimates from a large Danish population at various time points following bone metastasis diagnosis for several primary cancer types.

When a patient presents with signs and symptoms suggestive of metastatic bone disease, inquire about a history of cancer—even if such a history is remote. It’s important.

When surgical intervention for bony metastasis is required, prognosis is generally poorer, likely due to more advanced disease. The overall 1-year survival following surgery varies, but several large studies have found a rate of around 40% when considering all primary tumors.^14,15 The most common metastases, from breast and prostate cancers, have 1-year survivals of around 50% and 30%, respectively, following surgical intervention.^16-18

What you’re likely to see on presentation

Bone metastases are one of the leading causes of morbidity in cancer patients from resultant pain, pathologic fractures, metabolic derangements, and reduced activities of daily living.^8,19 The most common cause of cancer pain is bone involvement.⁶ Patients report pain that is usually worse at night, poorly localized, and not alleviated with rest. They often mistakenly relate the pain to an injury.²⁰ The pathophysiology of bone pain is not completely understood but is likely multifactorial and includes inflammatory and mechanical processes.^7,21 Spine involvement can lead to stenosis or nerve root compression, with symptoms dependent on level and severity of nerve or cord compromise.²⁰ Overall, the most common site of bone metastasis is the thoracic spine, followed by the ribs, pelvis, and proximal long bones.²⁰

Continue to: Pathologic fractures

Pathologic fractures occur frequently in cancer patients. Bone destruction leads to a loss of mechanical support which, in turn, causes microfractures and pain. These microfractures can proliferate and coalesce, causing a pathologic fracture, often in weight-bearing bones.⁶ Breast cancer with lytic lesions is the single leading cause of all pathologic fractures.²² Lung cancer with its short survival time and prostate cancer with blastic lesions are less common causes.²³ In the appendicular skeleton, the vast majority of these fractures occur in the femur and humerus.¹¹

Symptomatic metabolic derangements. The most common metabolic disorder is hypercalcemia, found predominantly in patients with hematologic malignancies, squamous cell lung cancer, renal cell cancer, and breast cancer.^6,7,12,24 The clinical presentation is nonspecific and can include polyuria, polydipsia, fatigue, constipation, and confusion. The prevalence is estimated to be 13% in breast cancer, 4% in lung cancers, and 1% in prostate cancer, although results in individual studies vary.¹² The pathophysiology is multifactorial and often includes osteolytic lesions and an increased circulating level of parathyroid hormone–related peptide, although other mechanisms contribute.^25,26 Ultimately, severe hypercalcemia may be fatal secondary to renal failure and cardiac arrhythmias.^6,7,12 Paraneoplastic hypercalcemia independently decreases survival; 1 study found the median survival to be 10 to 12 weeks.¹¹

Primary care work-up and diagnosis

When a patient presents with signs and symptoms suggestive of metastatic bone disease, inquire about a history of cancer. Even if such a history is remote, it is important—­particularly so if the patient received chemotherapy or radiation, which can lead to secondary cancers such as leukemia or sarcoma.²⁰ If a primary site of malignancy is unknown, pursue a general review of systems. Clues to the primary site of disease could be a history of chest pain, shortness of breath, hemoptysis, heat/cold intolerance, or changes in bowel/bladder habits. Also ask about risk factors such as smoking, chemical exposure, and sun exposure.

Pointers on radiographic imaging. If you suspect a destructive bone lesion, order appropriate radiographic imaging. Arrange for plain radiographs with at least 2 views of the specific area of interest that include the entire bone along with the joints above and below. Importantly, the entire bone must be imaged before any surgical procedure to avoid periprosthetic fractures from undetected bone metastases around hardware.²⁰ Keep in mind that plain films can miss early lesions, and computed tomography (CT) or magnetic resonance imaging (MRI) may be needed if suspicion of a pathologic process is still strong and especially if a primary malignancy is known.²⁷

Working back to a primary diagnosis

If imaging confirms a suspicious lesion and the patient has no known primary tumor, order labs, a CT scan with contrast of the chest, abdomen, and pelvis, and a bone scan, and refer the patient to an oncologist. If the bone lesion is painful, initiate protected weight-bearing and additionally refer the patient to an orthopedic surgeon.

Continue to: Appropriate laboratory evaluation

Appropriate laboratory evaluation entails a complete blood count; metabolic panel that includes serum calcium and phosphorus, vitamin D, alkaline phosphatase, thyroid-stimulating hormone, and parathyroid hormone; and serum protein electrophoresis to rule out multiple myeloma.^7,11 Tumor markers are useful to monitor a patient’s response to cancer treatment or to determine recurrence, but they play only a limited role in the initial work-up of an unknown bone tumor.²⁸

Further imaging. A CT scan with intravenous contrast of the chest, abdomen, and pelvis is done to screen for visceral malignancy; however, 15% of bone lesions in patients with an unknown primary lesion never have a source identified.²⁹ Bone scans can be useful in identifying the extent of a single lesion seen on plain films and to assess for additional asymptomatic lesions. Additional imaging—eg, CT or MRI of the lesion, or positron emission tomography (PET)—can be left to the discretion of the oncologist or surgeon.

Order plain radiographs if you suspect a bone lesion. Request at least 2 views of the area that include the entire bone with the joints above and below.

CT scans have significantly higher sensitivity than radiographs and offer better visualization of bone quality, bone destruction, and soft-tissue extension.³⁰ MRI can be used to assess changes in bone marrow and soft-tissue involvement. PET scans, which detect tumors by quantifying metabolic activity, remain controversial. PET is superior to bone scans in detecting bone metastases from lung and breast cancers, but worse in renal and prostate cancers due to slow growth of metastases.^31-33

Caveat. Do not assume that a bone lesion is metastatic. Delayed diagnosis of a primary bone tumor can lead to significant changes in clinical course and patient outcome.³⁴ If any doubt exists as to the type of lesion, arrange for a biopsy using proper technique and delay bone fixation until a histologic diagnosis is complete.³⁵ Biopsy may be performed via image-guided fine-needle aspiration, core biopsy, or open incisional biopsy.

Treatment options

Metastatic bone disease is typically managed nonsurgically with radiation, chemo- or immunotherapies, hormone suppression, bone-modifying agents, or ablation.³⁶ An overview of the cancer treatment guidelines for bone metastasis from the 2017 National Comprehensive Cancer Network is shown in TABLE 2.³⁶

Continue to: Radiotherapy

Radiotherapy can take the form of external-beam or radioisotope radiation. With localized irradiation, most patients who have painful lesions experience at least partial relief, often within a few weeks.^12,37 It may be used postoperatively, as well, to decrease the chances of disease progession.²⁰

Systemic therapies include chemo- and hormone therapies. Chemotherapy effectiveness is highly dependent on the primary tumor type. For example, renal cell carcinoma and melanoma are often resistant, while lymphoma and germ-cell tumors may be eliminated and sometimes even cured.⁷ Hormone therapy can be highly effective in selective cancers, primarily breast and prostate cancers. Immunotherapy options may also be used to specifically target bone metastasis sites.

Bone-modifying agents include bisphosphonates and denosumab (Prolia, Xgeva). These are generally initiated at the discretion of the oncologist, but primary care physicians should be familiar with their use. Bisphosphonates, which includes zoledronic acid, pamidronate, and other agents, are analogues of pyrophosphate that inhibit bone demineralization.³⁸ These agents target bone resorption through incorporation into osteoclasts and have been effective in the treatment of hypercalcemia and bone lesions.^6,12,39 Not only do they reduce the incidence of all skeleton-related events, including pathologic fractures and pain, they also appear to have antitumor activity with prolonged survival in certain cancers.^7,12

Denosumab, which has a much shorter half-life than bisphosphonates, is a monoclonal antibody that targets the gene RANKL, a key activator of osteoclasts, and thereby prevents the development of osteoclasts and related bone resorption.⁴⁰

Radiofrequency ablation or cryoablation, using image-guided needle placement, specifically targets individual bone lesions, destroying tumor cells with extreme heat or cold, respectively. This has been shown to reduce pain and opioid consumption.⁴¹

Continue to: Managing pain

 

 

Managing pain

Pain management can be difficult, especially as patients live longer and undergo additional treatments such as surgery, radiation, and chemotherapy, each with the potential to produce chronic pain.⁴² A multidisciplinary team with a stepwise and multimodal approach can improve the patient’s function and comfort while decreasing drug adverse effects.⁴³

For mild-to-moderate pain, nonsteroidal anti-inflammatory drugs, acetaminophen, and tramadol may provide effective relief. For more severe pain, narcotics are often required on a fixed-dose schedule along with breakthrough options such as short-acting hydromorphone, oxycodone, or transmucosal fentanyl.^42-44 Opioid adverse effects such as constipation and nausea/vomiting must be managed with laxatives and metoclopramide/antidopaminergics, respectively.

