Most hospitalists’ training likely included caring for patients in the ambulatory clinic, urgent care, and ED settings. One of the most important aspects of medical training is deciding which of the patients seen in these settings need to “be admitted” to a hospital because of risk, severity of illness, and/or need for certain medical services. In this context, “admit” is a synonym for “hospitalize.”

However, in today’s health care system, in which hospitalization costs are usually borne by a third-party payer, “admit” can have a very different meaning. For most payers, “admit” means “hospitalize as inpatient.” This is distinct from “hospitalize as an outpatient.” (“Observation” or “obs” is the most common example of a hospitalization as an outpatient.) In the medical payer world, inpatient and outpatient are often referred to as “statuses.” The distinction between inpatient versus outpatient status can affect payment and is based on rules that a hospital and payer have agreed upon. (Inpatient hospital care is generally paid at a higher rate than outpatient hospital care.) It is important for hospitalists to have a basic understanding of these rules because it can affect hospital billing, the hospitalist’s professional fees, beneficiary liability, and payer denials of inpatient care.

For years, Medicare’s definition of an inpatient hospitalization was primarily based on an expectation of a hospitalization of at least 24 hours and a physician’s judgment of the beneficiary’s need for inpatient hospital services. This judgment was to be based on the physician’s assessment of the patient’s severity of illness, the risk of an adverse outcome, and the hospital services required. (The exact definition by Centers for Medicare & Medicaid Services is much longer and can be found in the Medicare Benefits Policy Manual.¹) Under Medicare, defining a hospitalization as inpatient versus outpatient is especially important because they are billed to different Medicare programs (Part A for inpatient, Part B for outpatient), and both hospital reimbursement and the patient liability can vary significantly.

Not surprisingly, CMS found that how physicians were making status decisions for medically similar hospitalized patients varied greatly. CMS noted two major concerns: an overuse of inpatient for patients hospitalized overnight leading to increased charges to CMS and multiday observation hospitalizations for lower-acuity patients leading to excessive liability for Medicare beneficiaries. (Observation stays are billed under Part B, under which the beneficiary generally has a 20% copay.)

To address these concerns, in October 2013, CMS adjusted the definition of inpatient to include “the two-midnight rule.” Basically, CMS said that, in order to qualify for inpatient, the admitting physician should expect the beneficiary to require hospital care spanning at least two midnights, rather than the previous 24-hour benchmark, regardless of the severity of illness or risk of adverse outcome. (There are exceptions and exemptions to the two-midnight rule, which are discussed later in this article.)

The idea of the two-midnight rule was to address the two concerns noted above. Under this rule, most expected overnight hospitalizations should be outpatients, even if they are more than 24 hours in length, and any medically necessary outpatient hospitalization should be “converted” to inpatient if and when it is clear that a second midnight of hospitalization is medically necessary.

In January 2016, CMS amended the two-midnight rule to recognize, as it had done prior to October 2013, that some hospitalizations, based on physician judgment, would be appropriate for inpatient without an expectation of a hospitalization that spans at least two midnights. Unfortunately, CMS has not been forthcoming with guidance of examples of which hospitalizations would fall into this new category, other than to say they expect the use of this new provision would generally not be appropriate for a hospital stay of less than 24 hours.

As of today, physicians should order inpatient services under the following three situations:

• The physician expects the beneficiary to require hospital care spanning at least two midnights.
• The physician provides a service on Medicare’s inpatient-only list.
• The physician expects the beneficiary to require hospital care for less than two midnights but feels that inpatient services are nevertheless appropriate.

This most recently updated version of the two-midnight rule can be found in Section 42 CFR §412.3 of the Code of Federal Regulations.² Each of these three situations warrants additional discussion.
 

Care expected to span two midnights

The first situation is the one most applicable to hospitalists. In this circumstance there are three key points to remember.

The first point is that the two-midnight rule is based on a reasonable expectation of a need for hospitalization for at least two nights, not the actual length of hospitalization. Auditors, based on long-standing guidance from the CMS, should consider only the information known (or that should have been known) to the provider at the time the inpatient decision is made.

For example, if the expectation of the need for hospitalization of at least 2 midnights is well documented in the admission note, but the beneficiary improves more rapidly than expected and can be discharged before the second midnight, billing Medicare under Part A for inpatient admission remains appropriate. Auditors may look for provider documentation describing the unexpected improvement, and while such documentation is not an absolute requirement, its presence can be helpful in defending inpatient billing.

Other situations in which there can be an expectation of hospitalization of at least two midnights, but the actual length of stay does not meet this benchmark, are death, patients leaving against medical advice, or transfer to another hospital. For example, if a patient is hospitalized as an inpatient for bacterial endocarditis, and the documented plan of care includes at least 2 days of IV antibiotics and monitoring of cultures, inpatient remains appropriate even if the patient signs out against medical advice the following day.

The second key point to understand is that a night must be “medically necessary” to count toward the two-midnight benchmark. Hospital time spent receiving custodial care, because of excessive delays, or incurred because of the convenience of the beneficiary or provider does not count toward the two-midnight benchmark. For example, imagine a patient hospitalized with chest pain on Saturday evening and the attending physician determines that the patient requires serial cardiac isoenzymes and ECGs followed, most likely, by a noninvasive stress test. The attending physician, knowing that the hospital does not offer stress testing on Sunday, expects the patient to remain hospitalized at least until Monday, thus two midnights. However, in this situation, the second midnight (Sunday night) was not medically necessary and does not count toward the two midnight expectation.

The third key point to know is that the clock for calculating the two-midnight rule begins when the beneficiary starts receiving hospital care, not when the inpatient order is placed. Further, care that starts in the ED or at another hospital counts, too. In contrast, care at an outpatient clinic, an urgent care facility, or waiting-room time in an ED does not count.

When CMS implemented the two-midnight rule in 2013, they said that they would be open to exceptions. The first and only exception to date to the two-midnight rule is newly initiated and unanticipated mechanical ventilation. (This excludes anticipated intubations related to other care, such as procedures.) For example, inpatient is appropriate for a patient who requires hospitalization for an anaphylactic reaction or a drug overdose and needs intubation and mechanical ventilation, even if discharge is expected before a second midnight of hospital care.
 

CMS’s inpatient-only list

Each year, CMS publishes a list of procedures that CMS will pay only under Part A (that is, as inpatient). This list is updated quarterly (Addendum E) and can be found on the CMS website.³ Hospitalizations associated with the procedures on this list should always be inpatient, regardless of the expected length of stay.

It is important to note that the inpatient-only list is dynamic; it is revised annually, and procedures can come on or off the list. Notably, in January 2018, elective total knee replacements and laparoscopic radical prostatectomies came off the inpatient-only list. Most surgeons and proceduralists know whether the procedure they are performing is on this list, and they should advise hospitalists accordingly if the hospitalist is to be the attending of record and will be writing the admission order.
 

Inpatient services are nevertheless appropriate

The third situation, in which an inpatient admission is appropriate even when the admitting provider does not expect a two-midnight stay, was added to the two-midnight rule in January 2016. CMS states that the factors used in making this determination can be based on physician judgment and documented in the medical record.

At first reading, one might think that CMS is, in effect, returning to the definition of an inpatient prior to the two-midnight rule’s implementation in 2013. However, CMS has not offered clear guidance for its use, and they did not remove any of the previous two-midnight rule guidance. In the absence of clear guidance, hospitalists may be best served by not using this latest change to the two-midnight rule in determining which Medicare beneficiary hospitalizations are appropriate for inpatient designation.

A final, and critical, point about the two-midnight rule is that it only applies to traditional Medicare, and it does not apply to other payers, including commercial insurance and Medicaid. Medicare Advantage plans may or may not follow the two-midnight rule, depending on their contract with the hospital. Which patients are appropriate for inpatient designations are usually determined by the individual contract that the hospital has signed with that payer.

A better understanding of the two-midnight rule including to whom it applies, when it applies, and how to apply it will help you accurately determine which hospitalizations are appropriate for inpatient payment. With this understanding you will quickly become the hero of your hospital’s case managers and billing department.

Dr. Locke is senior physician advisor at the Johns Hopkins Hospital in Baltimore and president-elect of the American College of Physician Advisors. Dr. Hu is executive director of physician advisor services at the University of North Carolina Health Care System, Chapel Hill, and president of the American College of Physician Advisors.

References

1. Medicare Benefit Policy Manual. Chapter 1 - Inpatient Hospital Services Covered Under Part A. https://www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/bp102c01.pdf.

2. Code of Federal Regulations. https://www.ecfr.gov/cgi-bin/text-idx?SID=958ee67a826285698204a34e1e5d6406&node=42:2.0.1.2.12.1.47.3&rgn=div8.

3. Current Procedural Terminology, Fourth Edition. https://www.cms.gov/apps/ama/license.asp?file=/Medicare/Medicare-Fee-for-Service-Payment/HospitalOutpatientPPS/Downloads/CMS-1695-FC-2019-OPPS-FR-Addenda.zip.

Most hospitalists’ training likely included caring for patients in the ambulatory clinic, urgent care, and ED settings. One of the most important aspects of medical training is deciding which of the patients seen in these settings need to “be admitted” to a hospital because of risk, severity of illness, and/or need for certain medical services. In this context, “admit” is a synonym for “hospitalize.”