Other important non-narcotic therapies are corticosteroids, tricyclic antidepressants, gabapentin, neuroleptics, and nerve blocks.⁴⁵ Physical therapy and acupuncture may also be useful, depending on the patient’s needs and desires. Despite the wide range of options, most patients continue to have a significant amount of pain that can impact daily activities and even cause them to feel that their quality of life was not an important factor in physician decision making.⁴⁶

Surgery options

Surgical intervention for metastatic bone disease differs from its use in primary bone tumors in that clinical indications are not clearly defined. In general, surgery for metastatic disease is used in patients who have pathologic fractures, a risk of pathologic fracture, or uncontrolled cancer-induced bone pain. Keep in mind that the overarching goal of surgery is to reduce morbidity, not mortality, although exceptions exist. Metastatic renal cell carcinoma is one such exception: improved survival may be achieved via aggressive surgical resection for solitary or oligometastatic lesions.⁴⁷

Before deciding on surgery, engage the patient in goals-of-care discussions and take into account factors specific to the individual, as operative complications can be devasting. Risk of postoperative infection is high, given that these patients are often immunocompromised and that irradiated tissue is prone to wound healing issues.⁸ Complications may require a pause in chemotherapy and a subsequent decrease in life expectancy.

Continue to: Another factor in surgical decision making...

Another factor in surgical decision making is that newer systemic therapies are leading to longer survival for those with various types of metastatic cancer.⁴⁸ Older methods of fixation designed to last a few years may now fail during the patient’s prolonged ­lifespan. As novel therapies continue to improve survival and complicate surgical indications, it may be prudent for the surgical management of metastatic bone disease to be handled by fellowship-trained orthopedic oncologists.

Factors that affect timing. Surgical intervention ideally occurs before the development of a pathologic fracture. Outcomes research has shown that intervention before fracture leads to reduced blood loss and length of hospital stay with improved functional recovery and survival.^12,49 Despite these improved outcomes, an adequate scoring system to guide surgical intervention has yet to be developed. Mirels’ criteria are cited most often, yet this scoring system fails to account for many important considerations such as primary tumor type, life expectancy, and other factors.^50,51

If a patient with no known primary tumor has a confirmed bone lesion, order labs, a CT scan with contrast of the chest, abdomen, and pelvis, and a bone scan.

Given the deleterious effects of fractures in cancer patients and the inadequacy of closed reduction and immobilization, surgical intervention is often warranted.⁵² Surgical technology has continued to progress; however, intramedullary nailing, plating, and endoprostheses are still the most commonly used methods.⁵³

Intramedullary nailing is commonly used in the prophylactic treatment of pathologic lesions and fractures of long bones in patients whose expected survival is as little as 6 to 12 weeks.⁵⁴ Plate and screw fixation is a viable alternative to intramedullary nailing when tumor resection is desired. Endoprostheses replacement is used when a tumor involves joint surfaces or if biological reconstruction cannot be achieved by nailing or plating.

Explicit communication with patients is critical

Of vital importance is your participation with patients and families in shared decision making throughout the diagnostic and treatment process, ensuring clear communication. Misunderstandings about cancer stages and prognoses are not uncommon and are sometimes due to insufficient explanation.^55,56 Additionally, expectations of survival and adverse effects of treatment often differ greatly between physicians and patients, which can lead to patient dissatisfaction.⁵⁷

Continue to: Finally, the long-term care...

Finally, the long-term care of patients with metastatic cancers necessarily involves multidisciplinary teams, which further complicates communication. To ensure that patients are receiving an appropriate course of treatment, evaluate their health literacy, confirm their understanding of the disease, and acknowledge their desires.

CORRESPONDENCE
Kyle Sweeney, MD, University of Kansas Medical Center, Department of Orthopedic Surgery, 3901 Rainbow Boulevard, MS 3017, Kansas City, KS 66160; ksweeney2@kumc.edu.

Since the early 1990s, modern treatments have steadily reduced overall cancer mortality from primary tumors.¹ Consequently, more people are at risk of metastatic bone disease, with subsequent pain and pathologic fractures^1,2 and death from metastasis.³ Patients who have bone metastases present with a variety of signs and symptoms including pain, fractures, and metabolic derangements. The primary care approach to work-up and diagnosis described in this article enables prompt treatment, either surgical or nonsurgical, to maintain a high quality of life for patients.

Primary tumors determine types of metastases and prognosis

Metastasis, a complex pathologic process in which cancerous cells migrate to distant organs, implant, and grow,³ is a poor prognostic indicator in cancer patients. Bone is the third most common site of metastasis, behind the liver and lungs.⁴ While the true prevalence of metastatic bone cancer is unknown, studies have estimated it to be > 280,000 cases in the United States.⁵

Bone metastases interfere with normal bone metabolism and turnover in several different characteristic patterns. These changes—radiographically defined as osteoblastic, osteolytic, or mixed lesions—are determined by the primary tumor type.

• Osteoblastic lesions, comprised of new, disorganized bone formation, often occur secondary to prostate cancer, small cell lung cancer, and carcinoid malignancies, among others.
• Osteolytic lesions, in which bone is destroyed, are more common with breast cancer, renal cell carcinoma, melanoma, and multiple myeloma.
• Mixed lesions, in which areas of bone destruction and growth are simultaneously found, occur with some GI cancers and a few breast cancers.^6,7

Most bone metastases result from carcinomas, of which up to 50% eventually spread to bone, although this process can take 10 to 15 years.^8,9 The likelihood of bone metastasis depends on the primary tumor and its stage. Breast and prostate cancer account for most skeletal metastases, although these lesions are often asymptomatic.^6,9 Other malignancies, such as ovarian and gastrointestinal, metastasize to bone much less frequently.^7,10 Virtually any cancer at an advanced stage can spread to bone. These metastases are usually multifocal and incurable, with the patient’s prognosis varying from a few months to years.^6,11,12

Factors that influence prognosis. Metastatic bone disease arising from melanoma and lung cancers has the shortest life expectancy of roughly 6 months from initial diagnosis; metastasis following prostate, breast, and thyroid cancers has the longest, usually 2 to 4 years.¹¹TABLE 1¹³ shows survival estimates from a large Danish population at various time points following bone metastasis diagnosis for several primary cancer types.

When a patient presents with signs and symptoms suggestive of metastatic bone disease, inquire about a history of cancer—even if such a history is remote. It’s important.

When surgical intervention for bony metastasis is required, prognosis is generally poorer, likely due to more advanced disease. The overall 1-year survival following surgery varies, but several large studies have found a rate of around 40% when considering all primary tumors.^14,15 The most common metastases, from breast and prostate cancers, have 1-year survivals of around 50% and 30%, respectively, following surgical intervention.^16-18

What you’re likely to see on presentation

Bone metastases are one of the leading causes of morbidity in cancer patients from resultant pain, pathologic fractures, metabolic derangements, and reduced activities of daily living.^8,19 The most common cause of cancer pain is bone involvement.⁶ Patients report pain that is usually worse at night, poorly localized, and not alleviated with rest. They often mistakenly relate the pain to an injury.²⁰ The pathophysiology of bone pain is not completely understood but is likely multifactorial and includes inflammatory and mechanical processes.^7,21 Spine involvement can lead to stenosis or nerve root compression, with symptoms dependent on level and severity of nerve or cord compromise.²⁰ Overall, the most common site of bone metastasis is the thoracic spine, followed by the ribs, pelvis, and proximal long bones.²⁰

Continue to: Pathologic fractures

Pathologic fractures occur frequently in cancer patients. Bone destruction leads to a loss of mechanical support which, in turn, causes microfractures and pain. These microfractures can proliferate and coalesce, causing a pathologic fracture, often in weight-bearing bones.⁶ Breast cancer with lytic lesions is the single leading cause of all pathologic fractures.²² Lung cancer with its short survival time and prostate cancer with blastic lesions are less common causes.²³ In the appendicular skeleton, the vast majority of these fractures occur in the femur and humerus.¹¹

Symptomatic metabolic derangements. The most common metabolic disorder is hypercalcemia, found predominantly in patients with hematologic malignancies, squamous cell lung cancer, renal cell cancer, and breast cancer.^6,7,12,24 The clinical presentation is nonspecific and can include polyuria, polydipsia, fatigue, constipation, and confusion. The prevalence is estimated to be 13% in breast cancer, 4% in lung cancers, and 1% in prostate cancer, although results in individual studies vary.¹² The pathophysiology is multifactorial and often includes osteolytic lesions and an increased circulating level of parathyroid hormone–related peptide, although other mechanisms contribute.^25,26 Ultimately, severe hypercalcemia may be fatal secondary to renal failure and cardiac arrhythmias.^6,7,12 Paraneoplastic hypercalcemia independently decreases survival; 1 study found the median survival to be 10 to 12 weeks.¹¹

Primary care work-up and diagnosis

When a patient presents with signs and symptoms suggestive of metastatic bone disease, inquire about a history of cancer. Even if such a history is remote, it is important—­particularly so if the patient received chemotherapy or radiation, which can lead to secondary cancers such as leukemia or sarcoma.²⁰ If a primary site of malignancy is unknown, pursue a general review of systems. Clues to the primary site of disease could be a history of chest pain, shortness of breath, hemoptysis, heat/cold intolerance, or changes in bowel/bladder habits. Also ask about risk factors such as smoking, chemical exposure, and sun exposure.