However, in today’s health care system, in which hospitalization costs are usually borne by a third-party payer, “admit” can have a very different meaning. For most payers, “admit” means “hospitalize as inpatient.” This is distinct from “hospitalize as an outpatient.” (“Observation” or “obs” is the most common example of a hospitalization as an outpatient.) In the medical payer world, inpatient and outpatient are often referred to as “statuses.” The distinction between inpatient versus outpatient status can affect payment and is based on rules that a hospital and payer have agreed upon. (Inpatient hospital care is generally paid at a higher rate than outpatient hospital care.) It is important for hospitalists to have a basic understanding of these rules because it can affect hospital billing, the hospitalist’s professional fees, beneficiary liability, and payer denials of inpatient care.

For years, Medicare’s definition of an inpatient hospitalization was primarily based on an expectation of a hospitalization of at least 24 hours and a physician’s judgment of the beneficiary’s need for inpatient hospital services. This judgment was to be based on the physician’s assessment of the patient’s severity of illness, the risk of an adverse outcome, and the hospital services required. (The exact definition by Centers for Medicare & Medicaid Services is much longer and can be found in the Medicare Benefits Policy Manual.¹) Under Medicare, defining a hospitalization as inpatient versus outpatient is especially important because they are billed to different Medicare programs (Part A for inpatient, Part B for outpatient), and both hospital reimbursement and the patient liability can vary significantly.

Not surprisingly, CMS found that how physicians were making status decisions for medically similar hospitalized patients varied greatly. CMS noted two major concerns: an overuse of inpatient for patients hospitalized overnight leading to increased charges to CMS and multiday observation hospitalizations for lower-acuity patients leading to excessive liability for Medicare beneficiaries. (Observation stays are billed under Part B, under which the beneficiary generally has a 20% copay.)

To address these concerns, in October 2013, CMS adjusted the definition of inpatient to include “the two-midnight rule.” Basically, CMS said that, in order to qualify for inpatient, the admitting physician should expect the beneficiary to require hospital care spanning at least two midnights, rather than the previous 24-hour benchmark, regardless of the severity of illness or risk of adverse outcome. (There are exceptions and exemptions to the two-midnight rule, which are discussed later in this article.)

The idea of the two-midnight rule was to address the two concerns noted above. Under this rule, most expected overnight hospitalizations should be outpatients, even if they are more than 24 hours in length, and any medically necessary outpatient hospitalization should be “converted” to inpatient if and when it is clear that a second midnight of hospitalization is medically necessary.

In January 2016, CMS amended the two-midnight rule to recognize, as it had done prior to October 2013, that some hospitalizations, based on physician judgment, would be appropriate for inpatient without an expectation of a hospitalization that spans at least two midnights. Unfortunately, CMS has not been forthcoming with guidance of examples of which hospitalizations would fall into this new category, other than to say they expect the use of this new provision would generally not be appropriate for a hospital stay of less than 24 hours.

As of today, physicians should order inpatient services under the following three situations:

• The physician expects the beneficiary to require hospital care spanning at least two midnights.
• The physician provides a service on Medicare’s inpatient-only list.
• The physician expects the beneficiary to require hospital care for less than two midnights but feels that inpatient services are nevertheless appropriate.

This most recently updated version of the two-midnight rule can be found in Section 42 CFR §412.3 of the Code of Federal Regulations.² Each of these three situations warrants additional discussion.
 

Care expected to span two midnights

The first situation is the one most applicable to hospitalists. In this circumstance there are three key points to remember.

The first point is that the two-midnight rule is based on a reasonable expectation of a need for hospitalization for at least two nights, not the actual length of hospitalization. Auditors, based on long-standing guidance from the CMS, should consider only the information known (or that should have been known) to the provider at the time the inpatient decision is made.

For example, if the expectation of the need for hospitalization of at least 2 midnights is well documented in the admission note, but the beneficiary improves more rapidly than expected and can be discharged before the second midnight, billing Medicare under Part A for inpatient admission remains appropriate. Auditors may look for provider documentation describing the unexpected improvement, and while such documentation is not an absolute requirement, its presence can be helpful in defending inpatient billing.

Other situations in which there can be an expectation of hospitalization of at least two midnights, but the actual length of stay does not meet this benchmark, are death, patients leaving against medical advice, or transfer to another hospital. For example, if a patient is hospitalized as an inpatient for bacterial endocarditis, and the documented plan of care includes at least 2 days of IV antibiotics and monitoring of cultures, inpatient remains appropriate even if the patient signs out against medical advice the following day.

The second key point to understand is that a night must be “medically necessary” to count toward the two-midnight benchmark. Hospital time spent receiving custodial care, because of excessive delays, or incurred because of the convenience of the beneficiary or provider does not count toward the two-midnight benchmark. For example, imagine a patient hospitalized with chest pain on Saturday evening and the attending physician determines that the patient requires serial cardiac isoenzymes and ECGs followed, most likely, by a noninvasive stress test. The attending physician, knowing that the hospital does not offer stress testing on Sunday, expects the patient to remain hospitalized at least until Monday, thus two midnights. However, in this situation, the second midnight (Sunday night) was not medically necessary and does not count toward the two midnight expectation.

The third key point to know is that the clock for calculating the two-midnight rule begins when the beneficiary starts receiving hospital care, not when the inpatient order is placed. Further, care that starts in the ED or at another hospital counts, too. In contrast, care at an outpatient clinic, an urgent care facility, or waiting-room time in an ED does not count.

When CMS implemented the two-midnight rule in 2013, they said that they would be open to exceptions. The first and only exception to date to the two-midnight rule is newly initiated and unanticipated mechanical ventilation. (This excludes anticipated intubations related to other care, such as procedures.) For example, inpatient is appropriate for a patient who requires hospitalization for an anaphylactic reaction or a drug overdose and needs intubation and mechanical ventilation, even if discharge is expected before a second midnight of hospital care.
 

CMS’s inpatient-only list

Each year, CMS publishes a list of procedures that CMS will pay only under Part A (that is, as inpatient). This list is updated quarterly (Addendum E) and can be found on the CMS website.³ Hospitalizations associated with the procedures on this list should always be inpatient, regardless of the expected length of stay.

It is important to note that the inpatient-only list is dynamic; it is revised annually, and procedures can come on or off the list. Notably, in January 2018, elective total knee replacements and laparoscopic radical prostatectomies came off the inpatient-only list. Most surgeons and proceduralists know whether the procedure they are performing is on this list, and they should advise hospitalists accordingly if the hospitalist is to be the attending of record and will be writing the admission order.
 

Inpatient services are nevertheless appropriate

The third situation, in which an inpatient admission is appropriate even when the admitting provider does not expect a two-midnight stay, was added to the two-midnight rule in January 2016. CMS states that the factors used in making this determination can be based on physician judgment and documented in the medical record.

At first reading, one might think that CMS is, in effect, returning to the definition of an inpatient prior to the two-midnight rule’s implementation in 2013. However, CMS has not offered clear guidance for its use, and they did not remove any of the previous two-midnight rule guidance. In the absence of clear guidance, hospitalists may be best served by not using this latest change to the two-midnight rule in determining which Medicare beneficiary hospitalizations are appropriate for inpatient designation.

A final, and critical, point about the two-midnight rule is that it only applies to traditional Medicare, and it does not apply to other payers, including commercial insurance and Medicaid. Medicare Advantage plans may or may not follow the two-midnight rule, depending on their contract with the hospital. Which patients are appropriate for inpatient designations are usually determined by the individual contract that the hospital has signed with that payer.

A better understanding of the two-midnight rule including to whom it applies, when it applies, and how to apply it will help you accurately determine which hospitalizations are appropriate for inpatient payment. With this understanding you will quickly become the hero of your hospital’s case managers and billing department.

Dr. Locke is senior physician advisor at the Johns Hopkins Hospital in Baltimore and president-elect of the American College of Physician Advisors. Dr. Hu is executive director of physician advisor services at the University of North Carolina Health Care System, Chapel Hill, and president of the American College of Physician Advisors.

References

1. Medicare Benefit Policy Manual. Chapter 1 - Inpatient Hospital Services Covered Under Part A. https://www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/bp102c01.pdf.

2. Code of Federal Regulations. https://www.ecfr.gov/cgi-bin/text-idx?SID=958ee67a826285698204a34e1e5d6406&node=42:2.0.1.2.12.1.47.3&rgn=div8.

3. Current Procedural Terminology, Fourth Edition. https://www.cms.gov/apps/ama/license.asp?file=/Medicare/Medicare-Fee-for-Service-Payment/HospitalOutpatientPPS/Downloads/CMS-1695-FC-2019-OPPS-FR-Addenda.zip.

Most hospitalists’ training likely included caring for patients in the ambulatory clinic, urgent care, and ED settings. One of the most important aspects of medical training is deciding which of the patients seen in these settings need to “be admitted” to a hospital because of risk, severity of illness, and/or need for certain medical services. In this context, “admit” is a synonym for “hospitalize.”

However, in today’s health care system, in which hospitalization costs are usually borne by a third-party payer, “admit” can have a very different meaning. For most payers, “admit” means “hospitalize as inpatient.” This is distinct from “hospitalize as an outpatient.” (“Observation” or “obs” is the most common example of a hospitalization as an outpatient.) In the medical payer world, inpatient and outpatient are often referred to as “statuses.” The distinction between inpatient versus outpatient status can affect payment and is based on rules that a hospital and payer have agreed upon. (Inpatient hospital care is generally paid at a higher rate than outpatient hospital care.) It is important for hospitalists to have a basic understanding of these rules because it can affect hospital billing, the hospitalist’s professional fees, beneficiary liability, and payer denials of inpatient care.