Pointers on radiographic imaging. If you suspect a destructive bone lesion, order appropriate radiographic imaging. Arrange for plain radiographs with at least 2 views of the specific area of interest that include the entire bone along with the joints above and below. Importantly, the entire bone must be imaged before any surgical procedure to avoid periprosthetic fractures from undetected bone metastases around hardware.²⁰ Keep in mind that plain films can miss early lesions, and computed tomography (CT) or magnetic resonance imaging (MRI) may be needed if suspicion of a pathologic process is still strong and especially if a primary malignancy is known.²⁷

Working back to a primary diagnosis

If imaging confirms a suspicious lesion and the patient has no known primary tumor, order labs, a CT scan with contrast of the chest, abdomen, and pelvis, and a bone scan, and refer the patient to an oncologist. If the bone lesion is painful, initiate protected weight-bearing and additionally refer the patient to an orthopedic surgeon.

Continue to: Appropriate laboratory evaluation

Appropriate laboratory evaluation entails a complete blood count; metabolic panel that includes serum calcium and phosphorus, vitamin D, alkaline phosphatase, thyroid-stimulating hormone, and parathyroid hormone; and serum protein electrophoresis to rule out multiple myeloma.^7,11 Tumor markers are useful to monitor a patient’s response to cancer treatment or to determine recurrence, but they play only a limited role in the initial work-up of an unknown bone tumor.²⁸

Further imaging. A CT scan with intravenous contrast of the chest, abdomen, and pelvis is done to screen for visceral malignancy; however, 15% of bone lesions in patients with an unknown primary lesion never have a source identified.²⁹ Bone scans can be useful in identifying the extent of a single lesion seen on plain films and to assess for additional asymptomatic lesions. Additional imaging—eg, CT or MRI of the lesion, or positron emission tomography (PET)—can be left to the discretion of the oncologist or surgeon.

Order plain radiographs if you suspect a bone lesion. Request at least 2 views of the area that include the entire bone with the joints above and below.

CT scans have significantly higher sensitivity than radiographs and offer better visualization of bone quality, bone destruction, and soft-tissue extension.³⁰ MRI can be used to assess changes in bone marrow and soft-tissue involvement. PET scans, which detect tumors by quantifying metabolic activity, remain controversial. PET is superior to bone scans in detecting bone metastases from lung and breast cancers, but worse in renal and prostate cancers due to slow growth of metastases.^31-33

Caveat. Do not assume that a bone lesion is metastatic. Delayed diagnosis of a primary bone tumor can lead to significant changes in clinical course and patient outcome.³⁴ If any doubt exists as to the type of lesion, arrange for a biopsy using proper technique and delay bone fixation until a histologic diagnosis is complete.³⁵ Biopsy may be performed via image-guided fine-needle aspiration, core biopsy, or open incisional biopsy.

Treatment options

Metastatic bone disease is typically managed nonsurgically with radiation, chemo- or immunotherapies, hormone suppression, bone-modifying agents, or ablation.³⁶ An overview of the cancer treatment guidelines for bone metastasis from the 2017 National Comprehensive Cancer Network is shown in TABLE 2.³⁶

Continue to: Radiotherapy

Radiotherapy can take the form of external-beam or radioisotope radiation. With localized irradiation, most patients who have painful lesions experience at least partial relief, often within a few weeks.^12,37 It may be used postoperatively, as well, to decrease the chances of disease progession.²⁰

Systemic therapies include chemo- and hormone therapies. Chemotherapy effectiveness is highly dependent on the primary tumor type. For example, renal cell carcinoma and melanoma are often resistant, while lymphoma and germ-cell tumors may be eliminated and sometimes even cured.⁷ Hormone therapy can be highly effective in selective cancers, primarily breast and prostate cancers. Immunotherapy options may also be used to specifically target bone metastasis sites.

Bone-modifying agents include bisphosphonates and denosumab (Prolia, Xgeva). These are generally initiated at the discretion of the oncologist, but primary care physicians should be familiar with their use. Bisphosphonates, which includes zoledronic acid, pamidronate, and other agents, are analogues of pyrophosphate that inhibit bone demineralization.³⁸ These agents target bone resorption through incorporation into osteoclasts and have been effective in the treatment of hypercalcemia and bone lesions.^6,12,39 Not only do they reduce the incidence of all skeleton-related events, including pathologic fractures and pain, they also appear to have antitumor activity with prolonged survival in certain cancers.^7,12

Denosumab, which has a much shorter half-life than bisphosphonates, is a monoclonal antibody that targets the gene RANKL, a key activator of osteoclasts, and thereby prevents the development of osteoclasts and related bone resorption.⁴⁰

Radiofrequency ablation or cryoablation, using image-guided needle placement, specifically targets individual bone lesions, destroying tumor cells with extreme heat or cold, respectively. This has been shown to reduce pain and opioid consumption.⁴¹

Continue to: Managing pain

 

 

Managing pain

Pain management can be difficult, especially as patients live longer and undergo additional treatments such as surgery, radiation, and chemotherapy, each with the potential to produce chronic pain.⁴² A multidisciplinary team with a stepwise and multimodal approach can improve the patient’s function and comfort while decreasing drug adverse effects.⁴³

For mild-to-moderate pain, nonsteroidal anti-inflammatory drugs, acetaminophen, and tramadol may provide effective relief. For more severe pain, narcotics are often required on a fixed-dose schedule along with breakthrough options such as short-acting hydromorphone, oxycodone, or transmucosal fentanyl.^42-44 Opioid adverse effects such as constipation and nausea/vomiting must be managed with laxatives and metoclopramide/antidopaminergics, respectively.

Other important non-narcotic therapies are corticosteroids, tricyclic antidepressants, gabapentin, neuroleptics, and nerve blocks.⁴⁵ Physical therapy and acupuncture may also be useful, depending on the patient’s needs and desires. Despite the wide range of options, most patients continue to have a significant amount of pain that can impact daily activities and even cause them to feel that their quality of life was not an important factor in physician decision making.⁴⁶

Surgery options

Surgical intervention for metastatic bone disease differs from its use in primary bone tumors in that clinical indications are not clearly defined. In general, surgery for metastatic disease is used in patients who have pathologic fractures, a risk of pathologic fracture, or uncontrolled cancer-induced bone pain. Keep in mind that the overarching goal of surgery is to reduce morbidity, not mortality, although exceptions exist. Metastatic renal cell carcinoma is one such exception: improved survival may be achieved via aggressive surgical resection for solitary or oligometastatic lesions.⁴⁷

Before deciding on surgery, engage the patient in goals-of-care discussions and take into account factors specific to the individual, as operative complications can be devasting. Risk of postoperative infection is high, given that these patients are often immunocompromised and that irradiated tissue is prone to wound healing issues.⁸ Complications may require a pause in chemotherapy and a subsequent decrease in life expectancy.

Continue to: Another factor in surgical decision making...

Another factor in surgical decision making is that newer systemic therapies are leading to longer survival for those with various types of metastatic cancer.⁴⁸ Older methods of fixation designed to last a few years may now fail during the patient’s prolonged ­lifespan. As novel therapies continue to improve survival and complicate surgical indications, it may be prudent for the surgical management of metastatic bone disease to be handled by fellowship-trained orthopedic oncologists.

Factors that affect timing. Surgical intervention ideally occurs before the development of a pathologic fracture. Outcomes research has shown that intervention before fracture leads to reduced blood loss and length of hospital stay with improved functional recovery and survival.^12,49 Despite these improved outcomes, an adequate scoring system to guide surgical intervention has yet to be developed. Mirels’ criteria are cited most often, yet this scoring system fails to account for many important considerations such as primary tumor type, life expectancy, and other factors.^50,51

If a patient with no known primary tumor has a confirmed bone lesion, order labs, a CT scan with contrast of the chest, abdomen, and pelvis, and a bone scan.

Given the deleterious effects of fractures in cancer patients and the inadequacy of closed reduction and immobilization, surgical intervention is often warranted.⁵² Surgical technology has continued to progress; however, intramedullary nailing, plating, and endoprostheses are still the most commonly used methods.⁵³

Intramedullary nailing is commonly used in the prophylactic treatment of pathologic lesions and fractures of long bones in patients whose expected survival is as little as 6 to 12 weeks.⁵⁴ Plate and screw fixation is a viable alternative to intramedullary nailing when tumor resection is desired. Endoprostheses replacement is used when a tumor involves joint surfaces or if biological reconstruction cannot be achieved by nailing or plating.