For years, Medicare’s definition of an inpatient hospitalization was primarily based on an expectation of a hospitalization of at least 24 hours and a physician’s judgment of the beneficiary’s need for inpatient hospital services. This judgment was to be based on the physician’s assessment of the patient’s severity of illness, the risk of an adverse outcome, and the hospital services required. (The exact definition by Centers for Medicare & Medicaid Services is much longer and can be found in the Medicare Benefits Policy Manual.¹) Under Medicare, defining a hospitalization as inpatient versus outpatient is especially important because they are billed to different Medicare programs (Part A for inpatient, Part B for outpatient), and both hospital reimbursement and the patient liability can vary significantly.

Not surprisingly, CMS found that how physicians were making status decisions for medically similar hospitalized patients varied greatly. CMS noted two major concerns: an overuse of inpatient for patients hospitalized overnight leading to increased charges to CMS and multiday observation hospitalizations for lower-acuity patients leading to excessive liability for Medicare beneficiaries. (Observation stays are billed under Part B, under which the beneficiary generally has a 20% copay.)

To address these concerns, in October 2013, CMS adjusted the definition of inpatient to include “the two-midnight rule.” Basically, CMS said that, in order to qualify for inpatient, the admitting physician should expect the beneficiary to require hospital care spanning at least two midnights, rather than the previous 24-hour benchmark, regardless of the severity of illness or risk of adverse outcome. (There are exceptions and exemptions to the two-midnight rule, which are discussed later in this article.)

The idea of the two-midnight rule was to address the two concerns noted above. Under this rule, most expected overnight hospitalizations should be outpatients, even if they are more than 24 hours in length, and any medically necessary outpatient hospitalization should be “converted” to inpatient if and when it is clear that a second midnight of hospitalization is medically necessary.

In January 2016, CMS amended the two-midnight rule to recognize, as it had done prior to October 2013, that some hospitalizations, based on physician judgment, would be appropriate for inpatient without an expectation of a hospitalization that spans at least two midnights. Unfortunately, CMS has not been forthcoming with guidance of examples of which hospitalizations would fall into this new category, other than to say they expect the use of this new provision would generally not be appropriate for a hospital stay of less than 24 hours.

As of today, physicians should order inpatient services under the following three situations:

• The physician expects the beneficiary to require hospital care spanning at least two midnights.
• The physician provides a service on Medicare’s inpatient-only list.
• The physician expects the beneficiary to require hospital care for less than two midnights but feels that inpatient services are nevertheless appropriate.

This most recently updated version of the two-midnight rule can be found in Section 42 CFR §412.3 of the Code of Federal Regulations.² Each of these three situations warrants additional discussion.
 

Care expected to span two midnights

The first situation is the one most applicable to hospitalists. In this circumstance there are three key points to remember.

The first point is that the two-midnight rule is based on a reasonable expectation of a need for hospitalization for at least two nights, not the actual length of hospitalization. Auditors, based on long-standing guidance from the CMS, should consider only the information known (or that should have been known) to the provider at the time the inpatient decision is made.

For example, if the expectation of the need for hospitalization of at least 2 midnights is well documented in the admission note, but the beneficiary improves more rapidly than expected and can be discharged before the second midnight, billing Medicare under Part A for inpatient admission remains appropriate. Auditors may look for provider documentation describing the unexpected improvement, and while such documentation is not an absolute requirement, its presence can be helpful in defending inpatient billing.

Other situations in which there can be an expectation of hospitalization of at least two midnights, but the actual length of stay does not meet this benchmark, are death, patients leaving against medical advice, or transfer to another hospital. For example, if a patient is hospitalized as an inpatient for bacterial endocarditis, and the documented plan of care includes at least 2 days of IV antibiotics and monitoring of cultures, inpatient remains appropriate even if the patient signs out against medical advice the following day.

The second key point to understand is that a night must be “medically necessary” to count toward the two-midnight benchmark. Hospital time spent receiving custodial care, because of excessive delays, or incurred because of the convenience of the beneficiary or provider does not count toward the two-midnight benchmark. For example, imagine a patient hospitalized with chest pain on Saturday evening and the attending physician determines that the patient requires serial cardiac isoenzymes and ECGs followed, most likely, by a noninvasive stress test. The attending physician, knowing that the hospital does not offer stress testing on Sunday, expects the patient to remain hospitalized at least until Monday, thus two midnights. However, in this situation, the second midnight (Sunday night) was not medically necessary and does not count toward the two midnight expectation.

The third key point to know is that the clock for calculating the two-midnight rule begins when the beneficiary starts receiving hospital care, not when the inpatient order is placed. Further, care that starts in the ED or at another hospital counts, too. In contrast, care at an outpatient clinic, an urgent care facility, or waiting-room time in an ED does not count.

When CMS implemented the two-midnight rule in 2013, they said that they would be open to exceptions. The first and only exception to date to the two-midnight rule is newly initiated and unanticipated mechanical ventilation. (This excludes anticipated intubations related to other care, such as procedures.) For example, inpatient is appropriate for a patient who requires hospitalization for an anaphylactic reaction or a drug overdose and needs intubation and mechanical ventilation, even if discharge is expected before a second midnight of hospital care.
 

CMS’s inpatient-only list

Each year, CMS publishes a list of procedures that CMS will pay only under Part A (that is, as inpatient). This list is updated quarterly (Addendum E) and can be found on the CMS website.³ Hospitalizations associated with the procedures on this list should always be inpatient, regardless of the expected length of stay.

It is important to note that the inpatient-only list is dynamic; it is revised annually, and procedures can come on or off the list. Notably, in January 2018, elective total knee replacements and laparoscopic radical prostatectomies came off the inpatient-only list. Most surgeons and proceduralists know whether the procedure they are performing is on this list, and they should advise hospitalists accordingly if the hospitalist is to be the attending of record and will be writing the admission order.
 

Inpatient services are nevertheless appropriate

The third situation, in which an inpatient admission is appropriate even when the admitting provider does not expect a two-midnight stay, was added to the two-midnight rule in January 2016. CMS states that the factors used in making this determination can be based on physician judgment and documented in the medical record.

At first reading, one might think that CMS is, in effect, returning to the definition of an inpatient prior to the two-midnight rule’s implementation in 2013. However, CMS has not offered clear guidance for its use, and they did not remove any of the previous two-midnight rule guidance. In the absence of clear guidance, hospitalists may be best served by not using this latest change to the two-midnight rule in determining which Medicare beneficiary hospitalizations are appropriate for inpatient designation.

A final, and critical, point about the two-midnight rule is that it only applies to traditional Medicare, and it does not apply to other payers, including commercial insurance and Medicaid. Medicare Advantage plans may or may not follow the two-midnight rule, depending on their contract with the hospital. Which patients are appropriate for inpatient designations are usually determined by the individual contract that the hospital has signed with that payer.

A better understanding of the two-midnight rule including to whom it applies, when it applies, and how to apply it will help you accurately determine which hospitalizations are appropriate for inpatient payment. With this understanding you will quickly become the hero of your hospital’s case managers and billing department.

Dr. Locke is senior physician advisor at the Johns Hopkins Hospital in Baltimore and president-elect of the American College of Physician Advisors. Dr. Hu is executive director of physician advisor services at the University of North Carolina Health Care System, Chapel Hill, and president of the American College of Physician Advisors.

References

1. Medicare Benefit Policy Manual. Chapter 1 - Inpatient Hospital Services Covered Under Part A. https://www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/bp102c01.pdf.

2. Code of Federal Regulations. https://www.ecfr.gov/cgi-bin/text-idx?SID=958ee67a826285698204a34e1e5d6406&node=42:2.0.1.2.12.1.47.3&rgn=div8.

3. Current Procedural Terminology, Fourth Edition. https://www.cms.gov/apps/ama/license.asp?file=/Medicare/Medicare-Fee-for-Service-Payment/HospitalOutpatientPPS/Downloads/CMS-1695-FC-2019-OPPS-FR-Addenda.zip.

The Food and Drug Administration has cleared Bio-Rad’s digital polymerase chain reaction (PCR) testing solution to monitor patients’ molecular response to treatment for chronic myeloid leukemia.

The QXDx AutoDG ddPCR System combines Bio-Rad’s Droplet Digital PCR technology and the QXDx BCR-ABL %IS Kit, according to the company.

This so-called liquid biopsy test can “precisely and reproducibly” monitor the molecular response to tyrosine kinase inhibitor therapy. The current standard – reverse transcription quantitative PCR – can have variable results, especially at low levels of disease, according to Bio-Rad.

FDA clearance means that the product is “substantially equivalent” to an already-approved product and can be sold in the United States, according to the agency.

[email protected]

The Food and Drug Administration has cleared Bio-Rad’s digital polymerase chain reaction (PCR) testing solution to monitor patients’ molecular response to treatment for chronic myeloid leukemia.

The QXDx AutoDG ddPCR System combines Bio-Rad’s Droplet Digital PCR technology and the QXDx BCR-ABL %IS Kit, according to the company.

This so-called liquid biopsy test can “precisely and reproducibly” monitor the molecular response to tyrosine kinase inhibitor therapy. The current standard – reverse transcription quantitative PCR – can have variable results, especially at low levels of disease, according to Bio-Rad.

FDA clearance means that the product is “substantially equivalent” to an already-approved product and can be sold in the United States, according to the agency.

[email protected]

The Food and Drug Administration has cleared Bio-Rad’s digital polymerase chain reaction (PCR) testing solution to monitor patients’ molecular response to treatment for chronic myeloid leukemia.

The QXDx AutoDG ddPCR System combines Bio-Rad’s Droplet Digital PCR technology and the QXDx BCR-ABL %IS Kit, according to the company.

This so-called liquid biopsy test can “precisely and reproducibly” monitor the molecular response to tyrosine kinase inhibitor therapy. The current standard – reverse transcription quantitative PCR – can have variable results, especially at low levels of disease, according to Bio-Rad.

FDA clearance means that the product is “substantially equivalent” to an already-approved product and can be sold in the United States, according to the agency.

[email protected]

The gout drug febuxostat (Uloric) poses a significantly higher risk of all-cause and heart-related death than does the popular alternative drug allopurinol, the Food and Drug Administration declared on Feb. 21. The agency is now mandating a black-box warning.

“Health care professionals should reserve Uloric for use only in patients who have failed or do not tolerate allopurinol,” the FDA announced. “Counsel patients about the cardiovascular risk with Uloric,” the agency suggested, and advise them to seek medical attention at once if they have cardiac symptoms such as chest pain, shortness of breath, rapid or irregular heartbeat, or dizziness.

The FDA’s move comes a decade after it approved febuxostat as a gout treatment. As the FDA noted in its announcement, “the number of medicines to treat gout is limited, and there is an unmet need for treatments for this disease.”

Research has suggested that both febuxostat and allopurinol have similar efficacy. Some experts have recommended febuxostat as an alternative for patients who shouldn’t take allopurinol (Semin Arthritis Rheum. 2013 Dec;43[3]:367-75).

However, research has raised concerns about febuxostat’s cardiac risk. In its Feb. 21 statement, the FDA pointed to the findings of a 2010-2017 postmarket clinical trial of 6,190 patients with gout who were treated with febuxostat or allopurinol (N Engl J Med. 2018;378:1200-10).

“In patients treated with Uloric, 15 deaths from heart-related causes were observed for every 1,000 patients treated for a year compared to 11 deaths from heart-related causes per 1,000 patients treated with allopurinol for a year,” the FDA said. “In addition, there were 26 deaths from any cause per 1,000 patients treated for a year with Uloric compared to 22 deaths per 1,000 patients treated for a year with allopurinol.”

The gout drug febuxostat (Uloric) poses a significantly higher risk of all-cause and heart-related death than does the popular alternative drug allopurinol, the Food and Drug Administration declared on Feb. 21. The agency is now mandating a black-box warning.

“Health care professionals should reserve Uloric for use only in patients who have failed or do not tolerate allopurinol,” the FDA announced. “Counsel patients about the cardiovascular risk with Uloric,” the agency suggested, and advise them to seek medical attention at once if they have cardiac symptoms such as chest pain, shortness of breath, rapid or irregular heartbeat, or dizziness.

The FDA’s move comes a decade after it approved febuxostat as a gout treatment. As the FDA noted in its announcement, “the number of medicines to treat gout is limited, and there is an unmet need for treatments for this disease.”

Research has suggested that both febuxostat and allopurinol have similar efficacy. Some experts have recommended febuxostat as an alternative for patients who shouldn’t take allopurinol (Semin Arthritis Rheum. 2013 Dec;43[3]:367-75).

However, research has raised concerns about febuxostat’s cardiac risk. In its Feb. 21 statement, the FDA pointed to the findings of a 2010-2017 postmarket clinical trial of 6,190 patients with gout who were treated with febuxostat or allopurinol (N Engl J Med. 2018;378:1200-10).

“In patients treated with Uloric, 15 deaths from heart-related causes were observed for every 1,000 patients treated for a year compared to 11 deaths from heart-related causes per 1,000 patients treated with allopurinol for a year,” the FDA said. “In addition, there were 26 deaths from any cause per 1,000 patients treated for a year with Uloric compared to 22 deaths per 1,000 patients treated for a year with allopurinol.”

The gout drug febuxostat (Uloric) poses a significantly higher risk of all-cause and heart-related death than does the popular alternative drug allopurinol, the Food and Drug Administration declared on Feb. 21. The agency is now mandating a black-box warning.

“Health care professionals should reserve Uloric for use only in patients who have failed or do not tolerate allopurinol,” the FDA announced. “Counsel patients about the cardiovascular risk with Uloric,” the agency suggested, and advise them to seek medical attention at once if they have cardiac symptoms such as chest pain, shortness of breath, rapid or irregular heartbeat, or dizziness.

The FDA’s move comes a decade after it approved febuxostat as a gout treatment. As the FDA noted in its announcement, “the number of medicines to treat gout is limited, and there is an unmet need for treatments for this disease.”

Research has suggested that both febuxostat and allopurinol have similar efficacy. Some experts have recommended febuxostat as an alternative for patients who shouldn’t take allopurinol (Semin Arthritis Rheum. 2013 Dec;43[3]:367-75).

However, research has raised concerns about febuxostat’s cardiac risk. In its Feb. 21 statement, the FDA pointed to the findings of a 2010-2017 postmarket clinical trial of 6,190 patients with gout who were treated with febuxostat or allopurinol (N Engl J Med. 2018;378:1200-10).

“In patients treated with Uloric, 15 deaths from heart-related causes were observed for every 1,000 patients treated for a year compared to 11 deaths from heart-related causes per 1,000 patients treated with allopurinol for a year,” the FDA said. “In addition, there were 26 deaths from any cause per 1,000 patients treated for a year with Uloric compared to 22 deaths per 1,000 patients treated for a year with allopurinol.”

For patients with resectable stage I non–small cell lung cancer (NSCLC), stereotactic ablative radiotherapy (SABR) may lack the efficacy needed to replace surgical intervention, according to a recent phase II trial.

SABR provided a pathologic complete response rate (pCR) of 60%, which was “lower than hypothesized,” reported lead author David A. Palma, MD, PhD, of London (Ont.) Health Sciences Centre, and his colleagues.

“In patients with cancer who are fit for resection ... the role of SABR is controversial,” the investigators wrote in JAMA Oncology. “Although some recent studies suggest that SABR may achieve outcomes similar to surgery, others do not, and randomized clinical trials are currently under way to compare these 2 modalities.”

The present trial involved 40 adult patients with stage I NSCLC, good pulmonary function, and good performance status. Of these, 35 were evaluable for the primary endpoint, which was tumor pCR rate after SABR. Secondary endpoints were toxic effects, quality of life, distant control, regional control, and local control. Patients with tumors no larger than 3 cm in diameter were given 54 Gy in 3 fractions, while bigger tumors received 55 Gy in 5 fractions. Patients with tumors 2 cm or closer to the brachial plexus or mediastinum were given 60 Gy in 8 fractions. Ten weeks after SABR, sublobar resection or lobectomy was performed, via an open approach or with video-assisted thoracoscopic surgery (VATS).

Analysis revealed a pCR rate of 60%, which was lower than anticipated. One-month and 3-month survival rates were both 100%. After a median follow-up of 19 months, local control rate was 100%, but only three out of four patients (76%) had distant control, and half (53%) had regional control. After 2 years, three out of four patients were still alive (77%). Eighteen percent of patients experienced grade 3 or higher toxic effects.

“[T]he pCR rate of 60% at 10 weeks suggests that practitioners should be cautious in the use of SABR in patients with cancers who are fit for resection,” the investigators concluded.

The Ontario Institute for Cancer Research funded the study. Dr. Palma and Dr. Ward are patent holders for a computed tomography technology that assesses responses after radiotherapy. Dr. Louie reported honoraria from AstraZeneca and Varian Medical Systems Inc.

SOURCE: Palma et al. 2019 Feb 21. doi: 10.1001/jamaoncol.2018.6993.

For patients with resectable stage I non–small cell lung cancer (NSCLC), stereotactic ablative radiotherapy (SABR) may lack the efficacy needed to replace surgical intervention, according to a recent phase II trial.

SABR provided a pathologic complete response rate (pCR) of 60%, which was “lower than hypothesized,” reported lead author David A. Palma, MD, PhD, of London (Ont.) Health Sciences Centre, and his colleagues.

“In patients with cancer who are fit for resection ... the role of SABR is controversial,” the investigators wrote in JAMA Oncology. “Although some recent studies suggest that SABR may achieve outcomes similar to surgery, others do not, and randomized clinical trials are currently under way to compare these 2 modalities.”

The present trial involved 40 adult patients with stage I NSCLC, good pulmonary function, and good performance status. Of these, 35 were evaluable for the primary endpoint, which was tumor pCR rate after SABR. Secondary endpoints were toxic effects, quality of life, distant control, regional control, and local control. Patients with tumors no larger than 3 cm in diameter were given 54 Gy in 3 fractions, while bigger tumors received 55 Gy in 5 fractions. Patients with tumors 2 cm or closer to the brachial plexus or mediastinum were given 60 Gy in 8 fractions. Ten weeks after SABR, sublobar resection or lobectomy was performed, via an open approach or with video-assisted thoracoscopic surgery (VATS).

Analysis revealed a pCR rate of 60%, which was lower than anticipated. One-month and 3-month survival rates were both 100%. After a median follow-up of 19 months, local control rate was 100%, but only three out of four patients (76%) had distant control, and half (53%) had regional control. After 2 years, three out of four patients were still alive (77%). Eighteen percent of patients experienced grade 3 or higher toxic effects.