Explicit communication with patients is critical

Of vital importance is your participation with patients and families in shared decision making throughout the diagnostic and treatment process, ensuring clear communication. Misunderstandings about cancer stages and prognoses are not uncommon and are sometimes due to insufficient explanation.^55,56 Additionally, expectations of survival and adverse effects of treatment often differ greatly between physicians and patients, which can lead to patient dissatisfaction.⁵⁷

Continue to: Finally, the long-term care...

Finally, the long-term care of patients with metastatic cancers necessarily involves multidisciplinary teams, which further complicates communication. To ensure that patients are receiving an appropriate course of treatment, evaluate their health literacy, confirm their understanding of the disease, and acknowledge their desires.

CORRESPONDENCE
Kyle Sweeney, MD, University of Kansas Medical Center, Department of Orthopedic Surgery, 3901 Rainbow Boulevard, MS 3017, Kansas City, KS 66160; ksweeney2@kumc.edu.

A new review offers fresh guidance to help stem the mental health toll of the COVID-19 pandemic on frontline clinicians.

Investigators gathered practice guidelines and resources from a wide range of health care organizations and professional societies to develop a conceptual framework of mental health support for health care professionals (HCPs) caring for COVID-19 patients.

An opportune moment

Coauthor Rebecca Margolis, DO, director of well-being in the division of medical education and faculty development, Children’s Hospital of Los Angeles, said that this is “an opportune moment to look at how we treat frontline providers in this country.”

Studies of previous pandemics have shown heightened distress in HCPs, even years after the pandemic, and the unique challenges posed by the COVID-19 pandemic surpass those of previous pandemics, Dr. Margolis said in an interview.

Dr. Schwartz, Dr. Margolis, and coauthors Uma Anand, PhD, LP, and Jina Sinskey, MD, met through the Collaborative for Healing and Renewal in Medicine network, a group of medical educators, leaders in academic medicine, experts in burnout research and interventions, and trainees working together to promote well-being among trainees and practicing physicians.

“We were brought together on a conference call in March, when things were particularly bad in New York, and started looking to see what resources we could get to frontline providers who were suffering. It was great to lean on each other and stand on the shoulders of colleagues in New York, who were the ones we learned from on these calls,” said Dr. Margolis.

The authors recommended addressing clinicians’ basic practical needs, including ensuring essentials like meals and transportation, establishing a “well-being area” within hospitals for staff to rest, and providing well-stocked living quarters so clinicians can safely quarantine from family, as well as personal protective equipment and child care.

Clinicians are often asked to “assume new professional roles to meet evolving needs” during a pandemic, which can increase stress. The authors recommended targeted training, assessment of clinician skills before redeployment to a new clinical role, and clear communication practices around redeployment.

Recognition from hospital and government leaders improves morale and supports clinicians’ ability to continue delivering care. Leadership should “leverage communication strategies to provide clinicians with up-to-date information and reassurance,” they wrote.
 

‘Uniquely isolated’

Dr. Margolis noted that clinicians “are uniquely isolated, especially those with children” because many parents do not want their children mingling with children of HCPs.

“My colleagues feel a sense of moral injury, putting their lives on the line at work, performing the most perilous job, and their kids can’t hang out with other kids, which just puts salt on the wound,” she said.

Additional sources of moral injury are deciding which patients should receive life support in the event of inadequate resources and bearing witness to, or enforcing, policies that lead to patients dying alone.

Leaders should encourage clinicians to “seek informal support from colleagues, managers, or chaplains” and to “provide rapid access to professional help,” the authors noted.

Furthermore, they contended that leaders should “proactively and routinely monitor the psychological well-being of their teams,” since guilt and shame often prevent clinicians from disclosing feelings of moral injury.

“Being provided with routine mental health support should be normalized and it should be part of the job – not only during COVID-19 but in general,” Dr. Schwartz said.
 

‘Battle buddies’

Dr. Margolis recommended the “battle buddy” model for mutual peer support.

Dr. Anand, a mental health clinician at Mayo Medical School, Rochester, Minn., elaborated.

Self-care critical

Marcus S. Shaker, MD, MSc, associate professor of pediatrics, medicine, and community and family medicine, Children’s Hospital at Dartmouth-Hitchcock in Lebanon, N.H., and Geisel School of Medicine at Dartmouth, Hanover, N.H., said the study was “a much appreciated, timely reminder of the importance of clinician wellness.”

Moreover, “without self-care, our ability to help our patients withers. This article provides a useful conceptual framework for individuals and organizations to provide the right care at the right time in these unprecedented times,” said Dr. Shaker, who was not involved with the study.

The authors agreed, stating that clinicians “require proactive psychological protection specifically because they are a population known for putting others’ needs before their own.”

They recommended several resources for HCPs, including the Physician Support Line; Headspace, a mindfulness Web-based app for reducing stress and anxiety; the National Suicide Prevention Lifeline; and the Crisis Text Line.

The authors and Dr. Shaker disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

A new review offers fresh guidance to help stem the mental health toll of the COVID-19 pandemic on frontline clinicians.

Investigators gathered practice guidelines and resources from a wide range of health care organizations and professional societies to develop a conceptual framework of mental health support for health care professionals (HCPs) caring for COVID-19 patients.

An opportune moment

Coauthor Rebecca Margolis, DO, director of well-being in the division of medical education and faculty development, Children’s Hospital of Los Angeles, said that this is “an opportune moment to look at how we treat frontline providers in this country.”

Studies of previous pandemics have shown heightened distress in HCPs, even years after the pandemic, and the unique challenges posed by the COVID-19 pandemic surpass those of previous pandemics, Dr. Margolis said in an interview.

Dr. Schwartz, Dr. Margolis, and coauthors Uma Anand, PhD, LP, and Jina Sinskey, MD, met through the Collaborative for Healing and Renewal in Medicine network, a group of medical educators, leaders in academic medicine, experts in burnout research and interventions, and trainees working together to promote well-being among trainees and practicing physicians.

“We were brought together on a conference call in March, when things were particularly bad in New York, and started looking to see what resources we could get to frontline providers who were suffering. It was great to lean on each other and stand on the shoulders of colleagues in New York, who were the ones we learned from on these calls,” said Dr. Margolis.

The authors recommended addressing clinicians’ basic practical needs, including ensuring essentials like meals and transportation, establishing a “well-being area” within hospitals for staff to rest, and providing well-stocked living quarters so clinicians can safely quarantine from family, as well as personal protective equipment and child care.

Clinicians are often asked to “assume new professional roles to meet evolving needs” during a pandemic, which can increase stress. The authors recommended targeted training, assessment of clinician skills before redeployment to a new clinical role, and clear communication practices around redeployment.

Recognition from hospital and government leaders improves morale and supports clinicians’ ability to continue delivering care. Leadership should “leverage communication strategies to provide clinicians with up-to-date information and reassurance,” they wrote.
 

‘Uniquely isolated’

Dr. Margolis noted that clinicians “are uniquely isolated, especially those with children” because many parents do not want their children mingling with children of HCPs.

“My colleagues feel a sense of moral injury, putting their lives on the line at work, performing the most perilous job, and their kids can’t hang out with other kids, which just puts salt on the wound,” she said.

Additional sources of moral injury are deciding which patients should receive life support in the event of inadequate resources and bearing witness to, or enforcing, policies that lead to patients dying alone.

Leaders should encourage clinicians to “seek informal support from colleagues, managers, or chaplains” and to “provide rapid access to professional help,” the authors noted.

Furthermore, they contended that leaders should “proactively and routinely monitor the psychological well-being of their teams,” since guilt and shame often prevent clinicians from disclosing feelings of moral injury.

“Being provided with routine mental health support should be normalized and it should be part of the job – not only during COVID-19 but in general,” Dr. Schwartz said.
 

‘Battle buddies’

Dr. Margolis recommended the “battle buddy” model for mutual peer support.

Dr. Anand, a mental health clinician at Mayo Medical School, Rochester, Minn., elaborated.

Self-care critical

Marcus S. Shaker, MD, MSc, associate professor of pediatrics, medicine, and community and family medicine, Children’s Hospital at Dartmouth-Hitchcock in Lebanon, N.H., and Geisel School of Medicine at Dartmouth, Hanover, N.H., said the study was “a much appreciated, timely reminder of the importance of clinician wellness.”

Moreover, “without self-care, our ability to help our patients withers. This article provides a useful conceptual framework for individuals and organizations to provide the right care at the right time in these unprecedented times,” said Dr. Shaker, who was not involved with the study.

The authors agreed, stating that clinicians “require proactive psychological protection specifically because they are a population known for putting others’ needs before their own.”

They recommended several resources for HCPs, including the Physician Support Line; Headspace, a mindfulness Web-based app for reducing stress and anxiety; the National Suicide Prevention Lifeline; and the Crisis Text Line.

The authors and Dr. Shaker disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

A new review offers fresh guidance to help stem the mental health toll of the COVID-19 pandemic on frontline clinicians.

Investigators gathered practice guidelines and resources from a wide range of health care organizations and professional societies to develop a conceptual framework of mental health support for health care professionals (HCPs) caring for COVID-19 patients.

An opportune moment

Coauthor Rebecca Margolis, DO, director of well-being in the division of medical education and faculty development, Children’s Hospital of Los Angeles, said that this is “an opportune moment to look at how we treat frontline providers in this country.”

Studies of previous pandemics have shown heightened distress in HCPs, even years after the pandemic, and the unique challenges posed by the COVID-19 pandemic surpass those of previous pandemics, Dr. Margolis said in an interview.

Dr. Schwartz, Dr. Margolis, and coauthors Uma Anand, PhD, LP, and Jina Sinskey, MD, met through the Collaborative for Healing and Renewal in Medicine network, a group of medical educators, leaders in academic medicine, experts in burnout research and interventions, and trainees working together to promote well-being among trainees and practicing physicians.

“We were brought together on a conference call in March, when things were particularly bad in New York, and started looking to see what resources we could get to frontline providers who were suffering. It was great to lean on each other and stand on the shoulders of colleagues in New York, who were the ones we learned from on these calls,” said Dr. Margolis.

The authors recommended addressing clinicians’ basic practical needs, including ensuring essentials like meals and transportation, establishing a “well-being area” within hospitals for staff to rest, and providing well-stocked living quarters so clinicians can safely quarantine from family, as well as personal protective equipment and child care.

Clinicians are often asked to “assume new professional roles to meet evolving needs” during a pandemic, which can increase stress. The authors recommended targeted training, assessment of clinician skills before redeployment to a new clinical role, and clear communication practices around redeployment.

Recognition from hospital and government leaders improves morale and supports clinicians’ ability to continue delivering care. Leadership should “leverage communication strategies to provide clinicians with up-to-date information and reassurance,” they wrote.
 

‘Uniquely isolated’

Dr. Margolis noted that clinicians “are uniquely isolated, especially those with children” because many parents do not want their children mingling with children of HCPs.

“My colleagues feel a sense of moral injury, putting their lives on the line at work, performing the most perilous job, and their kids can’t hang out with other kids, which just puts salt on the wound,” she said.

Additional sources of moral injury are deciding which patients should receive life support in the event of inadequate resources and bearing witness to, or enforcing, policies that lead to patients dying alone.

Leaders should encourage clinicians to “seek informal support from colleagues, managers, or chaplains” and to “provide rapid access to professional help,” the authors noted.

Furthermore, they contended that leaders should “proactively and routinely monitor the psychological well-being of their teams,” since guilt and shame often prevent clinicians from disclosing feelings of moral injury.

“Being provided with routine mental health support should be normalized and it should be part of the job – not only during COVID-19 but in general,” Dr. Schwartz said.
 

‘Battle buddies’

Dr. Margolis recommended the “battle buddy” model for mutual peer support.

Dr. Anand, a mental health clinician at Mayo Medical School, Rochester, Minn., elaborated.

Self-care critical

Marcus S. Shaker, MD, MSc, associate professor of pediatrics, medicine, and community and family medicine, Children’s Hospital at Dartmouth-Hitchcock in Lebanon, N.H., and Geisel School of Medicine at Dartmouth, Hanover, N.H., said the study was “a much appreciated, timely reminder of the importance of clinician wellness.”

Moreover, “without self-care, our ability to help our patients withers. This article provides a useful conceptual framework for individuals and organizations to provide the right care at the right time in these unprecedented times,” said Dr. Shaker, who was not involved with the study.

The authors agreed, stating that clinicians “require proactive psychological protection specifically because they are a population known for putting others’ needs before their own.”

They recommended several resources for HCPs, including the Physician Support Line; Headspace, a mindfulness Web-based app for reducing stress and anxiety; the National Suicide Prevention Lifeline; and the Crisis Text Line.

The authors and Dr. Shaker disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

In this issue of JFP, there is an extraordinarily valuable PURL (Priority Updates from the Research Literature) for you. PURLs^® are written by academic family physicians who comb through volumes of research to identify and then summarize for JFP important studies we believe should change your practice. After reading a PURL, you may find that you have already implemented this new evidence into your practice. In that case, the PURL confirms that you are doing the right thing.

We should all tell our patients to take their BP medication in the evening from now on. What could be an easier way to reduce CV morbidity and mortality?

Here is the good news from this month’s PURL: Having patients take their blood pressure (BP) medication in the evening, rather than in the morning, leads not only to better BP control but also to a reduction in cardiovascular events.¹ How large is this effect? This simple intervention nearly cut in half the number of major cardiovascular events—including myocardial infarction, stroke, and congestive heart failure—and the risk for death from a cardiovascular event was reduced 56%. The number needed to treat to prevent 1 major cardiovascular event over the course of 6.3 years was 20. That means this intervention is more powerful than taking a statin!

The investigators, who call this intervention “chronotherapy” since it takes into account the body’s circadian rhythms, have been studying the effect of this simple intervention for many years, and this large randomized trial provides very strong evidence that it’s effective. Despite the excellent trial design and execution, some cardiovascular researchers have questioned the integrity of the trial and believe patients should continue to take their antihypertensives in the morning.² The main investigator of the study, however, has provided a very strong rebuttal in print.³

I am delighted to see the positive results of this definitive trial of chronotherapy for hypertension. When these investigators published their first randomized trial of chronotherapy in 2010,⁴ which demonstrated a significant BP reduction with evening dosing of antihypertensives, I began telling all of my patients to take at least 1 of their antihypertensive meds in the evening. Maybe I was jumping the gun at that time, but we should all tell our patients to take their BP medication in the evening from now on. What could be an easier way to reduce cardiovascular morbidity and mortality?

In this issue of JFP, there is an extraordinarily valuable PURL (Priority Updates from the Research Literature) for you. PURLs^® are written by academic family physicians who comb through volumes of research to identify and then summarize for JFP important studies we believe should change your practice. After reading a PURL, you may find that you have already implemented this new evidence into your practice. In that case, the PURL confirms that you are doing the right thing.

We should all tell our patients to take their BP medication in the evening from now on. What could be an easier way to reduce CV morbidity and mortality?

Here is the good news from this month’s PURL: Having patients take their blood pressure (BP) medication in the evening, rather than in the morning, leads not only to better BP control but also to a reduction in cardiovascular events.¹ How large is this effect? This simple intervention nearly cut in half the number of major cardiovascular events—including myocardial infarction, stroke, and congestive heart failure—and the risk for death from a cardiovascular event was reduced 56%. The number needed to treat to prevent 1 major cardiovascular event over the course of 6.3 years was 20. That means this intervention is more powerful than taking a statin!

The investigators, who call this intervention “chronotherapy” since it takes into account the body’s circadian rhythms, have been studying the effect of this simple intervention for many years, and this large randomized trial provides very strong evidence that it’s effective. Despite the excellent trial design and execution, some cardiovascular researchers have questioned the integrity of the trial and believe patients should continue to take their antihypertensives in the morning.² The main investigator of the study, however, has provided a very strong rebuttal in print.³

I am delighted to see the positive results of this definitive trial of chronotherapy for hypertension. When these investigators published their first randomized trial of chronotherapy in 2010,⁴ which demonstrated a significant BP reduction with evening dosing of antihypertensives, I began telling all of my patients to take at least 1 of their antihypertensive meds in the evening. Maybe I was jumping the gun at that time, but we should all tell our patients to take their BP medication in the evening from now on. What could be an easier way to reduce cardiovascular morbidity and mortality?

In this issue of JFP, there is an extraordinarily valuable PURL (Priority Updates from the Research Literature) for you. PURLs^® are written by academic family physicians who comb through volumes of research to identify and then summarize for JFP important studies we believe should change your practice. After reading a PURL, you may find that you have already implemented this new evidence into your practice. In that case, the PURL confirms that you are doing the right thing.

We should all tell our patients to take their BP medication in the evening from now on. What could be an easier way to reduce CV morbidity and mortality?

Here is the good news from this month’s PURL: Having patients take their blood pressure (BP) medication in the evening, rather than in the morning, leads not only to better BP control but also to a reduction in cardiovascular events.¹ How large is this effect? This simple intervention nearly cut in half the number of major cardiovascular events—including myocardial infarction, stroke, and congestive heart failure—and the risk for death from a cardiovascular event was reduced 56%. The number needed to treat to prevent 1 major cardiovascular event over the course of 6.3 years was 20. That means this intervention is more powerful than taking a statin!

The investigators, who call this intervention “chronotherapy” since it takes into account the body’s circadian rhythms, have been studying the effect of this simple intervention for many years, and this large randomized trial provides very strong evidence that it’s effective. Despite the excellent trial design and execution, some cardiovascular researchers have questioned the integrity of the trial and believe patients should continue to take their antihypertensives in the morning.² The main investigator of the study, however, has provided a very strong rebuttal in print.³

I am delighted to see the positive results of this definitive trial of chronotherapy for hypertension. When these investigators published their first randomized trial of chronotherapy in 2010,⁴ which demonstrated a significant BP reduction with evening dosing of antihypertensives, I began telling all of my patients to take at least 1 of their antihypertensive meds in the evening. Maybe I was jumping the gun at that time, but we should all tell our patients to take their BP medication in the evening from now on. What could be an easier way to reduce cardiovascular morbidity and mortality?