“[T]he pCR rate of 60% at 10 weeks suggests that practitioners should be cautious in the use of SABR in patients with cancers who are fit for resection,” the investigators concluded.

The Ontario Institute for Cancer Research funded the study. Dr. Palma and Dr. Ward are patent holders for a computed tomography technology that assesses responses after radiotherapy. Dr. Louie reported honoraria from AstraZeneca and Varian Medical Systems Inc.

SOURCE: Palma et al. 2019 Feb 21. doi: 10.1001/jamaoncol.2018.6993.

For patients with resectable stage I non–small cell lung cancer (NSCLC), stereotactic ablative radiotherapy (SABR) may lack the efficacy needed to replace surgical intervention, according to a recent phase II trial.

SABR provided a pathologic complete response rate (pCR) of 60%, which was “lower than hypothesized,” reported lead author David A. Palma, MD, PhD, of London (Ont.) Health Sciences Centre, and his colleagues.

“In patients with cancer who are fit for resection ... the role of SABR is controversial,” the investigators wrote in JAMA Oncology. “Although some recent studies suggest that SABR may achieve outcomes similar to surgery, others do not, and randomized clinical trials are currently under way to compare these 2 modalities.”

The present trial involved 40 adult patients with stage I NSCLC, good pulmonary function, and good performance status. Of these, 35 were evaluable for the primary endpoint, which was tumor pCR rate after SABR. Secondary endpoints were toxic effects, quality of life, distant control, regional control, and local control. Patients with tumors no larger than 3 cm in diameter were given 54 Gy in 3 fractions, while bigger tumors received 55 Gy in 5 fractions. Patients with tumors 2 cm or closer to the brachial plexus or mediastinum were given 60 Gy in 8 fractions. Ten weeks after SABR, sublobar resection or lobectomy was performed, via an open approach or with video-assisted thoracoscopic surgery (VATS).

Analysis revealed a pCR rate of 60%, which was lower than anticipated. One-month and 3-month survival rates were both 100%. After a median follow-up of 19 months, local control rate was 100%, but only three out of four patients (76%) had distant control, and half (53%) had regional control. After 2 years, three out of four patients were still alive (77%). Eighteen percent of patients experienced grade 3 or higher toxic effects.

“[T]he pCR rate of 60% at 10 weeks suggests that practitioners should be cautious in the use of SABR in patients with cancers who are fit for resection,” the investigators concluded.

The Ontario Institute for Cancer Research funded the study. Dr. Palma and Dr. Ward are patent holders for a computed tomography technology that assesses responses after radiotherapy. Dr. Louie reported honoraria from AstraZeneca and Varian Medical Systems Inc.

SOURCE: Palma et al. 2019 Feb 21. doi: 10.1001/jamaoncol.2018.6993.

Antipsychotics show no link to increased risk of major congenital malformations. Boomers will spike U.S. health costs, but growing uninsured will soften their impact. Don’t miss early joint involvement in psoriasis. And an algorithm provides practical clinical guidance on managing diabetes.

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Antipsychotics show no link to increased risk of major congenital malformations. Boomers will spike U.S. health costs, but growing uninsured will soften their impact. Don’t miss early joint involvement in psoriasis. And an algorithm provides practical clinical guidance on managing diabetes.

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Apple Podcasts

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Spotify

Antipsychotics show no link to increased risk of major congenital malformations. Boomers will spike U.S. health costs, but growing uninsured will soften their impact. Don’t miss early joint involvement in psoriasis. And an algorithm provides practical clinical guidance on managing diabetes.

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Apple Podcasts

Google Podcasts

Spotify

In this episode, Kirti Magudia, MD, and Thomas Ng, MD, join host Nick Andrews to talk about their research regarding family leave for resident physicians in the nation’s top medical schools. The research was published in JAMA. Dr. Magudia talks about their experience doing this research, what they learned, and what the next steps are.

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In this episode, Kirti Magudia, MD, and Thomas Ng, MD, join host Nick Andrews to talk about their research regarding family leave for resident physicians in the nation’s top medical schools. The research was published in JAMA. Dr. Magudia talks about their experience doing this research, what they learned, and what the next steps are.

Apple Podcasts

Google Podcasts

Spotify
 

In this episode, Kirti Magudia, MD, and Thomas Ng, MD, join host Nick Andrews to talk about their research regarding family leave for resident physicians in the nation’s top medical schools. The research was published in JAMA. Dr. Magudia talks about their experience doing this research, what they learned, and what the next steps are.

Apple Podcasts

Google Podcasts

Spotify
 

One of the tricky parts of HIV drug therapy is determining how well the drugs have worked. The HIV DNA (provirus) in resting cells is usually too defective to replicate itself the way intact provirus can. But most current tests cannot tell the difference between the two. However, researchers from Johns Hopkins University School of Medicine in Baltimore have developed an accurate and scalable assay to easily count the cells in the HIV reservoir.

A stable, latent reservoir for HIV-1 in resting CD4+ T cells is “the principle barrier to a cure,” the researchers say. Quantitative outgrowth assays and assays for cells that produce viral RNA after T-cell activation may underestimate the reservoir size because 1 round of activation does not induce all proviruses. Many studies, the researchers say, rely on simple assays based on polymerase chain reaction to detect proviral DNA regardless of transcriptional status, but the clinical relevance of those assays is unclear since the vast majority of proviruses are defective.

In their study, supported by the National Institute of Allergy and Infectious Diseases, the researchers analyzed DNA sequences from > 400 HIV proviruses from 28 people with HIV. They mapped 2 types of flaws: deletions and lethal mutations. They then developed strategically placed “genetic probes” that could distinguish between deleted or highly mutated proviruses and intact ones. Finally, they developed a nanotechnology-based method to analyze 1 provirus at a time to determine how many in a sample are intact.

The researchers say their findings show that the dynamics of cells that carry intact and defective proviruses are different in vitro and in vivo. Their hope is that their method will speed HIV research by allowing scientists to easily quantify the number of proviruses in an individual, which must be eliminated to achieve a cure.

One of the tricky parts of HIV drug therapy is determining how well the drugs have worked. The HIV DNA (provirus) in resting cells is usually too defective to replicate itself the way intact provirus can. But most current tests cannot tell the difference between the two. However, researchers from Johns Hopkins University School of Medicine in Baltimore have developed an accurate and scalable assay to easily count the cells in the HIV reservoir.

A stable, latent reservoir for HIV-1 in resting CD4+ T cells is “the principle barrier to a cure,” the researchers say. Quantitative outgrowth assays and assays for cells that produce viral RNA after T-cell activation may underestimate the reservoir size because 1 round of activation does not induce all proviruses. Many studies, the researchers say, rely on simple assays based on polymerase chain reaction to detect proviral DNA regardless of transcriptional status, but the clinical relevance of those assays is unclear since the vast majority of proviruses are defective.

In their study, supported by the National Institute of Allergy and Infectious Diseases, the researchers analyzed DNA sequences from > 400 HIV proviruses from 28 people with HIV. They mapped 2 types of flaws: deletions and lethal mutations. They then developed strategically placed “genetic probes” that could distinguish between deleted or highly mutated proviruses and intact ones. Finally, they developed a nanotechnology-based method to analyze 1 provirus at a time to determine how many in a sample are intact.

The researchers say their findings show that the dynamics of cells that carry intact and defective proviruses are different in vitro and in vivo. Their hope is that their method will speed HIV research by allowing scientists to easily quantify the number of proviruses in an individual, which must be eliminated to achieve a cure.

One of the tricky parts of HIV drug therapy is determining how well the drugs have worked. The HIV DNA (provirus) in resting cells is usually too defective to replicate itself the way intact provirus can. But most current tests cannot tell the difference between the two. However, researchers from Johns Hopkins University School of Medicine in Baltimore have developed an accurate and scalable assay to easily count the cells in the HIV reservoir.

A stable, latent reservoir for HIV-1 in resting CD4+ T cells is “the principle barrier to a cure,” the researchers say. Quantitative outgrowth assays and assays for cells that produce viral RNA after T-cell activation may underestimate the reservoir size because 1 round of activation does not induce all proviruses. Many studies, the researchers say, rely on simple assays based on polymerase chain reaction to detect proviral DNA regardless of transcriptional status, but the clinical relevance of those assays is unclear since the vast majority of proviruses are defective.

In their study, supported by the National Institute of Allergy and Infectious Diseases, the researchers analyzed DNA sequences from > 400 HIV proviruses from 28 people with HIV. They mapped 2 types of flaws: deletions and lethal mutations. They then developed strategically placed “genetic probes” that could distinguish between deleted or highly mutated proviruses and intact ones. Finally, they developed a nanotechnology-based method to analyze 1 provirus at a time to determine how many in a sample are intact.

The researchers say their findings show that the dynamics of cells that carry intact and defective proviruses are different in vitro and in vivo. Their hope is that their method will speed HIV research by allowing scientists to easily quantify the number of proviruses in an individual, which must be eliminated to achieve a cure.

A triple test was a significantly more effective predictor of preeclampsia than was either angiogenic placental growth factor (PlGF) alone or the antiangiogenic factor soluble fms-like tyrosine kinase-1(sFLT)/PlGF ratio, based on data from more than 15,000 pregnancies.