ILLUSTRATIVE CASE

A 54-year-old White woman presents to your office with new-onset hypertension. As you are discussing options for treatment, she mentions she would prefer once-daily dosing to help her remember to take her medication. She also wants to know what the best time of day is to take her medication to reduce her risk of cardiovascular disease (CVD). What do you advise?

The burden of hypertension is significant and growing in the United States. The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines reported that more than 108 million people were affected in 2015-2016—up from 87 million in 1999-2000.² Yet control of hypertension is improving among those receiving antihypertension pharmacotherapy. As reported in the ACC/AHA guidelines, data from the 2016 National Health and Nutrition Examination Survey (NHANES) indicate an increase of controlled hypertension among those receiving treatment from 25.6% (1999-2000) to 43.5% (2015-2016).²

Chronotherapy involves the administration of medication in coordination with the body’s circadian rhythms to maximize therapeutic effectiveness and/or minimize adverse effects. It is not a new concept as it applies to hypertension. Circadian rhythm–­dependent mechanisms influence the natural rise and fall of blood pressure (BP).¹ The ­renin-­angiotensin-aldosterone system, known to be most active at night, is a target mechanism for BP control.¹ Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are more effective (alone or in combination with other agents) at reducing BP during sleep and wakefulness when they are taken at night.^3,4 Additional prospective clinical trials and systematic reviews have documented improved BP during sleep and on 24-hour ambulatory monitoring when antihypertensives are taken at bedtime.^3-5

However, there have been few long-term studies assessing the effects of bedtime administration of antihypertensive medication on CVD risk reduction with patient-oriented outcomes.^6,7 Additionally, no studies have evaluated morning vs bedtime administration of antihypertensive medication for CVD risk reduction in a primary care setting. The 2019 ACC/AHA guideline on the primary prevention of CVD offers no recommendation regarding when to take antihypertensive medication.⁸ Timing of medication administration also is not addressed in the NHANES study of hypertension awareness, treatment, and control in US adults.⁹

This study sought to determine in a primary care setting whether taking antihypertensives at bedtime, as opposed to upon waking, more effectively reduces CVD risk.

STUDY SUMMARY

PM vs AM antihypertensive dosing reduces CV events

This prospective, randomized, open-label, blinded endpoint trial of antihypertensive medication administration timing was part of a large, multicenter Spanish study investigating ambulatory BP monitoring (ABPM) as a routine diagnostic tool.

A simple change in administration time has the potential to significantly improve the lives of our patients by reducing the risk for cardiovascular events and their medication burden.

Study participants were randomly assigned in a 1:1 ratio to 2 treatment arms; participants either took all of their BP medications in the morning upon waking (n = 9532) or right before bedtime (n = 9552). The study was conducted in a primary care clinical setting. It included adult participants (age ≥ 18 years) with hypertension (defined as having at least 1 of the following benchmarks: awake systolic BP [SBP] mean ≥ 135 mm Hg, awake diastolic BP (DBP) mean ≥ 85 mm Hg, asleep SBP mean ≥ 120 mm Hg, asleep DBP mean ≥ 70 mm Hg as corroborated by 48-hour ABPM) who were taking at least 1 antihypertensive medication.

Continue to: Any antihypertension medication...

Any antihypertension medication included in the Spanish national formulary was allowed (exact agents were not delineated, but the following classes were included: ARB, ACE inhibitor, calcium channel blocker [CCB], beta-blocker, and/or diuretic). All BP medications had to be dosed once daily for inclusion. Exclusion criteria included pregnancy, night or rotating-shift work, alcohol or other substance dependence, acquired immunodeficiency syndrome, preexisting CVD (unstable angina, heart failure, arrhythmia, kidney failure, and retinopathy), inability to tolerate ABPM, and inability to comply with required 1-year follow-up.

Upon enrollment and at every subsequent clinic visit (scheduled at least annually), participants underwent 48-hour ABPM. Those with uncontrolled BP or elevated CVD risk had scheduled follow-up and ABPM more frequently. The primary outcome was a composite of CVD events including new-onset myocardial infarction, coronary revascularization, heart failure, ischemic stroke, hemorrhagic stroke, and CVD death. Secondary endpoints were individually analyzed primary outcomes of CVD events. The typical patient at baseline was 60.5 years of age with a body mass index of 29.7, an almost 9-year duration of hypertension, and a baseline office BP of 149/86 mm Hg. The patient break-out by antihypertensive class (awakening vs bedtime groups) was as follows: ARB (53% vs 53%), ACE inhibitor (25% vs 23%), CCB (33% vs 37%), beta-blocker (22% vs 18%), and diuretic (47% vs 40%).

See “It’s time to change when BP meds are taken” for more on the controversy that surrounded the initial release of this study.

During the median 6.3-year patient follow-up period, 1752 participants experienced a total of 2454 CVD events. Patients in the bedtime administration group, compared with those in the morning group, showed significantly lower risk for a CVD event (hazard ratio [HR] = 0.55; 95% confidence interval [CI], 0.50-0.61; P < .001). Also, there was a lower risk for individual CVD events in the bedtime administration group: CVD death (HR = 0.44; 95% CI, 0.34-0.56), myocardial infarction (HR = 0.66; 95% CI, 0.52-0.84), coronary revascularization (HR = 0.60; 95% CI, 0.47-0.75), heart failure (HR = 0.58; 95% CI, 0.49-0.70), and stroke (HR = 0.51; 95% CI, 0.41-0.63). This difference remained after correction for multiple potential confounders. There were no differences in adverse events, such as sleep-time hypotension, between groups.

WHAT’S NEW

First RCT in primary care to show dosing time change reduces CV risk

This is the first randomized controlled trial (RCT) performed in a primary care setting to compare before-bedtime to upon-waking administration of antihypertensive medications using clinically significant endpoints. The study demonstrates that a simple change in administration time has the potential to significantly improve the lives of our patients by reducing the risk for cardiovascular events and their medication burden.

CAVEATS

Homogenous population and exclusions limit generalizability

Because the study population consisted of white Spanish men and women, the results may not be generalizable beyond that ethnic group. In addition, the study exclusions limit interpretation in night/rotating-shift employees, patients with secondary hypertension, and those with CVD, chronic kidney disease, or severe retinopathy looking to reduce their risk.

Continue to: CHALLENGES TO IMPLEMENTATION

 

 

CHALLENGES TO IMPLEMENTATION

Nighttime urination could lead to nonadherence

Taking diuretics at bedtime may result in unwanted nighttime awakenings for visits to the bathroom, which could lead to nonadherence in some patients.

ACKNOWLEDGMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 54-year-old White woman presents to your office with new-onset hypertension. As you are discussing options for treatment, she mentions she would prefer once-daily dosing to help her remember to take her medication. She also wants to know what the best time of day is to take her medication to reduce her risk of cardiovascular disease (CVD). What do you advise?

The burden of hypertension is significant and growing in the United States. The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines reported that more than 108 million people were affected in 2015-2016—up from 87 million in 1999-2000.² Yet control of hypertension is improving among those receiving antihypertension pharmacotherapy. As reported in the ACC/AHA guidelines, data from the 2016 National Health and Nutrition Examination Survey (NHANES) indicate an increase of controlled hypertension among those receiving treatment from 25.6% (1999-2000) to 43.5% (2015-2016).²

Chronotherapy involves the administration of medication in coordination with the body’s circadian rhythms to maximize therapeutic effectiveness and/or minimize adverse effects. It is not a new concept as it applies to hypertension. Circadian rhythm–­dependent mechanisms influence the natural rise and fall of blood pressure (BP).¹ The ­renin-­angiotensin-aldosterone system, known to be most active at night, is a target mechanism for BP control.¹ Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are more effective (alone or in combination with other agents) at reducing BP during sleep and wakefulness when they are taken at night.^3,4 Additional prospective clinical trials and systematic reviews have documented improved BP during sleep and on 24-hour ambulatory monitoring when antihypertensives are taken at bedtime.^3-5

However, there have been few long-term studies assessing the effects of bedtime administration of antihypertensive medication on CVD risk reduction with patient-oriented outcomes.^6,7 Additionally, no studies have evaluated morning vs bedtime administration of antihypertensive medication for CVD risk reduction in a primary care setting. The 2019 ACC/AHA guideline on the primary prevention of CVD offers no recommendation regarding when to take antihypertensive medication.⁸ Timing of medication administration also is not addressed in the NHANES study of hypertension awareness, treatment, and control in US adults.⁹

This study sought to determine in a primary care setting whether taking antihypertensives at bedtime, as opposed to upon waking, more effectively reduces CVD risk.

STUDY SUMMARY

PM vs AM antihypertensive dosing reduces CV events

This prospective, randomized, open-label, blinded endpoint trial of antihypertensive medication administration timing was part of a large, multicenter Spanish study investigating ambulatory BP monitoring (ABPM) as a routine diagnostic tool.

A simple change in administration time has the potential to significantly improve the lives of our patients by reducing the risk for cardiovascular events and their medication burden.

Study participants were randomly assigned in a 1:1 ratio to 2 treatment arms; participants either took all of their BP medications in the morning upon waking (n = 9532) or right before bedtime (n = 9552). The study was conducted in a primary care clinical setting. It included adult participants (age ≥ 18 years) with hypertension (defined as having at least 1 of the following benchmarks: awake systolic BP [SBP] mean ≥ 135 mm Hg, awake diastolic BP (DBP) mean ≥ 85 mm Hg, asleep SBP mean ≥ 120 mm Hg, asleep DBP mean ≥ 70 mm Hg as corroborated by 48-hour ABPM) who were taking at least 1 antihypertensive medication.

Continue to: Any antihypertension medication...

Any antihypertension medication included in the Spanish national formulary was allowed (exact agents were not delineated, but the following classes were included: ARB, ACE inhibitor, calcium channel blocker [CCB], beta-blocker, and/or diuretic). All BP medications had to be dosed once daily for inclusion. Exclusion criteria included pregnancy, night or rotating-shift work, alcohol or other substance dependence, acquired immunodeficiency syndrome, preexisting CVD (unstable angina, heart failure, arrhythmia, kidney failure, and retinopathy), inability to tolerate ABPM, and inability to comply with required 1-year follow-up.

Upon enrollment and at every subsequent clinic visit (scheduled at least annually), participants underwent 48-hour ABPM. Those with uncontrolled BP or elevated CVD risk had scheduled follow-up and ABPM more frequently. The primary outcome was a composite of CVD events including new-onset myocardial infarction, coronary revascularization, heart failure, ischemic stroke, hemorrhagic stroke, and CVD death. Secondary endpoints were individually analyzed primary outcomes of CVD events. The typical patient at baseline was 60.5 years of age with a body mass index of 29.7, an almost 9-year duration of hypertension, and a baseline office BP of 149/86 mm Hg. The patient break-out by antihypertensive class (awakening vs bedtime groups) was as follows: ARB (53% vs 53%), ACE inhibitor (25% vs 23%), CCB (33% vs 37%), beta-blocker (22% vs 18%), and diuretic (47% vs 40%).

See “It’s time to change when BP meds are taken” for more on the controversy that surrounded the initial release of this study.

During the median 6.3-year patient follow-up period, 1752 participants experienced a total of 2454 CVD events. Patients in the bedtime administration group, compared with those in the morning group, showed significantly lower risk for a CVD event (hazard ratio [HR] = 0.55; 95% confidence interval [CI], 0.50-0.61; P < .001). Also, there was a lower risk for individual CVD events in the bedtime administration group: CVD death (HR = 0.44; 95% CI, 0.34-0.56), myocardial infarction (HR = 0.66; 95% CI, 0.52-0.84), coronary revascularization (HR = 0.60; 95% CI, 0.47-0.75), heart failure (HR = 0.58; 95% CI, 0.49-0.70), and stroke (HR = 0.51; 95% CI, 0.41-0.63). This difference remained after correction for multiple potential confounders. There were no differences in adverse events, such as sleep-time hypotension, between groups.

WHAT’S NEW

First RCT in primary care to show dosing time change reduces CV risk

This is the first randomized controlled trial (RCT) performed in a primary care setting to compare before-bedtime to upon-waking administration of antihypertensive medications using clinically significant endpoints. The study demonstrates that a simple change in administration time has the potential to significantly improve the lives of our patients by reducing the risk for cardiovascular events and their medication burden.

CAVEATS

Homogenous population and exclusions limit generalizability

Because the study population consisted of white Spanish men and women, the results may not be generalizable beyond that ethnic group. In addition, the study exclusions limit interpretation in night/rotating-shift employees, patients with secondary hypertension, and those with CVD, chronic kidney disease, or severe retinopathy looking to reduce their risk.

Continue to: CHALLENGES TO IMPLEMENTATION

 

 

CHALLENGES TO IMPLEMENTATION

Nighttime urination could lead to nonadherence

Taking diuretics at bedtime may result in unwanted nighttime awakenings for visits to the bathroom, which could lead to nonadherence in some patients.

ACKNOWLEDGMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 54-year-old White woman presents to your office with new-onset hypertension. As you are discussing options for treatment, she mentions she would prefer once-daily dosing to help her remember to take her medication. She also wants to know what the best time of day is to take her medication to reduce her risk of cardiovascular disease (CVD). What do you advise?

The burden of hypertension is significant and growing in the United States. The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines reported that more than 108 million people were affected in 2015-2016—up from 87 million in 1999-2000.² Yet control of hypertension is improving among those receiving antihypertension pharmacotherapy. As reported in the ACC/AHA guidelines, data from the 2016 National Health and Nutrition Examination Survey (NHANES) indicate an increase of controlled hypertension among those receiving treatment from 25.6% (1999-2000) to 43.5% (2015-2016).²

Chronotherapy involves the administration of medication in coordination with the body’s circadian rhythms to maximize therapeutic effectiveness and/or minimize adverse effects. It is not a new concept as it applies to hypertension. Circadian rhythm–­dependent mechanisms influence the natural rise and fall of blood pressure (BP).¹ The ­renin-­angiotensin-aldosterone system, known to be most active at night, is a target mechanism for BP control.¹ Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are more effective (alone or in combination with other agents) at reducing BP during sleep and wakefulness when they are taken at night.^3,4 Additional prospective clinical trials and systematic reviews have documented improved BP during sleep and on 24-hour ambulatory monitoring when antihypertensives are taken at bedtime.^3-5

However, there have been few long-term studies assessing the effects of bedtime administration of antihypertensive medication on CVD risk reduction with patient-oriented outcomes.^6,7 Additionally, no studies have evaluated morning vs bedtime administration of antihypertensive medication for CVD risk reduction in a primary care setting. The 2019 ACC/AHA guideline on the primary prevention of CVD offers no recommendation regarding when to take antihypertensive medication.⁸ Timing of medication administration also is not addressed in the NHANES study of hypertension awareness, treatment, and control in US adults.⁹

This study sought to determine in a primary care setting whether taking antihypertensives at bedtime, as opposed to upon waking, more effectively reduces CVD risk.

STUDY SUMMARY

PM vs AM antihypertensive dosing reduces CV events

This prospective, randomized, open-label, blinded endpoint trial of antihypertensive medication administration timing was part of a large, multicenter Spanish study investigating ambulatory BP monitoring (ABPM) as a routine diagnostic tool.

A simple change in administration time has the potential to significantly improve the lives of our patients by reducing the risk for cardiovascular events and their medication burden.

Study participants were randomly assigned in a 1:1 ratio to 2 treatment arms; participants either took all of their BP medications in the morning upon waking (n = 9532) or right before bedtime (n = 9552). The study was conducted in a primary care clinical setting. It included adult participants (age ≥ 18 years) with hypertension (defined as having at least 1 of the following benchmarks: awake systolic BP [SBP] mean ≥ 135 mm Hg, awake diastolic BP (DBP) mean ≥ 85 mm Hg, asleep SBP mean ≥ 120 mm Hg, asleep DBP mean ≥ 70 mm Hg as corroborated by 48-hour ABPM) who were taking at least 1 antihypertensive medication.

Continue to: Any antihypertension medication...

Any antihypertension medication included in the Spanish national formulary was allowed (exact agents were not delineated, but the following classes were included: ARB, ACE inhibitor, calcium channel blocker [CCB], beta-blocker, and/or diuretic). All BP medications had to be dosed once daily for inclusion. Exclusion criteria included pregnancy, night or rotating-shift work, alcohol or other substance dependence, acquired immunodeficiency syndrome, preexisting CVD (unstable angina, heart failure, arrhythmia, kidney failure, and retinopathy), inability to tolerate ABPM, and inability to comply with required 1-year follow-up.

Upon enrollment and at every subsequent clinic visit (scheduled at least annually), participants underwent 48-hour ABPM. Those with uncontrolled BP or elevated CVD risk had scheduled follow-up and ABPM more frequently. The primary outcome was a composite of CVD events including new-onset myocardial infarction, coronary revascularization, heart failure, ischemic stroke, hemorrhagic stroke, and CVD death. Secondary endpoints were individually analyzed primary outcomes of CVD events. The typical patient at baseline was 60.5 years of age with a body mass index of 29.7, an almost 9-year duration of hypertension, and a baseline office BP of 149/86 mm Hg. The patient break-out by antihypertensive class (awakening vs bedtime groups) was as follows: ARB (53% vs 53%), ACE inhibitor (25% vs 23%), CCB (33% vs 37%), beta-blocker (22% vs 18%), and diuretic (47% vs 40%).