Jovanmandic/Getty Images

The use of either PlGF or sFLT/PlGF alone to predict preeclampsia fails to account for individual maternal risk factors or the measurement of blood pressure at presentation, wrote Anca Ciobanu, MD, of King’s College London, and her colleagues.

In a study published in the American Journal of Obstetrics & Gynecology, the researchers reviewed data from 15,247 singleton pregnancies with live births of healthy babies and compared the preeclampsia detection rates of PlGF, sFLT/PlGF and a competing risks model that included a combination of maternal factors and median values of PlGF, sFLT, and mean arterial pressure (triple test). Preeclampsia developed in 2.1% of pregnancies.

Overall, the triple-test detection rate for delivery with preeclampsia was 10% higher than the sFLT/PlGF ratio and 20% higher than PlGF alone based on assessment at 2 weeks or less or 4 weeks or less before delivery. The negative predictive value was similar for the three tests.

At 2 weeks or less before delivery, the area under the receiver operating characteristic curves (AUROC) for preeclampsia was significantly higher for the combination model (0.975), compared with PlGF (0.900) or the sFLT/PlGF ratio (0.932), with P less than .0001 in each case. Similarly, at 4 weeks or less before delivery, the AUROC for preeclampsia was 0.907 for the triple test, 0.827 for PlGF alone, and 0.857 for the sFLT/PlGF ratio, with P less than .0001 in each case.

The competing risks model allows clinicians more flexibility to identify patients at increased risk by considering factors including maternal characteristics and variations from normal blood pressure, Dr. Ciobanu and her associates noted. Also, the combination model, “can form the basis of future research that would quantify and incorporate into the model, symptoms such as headache and epigastric pain, as well as proteinuria, creatinine, liver enzymes and platelets.”

The study findings were limited by several factors including the potential predictive value of screening for women with hypertensive symptoms attending specialist clinics, and whether mean arterial pressure would be an effective measure in patients seen at these clinics, the researchers noted. However, the results support the value of the competing risks model, which “provides a personalized risk for delivery with preeclampsia that could lead to personalized stratification of the intensity of monitoring and timing of delivery.”

The study was supported by a grant from the Fetal Medicine Foundation; Thermo Fisher Scientific provided the reagents and equipment. The researchers had no financial conflicts of interest.

SOURCE: Ciobanu A et al. Am J Obstet Gynecol. 2019 Feb 7. doi. org/10.1016/j.ajog.2019.01.235.

A triple test was a significantly more effective predictor of preeclampsia than was either angiogenic placental growth factor (PlGF) alone or the antiangiogenic factor soluble fms-like tyrosine kinase-1(sFLT)/PlGF ratio, based on data from more than 15,000 pregnancies.

Jovanmandic/Getty Images

The use of either PlGF or sFLT/PlGF alone to predict preeclampsia fails to account for individual maternal risk factors or the measurement of blood pressure at presentation, wrote Anca Ciobanu, MD, of King’s College London, and her colleagues.

In a study published in the American Journal of Obstetrics & Gynecology, the researchers reviewed data from 15,247 singleton pregnancies with live births of healthy babies and compared the preeclampsia detection rates of PlGF, sFLT/PlGF and a competing risks model that included a combination of maternal factors and median values of PlGF, sFLT, and mean arterial pressure (triple test). Preeclampsia developed in 2.1% of pregnancies.

Overall, the triple-test detection rate for delivery with preeclampsia was 10% higher than the sFLT/PlGF ratio and 20% higher than PlGF alone based on assessment at 2 weeks or less or 4 weeks or less before delivery. The negative predictive value was similar for the three tests.

At 2 weeks or less before delivery, the area under the receiver operating characteristic curves (AUROC) for preeclampsia was significantly higher for the combination model (0.975), compared with PlGF (0.900) or the sFLT/PlGF ratio (0.932), with P less than .0001 in each case. Similarly, at 4 weeks or less before delivery, the AUROC for preeclampsia was 0.907 for the triple test, 0.827 for PlGF alone, and 0.857 for the sFLT/PlGF ratio, with P less than .0001 in each case.

The competing risks model allows clinicians more flexibility to identify patients at increased risk by considering factors including maternal characteristics and variations from normal blood pressure, Dr. Ciobanu and her associates noted. Also, the combination model, “can form the basis of future research that would quantify and incorporate into the model, symptoms such as headache and epigastric pain, as well as proteinuria, creatinine, liver enzymes and platelets.”

The study findings were limited by several factors including the potential predictive value of screening for women with hypertensive symptoms attending specialist clinics, and whether mean arterial pressure would be an effective measure in patients seen at these clinics, the researchers noted. However, the results support the value of the competing risks model, which “provides a personalized risk for delivery with preeclampsia that could lead to personalized stratification of the intensity of monitoring and timing of delivery.”

The study was supported by a grant from the Fetal Medicine Foundation; Thermo Fisher Scientific provided the reagents and equipment. The researchers had no financial conflicts of interest.

SOURCE: Ciobanu A et al. Am J Obstet Gynecol. 2019 Feb 7. doi. org/10.1016/j.ajog.2019.01.235.

A triple test was a significantly more effective predictor of preeclampsia than was either angiogenic placental growth factor (PlGF) alone or the antiangiogenic factor soluble fms-like tyrosine kinase-1(sFLT)/PlGF ratio, based on data from more than 15,000 pregnancies.

Jovanmandic/Getty Images

The use of either PlGF or sFLT/PlGF alone to predict preeclampsia fails to account for individual maternal risk factors or the measurement of blood pressure at presentation, wrote Anca Ciobanu, MD, of King’s College London, and her colleagues.

In a study published in the American Journal of Obstetrics & Gynecology, the researchers reviewed data from 15,247 singleton pregnancies with live births of healthy babies and compared the preeclampsia detection rates of PlGF, sFLT/PlGF and a competing risks model that included a combination of maternal factors and median values of PlGF, sFLT, and mean arterial pressure (triple test). Preeclampsia developed in 2.1% of pregnancies.

Overall, the triple-test detection rate for delivery with preeclampsia was 10% higher than the sFLT/PlGF ratio and 20% higher than PlGF alone based on assessment at 2 weeks or less or 4 weeks or less before delivery. The negative predictive value was similar for the three tests.

At 2 weeks or less before delivery, the area under the receiver operating characteristic curves (AUROC) for preeclampsia was significantly higher for the combination model (0.975), compared with PlGF (0.900) or the sFLT/PlGF ratio (0.932), with P less than .0001 in each case. Similarly, at 4 weeks or less before delivery, the AUROC for preeclampsia was 0.907 for the triple test, 0.827 for PlGF alone, and 0.857 for the sFLT/PlGF ratio, with P less than .0001 in each case.

The competing risks model allows clinicians more flexibility to identify patients at increased risk by considering factors including maternal characteristics and variations from normal blood pressure, Dr. Ciobanu and her associates noted. Also, the combination model, “can form the basis of future research that would quantify and incorporate into the model, symptoms such as headache and epigastric pain, as well as proteinuria, creatinine, liver enzymes and platelets.”

The study findings were limited by several factors including the potential predictive value of screening for women with hypertensive symptoms attending specialist clinics, and whether mean arterial pressure would be an effective measure in patients seen at these clinics, the researchers noted. However, the results support the value of the competing risks model, which “provides a personalized risk for delivery with preeclampsia that could lead to personalized stratification of the intensity of monitoring and timing of delivery.”

The study was supported by a grant from the Fetal Medicine Foundation; Thermo Fisher Scientific provided the reagents and equipment. The researchers had no financial conflicts of interest.

SOURCE: Ciobanu A et al. Am J Obstet Gynecol. 2019 Feb 7. doi. org/10.1016/j.ajog.2019.01.235.

Certain antipsychotic polytherapies, including aripiprazole and clozapine, are associated with a lower risk of psychiatric rehospitalization in patients with schizophrenia, according to Jari Tiihonen, MD, PhD, of the Karolinska Institute in Stockholm, and his associates.

The study population included a total of 62,250 patients from the Finnish Hospital Discharge register who were treated for schizophrenia in the inpatient setting from 1972 to 2014. The median patient age was 45.6 years and the median length of follow-up was 14.1 years. Over the study period, 58.8% of this cohort were readmitted for psychiatric inpatient care, 67.2% used antipsychotic polypharmacy during the follow-up, and 57.5% were exposed to antipsychotic polypharmacy for at least 90 days, Dr. Tiihonen and his associates wrote in JAMA Psychiatry.

The combination of aripiprazole and clozapine was associated with the lowest risk of psychiatric rehospitalization, compared with those who received no therapy (hazard ratio, 0.42, 95% confidence interval, 0.39-0.46). Clozapine alone was the most effective antipsychotic monotherapy (HR, 0.49; 95% CI, 0.47-0.51), and when aripiprazole/clozapine was compared with clozapine alone, the polytherapy was significantly more effective (HR, 0.86; 95% CI, 0.79-0.94).

The difference between aripiprazole/clozapine and clozapine alone was even greater in patients who initially were hospitalized for their first episode of schizophrenia (HR, 0.78; 95% CI, 0.63-0.96). Overall, any antipsychotic polypharmacy was associated with a 7%-13% lower risk of hospitalization, compared with any monotherapy; clozapine alone was the only monotherapy among the 10 most effective treatments, the authors noted.

“It should be acknowledged that statements about a preferential use of antipsychotic monotherapy for maintenance treatment of schizophrenia lack evidence, and that currently available evidence – although gathered with few nonrandomized cohort studies that have their own limitations – indicates the opposite,” they concluded.

Dr. Tiihonen and several of his associates reported numerous conflicts of interest.

[email protected]

SOURCE: Tiihonen J et al. JAMA Psychiatry. 2019 Feb 20. doi: 10.1001/jamapsychiatry.2018.4320.

Certain antipsychotic polytherapies, including aripiprazole and clozapine, are associated with a lower risk of psychiatric rehospitalization in patients with schizophrenia, according to Jari Tiihonen, MD, PhD, of the Karolinska Institute in Stockholm, and his associates.

The study population included a total of 62,250 patients from the Finnish Hospital Discharge register who were treated for schizophrenia in the inpatient setting from 1972 to 2014. The median patient age was 45.6 years and the median length of follow-up was 14.1 years. Over the study period, 58.8% of this cohort were readmitted for psychiatric inpatient care, 67.2% used antipsychotic polypharmacy during the follow-up, and 57.5% were exposed to antipsychotic polypharmacy for at least 90 days, Dr. Tiihonen and his associates wrote in JAMA Psychiatry.

The combination of aripiprazole and clozapine was associated with the lowest risk of psychiatric rehospitalization, compared with those who received no therapy (hazard ratio, 0.42, 95% confidence interval, 0.39-0.46). Clozapine alone was the most effective antipsychotic monotherapy (HR, 0.49; 95% CI, 0.47-0.51), and when aripiprazole/clozapine was compared with clozapine alone, the polytherapy was significantly more effective (HR, 0.86; 95% CI, 0.79-0.94).

The difference between aripiprazole/clozapine and clozapine alone was even greater in patients who initially were hospitalized for their first episode of schizophrenia (HR, 0.78; 95% CI, 0.63-0.96). Overall, any antipsychotic polypharmacy was associated with a 7%-13% lower risk of hospitalization, compared with any monotherapy; clozapine alone was the only monotherapy among the 10 most effective treatments, the authors noted.

“It should be acknowledged that statements about a preferential use of antipsychotic monotherapy for maintenance treatment of schizophrenia lack evidence, and that currently available evidence – although gathered with few nonrandomized cohort studies that have their own limitations – indicates the opposite,” they concluded.

Dr. Tiihonen and several of his associates reported numerous conflicts of interest.

[email protected]

SOURCE: Tiihonen J et al. JAMA Psychiatry. 2019 Feb 20. doi: 10.1001/jamapsychiatry.2018.4320.

Certain antipsychotic polytherapies, including aripiprazole and clozapine, are associated with a lower risk of psychiatric rehospitalization in patients with schizophrenia, according to Jari Tiihonen, MD, PhD, of the Karolinska Institute in Stockholm, and his associates.

The study population included a total of 62,250 patients from the Finnish Hospital Discharge register who were treated for schizophrenia in the inpatient setting from 1972 to 2014. The median patient age was 45.6 years and the median length of follow-up was 14.1 years. Over the study period, 58.8% of this cohort were readmitted for psychiatric inpatient care, 67.2% used antipsychotic polypharmacy during the follow-up, and 57.5% were exposed to antipsychotic polypharmacy for at least 90 days, Dr. Tiihonen and his associates wrote in JAMA Psychiatry.

The combination of aripiprazole and clozapine was associated with the lowest risk of psychiatric rehospitalization, compared with those who received no therapy (hazard ratio, 0.42, 95% confidence interval, 0.39-0.46). Clozapine alone was the most effective antipsychotic monotherapy (HR, 0.49; 95% CI, 0.47-0.51), and when aripiprazole/clozapine was compared with clozapine alone, the polytherapy was significantly more effective (HR, 0.86; 95% CI, 0.79-0.94).

The difference between aripiprazole/clozapine and clozapine alone was even greater in patients who initially were hospitalized for their first episode of schizophrenia (HR, 0.78; 95% CI, 0.63-0.96). Overall, any antipsychotic polypharmacy was associated with a 7%-13% lower risk of hospitalization, compared with any monotherapy; clozapine alone was the only monotherapy among the 10 most effective treatments, the authors noted.

“It should be acknowledged that statements about a preferential use of antipsychotic monotherapy for maintenance treatment of schizophrenia lack evidence, and that currently available evidence – although gathered with few nonrandomized cohort studies that have their own limitations – indicates the opposite,” they concluded.

Dr. Tiihonen and several of his associates reported numerous conflicts of interest.

[email protected]

SOURCE: Tiihonen J et al. JAMA Psychiatry. 2019 Feb 20. doi: 10.1001/jamapsychiatry.2018.4320.

LAS VEGAS – Delayed umbilical cord clamping did not significantly increase maternal blood loss for women undergoing term cesarean delivery, according to a recent study.

Martin Valigursky/Thinkstock

The change in maternal hemoglobin from preoperative level to postoperative day 1, the study’s primary outcome measure, was not significantly different whether the umbilical cord was clamped within 15 seconds of delivery or clamping was delayed for 1 minute.

For the 56 women who received immediate cord clamping, hemoglobin dropped a mean 1.78 g/dL; for the 57 women who received delayed cord clamping, the drop was 1.85 g/dL (P = .69). Mean estimated blood loss for the delayed clamping group was numerically higher at 884 mL, compared with 830 mL for the immediate clamping group, but this was not a statistically significant difference (P = .13)

However, the practice did result in significantly greater neonatal hemoglobin measured at 24-72 hours post delivery. Hemoglobin data were available for 90 infants, or about 80% of participants. For the 44 infants in the immediate clamping group, mean hemoglobin was 16.4 g/dL; for the delayed clamping group, the figure was 18.1 g/dL (P less than .01).

Although delayed cord clamping has clear benefits to the neonate, whether the practice adversely affects women undergoing cesarean was not clear, said Stephanie Purisch, MD, who discussed the findings of the two-site, randomized, clinical trial during a fellows research session at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“Maternal outcomes have not been a focus of research” in the cord clamping literature, said Dr. Purisch, from Columbia University, New York. A 2013 Cochrane review found that delayed cord clamping did not change postpartum hemoglobin levels or increase blood loss or the need for transfusion. However, she said, the review included only healthy women who expected a vaginal delivery, so cesarean deliveries were undersampled in the data.

Of the 3,911 deliveries included in all prior randomized, controlled trials of delayed cord clamping, just 87, or 2.2%, were cesarean deliveries, she said. In cesarean deliveries, mean blood loss is double that of vaginal deliveries. Delayed clamping could further increase bleeding because the hysterotomy closure is delayed, said Dr. Purisch, so the question of safety in cesarean deliveries is clinically important.

Faced with this knowledge gap, Dr. Purisch and her colleagues constructed a prospective, randomized, controlled trial of delayed cord clamping in cesarean delivery at term, with the hypothesis that maternal blood loss would be increased by the practice.

Patients were eligible if they had singleton gestations with cesarean deliveries scheduled at 37 weeks’ gestation or more. Patients with known placentation problems, significant maternal or known fetal anemia, maternal bleeding disorders, and preeclampsia were excluded. The study also did not include pregnancies with known fetal anomalies or intrauterine growth retardation, or those in which cord blood banking was planned or the mother would refuse blood products.

In an intention-to-treat analysis, Dr. Purisch and her colleagues randomly assigned participants 1:1 to immediate cord clamping, defined as clamping the cord by 15 seconds after delivery, or delayed cord clamping, in which the umbilical cord was clamped 1 minute after delivery.

Oxytocin was routinely administered to each group on delivery, and there was no umbilical cord milking in either group. For the delayed-clamping group, the infant was kept at the level of the placenta and tended by the pediatric team during the minute before clamping. Dr. Purisch explained that cord clamping was performed before 60 seconds in the intervention group if needed for neonatal resuscitation.

Participants were similar in the two study arms, with a median gestational age of 39.1 weeks at delivery. Most women (60%-64%) had one prior cesarean delivery, with about a quarter having two or more prior cesarean deliveries. Preoperative maternal hemoglobin was 11.6-12.0 g/dL. About 41% of participants were Hispanic, and the median prepregnancy body mass index for participants was about 27 kg/m².

Looking at secondary outcome measures, there was no difference in rates of postpartum hemorrhage or uterotonic administration between the two groups (P = .99 for both). Hemoglobin levels at postoperative day 1 were numerically higher for the delayed cord clamping group, but the difference wasn’t significant (10.2 vs. 9.8 g/dL; P = .18). Just two women, both in the immediate cord clamping group, required blood transfusions.

Additional neonatal secondary outcome measures included birth weight, Apgar scores at 1 and 5 minutes, the need for phototherapy for jaundice, and umbilical cord artery pH. There were no between-group differences except that umbilical cord artery pH was slightly lower in the delayed group (7.2 vs. 7.3; P = .04).

“Delayed cord clamping is not associated with increased maternal blood loss … but it does achieve higher neonatal hemoglobin levels at 24-72 hours of life,” said Dr. Purisch. “These results provide support for the application of current [American College of Obstetricians and Gynecologists] recommendations to women planned for cesarean delivery.”

The study was funded by the Columbia Maternal-Fetal Medicine Fellow Research Fund. Dr. Purisch reported no conflicts of interest.

[email protected]

SOURCE: Purisch, S. et al. Am J Obstet Gynecol. 2019 Jan;220(1):S37-38, Abstract 47.

LAS VEGAS – Delayed umbilical cord clamping did not significantly increase maternal blood loss for women undergoing term cesarean delivery, according to a recent study.