See “It’s time to change when BP meds are taken” for more on the controversy that surrounded the initial release of this study.

During the median 6.3-year patient follow-up period, 1752 participants experienced a total of 2454 CVD events. Patients in the bedtime administration group, compared with those in the morning group, showed significantly lower risk for a CVD event (hazard ratio [HR] = 0.55; 95% confidence interval [CI], 0.50-0.61; P < .001). Also, there was a lower risk for individual CVD events in the bedtime administration group: CVD death (HR = 0.44; 95% CI, 0.34-0.56), myocardial infarction (HR = 0.66; 95% CI, 0.52-0.84), coronary revascularization (HR = 0.60; 95% CI, 0.47-0.75), heart failure (HR = 0.58; 95% CI, 0.49-0.70), and stroke (HR = 0.51; 95% CI, 0.41-0.63). This difference remained after correction for multiple potential confounders. There were no differences in adverse events, such as sleep-time hypotension, between groups.

WHAT’S NEW

First RCT in primary care to show dosing time change reduces CV risk

This is the first randomized controlled trial (RCT) performed in a primary care setting to compare before-bedtime to upon-waking administration of antihypertensive medications using clinically significant endpoints. The study demonstrates that a simple change in administration time has the potential to significantly improve the lives of our patients by reducing the risk for cardiovascular events and their medication burden.

CAVEATS

Homogenous population and exclusions limit generalizability

Because the study population consisted of white Spanish men and women, the results may not be generalizable beyond that ethnic group. In addition, the study exclusions limit interpretation in night/rotating-shift employees, patients with secondary hypertension, and those with CVD, chronic kidney disease, or severe retinopathy looking to reduce their risk.

Continue to: CHALLENGES TO IMPLEMENTATION

 

 

CHALLENGES TO IMPLEMENTATION

Nighttime urination could lead to nonadherence

Taking diuretics at bedtime may result in unwanted nighttime awakenings for visits to the bathroom, which could lead to nonadherence in some patients.

ACKNOWLEDGMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Click here to access August 2020 Advances in Precision Oncology

Table of Contents

• Foreword
• Introduction: Precision Oncology Changes the Game for VA Health Care
• VA National Precision Oncology Program
• Prostate Cancer Foundation-Department of Veterans Affairs Partnership: A Model to Advance Treatment and Care of Invasive Cancers
• The Precision Oncology Program for Cancer of the Prostate Network: A VA-Prostate Cancer Foundation Alliance
• Leveraging Veterans Health Administration Clinical and Research Resources to Accelerate Discovery and Testing in Precision Oncology
• Strategic Initiatives for Veterans With Lung Cancer
• Integrating Germline Genetics Into Precision Oncology Practice in the Veterans Health Administration: Challenges and Opportunities

Click here to access August 2020 Advances in Precision Oncology

Table of Contents

• Foreword
• Introduction: Precision Oncology Changes the Game for VA Health Care
• VA National Precision Oncology Program
• Prostate Cancer Foundation-Department of Veterans Affairs Partnership: A Model to Advance Treatment and Care of Invasive Cancers
• The Precision Oncology Program for Cancer of the Prostate Network: A VA-Prostate Cancer Foundation Alliance
• Leveraging Veterans Health Administration Clinical and Research Resources to Accelerate Discovery and Testing in Precision Oncology
• Strategic Initiatives for Veterans With Lung Cancer
• Integrating Germline Genetics Into Precision Oncology Practice in the Veterans Health Administration: Challenges and Opportunities

Click here to access August 2020 Advances in Precision Oncology

Table of Contents

• Foreword
• Introduction: Precision Oncology Changes the Game for VA Health Care
• VA National Precision Oncology Program
• Prostate Cancer Foundation-Department of Veterans Affairs Partnership: A Model to Advance Treatment and Care of Invasive Cancers
• The Precision Oncology Program for Cancer of the Prostate Network: A VA-Prostate Cancer Foundation Alliance
• Leveraging Veterans Health Administration Clinical and Research Resources to Accelerate Discovery and Testing in Precision Oncology
• Strategic Initiatives for Veterans With Lung Cancer
• Integrating Germline Genetics Into Precision Oncology Practice in the Veterans Health Administration: Challenges and Opportunities

One high school student out of every seven ever has either misused a prescription pain medicine or taken one without a prescription, according to an analysis from the Centers for Disease Control and Prevention.

That type of opioid use/misuse, reported by 14.3% of respondents to the 2019 Youth Risk Behavior Survey, was more common among females (16.1%) than males (12.4%) and even more prevalent among nonheterosexuals and those who are unsure about their sexual identity, Christopher M. Jones, PharmD, DrPH, and associates at the CDC said in the Morbidity and Mortality Weekly Report.

The YRBS data show that 18.5% of gay or lesbian students had, at some point in their lives, used a prescription opioid differently than a physician had told them to or taken one without a prescription. That figure was slightly higher (19.1%) for those unsure of their sexual identity, considerably higher (25.4%) for bisexuals, and lower for heterosexuals (12.7%), they reported.

The pattern for current use/misuse of opioids, defined as use one or more times in the 30 days before the survey, was similar to ever use but somewhat less pronounced in 2019. Prevalence was 7.2% for all students in grades 9-12, 8.3% for females, and 6.1% for males. By sexual identity, prevalence was 6.4% for heterosexuals, 7.6% for gays or lesbians, 11.5% for those unsure about their sexual identity, and 13.1% for bisexuals, based on the YRBS data.

This increased misuse of opioids among sexual minority youths, “even after controlling for other demographic and substance use characteristics ... emphasizes the importance of identifying tailored prevention strategies to address disparities among this vulnerable population,” the CDC researchers wrote.

rfranki@mdedge.com

SOURCE: Jones CM et al. MMWR Suppl. 2020 Aug 21;69(1):38-46.

One high school student out of every seven ever has either misused a prescription pain medicine or taken one without a prescription, according to an analysis from the Centers for Disease Control and Prevention.

That type of opioid use/misuse, reported by 14.3% of respondents to the 2019 Youth Risk Behavior Survey, was more common among females (16.1%) than males (12.4%) and even more prevalent among nonheterosexuals and those who are unsure about their sexual identity, Christopher M. Jones, PharmD, DrPH, and associates at the CDC said in the Morbidity and Mortality Weekly Report.

The YRBS data show that 18.5% of gay or lesbian students had, at some point in their lives, used a prescription opioid differently than a physician had told them to or taken one without a prescription. That figure was slightly higher (19.1%) for those unsure of their sexual identity, considerably higher (25.4%) for bisexuals, and lower for heterosexuals (12.7%), they reported.

The pattern for current use/misuse of opioids, defined as use one or more times in the 30 days before the survey, was similar to ever use but somewhat less pronounced in 2019. Prevalence was 7.2% for all students in grades 9-12, 8.3% for females, and 6.1% for males. By sexual identity, prevalence was 6.4% for heterosexuals, 7.6% for gays or lesbians, 11.5% for those unsure about their sexual identity, and 13.1% for bisexuals, based on the YRBS data.

This increased misuse of opioids among sexual minority youths, “even after controlling for other demographic and substance use characteristics ... emphasizes the importance of identifying tailored prevention strategies to address disparities among this vulnerable population,” the CDC researchers wrote.

rfranki@mdedge.com

SOURCE: Jones CM et al. MMWR Suppl. 2020 Aug 21;69(1):38-46.

One high school student out of every seven ever has either misused a prescription pain medicine or taken one without a prescription, according to an analysis from the Centers for Disease Control and Prevention.

That type of opioid use/misuse, reported by 14.3% of respondents to the 2019 Youth Risk Behavior Survey, was more common among females (16.1%) than males (12.4%) and even more prevalent among nonheterosexuals and those who are unsure about their sexual identity, Christopher M. Jones, PharmD, DrPH, and associates at the CDC said in the Morbidity and Mortality Weekly Report.

The YRBS data show that 18.5% of gay or lesbian students had, at some point in their lives, used a prescription opioid differently than a physician had told them to or taken one without a prescription. That figure was slightly higher (19.1%) for those unsure of their sexual identity, considerably higher (25.4%) for bisexuals, and lower for heterosexuals (12.7%), they reported.

The pattern for current use/misuse of opioids, defined as use one or more times in the 30 days before the survey, was similar to ever use but somewhat less pronounced in 2019. Prevalence was 7.2% for all students in grades 9-12, 8.3% for females, and 6.1% for males. By sexual identity, prevalence was 6.4% for heterosexuals, 7.6% for gays or lesbians, 11.5% for those unsure about their sexual identity, and 13.1% for bisexuals, based on the YRBS data.

This increased misuse of opioids among sexual minority youths, “even after controlling for other demographic and substance use characteristics ... emphasizes the importance of identifying tailored prevention strategies to address disparities among this vulnerable population,” the CDC researchers wrote.

rfranki@mdedge.com

SOURCE: Jones CM et al. MMWR Suppl. 2020 Aug 21;69(1):38-46.