Martin Valigursky/Thinkstock

The change in maternal hemoglobin from preoperative level to postoperative day 1, the study’s primary outcome measure, was not significantly different whether the umbilical cord was clamped within 15 seconds of delivery or clamping was delayed for 1 minute.

For the 56 women who received immediate cord clamping, hemoglobin dropped a mean 1.78 g/dL; for the 57 women who received delayed cord clamping, the drop was 1.85 g/dL (P = .69). Mean estimated blood loss for the delayed clamping group was numerically higher at 884 mL, compared with 830 mL for the immediate clamping group, but this was not a statistically significant difference (P = .13)

However, the practice did result in significantly greater neonatal hemoglobin measured at 24-72 hours post delivery. Hemoglobin data were available for 90 infants, or about 80% of participants. For the 44 infants in the immediate clamping group, mean hemoglobin was 16.4 g/dL; for the delayed clamping group, the figure was 18.1 g/dL (P less than .01).

Although delayed cord clamping has clear benefits to the neonate, whether the practice adversely affects women undergoing cesarean was not clear, said Stephanie Purisch, MD, who discussed the findings of the two-site, randomized, clinical trial during a fellows research session at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“Maternal outcomes have not been a focus of research” in the cord clamping literature, said Dr. Purisch, from Columbia University, New York. A 2013 Cochrane review found that delayed cord clamping did not change postpartum hemoglobin levels or increase blood loss or the need for transfusion. However, she said, the review included only healthy women who expected a vaginal delivery, so cesarean deliveries were undersampled in the data.

Of the 3,911 deliveries included in all prior randomized, controlled trials of delayed cord clamping, just 87, or 2.2%, were cesarean deliveries, she said. In cesarean deliveries, mean blood loss is double that of vaginal deliveries. Delayed clamping could further increase bleeding because the hysterotomy closure is delayed, said Dr. Purisch, so the question of safety in cesarean deliveries is clinically important.

Faced with this knowledge gap, Dr. Purisch and her colleagues constructed a prospective, randomized, controlled trial of delayed cord clamping in cesarean delivery at term, with the hypothesis that maternal blood loss would be increased by the practice.

Patients were eligible if they had singleton gestations with cesarean deliveries scheduled at 37 weeks’ gestation or more. Patients with known placentation problems, significant maternal or known fetal anemia, maternal bleeding disorders, and preeclampsia were excluded. The study also did not include pregnancies with known fetal anomalies or intrauterine growth retardation, or those in which cord blood banking was planned or the mother would refuse blood products.

In an intention-to-treat analysis, Dr. Purisch and her colleagues randomly assigned participants 1:1 to immediate cord clamping, defined as clamping the cord by 15 seconds after delivery, or delayed cord clamping, in which the umbilical cord was clamped 1 minute after delivery.

Oxytocin was routinely administered to each group on delivery, and there was no umbilical cord milking in either group. For the delayed-clamping group, the infant was kept at the level of the placenta and tended by the pediatric team during the minute before clamping. Dr. Purisch explained that cord clamping was performed before 60 seconds in the intervention group if needed for neonatal resuscitation.

Participants were similar in the two study arms, with a median gestational age of 39.1 weeks at delivery. Most women (60%-64%) had one prior cesarean delivery, with about a quarter having two or more prior cesarean deliveries. Preoperative maternal hemoglobin was 11.6-12.0 g/dL. About 41% of participants were Hispanic, and the median prepregnancy body mass index for participants was about 27 kg/m².

Looking at secondary outcome measures, there was no difference in rates of postpartum hemorrhage or uterotonic administration between the two groups (P = .99 for both). Hemoglobin levels at postoperative day 1 were numerically higher for the delayed cord clamping group, but the difference wasn’t significant (10.2 vs. 9.8 g/dL; P = .18). Just two women, both in the immediate cord clamping group, required blood transfusions.

Additional neonatal secondary outcome measures included birth weight, Apgar scores at 1 and 5 minutes, the need for phototherapy for jaundice, and umbilical cord artery pH. There were no between-group differences except that umbilical cord artery pH was slightly lower in the delayed group (7.2 vs. 7.3; P = .04).

“Delayed cord clamping is not associated with increased maternal blood loss … but it does achieve higher neonatal hemoglobin levels at 24-72 hours of life,” said Dr. Purisch. “These results provide support for the application of current [American College of Obstetricians and Gynecologists] recommendations to women planned for cesarean delivery.”

The study was funded by the Columbia Maternal-Fetal Medicine Fellow Research Fund. Dr. Purisch reported no conflicts of interest.

[email protected]

SOURCE: Purisch, S. et al. Am J Obstet Gynecol. 2019 Jan;220(1):S37-38, Abstract 47.

LAS VEGAS – Delayed umbilical cord clamping did not significantly increase maternal blood loss for women undergoing term cesarean delivery, according to a recent study.

Martin Valigursky/Thinkstock

The change in maternal hemoglobin from preoperative level to postoperative day 1, the study’s primary outcome measure, was not significantly different whether the umbilical cord was clamped within 15 seconds of delivery or clamping was delayed for 1 minute.

For the 56 women who received immediate cord clamping, hemoglobin dropped a mean 1.78 g/dL; for the 57 women who received delayed cord clamping, the drop was 1.85 g/dL (P = .69). Mean estimated blood loss for the delayed clamping group was numerically higher at 884 mL, compared with 830 mL for the immediate clamping group, but this was not a statistically significant difference (P = .13)

However, the practice did result in significantly greater neonatal hemoglobin measured at 24-72 hours post delivery. Hemoglobin data were available for 90 infants, or about 80% of participants. For the 44 infants in the immediate clamping group, mean hemoglobin was 16.4 g/dL; for the delayed clamping group, the figure was 18.1 g/dL (P less than .01).

Although delayed cord clamping has clear benefits to the neonate, whether the practice adversely affects women undergoing cesarean was not clear, said Stephanie Purisch, MD, who discussed the findings of the two-site, randomized, clinical trial during a fellows research session at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“Maternal outcomes have not been a focus of research” in the cord clamping literature, said Dr. Purisch, from Columbia University, New York. A 2013 Cochrane review found that delayed cord clamping did not change postpartum hemoglobin levels or increase blood loss or the need for transfusion. However, she said, the review included only healthy women who expected a vaginal delivery, so cesarean deliveries were undersampled in the data.

Of the 3,911 deliveries included in all prior randomized, controlled trials of delayed cord clamping, just 87, or 2.2%, were cesarean deliveries, she said. In cesarean deliveries, mean blood loss is double that of vaginal deliveries. Delayed clamping could further increase bleeding because the hysterotomy closure is delayed, said Dr. Purisch, so the question of safety in cesarean deliveries is clinically important.

Faced with this knowledge gap, Dr. Purisch and her colleagues constructed a prospective, randomized, controlled trial of delayed cord clamping in cesarean delivery at term, with the hypothesis that maternal blood loss would be increased by the practice.

Patients were eligible if they had singleton gestations with cesarean deliveries scheduled at 37 weeks’ gestation or more. Patients with known placentation problems, significant maternal or known fetal anemia, maternal bleeding disorders, and preeclampsia were excluded. The study also did not include pregnancies with known fetal anomalies or intrauterine growth retardation, or those in which cord blood banking was planned or the mother would refuse blood products.

In an intention-to-treat analysis, Dr. Purisch and her colleagues randomly assigned participants 1:1 to immediate cord clamping, defined as clamping the cord by 15 seconds after delivery, or delayed cord clamping, in which the umbilical cord was clamped 1 minute after delivery.

Oxytocin was routinely administered to each group on delivery, and there was no umbilical cord milking in either group. For the delayed-clamping group, the infant was kept at the level of the placenta and tended by the pediatric team during the minute before clamping. Dr. Purisch explained that cord clamping was performed before 60 seconds in the intervention group if needed for neonatal resuscitation.

Participants were similar in the two study arms, with a median gestational age of 39.1 weeks at delivery. Most women (60%-64%) had one prior cesarean delivery, with about a quarter having two or more prior cesarean deliveries. Preoperative maternal hemoglobin was 11.6-12.0 g/dL. About 41% of participants were Hispanic, and the median prepregnancy body mass index for participants was about 27 kg/m².

Looking at secondary outcome measures, there was no difference in rates of postpartum hemorrhage or uterotonic administration between the two groups (P = .99 for both). Hemoglobin levels at postoperative day 1 were numerically higher for the delayed cord clamping group, but the difference wasn’t significant (10.2 vs. 9.8 g/dL; P = .18). Just two women, both in the immediate cord clamping group, required blood transfusions.

Additional neonatal secondary outcome measures included birth weight, Apgar scores at 1 and 5 minutes, the need for phototherapy for jaundice, and umbilical cord artery pH. There were no between-group differences except that umbilical cord artery pH was slightly lower in the delayed group (7.2 vs. 7.3; P = .04).

“Delayed cord clamping is not associated with increased maternal blood loss … but it does achieve higher neonatal hemoglobin levels at 24-72 hours of life,” said Dr. Purisch. “These results provide support for the application of current [American College of Obstetricians and Gynecologists] recommendations to women planned for cesarean delivery.”

The study was funded by the Columbia Maternal-Fetal Medicine Fellow Research Fund. Dr. Purisch reported no conflicts of interest.

[email protected]

SOURCE: Purisch, S. et al. Am J Obstet Gynecol. 2019 Jan;220(1):S37-38, Abstract 47.